# Association between the frailty index and all-cause and cardiovascular mortality in a population with cardiovascular-kidney-metabolic syndrome: Insights from the NHANES 2011-2018

**Authors:** Xin Wang, Xinrui Hai, Ali Ma, Xiaolan Liang, Hua Cheng, Peng Wu, Yu Hao, Dapeng Chen, Ning Yan

PMC · DOI: 10.1016/j.tjfa.2025.100131 · 2026-01-29

## TL;DR

The study finds that higher frailty index levels are strongly linked to increased all-cause and cardiovascular mortality in people with cardiovascular-kidney-metabolic syndrome.

## Contribution

This study is the first to evaluate the predictive value of the Frailty Index in patients with Cardiovascular-Kidney-Metabolic Syndrome.

## Key findings

- Each 10-unit increase in the Frailty Index was associated with a 54% higher risk of cardiovascular mortality.
- Higher Frailty Index levels were robustly linked to increased all-cause mortality in CKM syndrome patients.
- The association between Frailty Index and mortality remained consistent across demographic and clinical subgroups.

## Abstract

The Frailty Index (FI) is a well-established predictor of accelerated biological aging and a reliable tool for estimating all-cause and cardiovascular disease (CVD) mortality in older adults in the United States. However, its predictive value remains unclear in other U.S. population subgroups. This study aimed to examine the association between FI levels and both all-cause and CVD mortality among patients diagnosed with Cardiovascular-Kidney-Metabolic Syndrome (CKM syndrome).

This study utilized the data from the National Health and Nutrition Examination Survey (NHANES 2011–2018), which included 7049 participants with complete information for CKM staging (stages 0–4). We employed multivariate Cox proportional hazards models in conjunction with restricted cubic splines (RCS) to account for potential non-linear relationships in the data. Additionally, segmented Cox proportional hazards models were used to examine the association between FI levels and both all-cause and CVD mortality in the CKM syndrome population. Subgroup analyses stratified by demographic and clinical factors, along with interaction tests, were performed to evaluate the consistency of these associations.

After adjusting for potential confounding variables, a nonlinear association was observed between the FI and CKM syndrome. Multivariable Cox regression analysis based on nationally representative data demonstrated that higher FI levels were significantly associated with increased risks of both all-cause and CVD mortality among patients with CKM syndrome. Multivariable analysis indicated a robust association between higher FI levels and the presence of CKM syndrome. Among patients diagnosed with CKM syndrome, each 10-unit increase in the FI was associated with a 54% higher risk of CVD mortality (HR = 1.54, 95% CI: 1.24–1.91; P < 0.001) and a 55% higher risk of all-cause mortality (HR = 1.55; 95% CI: 1.38–1.73, P < 0.0001). Stratified analyses revealed no significant interaction effects between the FI and demographic or clinical factors on mortality outcomes.

The results highlight a robust and statistically significant association between FI and increased risk of both all-cause and CVD mortality among individuals with KM syndrome. Notably, FI may serve as a valuable marker for CKM stage stratification and for identifying high-risk patients.

## Linked entities

- **Diseases:** Cardiovascular-Kidney-Metabolic Syndrome (MONDO:0976301), cardiovascular disease (MONDO:0004995)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, NPPB (natriuretic peptide B) [NCBI Gene 4879] {aka BNP, Iso-ANP}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CKM (creatine kinase, M-type) [NCBI Gene 1158] {aka CKMM, CPK-M, M-CK}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}
- **Diseases:** arterial hypertension (MESH:D000081029), Chronic low- (MESH:D009800), coronary artery disease (MESH:D003324), endothelial dysfunction (MESH:D014652), CKD (MESH:D051436), adipose tissue dysfunction (MESH:D018205), myocardial infarction (MESH:D009203), impaired glucose metabolism (MESH:D044882), hepatic steatosis (MESH:D005234), anorexia (MESH:D000855), CKM Syndrome (MESH:D007674), renal decline (MESH:D006030), dyslipidemia (MESH:D050171), arrhythmias (MESH:D001145), metabolic dysfunction (MESH:D008659), mood disturbances (MESH:D019964), chronic inflammation (MESH:D007249), Diabetes (MESH:D003920), atherosclerotic plaques (MESH:D058226), atrial fibrillation (MESH:D001281), metabolic syndrome (MESH:D024821), abnormal glucose tolerance (MESH:D018149), chronic (MESH:D002908), impaired insulin sensitivity (MESH:D007333), organ damage (MESH:D000092124), atherosclerosis (MESH:D050197), health deficits (MESH:D009461), CVD (MESH:D002318), death (MESH:D003643), malnutrition (MESH:D044342), heart failure (MESH:D006333), PEW (MESH:D011502), CKM syndrome (MESH:D013577), DM (MESH:D009223), peripheral artery disease (MESH:D058729), T2DM (MESH:D003924), acidosis (MESH:D000138), multiorgan disorder (MESH:D009102), cancer (MESH:D009369), loss of physiological reserve (MESH:D012735), protein (MESH:D011488), muscle loss (MESH:D009135), obesity (MESH:D009765), renal deterioration (MESH:D058186), FI (MESH:D000073496), ischemic (MESH:D002545), Hyperlipidemia (MESH:D006949), stroke (MESH:D020521), sarcopenia (MESH:D055948), uremic (MESH:D006463), multiorgan failure (MESH:D051437), Hypertension (MESH:D006973), glomerular and tubulointerstitial damage (OMIM:162000)
- **Chemicals:** cholesterol (MESH:D002784), blood glucose (MESH:D001786), triglycerides (MESH:D014280), Alcohol (MESH:D000438), TC (MESH:D013667), TG (MESH:D013866), Creatinine (MESH:D003404), LDL-C (-), uric acid (MESH:D014527), urea nitrogen (MESH:C530477), nitrogen (MESH:D009584), lipid (MESH:D008055), glucose (MESH:D005947)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12873725/full.md

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Source: https://tomesphere.com/paper/PMC12873725