Modifiable cardiovascular health, inflammatory biomarkers, and risk of cardiovascular disease and mortality among Cancer survivors

BACKGROUND: Cancer survivors are at increased risk of cardiovascular disease (CVD) and mortality, but the roles of modifiable cardiovascular health (CVH) and systemic inflammation remain incompletely understood. We examined the associations of CVH with incident CVD and mortality and assessed potential mediation by inflammatory biomarkers. METHODS: This prospective cohort study included 11,825 cancer survivors free of major adverse cardiovascular events (MACE) at baseline. CVH was assessed using the Life's Essential 8 (LE8) score and the number of LE8 components meeting guideline-based thresholds. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular events and mortality. Mediation analyses evaluated the contributions of inflammatory biomarkers. RESULTS: During a median follow-up of 13.5 years, 1923 MACE events and 2082 deaths occurred. Compared with the lowest CVH tertile, the highest tertile was associated with lower risks of MACE (HR, 0.60; 95% CI, 0.54-0.68), coronary heart disease (0.56; 0.48-0.65), heart failure (0.65; 0.52-0.81), stroke (0.60; 0.45-0.80), all-cause mortality (0.72; 0.64-0.80), CVD mortality (0.48; 0.32-0.72), and cancer mortality (0.74; 0.66-0.85). Each additional LE8 component under control was associated with 7%-20% lower risks across outcomes. Among significant mediation effects, C-reactive protein and the INFLA score mediated 9.7%-48.7% and 6.8%-17.9% of the associations, respectively. CONCLUSIONS: Favorable modifiable CVH is consistently associated with substantially lower risks of cardiovascular events and mortality among cancer survivors. Inflammation biomarkers partially mediated these associations, implicating inflammation as a key biological pathway.