SYSTEMATIC REVIEW article
Front. Public Health
Sec. Aging and Public Health
This article is part of the Research TopicDiagnosing and Treating Frailty and Sarcopenia in Middle-aged and Older Adults - Volume IIView all articles
Association of Frailty and Pre-frailty with Cardiovascular Mortality: A Meta-analysis of 26 Cohort Studies
Provisionally accepted
- 1Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University School of Basic Medical Sciences, Hangzhou, China
- 2Zhejiang Engineering Research Center for "Preventive Treatment" Smart Health of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, China
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Objective This meta-analysis evaluated the association of frailty and pre-frailty with cardiovascular mortality in cohort studies. While frailty is a recognized predictor of poor outcomes, the prognostic role of pre-frailty—a critical intermediate stage—remains less clear. We assessed their associations with cardiovascular mortality, explored heterogeneity, and examined the robustness of findings through publication bias analyses. Methods Cohort studies published up to 2025 were systematically searched. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using random-effects models. Heterogeneity was assessed using the I² statistic. Subgroup analyses and meta-regression were performed to explore sources of heterogeneity, but no single factor fully explained the high variability observed (I² > 80%). Publication bias was evaluated using funnel plots and statistical tests, with no significant bias detected. Results Twenty-six cohort studies involving over 4 million participants were included. Frailty was significantly associated with higher cardiovascular mortality (HR = 2.11, 95% CI: 1.86–2.40), and pre-frailty also conferred elevated risk (HR = 1.80, 95% CI: 1.46–2.23). Despite substantial heterogeneity (I² > 80%), subgroup analyses and meta-regression did not identify a clear source. No publication bias was found. Conclusion Frailty and pre-frailty are consistently associated with increased cardiovascular mortality, emphasizing their value for early risk identification and preventive strategies. Given the observational nature and residual heterogeneity, findings should be interpreted cautiously, and future research is needed to establish standardized assessment tools and test targeted interventions.
Keywords: Frailty, pre-frailty, risk stratification, older adults, Cardiovascular disease (CVD), Public Health, Meta-analysis
Received: 18 Aug 2025; Accepted: 28 Oct 2025.
Copyright: © 2025 Zhao, Wu, Liu and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Aisong Zhu, liaoningzhongy@hotmail.com
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