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Latest Research on Hyperlipidemia
     
Neurology. 2008 Feb 13 [Epub ahead of print]
Dyslipidemia is a protective factor in amyotrophic lateral sclerosis.
Dupuis L, Corcia P, Fergani A, De Aguilar JL, Bonnefont-Rousselot D, Bittar R, Seilhean D, Hauw JJ, Lacomblez L, Loeffler JP, Meininger V.
From INSERM (L.D., A.F., J.-L.G.D.A., J.-P.L.), U692, Laboratoire de Signalisations Moléculaires et Neurodégénérescence, Strasbourg; Université Louis Pasteur (L.D., A.F., J.-L.G.D.A., J.-P.L.), Faculté de Médecine, UMRS692, Strasbourg; Service de Neurologie (P.C.), Centre SLA, CHU Bretonneau, Tours; Laboratoire des Lipides (D.B.-R., R.B.), Groupe Hospitalier Pitié-Salpêtrière (AP-HP), Paris; Laboratoire de Neuropathologie (D.S., J.-J.H.) and Fédération des Maladies du Système Nerveux, Centre référent maladie rare SLA (L.L., V.M.), Hôpital de la Pitié-Salpêtrière (AP-HP), Paris; and Université Pierre et Marie Curie (D.B.-R., R.B., D.S., J.-J.H., L.L., V.M.), Paris, France.

ABSTRACT BACKGROUND: Amyotrophic lateral sclerosis (ALS) is the most serious form of degenerative motor neuron disease in adults, characterized by upper and lower motor neuron degeneration, skeletal muscle atrophy, paralysis, and death. High prevalence of malnutrition and weight loss adversely affect quality of life. Moreover, two thirds of patients develop a hypermetabolism of unknown cause, leading to increased resting energy expenditure. Inasmuch as lipids are the major source of energy for muscles, we determined the status of lipids in a population of patients with ALS and investigated whether lipid contents may have an impact on disease progression and survival. METHODS: Blood concentrations of triglycerides, cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were measured in a cohort of 369 patients with ALS and compared to a control group of 286 healthy subjects. Postmortem histologic examination was performed on liver specimens from 59 other patients with ALS and 16 patients with Parkinson disease (PD). RESULTS: The frequency of hyperlipidemia, as revealed by increased plasma levels of total cholesterol or LDL, was twofold higher in patients with ALS than in control subjects. As a result, steatosis of the liver was more pronounced in patients with ALS than in patients with PD. Correlation studies demonstrated that bearing an abnormally elevated LDL/HDL ratio significantly increased survival by more than 12 months. CONCLUSIONS: Hyperlipidemia is a significant prognostic factor for survival of patients with amyotrophic lateral sclerosis. This finding highlights the importance of nutritional intervention strategies on disease progression and claims our attention when treating these patients with lipid-lowering drugs.

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J Am Coll Cardiol. 2008 Jan 22;51(3):249-55.
Dietary strategies for improving post-prandial glucose, lipids, inflammation, and cardiovascular health.
O'Keefe JH, Gheewala NM, O'Keefe JO.
Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, Missouri, USA. jhokeefe@cc-pc.com

The highly processed, calorie-dense, nutrient-depleted diet favored in the current American culture frequently leads to exaggerated supraphysiological post-prandial spikes in blood glucose and lipids. This state, called post-prandial dysmetabolism, induces immediate oxidant stress, which increases in direct proportion to the increases in glucose and triglycerides after a meal. The transient increase in free radicals acutely triggers atherogenic changes including inflammation, endothelial dysfunction, hypercoagulability, and sympathetic hyperactivity. Post-prandial dysmetabolism is an independent predictor of future cardiovascular events even in nondiabetic individuals. Improvements in diet exert profound and immediate favorable changes in the post-prandial dysmetabolism. Specifically, a diet high in minimally processed, high-fiber, plant-based foods such as vegetables and fruits, whole grains, legumes, and nuts will markedly blunt the post-meal increase in glucose, triglycerides, and inflammation. Additionally, lean protein, vinegar, fish oil, tea, cinnamon, calorie restriction, weight loss, exercise, and low-dose to moderate-dose alcohol each positively impact post-prandial dysmetabolism. Experimental and epidemiological studies indicate that eating patterns, such as the traditional Mediterranean or Okinawan diets, that incorporate these types of foods and beverages reduce inflammation and cardiovascular risk. This anti-inflammatory diet should be considered for the primary and secondary prevention of coronary artery disease and diabetes.

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Vasc Health Risk Manag. 2007;3(6):877-86.
Practical guidelines for familial combined hyperlipidemia diagnosis: an up-date.
Gaddi A, Cicero AF, Odoo FO, Poli AA, Paoletti R; Atherosclerosis and Metabolic Diseases Study Group.
Center for Metabolic diseases and Atherosclerosis, University of Bologna, Italy. gaddiats@med.unibo.it

Familial combined hyperlidemia (FCH) is a common metabolic disorder characterized by: (a) increase in cholesterolemia and/or triglyceridemia in at least two members of the same family, (b) intra-individual and intrafamilial variability of the lipid phenotype, and (c) increased risk of premature coronary heart disease (CHD). FCH is very frequent and is one of the most common genetic hyperlipidemias in the general population (prevalence estimated: 0.5%-2.0%), being the most frequent in patients affected by CHD (10%) and among acute myocardial infarction survivors aged less than 60 (11.3%). This percentage increases to 40% when all the myocardial infarction survivors are considered without age limits. However, because of the peculiar variability of laboratory parameters, and because of the frequent overlapping with the features of metabolic syndrome, this serious disease is often not recognized and treated. The aim of this review is to define the main characteristics of the disease in order to simplify its detection and early treatment by all physicians by mean of practical guidelines.

