Association of the FRAIL scale with major adverse cardiovascular events beyond conventional cardiovascular risk scores: a multicohort analysis

Cardiovascular disease (CVD) risk stratification relies largely on laboratory-based algorithms, which may limit feasibility in resource-constrained settings. Frailty reflects biological aging and multisystem vulnerability, but its association with cardiovascular outcomes relative to established risk scores remains understudied. This study aimed to evaluate the independent association between the FRAIL scale and subsequent cardiovascular outcomes and to determine whether frailty provides additional prognostic information beyond established cardiovascular risk scores. We analyzed data from three prospective cohorts: ARIC and MESA from the United States and CHARLS from China. The FRAIL scale and four established risk scores were evaluated in relation to incident MACE and all-cause mortality using cohort-specific Cox models. Random-effects meta-analysis and incremental prognostic analyses were performed to assess the consistency and additional prognostic information of the FRAIL scale. Among 17,769 participants from three cohort-specific analyses, the FRAIL scale was consistently associated with 5-year MACE after adjustment for conventional cardiovascular risk factors. The adjusted HRs per 1-point increase in FRAIL scale were 1.32 (95% CI 1.18–1.47) in ARIC, 1.19 (95% CI 1.00–1.41) in MESA, and 1.82 (95% CI 1.30–2.55) in CHARLS. Random-effects meta-analysis yielded a pooled HR of 1.35 (95% CI 1.13–1.62). Adding the FRAIL scale provided incremental prognostic information beyond conventional cardiovascular risk models, with increases in C-statistics ranging from 0.01 to 0.05 across cohorts. Associations with secondary outcomes and all-cause mortality were generally consistent but showed some heterogeneity across cohorts. The simple, questionnaire-based FRAIL scale was independently associated with cardiovascular outcomes across diverse populations and provided additional prognostic information beyond established cardiovascular risk models. Rather than replacing conventional risk scores, frailty assessment may complement existing cardiovascular risk assessment by capturing aspects of biological vulnerability not fully reflected by traditional risk factors. Further studies are needed to determine its clinical utility in cardiovascular prevention strategies.