Background: Venous thromboembolism (VTE) is a common disease with a strong genetic basis. Unhealthy lifestyle factors contribute to risk, but it is unknown whether healthier lifestyle can mitigate the risk for VTE in those at high genetic risk. We studied whether greater adherence to the American Heart Association's (AHA's) cardiovascular health metric called Life's Simple 7 (LS7) is associated with a lower rate of VTE in individuals with high genetic risk score (GRS) for VTE.
Methods: We followed 9,026 middle-aged white participants from the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort of 15,792 individuals enrolled in 1987-89. A validated GRS was used, comprising 5 well known genetic conditions associated with VTE (factor V Leiden, prothrombin 20210A, non-O blood group, factor XI rs4241824, and fibrinogen gamma FGG rs2066865). Only white participants were included, as the GRS did not predict VTE in others. AHA's LS7 categories of inadequate, average, and optimal health were determined based on smoking status, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting glucose. VTE events were adjudicated by expert medical record review. We calculated hazard ratios (HRs) and 95% confidence intervals (CI) of incident VTE by LS7 categories, stratified by GRS (low, intermediate, high), adjusting for age, sex, and education. HRs were also calculated for individual LS7 components stratified by GRS.
Results: There were 466 incident VTE over 22.8 years of follow-up. Compared to those with optimal health, those with inadequate LS7 score had higher rates of VTE (5.7% vs. 3.9%). In Figure 1, compared to the high GRS / inadequate LS7 group, the HR of VTE in the low GRS group with optimal health was lowest at 0.39 (95% CI 0.25-0.61), but moreover, the HR in the high GRS group with optimal health was also attenuated to 0.65 (95% CI 0.48-0.89). The pattern of association was similar for provoked and unprovoked VTE. Of the LS7 components, obesity was most strongly related to VTE. In Figure 2, compared to obese / high GRS participants, the HR of VTE with normal weight / low GRS was 0.36 (95% CI 0.23-0.57), while the HR in high GRS / normal weight participants was reduced by 45%, at 0.55 (95% CI 0.4-0.76).
Conclusion: Among all participants, even those at high genetic risk, healthier lifestyle factors, particularly obesity, were associated with decreased incidence of VTE. Further studies should determine the impact of lifestyle change among patients at high genetic risk of VTE, such as in thrombophilic families.
Heckbert:National Institutes of Health: Other: Grants.
