Hyperlipidemia Research:
2002-2006
     
Eur J Clin Invest. 2006 Aug;36(8):519-27.
Statin therapy in patients with chronic kidney disease: to use or not to use.
Steinmetz OM, Panzer U, Stahl RA, Wenzel UO.
Department of Medicine, Division of Nephrology, University Hospital of Hamburg Eppendorf, Hamburg, Germany.

Dyslipdemia is a common complication of chronic kidney disease (CKD) and contributes to high cardiovascular morbidity and mortality of CKD patients. Experimental studies have demonstrated that lipids induce glomerular and tubulointerstitial injury and that lipid-lowering treatments ameliorate renal injury. Therapy with statins not only has the potential to lower cardiovascular morbidity and mortality in patients with CKD but also to slow progression of renal disease. Whereas the guidelines for treatment of hyperlipidaemia in nonrenal patients are based on prospective, randomized, placebo-controlled mega-trials, such data are not available for CKD patients. This review outlines the limited information currently available on the effect of statins among patients with CKD and summarizes the ongoing randomized trials designed to address this question.

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J Fam Pract. 2006 Jul;55(7):S1-8.
Hypertriglyceridemia: management of atherogenic dyslipidemia.
Bersot T, Haffner S, Harris WS, Kellick KA, Morris CM.
Gladstone Institute of Cardiovascular Disease, School of Medicine, University of California-San Francisco, San Francisco, CA, USA.

Elevated triglycerides are now considered an independent risk factor for coronary heart disease and continue to be a major risk for acute pancreatitis, especially when levels exceed 1000 mg/dL (SOR: B). Elevated triglycerides are a component of atherogenic dyslipidemia and often signal the presence of other conditions (eg, metabolic syndrome, type 2 diabetes mellitus) associated with an increased cardiovascular risk (SOR: A). When evaluating a patient with elevated triglycerides, it is important to be cognizant of all atherogenic lipoproteins to more accurately determine the risk of coronary heart disease (SOR: C). Patients with hypertriglyceridemia should first achieve their low-density lipoprotein cholesterol goal, followed by their non-high-density lipoprotein cholesterol goal (SOR: C). Fibrates, niacin, and omega-3 acid ethyl esters are highly effective at reducing triglycerides, while statins are considered moderately efficacious (SOR: A).

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Metabolism. 2006 Jul;55(7):972-9.
Effects of raloxifene on lipid and lipoprotein levels in postmenopausal osteoporotic women with and without hypertriglyceridemia.
Dayspring T, Qu Y, Keech C.
North Jersey Institute of Menopausal Lipidology, Wayne, NJ 07470, USA. tdayspring@aol.com

This post hoc analysis reports the effects of raloxifene on lipids and lipoproteins in 2659 women with either normal (< or =150 mg/dL) or high (>150 mg/dL) triglyceride levels from a substudy of the Multiple Outcomes of Raloxifene Evaluation (MORE) trial. In both triglyceride subgroups, raloxifene significantly improved low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol (HDL-C), apolipoprotein B, apolipoprotein A-I, and fibrinogen compared with placebo (P < .05). After raloxifene treatment, women with high triglycerides experienced an equal or more robust reduction in cholesterol, lipoprotein parameters, and ratios of total cholesterol to HDL-C and non-HDL-C to HDL-C than was observed in women with normal triglycerides (P < .05). Mean levels of low-density lipoprotein cholesterol and apolipoprotein B were reduced by 16.5% and 15.8%, respectively, in women with high triglycerides, and by 12.7% and 11.3%, respectively, in women with normal triglycerides. These findings further substantiate that raloxifene improves concentrations of both cholesterol and beta-lipoprotein. The subgroup of women with high triglycerides, who have elevated cardiovascular risk, appear to derive at least equal, if not greater, overall effect on lipid and lipoprotein lowering with raloxifene.

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Curr Med Res Opin. 2006 Jun;22(6):1123-31.
Treating to target patients with primary hyperlipidaemia: comparison of the effects of ATOrvastatin and ROSuvastatin (the ATOROS study).
Milionis HJ, Rizos E, Kostapanos M, Filippatos TD, Gazi IF, Ganotakis ES, Goudevenos J, Mikhailidis DP, Elisaf MS.
Department of Internal Medicine School of Medicine, University of Ioannina, Greece. hmilioni@ccuoi.gr

OBJECTIVES: In a 24-week, open-label, randomized, parallel-group study, we compared the efficacy and metabolic effects, beyond low density lipoprotein cholesterol (LDL-C)-lowering, of atorvastatin (ATV) and rosuvastatin (RSV) in cardiovascular disease-free subjects with primary hyperlipidaemia, treated to an LDL-C target (130 mg/dL). METHODS: After a 6-week dietary lead-in period, patients were randomized to RSV 10 mg/day (n = 60) or ATV 20 mg/day (n = 60). After 6 weeks on treatment the dose of the statin was increased (to RSV 20 mg/day or ATV 40 mg/day) if the treatment goal was not achieved. A control group of healthy volunteers (n = 60) was also included for the validation of baseline serum and urinary laboratory parameters. The primary outcome was the percentage of patients reaching the LDL-C goal; secondary outcomes were changes in lipid and non-lipid metabolic parameters. RESULTS: A total of 45 patients (75.0%) in the RSV-treated group and 43 (71.7%) in the ATV-treated group achieved the treatment target at the initial dose. Both regimens were generally well tolerated and there were no withdrawals due to treatment-related serious adverse events. Similar significant reductions in total cholesterol, LDL-C, apolipoprotein (apo) B, triglycerides, apoB/apoA1 ratio, fibrinogen and high-sensitivity C-reactive protein levels were seen. RSV had a significant high density lipoprotein cholesterol (HDL-C)-raising effect and showed a trend towards increasing apoA1 levels. Glycaemic control and renal function parameters were not influenced by statin therapy. ATV, but not RSV, showed a significant hypouricaemic effect. CONCLUSIONS: RSV and ATV were equally efficacious in achieving LDL-C treatment goals in patients with primary hyperlipidaemia at the initial dose and following dose titration. RSV seems to have a significantly higher HDL-C-raising effect, while ATV lowers serum uric acid levels.

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Arq Bras Cardiol. 2006 May;86(5):361-5. Epub 2006 May 29.
[Lipid profile and nutrition counseling effects in adolescents with family history of premature coronary artery disease]
[Article in Portuguese]
Mendes GA, Martinez TL, Izar MC, Amancio OM, Novo NF, Matheus SC, Bertolami MC, Fonseca FA.
Universidade Federal de Sao Paulo, SP.

OBJECTIVE: To assess lipid profile and nutritional parameters from adolescents with family history of premature coronary artery disease (CAD) and assess the effects of nutritional counseling. METHODS: The study included 48 adolescents of both gender and with ages ranging from 10 and 19 years old (case group, n=18; control group, n=30). RESULTS: Offspring of young individuals with coronary artery disease showed higher values of total cholesterol (189 +/- 30 vs. 167 +/- 26 mg/dl, p < 0.01), LDL-C (144 +/- 20 vs. 100 +/- 27 mg/dl, p < 0.001) and apoB (80 +/- 15 vs. 61 +/- 18 mg/dl, p = 0.001) and lower values of HDL-C (45 +/- 9 vs. 51 +/- 13 mg/dl, p < 0.02) than control young individuals. Differences were not found for triglycerides and apoA-I. With a dietotherapeutic counseling, we obtained a reduction in alimentary consumption of saturated fatty acids (pre: 15.5 +/- 4.7% vs. post: 6.6 +/- 3.7%, p = 0.003) and an improvement in lipid profile: TC (-8%, p = 0.033), LDL-C (-18.2%, p = 0.001), TG (-53%, p = 0.002) rates in offspring of premature CAD patients who showed hyperlipidemia. CONCLUSION: The presence of dyslipidemia was more prevalent among offspring adolescents of premature CAD patients, but it was responsive to nutritional intervention.

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J Natl Med Assoc. 2006 May;98(5):772-8.
Efficacy and safety of coadministration of ezetimibe and simvastatin in African-American patients with primary hypercholesterolemia.
Rodney RA, Sugimoto D, Wagman B, Zieve F, Kerzner B, Strony J, Yang B, Suresh R, Veltri E.
Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-1300, USA. roxanne.rodney@spcorp.com

The purpose of this study was to examine the efficacy and safety of ezetimibe (EZE) coadministered with simvastatin (SIMVA) in a large cohort of African Americans with primary hypercholesterolemia. In a multicenter, randomized, double-blind study, patients were considered eligible for enrollment if after a washout/placebo run-in period, low-density-lipoprotein (LDL) cholesterol level was > or = 145 and < or = 250 mg/dl and triglyceride level was < or = 350 mg/dl. Eligible patients were randomized to SIMVA 20 mg coadministered with either EZE 10 mg (n = 124) or placebo (n = 123) for 12 weeks. At study endpoint, EZE/SIMVA 10/20 mg resulted in a significant mean percent reduction in LDL cholesterol from baseline of 45.6% compared with 28.3% for SIMVA 20 mg alone (p < or = 0.01). There were significantly greater mean reductions in total cholesterol (33% vs. 21%), triglycerides (median 22% vs. 15%), nonhigh-density-lipoprotein (non-HDL) cholesterol (42% vs. 26%), and apolipoprotein B (38% vs. 25%) with EZE/SIMVA 10/20 mg compared with SIMVA 20 mg alone, respectively (p < or = 0.01). There was no difference in HDL cholesterol between the EZE/SIMVA 10/20-mg and SIMVA 20-mg alone groups (+1% vs. +2%, respectively). Coadministration of EZE/SIMVA 10/20 mg demonstrated a safety profile similar to that of SIMVA 20 mg. In conclusion, EZE/SIMVA 10/20 mg provided significantly greater improvement in atherogenic lipid profiles and was well tolerated compared with SIMVA 20-mg monotherapy in a large cohort of African Americans with primary hypercholesterolemia.

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Arq Bras Endocrinol Metabol. 2006 Apr;50(2):344-59. Epub 2006 May 23.
[Treatment of dyslipidemia: how and when to combine lipid lowering drugs]
[Article in Portuguese]
Schulz I.
Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP. ischulz@uol.com.br

Familial combined hyperlipidemia (FCH) is a frequent familial lipid disorder associated with insulin resistance, low HDL cholesterol, high triglycerides and cholesterol levels with variable phenotypes within the same family. FCH is linked to a high risk for cardiovascular diseases. Treatment goals for lipid abnormalities are changing in recent years. Lowering elevated levels of LDL e Non HDL-cholesterol levels are primary targets of therapy. Lower LDL-C than 70 mg/dL seems to be useful to lower cardiovascular risk in patients with very high risk. Many statins are available, with different potencies and drug interactions. Combination therapy of statins and bile acid sequestrants or ezitimibe may be necessary to further decrease LDL cholesterol levels in order to meet guideline goals. High triglycerides and low HDL cholesterol are also important goals in the treatment of these patients, and frequently statins alone are insufficient to normalize the lipid profile. Combination therapy with fibrates will further lower triglycerides and increase HDL cholesterol levels; this combination is also associated with higher incidence of myopathy and liver toxicity; appropriate evaluation of patients' risk and benefits is necessary. Association of statin/niacin seems be very useful in patients with FCH, especially as niacin is the best drug to increase HDL cholesterol; this association is not linked to a higher frequency of myopathy. Niacin causes flushing, that can in part be managed with use of aspirin and extended release forms (Niaspan); niacin also may increase plasma glucose and uric acid levels. Evaluation of risks and benefits for each patient is needed.

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Prog Cardiovasc Nurs. 2006 Spring;21(2):89-93.
Dietary and nutraceutical options for managing the hypertriglyceridemic patient.
Pins JJ, Keenan JM.
Department of Family Medicine and Community Health, University of Minnesota Medical School, Minneapolis, MN 55455, USA. pinsx001@umn.edu

Scientific evidence continues to accumulate regarding fasting serum triglycerides as an independent risk factor for coronary heart disease. In response, the National Cholesterol Education Program has revised the acceptable level of fasting triglycerides from <200 mg/dL to <150 mg/dL. A significant percentage of Americans suffer from hypertriglyceridemia, and considering the expanding numbers of individuals who are physically inactive, overweight, and suffering from the metabolic syndrome, it is expected that these numbers will continue to rise over the next decade. Fortunately, nutraceutical and lifestyle options have been shown to substantially and consistently reduce this risk factor. This review will focus on management options for the hypertriglyceridemic patient with an emphasis on nicotinic acid, pantethine, fish oils (eicosapentaenoic and docosahexaenoic acids), and modified carbohydrate diets.

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J Atheroscler Thromb. 2006 Apr;13(2):108-13.
Efficacy of a low dose of pitavastatin compared with atorvastatin in primary hyperlipidemia: results of a 12-week, open label study.
Yoshitomi Y, Ishii T, Kaneki M, Tsujibayashi T, Sakurai S, Nagakura C, Miyauchi A.
Miyauchi Makoto Memorial Clinic, 9-44 Isumi-cho, Mishima, Shizuoka 411-0037, Japan. ytommy@sage.ocn.ne.jp

BACKGROUND: Pitavastatin has a potent cholesterol-lowering action. The clinical efficacy and safety of a low dose, 1 mg, of pitavastatin were examined. METHODS: The effect of 12 weeks' treatment with pitavastatin 1 mg in an open label, non-randomized trial involving 137 patients with hypercholesterolemia as compared with treatment with atorvastatin 10 mg. RESULTS: Total cholesterol, low-density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride (TG) levels at baseline did not differ between the two groups. At follow-up, there were no significant differences in total cholesterol, LDL cholesterol and HDL cholesterol levels between the groups. The TG levels at follow-up were higher in the pitavastatin group than atorvastatin group (p < 0.01). In patients with hyperlipidemia type IIa, TG levels at follow-up were lower in the atorvastatin subgroup (p < 0.01). However, there was no significant difference in TG levels at follow-up between the two subgroups in patients with hyperlipidemia type IIb. CONCLUSION: Pitavastatin 1 mg daily was safe and efficacious in reducing LDL cholesterol levels as compared with atorvastatin 10 mg daily. Further randomized comparative studies are needed to clarify the effect of a low dose of pitavastatin.

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Cell Mol Life Sci. 2006 Mar 29; [Epub ahead of print]
Biomedicine and diseases: lipid-lowering drugs.
Pahan K.
Section of Neuroscience, Department of Oral Biology, University of Nebraska Medical Center, 40th and Holdrege, Lincoln, Nebraska, 68583, USA, kpahan@unmc.edu.

Although a change in life-style is often the method of first choice for lipid lowering, lipid-lowering drugs, in general, help to control elevated levels of different forms of lipids in patients with hyperlipidemia. While one group of drugs, statins, lowers cholesterol, the other group, fibrates, is known to take care of fatty acids and triglycerides. In addition, other drugs, such as ezetimibe, colesevelam, torcetrapib, avasimibe, implitapide, and niacin are also being considered to manage hyperlipidemia. As lipids are very critical for cardiovascular diseases, these drugs reduce fatal and nonfatal cardiovascular abnormalities in the general population. However, a number of recent studies indicate that apart from their lipidlowering activities, statins and fibrates exhibit multiple functions to modulate intracellular signaling pathways, inhibit inflammation, suppress the production of reactive oxygen species, and modulate T cell activity. Therefore, nowadays, these drugs are being considered as possible therapeutics for several forms of human disorders including cancer, autoimmunity, inflammation, and neurodegeneration. Here I discuss these applications in the light of newly discovered modes of action of these drugs.

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Transplantation. 2006 Mar 15;81(5):804-7.
Ezetimibe in renal transplant patients with hyperlipidemia resistant to HMG-CoA reductase inhibitors.
Langone AJ, Chuang P.
Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA. anthony.langone@vanderbilt.edu

Hyperlipidemia affects the majority of renal transplant patients. Multiple risk factors contribute to elevated serum cholesterol including the use of certain immunosuppressant agents. HMG-Co A reductase inhibitors have become the preferred class of cholesterol-lowering medication with an increasing body of evidence to support their safety, efficacy, and outcomes in both the normal and renal transplant populations. New guidelines recommend lowering previous LDL-c goals as outcomes appears to continually improve. As a result, ezetimibe has been added to patients with persistently elevated triglycerides and/or LDL-c in individuals who possessed a renal transplant and were deemed to be on a maximum safe dose of statin agent. After the addition of ezetimibe, total cholesterol, LDL-c, and triglycerides fell by 21%, 31%, and 13%, respectively. Creatinine phosphokinase, liver enzyme serum levels, and renal function were not affected to any level of clinical significance with the addition of ezetimibe. Large interpatient variability of measurable immunosuppressant levels was seen but no serious adverse events were attributed to a change in levels.

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Med Sci Monit. 2006 Feb;12(2):RA34-9. Epub 2006 Jan 26.
Management of hyperlipidemia: new LDL-C targets for persons at high-risk for cardiovascular events.
Balbisi EA.
Department of Clinical Pharmacy Practice, College Of Pharmacy & Allied Health Professions, St. John's University, New York, NY, USA. balbisie@stjohns.edu
Full article: http://www.medscimonit.com/pub/vol_12/no_2/7811.pdf

Coronary heart disease (CHD) remains the leading cause of mortality in the United States, and is associated with significant health care costs. Current evidence overwhelmingly confirms the role of low-density lipoprotein cholesterol (LDL-C) in the pathogenesis of atherosclerosis and the risk of CHD events. The approach to the management of hyperlipidemia has evolved dramatically over the past decade. Randomized clinical trails have provided strong evidence that lowering plasma cholesterol with statins reduces the risk of cardiovascular events, particularly in high-risk patients, irrespective of baseline cholesterol levels. The National Cholesterol Education Program (NCEP) report was released in July 2004. The report examined the results of recently concluded clinical trials and provided consensus recommendations on the management of hyperlipidemia. The report expands on the core content of the previously published guidelines. However, it is by far the most aggressive approach to date for reducing CHD risk. A focal element of the report is the modification of LDL-C goal in high-risk patients to <70 mg/dL. This goal is provided as a therapeutic option and is based on findings of recently concluded clinical trials. The more aggressive recommendations add challenges to the health care system, as the number of patients requiring drug therapy is likely to increase. In spite of the challenges, there are ample opportunities for improving the management of hyperlipidemia. Adherence to the recommendations will vastly reduce morbidity and mortality associated with CHD.

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Curr Atheroscler Rep. 2006 Jan;8(1):76-84.
Effective use of combination lipid therapy.
Vasudevan AR, Jones PH.
Center for Cardiovascular Disease Prevention, Lipid and Atherosclerosis Section, Baylor College of Medicine, Houston, TX 77030, USA.

Despite the benefits of statin therapy, low-density lipoprotein (LDL) cholesterol management remains suboptimal and many patients do not achieve their recommended target goals. The aim of combination lipid drug therapy in high-risk patients is to achieve LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol goals with a minimum of serious adverse effects. Although statins are the drug of first choice, statin monotherapy may be limited by intolerance of dose escalation or failure to attain non-HDL cholesterol goals in those with mixed hyperlipidemia. Statins plus bile acid resins or ezetimibe can achieve greater than 50% reduction in LDL cholesterol, with little or no increase in adverse effects. Fibrates, niacin, and omega-3 fatty acids, when added to statins, can reduce triglycerides, increase HDL cholesterol, and reduce non-HDL cholesterol to a greater extent than statin monotherapy. The safety profile of combination lipid therapy is acceptable if the global coronary heart disease risk of the patient is high, thus producing a favorable risk to benefit ratio. Careful surveillance of hepatic transaminases, avoidance of gemfibrozil in statin-fibrate combinations, and awareness of statin-concomitant drug interactions is key to safe and efficacious use of combination lipid drug therapy.

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Curr Drug Targets Cardiovasc Haematol Disord. 2005 Dec;5(6):455-62.
Cholesterol absorption blockade with ezetimibe.
Toth PP, Davidson MH.
Director of Preventive Cardiology, Sterling Rock Falls Clinic, Illinois, University of Illnois School of Medicine, Peoria, 61081, USA. peter.toth@srfc.com

The reduction of circulating atherogenic lipoproteins through lifestyle modification and pharmacologic intervention is an important therapeutic goal in patients at risk for acute cardiovascular events. A large number of clinical trials have demonstrated that the reduction of low-density lipoprotein cholesterol (LDL-C) is associated with significant decreases in the incidence of all cause mortality, stroke, fatal and nonfatal myocardial infarction, and the need for revascularization with coronary artery bypass grafting and percutaneous transluminal coronary angioplasty. Therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (i.e., statins) are the agents of choice for treating a variety of dyslipidemias, particularly when LDL-C levels are elevated. The statins are highly efficacious; however, not all patients are able to tolerate the higher doses of these medications due to adverse side-effects such as hepatoxicity and myotoxicity. Moreover, many patients cannot achieve their various lipoprotein targets at even the highest doses of these medications. Ezetimibe is a novel cholesterol absorption inhibitor that blocks the translocation of dietary and biliary cholesterol from the gastrointestinal lumen into the intracellular space of jejunal enterocytes. Ezetimibe undergoes enterohepatic recirculation with minimal systemic exposure and not does not adversely impact the pharmacokinetic profile of statins. Ezetimibe significantly reduces serum LDL-C. It is safe when used as monotherapy or when used in combination with statins. Ezetimibe is indicated in the management of hyperlipidemia, familial hypercholesterolemia, and sitosterolemia and significantly increases the percentage of patients able to reach their lipid-lowering goals.

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J Intern Med. 2006 Jan;259(1):107-16.
Effects of pioglitazone in familial combined hyperlipidaemia.
Abbink EJ, Graaf J, Haan JH, Heerschap A, Stalenhoef AF, Tack CJ.
Division of General Internal Medicine, Department of Medicine, University Medical Centre Nijmegen, Nijmegen, the Netherlands.

Objectives. Familial combined hyperlipidaemia (FCH) is associated with insulin resistance. We hypothesized that pioglitazone treatment of FCH patients might increase insulin sensitivity, but may also improve serum lipid levels, body fat distribution, intramyocellular lipids (IMCL) and endothelial function. Design. Double blind, randomized, cross-over study. Subjects. Seventeen FCH patients. Interventions. Sixteen weeks of pioglitazone treatment (30 mg) compared with 16 weeks of placebo. Main outcome measurements. Insulin sensitivity was measured using the hyperinsulinaemic euglycaemic clamp procedure, body fat distribution and IMCL using magnetic resonance techniques and endothelial function using flow-mediated vasodilatation. Results. Pioglitazone improved insulin sensitivity (M value 37.7 +/- 3.6 mumol min(-1) kg(-1) vs. 33.0 +/- 3.3 mumol min(-1) kg(-1) during placebo, P < 0.05) and LDL composition by increasing the K value (-0.11 +/- 0.06 vs. -0.20 +/- 0.06 during placebo, P < 0.05). However, pioglitazone did not affect other serum lipid levels. Endothelial function, body fat distribution and IMCL were also not affected. In addition, pioglitazone was associated with a decrease in liver enzymes (alkaline phosphatase). Conclusion. Pioglitazone treatment of FCH patients without type 2 diabetes mellitus increases insulin sensitivity, decreases liver enzymes and improves LDL composition but has a neutral effect on total serum lipid levels. The change in insulin sensitivity might be too small to induce changes in endothelial function, body fat distribution and IMCL.

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Int J Clin Pract. 2005 Dec;59(12):1464-71.
Ezetimibe/simvastatin (INEGY) in the treatment of hyperlipidaemia.
Kastelein JJ, Sankatsing RR.
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef, The Netherlands.

Ezetimibe/simvastatin (INEGY), a dual inhibitor of both cholesterol production and absorption, is a new approach to the management of hyperlipidaemia. Recent studies have shown that it produces greater reductions in low-density lipoprotein (LDL) cholesterol than the single inhibition of statin therapy, enabling many more patients to achieve their LDL cholesterol treatment goals. With ezetimibe/simvastatin therapy, reductions of up to 61% from baseline have been seen in LDL cholesterol, with clear improvements in other associated lipid fractions. It has been well tolerated across all studies, with a safety profile similar to that of statin therapy. This article will review clinical experience to date with ezetimibe/simvastatin, commenting upon its place and potential value in the prevention of cardiovascular disease.

