Understanding risk in hypercholesterolemia.

Atherosclerosis was relatively uncommon 100 years ago, when researchers first established its link to elevated cholesterol. As the twentieth century progressed, however, factors such as high-fat diets, sedentary lifestyles, cigarette smoking, and urbanization combined to increase the prevalence of both hypercholesterolemia and coronary heart disease (CHD) throughout the developed world. Atherogenesis begins at an early age and progresses throughout life, and cholesterol levels during young adulthood strongly predict the risk of CHD and related mortality during the ensuing decades. The total cholesterol level in youth also determines the actual age at which a critical level of atherosclerosis will be reached. Early studies on the primary and secondary prevention of CHD failed to identify a linear relationship between lipid lowering and risk reduction, primarily because older lipid-lowering agents lacked the potency to reduce cholesterol levels significantly enough to achieve lower cardiovascular event and mortality rates. The introduction of the statins, with their powerful lipid-lowering activity, overcame this limitation. Several large-scale trials of statins firmly established the efficacy of these agents in both primary and secondary CHD prevention. With the availability of statin therapy, we are now able to reduce the risk of major adverse CHD events by an average of 30%, regardless of patient age or gender.