Life’s Essential 8 and Brain Health Clinical Outcomes in Middle-aged Adults
Santiago Clocchiatti-Tuozzo1, Cyprien Rivier2, Daniela Renedo2, Shufan Huo3, Victor Torres-Lopez2, Adam De Havenon2, Kevin Sheth4, Thomas Gill3, Guido Falcone3
1Yale University, Department of Neurology, 2Yale University, 3Yale School of Medicine, 4Yale UniversityDivision of Neuro and Critical Care
Objective:
To test the hypothesis that worse Life’s Essential 8 (LE8) profiles are associated with higher composite risk of the most important clinical endpoints related to brain health.
Background:
There is a strong connection between cardiovascular risk during middle age and brain health later in life. The American Heart Association’s LE8 constitute a validated tool that captures key determinants of cardiovascular health.
Design/Methods:
We conducted a two-stage (discovery and replication) prospective study using the UK Biobank (UKB) and All of Us (AoU). Participants with prior stroke, dementia, or late life depression (LLD) were excluded. The exposure was the LE8 score, comprised of eight components (blood pressure, glucose, and cholesterol, body mass index, smoking, physical activity, diet, and sleep), organized in 3 categories (optimal, intermediate, and poor). The outcome was a composite of stroke, dementia, or LLD. We evaluated the associations of interest via multivariable Cox proportional hazard models.
Results:
The discovery included 303,951 UKB participants (mean age 57, 52% female), in whom the unadjusted incidence of the composite outcome was 442 (0.7%), 2,082 (1.1%) and 1,015 (1.8%) in participants with optimal, intermediate, and poor cardiovascular health, respectively (p<0.001). Results remained significant in multivariable Cox models (optimal versus poor cardiovascular health HR 2.01;95%CI 1.80 – 2.25;p-trend<0.001). The replication included 92,551 AoU participants (mean age 57, 59% female), in whom the unadjusted incidence of the composite outcome was 547 (3%), 3,449 (6.2%) and 1,833 (10%) in participants with optimal, intermediate, and poor cardiovascular health, respectively (p<0.001). Results remained significant in multivariable Cox models (optimal versus poor cardiovascular health HR 2.02;95%CI 1.83 – 2.23;p-trend<0.001).
Conclusions:
Among middle-aged UKB and AoU participants, poorer cardiovascular health profiles were strongly associated with higher risks of developing a composite endpoint capturing the most important brain health related diseases. These findings support the utilization of this endpoint in brain health focused clinical trials.