Cholesterol and cardiovascular risk: the merits and limitations of current therapies

Cardiovascular disease is the leading cause of premature death in Europe. High blood cholesterol is one of the major cardiovascular risk factors and plays a crucial role in causing cardiovascular disease. A strong positive and linear association between total and LDL cholesterol levels and the risk of cardiovascular events has been widely documented. Every 1.0 mmol/l decrease in LDL cholesterol levels results in a significant reduction in cardiovascular mortality and in the risk of nonfatal myocardial infarction. Lipid-lowering guidelines suggest as first step the use of statins as monotherapy and, in case of failure to achieve the recommended targets, combination therapy of statins with other cholesterol-lowering drugs such as ezetimibe. The results from the recent IMPROVE-IT trial provide evidence that further LDL-cholesterol lowering beyond the recommended targets significantly reduces the rate of cardiovascular events, supporting the concept that "Lower Is Better" while additional long-term data are collected. Non-adherence to statin therapy, often due to adverse drug reactions, results in an increased risk for cardiovascular events. In a non-negligible proportion of patients with hypercholesterolemia receiving maximally tolerated statin therapy, the residual risk remains high. In addition, statin use has been associated with accelerated onset of diabetes in individuals already predisposed to developing diabetes. In conclusion, it is clear that statins are not the universal solution to the problem of high cholesterol levels, and the optimization of lipid-lowering therapy remains a therapeutic challenge.