Metabolite Signature of Life’s Essential 8 and Risk of Coronary Heart Disease Among Low-Income Black and White Americans

Background: Life’s essential 8 (LE8) is a comprehensive construct of cardiovascular health. Yet, little is known about the LE8 score, its metabolic correlates, and its predictive implications among Black Americans and low-income individuals. Methods: In a nested case-control study of coronary heart disease (CHD) among 299 pairs of Black and 298 pairs of White low-income Americans from the Southern Community Cohort Study, we estimated LE8 score and applied untargeted plasma metabolomics and elastic net with leave-one-out cross-validation to identify metabolite signature (MetaSig) of LE8. Associations of LE8 score and MetaSig with incident CHD were examined using conditional logistic regression. The mediation effect of MetaSig on the LE8-CHD association was also examined. The external validity of MetaSig was evaluated in another nested CHD case-control study among 299 pairs of Chinese adults. Results: Higher LE8 score was associated with lower CHD risk (standardized odds ratio, 0.61 [95% CI, 0.53–0.69]). The MetaSig, consisting of 133 metabolites, showed significant correlation with LE8 score ( r =0.61) and inverse association with CHD (odds ratio, 0.57 [0.49–0.65]), robust to adjustment for LE8 score and across participants with different sociodemographic and health status ([odds ratios, 0.42–0.69]; all P <0.05). MetaSig mediated a large portion of the LE8-CHD association: 53% (32%–80%). Significant associations of MetaSig with LE8 score and CHD risk were found in validation cohort ( r =0.49; odds ratio, 0.57 [0.46–0.69]). Conclusions: Higher LE8 score and its MetaSig were associated with lower CHD risk among low-income Black and White Americans. Metabolomics may offer an objective measure of LE8 and its metabolic phenotype relevant to CHD prevention among diverse populations.