To investigate the association between the Life's Essential 8 (LE8) score and the incidence of four cardiovascular outcomes (ischemic heart disease, myocardial infarction, stroke, and heart failure [HF]) - separately and as a composite outcome of major adverse cardiovascular events (MACE) - in UK Biobank. 250,825 participants were included in this prospective study. Smoking, non-HDL cholesterol, blood pressure, body mass index, HbA1c, physical activity, diet, and sleep were used to create a modified version of the LE8 score. Associations between the score (both as a continuous score and as quartiles) and outcomes were investigated using adjusted Cox proportional hazard models. The potential impact fractions of two scenarios were also calculated. Over a median follow-up of 10.4 years, there were 25,068 MACE. Compared to individuals in the highest quartile of the score (healthiest), those in the lowest quartile (least healthy) had 2.07 (95% CI: 1.99; 2.16) higher risk for MACE. The highest relative risk gradient of the individual outcomes was observed for HF (HRlowest quartile: 2.67 [95% CI: 2.42; 2.94]). The magnitude of association was stronger in participants below 50 years, women, and ethnic minorities. A targeted intervention that increased, by 10-points, the score among individuals in the lowest quartile could have prevented 9.2% of MACE. Individuals with a lower LE8 score experienced more MACE, driven especially by incident HF. Our scenarios suggested that relevant interventions targeted towards those in the lowest quartile may have a greater impact than interventions producing small equal changes across all quartiles.
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