Insights from recent meta-analysis: role of high-density lipoprotein cholesterol in reducing cardiovascular events and rates of atherosclerotic disease progression

Abstract

Background: Although low-density lipoprotein cholesterol (LDL-C) traditionally has been the focus of treatment guidelines and clinical trials of lipid therapy, patients continue to have cardiovascular disease (CVD) events despite effective lowering of their LDL-C levels, suggesting the influence of other risk factors. High-density lipoprotein cholesterol (HDL-C) levels have been shown to be inversely associated with CVD risk in epidemiological studies.

Methods: Meta-analyses and clinical trials that reported on the potential relation between HDL-C and CVD were reviewed.

Results: Low HDL-C level is associated with increased CVD risk. Statins reduce CVD events in patients with low HDL-C, and fibrates benefit patients with low HDL-C and high triglyceride levels. The benefit of statins on event reduction may be related to their effects on HDL-C. However, not all therapies that increase HDL-C reduce CVD events. Imaging trials have provided evidence of the combined influence of HDL-C and LDL-C on surrogate end points.

Conclusion: Drugs in the same class may have different effects on HDL-C, and these different lipid effects may translate into different effects on atherosclerosis and CVD events. A new class of agents, cholesteryl ester transfer protein inhibitors, is being examined in ongoing trials to determine whether dalcetrapib may have different effects than torcetrapib, which increased levels of HDL-C but was associated with increased adverse events. In addition, ongoing trials are examining whether targeting both HDL-C and LDL-C, by combining a second agent such as niacin with a statin, leads to greater benefit on CVD and clinical events.