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Am J Manag Care. 2007 Dec;13 Suppl 10:S270-5.
Comparison of low-density lipoprotein cholesterol reduction after switching patients on other statins to rosuvastatin or simvastatin in a real-world clinical practice setting.
Fox KM, Gandhi SK, Ohsfeldt RL, Davidson MH.
kathyfox@comcast.net

OBJECTIVE: The study compared low-density lipoprotein cholesterol (LDL-C) reduction obtained after switching patients on a statin therapy to rosuvastatin or simvastatin in real-world clinical practice. METHODS: Using information from an electronic medical records database, for patients >or=18 years of age who received newly prescribed statin therapy during August 2003 to March 2006, who were switched to either rosuvastatin or simvastatin, and who had LDL-C values at baseline, switch and postswitch data were included (N = 277). Percent LDL-C reduction between patients switched to rosuvastatin (n = 155) and those switched to simvastatin (n = 122) were compared. Linear regression model was adjusted for percent LDL-C change from preswitch to switch, LDL-C at time of switch, age, sex, smoking, statin aggressiveness, and therapy duration postswitch. Percent LDL-C reduction for patients switched from atorvastatin to rosuvastatin versus atorvastatin to simvastatin was also compared.
RESULTS: Patients switched to rosuvastatin or simvastatin were similar in age, sex, and baseline LDL-C (mean, 146 mg/dL). Patients switched to rosuvastatin from any other statin had a significantly greater percent LDL-C reduction (18.4%) postswitch than patients switched to simvastatin (5.8%; P = .0003). After adjusting for baseline covariates, rosuvastatin patients had a significantly greater percent LDL-C reduction postswitch than simvastatin patients (16.0% vs 8.8%, respectively; P = .0002). In the subgroup of patients switched from atorvastatin, patients switched to rosuvastatin (n = 67) had a significantly greater adjusted percent LDL-C reduction (13.6%) postswitch than patients switched to simvastatin (5.5%; n = 75; P = .001). CONCLUSION: Rosuvastatin achieves greater percent LDL-C reduction than simvastatin as a switch therapy in a real-world clinical practice setting. This highlights the need to select the statin to switch to based on additional needed percent LDL-C reduction to meet individual patient targets. Availability of simvastatin (generic statin) and rosuvastatin (branded statin) as treatment options would facilitate efficient and effective management of patients with dyslipidemia.

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Eur J Neurol. 2007 Dec;14(12):1334-7. Epub 2007 Oct 3.
Topiramate: effects on serum lipids and lipoproteins levels in children.
Franzoni E, Verrotti A, Sarajlija J, Garone C, Matricardi S, Salerno GG, Monti M, Chiarelli F.
Child Neuropsychiatry Unit, University of Bologna, Bologna, Italy. emailio.franzoni@unibo.it

The present controlled study aims to evaluate topiramate (TPM) effect on total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein, very low-density lipoprotein, apolipoproteins A1, B and lipoprotein (a). Seventy patients in evolving age suffering from various types of epilepsy, treated with TPM, (age range: 6 months-22 years) were evaluated before and after 12 months of treatment and compared with 110 sex- and age-matched subjects. At baseline, no significant difference was present between controls and children treated with TPM. After a year, the BMI did not show significant change in adults and remained into respective growth curve. No significant difference in lipids and lipoproteins neither between first and second evaluation nor between patients and controls was found. Some intra-group variation has been noticed: whilst controls maintained similar levels, the 70 patients on TPM monotherapy showed a slight decrease in TC, triglycerides and HDL. These fluctuations, however, occurred in the normal range so neither dietary nor pharmacological treatment of hyperlipidaemia after a year of TPM was necessary.

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Am J Cardiovasc Drugs. 2007;7(6):453-65.
Colesevelam: a review of its use in hypercholesterolemia.
Robinson DM, Keating GM.
Wolters Kluwer Health | Adis, Auckland, New Zealand, an editorial office of Wolters Kluwer Health, Conshohocken, Pennsylvania, USA.

Colesevelam hydrochloride (Cholestagel((R)), WelChol((R))) is an orally administered, non-absorbable, polymeric, bile-acid-binding agent with a higher affinity for glycocholic acid in vitro and greater capacity for binding bile acids in vivo than other bile-acid-binding agents.In randomized controlled trials in patients with primary hypercholesterolemia, colesevelam monotherapy reduced mean serum low-density lipoprotein-cholesterol (LDL-C) levels by 9-19%. In combination with an HMG-CoA reductase inhibitor (statin) or fenofibrate, colesevelam induced additive reductions in LDL-C 10-16% greater than those achieved by monotherapy with a statin (in patients with primary hypercholesterolemia) or fenofibrate (in patients with mixed hyperlipidemia). Colesevelam was generally well tolerated, with a relatively low incidence of gastrointestinal adverse events and a high compliance rate. Thus, colesevelam provides a useful addition to primary therapy with statins in the treatment of primary hypercholesterolemia, or fenofibrate in the treatment of mixed hyperlipidemia.

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Fundam Clin Pharmacol. 2007 Nov;21 Suppl 2:5-6.
Nicotinic acid in the treatment of hyperlipidaemia.
Drexel H.
Abteilung für Innere Medizin, Landeskrankenhaus Feldkirch, Carinagasse 47, A-6807 Feldkirch, Austria.

Nicotinic acid has been in use as a lipid-lowering drug for five decades now. It is effective in lowering low-density lipoprotein (LDL)-cholesterol, triglycerides, and lipoprotein (a), and in increasing high-density lipoprotein (HDL)-cholesterol. All these effects are pronounced, and at present greater increase of HDL-cholesterol cannot be obtained by any other drug. Patients with hypertriglyceridaemia/low HDL-cholesterol are the most suitable candidates for being treated with this drug. This pattern is typical for type 2 diabetic patients, for patients with metabolic syndrome, and for those with impaired glucose tolerance. From a few studies, there is evidence that nicotinic acid is effective in reducing cardiovascular events. Although overall safety is good, the unpleasant side effect of flushing, albeit not harmful, precludes many patients from taking the drug. New formulations of intermediate release or a combination with anti-flush compounds should increase the compliance with the drug.

