Association of Cardiovascular Health and Genetic Risk for Left Ventricular Mass with Left Ventricular Structure, Function, and Incident Cardiovascular Outcomes

Background: Cardiovascular health (CVH) and genetic susceptibility to adverse left ventricular (LV) remodeling are each linked to cardiovascular diseases (CVD); however, their combined role remains unclear. Methods: Framingham Heart Study participants [n=1,255 Offspring-Exam 8 (2005-2008), n=2,835 Generation 3-Exam 1 (2002-2005)] had assessment of modifiable risk factors comprising the American Heart Association's Life's Essential 8 (LE8) score with higher scores indicating better CVH health. A Polygenic Risk Score (PRS) for LV mass index (LVMI) was also calculated based on published PRS(PGS003427). We created 9 groups combining LE8 and PRS tertiles (high LE8+low PRS served as referent group reflecting optimal risk) and related these groups to presence of LVMI, LV ejection fraction (LVEF), and the ratio of the peak early diastolic mitral inflow velocity (E wave) to the peak early diastolic mitral annular velocity (e' wave; E/e'; separate model for each outcome), and incident cardiovascular disease (CVD; a composite of coronary heart disease [CHD], heart failure, stroke, peripheral arterial disease). We applied linear mixed regression and Cox regression models to evaluate the relation of LE8-PRS groups with all outcomes mentioned above. Results: , LVEF 65±5%, E/e' 6 ±1.8 cm/s). Over 19 years of follow-up, composite CV events and CHD occurred in n=188 and n=99, respectively, of Offspring and n=83 and n=49 respectively, of Gen 3 participants. Compared to the referent group, individuals in the low LE8-high PRS group had high LVMI, E/e', and over three-fold higher risks for CVD and CHD, with incidence rates of approximately 1.84 versus 4.06 per 1,000 person-year, respectively. Conclusion: Lower LE8 scores (indicating worse CVH) combined with high genetic risk confer higher conjoint risks for adverse LV structure, function, and CVD development.