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Genetic influences on angina pectoris and its impact on coronary heart disease
Slobodan Zdravkovic1, Andreas Wienke, Nancy L Pedersen
1Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. slobodan.zdravkovic@ki.se
Insights
Genetic factors influence angina pectoris (AP) and coronary heart disease (CHD) death. AP significantly increases CHD mortality risk in both sexes, partly due to shared genetic pathways.
Area of Science:
- Cardiovascular Genetics
- Twin Studies
- Epidemiology
Background:
- Coronary heart disease (CHD) presents varied phenotypes, potentially linked to distinct genetic mechanisms.
- Angina pectoris (AP) is a common symptom of CHD, but its specific genetic underpinnings and impact on mortality require further investigation.
Purpose of the Study:
- To investigate the genetic contribution to angina pectoris (AP).
- To assess the impact of AP on the risk of coronary heart disease (CHD) death.
- To explore shared genetic factors between AP and CHD death.
Main Methods:
- Utilized the Swedish Twin Registry for a cohort born between 1886-1958.
- Employed survival and quantitative genetic models.
- Analyzed data on CHD death from the Swedish Cause of Death Register.
Main Results:
- AP significantly increases CHD death risk in both males (HR 2.0) and females (HR 1.6).
- Higher concordance rates for AP and CHD death observed in monozygotic compared to dizygotic twins.
- Moderate heritability estimates for AP (males: 0.39, females: 0.43) and familial factors explained the AP-CHD correlation.
Conclusions:
- Genetic factors play a significant role in both AP and CHD mortality.
- AP is a crucial risk factor for CHD death in both sexes.
- Shared genetic pathways contribute to the association between AP and increased CHD death risk.
Abstract:
As functional properties of the coronaries may differ between coronary heart disease (CHD) patients with or without angina pectoris (AP), it is possible that different genetic mechanisms could be involved in the various CHD phenotypes. The primary aim of this study was, therefore, to determine the relative importance of genetic factors for AP as well as the impact of AP on CHD death in general. All same-sexed twins born between 1886 and 1958 included in the Swedish Twin Registry served as a base for this study. Information from the Swedish Cause of Death Register was used for diagnosing CHD death. Standard methods applied in twin research such as survival and quantitative genetic models were used. The impact of AP on CHD death was significant among both sexes, with larger estimates for males (hazard ratio and 95% CI 2.0 (1.8-2.3)) than females (1.6 (1.4-1.8)). Probandwise concordances and intraclass correlations for AP and CHD death were in general greater in monozygotic than dizygotic twins among both sexes. Heritability analyses resulted in moderate heritability estimates for AP in both sexes (0.39 (0.29-0.49) for males and 0.43 (0.08-0.51) for females). The correlation between AP and CHD was exclusively explained by the influence of familial factors in both sexes. In conclusion, our data imply genetic influences for AP and CHD death among both sexes and that AP is important as a risk factor for CHD death in both males and females, due in part to shared genetic pathways.
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