Metabol Open. 2026 Jul 20;31:100487. doi: 10.1016/j.metop.2026.100487. eCollection 2026 Sep.
ABSTRACT
BACKGROUND: Life's Essential 8 (LE8) is an American Heart Association framework of modifiable behaviors and factors for measuring cardiovascular health. However, the underlying metabolic signature of individual LE8 metrics is less known. The purpose of this study is to identify the metabolites associated with all 8 components of LE8 and evaluate association with adverse cardiovascular events.
METHODS: Modified baseline LE8 metrics were collected and metabolomic profiling (Metabolon, Inc) was completed in the Heart SCORE study participants. For each LE8 component pathway enrichment was assessed using Fisher's exact test across metabolite subpathways. A metabolic age (metAge) was derived via elastic net regression using 987 plasma metabolites, predicting chronological age while adjusting for sex and race. Cox proportional hazard ratios (HR) were used to assess the association between metAge and ASCVD or major adverse events (MAE).
FINDINGS: Amongst 1,218 participants (mean age 59.1 ± 5.1 years; 67.1% women and 39.2% self-identified as Black), distinct metabolite patterns linked to different modified LE8 components were identified. Notably, favorable exercise scores had significant associations with plasmalogen metabolites. Optimal sleep health was most strongly associated with lower activity of the phosphatidylethanolamine pathway. In adults aged 65 years and older, higher accelerated metAge was associated with increased risk of ASCVD (HR = 1.12, 95% CI: 1.00-1.26, two-sided p = 0.059; prespecified one-sided p = 0.030) and MAE (HR = 1.10, 95% CI: 1.01-1.18, two-sided p = 0.028; prespecified one-sided p = 0.014) after multivariable adjustment, with effect estimates suggesting higher risk per one-year increase in accelerated metAge.
INTERPRETATION: All modified LE8 components show distinct metabolic patterns underscoring the biological heterogeneity of cardiovascular health behaviors. Notably, metAge was independently associated with ASCVD and MAE than many LE8 variables in older adults.
PMID:42571324 | PMC:PMC13452154 | DOI:10.1016/j.metop.2026.100487