Mortality over two centuries in large pedigree with familial hypercholesterolaemia: family tree mortality study.
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.
Sijbrands
E J
EJ
Department of Vascular Medicine and General Internal Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands. mrexpert@euronet.nl
Westendorp
R G
RG
Defesche
J C
JC
de Meier
P H
PH
Smelt
A H
AH
Kastelein
J J
JJ
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