Vascular Calcifications in Homozygote Familial Hypercholesterolemia

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 28; no. 4; pp. 777 - 785
• Main Authors: Awan, Z, Alrasadi, K, Francis, G A., Hegele, R A., McPherson, R, Frohlich, J, Valenti, D, de Varennes, B, Marcil, M, Gagne, C, Genest, J, Couture, P
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.04.2008; Hagerstown, MD Lippincott
• Subjects: Adolescent; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Aortic Diseases - blood; Aortic Diseases - complications; Aortic Diseases - genetics; Aortic Diseases - pathology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Calcinosis - blood; Calcinosis - complications; Calcinosis - genetics; Calcinosis - pathology; Canada; Cardiology. Vascular system; Child; Child, Preschool; Cholesterol, LDL - blood; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Emergency and intensive care: renal failure. Dialysis management; Ethnic Groups - genetics; Female; Follow-Up Studies; Homozygote; Humans; Hyperlipoproteinemia Type II - blood; Hyperlipoproteinemia Type II - complications; Hyperlipoproteinemia Type II - genetics; Hyperlipoproteinemia Type II - pathology; Intensive care medicine; Male; Medical sciences; Middle Aged; Mutation; Receptors, LDL - genetics; Canada; Metabolic diseases; Lipids; Cardiovascular disease; Hyperlipoproteinemia; Lipoprotein; Artery; Cholesterol; Genetic disease; Vascular disease; Hypercholesterolemia; Blood vessel; Atherosclerosis; familial hypercholesterolemia; Calcification; Aorta; Circulatory system; Dyslipemia
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/ATVBAHA.107.160408

BACKGROUND—Patients with homozygous familial hypercholesterolemia (hmzFH) attributable to LDL receptor gene mutations have shown a remarkable increase in survival over the last 20 years. Early onset coronary heart disease (CHD) and calcific aortic valve stenosis are the major complications of this disorder. We now report extensive premature calcification of the aorta in patients with hmzFH. METHODS AND RESULTS—We examined 25 hmzFH patients from Canada; mean age was 32 years (range 5 to 54), and mean baseline cholesterol before treatment was 19±5 mmol/L (737±206 mg/dL). Aortic calcification was quantified using computed tomography (CT). An elevated mean calcium score was found in patients by age 20 and correlated with age (r=0.53, P=0.001). One quarter (24%) of patients underwent aortic valve surgery. CONCLUSIONS—We document premature severe aortic calcifications in all adult hmzFH patients studied. These presented considerable surgical management challenges. Strategies to identify and monitor aortic calcification in hmzFH by noninvasive techniques are required, as are clinical trials to determine whether additional or more intensive therapies will prevent the progression of such calcifications. Whether vascular calcifications in hmzFH subjects are related to sustained increases in LDL-C levels or to other mechanisms, such as abnormal osteoblast activity, remains to be determined.