Abstract WP178: Biological Age Influences Clinically-evident And Asymptomatic Cerebrovascular Disease: Combined Analysis In The Uk Biobank And All Of Us

Background: While chronological age is defined by time, biological age (also known as phenotypic age) is defined by biological variables that summarize the status of key physiological processes. Mounting evidence indicates that biological age is a crucial determinant of longevity and other aging-related traits. We hypothesize that biological age influences clinically-evident and asymptomatic cerebrovascular disease. Methods: We analyzed data from the UK Biobank (discovery) and All of Us (replication) studies. We ascertained ischemic and hemorrhagic stroke using questionnaires and EHR data. In the UK Biobank we also evaluated MRI-defined white matter hyperintensity (WMH) volume and brain volume (BV). We estimated biological age using PhenoAge, a validated tool that integrates information on albumin, creatinine, glucose, C reactive protein, lymphocyte percentage, mean corpuscular volume, red blood cell distribution width, alkaline phosphatase and white blood cell count. Biological age was divided into tertiles and entered in multivariate Cox and linear regression models adjusting for chronological age and vascular risk factors. Results: The discovery phase included 416,415 UK Biobank participants. Compared to the biologically youngest tertile, the risk of stroke was 17% (HR 1.17, 95%CI 1.04-1.32) and 61% (HR 1.61, 95%CI 1.40-1.86) higher in tertiles 2 and 3 of biological age, respectively (test-for-trend p<0.001). All results were replicated on 56,513 All of Us participants (all associations p<0.05). In 34,095 UK Biobank participants with MRI data, compared to the biologically youngest tertile, those in tertile 2 had 83% (beta 0.003, se 0.014) higher WMH volume and 3.3% (beta -0.012, se 0.013) lower BV, whereas those in tertile 3 had 177% (beta 0.041, se 0.02) higher WMH volume and 5.6% (beta -0.049, se 0.019) lower BV (test-for-trend p<0.001). Conclusion: Biological age is a significant contributor to clinically evident and silent cerebrovascular disease. Combined interventions targeting the biological processes that determine biological age could result in important synergistic effects for primary and secondary prevention. Further research is needed to determine the role of biological age in stroke outcome and recurrence.