Abstract 73: Blood-based Biological Aging Measures Are Easy-to-access Biomarkers For Detection Of Incident Stroke

Abstract

Introduction: The relationship between biological age and stroke remains unclear. We assessed the role of six DNA methylation and physiology-based biological aging measures as biomarkers of stroke risk. Methods: Participants (N=3520, mean age=69±9 years) in the US Health and Retirement Study’s 2016 Venous Blood and DNA methylation studies. Biological aging measures included: Horvath, Hannum, GrimAge, Levine, Pace of Aging (POA) and Phenotypic Age. The clocks and POA were based on DNA methylation and Phenotypic age was based on serum physiology biomarkers (albumin, creatinine, glucose, C reactive protein, lymphocyte percent, mean cell volume, red blood cell distribution width, alkaline phosphatase, and white blood cell count). All measures were regressed on chronological age and residual values were computed. Multivariable logistic regression and three-way decomposition models were conducted. Total, direct and indirect effect of modifiable risk factors (smoking, BMI, blood pressure, diabetes mellitus, and education) on stroke through biological aging was assessed. Results: A total of 291 incident strokes were included. Individuals who were biologically older had higher odds of stroke with statistically significant estimates for GrimAge (DNA methylation-based) OR (95%CI): 1.32(1.07, 1.62), P=0.009 and PhenoAge (physiology-based) OR: 1.39(1.15, 1.69), P=0.001. In tertiles analysis (lowest tertile as reference), the odds of a new stroke were two to three times higher in biologically older individuals: GrimAge OR 3rd tertile: 2.42(1.08, 5.42), P=0.03; PhenoAge OR: 3.49(1.60, 7.65), P=0.002. Modifiable factors that showed highly significant indirect effect on incident stroke through biological aging are smoking, high blood pressure, diabetes mellitus and education (college or above). Conclusions: Biologically older individuals have 2 to 3 folds higher odds of new stroke occurrence compared to biologically younger individuals. The time lag between biological aging acceleration and manifestation of clinical disease is an opportunity for interventions targeted towards primary stroke prevention.