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.
Xin Wang, Xinrui Hai, Ali Ma, Xiaolan Liang, Hua Cheng, Peng Wu, Yu Hao, Dapeng Chen, Ning Yan
{"title":"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","doi":"10.1016/j.tjfa.2025.100131","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":51629,"journal":{"name":"Journal of Frailty & Aging","volume":"15 2","pages":"100131"},"PeriodicalIF":3.3000,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12873725/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Frailty & Aging","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.tjfa.2025.100131","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/1/29 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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).
Methods: 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.
Results: 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.
Conclusion: 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.
期刊介绍:
The Journal of Frailty & Aging is a peer-reviewed international journal aimed at presenting articles that are related to research in the area of aging and age-related (sub)clinical conditions. In particular, the journal publishes high-quality papers describing and discussing social, biological, and clinical features underlying the onset and development of frailty in older persons. The Journal of Frailty & Aging is composed by five different sections: - Biology of frailty and aging In this section, the journal presents reports from preclinical studies and experiences focused at identifying, describing, and understanding the subclinical pathophysiological mechanisms at the basis of frailty and aging. - Physical frailty and age-related body composition modifications Studies exploring the physical and functional components of frailty are contained in this section. Moreover, since body composition plays a major role in determining physical frailty and, at the same time, represents the most evident feature of the aging process, special attention is given to studies focused on sarcopenia and obesity at older age. - Neurosciences of frailty and aging The section presents results from studies exploring the cognitive and neurological aspects of frailty and age-related conditions. In particular, papers on neurodegenerative conditions of advanced age are welcomed. - Frailty and aging in clinical practice and public health This journal’s section is devoted at presenting studies on clinical issues of frailty and age-related conditions. This multidisciplinary section particularly welcomes reports from clinicians coming from different backgrounds and specialties dealing with the heterogeneous clinical manifestations of advanced age. Moreover, this part of the journal also contains reports on frailty- and age-related social and public health issues. - Clinical trials and therapeutics This final section contains all the manuscripts presenting data on (pharmacological and non-pharmacological) interventions aimed at preventing, delaying, or treating frailty and age-related conditions.The Journal of Frailty & Aging is a quarterly publication of original papers, review articles, case reports, controversies, letters to the Editor, and book reviews. Manuscripts will be evaluated by the editorial staff and, if suitable, by expert reviewers assigned by the editors. The journal particularly welcomes papers by researchers from different backgrounds and specialities who may want to share their views and experiences on the common themes of frailty and aging.The abstracting and indexing of the Journal of Frailty & Aging is covered by MEDLINE (approval by the National Library of Medicine in February 2016).