Abstract
BACKGROUND: : Cardiovascular health (CVH), as defined by the American Heart Association's Life's Essential 8 (LE8) metric, is associated with reduced cardiovascular disease (CVD) risk. However, its quantitative impact on acute myocardial infarction (AMI)-including risk reduction magnitude, onset delays, and population-level preventable burden-remains unclear. METHODS: : In this prospective cohort study, we analysed 122,914 UK Biobank participants aged 40-69 years who were free from CVD at baseline. CVH was evaluated using LE8 metrics, and was categorised as low (<50), moderate (50-79), or high (≥80). Associations between CVH and AMI risk/onset were assessed through multivariable Cox regression, accelerated failure time models, and restricted cubic splines. Mediation analysis evaluated the contributions of inflammatory (hs-CRP, leukocytes, platelets), metabolic (triglycerides, urate), renal function (eGFR), and mental health status (anxiety and depression). RESULTS: : Over 163.2-month median follow-up, 2892 AMI cases (844 STEMI, 1490 NSTEMI) occurred. Each 1-unit LE8 increase reduced AMI risk by 3 % (HR 0.970, 95 % CI: 0.967-0.973). Moderate and high CVH groups exhibited 41.2 % (HR 0.588, 95 % CI: 0.534-0.648) and 75 % (HR 0.25, 95 % CI: 0.205-0.306) risk reductions versus low CVH, with consistent trends for STEMI/NSTEMI. AMI onset was delayed by 14.5 months in the moderate CVH group and 33.6 months in the high group compared with the low group. The population attributable fraction for AMI was 58.01 % (95 % CI, 57.15 %-58.86 %) when comparing the combined moderate or high CVH group with the low CVH group. Inflammatory/metabolic biomarkers mediated 1.57-8.62 % of the CVH-AMI relationship. CONCLUSION: : Higher CVH levels were associated with reduced AMI risk and delayed onset, with inflammatory and metabolic biomarkers partially mediating this relationship. In the low-CVH group, a hypothetical shift to higher CVH levels was associated with a scenario-based population attributable fraction of approximately 60 %, highlighting the potential population impact of improving cardiovascular health.