Een eeuwen omspannende stamboom met familiaire hypercholesterolemie: betekenis van omgevingsfactoren voor het sterfterisico

To estimate the mortality caused by familial hypercholesterolaemia (FH) without selection based on cardiovascular disease.

Design

Genealogical investigation with identification of carriers of the V408M-mutation and determination of the standardised mortality ratio (SMR).

Method

The mortality in a large pedigree with FH going back to the 18th century was compared with the mortality in the Dutch population. In the pedigree, the mortality due to all causes was studied in all subjects older than 20 years with a 50 chance of having the abnormality.

Results

Among 250 persons accounting for a total of 6950 person-years, there were 70 deaths. There was no excess mortality due to the abnormality in the 19th and early 20th centuries; after 1915, the mortality began to rise, reaching a maximum in 1935-1964 (SMR: 1.78; 95-CI: 1.13-2.76; p = 0.003), after which it again decreased. Moreover, there was a significant difference in mortality between two large branches of the pedigree (relative risk: 3.26; 95-CI: 1.74-6.11; p = 0.001).

Conclusion

The mortality among the subjects with FH varied significantly. Such an extensive variation over the centuries and between the branches of a pedigree suggests a strong interaction with environmental factors. Additional research is required to be able to identify FH-patients with a sharply increased risk of mortality so that optimal preventive measures may be offered.