SUN-070 Asymptomatic Patients with Homozygous Familial Hypercholesterolemia: A Challenge

Abstract

Background: Homozygous familial hypercholesterolemia (HoFH), a very rare autosomal dominant disease, mainly caused by LDL receptor (LDL-R) alterations, with aortic valve compromise reaching nearly 100% and vascular calcifications that can progress independently of marked decrease in total and LDL cholesterol levels. Clinical case: A 21-year-old Hispanic woman diagnosed with HoFH at the age of 6 was referred to our hospital for follow up. Her father had died of acute myocardial infarction at the age of 40. Her mother had an LDLc of 309 mg/dl (8.06 mmol/l) and total cholesterol (TC) 400 mg/dl (10.44 mmol/l) with Achilles tendon xanthomas. She had one elder-brother and sister with elevated levels of TC without xanthomas. She had initially been treated with a statin and ezetimibe at age of 15, but had discontinued these drugs several years ago. Her lipid profile showed TC 700 mg/dl (18.2 mmol/l), triglycerides (Tg) 100 mg/dl (1.31 mmol/l), high density lipoprotein cholesterol (HDL-C) 32 mg/dl (0.83 mmol/l) and LDL-C 546 (14.2 mmol/l). Physical examination showed, xanthomas in Achilles tendons and elbows, and tuberous xanthomas on the knees. She had a systolic ejection murmur, which irradiated to the axillar region. Her EKG was normal. Carotid arterial intima-media thickness (cIMT) revealed non-obstructive plaque formation in both right and left carotid arteries. CT coronary angiography showed severe calcification in the right coronary, left anterior descending arteries, ascending and descending aorta with calcium score of 890 AU. Strain echocardiography showed thickened and flared valves in the aortic, tricuspid and mitral regions. PET/CT with 18F Sodium-Fluoride (18F-NaF) radiotracer showed significant aortic valve uptake with active tissue calcifications. The patient is currently receiving PCSK-9 inhibitor bi-monthly. Conclusion: Despite of the symptoms and cholesterol levels, the clinical course of atherosclerotic manifestations in HoHF individual is highly variable. Premature malignant atherosclerosis leading to aortic valve and root abnormalities is a recognized complication of HoFH and has a strong correlation with age and calcium scores. Greater access to imaging techniques are critical to define the clinical variability of HoFH that have important prognostic and therapeutic implications. Reference: M. Cuchel, E. Bruckert, H.N. Ginsberg, et al., Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society, Eur. Heart J. 35 (32) (2014) 2146e2157 ehu274