Are lower levels of low-density lipoprotein cholesterol beneficial? A review of recent data

Abstract

In the 1960s, epidemiologic studies established a link between elevated serum cholesterol and increased risk of cardiovascular events. Extensive clinical trial data subsequently highlighted 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (ie, statins) as the most effective pharmacotherapy for lowering low-density lipoprotein (LDL) cholesterol, and showed that statin-mediated LDL cholesterol reductions were associated with significant improvements in cardiovascular outcomes. Such findings are reflected in current cardiovascular disease management guidelines, which focus on LDL cholesterol as the primary therapeutic target. These guidelines recommend target LDL cholesterol levels. However, a number of clinical trials have failed to identify an LDL cholesterol threshold level below which no further cardiovascular risk reduction occurs. Such findings suggest that optimal risk reduction may require greater reductions in LDL cholesterol than are currently being achieved. This review examines recent data highlighting the benefits of more pronounced LDL cholesterol reductions and considers how this could be achieved in clinical practice when many patients are not even reaching current targets.