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J Thorac Cardiovasc Surg. 2007 Nov;134(5):1143-9.
Lipid-lowering effect of preoperative statin therapy on postoperative major adverse cardiac events after coronary artery bypass surgery.

Thielmann M, Neuhäuser M, Marr A, Jaeger BR, Wendt D, Schuetze B, Kamler M, Massoudy P, Erbel R, Jakob H.
Department of Thoracic and Cardiovascular Surgery, West German Heart Center Essen, University Hospital Essen, Essen, Germany. matthias.thielmann@uni-due.de

OBJECTIVE: Statins are powerful lipid-lowering drugs that have been proved effective in the prevention of coronary artery disease, clearly reducing the risk of mortality and cardiovascular events. Whether hyperlipidemic patients undergoing coronary artery bypass grafting profit from the lipid-lowering beneficial effects of statins is as yet uncertain. We sought to determine whether preoperative statin therapy may have an effect on outcome among hyperlipidemic patients undergoing coronary artery bypass grafting. METHODS: From January 2000 through March 2006, prospectively recorded clinical data from 3346 consecutive patients undergoing isolated first-time elective coronary artery bypass grafting were analyzed for major adverse cardiac events and all-cause in-hospital mortality. Of these, 167 patients had preoperative statin-untreated hyperlipidemia (group 1), 2592 had statin-treated hyperlipidemia (group 2), and 587 had statin-untreated normolipidemia (group 3). RESULTS: Risk-adjusted multivariate logistic regression analysis revealed statin-treated hyperlipidemia (odds ratio, 0.42; 95% confidence interval, 0.26-0.69; P = .0007) and statin-untreated normolipidemia (odds ratio, 0.42; confidence interval, 0.26-0.69; P = .0007) to be independently associated with reduced in-hospital major adverse cardiac events but not with in-hospital mortality. To further control for selection bias, a computed propensity score matching based on 14 major preoperative risk factors was performed. After propensity matching, conditional logistic regression analysis confirmed statin-treated hyperlipidemia and statin-untreated normolipidemia to be strongly related to reduced in-hospital major adverse cardiac events (odds ratio, 0.41; 95% confidence interval, 0.24-0.71 [P = .0013] and odds ratio, 0.23; 95% confidence interval, 0.11-0.48 [P = .0001]) but not with in-hospital mortality (odds ratio, 1.18; 95% confidence interval, 0.36-3.87 [P = .79] and odds ratio, 1.10; 95% confidence interval, 0.32-4.41 [P = .80]) after coronary artery bypass grafting surgery. CONCLUSIONS: Hyperlipidemic, but not normolipidemic, patients have an increased risk for in-hospital major adverse cardiac events and therefore clearly benefit from preoperative statin therapy before coronary artery bypass grafting surgery.

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Metabolism. 2007 Nov;56(11):1534-41.
Comparison of atorvastatin versus fenofibrate in reaching lipid targets and influencing biomarkers of endothelial damage in patients with familial combined hyperlipidemia.
Arca M, Montali A, Pigna G, Antonini R, Antonini TM, Luigi P, Fraioli A, Mastrantoni M, Maddaloni M, Letizia C.
Unit of Medical Therapy, Department of Clinical and Medical Therapy, University La Sapienza, Rome, Italy. marcelloarca@libero.it

Statins and fibrates have different effects on lipid abnormalities of familial combined hyperlipidemia (FCHL); thus, the selection of the first-line drug is troublesome. We evaluated to what extent monotherapy with a potent statin is more effective than fibrate in reaching the recommended lipid targets in FCHL. Fifty-six patients were randomized to receive optimal dosage of atorvastatin (n = 27) or 200 mg/d micronized fenofibrate (n = 29) for 24 weeks. To reach the optimal dosage, atorvastatin was up-titrated at each follow-up visit if low-density lipoprotein (LDL) cholesterol >130 mg/dL (>100 mg/dL in patients with coronary or cerebrovascular disease). The effects of fenofibrate and atorvastatin on lipoprotein fractions as well as on plasma levels of endothelin-1 (ET-1) and adrenomedullin (AM) were also evaluated. At end of trial, a greater proportion of patients on atorvastatin (average dosage, 20.8 mg/d) reached lipid targets in comparison with those on fenofibrate (64% vs 32.1%, P = .02). Atorvastatin was significantly more effective in reducing total cholesterol, LDL cholesterol, apolipoprotein B, and non-high-density lipoprotein (HDL) cholesterol. Conversely, triglycerides decreased and HDL increased more during fenofibrate. Nevertheless, atorvastatin produced a marked reduction in very low-density lipoprotein and very low-density lipoprotein remnants. Atorvastatin lowered all LDL subtypes, although fenofibrate appeared to be more effective on denser LDL. Compared with 43 normolipemic controls, FCHL patients presented increased baseline plasma levels of ET-1 (P = .007) but not of AM. Fenofibrate, but not atorvastatin, significantly lowered ET-1 levels by 16.7% (P < .05). Neither drug significantly affected plasma concentrations of AM. In summary, although fenofibrate showed superiority in raising HDL and reducing ET-1, atorvastatin was more effective in reaching lipid targets in FCHL so that it can be proposed as the first-line option in the management of this atherogenic hyperlipidemia.

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Am J Cardiol. 2007 Oct 15;100(8):1245-8. Epub 2007 Aug 2.
Comparison of effectiveness of rosuvastatin versus atorvastatin on the achievement of combined C-reactive protein (<2 mg/L) and low-density lipoprotein cholesterol (< 70 mg/dl) targets in patients with type 2 diabetes mellitus (from the ANDROMEDA study).
Betteridge DJ, Gibson JM, Sager PT.
Department of Medicine, University College London, London, United Kingdom. rmhajbe@ucl.ac.uk

Decreasing C-reactive protein (CRP) in addition to decreasing low-density lipoprotein (LDL) cholesterol may further decrease coronary heart disease risk. The effects of rosuvastatin compared with atorvastatin in achieving a combined target of LDL cholesterol <70 mg/dl and CRP <2 mg/L in 509 patients with type 2 diabetes mellitus was evaluated. CRP decreased significantly versus baseline in both treatment groups. Significantly more patients treated with rosuvastatin achieved the combined end point of LDL cholesterol <70 mg/dl and CRP <2 mg/L compared with atorvastatin by the end of the study period (58% vs 37%; p <0.001 vs atorvastatin). In conclusion, CRP was effectively decreased in patients with type 2 diabetes receiving rosuvastatin or atorvastatin, whereas rosuvastatin decreased LDL cholesterol significantly more than atorvastatin.

