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Mortality over two centuries in large pedigree with familial hypercholesterolaemia: family tree mortality study
E J Sijbrands1, R G Westendorp, J C Defesche
1Department of Vascular Medicine and General Internal Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands. mrexpert@euronet.nl
Objective:
To estimate all cause mortality from untreated familial hypercholesterolaemia free from selection for coronary artery disease.
Design:
Family tree mortality study.
Setting:
Large pedigree in Netherlands traced back to a single pair of ancestors in the 19th century.
Subjects:
All members of pedigree aged over 20 years with 0.5 probability of carrying a mutation for familial hypercholesterolaemia.
Main Outcome Measure:
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.