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Should we target HDL-cholesterol to reduce coronary heart disease risk?

Nature Clinical Practice Endocrinology & Metabolism volume 2, pages 358–359 (2006)Cite this article

Elevated LDL-cholesterol and decreased HDL-cholesterol levels are independent predictors of coronary heart disease (CHD) risk. Although there is consensus regarding the benefits of lowering LDL-cholesterol, the value of elevating HDL-cholesterol remains controversial. Increases in HDL-cholesterol levels of 3%, seen with cholestyramine treatment in the Lipid Research Clinic Coronary Primary Prevention Trial (LRC-CPPT), of 10% with gemfibrozil in the Helsinki Heart Study, of 6% with gemfibrozil in the Veterans Affairs HDL Intervention Trial (VA-HIT), of 8% with simvastatin in the Scandinavian Simvastatin Survival Study (4S), and of 30% with a combination of niacin and simvastatin in the HDL Atherosclerosis Treatment Study (HATS) have all been associated with benefit in terms of CHD risk reduction. Analyses of coronary angiographic intervention studies support the concept of benefit being gained from lowering LDL-cholesterol and raising HDL-cholesterol levels. Five once-weekly infusions of the recombinant apolipoprotein A-IMilano–phospholipid complex were associated with greater benefit in terms of atheroma regression (as assessed by intravascular ultrasound) than was 18 months of treatment with 80 mg daily atorvastatin in the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial. Today, we have more data supporting the elevation of HDL-cholesterol than we did in 1988 supporting the reduction of LDL-cholesterol, which was when the first cholesterol guidelines were formulated following publication of the LRC-CPPT; however, the focus of current guidelines for cholesterol management remains on strategies for lowering LDL-cholesterol levels.

The 2001 update of the US National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) recommended reducing the LDL-cholesterol level to <2.6 mmol/l in individuals with CHD or diabetes, or those who have a 10-year risk of developing CHD of >20%. These guidelines have recently been amended to include an optional LDL-cholesterol goal of <1.8 mmol/l in patients with CHD.1 This value is at about the 5th percentile of the normal range for the US population. The US guidelines do suggest using niacin or a fibrate to raise HDL-cholesterol levels in high-risk patients with HDL-cholesterol levels <1.0 mmol/l; however, no specific target for HDL-cholesterol was established. The 2003 Canadian dyslipidemia guidelines2 recommend reducing LDL-cholesterol levels to <2.5 mmol/l, which is very similar to recommendations in the 2001 US guidelines; the Canadian guidelines also recommend achieving a total-cholesterol:HDL-cholesterol ratio <4 in patients with CHD, and in those at very high risk of developing CHD.2 The European guidelines3 are almost identical to the Canadian guidelines.The only guidelines that provide a clear-cut target for increasing HDL-cholesterol levels are those of the American Diabetes Association, which recommend raising HDL-cholesterol to >1.0 mmol/l in men with diabetes, and >1.3 mmol/l in women with diabetes.4

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Authors and Affiliations

  1. a Professor and Laboratory Director Cardiovascular Research and Lipid Metabolism Laboratories, Tufts University School of Medicine, Boston, MA, USA

    Ernst J Schaefer

  2. an Associate Professor in the Cardiovascular Research and Lipid Metabolism Laboratories, Tufts University School of Medicine, Boston, MA, USA

    Bela F Asztalos

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  1. Ernst J Schaefer
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  2. Bela F Asztalos
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Correspondence to Ernst J Schaefer.

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Competing interests

Dr. Schaefer has served as a consultant, and speaker for AstraZeneca, Kos, Merck-Schering Plough, and Pfizer Pharmaceuticals. He and Dr. Asztalos have received research grants from all these companies except Merck-Schering Plough.

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Schaefer, E., Asztalos, B. Should we target HDL-cholesterol to reduce coronary heart disease risk?. Nat Rev Endocrinol 2, 358–359 (2006). https://doi.org/10.1038/ncpendmet0224

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