title: Mortality over two centuries in large pedigree with familial hypercholesterolaemia: family tree mortality study.
abstract: OBJECTIVE
  To estimate all cause mortality from untreated familial hypercholesterolaemia free from selection for coronary artery disease.
  
  
  METHODS
  Family tree mortality study.
  
  
  METHODS
  Large pedigree in Netherlands traced back to a single pair of ancestors in the 19th century.
  
  
  METHODS
  All members of pedigree aged over 20 years with 0.5 probability of carrying a mutation for familial hypercholesterolaemia.
  
  
  METHODS
  All cause mortality.
  
  
  RESULTS
  A total of 70 deaths took place among 250 people analysed for 6950 person years. Mortality was not increased in carriers of the mutation during the 19th and early 20th century; it rose after 1915, reached its maximum between 1935 and 1964 (standardised mortality ratio 1.78, 95% confidence interval 1.13 to 2.76; P=0.003), and fell thereafter. Mortality differed significantly between two branches of the pedigree (relative risk 3.26, 95% confidence interval 1.74 to 6.11; P=0.001).
  
  
  CONCLUSIONS
  Risk of death varies significantly among patients with familial hypercholesterolaemia. This large variability over time and between branches of the pedigree points to a strong interaction with environmental factors. Future research is required to identify patients with familial hypercholesterolaemia who are at extreme risk and need early and vigorous preventive measures.
authors.affiliation: Department of Vascular Medicine and General Internal Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands. mrexpert@euronet.nl
authors.forename: E J
authors.initials: EJ
authors.lastname: Sijbrands
authors.forename: R G
authors.initials: RG
authors.lastname: Westendorp
authors.forename: J C
authors.initials: JC
authors.lastname: Defesche
authors.forename: P H
authors.initials: PH
authors.lastname: de Meier
authors.forename: A H
authors.initials: AH
authors.lastname: Smelt
authors.forename: J J
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands / Q000453:epidemiology; D010375:Pedigree; D012044:Regression Analysis; D012737:Sex Factors; D015996:Survival Rate / Q000639:trends