Association between biological aging and the risk of stroke: Results from the National Health and Nutrition Examination Survey and Mendelian randomization analysis

Introduction: Stroke is an acute cerebrovascular disease that seriously affects lifespan, and aging is generally considered an important risk factor for stroke. This study aimed to explore the association between biological aging and stroke risk using well-validated measures of aging. Methods We employed the methods of Klemera-Doubal (KDMAge) and phenotypic age (PhenoAge) as alternative measures of biological aging in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. In order to analyze the data, we employed logistic regression, trend p-value, restricted cubic spline (RCS) analysis, and subgroup analysis. Furthermore, a bidirectional two-sample Mendelian randomization (MR) analysis was conducted to assess the potential causal impact of biological aging (including intrinsic age acceleration, telomere length, facial aging, and frailty index) on stroke and stroke subtypes. Results A cross-sectional analysis of 34,856 participants revealed that higher biological age or biological age acceleration was associated with an increased risk of stroke. Furthermore, multivariate logistic regression analysis performed in 5 models revealed a statistically significant association between biological age or biological age acceleration and stroke risk. RCS analysis showed that there is a nonlinear relationship between KDMAge and KDMAge acceleration and stroke. Subgroup analysis revealed a moderating effect of alcohol consumption on the association between KDMAge acceleration and stroke risk. Finally, MR analysis revealed that the frailty index was associated with an increased risk of stroke (OR: 1.57, 95% CI: 1.36–1.83, p < 0.001). In contrast, reverse MR analysis revealed that stroke was associated with PhenoAge accelerated (OR: 1.54, 95% CI:1.12–2.12,p = 0.008), frailty index (OR:1.11,95% CI:1.05–1.17, p < 0.001) and facial aging (OR:1.02, 95% CI:1.01–1.03, p = 0.001). These findings provide evidence for a potential causal relationship between biological aging and stroke risk. Conclusion There is a significant association between biological aging and stroke. It is possible that biological aging may be a risk factor for stroke, and that stroke may further accelerate the process of biological aging. Consequently, it is of paramount importance to identify the acceleration of biological aging through biological aging measures with the objective of reducing the risk of stroke and the occurrence of adverse events.