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J Endocrinol Invest. 2007 Sep;30(8):700-19.
Rational approach to the treatment for heterozygous familial hypercholesterolemia in childhood and adolescence: a review.
Iughetti L, Predieri B, Balli F, Calandra S.
Department of Pediatrics, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy. iughetti.lorenzo@unimore.it

Atherosclerosis represents a disease that begins in childhood and in which LDL cholesterol plays a pivotal role for the development of the pathology. Children and adolescents with high cholesterol levels are more likely than their peers to present cholesterol elevation as adults. The identification of genetic dyslipidemias associated with premature cardiovascular disease is crucial during childhood to delay or prevent the atherosclerotic process. Guidelines for the diagnosis and treatment of hypercholesterolemia during pediatric age are available from the National Cholesterol Education Program. A heart-healthy diet should begin at the age of 2 yr and a large number of studies have demonstrated no adverse effects on nutritional status, growth, pubertal development, and psychological aspects in children and adolescents limiting total and saturated fat intake. Pharmacotherapy should be considered in children over 10 yr of age when LDL cholesterol concentrations remain very high despite severe dietary therapy, especially when multiple risk factors are present. The only lipid-lowering drugs recommended up to now for childhood and adolescence are resins reported to be effective and well tolerated, although compliance is very poor because of unpalatability. The use of statins is increasing and seems to be effective and safe in children, even if studies enrolled a small number of patients and evaluated efficacy and safety for short-term periods. Recently, an interesting drug represented by ezetimibe has been found that may provide cholesterol-lowering additive to that reached with statin treatment. This review provides an update on recent advances in the diagnosis, therapy, and follow-up of familial hypercholesterolemia during pediatric age and adolescence.

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Expert Opin Pharmacother. 2007 Jun;8(9):1345-52.
Ezetimibe plus fenofibrate: a new combination therapy for the management of mixed hyperlipidaemia?
Farnier M.
Point Médical, Rond Point de la Nation, 21000 Dijon, France. michelfarnier@nerim.net

Mixed hyperlipidaemia is an important risk factor for the development of cardiovascular disease. The global management of mixed hyperlipidaemia is often more difficult than the treatment of pure hypercholesterolaemia in terms of goal attainments. Despite the significant clinical benefits provided by statins, many patients with mixed hyperlipidaemia do not achieve their recommended low-density and non-high-density lipoprotein cholesterol target goals with statin monotherapy. The combination of ezetimibe plus fenofibrate is a new alternative to improve the overall atherogenic lipid profile of patients with mixed hyperlipidaemia. However, the absence of comparative data with statin monotherapy and of long-term clinical studies suggests reservation of the combination of ezetimibe plus fenofibrate as a second-line therapy. Nevertheless, this combination therapy of ezetimibe plus fenofibrate seems particularly useful for patients with a poor response or intolerance to statin monotherapy.

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Am Fam Physician. 2007 May 1;75(9):1365-71.
Management of hypertriglyceridemia.
Oh RC, Lanier JB.
Family Medicine Residency Program, Tripler Army Medical Center, Honolulu, Hawaii 96859, USA. roboh98@gmail.com

Hypertriglyceridemia is associated with an increased risk of cardiovascular events and acute pancreatitis. Along with lowering low-density lipoprotein cholesterol levels and raising high-density lipoprotein cholesterol levels, lowering triglyceride levels in high-risk patients (e.g., those with cardiovascular disease or diabetes) has been associated with decreased cardiovascular morbidity and mortality. Although the management of mixed dyslipidemia is controversial, treatment should focus primarily on lowering low-density lipoprotein cholesterol levels. Secondary goals should include lowering non-high-density lipoprotein cholesterol levels (calculated by subtracting high-density lipoprotein cholesterol from total cholesterol). If serum triglyceride levels are high, lowering these levels can be effective at reaching non-high-density lipoprotein cholesterol goals. Initially, patients with hypertriglyceridemia should be counseled about therapeutic lifestyle changes (e.g., healthy diet, regular exercise, tobacco-use cessation). Patients also should be screened for metabolic syndrome and other acquired or secondary causes. Patients with borderline-high serum triglyceride levels (i.e., 150 to 199 mg per dL [1.70 to 2.25 mmol per L]) and high serum triglyceride levels (i.e., 200 to 499 mg per dL [2.26 to 5.64 mmol per L]) require an overall cardiac risk assessment. Treatment of very high triglyceride levels (i.e., 500 mg per dL [5.65 mmol per L] or higher) is aimed at reducing the risk of acute pancreatitis. Statins, fibrates, niacin, and fish oil (alone or in various combinations) are effective when pharmacotherapy is indicated.