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Am J Health Syst Pharm. 2005 Dec 1;62(23):2491-4.
Effects of morning versus evening administration of atorvastatin in patients with hyperlipidemia.
Plakogiannis R, Cohen H, Taft D.
Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University (LIU), 75 DeKalb Avenue, Brooklyn, NY 11201-5497, USA. roda.piakogiannis@liu.edu

PURPOSE: The effects of morning versus evening administration of atorvastatin in hyperlipidemic patients were studied. METHODS: Patients whose care was managed by a teaching hospital run by the Department of Veterans Affairs who were prescribed atorvastatin calcium 40 mg p.o. daily by their primary care physician were interviewed by a clinical pharmacist in the ambulatory care clinic for study enrollment. Patients were excluded if they had diseases or conditions or took medication known to affect serum lipoprotein levels, as were patients who consumed more than three alcoholic drinks per day and those who could not verify the time of atorvastatin administration. Blood samples were collected after a 12-hour fasting period and serum lipoprotein levels were measured at baseline and after four weeks. RESULTS: Of the 204 hyperlipidemic patients receiving atorvastatin, 64 met the inclusion criteria and were enrolled in the study, 32 of whom took the drug in the morning (before noon) and an equal number who took the drug at night (after 6 p.m. but before midnight). All patients were male outpatients with a mean +/- S.D. age of 57.8 +/- 7.8 years and 58.5 +/- 7.8 years for the morning and evening administration groups, respectively. No statistically significant differences in lipid values measured were found between the morning and evening administration group after four weeks. CONCLUSION: Changes in the levels of total cholesterol, low-density-lipoprotein cholesterol, triglycerides, and high-density-lipoprotein cholesterol were similar among hyperlipidemic patients receiving atorvastatin calcium 40 mg, regardless of the time of day the drug was administered.

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Paediatr Drugs. 2005;7(6):391-6.
Pharmacotherapy of hyperlipidemia in pediatric heart transplant recipients : current practice and future directions.
Chin C, Bernstein D.
Division of Pediatric Cardiology, Department of Pediatrics, Stanford University, Stanford, California, USA.

Lipoprotein abnormalities are fairly common after pediatric heart transplantation. Graft coronary artery disease (GCAD) limits long-term survival and has been linked to elevated serum triglyceride levels and decreased high-density lipoprotein levels. Histologically, GCAD represents intimal hyperplasia of the coronary vessel and is best imaged by intravascular ultrasound.A number of pharmacologic agents are available for the management of lipid disorders but experience with these drugs has mainly been in adults. HMG-CoA reductase inhibitors (statins) are currently used by many adult transplantation centers to alter lipid profiles in the hope of reducing GCAD. The use of statins among pediatric heart transplant centers is more limited. Although rhabdomyolysis is a concern with these agents, the incidence among individuals receiving immunosuppressant therapy is low. Aside from their lipid-lowering properties, statins may also protect against graft failure and rejection.

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J Wound Ostomy Continence Nurs. 2005 Nov-Dec;32(6):393-401.
Surgical treatment for obesity: ensuring success.
Andris DA.
Deborah A. Andris, MSN, RN-CS, APNP, Bariatric Surgery Program Coordinator, Medical College of Wisconsin, Department of Surgery.

In the United States, obesity has reached epidemic proportions. Serious medical complications, impaired quality of life, and premature mortality are all associated with obesity. Medical conditions such as type 2 diabetes mellitus, hypertension, hyperlipidemia, or sleep apnea can improve or be cured with weight loss. Medical treatment programs focused on diet, behavior modification, and/or pharmacologic intervention have met with limited long-term success. Although surgical treatments for obesity have become popular in recent years, they should only be used as a last resort for weight loss. Not all patients can be considered appropriate candidates for surgery; therefore, guidelines based on criteria from the National Institutes of Health should be used preoperatively to help identify suitable persons. Most individuals who opt for weight-loss surgery have usually struggled for many years with losing weight and keeping it off, but surgery alone will not ensure successful weight loss. Patient education is imperative for long-term success. Moreover, any such educational regimen should include information on diet, vitamin and mineral supplementation, and lifestyle changes, as well as expected weight-loss results and improvements in comorbid conditions. Patients must be willing to commit to a long-term follow-up program intended to promote successful weight loss and weight maintenance and to prevent metabolic and nutritional complications.

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Eur J Endocrinol. 2005 Nov;153(5):679-86.
Efficacy and safety of Monascus purpureus Went rice in subjects with hyperlipidemia.
Lin CC, Li TC, Lai MM.
Department of Family Medicine, China Medical University Hospital, Taichung 40447, Taiwan.

OBJECTIVE: The purpose of this study was to assess the lipid-lowering effect of Monascus purpureus Went rice on serum lipids in patients with hyperlipidemia, and to assess its safety by reporting adverse events and clinical laboratory measurements. DESIGN AND METHODS: This was a randomized, double-blind, placebo-controlled study. In all, 79 patients (aged 23-65 years) with a mean baseline low-density lipoprotein cholesterol (LDL-C) level of 5.28 mmol/l (203.9 mg/dl) received a twice daily dose of placebo or Monascus purpureus Went rice (600 mg) for 8 weeks. RESULTS: At week 8, Monascus purpureus Went rice therapy reduced LDL-C by 27.7%, total cholesterol by 21.5%, triglycerides by 15.8% and apolipoprotein B by 26.0%. High-density lipoprotein cholesterol and apolipoprotein A-I levels were increased by 0.9 and 3.4% respectively (not significant). No patient in the Monascus purpureus Went rice treatment group had an alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatine phosphokinase (CPK) measurement that was > or = 3 times the upper limit of normal at week 4 and week 8. CONCLUSION: Monascus purpureus Went rice significantly reduced LDL-C, total cholesterol, triglycerides and apolipoprotein B levels, and was well tolerated in patients with hyperlipidemia. However, this study only provides data from an 8-week trial and long-term safety and efficacy data are needed.

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Curr Cardiol Rep. 2005 Nov;7(6):471-9.
Effective use of combination lipid therapy.
Vasudevan AR, Jones PH.
Center for Cardiovascular Disease Prevention, Lipid and Atherosclerosis Section, Baylor College of Medicine, 6565 Fannin, Suite B160A, MS A601, Houston, TX 77030, USA.

Despite the benefits of statin therapy, low-density lipoprotein cholesterol (LDL-C) management remains suboptimal and many patients do not achieve their recommended target goals. The aim of combination lipid drug therapy in high-risk patients is to achieve LDL-C and non-high-density lipoprotein cholesterol (HDL-C) goals with a minimum of serious adverse effects. Although statins are the drug of first choice, statin monotherapy may be limited by intolerance of dose escalation or failure to attain non-HDL-C goals in those with mixed hyperlipidemia. Statins plus bile acid resins or ezetimibe can achieve greater than 50% reduction in LDL-C, with little or no increase in adverse effects. Fibrates, niacin, and omega-3 fatty acids, when added to statins, can reduce triglycerides, increase HDL-C, and reduce non-HDL-C to a greater extent than statin monotherapy. The safety profile of combination lipid therapy is acceptable, if the global coronary heart disease risk of the patient is high, thus producing a favorable risk to benefit ratio. Careful surveillance of hepatic transaminases, avoidance of gemfibrozil in statin-fibrate combinations, and awareness of statin-concomitant drug interactions is key to safe and efficacious use of combination lipid drug therapy.

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Curr Cardiol Rep. 2005 Nov;7(6):445-56.
Treatment of dyslipidemia in children and adolescents.
Holmes KW, Kwiterovich PO Jr.
Divisions of Pediatric Cardiology and Lipid Research Atherosclerosis, Johns Hopkins Medical Institutions, 550 North Broadway, Suite 312, Baltimore, MD 21205, USA.

The early lesions of atherosclerosis begin in childhood, and are related to antecedent cardiovascular disease risk factors. Environmental and genetic factors such as diet, obesity, exercise, and certain inherited dyslipidemias influence the progression of such lesions. The identification of youth at risk for atherosclerosis includes an integrated assessment of these predisposing factors. Treatment starts with a diet low in total and saturated fat and cholesterol, the use of water-soluble fiber and plant sterols, weight control, and exercise. Drug therapy, for example, with inhibitors of hydroxymethylglutaryl CoA reductase, bile acid sequestrants, and cholesterol absorption inhibitors, can be considered in those with a positive family history of premature coronary artery disease and a low-density lipoprotein cholesterol above 160 mg/dL, after dietary and hygienic measures. Candidates for drug therapy often include those with familial hypercholesterolemia, familial combined hyperlipidemia, the metabolic syndrome, polycystic ovarian syndrome, type I diabetes, and the nephrotic syndrome. We review the safety and efficacy of dietary and drug therapy, and propose an updated diagnostic and therapeutic algorithm that includes the metabolic syndrome. The early identification and treatment of youth with dyslipidemias is likely to retard the atherosclerotic process.

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Am Heart Hosp J. 2005 Fall;3(4):256-62.
Lipid-lowering therapy for elderly patients at risk for coronary events and stroke.
Courville KA, Lavie CJ, Milani RV.
Department of Cardiovascular Diseases, Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121, USA.

Hyperlipidemia continues to be a major risk factor for cardiovascular diseases, particularly coronary heart disease, in the elderly population. Despite the fact that hyperlipidemia does not seem to be a major risk factor for stroke, therapy for hyperlipidemia, especially with statins, has clearly been demonstrated to reduce both coronary heart disease events and stroke, with the most convincing data being for the elderly population. Although we review some safety concerns with statin therapy applicable to the elderly, statins alone or with other proved therapies, including fibrates, niacin, and exercise training, have been demonstrated to reduce major cardiovascular diseases, including coronary heart disease and stroke in the elderly. In addition, this therapy can be safely administered to most elderly patients and seems to have either neutral or slightly beneficial effects on dementia. Therefore, aggressive lipid treatment, particularly with statins, is needed in the primary and secondary prevention of cardiovascular diseases in the elderly.

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Cardiol Rev. 2005 Sep-Oct;13(5):247-55.
Nonpharmacologic approaches for the treatment of hyperlipidemia.
Kermani T, Frishman WH.
Department of Medicine, Mayo Clinic/Mayo Clinic School of Medicine, Rochester, Minnesota, USA.

Coronary heart disease (CHD) is the leading cause of death in the United States. Dyslipidemias, like decreased high-density lipoprotein (HDL) and increased low-density lipoprotein (LDL), have been linked through epidemiologic and experimental studies with the development of atherosclerosis and an increased risk of CHD. The introduction of various classes of lipid-lowering drugs, especially the hydroxymethylglutaryl-coenzyme-A-reductase inhibitors (statins), has allowed for effective treatment of hyperlipidemia. This article reviews the following nonpharmacologic approaches to hyperlipidemia: LDL apheresis, surgery, the emergence of HDL as a therapeutic target, gene therapy, and finally, the possibility of developing a vaccine against atherosclerosis.

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Expert Opin Pharmacother. 2005 Sep;6(11):1897-910.
Rosuvastatin: a risk-benefit assessment for intensive lipid lowering.
Ferdinand KC.
College of Pharmacy, Xavier University, New Orleans, LA 70117, USA. kcferdmd@aol.com

Cardiovascular disease is the leading cause of death in the US and other industrialised societies. Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is the most efficacious lipid-lowering agent of the statin class. New guidelines and recent evidence-based studies confirm the benefit of intensive reduction of low-density lipoprotein cholesterol in terms of cardiovascular risk reduction. Both naturally occurring and synthetic statins have demonstrated significant lowering of low-density lipoprotein cholesterol, the primary target of cholesterol-lowering therapy. Rosuvastatin, specifically, is a synthetic statin shown to lower low-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, non-high-density lipoprotein cholesterol and triglycerides, in addition to increasing high-density lipoprotein cholesterol. Compared with other statins, there is a similar low risk of serious muscle damage (myopathy and rhabdomyolysis), and no consistent pattern of renal failure or renal injury, despite mild transient tubular proteinuria, as seen with all statins. Therefore, rosuvastatin offers an effective alternative in the clinical management of hyperlipidaemia, while awaiting the results of ongoing cardiovascular risk reduction trials.

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J Heart Lung Transplant. 2005 Aug;24(8):1008-13.
Safety and efficacy of rosuvastatin therapy for the prevention of hyperlipidemia in adult cardiac transplant recipients.
Samman A, Imai C, Straatman L, Frolich J, Humphries K, Ignaszewski A.
Department of Cardiology, St. Paul's Hospital, Vancouver, British Columbia, Canada. sammanahmad@hotmail.com

BACKGROUND: Hyperlipidemia after orthotopic heart transplantation (OHT) is associated with immunosuppression. Many OHT patients have increased lipid levels above published guidelines despite treatment with high doses of statins. Treatment with rosuvastatin (ROS) in OHT patients has not yet been evaluated. Therefore, we assessed its efficacy and safety in an OHT population. METHODS: Twenty-one OHT recipients, median age 66 years, whose lipid levels were sub-optimal on the highest tolerated doses of statins, received ROS in addition to standard immunosuppression. Total cholesterol (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), liver transaminases (AST) and creatinine kinase (CK) were measured before and during treatment with ROS. RESULTS: After 6 weeks on an average ROS dose of 10 mg/day, a TC:HDL-C ratio of <4 was reached in 76% of patients, and 70% of patients reached an LDL-C level of <2.5 mmol/liter (100 mg/dl). TC decreased to <5.2 mmol/liter (200 mg/dl) in 80% of patients and TG decreased to <2 mmol/liter (175 mg/dl) in 61% of patients. Except for the HDL-C increase, all changes were statistically significant. The decrease in the median TC:HDL-C ratio between baseline and 6 weeks was also statistically significant (p = 0.001). There were no significant changes in CK or AST levels, and no clinical evidence of myositis. One patient developed myalgia and 2 were withdrawn from the study because of mild elevation of CK (<3-fold upper limit of normal [ULN]). CONCLUSIONS: In the setting of tertiary referral centers, ROS appears to be safe and effective in lowering LDL-C in OHT recipients in whom treatment with other statins failed to achieve target LDL-C. No evidence of liver or muscle dysfunction was noted. Long-term studies are needed to ascertain the effect of ROS therapy on incidence of coronary artery disease (CAD) in this population.

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Br J Cancer. 2005 Aug;93 Suppl 1:S23-7.
The effects of aromatase inhibitors on lipids and thrombosis.
Bundred NJ.
South Manchester University Hospital, Academic Surgery, Education and Research Centre, Southmoor Road, Manchester M23 9LT, UK. Nigel.J.Bundred@manchester.ac.uk

Oestrogen is known to influence blood lipid levels and though its cardioprotective effects are less clear than once thought, there remains concern that reduction of oestrogen levels during hormonal treatment for breast cancer may have an adverse effect on cardiovascular risk. While tamoxifen has been shown to improve lipid profiles, the aromatase inhibitors have a very different mode of action and do not possess the oestrogen-agonistic effects of tamoxifen. At present, there are few data on the effects of these agents on lipid profiles. Available data are mixed, but suggest that the different aromatase inhibitors have different effects on lipid profiles. Some studies show anastrozole as generally having little effect on lipids, while others have indicated adverse effects on lipid profiles/increased hypercholesterolaemia. Letrozole has been associated with adverse effects on lipid profiles in some studies, including BIG 1-98, but short-term data from randomised trials do not show increased cardiovascular morbidity. By contrast, exemestane, which has been studied in slightly more detail, may either have little effect or may be associated with slightly improved lipid profiles. In general, the changes have been small and are likely to be of little relevance in women with advanced breast cancer, but if these agents come to be used in early breast cancer, their impact on lipid profiles may become more important. Many studies are currently underway with the aromatase inhibitors, with safety assessments including monitoring lipid levels. The results of these studies are keenly awaited.

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J Intern Med. 2005 Aug;258(2):94-114.
Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review.
Carlson LA.
King Gustaf V Research Institute, Karolinska Institutet, Stockholm, Sweden. lars.a.carlson@bredband.net

Nicotinic acid has, like the Roman God Janus, two faces. One is the vitamin. The other is the broad-spectrum lipid drug. The Canadian pathologist Rudolf Altschul discovered 50 years ago that nicotinic acid in gram doses lowered plasma levels of cholesterol. From the point of view of treatment of the dyslipidaemias that are risk factors for clinical atherosclerosis nicotinic acid is a miracle drug. It lowers the levels of all atherogenic lipoproteins--VLDL and LDL with subclasses as well as Lp(a)--and in addition it raises more than any other drug the levels of the protective HDL lipoproteins. Trials have shown that treatment with nicotinic acid reduces progression of atherosclerosis, and clinical events and mortality from coronary heart disease. The new combination treatment with statin-lowering LDL and nicotinic acid-raising HDL is reviewed. A basic effect of nicotinic acid is the inhibition of fat-mobilizing lipolysis in adipose tissue leading to a lowering of plasma free fatty acids, which has many metabolic implications which are reviewed. The very recent discovery of a nicotinic acid receptor and the finding that the drug stimulates the expression of the ABCA 1 membrane cholesterol transporter have paved the way for exciting and promising new 50 years in the history of nicotinic acid.

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Am Fam Physician. 2005 Jul 1;72(1):103-6.
Health effects of garlic.
Tattelman E.
Department of Family and Social Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10467, USA. etattelm@montefiore.org

Garlic has long been used medicinally, most recently for its cardiovascular, antineoplastic, and antimicrobial properties. Sulfur compounds, including allicin, appear to be the active components in the root bulb of the garlic plant. Studies show significant but modest lipid-lowering effects and antiplatelet activity. Significant blood pressure reduction is not consistently noted. There is some evidence for antineoplastic activity and insufficient evidence for clinical antimicrobial activity. Side effects generally are mild and uncommon. Garlic appears to have no effect on drug metabolism, but patients taking anticoagulants should be cautious. It seems prudent to stop taking high dosages of garlic seven to 10 days before surgery because garlic can prolong bleeding time.

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Expert Opin Biol Ther. 2005 Jul;5(7):907-17.
Antisense oligonucleotides as therapeutics for hyperlipidaemias.
Crooke RM.
Isis Pharmaceuticals, Inc., 1896 Rutherford Avenue, Carlsbad, CA 92008, USA. rcrooke@isisph.com

Hyperlipidaemia, due to elevations of low-density lipoprotein cholesterol (LDL-C) or triglycerides (TGs), is recognised as a significant risk factor contributing to the development of coronary heart disease (CHD), the leading cause of morbidity and mortality in the Western world. Even though a variety of established antihyperlipidaemic agents are available, the majority of high-risk patients do not reach their lipid goals, indicating the need for new and more effective therapeutics to be used alone or as combination agents with existing drugs. Antisense oligonucleotides (ASOs), designed to specifically and selectively inhibit novel targets involved in cholesterol/TG homeostasis, represent a new class of agents that may prove beneficial for the treatment of hyperlipidaemias resulting from various genetic, metabolic or behavioural factors. This article describes the antisense technology platform, highlights the advantages of these novel drugs for the treatment of hyperlipidaemia and reviews the current research in this area.

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Curr Med Res Opin. 2005 Jul;21(7):1123-30.
Lipid altering-efficacy of ezetimibe co-administered with simvastatin compared with rosuvastatin: a meta-analysis of pooled data from 14 clinical trials.
Catapano A, Brady WE, King TR, Palmisano J.
Marie Curie Training Centre for Cardiovascular Diseases, Milan, Italy. Alberico.Carapano@unimi.it

OBJECTIVE: Results of direct comparative studies between ezetimibe/simvastatin and rosuvastatin therapies have not been reported. Both of these treatment options offer significant reductions in LDL-C. To evaluate the lipid efficacy of each of these therapies relative to each other, a meta-analysis of data from 14 randomized, double-blind clinical trials that compared the effectiveness of two new options for cholesterol lowering was performed. DATA SOURCES: PubMed, EMBASE and BIOSIS databases were searched up to March 14, 2004. METHODS OF STUDY SELECTION: Efficacy results from clinical trials with the co-administration of ezetimibe 10 mg with simvastatin or with the ezetimibe/simvastatin combination product (ezetimibe/simvastatin 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg) were compared with efficacy results from clinical trials of rosuvastatin 5 mg, 10 mg, 20 mg, and 40 mg in patients with primary hypercholesterolemia. Trials in healthy patients, heterozygous familial hypercholesterolemia or combined hyperlipidemia, and pharmacokinetic trials were excluded. DATA EXTRACTION AND SYNTHESIS: This analysis used pooled data for LDL-C, HDL-C, non-HDL-C, triglycerides, total cholesterol, apolipoprotein (apo) A-I, and apo B for the two therapies at their lowest doses (ezetimibe/simvastatin 10/10 mg and rosuvastatin 5 mg) through their highest doses (ezetimibe/simvastatin 10/80 mg and rosuvastatin 40 mg), and estimated within-treatment percentage changes in these parameters. Percentage reductions from baseline in LDL-C for the pooled data were 46.2% and 41.8% for ezetimibe/simvastatin 10/10 mg and rosuvastatin 5 mg, respectively; 50.6% and 47.4% for ezetimibe/simvastatin 10/20 mg and rosuvastatin 10 mg, respectively; 55.9% and 52.1% for ezetimibe/simvastatin 10/40 mg and rosuvastatin 20 mg, respectively; and 59.7% and 58.5% for ezetimibe/simvastatin 10/80 mg and rosuvastatin 40 mg, respectively. CONCLUSIONS: The results of this meta-analysis suggest greater LDL-C lowering with ezetimibe/simvastatin compared with rosuvastatin. These results need to be confirmed in a head-to-head comparison of both therapies.

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Eur Rev Med Pharmacol Sci. 2005 May-Jun;9(3):141-9.
The diagnosis and management of familial hypercholesterolaemia.
Marais AD, Firth JC.
Lipidology Division of Internal Medicine & MRC Cape Heart Group, Groote Schuur Hospital and University of Cape Town Health Science Faculty, Cape Town, South Africa.

Familial hypercholesterolaemia is a clinical entity comprising high concentrations of low density lipoproteins, tendinous deposition of cholesterol in a large proportion of affected subjects, and a propensity for the development of atherosclerosis and its complications in the coronary arteries. The aim of this review is to integrate publications with clinical experience into a concise profile of the disorder and its management. In less than a century this disease has been recognised, its lipoprotein derangement identified and numerous causal mutations have been detected. Although the phenotype is most commonly due to the occurrence of mutations in the low density lipoprotein receptor, defects in the apolipoprotein B100 may result in a similar phenotype. The same phenotype has also been linked to a gene and its product, PCSK9 and NARC1, that may be involved in the regulation of cholesterol in the cell. In the past few decades statins, by inhibiting cholesterol synthesis at the rate-limiting enzyme (hydroxymethylglutaryl coenzyme A reductase) have been developed and proven safe and effective in reducing the low density lipoprotein cholesterol, promoting regression and reducing mortality and morbidity. Additionally, advances in imaging techniques are allowing non-invasive insights into the impact of the disease on atherosclerosis. For these reasons there should be a high index of suspicion for this treatable condition in which genetic therapy and further modulation of atherosclerosis can be expected in the future.

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Nippon Rinsho. 2005 Jun;63(6):1061-6.
[Management of elderly hypertensive individuals with hyperlipidemia]
[Article in Japanese]
Kozaki K.
Department of Geriatric Medicine, Kyorin University School of Medicine.

Elderly people with hypertension and hyperlipidemia are regarded as high-risk patients and are supposed to be treated with appropriate drugs. From the evidence of clinical trials, renin-angiotensin system inhibitors and calcium channel blockers would be the first choices, and the combination therapy with diuretics or alpha-blockers would be the next choice. However, since the effect of anti-hypertensive drugs on plasma lipids is much less than that of the lipid-lowering drugs, anti-hypertensive drugs should be chosen in consideration of the patient's complicated diseases, because elderly people are often affected with other more serious complications such as ischemic heart disease, cerebrovascular disease, renal dysfunction, and chronic lung disease. If hyperlipidemia remains after anti-hypertensive drugs are used, the use of lipid-lowering drugs such as statins is recommended.

