Frailty status and mortality among patients with cardiometabolic diseases in an international multi-cohort study

Q: What are the key findings of this study?

Frail participants with cardiometabolic diseases had a 98% higher risk of all-cause mortality compared to non-frail individuals (pooled HR 1.98, 95% CI 1.73-2.27).

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiometabolic diseases (n=129025). Intervention: Frailty vs. Non-frail status. Primary outcome: All-cause mortality (HR 1.98, 95% CI 1.73-2.27).

Q: What does this research mean for the field?

Frail individuals with cardiometabolic diseases have a 98% higher risk of all-cause mortality compared to non-frail individuals. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Rui Ren; Yao Zhang; Meilin Du; Wenxu Wang; Liying Wang; Jilong Bai; Yibin Lu; Yanan Ma; Difei Wang

doi:10.1016/j.isci.2026.115615

April 8, 2026iScienceOpen Access

Frailty status and mortality among patients with cardiometabolic diseases in an international multi-cohort study

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Key result

Frailty linked to ~98% higher all-cause mortality in patients with cardiometabolic disease.

HR 1.98
95% CI 1.73-2.27
n=129,025

Figures

Graphical abstract published by iScience — Graphical abstract · Published by iScience · CC BY-NC-ND

Why the study?

Frailty indicates biological aging and is linked to adverse outcomes in cardiometabolic diseases, prompting evaluation of its association with mortality risk.

Does frailty status increase mortality risk in patients with cardiometabolic diseases?

Key Points

To evaluate the association between frailty status and the risk of all-cause and cause-specific mortality among individuals diagnosed with cardiometabolic diseases.
Analyzed 129,025 participants with cardiometabolic diseases across five prospective cohorts: UK Biobank (UK, n = 110,777), NHANES (USA, n = 4,634), CHARLS (China, n = 4,479), ELSA (England, n = 2,674), and HRS (USA, n = 6,461).
Evaluated frailty categories and continuous frailty index across cohorts over median follow-up periods ranging from 8.9 to 12.5 years using multivariable-adjusted Cox proportional hazards models.
Compared with non-frail individuals, pre-frail participants had a significantly higher risk of all-cause mortality (pooled HR = 1.30, 95% CI: 1.21–1.39), while frail participants exhibited nearly double the risk (pooled HR = 1.98, 95% CI: 1.73–2.27).
Each 0.1-unit increase in frailty index was associated with elevated all-cause mortality (pooled HR = 1.32, 95% CI: 1.25–1.39), cardiovascular mortality (pooled HR = 1.40, 95% CI: 1.27–1.56), non-cardiovascular mortality (pooled HR = 1.38, 95% CI: 1.22–1.55), and cancer mortality (pooled HR = 1.11, 95% CI: 1.03–1.20).

Study Design

Type

Cohort (n=129,025)

Multicenter

Yes

Structured PICO

Does frailty status increase mortality risk in patients with cardiometabolic diseases?

P

Population

129,025 adults with cardiometabolic diseases from five international prospective cohorts, followed for a median of 8.9 to 12.5 years to assess the association between frailty status and mortality.

E

Exposure

Frailty status (pre-frail or frail) assessed by Frailty Index (FI)

C

Comparator

Non-frail individuals

O

Outcome

All-cause mortalityhard clinical

Main Result

Hazard Ratio: 1.98 (95% CI 1.73–2.27)

Frailty is a significant independent predictor of all-cause and cause-specific mortality in patients with cardiometabolic diseases, highlighting its value for risk stratification.

Limitations

Use of self-reported data for frailty index construction may introduce recall bias
Frailty is a dynamic condition, and single baseline assessment may underestimate associations
Differences in specific items and covariate availability across cohorts limit direct comparability
Substantial heterogeneity across cohorts in population structure and follow-up duration
Lack of consensus on the definition of cardiometabolic diseases
Observational design limits causal inference

Implication

Frailty may aid mortality risk stratification in cardiometabolic disease; leaves open whether frailty-targeted interventions improve survival.

Abstract

Frailty is an indicator of biological aging associated with adverse outcomes in cardiometabolic diseases (CMD). We investigated the association between frailty status and mortality risk using data from five prospective cohorts including the UK Biobank, NHANES, CHARLS, ELSA, and HRS. Across these cohorts, pre-frail participants had a 21%-66% higher risk of all-cause mortality, while frail participants had a 54%-132% higher risk compared with non-frail individuals. Frailty was also associated with increased risks of cardiovascular and non-cardiovascular mortality, while associations with cancer-related mortality were mainly observed among individuals classified as frail. Subgroup analyses revealed heterogeneity across age, body mass index (BMI), sex, and CMD burden, with stronger associations among younger individuals (<65 years), those with lower BMI, and individuals with multiple CMDs. Sensitivity analyses yielded consistent results. These findings suggest that frailty may serve as an important prognostic marker in CMD populations and support risk stratification in clinical management.

Discussion

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Cite This Study

Ren et al. (2026) conducted a cohort in Cardiometabolic diseases (n=129,025). Frailty vs. Non-frail status was evaluated on All-cause mortality (HR 1.98, 95% CI 1.73-2.27). Frail participants with cardiometabolic diseases had a 98% higher risk of all-cause mortality compared to non-frail individuals (pooled HR 1.98, 95% CI 1.73-2.27).

synapsesocial.com/papers/6a12a06be407b26696354d0e https://doi.org/10.1016/j.isci.2026.115615

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Frailty status and mortality among patients with cardiometabolic diseases in an international multi-cohort study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Frailty status and mortality among patients with cardiometabolic diseases in an international multi-cohort study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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