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Mayo Clin Proc. 2007 May;82(5):543-50. Erratum in: Mayo Clin Proc. 2007 Jul;82(7):890. Comment in: Mayo Clin Proc. 2007 May;82(5):539-42.
Achieving low-density lipoprotein cholesterol goals in high-risk patients in managed care: comparison of rosuvastatin, atorvastatin, and simvastatin in the SOLAR trial.
Insull W, Ghali JK, Hassman DR, Y As JW, Gandhi SK, Miller E; SOLAR Study Group.
Baylor College of Medicine and The Methodist Hospital, Houston, TX, 77030-3411, USA. winsull@bcm.edu

OBJECTIVE: To evaluate attainment of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein cholesterol (LDL-C) goal of less than 100 mg/dL with statin treatments in managed care patients at high risk for coronary heart disease. PATIENTS AND METHODS: In a randomized, open-label, multicenter trial (SOLAR [Satisfying Optimal LDL-C ATP III goals with Rosuvastatin]) performed at 145 US clinical centers from June 5, 2002 to July 12, 2004, high-risk men and women in a managed care population received typical starting doses of rosuvastatin (10 mg/d), atorvastatin (10 mg/d), or simvastatin (20 mg/d) for 6 weeks. Those who did not meet the LDL-C target of less than 100 mg/dL at 6 weeks had their dose titrated (doubled), and all patients were followed up for another 6 weeks. RESULTS: A total of 1632 patients were randomized to 1 of the 3 treatment regimens. After 6 weeks, 65% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 41% with atorvastatin and 39% with simvastatin (P<.001 vs rosuvastatin for both). After 12 weeks, 76% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 58% with atorvastatin and 53% with simvastatin (P<.001 vs rosuvastatin for both). Reductions in the LDL-C level, total cholesterol level, non-high-density lipoprotein cholesterol (non-HDL-C) level, and non-HDL-C/HDL-C ratio were significantly greater with rosuvastatin at both 6 and 12 weeks compared with the other statins. Adverse events were similar in type and frequency in all treatment groups, and only 3% of all patients discontinued treatment because of adverse events. No myopathy was observed, no clinically important impact on renal function was attributed to study medications, and clinically important increases in serum transaminases were rare. CONCLUSION: In a managed care population, 10 mg of rosuvastatin treatment resulted in more patients reaching the NCEP ATP III LDL-C goal compared with 10 mg of atorvastatin and 20 mg of simvastatin, potentially reducing the need for titration visits.

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J Clin Endocrinol Metab. 2007 May;92(5):1581-9.
Update on dyslipidemia.
Garg A, Simha V.
Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9052, USA. abhimanyu.garg@utsouthwestern.edu

Recently, considerable progress has been made in understanding the genetic basis of dyslipidemias and in studying the safety and efficacy of lipid-lowering drugs for coronary heart disease (CHD) prevention. Novel loci have been identified for monogenic hypercholesterolemia, such as low-density lipoprotein (LDL) receptor (LDLR)-associated protein, proprotein convertase subtilisin-like kexin type 9, and ATP-binding cassette transporters ABCG5 and ABCG8. LDLR-associated protein promotes clustering of LDLRs into clathrin-coated pits for LDL uptake; proprotein convertase subtilisin-like kexin type 9 is involved in LDLR degradation; and ABCG5 and 8 pump sterols out of the hepatic and intestinal cells into bile and intestinal lumen, respectively. A novel gene encoding apolipoprotein AV, an activator of lipoprotein lipase, has also been linked to familial hypertriglyceridemia. Linkage of familial combined hyperlipidemia to upstream stimulatory factor 1 remains controversial. Recent guidelines of the Adult Treatment Panel III emphasize intensive reduction of LDL or non-high-density lipoprotein cholesterol in patients at high risk of CHD. However, of the four recently concluded trials comparing high- vs. low-dose statin therapy, only two showed an unequivocal reduction in cardiovascular endpoints. Because intensive statin therapy can increase the risk of myopathy and hepatotoxicity, it is important to consider its risk-benefit ratio in individual patients. Restriction of dietary saturated and trans-fat and cholesterol, along with increased intake of soluble fiber, can also achieve substantial LDL cholesterol lowering. Fibrates may reduce the risk of acute pancreatitis in severely hypertriglyceridemic patients and may be beneficial for CHD prevention. However, the safety and efficacy of combined therapy of fibrates and statins needs to be established.

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Urol Nurs. 2007 Apr;27(2):169-73.
Cholesterol, cholesterol-lowering agents/statins, and urologic disease: Part VI—The recent rise and fall of the HDL-boosting drug torceptrapib.
Moyad MA, Merrick GS.
University of Michigan Medical Center, Department of Urology, Ann Arbor, MI, USA.

Pfizer Inc. recently discontinued its billion-dollar investment and phase III clinical trial of their new high-density lipoprotein (HDL) or "good cholesterol" boosting drug torceptrapib because of unexpected life-threatening side effects. To provide an objective discussion with patients looking for the next miracle drug or even dietary supplement in medicine, it is important to provide an overview of the history of this drug. It should serve as an important lesson that traditional lifestyle factors and proven heart healthy medications have stood the test of time in terms of research. Despite the current interest in drug development, traditional HDL-boosting lifestyle initiatives such as exercise, weight loss, and smoking cessation can be incorporated now and are heart and urologic healthy.

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Urol Nurs. 2007 Apr;27(2):166-8.
Cholesterol, cholesterol-lowering agents/statins, and urologic disease: Part V—Statins versus aspirin for primary prevention, and the winner is...?
Moyad MA, Merrick GS.
University of Michigan Medical Center, Department of Urology, Ann Arbor, MI, USA.

There are no national guidelines when comparing an aspirin daily to a statin drug in individuals with no history of a cardiovascular event (primary prevention). However, recent reviews of the medical clinical research on statins and aspirin for preventing a first coronary heart disease (CHD) event concluded that compared to no treatment, aspirin is cheaper and has more of an impact in middle-aged men whose 10-year risk for CHD is 7.5% or higher, and adding a statin to aspirin therapy is better in terms of cost effectiveness when a patient's 10-year CHD risk before any treatment is greater than 10%. However, when scrutinizing these data it seems that statins beat aspirin in every single risk-reduction category, and has equal to perhaps less side effects, but a statin costs more. In addition, patients should be informed about the recent observational data suggesting that statins may reduce mortality from other causes such as prostate cancer.

