Abundant and compelling data demonstrate that interventions to reduce LDL-C substantially reduce the risk of cardiovascular disease, including MI and stroke, as well as total mortality. Thus, is it imperative that pts with hypercholesterolemia be assessed for cardiovascular risk and for the need for intervention. Pts at high risk for cardiovascular disease who have plasma LDL-C levels in the “normal” range also benefit from intervention to reduce LDL-C levels.

Lifestyle The first approach to a pt with hypercholesterolemia and high cardiovascular risk is to make any necessary lifestyle changes. In obese pts, efforts should be made to reduce body weight to the ideal level. Dietary counseling to reduce the content of saturated fats, trans fats, and cholesterol in the diet. Regular aerobic exercise has relatively little impact on reducing plasma LDL-C levels, though has cardiovascular benefits independent of LDL lowering.

Pharmacologic therapy for hypercholesterolemia The decision to use LDL-lowering drug therapy—with a statin being first-line therapy—depends on the level of LDL-C as well as the level of cardiovascular risk. In general, pts with a Mendelian disorder of elevated LDL-C such as FH must be treated to reduce the very high lifetime risk of cardiovascular disease, and treatment should be initiated as early as possible in adulthood, and in some cases during childhood. Otherwise, the decision to initiate LDL-lowering drug therapy is generally determined by the level of cardiovascular risk. In pts with established CVD, statin therapy is well supported by clinical trial data and should be used regardless of the LDL-C level. For pts >40 years old without clinical CVD, the AHA/ACC risk calculator ( can be used to determine the 10-year absolute risk for CVD, and current guidelines suggest that a 10-year risk >7.5% merits consideration of statin therapy regardless of plasma LDL-C level. For younger pts, the assessment of lifetime risk of CVD may help inform the decision to start a statin. For those who do not respond adequately to statins, or cannot tolerate them, additional therapeutic options include ezetimibe, bile acid sequestrants, nicotinic acid, and PCSK9 inhibitors (Table 181-2).

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