Reducing risk by raising HDL-cholesterol: the evidence

Low HDL-cholesterol is common among patients with cardiovascular disease. Well-designed epidemiological studies carried out over the previous three decades have defined the prognostic significance of low HDL-cholesterol. Indeed, a recent evaluation of patients undergoing coronary angiography showed that factors related to HDL-cholesterol, but not to LDL-cholesterol, were primarily responsible for driving the elevated risk of atherosclerosis and cardiovascular events associated with dysglycaemia within this population. Randomized intervention studies have demonstrated significant inhibition of atherosclerosis and/or improvement in cardiovascular event rates with treatments that increase HDL-cholesterol (nicotinic acid or a fibrate). Nicotinic acid is the most powerful HDL-cholesterol raising agent currently available, and a combination of this agent with a statin facilitates simultaneous control of both HDL-chotesterol and LDL-cholesterol. Indeed, the HDL Atherosclerosis Treatment Study demonstrated a reduction in major cardiovascular events of 90% vs. placebo in patients randomized to nicotinic acid + simvastatin. In addition, patients randomized to nicotinic acid in the Coronary Drug Project benefited from a significant reduction in mortality after 15 years, 9 years after the trial ended. A new prolonged-release formulation of nicotinic acid, Niaspan(R), has superior tolerability compared with immediate-release nicotinic acid and facilitates the delivery of this therapy. The evidence base supporting intervention to correct low HDL-chotesterol in addition to reducing LDL-cholesterol is now sufficiently strong to support the introduction of this strategy into routine clinical practice.