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Low HDL

The Medical Research

Low HDL

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More than 18 million North Americans have coronary heart disease, and despite profound advances in both pharmacologic and interventional management, both morbidity and mortality remain appreciable.1,2 Elevated low-density lipoprotein (LDL) cholesterol levels are an established predictor of the risk of coronary heart disease.

Multiple primary and secondary prevention trials have shown a significant reduction of 25 to 35% in the risk of cardiovascular events with statin therapy3; however, residual risk persists despite the achievement of target LDL cholesterol levels.

Epidemiologic studies have shown that, in addition to elevated LDL cholesterol levels, low levels of high-density lipoprotein (HDL) cholesterol are an independent predictor of the risk of coronary heart disease,4,5 with a strong inverse association between HDL cholesterol levels and the rates of incident coronary heart disease events. Previously, studies from the Coronary Drug Project showed that the rate of cardiovascular events was decreased among patients with established coronary heart disease who had been randomly assigned to receive immediate-release niacin as compared with those assigned to receive placebo,6,7 and the Veterans Affairs HDL Intervention Trial (VA-HIT; ClinicalTrials.gov number, NCT00283335)8 suggested that raising low levels of HDL cholesterol with gemfibrozil in men with coronary heart disease and normal LDL cholesterol levels was associated with reductions in the rate of cardiovascular events. Subsequently, the HDL-Atherosclerosis Treatment Study (HATS, NCT00000553)9 showed that treatment with simvastatin plus niacin resulted in significant regression of angiographic coronary atherosclerosis and reductions in the rate of clinical events.

At least two studies10,11 focusing on aggressive lowering of lipid levels with high doses of statins to achieve a target LDL cholesterol level of less than 70 mg per deciliter (1.81 mmol per liter) in very-high-risk patients have shown major reductions in clinical end points. A post hoc analysis of the Treating to New Targets trial (TNT, NCT00327691)11 showed that, among patients who had achieved LDL cholesterol values of less than 70 mg per deciliter, the 5-year rate of cardiovascular events was 25% lower among those in the highest quintile of HDL cholesterol levels than among those in the lowest quintile. This suggests that HDL cholesterol levels have a prognostic value for patients receiving statin therapy that is independent of LDL cholesterol levels.

The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial tested whether extended-release niacin added to intensive statin therapy, as compared with statin therapy alone, would reduce the risk of cardiovascular events in patients with established atherosclerotic cardiovascular disease and atherogenic dyslipidemia (low levels of HDL cholesterol, elevated triglyceride levels, and small, dense particles of LDL cholesterol). Patients with this profile represent an expanding reservoir of patients at increased risk for cardiovascular events,12,13 for whom more effective treatment is needed.

LDL cholesterol goals

Statins are the most commonly prescribed drugs for lowering low-density lipoprotein (LDL) cholesterol levels.