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.