Life’s Essential 8, Genetic Susceptibility, and Incident Cardiovascular Disease: A Prospective Study

Background: The American Heart Association recently released a new cardiovascular health (CVH) metric, Life’s Essential 8 (LE8), for health promotion. However, the association between levels of LE8 and the risk of cardiovascular disease (CVD) outcomes is not known from a large prospective cohort. We aim to analyze the relationship between CVH, indicated by LE8, and risks of coronary heart disease (CHD), stroke, and CVD. Moreover, we sought to test whether the genetic susceptibility to CHD or stroke could be modified by LE8. Methods: A total of 137 794 participants free of CVD from the UK Biobank were included. CVH was scored using LE8 and categorized as low, moderate, and high. Results: During a median of 10 years, 8595 CVD cases (6968 CHDs and 1948 strokes) were documented. A higher LE8 score was associated with remarkably lower risks of CHD, stroke, and CVD ( P <0.001 for all). Comparing the high CVH to the low CVH, the hazard ratios (95% CI) were 0.34 (0.30–0.38) for CHD, 0.45 (0.37–0.54) for stroke, and 0.36 (0.33–0.40) for CVD. Moreover, the model with LE8 achieved higher accuracy and outperformed the model with Life’s Simple 7 for CHD, stroke, and CVD ( P <0.001 for all). The protective associations of the LE8 score with CVD outcomes were more pronounced among women ( P interaction, <0.001 for CHD and 0.0013 for CVD, respectively) and among younger adults ( P interaction, <0.001, 0.007, and <0.001 for CHD, stroke, and CVD, respectively). In addition, a significant interaction was found between the genetic risk of CHD and the LE8 score ( P interaction, <0.001). The inverse association was stronger among those with a lower genetic risk of CHD. Conclusions: High level of CVH, defined by LE8, was associated with significantly lower risks of CHD, stroke, and CVD.