Familial Hypercholesterolemia and the Atherosclerotic Disease

Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular diseases, and is inherited as an autosomal dominant trait. The prevalence of heterozygous FH is one in five hundred people. Owing to dysfunctional low density lipoprotein (LDL) receptors due to genetic mutations, serum low density lipoprotein-cholesterol (LDL-C) levels are considerably increased from birth. FH is clinically diagnosed by confirmation of family history and characteristic findings such as tendon xanthoma or xanthelasma. Thus, clinical concern and suspicion are important for early diagnosis of the disease. Current guidelines recommend lowering LDL-C concentration to at least 50% from baseline. Statins are shown to lower LDL-C levels with high safety, and thus, have been the drug of choice. However, it is difficult to achieve an ideal level of LDL-C with a single statin therapy in the majority of FH patients. Alternatively, lipid lowering combination therapy with the recently-introduced ezetimibe has shown more encouraging results.