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Arch Intern Med. 2005 May 23;165(10):1161-6.
Effect of combining psyllium fiber with simvastatin in lowering cholesterol.
Moreyra AE, Wilson AC, Koraym A.
Division of Cardiology Lipid Disorder Center, Department of Medicine, Robert Wood Johnson Medical School, University of Medicine & Dentistry of New Jersey, New Brunswick, USA. abel.moreyra@rwjuh.edu

BACKGROUND: Soluble fiber supplements are recommended to reduce levels of low-density lipoprotein cholesterol (LDL-C). We evaluated the LDL-C-lowering effect of psyllium husk added to low-dose simvastatin therapy. METHODS: In a 12-week blinded placebo-controlled study, patients were randomized to receive 20 mg of simvastatin plus placebo, 10 mg of simvastatin plus placebo, or 10 mg of simvastatin plus 15 g of psyllium (Metamucil) daily. Levels of total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were determined after 4 and 8 weeks of treatment. RESULTS: The study group comprised 68 patients. All treatments were well tolerated, and after 8 weeks the mean LDL-C levels in the group receiving 10 mg of simvastatin plus placebo fell by 55 mg/dL (1.42 mmol/L) from baseline, compared with 63 mg/dL (1.63 mmol/L) in the group receiving 10 mg of simvastatin plus psyllium (P = .03). The mean lowering of LDL-C in the group receiving 20 mg of simvastatin plus placebo was the same as that in the group receiving 10 mg of simvastatin plus psyllium. Similar results were seen for apolipoprotein B and total cholesterol. No significant changes from baseline triglyceride or high-density lipoprotein cholesterol levels occurred. CONCLUSIONS: Dietary psyllium supplementation in patients taking 10 mg of simvastatin is as effective in lowering cholesterol as 20 mg of simvastatin alone. Psyllium soluble fiber should be considered as a safe and well-tolerated dietary supplement option to enhance LDL-C and apolipoprotein B lowering.

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Ann Intern Med. 2005 May 3;142(9):725-33.
The effect of a plant-based diet on plasma lipids in hypercholesterolemic adults: a randomized trial.
Gardner CD, Coulston A, Chatterjee L, Rigby A, Spiller G, Farquhar JW.
Stanford University Medical School and Stanford University Medical Center, Stanford, California, USA. cgardner@stanford.edu

BACKGROUND: A variety of food combinations can be used to meet national U.S. guidelines for obtaining 30% of energy or less from total fat and 10% of energy or less from saturated fat. OBJECTIVE: To contrast plasma lipid responses to 2 low-fat diet patterns. DESIGN: Randomized clinical trial. SETTING: 4-week outpatient feeding study with weight held constant. PARTICIPANTS: 120 adults 30 to 65 years of age with prestudy low-density lipoprotein (LDL) cholesterol concentrations of 3.3 to 4.8 mmol/L (130 to 190 mg/dL), body mass index less than 31 kg/m2, estimated dietary saturated fat at least 10% of calories, and otherwise general good health. MEASUREMENTS: Plasma lipid levels. INTERVENTION: Two diets, the Low-Fat diet and the Low-Fat Plus diet, designed to be identical in total fat, saturated fat, protein, carbohydrate, and cholesterol content, consistent with former American Heart Association Step I guidelines. The Low-Fat diet was relatively typical of a low-fat U.S. diet. The Low-Fat Plus diet incorporated considerably more vegetables, legumes, and whole grains, consistent with the 2000 American Heart Association revised guidelines. RESULTS: Four-week changes in the Low-Fat and Low-Fat Plus groups were -0.24 mmol/L (-9.2 mg/dL) versus -0.46 mmol/L (-17.6 mg/dL) for total cholesterol (P = 0.01) and -0.18 mmol/L (-7.0 mg/dL) versus -0.36 mmol/L (-13.8 mg/dL) for LDL cholesterol (P = 0.02); between-group differences were -0.22 mmol/L (-9 mg/dL) (95% CI, -0.05 to -0.39 mmol/L [-2 to -15 mg/dL]) and -0.18 mmol/L (-7 mg/dL) (CI, -0.04 to -0.32 mmol/L [-2 to -12 mg/dL]) for total and LDL cholesterol, respectively. The 2 diet groups did not differ significantly in high-density lipoprotein cholesterol and triglyceride levels. LIMITATIONS: 4-week duration. CONCLUSIONS: Previous national dietary guidelines primarily emphasized avoiding saturated fat and cholesterol; as a result, the guidelines probably underestimated the potential LDL cholesterol-lowering effect of diet. In this study, emphasis on including nutrient-dense plant-based foods, consistent with recently revised national guidelines, increased the total and LDL cholesterol-lowering effect of a low-fat diet.

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Tokai J Exp Clin Med. 2005 Apr;30(1):63-9.
Effect of anticholesterol therapy on soluble ICAM-1 in chronic stroke patients with hyperlipidemia.
Tomiyasu H, Ishikawa K, Yamamoto M, Hata T, Ohta T, Kitagawa Y, Shinohara Y.
Department of Internal Medicine, Tokai University School of Medicine, Boseidai, Isehara, Kanagawa 259-1193, Japan.

OBJECTIVE: We examined the effects of drug therapy with pravastatin (P) or bezafibrate (B) and diet (D) therapy on serum lipids and soluble intercellular adhesion molecule-1 (sICAM-1) in hyperlipidemic cerebrovascular disease (CVD) patients in the chronic stage. METHODS: This study included 36 patients (28 with cerebral infarction and hyperlipidemia and eight with cerebral hemorrhage and hyperlipidemia) divided into three groups: Group P (12 patients), Group B (10 patients), and Group D (14 patients). Before and after treatment, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and sICAM-1 levels were measured. RESULTS: In Group P, Group B and Group D, TC levels were decreased by 30% (p < 0.005), 21% (p < 0.01), and 21% (p < 0.001), LDL-C levels were decreased by 38% (p < 0.005), 18% (not significant), and 25% (p < 0.005) and TG levels were decreased by 27% (p < 0.05), 53% (p < 0.005) and 22% (p < 0.05), respectively. sICAM-1 levels were decreased by 20% (p < 0.005) in Group P, but were not decreased in Group B or Group D. There was no correlation between deltaTC and delta sICAM-1 (r = 0.172). CONCLUSION: Administration of pravastatin significantly reduced sICAM-1 levels, independently of its decreasing effect on TC and TG in chronic CVD patients. Pravastatin may exert anti-atherosclerotic activity via two distinct mechanisms.

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Essent Psychopharmacol. 2005;6(3):148-57.
Atypical antipsychotic therapy and hyperlipidemia: a review.
Koro CE, Meyer JM.
GlaxoSmithKline, Upper Providence, Pennsylvania, USA.

Ziprasidone (Geodon), risperidone (Risperdal), and aripiprazole (Abilify) appear to be associated with a relatively low risk for hyperlipidemia, whereas quetiapine (Seroquel), olanzapine (Zyprexa), and clozapine (Clozaril) are associated with a relatively high risk for hyperlipidemia. Possible underlying causes of lipid dysregulation include weight gain, dietary changes, and glucose intolerance. Given the multiple cardiovascular risk factors reported for patients with schizophrenia, great care must be exercised to minimize the additional risk for hyperlipidemia when choosing antipsychotic therapy. It is recommended that a lipid panel be obtained at baseline for all patients with schizophrenia and annually thereafter for patients taking relatively low-risk agents or quarterly thereafter for patients taking relatively high-risk agents. Patients with persistent dyslipidemia should be referred for lipid-lowering therapy or switched to a less lipid-enhancing antipsychotic agent.

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Med Klin (Munich). 2005 Apr 15;100(4):186-92.
[Niacin--an additive therapeutic approach for optimizing lipid profile]
[Article in German]
Wieneke H, Schmermund A, Erbel R.
Klinik fur Kardiologie, Universitat Duisburg-Essen, Hufelandstrasse 55, 45122 Essen. heinrich.wieneke@uni-essen.de

BACKGROUND: Large interventional studies have shown that the reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C) is one of the cornerstones in the prevention of coronary artery disease. However, in up to 40% of patients the recommended target of LDL-C is not reached with a monotherapy. Furthermore, risk stratification only by LDL-C disregards a substantial number of patients with dyslipidemia with increased triglycerides and decreased high-density lipoprotein cholesterol (HDL-C). EFFECT OF NIACIN ON LIPID METABOLISM: In consequence, niacin has gained attention as a component of a combined therapeutic approach in patients with dyslipidemia. Niacin substantially increases HDL-C and decreases triglycerides, LDL-C and lipoprotein (a). By this mechanism of action niacin exhibited, in combination with statins or bile acid-binding resins, favorable effects on the incidence of cardiovascular events in selected patients. Side effects like flush and hepatotoxicity seem to be in part dependent on the niacin formulations used. However, niacin has been shown to be a well-tolerated and safe therapy in controlled studies. CONCLUSION: On the basis of current data niacin should be considered a valuable therapy component in patients with dyslipidemia, in which a monotherapy fails to optimize an increased risk of coronary artery disease.

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Curr Med Res Opin. 2005;21 Suppl 1:S29-40.
Diabetic dyslipidaemia: insights for optimizing patient management.
Verges B.
Service Endocrinologie-Diabetologie et Maladies Metaboliques, Hopital du Bocage, Dijon, France. bruno.verges@chu-dijon.fr

BACKGROUND: Lipid abnormalities in people with diabetes are likely to play an important role in the development of atherogenesis. These lipid disorders include potentially atherogenic quantitative (increased triglyceride levels and decreased high-density lipoprotein-cholesterol [HDL-C] levels) and qualitative abnormalities of lipoproteins (changes in lipoprotein size, increase in triglyceride content of low-density lipoprotein (LDL) and HDL, glycation of apoproteins and increased susceptibility of LDL to oxidation). Guidelines from the two main diabetes organizations, the International Diabetes Federation and the American Diabetes Association, recommend the aggressive management of diabetic dyslipidaemia to reduce the risk of cardiovascular disease (CVD). Statins are the first choice pharmacological therapy to address diabetic dyslipidaemia due to their effectiveness at lowering LDL-C levels in patients with diabetes. Fibrates (peroxisome proliferator-activated receptor [PPAR]alpha ligands) target another aspect of dyslipidaemia by lower ing triglycerides (to a greater extent than statins) and raising HDL-C levels, especially when baseline levels are low. The PPARgamma agonist, pioglitazone appears to affect lipid metabolism by decreasing plasma triglycerides, increasing HDL-C and decreasing the number of small, dense atherogenic LDL particles. SCOPE: This paper provides a review of the current literature (based on searches of MEDLINE and EMBASE from 1985 to 2005, inclusive) supporting the recommendations for the management of dyslipidaemia among patients with type 2 diabetes, including new strategies involving drug combinations that achieve good glycaemic and lipidaemic control that could potentially reduce the morbidity and mortality associated with type 2 diabetes.

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Am J Cardiol. 2005 Apr 1;95(7):869-71.
Effect of docosahexaenoic acid on lipoprotein subclasses in hyperlipidemic children (the EARLY study).
Engler MM, Engler MB, Malloy MJ, Paul SM, Kulkarni KR, Mietus-Snyder ML.
University of California at San Francisco, San Francisco, California.

To test the hypothesis that a dietary omega-3 fatty acid, docosahexaenoic acid, improves the lipoprotein subclass profile of children who have hyperlipidemia, we conducted a randomized, double-blind, placebo-controlled study. Children who had hyperlipidemia (n = 20) were stabilized on a low-fat diet for 6 weeks and then randomized to receive 1.2 g/day of docosahexaenoic acid for 6 weeks or placebo. Supplementation with docosahexaenoic acid significantly increased low-density lipoprotein subclass 1 and high-density lipoprotein subclass 2 (large and buoyant; less atherogenic particles) by 91% and 14%, respectively, compared with the placebo phase. Low-density lipoprotein subclass 3 (small and dense; more atherogenic particles) decreased by 48%.

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Eur Heart J. 2005 Mar 21; [Epub ahead of print]
Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia.
Farnier M, Freeman MW, Macdonell G, Perevozskaya I, Davies MJ, Mitchel YB, Gumbiner B.
Point Medical, Rond Point de la Nation, Dijon F-21 000, France.

AIMS: To examine the efficacy and safety of coadministered ezetimibe (EZE) with fenofibrate (FENO) in patients with mixed hyperlipidaemia. METHODS AND RESULTS: This was a multicentre, randomized, double-blind, placebo-controlled, parallel arm trial in patients with mixed hyperlipidaemia [LDL-cholesterol (LDL-C), 3.4-5.7 mmol/L (2.6-4.7 mmol/L for patients with type 2 diabetes); triglycerides (TG), 2.3-5.7 mmol/L] and no history of coronary heart disease (CHD), CHD-equivalent disease (except for type 2 diabetes), or CHD risk score >20%. A total of 625 patients was randomized in a 1 : 3 : 3 : 3 ratio to one of four daily treatments for 12 weeks: placebo; EZE 10 mg; FENO 160 mg; FENO 160 mg plus EZE 10 mg (FENO + EZE). The primary endpoint compared the LDL-C lowering efficacy of FENO + EZE vs. FENO alone. LDL-C, non-HDL-cholesterol (non-HDL-C), and apolipoprotein B were significantly (P < 0.001) reduced with FENO + EZE when compared with FENO or EZE alone. TG levels were significantly decreased and HDL-C was significantly increased with FENO + EZE and FENO treatments when compared with placebo (P < 0.001). Coadministration therapy reduced LDL-C by 20.4%, non-HDL-C by 30.4%, TG by 44.0%, and increased HDL-C by 19.0%. At baseline, >70% of all patients exhibited the small, dense LDL pattern B profile. A greater proportion of patients on FENO + EZE and FENO alone treatments shifted from a more atherogenic LDL size pattern to a larger, more buoyant, and less atherogenic LDL size pattern at study endpoint than those on placebo or EZE. All three active therapies were well tolerated. CONCLUSION: Coadministration of EZE with FENO provided a complementary efficacy therapy that improves the atherogenic lipid profile of patients with mixed hyperlipidaemia.

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Med J Aust. 2005 Mar 21;182(6):286-289.
Lipid-modifying drugs.
Simons LA, Sullivan DR.
Lipid Research Department, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia. L.Simons@notes.med.unsw.edu.au.

An elevated concentration of low-density-lipoprotein cholesterol (LDL-C) plays a causal role in the development of coronary heart disease and ischaemic stroke. Placebo-controlled intervention studies of statin drugs for lowering LDL-C provide clear evidence of cardiovascular disease prevention. LDL-C concentration below 2.5 mmol/L is an arbitrary goal, and recent trials support the benefit of achieving this goal, or even lower levels. Pharmacological treatment is warranted in patients with high absolute risk of future cardiovascular events. Effective monotherapy is available for predominant hypercholesterolaemia and predominant hypertriglyceridaemia, but combination therapy may be required for severe cases or in those with mixed hyperlipidaemia. Side-effects are infrequent and usually mild, but widespread use of lipid-modifying medication demands caution because of the possibility of muscle or liver dysfunction or drug interactions.

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Pharmacotherapy. 2005 Feb;25(2):171-83.
Meta-analysis of natural therapies for hyperlipidemia: plant sterols and stanols versus policosanol.
Chen JT, Wesley R, Shamburek RD, Pucino F, Csako G.
School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907-2091, USA. jtchen@pharmacy.purdue.edu

STUDY OBJECTIVE: To compare the efficacy and safety of plant sterols and stanols as well as policosanol in the treatment of coronary heart disease, as measured by a reduction in low-density lipoprotein cholesterol (LDL) levels. DESIGN: Systematic review and meta-analysis of randomized controlled trials. PATIENTS: A total of 4596 patients from 52 eligible studies. MEASUREMENTS AND MAIN RESULTS: We searched MEDLINE, EMBASE, the Web of Science, and the Cochrane Library from January 1967-June 2003 to identify pertinent studies. Reduction of LDL levels was the primary end point; effects on other lipid parameters and withdrawal of study patients due to adverse effects were the secondary end points. Weighted estimates of percent change in LDL were -11.0% for plant sterol and stanol esters 3.4 g/day (range 2-9 g/day [893 patients]) versus -2.3% for placebo (769 patients) in 23 eligible studies, compared with -23.7% for policosanol 12 mg/day (range 5-40 mg/day [1528 patients]) versus -0.11% for placebo (1406 patients) in 29 eligible studies. Cumulative p values were significantly different from placebo for both (p<0.0001). The net LDL reduction in the treatment groups minus that in the placebo groups was greater with policosanol than plant sterols and stanols (-24% versus -10%, p<0.0001). Policosanol also affected total cholesterol, high-density lipoprotein cholesterol (HDL), and triglyceride levels more favorably than plant sterols and stanols. Policosanol caused a clinically significant decrease in the LDL:HDL ratio. Pooled withdrawal rate due to adverse effects and combined relative risk for patients who withdrew were 0% and 0.84, respectively (95% confidence interval [CI] 0.36-1.95, p=0.69), for plant sterols and stanols across 20 studies versus 0.86% and 0.31, respectively (95% CI 0.20-0.48, p<0.0001), for policosanol across 28 studies. CONCLUSION: Plant sterols and stanols and policosanol are well tolerated and safe; however, policosanol is more effective than plant sterols and stanols for LDL level reduction and more favorably alters the lipid profile, approaching antilipemic drug efficacy.

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Am J Clin Nutr. 2005 Feb;81(2):380-7.
Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants.
Jenkins DJ, Kendall CW, Marchie A, Faulkner DA, Wong JM, de Souza R, Emam A, Parker TL, Vidgen E, Trautwein EA, Lapsley KG, Josse RG, Leiter LA, Singer W, Connelly PW.
Clinical Nutrition and Risk Factor Modification Center, St Michael's Hospital, Toronto, Canada. cyril.kendall@utoronto.ca

BACKGROUND: 3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce serum cholesterol and are increasingly advocated in primary prevention to achieve reductions in LDL cholesterol. Newer dietary approaches combining cholesterol-lowering foods may offer another option, but these approaches have not been compared directly with statins in the same persons. OBJECTIVE: The objective was to compare, in the same subjects, the cholesterol-lowering potential of a dietary portfolio with that of a statin. DESIGN: Thirty-four hyperlipidemic participants underwent all three 1-mo treatments in random order as outpatients: a very-low-saturated-fat diet (control diet), the same diet plus 20 mg lovastatin (statin diet), and a diet high in plant sterols (1.0 g/1000 kcal), soy-protein foods (including soy milks and soy burgers, 21.4 g/1000 kcal), almonds (14 g/1000 kcal), and viscous fibers from oats, barley, psyllium, and the vegetables okra and eggplant (10 g/1000 kcal) (portfolio diets). Fasting blood samples were obtained at 0, 2, and 4 wk. RESULTS: LDL-cholesterol concentrations decreased by 8.5+/-1.9%, 33.3+/-1.9%, and 29.6+/-1.3% after 4 wk of the control, statin, and portfolio diets, respectively. Although the absolute difference between the statin and the portfolio treatments was significant at 4 wk (P=0.013), 9 participants (26%) achieved their lowest LDL-cholesterol concentrations with the portfolio diet. Moreover, the statin (n=27) and the portfolio (n=24) diets did not differ significantly (P=0.288) in their ability to reduce LDL cholesterol below the 3.4-mmol/L primary prevention cutoff. CONCLUSIONS: Dietary combinations may not differ in potency from first-generation statins in achieving current lipid goals for primary prevention. They may, therefore, bridge the treatment gap between current therapeutic diets and newer statins.

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Am J Cardiol. 2005 Feb 15;95(4):462-8.
Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI trial).
Grundy SM, Vega GL, Yuan Z, Battisti WP, Brady WE, Palmisano J.
UT Southwestern Medical Center, Dallas, Texas, USA. scott.grundy@UTsouthwestern.edu

Patients with combined hyperlipidemia (elevated triglyceride [TG] levels, elevated low-density lipoprotein [LDL] cholesterol, and multiple lipoprotein abnormalities) are at increased risk for coronary heart disease. We conducted a multicenter (in the United States), randomized, double-blind, active-controlled, 18-week study to determine if combination therapy with simvastatin plus fenofibrate is more effective in reducing elevated TG levels, thus improving the lipoprotein pattern in patients with combined hyperlipidemia compared with simvastatin monotherapy, and to evaluate safety and tolerability. Patients (aged 21 to 68 years) with a diagnosis of combined hyperlipidemia (fasting TG levels >/=150 and </=500 mg/dl, and LDL cholesterol >130 mg/dl) received simvastatin monotherapy (20 mg/day, n = 207) or simvastatin 20 mg plus fenofibrate (160 mg/day) combination therapy (n = 411) for 12 weeks following a 6-week diet and placebo run-in period. From baseline to week 12, median TG levels decreased 43.0% (combination therapy) and 20.1% (simvastatin monotherapy [treatment difference -23.6%, p <0.001]). Mean LDL cholesterol levels decreased 31.2% and 25.8% (treatment difference -5.4%, p <0.001), and high-density lipoprotein cholesterol levels increased 18.6% and 9.7% (treatment difference 8.8%, p <0.001) in the combination therapy versus monotherapy groups, respectively. No drug-related serious adverse experiences were observed. No patient experienced clinical myopathy or severe abnormalities in liver function. Combination therapy with simvastatin 20 mg and fenofibrate 160 mg in patients with combined hyperlipidemia resulted in additional improvement in all lipoprotein parameters measured compared with simvastatin 20 mg monotherapy and was well tolerated. Thus, this combination therapy is a beneficial therapeutic option for managing combined hyperlipidemia.

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Expert Opin Pharmacother. 2005 Jan;6(1):131-9.
Simvastatin plus ezetimibe: combination therapy for the management of dyslipidaemia.
Toth PP, Davidson MH.
Sterling Rock Falls Clinic, Sterling, Illinois, USA. peter.toth@srfc.com.

Hyperlipidaemia is a pivotal risk factor for the development of atherosclerotic disease. A large number of studies have demonstrated that the treatment of abnormalities in lipoprotein levels reduces the risk for myocardial infarction, peripheral vascular disease, carotid artery disease, stroke, and cardiovascular mortality. Despite the development of multiple drug classes to treat dyslipidaemias and the promulgation of clearly defined guidelines for the management of lipid disorders, dyslipidaemia tends to be undertreated in the majority of patients at risk for cardiovascular disease. A part of the reluctance to treat different lipoprotein fractions to goal levels is attributable to physician- and patient-related concerns over the increasing toxicity of available therapies, as their dosages are increased. The risks of hepatotoxicity, myalgia, and rhabdo-myolysis are fairly well characterised in patients receiving statins, fibrates and niacin. Another issue affecting treatment success rates is the fact that many patients with complex dyslipidaemias are inadequately responsive to single-agent therapy. As the epidemics of obesity, metabolic syndrome and diabetes mellitus continue to worsen, physicians will encounter severe, mixed dyslipidaemias more frequently. Many of these patients will require combinations of drugs to address the various metabolic derangements causing changes in multiple lipoprotein fractions. Although the need for combination therapy is well-established in the management of disorders, such as hypertension and diabetes, it is less often used for the treatment of dyslipidaemias. The development of safe, cost-effective, and efficacious combination dyslipidaemic therapy is an important goal in cardiovascular medicine. Simvastatin plus ezetimibe has recently been combined as a fixed dose therapy, which offers clinicians the opportunity to simultaneously inhibit two key pathways in cholesterol metabo-lism: hepatic cholesterol biosynthesis and the absorption of cholesterol at the level of the proximal jejunum. This dual mechanism of inhibition substantially increases the capacity to decrease serum levels of atherogenic low-density lipoproteins and increase high-density lipoprotein, compared with that observed when either drug is used alone. This combination increases the like-lihood of therapeutic success in patients with dyslipidaemia.

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Drugs. 2004;64 Suppl 2:19-41.
Lipaemia, inflammation and atherosclerosis: novel opportunities in the understanding and treatment of atherosclerosis.
van Oostrom AJ, van Wijk J, Cabezas MC.
Departments of Internal Medicine and Endocrinology, University Medical Centre Utrecht, The Netherlands.

