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Post mortem molecularly defined familial hypercholesterolemia and sudden cardiac death of young men
A F Vuorio1, K Kontula, H Turtola
1Department of Internal Medicine, University of Helsinki, Finland.
Insights
Familial hypercholesterolemia (FH), a common genetic disorder, significantly increases the risk of early cardiac deaths. This study suggests FH may underlie 3-5% of unexpected early heart attacks in Finland.
Area of Science:
- Genetics
- Cardiology
- Epidemiology
Background:
- Familial hypercholesterolemia (FH) is a prevalent single-gene disorder caused by low-density lipoprotein (LDL) receptor gene mutations.
- Heterozygous FH elevates serum LDL-cholesterol, increasing premature atherosclerosis and cardiac death risk, particularly in men.
- Limited data exist on the incidence of premature mortality in FH patients.
Purpose of the Study:
- To investigate the prevalence of heterozygous FH in individuals experiencing unexpected early cardiac death.
- To assess the potential contribution of FH to coronary heart disease (CHD) mortality in Finland.
Main Methods:
- A case-control study involving 149 deceased individuals (< or = 50 years) with unexpected cardiac death due to CHD.
- Molecular genetic analysis to identify FH-causing mutations in LDL receptor genes.
- Prevalence of heterozygous FH determined in the overall cohort and in subjects with acute myocardial infarction (AMI).
Main Results:
- Three individuals (2%) among the 149 deceased had molecularly defined heterozygous FH.
- Heterozygous FH was identified in two (3%) of the 67 subjects with demonstrable AMI.
- Given Finland's specific FH founder mutations, FH may account for 3-5% of early cardiac deaths from AMI.
Conclusions:
- Familial hypercholesterolemia is a significant, underrecognized contributor to premature cardiac death.
- The findings highlight the importance of screening for FH in cases of early, unexpected coronary heart disease mortality.
Abstract:
Familial hypercholesterolemia (FH) is among the most common single-gene diseases and is due to mutations of the low-density lipoprotein (LDL) receptor gene. In heterozygous FH, serum LDL-cholesterol level is elevated two- to threefold compared to unaffected individuals, men in particular are prone to premature atherosclerosis and early cardiac deaths. However, very little data are available concerning the incidence of premature deaths in FH patients. In Finland two LDL receptor founder mutations cover two-thirds of FH cases, offering a unique possibility to study the potential role of FH in unexpected early cardiac deaths. We studied a total of 149 deceased who had suffered early (< or = 50 years) unexpected cardiac death due to coronary heart disease (CHD). Three individuals (2%) had molecularly defined heterozygous FH, and heterozygous FH was present in two (3%) of the 67 subjects who had demonstrable acute myocardial infarction (AMI). Considering that the two FH mutations cover two-thirds of FH cases in Finland, the overall prevalence of FH underlying early cardiac deaths caused by AMI may be estimated to be in the range 3 to 5%.