Familial hypercholesterolemia (FH) is an autosomal codominant genetic condition, which results in heightened levels of LDL-C in the blood. It is diagnosed by the presence of mutations in low-density lipoprotein receptor (LDLR), apolipoprotein (ApoB), or proprotein convertase subtilisin/kexin 9 (PCSK9), with the LDLR mutation most common. The LDLR variant results in the malfunction of LDLR and problems with the clearance of LDL-C from the blood.
The worldwide mortality rate of FH is between 1:200 and 1:300, and if left untreated, FH can lead to premature atherosclerosis and an elevated risk of cardiovascular events. Because lifestyle modification alone is insufficient to maintain decreased LDL-C concentrations in FH patients, lipid-lowering therapy is necessary. Newer treatment options include small-molecule- or antibody-based approaches.
How do you treat patients with heterozygous FH who need additional lowering of LDL-C levels than that conferred by maximally tolerated statin dosages and lifestyle intervention? How do you determine when and what agents to use based on patient type?