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J Am Pharm Assoc (2003). 2007 Mar-Apr;47(2):140-6.
Therapeutic rationale of combining therapy with gemfibrozil and simvastatin.
Curtin PO, Jones WN.
Southern Arizona Veterans Affairs (VA) Health Care System, Tucson, AZ, USA. curtin2@med.va.gov

OBJECTIVES: To examine specific indications for patients receiving therapy with gemfibrozil plus simvastatin at doses of more than 10 mg daily and determine whether these patient-specific indications met Adult Treatment Panel (ATP) III criteria for combination therapy; and secondarily to identify any complications occurring between August 30, 2002, and May 1, 2003. DESIGN: Retrospective cohort study. SETTING: Tertiary care, university-affiliated, Southern Arizona Veterans Affairs Healthcare System from August 30, 2002, to May 1, 2003. PATIENTS: 80 patients with active prescriptions for gemfibrozil at any dose and simvastatin at doses of more than 10 mg daily as of August 30, 2002; and 23 patients who had been prescribed this drug at other institutions. INTERVENTION: Retrospective chart review. MAIN OUTCOME MEASURES: Frequency of meeting ATP III criteria for combination therapy with gemfibrozil and simvastatin was the primary outcome measure (primary). RESULTS: Of the 80 patients, 45 (56%) met ATP III guidelines for combination therapy. Among the 80 patients started on these drugs at this VA facility, gemfibrozil was added to simvastatin in 61 patients, simvastatin was added to gemfibrozil in 18, and the agents were begun simultaneously for 1 patient. Common errors included combination treatment when LDL cholesterol values could not be calculated (because of serum triglycerides levels exceeding 400 mg/dL); use of gemfibrozil at triglyceride levels lower than the 500 mg/dL with attainment of non-HDL goals; and use of gemfibrozil when triglyceride levels were not measured. One death secondary to rhabdomyolysis occurred in a patient whose care did not meet ATP III guidelines. CONCLUSION: Combination therapy with simvastatin and gemfibrozil often did not meet ATP III standards. A higher risk of serious adverse events results from combining these drugs, and systems to improve adherence to guidelines may improve the safety of treating dyslipidemic patients.

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Am Heart J. 2007 Feb;153(2):335.e1-8.
Efficacy and safety of the coadministration of ezetimibe/simvastatin with fenofibrate in patients with mixed hyperlipidemia.
Farnier M, Roth E, Gil-Extremera B, Mendez GF, Macdonell G, Hamlin C, Perevozskaya I, Davies MJ, Kush D, Mitchel YB; Ezetimibe/Simvastatin + Fenofibrate Study Group.
Point Medical, Dijon, France. michelfarnier@nerim.net

BACKGROUND: Mixed hyperlipidemia is characterized by elevated low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and TG-rich lipoprotein levels. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel arm trial, eligible patients were 18 to 79 years of age, with mixed hyperlipidemia (LDL-C 130-220 mg/dL, TG 150-500 mg/dL). Patients with type 2 diabetes were limited to those with LDL-C of 100 to 180 mg/dL. Patients (N = 611) were randomized in a 3:3:3:1 ratio to one of 4 treatment arms for 12 weeks: ezetimibe/simvastatin 10/20 mg (EZE/SIMVA) + fenofibrate 160 mg (FENO), EZE/SIMVA 10/20 mg, FENO 160 mg, or placebo. The primary objective was to evaluate the LDL-C-lowering efficacy of EZE/SIMVA + FENO versus FENO monotherapy. RESULTS: Low-density lipoprotein cholesterol level was significantly (P < .05) reduced with EZE/SIMVA + FENO (-45.8%) compared with FENO (-15.7%) or placebo (-3.5%), but not when compared with EZE/SIMVA (-47.1%). High-density lipoprotein cholesterol and apolipoprotein A-I levels were significantly increased with EZE/SIMVA + FENO (18.7% and 11.1%, respectively) treatment compared with EZE/SIMVA (9.3% and 6.6%) or placebo (1.1% and 1.6%), but not when compared with FENO (18.2% and 10.8%). Triglyceride, non-high-density lipoprotein cholesterol, and apolipoprotein B levels were significantly reduced with EZE/SIMVA + FENO (-50.0%, -50.5%, and -44.7%, respectively) versus all other treatments. Treatment with EZE/SIMVA + FENO was generally well tolerated with a safety profile similar to the EZE/SIMVA and FENO therapies. CONCLUSIONS: Coadministration of EZE/SIMVA + FENO effectively improved the overall atherogenic lipid profile of patients with mixed hyperlipidemia. Clinical trial registry number: NCT 00093899 (http://www.ClinicalTrials.gov).

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Expert Opin Ther Targets. 2007 Feb;11(2):181-9.
MTP inhibition as a treatment for dyslipidaemias: time to deliver or empty promises?
Burnett JR, Watts GF.
PathWest Laboratory Medicine, Department of Core Clinical Pathology & Biochemistry, Royal Perth Hospital, Wellington Street Campus, GPO Box X2213, Perth, WA 6847, Australia. john.burnett@health.wa.gov.au

The development of cholesterol-lowering drugs, including a statins, bile acid sequestrants and cholesterol absorption inhibitors has expanded the options for cardiovascular prevention. Recent treatment guidelines emphasise that individuals at substantial risk for atherosclerotic coronary heart disease should meet defined lipid targets. Combination therapy with drugs that have different and complementary mechanisms of action is often needed to achieve these goals. Existing approaches to the treatment of hypercholesterolaemia are still ineffective in halting the progression of coronary artery disease in some patients despite combination therapies. Other patients are resistant to, or intolerant of, conventional pharmacotherapy and remain at high-risk of atherosclerotic cardiovascular disease, so that alternative approaches are needed. New agents, including inhibitors of microsomal triglyceride transfer protein (MTP), may play a future role, either alone or in combination, in the treatment of hyperlipidaemias. This review focuses on novel approaches to treat dyslipidaemias via the inhibition of MTP. Patients most suitable for use of MTP inhibitors include those with hepatic hypersecretion of apoB, including the metabolic syndrome, Type 2 diabetes mellitus and familial combined hyperlipidaemia, as well as homozygous and heterozygous familial hypercholesterolaemia. However, certain safety issues with these agents need resolving, particularly fatty liver disease.

