High-density lipoprotein cholesterol: ready for prime time?

INTRODUCTION Statins reduce the incidence of cardiovascular events by about 25-35% compared with placebos, both in patients with and without clinical atheroslcerotic disease, across a wide range of low-density lipoprotein cholesterol (LDL-C) levels. All the landmark statin mega-trials provide solid evidence for reducing LDL-C as a primary target, yet these studies also show that up to 65-75% of events cannot be prevented by LDL-C lowering with statin therapy. This has led to a more aggressive approach to LDL-C lowering, as well as targeting other lipid targets such as high-density lipoprotein cholesterol (HDL-C). A low HDL-C has been found in more than 40% of patients experiencing a myocardial infarction (MI)(1). A low HDL-C level indicates reduced reverse cholesterol transport, reduced anti-inflammatory and anti-oxidative protection, and often indicates high levels of atherogenic remnant lipoproteins. Currently, it is possible to achieve mild to moderate increases in HDL-C levels with non-statin drugs such as fibrates (10-20%) and niacin (15-35%). These drugs can, by and large, be combined safely with statins. Hence, the article by Tavintharan et al in this issue of the Singapore Medical Journal is timely, by drawing attention to low HDL-C as a potent independent cardiovascular risk factor and potential therapeutic target(2). Given that the cardiovascular benefits of LDL-C reduction and HDL-C improvement may be additive, such a multi-targeted, complementary approach is especially relevant in high-risk individuals(3). Low HDL-C may occur in isolation, but usually occurs with raised plasma triglyceride levels, in familial combined hyperlipidaemia, or more commonly as part of the atherogenic dyslipid triad (↓ HDL-C, ↑ VLDL-C, and ↑ small dense LDL-C) associated with the metabolic syndrome. Two potentially complementary approaches have emerged regarding the management of dyslipidaemia in patients with the metabolic syndrome: either aggressive statin therapy or combination therapy to achieve therapeutic targets.