- Country: Netherlands
- Official Title: doctor of philosophy
- Department: Medical Center Rotterdam
- Institute: Erasmus MC University The Netherlands
- E-Mail: e.sijbrands@erasmusmc.nl
Speech Title
Beneficial Spatial Impact on Life Expectancy Does Not Correct for Familial Hypercholesterolemia
After diagnosis, patients with familial hypercholesterolemia (FH) are advised lifelong cholesterol-lowering treatment. They prefer adopting a beneficial lifestyle over medication. Without any trial evidence, we propose combining a healthy lifestyle with statins as the first line of therapy. Our nationwide cascade screening obtained a large pedigree with the S306L mutation in the low-density lipoprotein receptor (LDLR) gene. Before the statins became available in 1990, we determined the all-cause standardised mortality ratio (SMR). The geographic variation of life expectancy in the Netherlands has enabled a trial by nature of the same untreated FH mutation in a beneficial and general environment.
Between 1800 and 1989, 147 deaths occurred in 14,152 person-years. The SMR was 1.25 (95% CI 1.05-1.46; P = 0.0056). The spouses in a small village had an SMR of 0.75 (95% CI 0.55-0.99; P =0.0547), pointing at a beneficial environment. The mortality of a large part of the FH pedigree in this beneficial environment was not increased (SMR 1.16; 95% CI 0.85-1.54; P =0.1794), while all other parts of the country confirmed the known overall excess mortality from untreated FH (SMR 1.29; 95% CI 1.05-1.57; P = 0.0076). However, the FH patients in the beneficial environment had 1.5 times more deaths relative to their spouses (RR 1.46; 95% CI 0.96-2.22; P =0.07388). A favourable local environment significantly decreased excess mortality. However, the S306L mutation in the LDLR gene still caused the expected excess mortality locally. Our findings show that a beneficial lifestyle is an add-on but not an alternative to the immediate start of cholesterol-lowering treatment.