Association between cardiovascular-kidney-metabolic syndrome and risks of 14 age-related health outcomes in primary prevention older population

BACKGROUND: The American Heart Association (AHA) recently introduced a new clinical entity; the cardiovascular-kidney-metabolic syndrome (CKMS), to promote a multi-disciplinary approach for chronic disease management. This study aims to investigate the relationship between CKMS and major adverse outcomes in older populations in primary care. METHODS: This study utilized data from 18,367 community-dwelling individuals aged ≥ 65, free from prior cardiovascular disease (CVD). Participants were classified into four CKMS stages (stage 0-no CKMS risk factor to stage 3-high CKMS risk) at baseline based on the AHA definition. The association with 14 health outcomes was analysed using multivariable cause-specific hazard models. Additional stratifications were performed by social disadvantage, inflammation levels, and number of CKMS components within each stage to refine risk staging. RESULTS: Over a median follow-up of 8.6 years, the prevalence of CKMS stages 0 to 3 was 2.8%, 8.2%, 52.6%, and 36.0%, respectively. Compared to stage 0, stage 3 associated with all-cause mortality (HR 1.31, 95%CI 1.01-1.69), CVD mortality (3.11, 1.46-6.60), incident total CVD events (2.78, 1.86-4.15), myocardial infarction (2.37, 1.21-4.62), stroke (2.75, 1.50-5.04), heart failure hospitalization (4.56, 1.45-14.37), atrial fibrillation (2.63, 1.61-4.29), cancer (1.31, 1.04-1.64), depression (1.20, 1.04-1.39), and physical disability (1.92, 1.20-3.08). Social disadvantage, high inflammation, and CKMS component count further amplified these associations. No linear trend was observed for cognitive outcomes and non-CVD cause-specific mortality. CONCLUSION: This study is the first to establish relationships between CKMS and multiple age-related outcomes in older adults, providing critical insights for developing holistic approaches to primary care in the aged.