Analysis of Clinical Traits Associated with Cardiovascular Health, Genomic Profiles, and Neuroimaging Markers of Brain Health in Adults Without Stroke or Dementia

Abstract

Importance: The American Heart Association (AHA) Life's Simple 7 (LS7) score captures 7 biological and lifestyle factors associated with promoting cardiovascular health. Objectives: To test whether healthier LS7 profiles are associated with significant brain health benefits in persons without stroke or dementia, and to evaluate whether genomic information can recapitulate the observed LS7. Design, Setting, and Participants: This genetic association study was a nested neuroimaging study within the UK Biobank, a large population-based cohort study in the United Kingdom. Between March 2006 and October 2010, the UK Biobank enrolled 502480 community-dwelling persons aged 40 to 69 years at recruitment. This study focused on a subset of 35914 participants without stroke or dementia who completed research brain magnetic resonance imaging (MRI) and had available genome-wide data. All analyses were conducted between March 2021 and March 2022. Exposures: The LS7 (blood pressure, low-density lipoprotein cholesterol, hemoglobin A1c, smoking, exercise, diet, and body mass index) profiles were ascertained clinically and genomically. Independent genetic variants known to influence each of the traits included in the LS7 were assessed. The total LS7 score ranges from 0 (worst) to 14 (best) and was categorized as poor (≤4), average (>4 to 9) and optimal (>9). Main Outcomes and Measures: The outcomes of interest were 2 neuroimaging markers of brain health: white matter hyperintensity (WMH) volume and brain volume (BV). Results: The final analytical sample included 35914 participants (mean [SD] age 64.1 [7.6] years; 18830 [52.4%] women). For WMH, compared with persons with poor observed LS7 profiles, those with average profiles had 16% (β = -0.18; SE, 0.03; P