Abstract
BackgroundDue to the paucity of direct evidence, we aimed to evaluate whether the association between postload plasma glucose levels (ppGlucose) and long-term risk of mortality from coronary heart disease was independent of or attributable to genes and common environment.Methods and FindingsFrom the prospective National Heart, Lung, and Blood Institute (NHLBI) Twin Study, we included 903 middle-aged male twins, who were nondiabetic, free of coronary heart disease at baseline (1969–1973), and followed for up to 38 years for coronary heart, cardiovascular, and all-cause mortality. Frailty survival models were used to estimate hazard ratio (HR) for various associations: overall (equivalent to singleton population association), within-pair (controlling for genes and environment common to co-twins), and between-pair association (reflecting influences of common factors). Overall associations were statistically significant for coronary heart and cardiovascular but not all-cause deaths after controlling for known risk factors. The associations were not statistically significant in within-pair analyses. The within-pair association was not statistically different by zygosity for specific and all-cause death risk. After the full adjustment for known risk factors, HR (95% confidence interval) for within-pair association was 1.07 (0.90, 1.28), 1.06 (0.94, 1.19), and 0.99 (0.94, 1.05) for coronary heart, cardiovascular, and all-cause mortality, respectively. The fully adjusted between-pair associations were statistically significant for specific and all-cause death risk: a 50 mg/dL increase in the mean value of ppGlucose for a twin pair was associated with a raised death risk [HR (95% confidence interval) 1.15 (1.02, 1.30), 1.10 (1.02, 1.20), and 1.05 (1.01, 1.09) for coronary heart, cardiovascular, and all-cause mortality, respectively]. Between-pair association was significant in dizygotic but not in monozygotic twins.ConclusionThe positive association between ppGlucose and long-term coronary heart mortality risk is largely explained by factors shared between co-twins, including familial factors; however, within-pair effects cannot be absolutely excluded.
Highlights
Hyperglycemia has been considered as a risk factor for cardiovascular events and postload hyperglycemia may be a stronger predictor of cardiovascular outcomes than fasting hyperglycemia [1,2,3,4,5,6]
The positive association between ppGlucose and long-term coronary heart mortality risk is largely explained by factors shared between co-twins, including familial factors; within-pair effects cannot be absolutely excluded
For this study, using a unique co-twin design, we primarily examined the prospective association between postload plasma glucose levels and the long-term risk of death due to coronary heart disease independent of influences of genes and common environment, and whether these shared factors contributed to the association
Summary
Hyperglycemia has been considered as a risk factor for cardiovascular events and postload hyperglycemia may be a stronger predictor of cardiovascular outcomes than fasting hyperglycemia [1,2,3,4,5,6]. Genetic and common environmental factors could influence hyperglycemiarelated cardiovascular outcomes, and might alternatively explain why significant improvement in glucose control did not necessarily prevent or retard diabetes-mediated macrovascular disease including coronary heart disease [11]. These genetic and common environmental factors have not been well-controlled for or evaluated in previous traditional observational prospective studies [1,4,5,6]. Due to the paucity of direct evidence, we aimed to evaluate whether the association between postload plasma glucose levels (ppGlucose) and long-term risk of mortality from coronary heart disease was independent of or attributable to genes and common environment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
