Optimal Low-density Lipoprotein Levels: Evidence from Epidemiology and Clinical Trials

Aggressive lipid lowering was initially controversial due to evidence from epidemiologic studies that implied an increase in total mortality with low cholesterol levels combined with equivocal results from early trials utilizing bile acid resins or fibric acid derivatives. The advent of statin therapy allowed significant reductions of circulating lipid levels and clearly reduced cardiovascular morbidity and mortality. Additionally, in adequately powered trials, total mortality was also reduced. The optimal level of circulating low-density lipoprotein (LDL) has not been definitely established. However, recent clinical trials with aggressive lipid goals have established that LDL cholesterol can be significantly lowered below 100 mg/dL with improvement in both surrogate measurements and hard clinical endpoints. Ongoing clinical trials have been initiated that will determine the optimal level of LDL cholesterol that will insure cardiovascular benefits and establish the risk-benefit relationship of aggressive pharmacologic lowering of circulating lipid levels.