Abstract WMP21: Life's Essential 8 and Brain Health Clinical Outcomes in Middle-Aged Adults

Abstract

Background: Mounting evidence points to a connection between cardiovascular risk during middle age and brain health later in life. The American Heart Association’s Life’s Essential 8 (LE8) constitute a research and public health construct capturing key determinants of cardiovascular health. We tested the hypothesis that worse LE8 profiles are associated with higher composite risk of the most important clinical endpoints related to brain health. Methods: We conducted a two-stage (discovery and replication) prospective study using data from the UK Biobank (UKB) and All of Us (AoU). We excluded participants with stroke, dementia, or late-life depression (LLD) at baseline. The exposure of interest was the LE8 score, a validated tool that captures the LE8 components (blood pressure, glucose, and cholesterol, body mass index, smoking, physical activity, diet, and sleep duration), organized in 3 categories. The outcome of interest was a composite of stroke, dementia, or LLD. We evaluated the associations of interest via multivariable Cox proportional hazard models. Results: The discovery stage included 334,505 UKB participants (mean age 56, 47% female), in whom the unadjusted risk of the composite outcome of interest was 471 (0.7%), 2,224 (1.1%) and 1,143 (1.7%) in participants with optimal, intermediate, and poor cardiovascular health (p<0.001). This association remained significant in multivariable Cox models (optimal versus poor cardiovascular health OR 2.14; 95% CI 1.92 - 2.39; p<0.001). The replication stage included 92,551 AoU participants (mean age 57, 59% female), in whom the unadjusted risk of the composite outcome was 547 (3%), 3,451 (6.2%) and 1,833 (10%) in participants with optimal, intermediate, and poor cardiovascular health (p<0.001). This association remained significant in multivariable Cox models (optimal versus poor cardiovascular health OR 2.20; 95% CI 1.99 - 2.42; p<0.001). Conclusions and Relevance: Among middle-aged UKB and AoU participants, poorer LE8 cardiovascular health profiles were strongly associated with a higher risk of developing a composite endpoint that captures the most important diseases related to brain health. These findings support the utilization of this endpoint in clinical trials focused on brain health.