Abstract 16300: Genetic Influences on Cardiovascular Deaths During Various Follow-Up Lengths in the 45-Year Longitudinal Twin Study

Abstract

Background: Genetic factors are known to affect cardiovascular and coronary heart death. The more deaths occur during the longer follow-up period in a longitudinal study. However, it is unclear whether follow-up lengths affect genetic influences on the mortality from total cardiovascular (CVD) and coronary heart diseases (CHD). Objective: To determine genetic influences on the mortality from CVD and CHD over various years of follow-up in the 45-year longitudinal National Heart, Lung, and Blood Institute (NHLBI) Twin Study. Method: A total of 1024 middle-aged, white male, veteran twins (512 pairs), including 253 monozygotic and 261 dizygotic twin pairs, were initially enrolled during 1969-1973 and then followed up on vital status and causes of death through December 31, 2015. Tetrachoric correlation coefficients were estimated for CHD and CVD death at 20, 30, and 45 years of follow-up, respectively. Genetic and environmental influences on the death were quantified using the best-fitting structural equation model selected with the smallest Akaike's Information Criterion value and the parsimony rule. Results: The age at death ranged from 43.9 to 97.3 years over a 45-year follow-up. Tetrachoric correlation coefficients in dizygotic twins were less than half of that in monozygotic twins over 20, 30, and 45 years of follow-up for CVD but over 20 and 30 years for CHD, respectively. Dominant genetic factors explained 40% (95% CI 5% ~ 68%), 39 % (16% ~ 59%), and 24% (4% ~ 43%) of variation in CVD death over 20, 30, and 45 years of follow-up, respectively, while the remaining variation in CVD death was explained by unique environmental factors during each follow-up period. For CHD death, unique environmental factors explained all variation over 20 and 45 years of follow-up. By contrast, dominant genetic factors explained 26% (95% CI -6% ~ 53%) variation in CHD death over 30 years of follow-up while the remaining variation was explained by unique environmental factors. Conclusion: Dominant genetic factors consistently influence cardiovascular mortality over 20 to 45 years of follow-up, implying a twin study of cardiovascular death can control for genetic confounding during this period.