Which of the following is the primary lipid abnormality associated with increased atherosclerotic risk in familial hypercholesterolemia?

Explanation

## Familial Hypercholesterolemia and LDL Receptor Defects **Key Point:** Familial hypercholesterolemia (FH) is caused by mutations in the LDL receptor gene, resulting in defective or absent LDL receptors on hepatocytes. ### Pathophysiology 1. LDL receptors normally mediate hepatic uptake of LDL particles 2. Defective receptors → impaired LDL clearance → markedly elevated plasma LDL cholesterol 3. Heterozygous FH: LDL levels 2–3× normal; homozygous FH: LDL levels 6–10× normal ### Lipid Profile in FH | Parameter | Finding | | --- | --- | | **LDL cholesterol** | Markedly elevated (primary abnormality) | | **Total cholesterol** | Elevated | | **HDL cholesterol** | Normal or slightly reduced | | **Triglycerides** | Normal | **High-Yield:** FH is one of the most common genetic causes of premature atherosclerosis and coronary artery disease, especially in the homozygous form, which can present with MI in childhood. **Clinical Pearl:** Tendon xanthomas (especially Achilles tendon) and corneal arcus are pathognomonic physical findings in FH and reflect chronic LDL deposition in tissues. [cite:Robbins 10e Ch 5]