Mehlman Cardiology Practice Exam

Familial hypercholesterolemia most commonly results from defective LDL receptor function, which impairs clearance of LDL cholesterol from the bloodstream. When hepatocyte LDL receptors are reduced in number or work poorly due to LDLR gene mutations, LDL remains circulating at high levels from birth, driving very high LDL cholesterol and accelerating atherosclerosis. The body’s normal route to remove LDL is via these receptors that bind apolipoprotein B-100 on LDL particles and internalize them into liver cells; if this pathway is compromised, LDL accumulates. That’s why this defect is the classic cause of familial hypercholesterolemia. In contrast, a lipase deficiency tends to raise triglycerides, not LDL; apolipoprotein E deficiency leads to a different dyslipoproteinemia (type III) with abnormal remnants, and “hypermastik” isn’t a recognized mechanism for FH.