Atherosclerosis is the major cause of death in the world. Fasting and postprandial hyperlipidaemia are important risk factors for coronary heart disease (CHD). Recent developments have undoubtedly indicated that inflammation is pathophysiologically closely linked to atherogenesis and its clinical consequences. Inflammatory markers such as C-reactive protein (CRP), leucocyte count and complement component 3 (C3) have been linked to CHD and to hyperlipidaemia and several other CHD risk factors. Increases in these markers may result from activation of endothelial cells (CRP, leucocytes, C3), disturbances in adipose tissue fatty acid metabolism (CRP, C3), or from direct effects of CHD risk factors (leucocytes). It has been shown that lipoproteins, triglycerides, fatty acids and glucose can activate endothelial cells, most probably as a result of the production of reactive oxygen species. Similar mechanisms may also lead to leucocyte activation. Increases in triglycerides, fatty acids and glucose are common disturbances in the metabolic syndrome and are most prominent in the postprandial phase. People are in a postprandial state most of the day, and this phase is proatherogenic. Inhibition of the activation of leucocytes, endothelial cells, or both, is an interesting target for intervention, as activation is obligatory for adherence of leucocytes to the endothelium, thereby initiating atherogenesis. Potential interventions include the use of unsaturated long-chain fatty acids, polyphenols, antioxidants, angiotensin converting enzyme inhibitors and high-dose aspirin, which have direct anti-inflammatory and antiatherogenic effects. Furthermore, peroxisome proliferator activating receptor gamma (PPARgamma) agonists and statins have similar properties, which are in part independent of their lipid-lowering effects.

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Arch Cardiol Mex. 2004 Oct-Dec;74(4):315-26.
[Dyslipidemia in the elderly]
[Article in Spanish]
Lasses y Ojeda LA, Gutierrez JL, Salazar E.
Servicio de Cardiologia Geriatrica, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico. dr.lasses@salud.gob.mx

Age is an independent and unmodifiable risk factor for coronary atherosclerosis. In Mexico, coronary heart disease is responsible for 50 % of the deaths for those older than 65 years of age. Aging produces major differences in the presentation, diagnosis, prognosis, and response to therapy in coronary heart disease. The goal of treatment is the prolongation of survival and the improvement of the quality of life. However, in the elderly, the aim of therapy should focus on attaining a meaningful quality of life thus allowing them to be functionally independent. Clinical trials demonstrate conclusively that lowering serum cholesterol levels will reduce the incidence of coronary heart disease irrespective of age. Dietary advise and life-style modifications are the first-line approach in the elderly. When these measures are insufficient to achieve target lipid reductions, statins are the drug of choice. Fibrates may be indicated if triglycerides are high and C-HDL is low. Given the grater coronary risk of older population, the absolute benefit will be greater in the elderly.

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Int J Cardiol. 2004 Dec;97(3):355-66.
Optimal management of hyperlipidemia in primary prevention of cardiovascular disease.
Raza JA, Babb JD, Movahed A.
Department of Medicine, Section of Cardiology, The Brody School of Medicine, East Carolina University, Greenville, NC 27834-4354, USA.

Cardiovascular disease (CVD) in the developed countries continues to grow at an epidemic proportion. There are a significant number of young adults with no clinical evidence of CVD, but who have two or more risk factors that predispose them to CV events and death. Many of these risk factors are modifiable, and by controlling these factors, the CVD burden can be decreased significantly. Recent statistics have shown that, if all major forms of CVD were eliminated, the life expectancy would rise by almost 7 years. Hence it is imperative that primary prevention efforts should be initiated at a young age to avert decades of unattended risk factors. Hyperlipidemia has been linked to CVD almost a century ago. Since then various clinical trials have not only supported this link, but have also shown the CV benefits in aggressively treating patients with hyperlipidemia. In this generation, we have various therapeutic agents that are capable of reducing the elevated lipid levels. With drugs like statins, we are able to reduce the risk of CVD by about 30% and avoid major adverse events. Newer drugs are being researched and introduced in the treatment of hyperlipidemia in humans. These can be used in combination therapy resulting in optimal levels of lipids. The new National Cholesterol Education Program (NCEP)/Adult Treatment Panel III (ATP III) guidelines have come as a wake-up call to clinicians about primary prevention of CVD through strict lipid management and multifaceted risk management approach in the prevention of CVD.

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Ann Pharmacother. 2004 Nov;38(11):1789-93. Epub 2004 Oct 12.
Comparing hyperlipidemia control with daily versus twice-weekly simvastatin.
Mangin EF, Robles GI, Jones WN, Ford MA, Thomson SP.
Southern Arizona Veterans Affairs HealthCare System, University of Arizona Center for Health Outcomes & Pharmaco-Economic Research, Tucson, AZ, USA.

BACKGROUND: Costs associated with the use of hydroxymethylglutaryl coenzyme A reductase inhibitors are increasing. Finding ways to manage hyperlipidemia at lower costs is critical to all healthcare systems. OBJECTIVE: To assess effectiveness, safety, cost, and patients' satisfaction when converting hyperlipemic patients taking simvastatin daily to simvastatin twice weekly. METHODS: This nonrandomized, open-label, proof-of-concept study converted patients treated with simvastatin 10 or 20 mg daily to 40 or 80 mg twice weekly, respectively, for 12 weeks. The lipid profiles at enrollment, week 6, and week 12 were compared using repeated-measures ANOVA. The percentage of patients attaining the appropriate low-density lipoprotein cholesterol (LDL-C) goal was determined. RESULTS: Thirty-one patients completed the study. The proportion of patients at the LDL-C goal was not statistically different between enrollment and week 12 (87% vs 68%; p = 0.068). The mean LDL-C value +/- SD at weeks 6 and 12 increased compared with enrollment (112 +/-20, 111 +/-17, and 97 +/- 17 mg/dL, respectively; p < 0.001). Three (10%) patients reported nonadherence to the twice-weekly regimen. Seventeen (55%) patients reported that both regimens were equally convenient or preferred the twice-weekly regimen. Estimated cost-savings at our institution associated with this regimen would be $32 000 per 1000 patients per year. CONCLUSIONS: The twice-weekly regimen safely maintained most of the patients at their LDL-C goal level, and over half the patients found this regimen to be the same or easier to follow than a daily regimen. Large outcome studies evaluating this approach are needed.

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Prev Cardiol. 2004 Fall;7(4):176-81.
Rosuvastatin alone or with extended-release niacin: a new therapeutic option for patients with combined hyperlipidemia.
Capuzzi DM, Morgan JM, Carey CM, Intenzo C, Tulenko T, Kearney D, Walker K, Cressman MD.
Department of Medicine, Cardiovascular Disease Prevention Center, Jefferson Heart Institute, Thomas Jefferson University, 925 Chestnut Street, 1st Floor, Philadelphia, PA 19107, USA. david.capuzzi@jefferson.edu

Combination therapy with a statin and niacin may provide optimal therapy for patients with combined hyperlipidemia and low levels of high-density lipoprotein (HDL) cholesterol. The authors assessed the efficacy and safety of rosuvastatin monotherapy, extended-release (ER) niacin monotherapy, or rosuvastatin and ER niacin combined therapy in patients with atherogenic dyslipidemia. In a 24-week, open-label, multicenter trial, men and women aged > or =18 years with fasting levels of total cholesterol > or =200 mg/dL, HDL cholesterol > or =45 mg/dL, triglycerides 200-800 mg/dL, and apolipoprotein B > or =110 mg/dL were randomly assigned to one of four treatment groups: rosuvastatin 10-40 mg, ER niacin 0.5-2 g, rosuvastatin 40 mg plus ER niacin 0.5-1 g, or rosuvastatin 10 mg plus ER niacin 0.5-2 g. Daily doses of rosuvastatin 40 mg monotherapy reduced low-density lipoprotein (LDL) cholesterol and non-HDL cholesterol levels significantly more than did either ER niacin 2 g monotherapy or rosuvastatin 10 mg combined with ER niacin 2 g. Addition of ER niacin 1 g to rosuvastatin 40 mg did not further reduce total or non-HDL cholesterol. Triglyceride reductions were similar among the four treatment groups. ER niacin mono- and combined therapy produced significantly greater rises in HDL cholesterol and apolipoprotein A-1 than did rosuvastatin monotherapy. Rosuvastatin monotherapy was better tolerated than ER niacin taken either alone or with rosuvastatin. In this study, rosuvastatin very effectively improved the three major lipoprotein-lipid abnormalities of combined hyperlipidemia.

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JAMA. 2004 Oct 13;292(14):1724-37.
Bariatric surgery: a systematic review and meta-analysis.
Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, Schoelles K.
Department of Surgery, University of Minnesota, Minneapolis 55455, USA. buchw001@umn.edu

CONTEXT: About 5% of the US population is morbidly obese. This disease remains largely refractory to diet and drug therapy, but generally responds well to bariatric surgery. OBJECTIVE: To determine the impact of bariatric surgery on weight loss, operative mortality outcome, and 4 obesity comorbidities (diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea). DATA SOURCES AND STUDY SELECTION: Electronic literature search of MEDLINE, Current Contents, and the Cochrane Library databases plus manual reference checks of all articles on bariatric surgery published in the English language between 1990 and 2003. Two levels of screening were used on 2738 citations. DATA EXTRACTION: A total of 136 fully extracted studies, which included 91 overlapping patient populations (kin studies), were included for a total of 22,094 patients. Nineteen percent of the patients were men and 72.6% were women, with a mean age of 39 years (range, 16-64 years). Sex was not reported for 1537 patients (8%). The baseline mean body mass index for 16 944 patients was 46.9 (range, 32.3-68.8). DATA SYNTHESIS: A random effects model was used in the meta-analysis. The mean (95% confidence interval) percentage of excess weight loss was 61.2% (58.1%-64.4%) for all patients; 47.5% (40.7%-54.2%) for patients who underwent gastric banding; 61.6% (56.7%-66.5%), gastric bypass; 68.2% (61.5%-74.8%), gastroplasty; and 70.1% (66.3%-73.9%), biliopancreatic diversion or duodenal switch. Operative mortality (< or =30 days) in the extracted studies was 0.1% for the purely restrictive procedures, 0.5% for gastric bypass, and 1.1% for biliopancreatic diversion or duodenal switch. Diabetes was completely resolved in 76.8% of patients and resolved or improved in 86.0%. Hyperlipidemia improved in 70% or more of patients. Hypertension was resolved in 61.7% of patients and resolved or improved in 78.5%. Obstructive sleep apnea was resolved in 85.7% of patients and was resolved or improved in 83.6% of patients. CONCLUSIONS: Effective weight loss was achieved in morbidly obese patients after undergoing bariatric surgery. A substantial majority of patients with diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete resolution or improvement.

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Prescrire Int. 2004 Oct;13(73):176-9.
Ezetimibe: new preparation. A cholesterol-lowering drug with no clinical advantage.
[No authors listed]

(1) Simvastatin and pravastatin are the drugs of choice for secondary or primary prevention of cardiovascular events in patients with hypercholesterolaemia. Both these statins have proven clinical efficacy. If statin therapy is inadequate, the dose can be increased or a drug combination can be tried, while keeping a lookout for adverse effects. (2) Ezetimibe is a cholesterol-lowering drug that is said to inhibit intestinal absorption of cholesterol and related phytosterols, while not affecting the uptake of other nutrients (unlike resins). (3) The clinical evaluation dossier contains no data from trials with relevant morbidity or mortality endpoints. Primary and secondary prevention were not studied separately. (4) In patients with hypercholesterolaemia, two placebo-controlled trials show that ezetimibe reduces total cholesterol concentration (by about 13%), and LDL-cholesterol (by about 18%). Its effects on HDL-cholesterol and triglyceride levels are at best moderate. It is not known whether these effects reduce mortality or prevent cardiovascular events. (5) Four trials tested initial combination therapy with a statin plus ezetimibe, in comparison with statin alone and ezetimibe alone. They showed an additive effect of the two drugs on LDL-cholesterol levels. Ezetimibe alone was no better than statin monotherapy. (6) A trial in patients who did not respond adequately to statin monotherapy showed that adding ezetimibe increased the number of patients whose LDL cholesterol level fell to a predetermined cutoff point. But the clinical relevance of this result is unknown. Two other trials have shown that, in this setting, adding ezetimibe to simvastatin or to atorvastatin increased the number of patients who reached the LDL-cholesterol cutoff relative to continued statin monotherapy at a higher dose. (7) In homozygous familial hypercholesterolaemia, high-dose statin and ezetimibe combination therapy reduced the LDL-cholesterol more effectively than high-dose statin alone. It is not known whether adding ezetimibe is more effective than LDL apheresis alone. (8) In homozygous familial sitosterolaemia, a very rare disorder due to increased absorption of dietary cholesterol and phytosterols, a placebo-controlled trial showed that ezetimibe had no significant impact on the absolute sitosterol value. (9) Comparative trials reported no major adverse effects associated with ezetimibe, but their duration (maximum three months) is too short to rule out long-term adverse effects. Initial pharmacovigilance reports cases of muscular and hepatic adverse effects. (10) In practice, ezetimibe has discernible effects in the laboratory. But the absence of data based on clinical endpoints and trials versus other cholesterol-lowering drugs with proven clinical benefits, together with the lack of information on possible long-term adverse effects, means ezetimibe must be evaluated more thoroughly before it can be recommended for routine use.

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Clin Ther. 2004 Sep;26(9):1368-87.
Rosuvastatin in the management of hyperlipidemia.
Cheng JW.
Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, New York, USA. judy.cheng@liu.edu

BACKGROUND: Rosuvastatin is a new statin indicated to reduce elevated levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides and to increase levels of high-density lipoprotein cholesterol (HDL-C) in patients with primary hypercholesterolemia, mixed dyslipidemia, and homozygous familial hypercholesterolemia. OBJECTIVE: The purpose of this article was to review the pharmacology, clinical efficacy, and tolerability of rosuvastatin as monotherapy and combination therapy for patients with hyperlipidemia. METHODS: A literature review was conducted using the search term rosuvastatin to identify English-language peer-reviewed articles and abstracts in the MEDLINE and Current Contents databases (both 1966 to March 2004). Citations from available articles were reviewed for additional references, and selected information from the manufacturer was discussed. RESULTS: Rosuvastatin 10 to 40 mg/d reduced LDL-C by 43% to 63% (P < 0.05). Compared with other statins, rosuvastatin had the highest dose-to-dose potency in lowering LDL-C (reduction of 60% vs 50% with atorvastatin, 40% with simvastatin, 30% with pravastatin or lovastatin, and 20% with fluvastatin) and better efficacy in raising HDL-C (increase of approximately 10% vs approximately 5% with other statins; P < 0.05). Rosuvastatin enabled significantly more patients to achieve the National Cholesterol Education Program (NCEP) goals for LDL-C with lower doses (P < 0.05). Rosuvastatin was well tolerated. Incidences of myopathy and liver function test abnormalities were rare and comparable to those of other statins. Because it is not metabolized by the cytochrome P-450 enzymes, rosuvastatin had fewer clinically significant drug interactions compared with other statins. Studies to assess the effect of rosuvastatin on cardiovascular outcomes are ongoing. CONCLUSIONS: Clinical studies continue to demonstrate that achieving optimal levels of LDL-C is an important goal in reducing cardiovascular events. Recent evidence suggests the need for an even lower LDL-C goal than that being recommended by the NCEP Based on the studies included in this review, rosuvastatin may help patients achieve optimal goals early with lower dosages, thus reducing the need for dose titration or combination therapy.

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Transplant Proc. 2004 Sep;36(7):2141-4.
Impact of fluvastatin on hyperlipidemia after renal transplantation.
Tokumoto T, Tanabe K, Ishida H, Shimmura H, Ishikawa N, Goya N, Akiba T, Toma H.
Department of Urology, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan. tokumoto@kc.twmu.ac.jp

BACKGROUND: Renal transplant recipients are at increased risk of atherosclerotic vascular disease with hyperlipidemia. Many recipients have preexisting cardiovascular disease at the time of transplantation, and immunosuppressive therapy may aggravate existing risk factors or promote development of new risk factors, notably hyperlipidemia and hypertension. Fluvastatin is one of the statins, an HMG-CoA reductase inhibitor, which has been shown to be effective in lowering cholesterol levels. We treated hyperlipidemia after renal transplantation with Fluvastatin for more than 6 months.We attempted to clarify the efficacy of fluvastatin on hyperlipidemia in renal transplant recipients. MATERIALS: Forty-five renal transplant recipients with hyperlipidemia were enrolled in this study. The mean age was 44.2 years, with 23 men and 22 women. Thirty-seven transplantations were from a living related donors and eight from cadaveric donors. Thirty-three recipients were ABO-compatible, seven recipients had minor mismatches, and five recipients were ABO-incompatible. The dose of fluvastatin was 20 mg per day. Levels of total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), serum creatinine (s-Cr), ALT, ALP, uric acid (UA), hematocrit (Ht), CPK, and blood pressure were examined in all recipients before treatment as well as 1, 3, and 6 months after Fluvastatin administration. RESULTS: The mean levels of TC and TG were significantly reduced from 256, to 224 and 215 mg/dL, and from 188 to 170 and 147 mg/dL at 1 and 6 months after treatment, respectively. The mean levels of HDL-C were 72 mg/dL before treatment, 81 mg/dL at 1 month, and 80 mg/dL at 6 months after treatment. The mean levels of LDL-C were 153 mg/dL before treatment, 145 mg/dL at 1 month, and 145 mg/dL at 6 months after treatment. Fluvastatin significantly produced a reduction rate in TC of 16%, TG of 22%, and LDL-C of 5% after 6 months of treatment, respectively. The mean levels of HDL-C of were increased 10% after 6 months of treatment. The serum creatinine and CPK were not significantly different. There were no clinically significant differences in other factors. No significant adverse effects were observed. CONCLUSIONS: Fluvastatin seemed to be safe and highly effective to control TC, TG, LDL-C, and HDL-C in renal transplant recipients.

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Curr Treat Options Cardiovasc Med. 2004 Oct;6(5):431-437.
Management of Hyperlipidemia in the Pediatric Population.
Tonstad S, Thompson GR.
Department of Preventive Cardiology, Preventive Medicine Clinic, Ulleval University Hospital, Oslo N-0407, Norway. serena.tonstad@uus.no

Heterozygous familial hypercholesterolemia (FH) affects one in every 500 persons and is the most common cause of markedly elevated cholesterol levels in children. Other causes of primary hyperlipidemia include familial combined hyperlipidemia, which is also common (approximately 1%) but not usually manifest until after puberty, and very rare genetic disorders that may lead to severe hypertriglyceridemia and chylomicronemia syndrome. In children with heterozygous FH, the short-term risk of clinical events is low; therefore, management starts with stratification of risk, followed by dietary modification, and in high-risk cases, pharmacologic treatment initiated after puberty. Male gender, a family history of premature coronary heart disease, and level of low-density lipoprotein (LDL) cholesterol above 4.9 mmol/L are important determinants of risk. Trials have shown that statins effectively lower LDL cholesterol levels; in one study, statins restored endothelial function, with no clinically adverse effects. The effects of statins for longer than 2 years have not been studied. The use of bile acid sequestrants (resins) is limited by compliance and side effects. Children with homozygous FH require expert management with LDL apheresis, high doses of effective statins, and cardiologic follow-up. Ezetimibe, the first in a new class of cholesterol absorption inhibitors, may provide additional efficacy in homozygous FH.

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J Am Board Fam Pract. 2004 Sep-Oct;17(5):359-69.
Diagnosis and treatment of obesity in adults: an applied evidence-based review.
Orzano AJ, Scott JG.
Department of Family Medicine, Robert Wood Johnson Medical School, Somerset, NJ.

BACKGROUND: Obesity is epidemic and leads to substantial morbidity/mortality. Effective strategies exist for managing obesity yet are rarely used by physicians. This applied evidence-based review provides a rationale for the diagnosis and treatment of obesity in adults by providing test characteristics for the body mass index (BMI) and number needed to treat (NNT) for relevant treatments. METHODS: We integrated evidence supporting recommendations from scientific bodies addressing obesity in adults, including: the National Heart, Lung, and Blood Institute, the World Health Organization, the Canadian Task Force on Preventive Health Care, and the US Preventive Task Force. In addition, pertinent studies were identified from MEDLINE, Database of Abstracts of Reviews of Effectiveness, and the Cochrane Database. RESULTS: (1) manage obesity as a chronic relapsing disease; (2) use BMI as a vital sign to screen for overweight/obese patients and to decide treatment (positive predictive value of 97%); (3) modest weight loss (10%) positively affects prevention/treatment of hypertension (NNT = 3), diabetes (NNT = 9), and hyperlipidemia; (4) effective treatments exist for overweight/obese patients and a combination of diet and exercise provides the best results (NNT = 7); (5) counsel patients to achieve a goal of 10% reduction in weight (500 to 800 kcal/day decrease to affect 1- to 2-pound loss/week); (6) counsel patients to exercise to achieve a goal of any increased energy expenditure. CONCLUSIONS: Weight loss has an impact on important disease states and risk factors. Effective strategies exist for the management of obesity when viewed as a chronic relapsing disease.

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Eur J Pharmacol. 2004 Aug 2;496(1-3):205-12.
Treatment of type IIb familial combined hyperlipidemia with the combination pravastatin-piperazine sultosilate.
Masana L, Villoria J, Sust M, Ros E, Plana N, Perez-Jimenez F, Franco M, Olivan JJ, Pinto X, Videla S.
School of Medicine, Rovira i Virgili University, Reus, Spain.

The risk of coronary heart disease is increased for any given low-density lipoprotein (LDL) cholesterol level in patients with high levels of triglycerides because some triglyceride-rich lipoproteins are atherogenic. This paper reports the results of a pilot clinical trial aimed to evaluate a novel triglyceride-lowering drug in combination with pravastatin to treat combined hyperlipidemia. Twenty-six patients with type 2b hyperlipoproteinemia were randomized to receive pravastatin 40 mg/day or pravastatin 40 mg/day plus piperazine-sultosilate 1000 mg/day for 12 weeks if their cholesterol levels, but not triglyceride levels, had responded to therapeutic lifestyle changes and treatment with 40 mg/day of pravastatin. Concentrations of triglycerides, cholesterol and apolipoproteins A and B were measured in duplicate before and after the intervention. There were no significant differences between groups in the change from baseline in the concentration of serum triglycerides. Conversely, significant differences were found for LDL cholesterol, which increased slightly with pravastatin alone but decreased with the combination (12.605+/-22.777% vs. -6.396+/-13.157%, respectively; p=0.022). Apolipoprotein-B levels increased with pravastatin alone but remained stable with the combined treatment (10.464+/-8.446% vs. 0.767+/-12.335%; P=0.028). The increase in the pravastatin group was significant. Although sultosilate was not efficacious in reducing triglycerides, it helped to decrease the concentration of small, dense, atherogenic LDL particles that are less receptor-sensitive and which could accumulate during long-term statin therapy in patients with high levels of triglycerides.

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Am J Cardiol. 2004 Aug 15;94(4):497-500.
Lipid-altering changes and pleiotropic effects of atorvastatin in patients with hypercholesterolemia.
Sakabe K, Fukuda N, Wakayama K, Nada T, Shinohara H, Tamura Y.
Department of Cardiology and Clinical Research, National Zentsuji Hospital, 2-1-1 Senyu-cho, Zentsuji, Kagawa 765-8507, Japan. ksakabe@jun.ncvc.go.jp

In this prospective study, we found beneficial short-term effects from atorvastatin therapy, including effects on low-density lipoprotein subfractions and remnant-like lipoprotein particle cholesterol, antioxidant effects, and alterations in endothelial function that may be important in early benefit from statin therapy; some effects would support much earlier benefit than previously reported. We also found long-term effects of atorvastatin, including decreased plasminogen activator inhibitor type-1 and additional significant alterations in low-density lipoprotein subfractions and endothelial function, supporting benefits from continuous long-term atorvastatin therapy beyond early reversal of hypercholesterolemia.