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Drugs Today (Barc). 2007 Jan;43(1):35-45.
Ezetimibe and fenofibrate combination therapy for mixed hyperlipidemia.
Moon YS, Chun P, Chung S.
The University of the Pacific, Thomas J. Long School of Pharmacy and Health Sciences, Stockton, California, and Veterans Affairs Healthcare System, Long Beach, California, USA. yskmoon@earthlink.net.

The ezetimibe and fenofibrate combination regimen was recently approved by the U.S. Food and Drug Administration for treatment of mixed hyperlipidemia. This powerful lipid-modifying therapy takes advantage of the different mechanisms of action of the two individual components. Ezetimibe selectively inhibits intestinal uptake of dietary and biliary cholesterol, and exerts its effect most notably on the low-density lipoprotein cholesterol (LDL-C). Fenofibrate activates the peroxisome proliferators-activated receptor alpha (PPAR-alpha), thereby increasing the tissue lipoprotein lipase activity and breakdown of triglycerides in very low-density lipoproteins (VLDL). The combination therapy of ezetimibe and fenofibrate has an excellent safety profile and exhibits potent synergistic actions on multiple lipid risk factors and represents another alternative in the clinical management of mixed hyperlipidemia. Further studies are needed to determine the effectiveness and safety of the ezetimibe and fenofibrate combination therapy used in conjunction with other lipid-modifying agents such as statins. Finally, outcome trials are warranted to evaluate if combination therapy would result in additive effects on morbidity and mortality. (c) 2007 Prous Science. All rights reserved.

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J Altern Complement Med. 2007 Jan;13(1):83-96.
Dietary supplements for the prevention and treatment of coronary artery disease.
Knox J, Gaster B.
Department of Medicine, University of Washington, Seattle, WA.

Purpose: With the recent growth in the use of dietary supplements, it is increasingly important for clinicians to be familiar with the evidence for and against their efficacy. We set out to systematically review the dietary supplements available for the prevention and treatment of coronary artery disease. Methods: Between May 2004 and May 2006, we searched MEDLINE,((R)) the Cochrane Library, and Pro-Quest using the MeSH terms hypertension, hypercholesterolemia, myocardial infarction, dietary supplements, and herb-drug interactions. The MeSH terms of individual supplements identified were then added to the search. Reference lists of pertinent papers were also searched to find appropriate papers for inclusion. We included randomized controlled trials published in English of at least 1 week's duration that studied the efficacy of supplements in the treatment of hypercholesterolemia, or hypertension, or in the prevention of cardiac events. Qualifying papers were identified and assigned a Jadad quality score. In areas of uncertainty, a second investigator independently scored the trial. Results: Fifteen (15) supplements were identified. Of these, most had little data available and most of the data were of poor quality. The supplements with the most supporting data were policosanol and garlic, both for hyperlipidemia. Conclusions: A growing body of literature exists for numerous supplements in the prevention of coronary artery disease, but much of these data are inconclusive. Clinicians should become familiar with the extent and limitations of this literature so that they may counsel their patients better.

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Transl Res. 2007 Jan;149(1):22-30.
Effect of plant sterols and exercise training on cholesterol absorption and synthesis in previously sedentary hypercholesterolemic subjects.
Varady KA, Houweling AH, Jones PJ.
School of Dietetics and Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Quebec, Canada.

Plant sterols combined with exercise beneficially alter lipid profiles in hypercholesterolemic adults. Although the mechanism by which plant sterols favorably modulate lipid levels is well established, no trial to date has examined the effect of exercise, alone or combined with plant sterols, on cholesterol kinetics. Thus, the current objective was to examine the effects of exercise, plant sterols, and the combination of exercise and plant sterols on cholesterol absorption and synthesis. In an 8-week, parallel-arm trial, 84 subjects were randomized to 1 of 4 interventions: plant sterols combined with exercise, plant sterols, exercise, or control. Diets were not controlled. Total cholesterol and triglyceride levels decreased (P<0.01) by 7.7% and 11.8%, respectively, whereas high-density lipoprotein (HDL) cholesterol levels increased (P<0.01) by 7.5% in the combination group. Mean posttreatment low-density lipoprotein (LDL) cholesterol levels decreased (P<0.01) by 0.30 mmol/L in the combination group. Cholesterol absorption was 16% lower (P<0.01) in the combination group and 18% lower (P<0.01) in the plant sterol group, when compared with control. Exercise had no effect on cholesterol absorption. Nonsignificant increases in cholesterol synthesis rates of 63% (0.084+/-0.014 pools/day), 59% (0.075+/-0.013 pools/day), and 57% (0.072+/-0.011 pools/day) were observed in the combination, exercise, and plant sterol groups, respectively, relative to the control group (0.031+/-0.019 pools/day). LDL cholesterol levels correlated with cholesterol absorption, as represented by the area under the deuterium enrichment curve (r=0.23, P=0.05), and with percent absorption relative to control (r=0.25, P=0.03). These findings suggest that exercise does not modulate lipid levels by altering to cholesterol absorption or synthesis, whereas plant sterols favorably alter levels of LDL cholesterol by suppressing intestinal absorption.

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J Natl Med Assoc. 2006 Dec;98(12):1895-903.
Challenges in making therapeutic lifestyle changes among hypercholesterolemic African-American patients and their physicians.
Dailey R, Schwartz KL, Binienda J, Moorman J, Neale AV.
Department of Family Medicine, Wayne State University, Detroit, MI 48201, USA. rdailey@med.wayne.edu

OBJECTIVE: We explored challenges faced by hypercholesterolemic African-American primary care patients and their physicians regarding therapeutic lifestyle changes (TLC) and provide patient-influenced recommendations to physicians. METHODS: In this qualitative study, 23 urban family medicine patients and their physicians (N=12) participated in separate focus groups, where they were asked semistructured, open-ended questions about knowledge and barriers to lifestyle treatment of high cholesterol. RESULTS: During the focus groups, barriers mentioned by physicians were: lack of time for TLC counseling, inadequate knowledge about counseling patients, and patient readiness and responsibility to change. Patient-revealed barriers included difficulty adhering to a diet/exercise regimen and a lack of knowledge about high cholesterol. Patients who were successful with adopting a healthy lifestyle identified personal experiences or those of family and friends as motivating. CONCLUSION: Physicians desire training and resources to better help patients adopt diet and exercise regimens specific to their general and health literacy and their access to healthy foods, along with their readiness to change. Patients desire that physicians tailor their TLC advice to be specific to their context and they want help from physicians in setting realistic goals. Such a patient-centered counseling approach may improve adherence to lifestyle guidelines and, thus, clinical outcomes.

