Mortality Over Two Centuries In Large Pedigree With Familial Hypercholesterolaemia: Family Tree Mortality Study

• Published in: BMJ (Online) Vol. 322; no. 7293; pp. 1019 - 1022
• Main Authors: Sijbrands, Eric J. G., Westendorp, Rudi G. J., Defesche, Joep C., de Meier, Paul H. E. M., Smelt, Augustinus H. M., Kastelein, John J. P.
• Format: Journal Article
• Language: English
• Published: England British Medical Association 28-04-2001; BMJ Group
• Subjects: Adult; Aged; Cardiovascular diseases; Confidence interval; Coronary artery disease; Death; Female; Genetic mutation; Heterozygote; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II - genetics; Hyperlipoproteinemia Type II - mortality; Male; Medical genetics; Middle Aged; Mortality; Mutation; Netherlands - epidemiology; Pedigree; Population genetics; Regression Analysis; Sex Factors; Survival Rate - trends; Transmission lines; Netherlands
• ISSN: 0959-8138; 1756-1833; 1468-5833
• DOI: 10.1136/bmj.322.7293.1019

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.