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Nutr Hosp. 2004 Jul-Aug;19(4):195-201.
[Interactions between foodstuffs and statins]
[Article in Spanish]
de Andres S, Lucena A, de Juana P.
Servicio de Farmacia, Hospital Severo Ochoa, Leganes. eduperedaca2@mi.madritel.es

The existence of interactions between different drugs or between drugs and the diet is becoming better and better known. Statins are medicines currently in widespread use for the treatment of hyperlipidaemias. Diet has a great influence on the prevention and/or treatment of these pathologies as the therapeutic strategy used comprises appropriate diet and, if this does not succeed, pharmacological therapy is begun in combination with dietary advice. For this reason it is necessary to be aware of the potential interactions between this kind of medication and foodstuffs in order to avoid alterations in the therapeutic benefits and even the onset of adverse side effects. All of the statins are absorbed orally, so the impact of food intake on administration is extremely important to achieve an appropriate therapeutic effect. Many of the interactions of statins lie in their metabolism through cytochrome P-450 (except for pravastatin), thus making them candidates for interaction with certain foodstuffs or compounds contained in them, such as in the case of grapefruit juice. This paper reviews the drug-nutrient interactions with special attention to the interactions specific to statins and the mechanism of these interactions is described so as to contribute to their avoidance and thus improve this form of treatment in individuals with hyperlipidaemia.

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Am Heart J. 2004 Jul;148(1 Suppl):S9-13.
Statins as the cornerstone of drug therapy for dyslipidemia: monotherapy and combination therapy options.
Jones PH.
Baylor College of Medicine, Houston, Tex 77030, USA. jones@bcm.tmc.edu

Low-density lipoprotein (LDL) cholesterol reduction with statin treatment remains the cornerstone of lipid-lowering therapy to reduce risk of coronary heart disease. Combination therapy with a statin poses advantages in certain settings and may allow use of lower doses of multiple drugs rather than maximum doses of a single drug. Bile-acid sequestrants or the cholesterol-absorption inhibitor ezetimibe can be added to a statin to achieve greater LDL cholesterol reductions. Niacin or fenofibrate can be added to a statin for treatment of mixed dyslipidemia. Differences in statin efficacy in reducing LDL cholesterol and meeting recommended LDL cholesterol targets as well as differences among these agents in beneficial effects on other lipid parameters can affect whether and how these agents are prescribed in monotherapy and combination therapy.

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JAMA. 2004 Jul 21;292(3):331-7.
Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial.
Wiegman A, Hutten BA, de Groot E, Rodenburg J, Bakker HD, Buller HR, Sijbrands EJ, Kastelein JJ.
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

CONTEXT: Children with familial hypercholesterolemia have endothelial dysfunction and increased carotid intima-media thickness (IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention therapy in the causal pathway of this disorder has been available for more than a decade, the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children. OBJECTIVE: To determine the 2-year efficacy and safety of pravastatin therapy in children with familial hypercholesterolemia. DESIGN: Randomized, double-blind, placebo-controlled trial that recruited children between December 7, 1997, and October 4, 1999, and followed them up for 2 years. SETTING AND PARTICIPANTS: Two hundred fourteen children with familial hypercholesterolemia, aged 8 to 18 years and recruited from an academic medical referral center in the Netherlands. INTERVENTION: After initiation of a fat-restricted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n = 106), or a placebo tablet (n = 108). MAIN OUTCOME MEASURES: The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 years; the principal safety outcomes were growth, maturation, and hormone level measurements over 2 years as well as changes in muscle and liver enzyme levels. RESULTS: Compared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean [SD], -0.010 [0.048] mm; P =.049), whereas a trend toward progression was observed in the placebo group (mean [SD], +0.005 [0.044] mm; P =.28). The mean (SD) change in IMT compared between the 2 groups (0.014 [0.046] mm) was significant (P =.02). Also, pravastatin significantly reduced mean low-density lipoprotein cholesterol levels compared with placebo (-24.1% vs +0.3%, respectively; P<.001). No differences were observed for growth, muscle or liver enzymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups. CONCLUSION: Two years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.

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Kardiol Pol. 2004 Jun;60(6):567-77.
Comparison of combined statin-fibrate treatment to monotherapy in patients with mixed hyperlipidemia.
[Article in English, Polish]
Klosiewicz-Latoszek L, Szostak WB, Grzybowska B, Bialobrzeska-Paluszkiewicz J, Wisniewska B, Stolarska I.
National Food and Nutrition Institute, Warsaw, Poland.

BACKGROUND: Statins are the preferred drugs for the treatment of hypercholesterolemia, and fibrates for hypertriglyceridemia. In patients with mixed hyperlipidemia, monotherapy with one of these agents may not be effective and combined treatment may be preferable. AIM: To compare retrospectively the efficacy and safety of combined statin-fibrate treatment in patients with mixed hyperlipidemia in whom previous montherapy with one of these agents occurred ineffective. METHODS AND RESULTS: The initial study group consisted of 327 patients who received micronised fenofibrate and 93 patients who received simvastatin for 12 months. Both agents caused significant changes in lipid profile. Following fibrate therapy, total cholesterol (TC), LDL-cholesterol (LDL-C) and triglyceride (TG) levels decreased by 27.9%, 28.2% and 58%, respectively, and following simvastatin therapy by 33.6%, 42.8% and 37.5%, respectively. The HDL-cholesterol (HDL-C) level increased after fenofibrate by 14.8% and remained unchanged following simvastatin therapy. The TC/HDL-C ratio decreased following fenofibrate by 35.6%, and following simvastatin by 35.3%. In some patients the required reduction in lipid parameters was not achieved fenofibrate or simvastatin. Subsequently, 93 patients underwent combined therapy by adding a second agent (simvastatin in a dose of 20 mg/day or fenofibrate in a dose of 200 mg per day) which was continued for another 12 months. The addition of simvastatin to fenofibrate decreased TC, LDL-C and TG levels by 35.5%, 42.1% and 59.6%, respectively in comparison to before treatment volumes. HDL-C level was increased by 11.1%, and TC/HDL-C ratio decreased by 45.3%. The addition of fenofibrate to simvastatin decreased TC, LDL-C and TG levels by 39.3%, 48.9% and 51,6%, respectively. HDL-C level was increased by 13.4%, and TC/HDL-C ratio decreased by 49.3%. No clinical side effects nor an increase in the transaminase levels, requiring termination of the treatment, were observed. CONCLUSIONS: Combined therapy with 20 mg of simvastatin and 200 mg of micronised fenofibrate is highly effective and safe in patients with mixed hyperlipidemia.

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Orthop Nurs. 2004 May-Jun;23(3):184-9.
An ounce of prevention. Drugs used to treat hyperlipidemia (Part 2).
Turkoski B.
Kent State University College of Nursing, Kent, OH, USA.

For more than a century, coronary heart disease (CHD) has been the number one cause of death in the United States. Today, we know that although treatment of CHD may reduce some of those deaths, it is the prevention that is the real answer to eliminating this national scourge. The key to prevention lies in identifying those persons who are at risk for developing CHD and reducing the primary risk factor--hyperlipidemia. Preventing or controlling hyperlipidemia involves therapeutic lifestyle changes (TLC) and antilipidemic medications. In part 1, two useful medications--niacin and fibric acid derivatives--were discussed; in this second section, three other classes of drugs used as antilipidemics--bile-acid binding resins, the newer intestinal sterol absorption inhibitors and HMG-CoA reductase inhibitors (the statins)--are reviewed. Knowledgeable nurses will be able to help educate patients about these drugs and their importance in preventing or controlling hyperlipidemia.

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Tidsskr Nor Laegeforen. 2004 Apr 22;124(8):1085-1087.
[LDL apheresis in severe hypercholesterolaemia.]
[Article in Norwegian]
Graesdal A, Hovland A, Bjorbaek E.
Lipidklinikken Nordlandssykehuset asg3@hotmail.com

BACKGROUND:Hypercholesterolaemia is usually successfully treated with statins but in some cases the medication has insufficient cholesterol-lowering effect or is not well tolerated. In these instances LDL apheresis is an option. MATERIAL AND METHODS:We share some of our own experience with this treatment and then review the literature regarding LDL apheresis. RESULTS:LDL apheresis seems a safe and effective way of lowering LDL cholesterol. Mortality and morbidity is reduced in selected patient groups. Quite probably, too few Norwegian patients are offered this treatment. INTERPRETATION:LDL apheresis should be available in all health regions of Norway and the treatment should be known to all those who treat severe hypercholesterolaemia or coronary artery disease.

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Arch Intern Med. 2004 Apr 26;164(8):863-70.
Seasonal variation in serum cholesterol levels: treatment implications and possible mechanisms.
Ockene IS, Chiriboga DE, Stanek EJ 3rd, Harmatz MG, Nicolosi R, Saperia G, Well AD, Freedson P, Merriam PA, Reed G, Ma Y, Matthews CE, Hebert JR.
Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA. Ira.Ockene@umassmed.edu

BACKGROUND: A variety of studies have noted seasonal variation in blood lipid levels. Although the mechanism for this phenomenon is not clear, such variation could result in larger numbers of people being diagnosed as having hypercholesterolemia during the winter. METHODS: We conducted a longitudinal study of seasonal variation in lipid levels in 517 healthy volunteers from a health maintenance organization serving central Massachusetts. Data collected during a 12-month period for each individual included baseline demographics and quarterly anthropometric, blood lipid, dietary, physical activity, light exposure, and behavioral information. Data were analyzed using sinusoidal regression modeling techniques. RESULTS: The average total cholesterol level was 222 mg/dL (5.75 mmol/L) in men and 213 mg/dL (5.52 mmol/L) in women. Amplitude of seasonal variation was 3.9 mg/dL (0.10 mmol/L) in men, with a peak in December, and 5.4 mg/dL (0.14 mmol/L) in women, with a peak in January. Seasonal amplitude was greater in hypercholesterolemic participants. Seasonal changes in plasma volume explained a substantial proportion of the observed variation. Overall, 22% more participants had total cholesterol levels of 240 mg/dL or greater (> or =6.22 mmol/L) in the winter than in the summer. CONCLUSIONS: This study confirms seasonal variation in blood lipid levels and suggests greater amplitude in seasonal variability in women and hypercholesterolemic individuals, with changes in plasma volume accounting for much of the variation. A relative plasma hypervolemia during the summer seems to be linked to increases in temperature and/or physical activity. These findings have implications for lipid screening guidelines. Further research is needed to better understand the effects of a relative winter hemoconcentration.

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Am J Cardiol. 2004 Mar 15;93(6):779-80.
Initial low-density lipoprotein response to statin therapy predicts subsequent low-density lipoprotein response to the addition of ezetimibe.
Ziajka PE, Reis M, Kreul S, King H.
The Florida Lipid Institute, Orlando, Florida 32806, USA.

This small retrospective study confirms the hypothesis that patients who are hyporesponders to statin therapy are hyper-responders to ezetimibe therapy and may help identify a patient population in whom ezetimibe would be particularly effective in lowering low-density lipoprotein cholesterol.

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Am J Med. 2004 Mar 15;116(6):408-16.
Current overview of statin-induced myopathy.
Rosenson RS.
Preventive Cardiology Center, Northwestern University, The Feinberg School of Medicine, Chicago, Illinois 60611, USA. r-rosenson@northwestern.edu

Statins are an efficacious and well-tolerated class of lipid-altering agents that have been shown to reduce the risk of initial and recurrent cardiovascular events. However, cerivastatin was withdrawn from the world market because of its potential for severe myotoxic effects. Since the benefits of statin treatment outweigh the small risk of adverse events, statins remain the first-line therapy for lipid lowering and preventing atherosclerotic cardiovascular diseases. The risk of myopathy may be minimized with the appropriate choice of agent and by identifying patients at risk of myotoxic effects. Elderly or female patients, or those with concomitant medications or impaired metabolic processes, may be at increased risk and should be monitored closely. The risk of myopathy may also be inferred from the pharmacologic and pharmacokinetic properties of the statin used. Since myotoxic events are more frequent at higher doses, statins that are effective in reducing cholesterol levels and helping patients to reach target levels at start doses may be useful. The lipophilicity of a statin and its potential for drug-drug interactions may also help to determine the likelihood of muscular effects. Drug-drug interactions may be avoided by selecting a statin that does not share the same metabolic pathway.

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J Med Food. 2004 Spring;7(1):100-7.
Natural honey lowers plasma glucose, C-reactive protein, homocysteine, and blood lipids in healthy, diabetic, and hyperlipidemic subjects: comparison with dextrose and sucrose.
Al-Waili NS.
Dubai Specialized Medical Center and Medical Research Laboratories, Islamic Establishment for Education, Dubai, United Arab Emirates. noori786@yahoo.com

This study included the following experiments: (1) effects of dextrose solution (250 mL of water containing 75 g of dextrose) or honey solution (250 mL of water containing 75 g of natural honey) on plasma glucose level (PGL), plasma insulin, and plasma C-peptide (eight subjects); (2) effects of dextrose, honey, or artificial honey (250 mL of water containing 35 g of dextrose and 40 g of fructose) on cholesterol and triglycerides (TG) (nine subjects); (3) effects of honey solution, administered for 15 days, on PGL, blood lipids, C-reactive protein (CRP), and homocysteine (eight subjects); (4) effects of honey or artificial honey on cholesterol and TG in six patients with hypercholesterolemia and five patients with hypertriglyceridemia; (5) effects of honey for 15 days on blood lipid and CRP in five patients with elevated cholesterol and CRP; (6) effects of 70 g of dextrose or 90 g of honey on PGL in seven patients with type 2 diabetes mellitus; and (7) effects of 30 g of sucrose or 30 g of honey on PGL, plasma insulin, and plasma C-peptide in five diabetic patients. In healthy subjects, dextrose elevated PGL at 1 (53%) and 2 (3%) hours, and decreased PGL after 3 hours (20%). Honey elevated PGL after 1 hour (14%) and decreased it after 3 hours (10%). Elevation of insulin and C-peptide was significantly higher after dextrose than after honey. Dextrose slightly reduced cholesterol and low-density lipoprotein-cholesterol (LDL-C) after 1 hour and significantly after 2 hours, and increased TG after 1, 2, and 3 hours. Artificial honey slightly decreased cholesterol and LDL-C and elevated TG. Honey reduced cholesterol, LDL-C, and TG and slightly elevated high-density lipoprotein-cholesterol (HDL-C). Honey consumed for 15 days decreased cholesterol (7%), LDL-C (1%), TG (2%), CRP (7%), homocysteine (6%), and PGL (6%), and increased HDL-C (2%). In patients with hypertriglyceridemia, artificial honey increased TG, while honey decreased TG. In patients with hyperlipidemia, artificial honey increased LDL-C, while honey decreased LDL-C. Honey decreased cholesterol (8%), LDL-C (11%), and CRP (75%) after 15 days. In diabetic patients, honey compared with dextrose caused a significantly lower rise of PGL. Elevation of PGL was greater after honey than after sucrose at 30 minutes, and was lower after honey than it was after sucrose at 60, 120, and 180 minutes. Honey caused greater elevation of insulin than sucrose did after 30, 120, and 180 minutes. Honey reduces blood lipids, homocysteine, and CRP in normal and hyperlipidemic subjects. Honey compared with dextrose and sucrose caused lower elevation of PGL in diabetics.

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Orthop Nurs. 2004 Jan-Feb;23(1):58-61.
An ounce of prevention. Drugs used to treat hyperlipidemia (Part 1).
Turkoski BB.
Kent State University College of Nursing, Kent, OH, USA.

My grandmother used to caution me. "An ounce of prevention is worth a pound of cure." That saying is certainly applicable to coronary heart disease (CHD). CHD remains a major cause of death in the United States today despite modern medical technology. The primary results of CHD, myocardial ischemia and myocardial infarct, when not deadly, often mean a seriously impaired lifestyle. However, since the 1960s, we have known that there were identifiable risk factors related to CHD. One of the major modifiable risk factors is an elevated lipoprotein level (e.g., hyperlipidemia), and today, we have an armament of lipid-lowering medications that are one means of preventing CHD for many individuals. In this article, the major classes of medications with lipid lowering effects are examined. Some of these medications are not new, but with the knowledge that the earlier they are used the more effective they may be, increasing numbers of people are now using nicotinic acid, bile acid-binding resins, fibric acid derivatives, or reductase inhibitors. As a result of the increased focus on lipid-lowering medications, nurses caring for middle-age and older adults are seeing and will continue to see larger numbers of their patients with prescriptions for these drugs. Nurses who are knowledgeable about the many antilipidemics on the market today will be more prepared to answer patient's questions and educate patients about reducing risk of CHD. A brief overview of the physiology of lipid metabolism, the pathophysiology of atherosclerosis, and risk factors for CHD make the rational for using these medications more understandable. Recommendations for early identification of individuals at risk for CHD are identified. In this Part 1 of a two-part series, two of the four major classes of lipid-lowering drugs are examined by looking at the mechanism of action and possible side effects of selected drugs in these classes. In Part 2 (May/June 2004), the other two classes of antilipidemic drugs will be examined and the recommendations of the National Cholesterol Education Program for clinical management of high blood cholesterol will be reviewed.

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Expert Opin Pharmacother. 2004 Feb;5(2):459-68.
Amlodipine and atorvastatin in atherosclerosis: a review of the potential of combination therapy.
Jukema JW, van der Hoorn JW.
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. j.w.jukema@lumc.nl

Hypertension and hyperlipidaemia are major risk factors for the development of atherosclerosis. Calcium channel blockers (CCBs) have been used for decades and have established antihypertensive effects. Statins have been extensively used because of their potent lipid lowering properties. Amongst other factors, inflammation and oxidation are involved in enhanced progression of atherosclerosis and new lesion development. Therefore, research has been initiated focusing on the antioxidant and anti-inflammatory properties of CCBs and statins, beyond their primary effect, in order to evaluate the possible additive effects of combined treatment of CCBs with statins as antiatherosclerotic therapy. Clinical studies (e.g., the International Nifedipine Trial on Antiatherosclerotic Therapy [INTACT]) have demonstrated that the antiatherosclerotic action of CCBs is limited to the attenuation of the first stage of atherosclerogenesis (fatty streak formation or new lesion growth). The lesions that pre-existed at the start of CCB therapy did not demonstrate progression or regression on angiography. However, because the mechanisms of action of lipid-lowering drugs and CCBs, and their role in preventing the progression of atherosclerosis differ, it is conceivable to conclude that these two classes may have an additive or synergic effect, not only on new lesion formation but also on inhibiting the progression of established coronary atherosclerosis. Indeed, this combined effect of lipid-lowering therapy and CCBs on human coronary atherosclerosis has been reported in the Regression Growth Evaluation Statin Study (REGRESS) trial. This beneficial effect of combining CCBs with statins has now been replicated in transgenic atherosclerotic mice, where the combination of amlodipine and atorvastatin produced an additional 60% reduction of atherosclerosis compared with that observed with the statin alone. Serum markers of atherosclerosis and vascular integrity also improved most in the combination group. Synergistic effects of the combination of atorvastatin and amlodipine on acute nitric oxide release/endothelial function, and additive effects of the combination of amlodipine and atorvastatin in the improvement of arterial compliance in hypertensive hyperlipidaemic patients has been demonstrated. Collectively, these studies support the clinical antiatherosclerotic advantages of combination of CCBs and statins and in particular, of atorvastatin with amlodipine beyond their established antihyperlipidaemic and antihypertensive modes of action.

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J Cardiovasc Nurs. 2003 Nov-Dec;18(5):389-95.
What ALLHAT tells us about treating high-risk patients with hypertension and hyperlipidemia.
Geraci TS, Geraci SA.
Research, Inc, Veterans Affairs Medical Center, Memphis, Tenn, USA. tsgeraci@aol.com

Hypertension and hyperlipidemia are potent cardiovascular risk factors. Treatment can lower blood pressure and reduce events, but the optimal drug for initial hypertension treatment and the benefits of long-term cholesterol reduction on clinical outcomes in understudied hypertensive subpopulations were unknown. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a long-term randomized, multicenter study undertaken to address these questions. In the hypertension component, 42,448 patients with mild-moderate hypertension and 1 or more other coronary risk factors were randomized to initial therapy with chlorthalidone, or to a newer antihypertensive agent--doxazosin (alpha blocker), amlodipine (calcium blocker), or lisinopril (angiotensin-converting enzyme inhibitor). The primary combined endpoint was coronary heart disease mortality or nonfatal myocardial infarction, with secondary endpoints including combinations of mortality, cardiac, and vascular complications. By interim analysis, doxazosin was shown inferior to diuretics in preventing secondary endpoints, resulting in early termination of this arm. There were no differences in primary endpoint frequency in chlorthalidone-amlodipine and chlorthalidone-lisinopril comparisons, but both amlodipine and lisinopril therapy resulted in more secondary events. In the lipid-lowering trial, 10,355 patients enrolled in the hypertensive trial with low-density-lipoprotein levels 100 to 189 mg/dL were randomized to pravastatin or usual care. There was no overall difference in the primary endpoint (total mortality) or most secondary endpoints, with statin therapy reducing stroke and coronary events modestly but nonsignificantly. Subgroup comparisons showed equivalent treatment effects in all groups except blacks, who had greater reduction in total coronary events but more strokes with pravastatin therapy and more strokes with lisinopril treatment.

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Metabolism. 2003 Nov;52(11):1478-83.
The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia.
Jenkins DJ, Kendall CW, Marchie A, Faulkner D, Vidgen E, Lapsley KG, Trautwein EA, Parker TL, Josse RG, Leiter LA, Connelly PW.
Clinical Nutrition and Risk Factor Modification Center, St. Michael's Hospital, Toronto, Ontario, Canada.

Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.

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Rev Med Liege. 2003 Oct;58(10):621-7.
[Statins for the brain?]
[Article in French]
Sadzot B, Hans G, Bottin P, Moonen G.
bsadzot@chu.ulg.ac.be

Whether cholesterol lowering decreases risk of stroke has long remained unclear. Large epidemiological studies have found only weak links between cholesterol levels and stroke. Recent studies with statins, more potent cholesterol lowering agents, have now demonstrated significant reductions of stroke incidence and total mortality when administered for secondary prevention in patients with wide ranges of cholesterol values. It remains unknown if a statin is superior to others for the secondary prevention of stroke.

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Am J Clin Nutr. 2003 Oct;78(4):711-8.
Randomized controlled crossover study of the effect of a highly beta-glucan-enriched barley on cardiovascular disease risk factors in mildly hypercholesterolemic men.
Keogh GF, Cooper GJ, Mulvey TB, McArdle BH, Coles GD, Monro JA, Poppitt SD.
Department of Medicine, the Human Nutrition & Metabolic Unit, University of Auckland, New Zealand.

BACKGROUND: Soluble-fiber beta-glucan derived from oats can reduce cardiovascular disease (CVD) risk through reductions in total and LDL cholesterol. Barley-derived beta-glucan may also improve serum cholesterol, but large quantities are required for clinical significance. OBJECTIVE: This trial investigated whether a beta-glucan-enriched form of barley can favorably modify cholesterol and other markers of CVD and diabetes risk. DESIGN: Eighteen mildly hyperlipidemic ( +/- SD: 4.0 +/- 0.6 mmol LDL cholesterol/L) men with a mean (+/- SD) body mass index (in kg/m(2)) of 27.4 +/- 4.6 were randomly assigned in this single-blind, 2 x 4-wk trial to either the treatment arm [8.1-11.9 g beta-glucan/d (scaled to body weight)] or the control arm (isoenergetic dose of 6.5-9.2 g glucose/d). After a washout period of 4 wk, dietary regimens were crossed over. The trial took place in a long-stay metabolic facility, and all foods were provided (38% of energy from fat). Fasted blood samples were collected on days 0, 1, 7, 14, 21, 28, and 29 in both study arms. An oral-glucose-tolerance test was carried out on days 0 and 29. RESULTS: There was no significant change (Delta) in total (Delta = -0.08 mmol/L, -1.3%), LDL (Delta = -0.15 mmol/L, -3.8%), or HDL (Delta = 0 mmol/L) cholesterol or in triacylglycerol (Delta = 0.18 mmol/L), fasting glucose (Delta = -0.05 mmol/L), or postprandial glucose when analyzed between treatments (P > 0.05; ANOVA). CONCLUSION: The effect of beta-glucan-enriched barley on lipid profile was highly variable between subjects, and there was no evidence of a clinically significant improvement in CVD risk across this group of mildly hyperlipidemic men.

