Life's Essential 8, Genetic Susceptibility, and Incident Ischemic Stroke: A Prospective Cohort Study

BACKGROUNDLifes Essential 8 (LE8) is an important indicator to assess cardiovascular health (CVH), yet its association with ischemic stroke (IS) remains unclear. We aimed to investigate the association of LE8 with IS, as well as the underlying inflammatory mechanisms. Furthermore, we also aimed to explore whether genetic susceptibility moderated this association. METHODSA total of 202,215 participants aged 40-69 from the UK Biobank were analyzed between 2006 and 2010, with follow-up conducted until 2022. The American Heart Associations LE8 framework was used to calculate the LE8 scores. The link between LE8 scores and IS risk was assessed using Cox proportional hazards models. 1000 non-parametric bootstrapping simulations were used to calculate the mediation effect. CVH levels and genetic susceptibility were classified as high, medium, and low based on their LE8 scores and polygenetic risk scores (PRS), respectively. RESULTS2,515 individuals experienced IS over a median follow-up period of 13.73 years. In comparison to the low CVH group, the medium CVH group exhibited a 26% reduction in the risk of IS (HR 0.74; 95% CI, 0.65-0.80), while the high CVH group demonstrated a 53% reduction (HR 0.47; 95% CI, 0.39-0.57). An increased LE8 scores were inversely correlated with the risk of IS (HR: 0.84; 95% CI: 0.80-0.87), partially mediated by inflammatory markers. According to the joint effect analysis, individuals with low genetic susceptibility and high CVH had the lowest IS risk (HR: 0.20; 95% CI: 0.13-0.30) when compared to those with genetic susceptibility and low CVH. CONCLUSIONSThe findings imply that higher LE8 scores and CVH levels are associated with a lower incidence of IS, partially mediated by inflammatory markers. This protective relationship can be strengthened in cases of lower genetic susceptibility.