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.