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J Nutr. 2003 Oct;133(10):3298S-3302S.
Black tea consumption reduces total and LDL cholesterol in mildly hypercholesterolemic adults.
Davies MJ, Judd JT, Baer DJ, Clevidence BA, Paul DR, Edwards AJ, Wiseman SA, Muesing RA, Chen SC.
Beltsville Human Nutrition Research Center, ARS-U.S. Department of Agriculture, Beltsville, MD, USA.

Despite epidemiological evidence that tea consumption is associated with the reduced risk of coronary heart disease, experimental studies designed to show that tea affects oxidative stress or blood cholesterol concentration have been unsuccessful. We assessed the effects of black tea consumption on lipid and lipoprotein concentrations in mildly hypercholesterolemic adults. Tea and other beverages were included in a carefully controlled weight-maintaining diet. Five servings/d of tea were compared with a placebo beverage in a blinded randomized crossover study (7 men and 8 women, consuming a controlled diet for 3 wk/treatment). The caffeine-free placebo was prepared to match the tea in color and taste. In a third period, caffeine was added to the placebo in an amount equal to that in the tea. Five servings/d of tea reduced total cholesterol 6.5%, LDL cholesterol 11.1%, apolipoprotein B 5% and lipoprotein(a) 16.4% compared with the placebo with added caffeine. Compared with the placebo without added caffeine, total cholesterol was reduced 3.8% and LDL cholesterol was reduced 7.5% whereas apolipoprotein B, Lp(a), HDL cholesterol, apolipoprotein A-I and triglycerides were unchanged. Plasma oxidized LDL, F2-isoprostanes, urinary 8-hydroxy-2'-deoxyguanosine, ex vivo ferric ion reducing capacity and thiobarbituric acid reactive substances in LDL were not affected by tea consumption compared with either placebo. Thus, inclusion of tea in a diet moderately low in fat reduces total and LDL cholesterol by significant amounts and may, therefore, reduce the risk of coronary heart disease. Tea consumption did not affect antioxidant status in this study.

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Am Fam Physician. 2003 Oct 15;68(8):1595-6.
Ezetimibe for hypercholesterolemia.
Morris S, Tiller R.
Montgomery Center for Family Medicine, Greenwood Family Practice Residency, Greenwood, South Carolina, USA.

Ezetimibe (Zetia) is a novel, selective cholesterol absorption inhibitor. Ezetimibe blocks the absorption of dietary and biliary cholesterol within the brush-border enzyme system of the small intestine. Ezetimibe does not appear to alter or decrease the absorption of bile acids, fatty acids, fat-soluble vitamins, or triglycerides. It is labeled for use in the treatment of primary hypercholesterolemia, either as monotherapy or in combination with statins. It also is labeled for the treatment of homozygous familial hypercholesterolemia in conjunction with statins and as adjunctive therapy to diet in the treatment of homozygous sitosterolemia (a rare, inherited, plant sterol storage disease).

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Curr Diab Rep. 2003 Oct;3(5):397-403.
Nutrition therapy for dyslipidemia.
Carson JA.
Department of Clinical Nutrition and Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-8877, USA. joann.carson@utsouthwestern.edu

National guidelines indicate patients with elevated low- density lipoprotein cholesterol should consume less than 7% of calories from saturated fat and less than 200 mg of cholesterol. Trans fatty acids should also be limited. Incorporation of functional foods, such as stanol-containing margarine, soy products, and soluble fiber-rich cereals and vegetables can provide further benefit. In addition to weight loss and physical activity, individuals with hypertriglyceridemia benefit from a diet moderate in fat and carbohydrate rather than a low-fat diet. Including monounsaturated or omega-3 fatty acids lowers serum triglycerides. Many of the dietary strategies to optimize serum lipids also contribute to glycemic control in patients with diabetes mellitus.

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Am J Cardiol. 2003 Oct 1;92(7):794-7.
Effects of baseline level of triglycerides on changes in lipid levels from combined fluvastatin + fibrate (bezafibrate, fenofibrate, or gemfibrozil).
Farnier M, Salko T, Isaacsohn JL, Troendle AJ, Dejager S, Gonasun L.
Point Medical, Dijon, France.

This analysis was conducted to evaluate the effect of baseline triglyceride levels on lipid and lipoprotein changes after treatment with the combination of fluvastatin and fibrates. The analysis involved pooling data from 10 studies that included 1,018 patients with either mixed hyperlipidemia or primary hypercholesterolemia. Patients received a combination of fluvastatin and a fibrate (bezafibrate, fenofibrate, or gemfibrozil) from 16 to 108 weeks. The combination of fluvastatin and a fibrate improved lipid profiles, with reductions in triglycerides, low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol that were dependent on baseline triglyceride levels. The greatest triglyceride reductions were observed in patients with high baseline triglyceride levels (> or =400 mg/dl) (41%, p <0.0001). The greatest LDL cholesterol and non-HDL cholesterol reductions occurred in patients with normal baseline triglyceride levels (<150 mg/dl) (35% and 33%, respectively; p <0.0001). The combined fluvastatin-fibrate therapy was well tolerated. Two patients (0.2%) (1 patient on fluvastatin 80 mg + gemfibrozil 1,200 mg and 1 patient on fluvastatin 20 mg + fenofibrate 200 mg) had creatine kinase levels > or =10 times the upper limit of normal, 11 patients (1.1%) had an elevation in alanine transaminase >3 times the upper limit of normal, and 7 patients (0.7%) had elevations in aspartate transaminase >3 times the upper limit of normal. Combined fluvastatin-fibrate therapy takes advantage of the complementary effects of the 2 agents, with the extent of triglyceride, LDL cholesterol, and non-HDL cholesterol lowering dependent on baseline triglyceride levels. The combination of fluvastatin and fibrates was well tolerated with no major safety concerns.

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Am J Cardiol. 2003 Sep 15;92(6):670-6.
Safety of atorvastatin derived from analysis of 44 completed trials in 9,416 patients.
Newman CB, Palmer G, Silbershatz H, Szarek M.
Pfizer Global Pharmaceuticals, 235 East 42nd Street, New York, NY 10017-5755, USA. connie.newman@pfizer.com

This analysis assessed the safety of atorvastatin in the 10- to 80-mg dose range using pooled data from 44 completed trials comprising 16,495 dyslipidemic patients treated with atorvastatin (n = 9,416), placebo (n = 1,789), and other statins (n = 5,290). A retrospective analysis was conducted and included treatment-associated adverse events, serious adverse events, and musculoskeletal and hepatic adverse events. Only 3% (n = 241) of atorvastatin-treated patients withdrew from studies due to treatment-associated adverse events, compared with 1% of those (n = 16) on placebo and 4% of those (n = 188) receiving other statins; the most frequently reported treatment-associated adverse events were related to the digestive system. Serious adverse events were rare and seldom led to withdrawal. Persistent elevations in hepatic transaminases to >3 times the upper limit of normal (ULN) were experienced by 0.5% (n = 47) of atorvastatin-treated patients. A persistent elevation in creatine phosphokinase (CPK) (>10 x ULN) was observed in only 1 atorvastatin-treated patient and was not associated with myopathy. The incidence of treatment-associated myalgia was low in the atorvastatin (1.9% [n = 181]), placebo (0.8% [n = 14]), and other statin (2.0% [n = 105]) groups, and was not related to the atorvastatin dose. No cases of rhabdomyolysis or myopathy were reported. Thus, the overall incidence of treatment-associated adverse events observed with atorvastatin did not increase in the 10- to 80-mg dose range, and was similar to that observed with placebo and in patients treated with other statins. Specific analysis of musculoskeletal and hepatic adverse events showed that these occurred infrequently and rarely resulted in treatment discontinuation.

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J Vasc Nurs. 2003 Sep;21(3):81-9; quiz 90-1.
Managing the spectrum of dyslipidemia in primary care.
Mason CM.
Heart and Lipid Institute of Florida, St Petersburg, Florida, USA.

Dyslipidemia, especially elevated low-density lipoprotein cholesterol (LDL-C), increases the risk of coronary heart disease and subsequent morbidity or mortality. For more than a decade, the National Cholesterol Education Program (NCEP) has endeavored to raise awareness of the dangers of dyslipidemia and to encourage the implementation of recommended treatment strategies. However, despite this initiative, previously published NCEP targets were not met. The recently released NCEP-Adult Treatment Panel III guidelines recommend more aggressive LDL-C reduction, elevation of categorical low high-density lipoprotein binding protein, and increased monitoring of moderate triglyceride elevations. Although the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are the most powerful medications available to reduce LDL-C, studies have shown that more than half of patients treated with these drugs do not achieve therapeutic targets and the resultant decrease in coronary heart disease events. There are a number of possible reasons for this, including potency of the statins and a lack of compliance on the part of patients and providers. Another concern with the available statins is the issue of drug-drug interactions. Some of these concerns may be addressed by newer agents in this drug class that are in development. They appear to have the potential to induce even greater reductions in LDL-C and to positively affect other lipoproteins. They also have the potential for less risk of drug-drug interactions. Nurse practitioners can play a pivotal role in improving the management of dyslipidemia by ensuring the proper implementation of current guidelines, helping patients adhere to treatment protocols, and remaining abreast of developments that may pave the way toward even more effective intervention in the future.

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Clin Ther. 2003 Sep;25(9):2352-87.
Pharmacology and therapeutics of ezetimibe (SCH 58235), a cholesterol-absorption inhibitor.
Jeu L, Cheng JW.
Pharmacy Services, Veterans Affairs Medical Center, Bronx, New York, USA.

BACKGROUND: Ezetimibe is the first of a new class of antihyperlipidemic agents, the cholesterol-absorption inhibitors. It is indicated for monotherapy or in combination with 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors (statins) in patients with primary hypercholesterolemia, in combination with simvastatin or atorvastatin in patients with homozygous familial hypercholesterolemia, and as monotherapy in patients with homozygous familial sitosterolemia. OBJECTIVE: This article reviews available data on the clinical pharmacology, clinical efficacy, and tolerability of ezetimibe. METHODS: A literature review was conducted using the search terms ezetimibe and SCH 58235 to identify articles and abstracts indexed in MEDLINE and the Iowa Drug Information Service from 1966 to February 2003. The reference lists of the identified articles were reviewed for additional publications. RESULTS: In adults, ezetimibe 10 mg PO given once daily has been reported to reduce intestinal cholesterol absorption by 54% from baseline in association with a compensatory increase in endogenous cholesterol synthesis. Within 2 weeks of its initiation, ezetimibe monotherapy produced a 17% to 20% reduction from baseline in low-density lipoprotein cholesterol (LDL-C); in combination with statins, ezetimibe produced a reduction in LDL-C of up to 40% over the same period. Based on studies performed to date, ezetimibe appears to be well tolerated, with a safety profile similar to that of placebo. Because ezetimibe is eliminated primarily by glucuronidation and not by cytochrome P450 (CYP) oxidation, it is subject to minimal drug interactions involving the CYP enzyme system. CONCLUSIONS: Ezetimibe is an option for monotherapy in patients with mild hypercholesterolemia or in those requiring adjunctive drug therapy for reduction of LDL-C levels. It may be useful in patients at risk for adverse events (eg, liver toxicity, myopathy) from other hypocholesterolemic agents. Additive LDL-C-lowering effects of ezetimibe may allow use of lower doses of conventional agents (eg, statins, fibric acid derivatives, niacin) to achieve an equivalent effect, thereby reducing the potential for adverse events and drug interactions. However, because trials have lasted no longer than 12 weeks, the long-term effect of ezetimibe on cardiovascular morbidity and mortality remains to be determined.

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Issues Emerg Health Technol. 2003 Sep;(49):1-4.
Ezetimibe for lowering blood cholesterol.
Husereau DR.

Ezetimibe is the first drug in a new class called cholesterol absorption inhibitors. There is no evidence that ezetimibe will reduce rates of death or hospitalization. When it is taken alone or when it is added to existing statin therapy, ezetimibe can reduce serum cholesterol in patients who have an increased risk of future coronary artery disease. The safety and tolerability of ezetimibe alone or combined with a statin has not been established in trials beyond 12 weeks.

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Isr Med Assoc J. 2003 Sep;5(9):637-40.
Effect of garlic on lipid profile and psychopathologic parameters in people with mild to moderate hypercholesterolemia.
Peleg A, Hershcovici T, Lipa R, Anbar R, Redler M, Beigel Y.
Department of Criminology, Bar Ilan University, Ramat Gan, Israel.

BACKGROUND: The beneficial effect of 3-hydroxy-3-methylglutyaryl co-enzyme A reductase inhibitors on cardiovascular risk reduction has been clearly established. Concerns have been raised that lowering blood cholesterol by other hypolipidemic drugs or by a non-pharmacologic approach may have deleterious effects on psychopathologic parameters. Garlic is one of the most commonly used herbal remedies and is considered to have hypocholesterolemic as well as other cardioprotective properties. Its effect on psychopathologic parameters has never been reported. OBJECTIVE: To evaluate the effect of garlic on lipid parameters and depression, impulsivity, hostility and temperament in patients with primary type 2 hyperlipidemia. METHODS: In a 16 week prospective double-blind placebo-controlled study, 33 patients with primary hypercholesterolemia and no evidence of cardiovascular disease were randomly assigned to receive either garlic or placebo. Garlic in the form of alliin 22.4 mg/day was given to 13 patients, and placebo to 20. Both groups received individual dietary counseling. The changes in lipid profile and the various psychopathologic parameters were determined at the beginning and end of the trial. The differences in lipid parameters were evaluated by Student's t-test. The psychological data were analyzed by one-way analysis of variance (ANOVA) with repeated measures and Neuman-Keuls test. RESULTS: No significant changes were observed in levels of total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglycerides, or in the psychopathologic parameters evaluated. CONCLUSION: Short-term garlic therapy in adults with mild to moderate hypercholesterolemia does not affect either lipid levels or various psychopathologic parameters.

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Int J Cardiol. 2003 Aug;90(2-3):141-5; discussion 145-6.
An open label crossover trial of effects of metronidazol on hyperlipidaemia.
Shamkhani K, Azarpira M, Akbar MH.
Guilan University of Medical Sciences, Dr Heshmat Cardiovascular Research Center, Rasht, 41937, Guilan, Iran. shamkhani@yahoo.com

Metronidazole, a synthetic derivative of tile nitroimidazole class, is a known antibacterial and antiprotozoal agent. Following an anecdotal observation of hypolipidemic effect of metronidazole, a randomized open trial of 250 mg three times daily was conducted in 30 subjects. This open label crossover trial was performed in three stages-14 days each-as challenge, wash out and re-challenge on 30 subjects, including six male and 24 female in the age limits of 40 to 73 years (mean 58.7+/-10.6 years). Results of this trial revealed that metronidazole 750 mg daily in divided doses for 14 days decreased the average of total blood cholesterol in 30 cases by 46+/-27 mg/dl (14.6%, P=0.025) and LDL cholesterol by 39+/-28 mg/dl (22%, P=0.005). Decrease in total and LDL cholesterol and increase in HDL cholesterol by 3.8+/-4.1 mg/dl also accompanied fall of triglyceride level cases by 68+/-13 mg/dl. This study suggests that metronidazole or its derivatives may form a new class of lipid lowering compounds.

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Lancet. 2003 Aug 30;362(9385):717-31.
Dyslipidaemia.
Durrington P.
University Department of Medicine, Manchester Royal Infirmary, Oxford Road, M13 9WL, Manchester, UK. pdurrington@man.ac.uk >

The lowering of serum cholesterol is increasingly recognised as essential in the prevention of coronary heart disease and other atherosclerotic disease. The success of statin trials and the need to deploy these drugs effectively in the population has led increasingly to the identification of many people whose serum cholesterol, triglycerides, and HDL-cholesterol require clinical assessment, and frequently treatment. Lipid disorders are mainly straightforward, but some are complex or resistant to simple treatment strategies. I have reviewed the clinical manifestations of disordered lipid metabolism (dyslipidaemia) and its management.

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Cas Lek Cesk. 2003 Aug;142(8):500-4.
[Long-term hypolipidemic treatment of mixed hyperlipidemia with a combination of statins and fibrates]
[Article in Czech]
Zeman M, Zak A, Vecka M, Romaniv S.
IV. interni klinika 1. LF UK a VFN, Praha. zemanm@vfn.cz

BACKGROUND: It is difficult to achieve satisfactory decreases of both plasma LDL-cholesterol (LDL-C) and triglycerides (TG) and increase of HDL-C with only single statin or fibrate treatment of patients with mixed hyperlipoproteinaemias (HLP). Combination treatment with both statin and fibrate has been shown to enhance achieving of recommended targets in these patients with high-risk of coronary heart disease. On the other hand unpleasant side effects including myopathy and rhabdomyolysis were described in some cases after statin-fibrate combination therapy. Aim of the study was to evaluate efficacy and safety of long-term treatment of pravastatin + fenofibrate or simvastatin + ciprofibrate therapy in the high-risk group of patients with severe mixed hyperlipoproteinemia. METHODS AND RESULTS: A set of 86 patients (55 M/31 F) was followed for a period at least one year (median 3 years). These patients were randomly assigned to combination of pravastatin 20 mg + fenofibrate 200 mg (n = 46) (group A), or simvastatin 20 mg + ciprofibrate 100 mg (n = 40) (group B). We have observed significant reduction in plasma TC (22% in group A, 20% in group B), in LDL-C (36%, resp. 33%), reduction of TG (44%, resp. 46%), apo-B (35%, resp. 33%) whilst HDL-C significantly increased (18%, resp. 16%). Concomitantly we have seen significant decreases in uricaemia (14%, resp. 18%). No patient needed to stop treatment due to abnormalities in liver function tests. Levels of creatinkinase became non-significantly elevated (by 16%, resp. 13%). No patient exhibited myopathy or rhabdomyolysis. CONCLUSIONS: The long-term combined therapy with statin-fibrate (pravastatin 20 mg + fenofirbrate 200 mg, or simvastatin 20 mg + ciprofibrate 100 mg) in severe mixed HLP was safe and effectively improved plasma lipid and apolipoprotein levels. Both combinations seemed to be similarly efficient and safe.

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Rev Cardiovasc Med. 2003 Summer;4(3):136-41.
Emerging non-statin LDL-lowering therapies for dyslipidemia and atherosclerosis.
Shah PK.
Division of Cardiology and Atherosclerosis Research Center, Cedars-Sinai Medical Center and The David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

Elevated low-density lipoprotein cholesterol is an important risk factor for atherothrombotic arterial disease. HMG-CoA reductase inhibitors, or statins, are very effective in lowering cholesterol levels, and several trials using statins have shown reductions in mortality and cardiovascular events, leading to the recent recommendations that all patients with known vascular disease, or who are at high risk for vascular disease, should be considered candidates for statin therapy. Yet statins reduce cardiovascular events by only about 20%-40%. Nonstatin therapies (either as monotherapy or in addition to statins) to reduce LDL cholesterol by mechanisms that do not involve inhibition of HMG-CoA reductase are likely to be useful for patients in need of LDL reduction; particularly those who either cannot take statins or respond only partially or not at all to statins alone. These therapies include cholesterol absorption inhibitors, Acyl-CoA cholesterol acyl transferase inhibitors, farnesoid X receptor antagonists, sterol-regulating binding protein cleavage activating protein, and microsomal triglyceride transfer protein.

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Geriatrics. 2003 Aug;58(8):18-20, 26-8, 31-2.
Hypercholesterolemia. The evidence supports use of statins.
Aronow WS.
Department of Medicine, Divisions of Cardiology and Geriatrics, New York Medical College, Valhalla, NY, USA.

Using statins to treat older men and women with coronary artery disease (CAD) and hypercholesterolemia reduces the risk of all-cause mortality, cardiovascular mortality, coronary events, coronary revascularization, stroke, Intermittent claudication, and congestive heart failure. The target serum low-density lipoprotein (LDL) cholesterol level is < 100 mg in older patients with CAD, prior stroke, peripheral arterial disease, extracranial carotid arterial disease, abdominal aortic aneurysm, diabetes meilitus, and the metabolic syndrome. Statins are also effective in reducing cardiovascular events in older persons with hypercholesterolemia without cardiovascular disease. Consider using statins in older persons without cardiovascular disease but with a serum LDL cholesterol > or = 130 mg/dL, or a serum high-density lipoprotein cholesterol < 50 mg/dL. Data from the Heart Protection Study favor treating patients at high risk for vascular events with statins regardless of age or initial serum lipids.

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MMW Fortschr Med. 2003 Aug 7;145(31-32):29-32.
[Diet in disordered lipid metabolism. A culinary balance act]
[Article in German]
Richter WO.
Institut fur Fettstoffwechsel und Hamorheologie, Windach. IFH-richter@t-online.de

When LDL cholesterol is elevated, HDL cholesterol is low or triglycerides are raised, dietary changes form the basis of treatment. Such changes are most important in the case of hypertriglyceridemia. Some 3 to 4 hours after a meal, triglycerides increase to an extent determined by the composition of the meal. Hypertriglyceridemia cannot be successfully treated unless alcohol is banished and rapidly assimilatable carbohydrates are restricted. In patients with elevated LDL cholesterol, a change in eating habits can have an appreciable effect (on average 10-15%). Since this measure can save the use or reduce the dose of medications, its value is obvious, and it must not be neglected. The measures aimed at elevating HDL cholesterol have only a moderate effect, so that more importance should be attached to lowering the LDL fraction.

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Mayo Clin Proc. 2003 Jun;78(6):735-42.
Niacin as a component of combination therapy for dyslipidemia.
Miller M.
Center for Preventive Cardiology, University of Maryland Medical Center, Baltimore 21201, USA. mmiller@heart.umaryland.edu

Dyslipidemia is one of the most important modifiable risk factors for coronary disease. Despite the availability of highly effective lipid-modifying agents, many patients still do not reach lipid targets established by national guidelines. Niacin has been known to be an effective treatment of dyslipidemia for almost half a century. Niacin substantially increases high-density lipoprotein cholesterol (HDL-C) levels while lowering levels of low-density lipoprotein cholesterol (LDL-C), triglycerides, and lipoprotein(a). In addition, niacin converts small LDL particles into more buoyant, less atherogenic LDL particles. Combined with other agents, niacin offers an important treatment option for patients with dyslipidemia. In particular, niacin complements LDL-C-lowering drugs; it is the most effective agent available for increasing HDL-C levels while lowering levels of LDL-C and triglycerides and improving other lipid risk factors such as lipoprotein(a). Combining niacin with statins or bile acid sequestrant therapy is safe and effective for improving lipid levels and decreasing coronary risk. Differences in niacin formulations dictate tolerability profiles and should be considered when selecting niacin as part of lipid therapy. Furthermore, adverse effects on glucose and insulin sensitivity should be considered when selecting candidates for niacin therapy. Adding niacin to lipid-lowering regimens is a valuable option for physicians treating patients with dyslipidemia and should be considered in appropriate patients.

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Neth J Med. 2003 May;61(5 Suppl):35-9.
The future of lipid-lowering therapy: the big picture.
Kastelein JJ.
Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam-Zuidoost, The Netherlands.

Several lipid-lowering intervention studies published in 2002 shed light on the current status and the future of cardiovascular risk reduction by drug therapy. The Heart Protection Study has demonstrated that simvastatin reduces heart attack, stroke and revascularisation risk by about one-third irrespective of total cholesterol, LDL cholesterol, patient's age or sex, or the nature of pre-existing cardiovascular disease. Coronary heart disease death and myocardial infarction risk reduction in elderly patients by pravastatin in the PROSPER study was similar to the benefit of statins in middle-aged populations in other studies. The ALLHAT-LLT study has failed to demonstrate a benefit of pravastatin on all-cause mortality, CHD death or nonfatal myocardial infarction, illustrating that too modest cholesterol lowering does not result in clinical benefit under all circumstances. The cholesterol absorption inhibitor ezetimibe has demonstrated significant LDL and total cholesterol lowering, and induced an additional 21% LDL cholesterol lowering when added to ongoing statin therapy. The cholesteryl ester transfer protein inhibitor JJT-705 produced a dose-dependent increase in HDL cholesterol concentrations of up to 34% and improved the total cholesterol/HDL cholesterol ratio in healthy individuals while having very mild side effects. Cholesterol absorption inhibitors and HDL cholesterol enhancers may become useful tools to achieve further improvements in cardiovascular risk reduction in the future.

