title: Cardiovascular disease in familial hypercholesterolaemia: influence of low-density lipoprotein receptor mutation type and classic risk factors.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Lipid Clinic, Fundación Jiménez Díaz, Madrid, Spain. ralonso@fjd.es
authors.forename: R
authors.initials: R
authors.lastname: Alonso
authors.forename: N
authors.initials: N
authors.lastname: Mata
authors.forename: S
authors.initials: S
authors.lastname: Castillo
authors.forename: F
authors.initials: F
authors.lastname: Fuentes
authors.forename: P
authors.initials: P
authors.lastname: Saenz
authors.forename: O
authors.initials: O
authors.lastname: Muñiz
authors.forename: J
authors.initials: J
authors.lastname: Galiana
authors.forename: R
authors.initials: R
authors.lastname: Figueras
authors.forename: J L
authors.initials: JL
authors.lastname: Diaz
authors.forename: P
authors.initials: P
authors.lastname: Gomez-Enterría
authors.forename: M
authors.initials: M
authors.lastname: Mauri
authors.forename: M
authors.initials: M
authors.lastname: Piedecausa
authors.forename: L
authors.initials: L
authors.lastname: Irigoyen
authors.forename: R
authors.initials: R
authors.lastname: Aguado
authors.forename: P
authors.initials: P
authors.lastname: Mata
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000150:complications* / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D011973:Receptors, LDL / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors; D013030:Spain
chemical_list: D011973:Receptors, LDL