Cardiovascular disease in familial hypercholesterolaemia: Influence of low-density lipoprotein receptor mutation type and classic risk factors

• Published in: Atherosclerosis Vol. 200; no. 2; pp. 315 - 321
• Main Authors: Alonso, R., Mata, N., Castillo, S., Fuentes, F., Saenz, P., Muñiz, O., Galiana, J., Figueras, R., Diaz, J.L., Gomez-Enterría, P., Mauri, M., Piedecausa, M., Irigoyen, L., Aguado, R., Mata, P.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.10.2008; Elsevier
• Subjects: Adult; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood. Blood coagulation. Reticuloendothelial system; Cardiology. Vascular system; Cardiovascular; Cardiovascular disease; Cardiovascular Diseases - complications; Cardiovascular Diseases - genetics; Cardiovascular risk factors; Cross-Sectional Studies; Familial hypercholesterolaemia; Female; Heterozygote; Humans; Hyperlipoproteinemia Type II - complications; Hyperlipoproteinemia Type II - genetics; LDL-receptor mutations; Male; Medical sciences; Middle Aged; Mutation; Odds Ratio; Pharmacology. Drug treatments; Receptors, LDL - genetics; Risk Factors; Sex Factors; Spain; Spain; Cardiovascular disease; LDL-receptor mutations; Cardiovascular risk factors; Familial hypercholesterolaemia; Metabolic diseases; Lipids; Hyperlipoproteinemia; Cholesterol; Genetic disease; Vascular disease; Lipoprotein LDL; Familial disease; Hypercholesterolemia; Atherosclerosis; Risk factor; Mutation; Dyslipemia
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2007.12.024

To determine the effect of the type of mutation in low-density lipoprotein receptor gene and the risk factors associated with the development of premature cardiovascular disease (PCVD) in a large cohort of heterozygous familial hypercholesterolemia (hFH) subjects with genetic diagnosis in Spain. A cross-sectional study was conducted on 811 non-related FH patients (mean age 47.1 ± 14 years, 383 males and 428 females) with a molecular defect in the low-density lipoprotein receptor ( LDLR) gene from the Spanish National FH Register. Prevalence of PCVD was 21.9% (30.2% in males and 14.5% in women, P < 0.001). Mean age of onset of cardiovascular event was 42.1 years in males and 50.8 years in females. Of those patients with PCVD, 59.5% of males and 27% of females suffered a second cardiovascular (CV) event. In multivariate analysis male gender, age, tobacco consumption (ever), and total cholesterol/HDL-cholesterol (TC/HDL-C) ratio were significantly associated with PCVD. Two hundred and twenty different mutations were found with a large heterogeneity. Patients carrying null-mutations had significantly higher frequency of PCVD and recurrence of CV events. No relationship with Lp(a) levels and genotype of Apo E were found. This study confirms the importance of identifying some classic risk factors such as smoking and TC/HDL-C ratio, and also the type of mutation in LDLR gene in order to implement early detection and intensive treatment for the prevention of cardiovascular disease in FH patients.