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Can J Clin Pharmacol. 2003 Winter;10 Suppl A:21A-5A.
Clinical use of ezetimibe.
Cheng AY, Leiter LA.
St Michael's Hospital, Toronto, Ontario.

Despite advances in pharmacological therapies to treat and prevent cardiovascular disease, it remains the leading cause of death in Canada. There now exists a large body of evidence demonstrating that reduction of low-density lipoprotein cholesterol (LDL-C) effectively reduces cardiovascular morbidity and mortality. Despite this, a large proportion of patients who would benefit from this intervention are still not achieving the recommended LDL-C levels. The currently available pharmacological agents, especially statins, are very effective but have rare, yet potentially significant, side effects. The likelihood of these side effects is small but does increase with increasing drug dose. As a result, dosages are often not titrated upward because they cannot be tolerated or their side effects are feared by either physicians or patients. Ezetimibe is a new cholesterol absorption inhibitor that is safe and effective in total cholesterol and LDL-C reduction. When used as monotherapy or in combination with a statin, ezetimibe has been shown to reduce LDL-C by an additional 15% to 20% and improve high-density lipoprotein cholesterol and triglycerides slightly. The addition of ezetimibe to a statin produces an LDL-C reduction of similar magnitude to a three-fold increase in statin dose. The combination of ezetimibe and either atorvastatin or simvastatin has also been found to be beneficial in patients with homozygous familial hypercholesterolemia. The safety profile is similar to placebo and no significant drug interactions have been observed. There is no clinical trial outcome evidence associated with the use of ezetimibe at this time. Thus, ezetimibe is a safe and effective addition to the current LDL-C lowering regimen and is most useful in those patients who cannot achieve sufficient LDL-C reduction with an adequate dose of statin alone, cannot tolerate a statin or are fearful of a statin.

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Arzneimittelforschung. 2003;53(9):605-11.
Pharmacological comparison of the statins.
Klotz U.
Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany. ulrich.klotz@ikp-stuttgart.de

The statins (3-hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors) represent drugs of first choice for treatment of hypercholesterolemia. The safety and efficacy of atorvastatin (CAS 134523-00-5), simvastatin (CAS 79902-63-9), lovastatin (CAS 75330-75-7), pravastatin (CAS 81093-37-0) and fluvastatin (CAS 93957-54-1) has been well documented. Statins decrease dose-dependently low-density lipoprotein (LDL) cholesterol as well as coronary events and total mortality. Clinical outcome data indicate that for simvastatin the lowest number of treated patients is needed to prevent one major coronary event (NNT 15). Based on an approximately 30% reduction of LDL (valid surrogate parameter) atorvastatin (5 mg/day) and simvastatin (10 mg/day) are the most potent agents whereas 40 mg of lovastatin or pravastatin and 60 mg of fluvastatin are needed to reach this "therapeutic target". While all statins share the same mode of action their pharmacokinetic properties and their susceptibility to drug interactions differ slightly. Agents inhibiting CYP3A4 (e.g. grapefruit juice, itraconazole, cyclosporine) should be discouraged if a patient is on atorvastatin, lovastatin or simvastatin. Likewise, fluconazole interferes with the CYP2C9-mediated hepatic elimination of fluvastatin. Moreover, coadministration of gemfibrozil should be avoided because it seems to increase the very low risk for statin-induced rhabdomyolysis. Several statins are available and their equieffective doses have been defined. Selection of a particular drug should be primarily based on clinical outcome data. However, costs and in certain situations the pharmacokinetic profile including the interaction potential of the statins should be taken into account.

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J Manag Care Pharm. 2003 Jan-Feb;9(1 Suppl):13-6.
A novel therapeutic approach.
Denke MA.
University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. Margo.Denke@UTSouthwestern.edu

Since 1988, the National Cholesterol Education Program has identified low-density lipoprotein cholesterol (LDL-C) as the target of therapy; the new Adult Treatment Panel III (ATP III) guidelines continue the tradition of matching the aggressiveness of LDL-lowering therapy according to the risk of coronary heart disease (CHD). A significant change in the new guidelines is the definition of.CHD risk equivalents. and the inclusion of a modified Framingham global risk score. These revisions significantly raise the number of patients who qualify for lipid-lowering therapy. ATP III recognizes statins as the drug of first choice for LDL-C lowering. Statins are proven to be safe and effective for LDL-C reduction and are proven to reduce CHD event rates and mortality. Some patients are not candidates for statin therapy, however, and must rely on nonstatin agents that are less effective in reducing LDL-C, less safe, or poorly tolerated. Consequently, new cholesterol-lowering therapies are needed. Ezetimibe, approved by the U.S. Food and Drug Administration (FDA) in October 2002, is the first in a new class of selective cholesterol absorption inhibitors and offers a novel approach to the treatment of dyslipidemia. Phase 2 data demonstrated that ezetimibe lowers LDL-C by 18% and has a tolerability and short-term safety profile similar to placebo. This paper reviews the cholesterol metabolic pathways and the mechanism of action of the currently available lipid-modifying agents and introduces ezetimibe, the first selective cholesterol absorption inhibitor.

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J Manag Care Pharm. 2003 Jan-Feb;9(1 Suppl):9-12.
Overview of pharmacologic therapy for the treatment of dyslipidemia.
Lipsy RJ.
Health Net of Arizona, 930 North Finance Center Dr., Tucson, Arizona 85710, USA. Robert.J.Lipsy@az.health.net

Although the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines stress the importance of nonpharmacologic lipid modification interventions such as diet and exercise, the guidelines also recognize that many patients will require drug therapy to achieve low-density lipoprotein cholesterol (LDL-C) target goals. Currently available lipid-modifying drugs include bile acid sequestrants (or resins), fibrates, nicotinic acid, and statins, with each class exerting different effects on the lipid profile. In addition, nonprescription agents such as plant stanols and sterols have been shown to be effective in modifying plasma lipids. Of these agents, the statins are the most effective, most widely prescribed, and best-tolerated form of lipid-lowering drug therapy. New formulations of other drugs, such as niacin and bile acid sequestrants, can also improve treatment regimes and reduce side effects, thereby improving patient compliance with these therapies. In patients who have high levels of LDL-C and triglycerides together with low concentrations of high-density lipoprotein cholesterol (HDL-C), combination therapy may be required. Ezetimibe, a selective cholesterol absorption inhibitor, is the first of a new class of lipid-lowering agents and provides a new agent for the management of patients with dyslipidemia. Data from the ezetimibe clinical development program suggests that this agent can be used alone or in combination with statins to reduce LDL-C, improve compliance, and bring more patients to ATP III target goal.

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Am J Kidney Dis 2003 Mar;41(3):565-70
A controlled, prospective study of the effects of atorvastatin on proteinuria and progression of
kidney disease.
Bianchi S, Bigazzi R, Caiazza A, Campese VM.
Unita Operativa Nefrologia, Spedali Riuniti di Livorno, Livorno, Italy.

BACKGROUND: Chronic kidney diseases, particularly if presenting with significant proteinuria, are commonly associated with substantial alteration of serum lipid levels. Experimental evidence suggests that lipid abnormalities may contribute to the progression of kidney disease. However, studies in humans on the subject are scarce. METHODS: In a prospective, controlled open-label study, the authors have evaluated the effects of one-year treatment with atorvastatin, a 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitor, versus no treatment on proteinuria and progression of kidney disease in 56 patients with chronic kidney disease. Before randomization, all patients had already been treated for one year with angiotensin-converting enzyme (ACE) inhibitors or angiotensin AT1 receptor antagonists (ARBs) and other antihypertensive drugs. RESULTS: By the end of one-year treatment, urine protein excretion decreased from 2.2 +/- 0.1 to 1.2 +/- 1.0 g every 24 hours (P < 0.01) in patients treated with atorvastatin in addition to ACE inhibitor and ARBs. By contrast, urinary protein excretion decreased only from 2.0 +/- 0.1 to 1.8 +/- 0.1 g every 24 hours (P value not significant) in patients who did not receive atorvastatin in addition to ACE inhibitor or ARBs. During this time, creatinine clearance decreased only slightly and not significantly (from 51 +/- 1.8 to 49.8 +/- 1.7) in patients treated with atorvastatin. By contrast, during the same period of observation, creatinine clearance decreased from 50 +/- 1.9 to 44.2 +/- 1.6 mL/min (P < 0.01) in patients who did not receive atorvastatin. CONCLUSIONS: This study has shown that treatment with atorvastatin in addition to a regimen with ACE inhibitors or ARBs may reduce proteinuria and the rate of progression of kidney disease in patients with chronic kidney disease, proteinuria, and hypercholesterolemia. The benefits appear to occur in addition to those of treatment with ACE inhibitor and ARBs. Copyright 2003 by the National Kidney Foundation, Inc.

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Am J Cardiol 2003 Feb 15;91(4):418-24
Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia.
Kerzner B, Corbelli J, Sharp S, Lipka LJ, Melani L, LeBeaut A, Suresh R, Mukhopadhyay P, Veltri EP; Ezetimibe Study Group.
Health Trends Research, Baltimore, Maryland, USA.

This multicenter, randomized, double-blind, placebo-controlled clinical study assessed the efficacy and safety of ezetimibe administered with lovastatin in primary hypercholesterolemia. After dietary stabilization, a 2- to 12-week washout period, and a 4-week single-blind placebo lead-in period, 548 patients with low-density lipoprotein (LDL) cholesterol > or =145 mg/dl (3.75 mmol/L) and < or =250 mg/dl (6.47 mmol/L) and triglycerides < or =350 mg/dl (3.99 mmol/L) were randomized to one of the following, administered daily for 12 weeks: ezetimibe 10 mg; lovastatin 10, 20, or 40 mg; ezetimibe 10 mg plus lovastatin 10, 20, or 40 mg; or placebo. The primary efficacy variable was percentage decrease in direct LDL cholesterol from baseline to end point for pooled ezetimibe plus lovastatin versus pooled lovastatin alone. Ezetimibe plus lovastatin significantly improved concentrations of LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides compared with lovastatin alone (p <0.01). The coadministration of ezetimibe provided an incremental 14% LDL cholesterol decrease, a 5% HDL cholesterol increase, and a 10% decrease in triglycerides compared with pooled lovastatin alone. Ezetimibe plus lovastatin provided mean LDL cholesterol decreases of 33% to 45%, median triglyceride decreases of 19% to 27%, and mean HDL cholesterol increases of 8% to 9%, depending on the statin dose. The coadministration of ezetimibe 10 mg plus the starting dose of lovastatin (10 mg) provided comparable efficacy to high-dose lovastatin (40 mg) across the lipid profile (LDL cholesterol, HDL cholesterol, and triglycerides). Ezetimibe plus lovastatin was well tolerated, with a safety profile similar to both lovastatin alone and placebo. The coadministration of ezetimibe and lovastatin may offer a new treatment option in lipid management of patients with hypercholesterolemia.

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J Am Osteopath Assoc 2003 Jan;103(1 Suppl 1):S16-20
A novel therapeutic approach to dyslipidemia.
Clearfield MB.
Office of the Dean, Texas College of Osteopathic Medicine, University of North Texas Health Science Center at Fort Worth, 76107-2699, USA. mclearfi@hsc.unt.edu

The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines call for more aggressive lowering of low-density lipoprotein cholesterol (LDL-C) and will substantially increase the number of patients eligible for lipid-lowering therapy. Statins, the current treatment standard, have proven to be highly efficacious in lowering LDL-C and reducing coronary heart disease (CHD) risk. Because some patients are unable to tolerate 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) or they are not candidates for statin therapy, however, other cholesterol-lowering modes of therapy are needed. Currently available nonstatin drugs often do not reliably reduce LDL-C to a desired extent or are limited in their safety and tolerability. Ezetimibe, a novel lipid-lowering agent until recently in phase III development, is the first in a new class of selective cholesterol absorption inhibitors and offers a promising new approach to the treatment of dyslipidemia. This article reviews the cholesterol metabolic pathways and the mechanism of action of the currently available lipid-modifying agents and introduces ezetimibe, the first selective cholesterol absorption inhibitor.

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Przegl Lek 2002;59(7):519-22
[Mechanisms of statin nephroprotective actions]
[Article in Polish]
Chmielewski M, Zdrojewski Z, Rutkowski B.
Klinika Nefrologii, Transplantologii i Chorob Wewnetrznych Akademii Medycznej w Gdansku. chmiel@amedec.amg.gda.pl

The great importance of HMGCoA reductase inhibitors (statins) in treatment of hyperlipidemia is well known, and accepted. Numerous multicenter trials have shown the effectiveness of statins in lowering cholesterol concentration, slowing down progression of atherosclerosis, and in decreasing number of cardio-vascular incidents. However, since the discovery of statins experiments have been carried out showing other mechanisms of action of these drugs. Many circumstances expose the antiproliferative, and antiinflammatory influence of HMGCoA reductase inhibitors. This paper presents a review of the studies on these mechanisms with a special emphasis on their nephroprotective role.

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Cleve Clin J Med 2002 Dec;69(12):985-9
Comment in: Cleve Clin J Med. 2002 Dec;69(12):927; Cleve Clin J Med. 2002 Dec;69(12):990-4.
A truly deadly quartet: obesity, hypertension, hypertriglyceridemia, and hyperinsulinemia.
Nambi V, Hoogwerf RJ, Sprecher DL.
Department of Internal Medicine, The Cleveland Clinic Foundation, OH 44195, USA.

The National Cholesterol Education Program recognizes the importance of the metabolic syndrome and has published guidelines for its diagnosis. Weight loss, physical activity, and treatment of the individual risk factors constitute the main strategies for treatment. For now, the goals and methods of treating hypertension and dyslipidemia are the same in people with the metabolic syndrome as in the general population. Thiazolidinedione drugs increase insulin sensitivity, but their use in the metabolic syndrome is only speculative at present. We recommend they be used only as indicated to treat diabetes mellitus.

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South Med J 2002 Nov;95(11):1255-61
Management of hyperlipidemia in the elderly population: an evidence-based approach.
Dalal D, Robbins JA.
Department of Education, Eastern Virginia Medical School, Norfolk, VA, USA.

Coronary heart disease (CHD) is the leading cause of morbidity and mortality in patients more than 65 years old. Within this population, elevated cholesterol levels are prevalent and associated with increased risk of CHD. Despite increasing emphasis on lipid-lowering treatment in the elderly population, questions remain regarding secondary and primary prevention of CHD. According to current clinical trial evidence, lipid-lowering therapy, specifically with HMG-CoA-reductase inhibitors, can reduce CHD morbidity and mortality without increased adverse effects in the elderly population. Lipid-lowering treatment should be considered for patients aged 65 to 75 years with a history of CHD or who are at moderate to high risk for CHD. Estrogen replacement therapy (ERT), which has also been shown to lower cholesterol levels, raises special considerations for postmenopausal women. However, recent findings suggest that postmenopausal women with a history of CHD should not be given estrogen solely for secondary prevention of CHD events.

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J Ky Med Assoc 2002 Dec;100(12):535-8
State of the art treatment of the most difficult low density lipoprotein (LDL) cholesterol problems:
LDL apheresis.
Whayne TF Jr, Zielke JC, Dickson LG, Winters JL.
Division of Cardiovascular, Medicine of the Gill Heart Institute, Lexington, Ky.

The patient benefit from reduction of an excessively elevated low density lipoprotein (LDL) cholesterol is now well established, especially when there is proven coronary atherosclerosis. Dietary adherence can lower LDL cholesterol by a maximum of 10% to 15%. The addition of a cholesterol-lowering medication frequently can achieve a major LDL cholesterol reduction. However, a small group of patients with a very high LDL cholesterol respond poorly to diet and pharmaceutical treatments. These same patients have the highest incidence for very premature coronary atherosclerosis and associated cardiac events. A few medical centers, including the University of Kentucky, have established a new program to benefit these difficult high-risk patients. The technique is known as LDL apheresis, an effective process for removal of LDL cholesterol. The procedure is highly effective but very costly and third-party approval barriers are preventing access to this essential treatment for some very high-risk coronary atherosclerosis patients.

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J Am Coll Cardiol 2002 Dec 18;40(12):2117-21
Comment in: J Am Coll Cardiol. 2002 Dec 18;40(12):2122-4.
Early statin therapy restores endothelial function in children with familial hypercholesterolemia.
de Jongh S, Lilien MR, op't Roodt J, Stroes ES, Bakker HD, Kastelein JJ.
Emma Children's Hospital, AMC, Amsterdam, Netherlands. s.dejongh@amc.uva.nl

OBJECTIVES: This study was designed to determine whether simvastatin improves endothelial function in children with familial hypercholesterolemia (FH). BACKGROUND: Endothelial function measured by flow-mediated dilation of the brachial artery (FMD) is used as a surrogate marker of cardiovascular disease (CVD). Adult studies have shown that statins reverse endothelial dysfunction and therefore reduce the risk for future CVD. METHODS: The study included 50 children with FH (9 to 18 years) and 19 healthy, non-FH controls. Children with FH were randomized to receive simvastatin or placebo for 28 weeks. The FMD was performed at baseline and at 28 weeks of treatment. RESULTS: At baseline, FMD was impaired in children with FH versus non-FH controls (p < 0.024). In the simvastatin FH group, FMD improved significantly, whereas the FMD remained unaltered in the placebo FH group throughout the study period (absolute increase 3.9% +/- 4.3% vs. 1.2% +/- 3.9%, p < 0.05). In the simvastatin FH group, FMD increased to a level similar to the non-FH controls (15.6% +/- 6.8% vs. 15.5% +/- 5.4%, p = 0.958). Upon treatment, the simvastatin FH group showed significant absolute reductions of total cholesterol (TC) (-2.16 +/- 1.04 mmol/l, 30.1%) and low-density lipoprotein cholesterol (LDL-C) (-2.13 +/- 0.99 mmol/l, 39.8%). The absolute change of FMD after 28 weeks of therapy was inversely correlated to changes of TC (r = -0.31, p < 0.05) and LDL-C (r = -0.31, p < 0.05). CONCLUSIONS: Our data show significant improvement of endothelial dysfunction towards normal levels after short-term simvastatin therapy in children with FH. These results emphasize the relevance of statin therapy in patients with FH at an early stage, when the atherosclerotic process is still reversible.

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Stroke 2003 Jan;34(1):22-5
Comment in: Stroke. 2003 Jan;34(1):22-5.
Risk of fatal stroke in patients with treated familial hypercholesterolemia: a prospective registry study.
Huxley RR, Hawkins MH, Humphries SE, Karpe F, Neil HA; Simon Broome Familial Hyperlipidaemia Register Group and Scientific Steering Committee.
Division Public Health and Primary Health Care, Institute of Health Sciences, University of Oxford, Oxford, UK.

BACKGROUND AND PURPOSE: Although it is recognized that in heterozygous familial hypercholesterolemia, large extracranial carotid vessels are affected by atherosclerosis, the risk of fatal stroke after treatment with cholesterol-lowering therapy remains uncertain. The goal of this study was to determine the risk of fatal stroke in patients with treated familial hypercholesterolemia. METHODS: A cohort of 1405 men and 1466 women with definite or possible heterozygous familial hypercholesterolemia was recruited from 21 outpatient lipid clinics in the United Kingdom. Patients were followed up prospectively from 1980 to 1998 for 22 992 person-years for a median duration of 7.9 years (interquartile range, 4.9 to 12.0 years). The mortality rate was calculated, and the standardized mortality ratio for men and women 20 to 79 years of age was derived from the ratio of the observed deaths to the number expected in the general population of England and Wales (standardized mortality ratio=100 for the standard population). RESULTS: A total of 169 deaths occurred; 9 (5.3%) were a result of stroke. The mortality rate from stroke was 0.39 per 1000 person-years (95% confidence interval, 0.18 to 0.74), and the standardized mortality ratio for fatal stroke was nonsignificantly lower than in the general population (79; 95% CI, 36 to 150). CONCLUSIONS: The results suggest that patients with treated familial hypercholesterolemia are not at increased risk of fatal stroke. However, the possibility cannot be excluded that untreated individuals are at increased risk, which would be consistent with the evidence that familial hypercholesterolemia is a panvascular disease.

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Yakugaku Zasshi 2002 Dec;122(12):1145-51
Pharmacoeconomic evaluation of anti-hyperlipidemic agent fenofibrate.
Hayakawa T, Shimoyama K, Sekiya S, Sekiguchi M, Inotsume N.
Department of Pharmacology and Therapeutics, Hokkaido College of Pharmacy, Department of Pharmacy, Sapporo Kosei Hospital, Hokkaido, Japan. hayakawa@hokuyakudai.ac.jp

We evaluated the economic efficiency as well as the clinical effectiveness on serum lipid levels of a change in drug therapy from bezafibrate or a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor to fenofibrate. Subjects were 26 outpatients suffering from type IIb or type IV hyperlipidemia who visited our hospital between October 2000 and January 2001. Medication doses, and serum lipid levels were recorded prior to the change to fenofibrate and at 6 months after the change. Medical costs were also calculated at the same time points. A significant reduction in medical costs of 14.9% was observed following the change to fenofibrate. Serum lipid levels were not significantly different, although an increase in low density lipoprotein-cholesterol (LDL-cholesterol) was observed in patients changing from the HMG-CoA reductase inhibitor. The actual drug costs were reduced by 21.8% in the bezafibrate to fenofibrate group and by 23.7% in the HMG-CoA reductase inhibitor to fenofibrate group. Although the drug costs of changing to fenofibrate decreased significantly, other costs remained almost unchanged.

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Am J Cardiol 2003 Jan 1;91(1):33-41
Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease.
Schneck DW, Knopp RH, Ballantyne CM, McPherson R, Chitra RR, Simonson SG.
AstraZeneca LP, Wilmington, Delaware 19850-5437, USA. dennis.schneck@astrazeneca.com

The lipid-lowering effects of rosuvastatin and atorvastatin were determined across their dose ranges in a 6-week, randomized, double-blind trial. Three hundred seventy-four hypercholesterolemic patients with fasting low-density lipoprotein (LDL) cholesterol > or =160 but <250 mg/dl (> or =4.14 but <6.47 mmol/L) and fasting triglycerides <400 mg/dl (<4.52 mmol/L) and without active arterial disease within 3 months of entry received once-daily rosuvastatin (5, 10, 20, 40, or 80 mg [n = 209]) or atorvastatin (10, 20, 40, or 80 mg [n = 165]). The percentage decrease in plasma LDL cholesterol versus dose was log-linear for each drug, ranging from -46.6% to -61.9% for rosuvastatin 10 and 80 mg, compared with -38.2% to -53.5% for atorvastatin 10 and 80 mg. The dose curve for rosuvastatin yielded an 8.4% greater decrease in LDL cholesterol compared with atorvastatin at any given dose (p <0.001). Similarly greater decreases were observed for rosuvastatin across the dose range in total cholesterol (-4.9%), non-high-density lipoprotein (non-HDL) cholesterol (-7.0%), apolipoprotein B (-6.3%), and related ratios versus atorvastatin (all p <0.001). Because dose responses for HDL cholesterol, triglycerides, and apolipoprotein A-I were non-log-linear and nonparallel between the 2 drugs, percentage changes from baseline were compared at each dose. Significantly greater increases for rosuvastatin compared with atorvastatin were observed for HDL cholesterol at 40 and 80 mg, and for apolipoprotein A-I at 80 mg. Significantly greater triglyceride decreases were seen at 80 mg with atorvastatin over rosuvastatin. Both rosuvastatin and atorvastatin were well tolerated over 6 weeks.

