Impact of life's essential eight and inflammatory markers on long-term cardiovascular disease risk and all-cause mortality: Insights from the Heart SCORE study

BACKGROUND: Life's Essential 8 (LE8) are the American Heart Association's metrics for cardiovascular health. Despite the association of cardiovascular diseases with inflammation, LE8 does not include inflammatory markers as a component. We examined the association of baseline LE8 components and inflammatory measures with long-term cardiovascular and mortality outcomes among a community-based population. OBJECTIVES: To determine if inflammatory markers independently predict atherosclerotic cardiovascular disease (ASCVD) or all-cause mortality beyond LE8 metrics. METHODS: Baseline LE8 metrics and inflammatory markers (interleukin-6 [IL-6] and high sensitivity C-reactive protein [hsCRP]) were measured among 1869 participants (age 59±7.5 years, 41.9% Black) in the longitudinal Heart SCORE study. Cox-proportional hazard ratios were used to assess associations between LE8 score, inflammatory markers, and risk of ASCVD and all-cause mortality over 12 years. RESULTS: Higher LE8 Scores were significantly associated with lower all-cause mortality and ASCVD. After adjusting for LE8 metrics and demographics, ideal level of blood glucose was the most significant factor associated with lower ASCVD (HR 0.26 [0.12-0.58], p = 0.001). For all-cause mortality, no smoking emerged as the main protective LE8 component (HR 0.29 [0.16-0.53], p < 0.001). Increased IL-6 was independently associated with ASCVD (HR 1.54 [1.05-2.25], p = 0.03), and lower IL-6 was associated with lower all-cause mortality (HR 0.52 [0.30-0.90], p = 0.02). HsCRP was not associated with either outcome. CONCLUSION: Higher LE8 Scores are linked to reduced risk of ASCVD and all-cause mortality. IL-6 independently predicts adverse outcomes beyond LE8, suggesting inflammatory burden may represent an additional, modifiable target for cardiovascular risk reduction.