Key result
Low Life's Essential 8 scores combined with high polygenic risk were associated with a 3.41-fold higher risk of incident cardiovascular disease compared to optimal cardiovascular health and low genetic risk.
Why the study?
Cardiovascular health and genetic susceptibility to adverse left ventricular remodeling are each linked to cardiovascular diseases, but their combined role remains unclear.
Does the combination of cardiovascular health (LE8 score) and genetic risk (PRS) predict adverse left ventricular remodeling and incident cardiovascular disease in adults without prevalent CVD?
Cohort (n=4,090)
Does the combination of cardiovascular health (LE8 score) and genetic risk (PRS) predict adverse left ventricular remodeling and incident cardiovascular disease in adults without prevalent CVD?
Lower cardiovascular health scores combined with high genetic risk confer a synergistic, three-fold higher risk for adverse left ventricular remodeling and incident cardiovascular disease.
Supports integrated LE8-PRS assessment for primary prevention; leaves open whether optimizing LE8 attenuates high genetic risk.
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. 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.
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Lobo et al. (2026) conducted a cohort in Cardiovascular Disease (n=4,090). Low Life's Essential 8 score and high polygenic risk score vs. High Life's Essential 8 score and low polygenic risk score (optimal risk) was evaluated on Incident cardiovascular disease (composite of coronary heart disease, heart failure, stroke, or peripheral artery disease) (HR 3.41, p=<0.001). Low Life's Essential 8 scores combined with high polygenic risk were associated with a 3.41-fold higher risk of incident cardiovascular disease compared to optimal cardiovascular health and low genetic risk.
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