[Lowering cholesterol: how low is low enough?].

Abstract

The mean cholesterol level of the civilized modern humans is above the one considered "physiological", and a biological gradient exists between serum cholesterol level and cardiovascular events. Clinical studies on cholesterol lowering revealed that cardiovascular risk can be lowered in parallel along this gradient, and the "lower is better" rule appears to be supported by the current evidence. LDL cholesterol level should minimally be reduced on average by 50% to approach the "physiological" cholesterol concentration in order to halt the progression of atherosclerosis. Using the initial doses of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), the first-line lipid lowering drugs, this goal cannot be reached. On the other hand, high doses of statins increase the frequency of adverse events, which should contribute to the common failure of putting patients to their lipid targets in a real-world setting. Consequently, the combination of low dose statins and another cholesterol lowering agent with a mechanism of action different than synthesis inhibition (such as ezetimibe) may be the optimal clinical approach to avoid the dose-dependent adverse events. The ongoing large head-to-head clinical trials will clarify the efficacy and safety of cholesterol lowering combination therapy relative to statins in the reduction of cardiovascular risk.