Key result
Higher modified frailty index links to ~16% greater incident stroke risk per increment, with genetic support.
Why the study?
This study aimed to evaluate the association between the frailty index and stroke risk in Chinese adults, describe stroke burden trends, and explore causality using Mendelian randomization.
Does a higher frailty index increase the risk of incident stroke in Chinese adults aged 45 years and older?
Cohort (n=13,473)
Yes
Does a higher frailty index increase the risk of incident stroke in Chinese adults aged 45 years and older?
A higher frailty index is causally associated with an increased risk of ischemic stroke, particularly large-artery atherosclerotic and small-vessel stroke, suggesting its utility in stroke risk assessment.
May enhance stroke risk assessment incorporating frailty in Chinese adults ≥45 years; extends data with causal genetic support but leaves practice change open.
Objective: This study aims to examine the association between the frailty index (FI) and stroke risk among Chinese adults, describe the burden of stroke in China, and explore the causal role of FI in ischemic stroke through Mendelian randomization. Methods: Data from the China Health and Retirement Longitudinal Study (CHARLS) included 13,473 participants aged 45 years and older without a history of stroke. Cox models, restricted cubic splines, and sensitivity analyses were employed to assess the association between the modified frailty index (mFI) and incident stroke. Additionally, data from the Global Burden of Disease (GBD) 2021 data report were utilized to describe stroke trends in China from 1990 to 2021. Two-sample Mendelian randomization was conducted to evaluate the causal effects of FI on ischemic stroke subtypes. Results: During a median follow-up period of approximately 7 years, 811 incident strokes were recorded. Each 0.1-point increase in mFI was associated with a 16% increase in stroke risk (HR = 1.16, 95% CI: 1.06–1.27), demonstrating a linear dose–response relationship. From 1990 to 2021, the proportion of ischemic stroke rose from 46.9% to 63.2%. Mendelian randomization analysis provided genetic evidence supporting a causal association between FI and ischemic stroke (OR = 1.191, 95% CI: 1.046–1.357), particularly driven by large-artery atherosclerotic (OR = 1.852) and small-vessel stroke (OR = 1.415), but not by cardioembolic stroke. Conclusions: A higher FI is associated with an increased risk of stroke among Chinese adults, with genetic evidence supporting a causal role in ischemic stroke. Therefore, FI may serve as a valuable addition to existing risk assessment tools.
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Zhou et al. (2026) conducted a cohort in Ischemic stroke (n=13,473). Modified frailty index (mFI) was evaluated on incident stroke (HR 1.16, 95% CI 1.06-1.27). Each 0.1-point increase in the modified frailty index was associated with a 16% increased risk of incident stroke (HR 1.16; 95% CI 1.06-1.27), with genetic evidence supporting a causal role.
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