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J Cardiovasc Pharmacol Ther. 2006 Dec;11(4):262-70.
Effect of atorvastatin on type 2 diabetic dyslipidemia.
Save V, Patil N, Moulik N, Rajadhyaksha G.
Department of Biochemistry, Lokamanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai, India; 2, Pragati CHS, Manjrekar Road, Dadar, Mumbai-400028, India. vipulcs@gmail.com

Hyperlipidemia is commonly observed in patients with type 2 diabetes and is an independent risk factor for cardiovascular disease. The authors tested the effect of atorvastatin (10 mg/d) on 110 hyperlipidemic type 2 diabetes patients with low-density lipoprotein cholesterol (LDL-C) levels exceeding 130 mg/d. The primary efficacy end point was the percentage change in LDL-C and high-density lipoprotein cholesterol (HDL-C), and secondary efficacy included the percentage change in apolipoproteins at weeks 6, 12, and 24. The tertiary goal was percentage change in free radical scavenger enzymes and oxidative stress. LDL-C was reduced by 25%, 39.3%, and 49.2%. A similar trend was observed in total cholesterol, triglyceride, non-HDL-C, and apolipoprotein (apo) B-100. HDL-C was raised by 3.2%, 6%, and 8.2%. A similar trend was seen in apo A-1. Copper zinc-superoxide dismutase and glutathione were raised significantly (P < .001); however, changes in glutathione-S-transferase and glutathione peroxidase activities were nonsignificant. Malondialdehyde was decreased significantly (P < .001). Atorvastatin improves the lipoprotein profile and oxidative status in patients with type 2 diabetes.

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Ann Nutr Metab. 2006;50(6):512-8. Epub 2006 Dec 21.
Dietary supplementation with chickpeas for at least 5 weeks results in small but significant reductions in serum total and low-density lipoprotein cholesterols in adult women and men.
Pittaway JK, Ahuja KD, Cehun M, Chronopoulos A, Robertson IK, Nestel PJ, Ball MJ.
School of Human Life Sciences, University of Tasmania, Launceston, Tas., Australia.

AIM: To compare the effects of a chickpea-supplemented diet and those of a wheat-supplemented diet on human serum lipids and lipoproteins. METHODS: Forty-seven free-living adults participated in a randomized crossover weight maintenance dietary intervention involving two dietary periods, chickpea-supplemented and wheat-supplemented diets, each of at least 5 weeks duration. RESULTS: The serum total cholesterol and low-density lipoprotein cholesterol levels were significantly lower (both p < 0.01) by 3.9 and 4.6%, respectively, after the chickpea-supplemented diet as compared with the wheat-supplemented diet. Protein (0.9% of energy, p = 0.01) and monounsaturated fat (3.3% of total fat, p < 0.001) intakes were slightly but significantly lower and the carbohydrate intake significantly higher (1.7% of energy, p < 0.001) on the chickpea-supplemented diet as compared with the wheat-supplemented diet. Multivariate analyses suggested that the differences in serum lipids were mainly due to small differences in polyunsaturated fatty acid and dietary fibre contents between the two intervention diets. CONCLUSIONS: Inclusion of chickpeas in an intervention diet results in lower serum total and low-density lipoprotein cholesterol levels as compared with a wheat-supplemented diet. Copyright 2006 S. Karger AG, Basel.

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Am J Clin Nutr. 2006 Dec;84(6):1543-8.
Policosanol is ineffective in the treatment of hypercholesterolemia: a randomized controlled trial.
Dulin MF, Hatcher LF, Sasser HC, Barringer TA.
Carolinas Medical Center Department of Family Medicine, Charlotte, NC, USA. michael.dulin@carolinashealthcare.org

BACKGROUND: Policosanol is one of the fastest growing over-the-counter supplements sold in the United States. The use of policosanol to treat elevated cholesterol is based on clinical trials conducted in Cuba, which showed sugar cane-derived policosanol to be similar in efficacy to statins. Recent studies have challenged these findings, but there have been no trials conducted in North America that have examined the ability of sugar cane-derived policosanol to lower cholesterol. OBJECTIVES: This study investigated the efficacy of sugar cane-derived policosanol in healthy adults with mild hypercholesterolemia. The primary outcome was the percentage change in LDL cholesterol after 8 wk of therapy. Secondary outcome measures included changes in total cholesterol, HDL cholesterol, triacylglycerols, C-reactive protein, and nuclear magnetic resonance-determined lipoprotein profile. Dietary habits, weight, and blood pressure were also monitored. DESIGN: Ambulatory, community-dwelling healthy adults with mild hypercholesterolemia (n = 40) were assigned to receive oral policosanol (20 mg) or placebo once daily for 8 wk. This was a double-blind, randomized controlled trial conducted from January through August 2005. RESULTS: No significant differences in the change in LDL cholesterol were observed between the placebo (n = 20) and policosanol (n = 20) groups. Also, no significant changes in secondary outcome measures, including total cholesterol, HDL cholesterol, triacylglycerol, C-reactive protein, and nuclear magnetic resonance spectroscopy-determined profiles were observed. Policosanol was well tolerated, and no significant adverse events were noted. CONCLUSION: Policosanol does not alter the serum lipid profile over an 8-wk period in adults with mild hypercholesterolemia.

   

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