A 37-year-old Caucasian gentleman presents to clinic to establish care. At age 18 years, he was diagnosed with homozygous familial hypercholesterolemia (HoFH) after his father died suddenly of a massive myocardial infarction at age 42 years. Two paternal uncles also died suddenly at ages 39 and 45 years. At that time, his low-density lipoprotein cholesterol (LDL-C) was 530 mg/dL, and he was started on a statin and advised to initiate LDL-C apheresis. He notes that he stopped the statin after seven months because "he did not like the way it made him feel." He also discontinued apheresis because it required a 3.5-hour drive each way to reach an academic medical center, and his health insurance only covered approximately 30% of the cost.
Despite much encouragement, he rejected the possibility of liver transplantation. He stopped following up with a physician. At age 35 years, he sustained an inferior wall myocardial infarction. On cardiac catheterization, he was found to have diffuse multivessel disease with an 80% obstruction in his left main coronary artery, a 75% obstruction in his proximal circumflex artery, and a completely occluded right coronary artery at approximately the middle portion of the vessel. He underwent a three-vessel coronary artery bypass without complication.
Which of the following physical findings can be found in patients with HoFH?
The correct answer is: E. Answers A, B, and C are correct.
Patients with HoFH, if untreated, can develop cutaneous and tendinous cholesterol deposits.1 Cutaneous deposits can develop along the buttocks, extremities, and the eyelids (xanthelasma). Xanthomas are most frequently encountered along the Achilles tendons, over the olecranon process, and the metacarpophalangeal joints. The aortic valve can become sclerotic and stenotic secondary to cholesterol deposition and progressive calcification.2 Patients can develop significant aortic outflow tract obstruction leading to heart failure and the need for aortic valve replacement.
Corneal arcus can develop because of cholesterol deposition in a ring-like distribution around the pupils. FH does not induce hepatic or visceral organ steatosis; if this is encountered, then the patient should be evaluated for possible insulin resistance. Regression of xanthomas and xanthelasmas can be induced with aggressive LDL-C reduction.
The patient reviewed here had mild xanthomatosis along his Achilles and infrapatellar tendons. He had xanthelasmas along his eyelids and a grade I/VI systolic murmur. Echocardiography revealed mild aortic valve stenosis with no significant gradient. Left ventricular ejection fraction was 57%, and he had no evidence of other cardiac valvular disease or of pulmonary hypertension.
Goldberg AC, Hopkins PN, Toth PP, et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol 2011;5:S1-8.
Alrasadi K, Alwaili K, Awan Z, Valenti D, Couture P, Genest J. Aortic calcifications in familial hypercholesterolemia: potential role of the low-density lipoprotein receptor gene. Am Heart J 2009;157:170-6.