title: Influence of LDL-receptor mutation type on age at first cardiovascular event in patients with familial hypercholesterolaemia.
abstract: OBJECTIVE
  To investigate the influence of different LDL-receptor (LDLR) gene mutations on age at first cardiovascular event in familial hypercholesterolaemia (FH) patients.
  
  
  RESULTS
  Dutch FH patients (n = 862) with known LDLR mutations from a retrospective cohort study were included. A gamma frailty Cox model was used. An event was defined as the first cardiovascular event. Gender, hypertension, smoking, diabetes, HDL cholesterol, LDL cholesterol (LDL-C), or triglycerides were included as covariates. Furthermore, the effect of LDLR mutation type on LDL and HDL cholesterol levels was investigated using mixed effects models, including gender, smoking, body mass index, and age at time of lipid measurement as covariates. A total of 86 different LDLR mutations were present in this cohort. Twenty-two percent of patients experienced an event (median age: 47.1 year; range: 25.6-85.8 years). The effect of LDLR mutation type on event-free survival is only significant in the models without LDL-C levels. Also, LDLR mutation type was significantly associated with LDL-C levels (P = 0.007), but not with HDL cholesterol levels (P = 0.12).
  
  
  CONCLUSIONS
  In the present study, LDL-C levels are a more important risk factor of event-free survival than the type of LDLR mutation.
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, PO Box 22700, 1100 DE Amsterdam, the Netherlands. o.w.souverein@amc.uva.nl
authors.forename: Olga W
authors.initials: OW
authors.lastname: Souverein
authors.forename: Joep C
authors.initials: JC
authors.lastname: Defesche
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Michael W T
authors.initials: MW
authors.lastname: Tanck
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D018572:Disease-Free Survival; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011973:Receptors, LDL / Q000097:blood / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D011973:Receptors, LDL