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J Am Coll Cardiol 2002 Dec 18;40(12):2125-34
Comment in: J Am Coll Cardiol. 2002 Dec 18;40(12):2135-8.
Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia.
Davidson MH, McGarry T, Bettis R, Melani L, Lipka LJ, LeBeaut AP, Suresh R, Sun S, Veltri EP.
Chicago Center for Clinical Research, Illinois 60610, USA. mdavidson@protocare.com

OBJECTIVES: The purpose of this study was to assess the efficacy and safety of ezetimibe administered with simvastatin in patients with primary hypercholesterolemia. BACKGROUND: Despite the availability of statins, many patients do not achieve lipid targets. Combination therapy with lipid-lowering agents that act via a complementary pathway may allow additional patients to achieve recommended cholesterol goals. METHODS: After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =145 mg/dl to < or =250 mg/dl and triglycerides (TG) < or =350 mg/dl were randomized to one of the following 10 groups administered daily for 12 consecutive weeks: ezetimibe 10 mg; simvastatin 10, 20, 40, or 80 mg; ezetimibe 10 mg plus simvastatin 10, 20, 40, or 80 mg; or placebo. The primary efficacy variable was percentage reduction from baseline to end point in direct LDL-C for the pooled ezetimibe plus simvastatin groups versus pooled simvastatin groups. RESULTS: Ezetimibe plus simvastatin significantly improved LDL-C (p < 0.01), high-density lipoprotein cholesterol (HDL-C) (p = 0.03), and TG (p < 0.01) compared with simvastatin alone. Ezetimibe plus simvastatin (pooled doses) provided an incremental 13.8% LDL-C reduction, 2.4% HDL-C increase, and 7.5% TG reduction compared with pooled simvastatin alone. Coadministration of ezetimibe and simvastatin provided LDL-C reductions of 44% to 57%, TG reductions of 20% to 28%, and HDL-C increases of 8% to 11%, depending on the simvastatin dose. Ezetimibe 10 mg plus simvastatin 10 mg and simvastatin 80 mg alone each provided a 44% LDL-C reduction. The coadministration of ezetimibe with simvastatin was well tolerated, with a safety profile similar to those of simvastatin and of placebo. CONCLUSIONS: When coadministered with simvastatin, ezetimibe provided significant incremental reductions in LDL-C and TG, as well as increases in HDL-C. Coadministration of ezetimibe with simvastatin was well tolerated and comparable to statin alone.

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Wien Klin Wochenschr 2002 Oct 31;114(19-20):840-6
Effect of prickly pear (Opuntia robusta) on glucose- and lipid-metabolism in non-diabetics with hyperlipidemia—a pilot study.
Wolfram RM, Kritz H, Efthimiou Y, Stomatopoulos J, Sinzinger H.
Department of Angiology, University of Vienna, Vienna, Austria.

BACKGROUND: Besides others pectin, a soluble fibre, has been reported to be effective in lowering cholesterol levels in both animals and man with hyperlipidemia as well as being able to slow carbohydrate absorption and hence reduce the postprandial rise in blood glucose and serum insulin in patients with type-II diabetes. Aim of this pilot study was to assess the effect of prickly pear consumption on glucose- and lipid metabolism. DESIGN: In 24 non-diabetic, non-obese males (aged 37-55 years) suffering from primary isolated hypercholesterolemia (n = 12; group A) or combined hyperlipidemia (n = 12; group B) respectively, the influence of prickly pear pectin (Opuntia robusta)-intake on glucose- and lipid metabolism was examined. After an 8 week pre-running phase with a 7506 KJ step-I diet (phase I), 625 KJ were replaced by prickly pear edible pulp (250 g/day) for 8 further weeks (phase II). RESULTS: Prickly pear leads to a decrease of total cholesterol (12%), low-density lipoprotein-cholesterol (15%), apolipoprotein B (9%), triglycerides (12%), fibrinogen (11%), blood glucose (11%), insulin (11%) and uric acid (10%), while body weight, high-density lipoprotein-cholesterol, apolipoprotein A-I, and lipoprotein(a) remained unchanged. CONCLUSION: The hypocholesterolemic action of prickly pear may be partly explained by the fibre (pectin) content, but the hypoglycaemic actions (improvement of insulin sensitivity) in the non-obese, non-diabetic need further investigation to get more insights on the potential advantage of treating the metabolic syndrome.

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Pharmacotherapy 2002 Dec;22(12):1527-32
Comparison of gemfibrozil and fenofibrate in patients with dyslipidemic coronary heart disease.
Packard KA, Backes JM, Lenz TL, Wurdeman RL, Destache C, Hilleman DE.
Creighton Cardiac Center, Creighton University, Omaha, Nebraska 68131, USA. Katie.Packard@cardiac.creighton.edu

STUDY OBJECTIVE: To compare the lipid-lowering effects of gemfibrozil and fenofibrate in patients with dyslipidemic coronary heart disease. DESIGN: Open label, fixed-dosage, retrospective-prospective, one-way crossover from gemfibrozil to fenofibrate. SETTING: University-affiliated outpatient clinics. PATIENTS: Eighty patients with coronary heart disease with a baseline low-density lipoprotein cholesterol (LDL) level above 130 mg/dl or a triglyceride level of 200 mg/dl or higher who had been receiving gemfibrozil 600 mg twice/day. Thirty-nine (49%) patients had received concomitant therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) for a minimum of 9 months. INTERVENTION: All patients received gemfibrozil 600 mg twice/day for at least 3 months before being switched to fenofibrate 201 mg/day. Patients receiving concomitant statin therapy before crossover continued the statin at the same dosage after crossover. Before crossover, a fasting lipid profile was determined and patients were queried about the side effects of lipid-lowering therapy. A repeat fasting lipid profile was obtained 12 weeks after the crossover. MEASUREMENTS AND MAIN RESULTS: Patients were stratified into those receiving versus those not receiving concomitant statin therapy. In both of these groups, fenofibrate was associated with significantly greater reductions in total cholesterol, LDL, and triglycerides than gemfibrozil (all p < 0.001). In addition, fenofibrate was associated with a significantly greater increase in high-density lipoprotein cholesterol (HDL) than gemfibrozil (p < 0.001). No patients reported new-onset adverse effects after the crossover. CONCLUSIONS: Compared with gemfibrozil, fenofibrate produced significantly greater reductions in total cholesterol, LDL, and triglycerides and significantly greater increases in HDL. These changes were evident in patients receiving and not receiving concomitant statin therapy.

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JAMA 2002 Dec 18;288(23):2998-3007
Comment in: JAMA. 2002 Dec 18;288(23):3042-4.
Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT).
The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

CONTEXT: Studies have demonstrated that statins administered to individuals with risk factors for coronary heart disease (CHD) reduce CHD events. However, many of these studies were too small to assess all-cause mortality or outcomes in important subgroups. OBJECTIVE: To determine whether pravastatin compared with usual care reduces all-cause mortality in older, moderately hypercholesterolemic, hypertensive participants with at least 1 additional CHD risk factor. DESIGN AND SETTING: Multicenter (513 primarily community-based North American clinical centers), randomized, nonblinded trial conducted from 1994 through March 2002 in a subset of participants from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). PARTICIPANTS: Ambulatory persons (n = 10 355), aged 55 years or older, with low-density lipoprotein cholesterol (LDL-C) of 120 to 189 mg/dL (100 to 129 mg/dL if known CHD) and triglycerides lower than 350 mg/dL, were randomized to pravastatin (n = 5170) or to usual care (n = 5185). Baseline mean total cholesterol was 224 mg/dL; LDL-C, 146 mg/dL; high-density lipoprotein cholesterol, 48 mg/dL; and triglycerides, 152 mg/dL. Mean age was 66 years, 49% were women, 38% black and 23% Hispanic, 14% had a history of CHD, and 35% had type 2 diabetes. INTERVENTION: Pravastatin, 40 mg/d, vs usual care. MAIN OUTCOME MEASURES: The primary outcome was all-cause mortality, with follow-up for up to 8 years. Secondary outcomes included nonfatal myocardial infarction or fatal CHD (CHD events) combined, cause-specific mortality, and cancer. RESULTS: Mean follow-up was 4.8 years. During the trial, 32% of usual care participants with and 29% without CHD started taking lipid-lowering drugs. At year 4, total cholesterol levels were reduced by 17% with pravastatin vs 8% with usual care; among the random sample who had LDL-C levels assessed, levels were reduced by 28% with pravastatin vs 11% with usual care. All-cause mortality was similar for the 2 groups (relative risk [RR], 0.99; 95% confidence interval [CI], 0.89-1.11; P =.88), with 6-year mortality rates of 14.9% for pravastatin vs 15.3% with usual care. CHD event rates were not significantly different between the groups (RR, 0.91; 95% CI, 0.79-1.04; P =.16), with 6-year CHD event rates of 9.3% for pravastatin and 10.4% for usual care. CONCLUSIONS: Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C. The results may be due to the modest differential in total cholesterol (9.6%) and LDL-C (16.7%) between pravastatin and usual care compared with prior statin trials supporting cardiovascular disease prevention.

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Metabolism 2002 Dec;51(12):1596-604
A dietary portfolio approach to cholesterol reduction: combined effects of plant sterols, vegetable proteins, and viscous fibers in hypercholesterolemia.
Jenkins DJ, Kendall CW, Faulkner D, Vidgen E, Trautwein EA, Parker TL, Marchie A, Koumbridis G, Lapsley KG, Josse RG, Leiter LA, Connelly PW.
Clinical Nutrition and Risk Factor Modification Center, Division of Endocrinology and Metabolism, St. Michael's Hospital, Toronto, Ontario, Canada.

Plant sterols, soy proteins, and viscous fibers are advised for cholesterol reduction but their combined effect has never been tested. We therefore assessed their combined effect on blood lipids in hyperlipidemic subjects who were already consuming a low-saturated fat, low-cholesterol diet before starting the study. The test (combination) diet was 1 month in duration and was very low in saturated fat and high in plant sterols (1 g/1,000 kcal), soy protein (23 g/1,000 kcal), and viscous fibers (9 g/1,000 kcal) obtained from foods available in supermarkets and health food stores. One subject also completed 2 further diet periods: a low-fat control diet and a control diet plus 20 mg/d lovastatin. Fasting blood lipids, blood pressure, and body weight were measured prior to and at weekly intervals during the study. The combination diet was rated as acceptable and very filling. The diet reduced low-density lipoprotein (LDL)-cholesterol by 29.0% +/- 2.7% (P <.001) and the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol by 26.5% +/- 3.4% (P <.001). Near maximal reductions were seen by week 2. In the subject who took Mevacor and control diets each for 4 weeks, the reduction in LDL:HDL-cholesterol on Mevacor was similar to the combination diet. We conclude that acceptable diets of foods from supermarkets and health food stores that contain recognized cholesterol-lowering dietary components in combination (a dietary portfolio) may be as effective as the starting dose of older first-line drugs in managing hypercholesterolemia. Copyright 2002, Elsevier Science (USA). All rights reserved.

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J Am Diet Assoc 2002 Dec;102(12):1807-11
Effects of a new soy/beta-sitosterol supplement on plasma lipids in moderately
hypercholesterolemic subjects.
Cicero AF, Fiorito A, Panourgia MP, Sangiorgi Z, Gaddi A.
Atherosclerosis and Dysmetabolic Disease Study Center G. Descovich, Clinical Medicine and Applied Biotechnologies D. Campanacci, University of Bologna, Italy. afgcicero@tiscalinet.it

Our aim was to test the hypocholesterolemic effect of a low-dose formulation of soy proteins supplemented with isolated b-sitosterol in a ratio of 4:1 in 20 moderately hypercholesterolemic subjects. The study has been divided in three different periods of forty days each: a stabilization diet period, then a treatment period during which all subjects assumed 10 g one time a day of the tested product and, finally, a wash out period. From the end of the stabilization diet period to the end of the soy protein added in b-sitosterol supplementation we observed a 0.45 +/- 0.30 mmol/L, 0.09 +/- 0.31 mmol/L and 0.17 +/- 0.22 mmol/L mean +/- SE decrease in respectively LDL-C, TG and apoB levels, associated with a 0.12 +/- 0.25 and 0.03 +/- 0.51 mg/dL mean increase respectively in HDL-C and apoA plasma concentrations. According to this recommends, low doses of soy protein added in b-sitosterol seems to be a practical and safe alternative for patients seeking modest reductions in LDL-C (< 15%).

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Am Heart J 2002 Dec;144(6):1044-51
Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolemia.
Olsson AG, Istad H, Luurila O, Ose L, Stender S, Tuomilehto J, Wiklund O, Southworth H, Pears J, Wilpshaar JW; Rosuvastatin Investigators Group.
Department of Medicine and Care, University Hospital, Linkoping, Sweden. andol@kfc.liu.se

BACKGROUND: Despite the demonstrated benefits of low-density lipoprotein cholesterol (LDL-C) reduction in reducing the risk of coronary heart disease, many patients receiving lipid-lowering therapy fail to achieve LDL-C goals. We compared the effects of rosuvastatin and atorvastatin in reducing LDL-C and achieving LDL-C goals in patients with primary hypercholesterolemia. METHODS AND RESULTS: In this 52-week, randomized, double-blind, multicenter trial (4522IL/0026), 412 patients with LDL-C 160 to <250 mg/dL received a 5-mg dose of rosuvastatin (n = 138), a 10-mg dose of rosuvastatin (n = 134), or a 10-mg dose of atorvastatin (n = 140) for 12 weeks; during the following 40 weeks, dosages could be sequentially doubled up to 80 mg if National Cholesterol Education Program Adult Treatment Panel II (ATP-II) LDL-C goals were not achieved. At 12 weeks, 5- and 10-mg doses of rosuvastatin were associated with significantly greater LDL-C reductions than 10-mg doses of atorvastatin (46% and 50% vs 39%, both P <.001). At 12 weeks, both rosuvastatin dosages brought more patients to within ATP-II and European LDL-C goals than atorvastatin (86% and 89% vs 73% and 75%, and 86% vs 55%, respectively). At 52 weeks, compared with atorvastatin, both initial rosuvastatin treatment groups significantly reduced LDL-C (47% and 53% vs 44%, P <.05 and P <.001). Overall, more patients in the initial rosuvastatin 10-mg group achieved their ATP-II LDL-C goal than those in the initial atorvastatin 10-mg group (98% vs 87%), with 82% of patients treated with rosuvastatin achieving their goal at the 10-mg starting dosage without the need for titration, compared with 59% of patients treated with atorvastatin. Both treatments were well tolerated over 52 weeks. CONCLUSION: Compared with atorvastatin, rosuvastatin produced greater reductions in LDL-C, which may offer advantages in LDL-C goal attainment over existing lipid-lowering therapies.

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Am Heart J 2002 Dec;144(6):1036-43
Efficacy and safety of rosuvastatin compared with pravastatin and simvastatin in patients with hypercholesterolemia: a randomized, double-blind, 52-week trial.
Brown WV, Bays HE, Hassman DR, McKenney J, Chitra R, Hutchinson H, Miller E; Rosuvastatin Study Group.
Emory University School of Medicine, Atlanta, Ga 30322, USA. w.virgil.brown@med.va.gov

OBJECTIVE: The primary objective of this trial was to compare the efficacy of rosuvastatin with that of pravastatin and simvastatin for lowering low-density lipoprotein cholesterol (LDL-C) levels. METHODS: In this randomized, double-blind, multicenter trial, lipid levels were measured in 477 patients (baseline LDL-C > or =160 and <250 mg/dL) who received fixed doses of 5 mg of rosuvastatin, 10 mg of rosuvastatin, 20 mg of pravastatin, or 20 mg of simvastatin for 12 weeks. For an additional 40 weeks, individual daily doses were sequentially doubled to a maximum of 80 mg of rosuvastatin, 40 mg of pravastatin, and 80 mg of simvastatin, according to investigator discretion and if National Cholesterol Education Program Adult Treatment Panel II (ATP II) LDL-C goals were not achieved. RESULTS: At 12 weeks, percent LDL-C reductions after both 5-mg and 10-mg rosuvastatin treatment, which were 39.1% and 47.4%, respectively, were significantly different (P <.05) from LDL-C reductions after 20-mg pravastatin (26.5%) and 20-mg simvastatin (34.6%) treatment. After 52 weeks, more rosuvastatin-treated patients remained at their starting dose than did simvastatin or pravastatin patients. After dose titration, 88% and 87.5% of the rosuvastatin 5-mg and 10-mg groups, respectively, achieved their ATP II LDL-C goals, compared with 60% for pravastatin and 72.5% for simvastatin. All study treatments were well tolerated. CONCLUSION: Rosuvastatin reduced LDL-C levels more than pravastatin or simvastatin in patients with hypercholesterolemia in a 52-week dose-titration study.

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Am Heart J 2002 Dec;144(6 Suppl):S43-50
Management of dyslipidemia in the high-risk patient.
Stein EA.
Metabolic and Atherosclerosis Research Center and Medical Research Laboratories International, Cincinnati, Ohio 45229, USA. ESteinMRL@aol.com

Lipid-lowering agents have been shown to reduce morbidity and mortality associated with coronary heart disease (CHD), particularly in high-risk patients. The identification and treatment of these patients should therefore be a high priority for clinicians. Guidelines from medical organizations, such as the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) and the American Diabetes Association (ADA), suggest that patients with low-density lipoprotein cholesterol (LDL-C) levels > or =130 mg/dL, and perhaps even those with levels > or =100 mg/dL, should receive drug therapy. Optimal LDL-C levels have been set at <100 mg/dL and <115 mg/dL for high-risk patients by US and European guidelines, respectively. However, a recent survey shows that only about 20% of high-risk patients currently meet these goals. In order to achieve therapeutic targets for LDL-C, the statins are the foundation of treatment, as they are the most effective and best-tolerated form of lipid-lowering therapy. Other therapeutic options include bile acid sequestrants, niacin, and plant stanols, although seldom as monotherapy. Combination therapy with a statin and one of these other lipid-lowering agents can be useful in patients who are unable to achieve target lipid levels through monotherapy. There remains, however, a need for additional agents. Some of the new options for reducing LDL-C levels that may be available in the near future include 2 new statins, pitavastatin and rosuvastatin. In patients with heterozygous familial hypercholesterolemia, rosuvastatin, which is currently under review by the Food and Drug Administration (FDA), has been shown to produce significantly greater reductions in LDL-C than atorvastatin over its full dose range. In comparative clinical trials, it has also enabled more patients with primary hypercholesterolemia to meet lipid goals than atorvastatin, simvastatin, and pravastatin. Inhibitors of bile acid transport or cholesterol absorption may also have therapeutic value. The first cholesterol absorption inhibitor, ezetimibe, which has just been approved by the FDA, appears to be most effective when combined with a statin. It is anticipated that such new options will allow clinicians to optimize the management of dyslipidemia in high-risk patients, thereby reducing the morbidity and mortality of CHD.

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Am J Clin Nutr 2002 Dec;76(6):1272-8
Unesterified plant sterols and stanols lower LDL-cholesterol concentrations equivalently in hypercholesterolemic persons.
Vanstone CA, Raeini-Sarjaz M, Parsons WE, Jones PJ.
School of Dietetics and Human Nutrition, McGill University, Ste Anne-de-Bellevue, Quebec, Canada.

BACKGROUND: Plant sterols, in various forms, have been shown to reduce total and LDL-cholesterol concentrations. Particularly controversial at present is the effect of the degree of hydrogenation of the plant sterols on cholesterol-lowering efficacy and the responsible mechanisms. OBJECTIVE: Our goal was to examine the effect of supplementation with unesterified plant sterols and stanols on plasma lipid and phytosterol concentrations and cholesterol absorption, synthesis, and turnover. DESIGN: Fifteen otherwise healthy hypercholesterolemic subjects consumed each of 4 dietary treatments in a randomized crossover design. Unesterified sterols and stanols were blended into the butter component of the diet at a dosage of 1.8 g/d. The diets contained plant sterols (NS), plant stanols (SS), a 50:50 mixture of sterols and stanols (NSS), or cornstarch (control). RESULTS: Plasma total cholesterol concentrations were 7.8%, 11.9%, and 13.1% lower (P < 0.01) in the NS, SS, and NSS groups, respectively, than in the control group. LDL-cholesterol concentrations were 11.3%, 13.4%, and 16.0% lower (P < 0.03) in the NS, SS, and NSS groups, respectively, than in the control group. Plasma triacylglycerols and HDL-cholesterol concentrations did not differ significantly across diets. Cholesterol absorption efficiency was 56.0%, 34.4%, and 48.9% lower (P < 0.001) in the NS, SS, and NSS groups, respectively, than in the control group. The fractional synthesis rate was higher by 45.5% (P < 0.003) in the NSS group than in the control group. Plasma campesterol and sitosterol concentrations were higher (P < 0.01) in the NS group and sitosterol concentrations were lower (P < 0.01) in the SS group than in the control group. CONCLUSION: These data indicate that, in their free unesterified form, sterols and stanols lower plasma LDL cholesterol equivalently in hypercholesterolemic persons by suppressing cholesterol absorption.

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Am J Med Sci 2002 Nov;324(5):247-53
Eicosapentaenoic acid improves endothelial function in hypertriglyceridemic subjects despite increased lipid oxidizability.
Okumura T, Fujioka Y, Morimoto S, Tsuboi S, Masai M, Tsujino T, Ohyanagi M, Iwasaki T.
Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.

BACKGROUND: Epidemiologic investigations suggest that fish oil, which contains eicosapentaenoic acid (EPA), has favorable cardiovascular effects. Fish oil improves endothelial function in subjects with hypercholesterolemia or diabetes. However, controversy persists regarding relationships between primary hypertriglyceridemia and endothelial dysfunction. Moreover, lipoproteins are more susceptible to oxidation in vitro after incorporation of fish oil. METHODS: We determined the effects of EPA on serum lipids, susceptibility of low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) to oxidation, and endothelial function in hypertriglyceridemic (HTG) subjects. In 8 men with untreated primary hypertriglyceridemia (plasma triglyceride between 150 and 500 mg/dL) and 7 control subjects (triglyceride below 150 mg/dL), forearm blood flow (FBF) responses were tested. In HTG subjects, this was repeated 3 months after initiation of EPA (1800 mg/day). Cu2+-induced oxidation of VLDL and LDL was determined by serial measurement of conjugated dienes. We used lag time, which corresponded to the period when the lipoproteins were resistant to oxidation, as a parameter of oxidizability. FBF responses to acetylcholine and sodium nitroprusside were determined by strain-gauge plethysmography. RESULTS: Plasma triglyceride in HTG subjects fell 31% with EPA supplementation. Before EPA, VLDL and LDL lag times in HTG subjects were shorter than in control subjects. EPA further reduced lag time for VLDL but not LDL. The FBF response to acetylcholine (but not to nitroprusside) was significantly less in HTG subjects before EPA than in control subjects. EPA normalized the FBF response to acetylcholine. CONCLUSIONS: EPA improves endothelial function in HTG subjects despite increasing in VLDL oxidizability.

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Expert Opin Investig Drugs 2002 Nov;11(11):1587-604
Ezetimibe.
Bays H.
Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Ave, Louisville, KY 40213, USA.

Ezetimibe is a cholesterol absorption inhibitor that significantly lowers low- density lipoprotein cholesterol (LDL-C), and favourably affects triglyceride and high-density lipoprotein cholesterol blood levels in monotherapy and in combination with statins. Hepatic and extrahepatic (peripheral) cholesterol synthesis are well-known sources of cholesterol found in LDL-C. However, the emergence of ezetimibe has highlighted intestinal cholesterol absorption as an additional, important source of cholesterol in LDL-C, and has better illuminated how genetic factors, dietary content, pharmaceutical agents, and nuclear receptor activation (such as liver X receptors) all influence the relative contribution of these important cholesterol sources to LDL-C. In fact, investigations into ezetimibe have sometimes challenged existing scientific dogma, has prompted reconsideration of older data, and has helped create 'new' paradigms in cholesterol metabolism. Thus, ezetimibe's efficacy, excellent tolerability, and safety has not only expanded potential treatment options for dyslipidaemic patients, but also has promoted exploration of new frontiers of lipid research towards a better understanding of cholesterol metabolism.

   

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