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

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.