Aims: Cancer survivors are at increased cardiovascular risk due to shared risk factors and treatment-related toxicity. The recently proposed cardiovascular-kidney-metabolic (CKM) syndrome framework provides a novel approach for cardiometabolic risk stratification, but its prognostic value in cancer patients remains unclear. In this study, we aimed to evaluate the association between CKM stages and cardiovascular outcomes in cancer patients using a large-scale nationwide dataset.
Methods and results: We conducted a retrospective cohort study of 76 111 cancer patients without prior CVD from the DeSC database (2014-2023). Participants were classified into CKM stages (0-3) at baseline, with Stage 4 defined as the composite outcome of myocardial infarction, heart failure, atrial fibrillation, stroke, or peripheral artery disease. Multivariable Cox proportional hazards models were used to assess the risk of progression to Stage 4. Over a median follow-up of 2.6 years, advancing CKM stages were associated with a graded increase in cardiovascular disease (CVD) risk. Compared to Stage 0-1 (reference), adjusted hazard ratios for Stage 4 were 1.23 (95% confidence interval: 1.13-1.33) for Stage 2 and 1.47 (1.36-1.60) for Stage 3. Sensitivity analyses confirmed consistent associations across different groups stratified by age, sex, chemotherapy history, and cancer types. Furthermore, sensitivity analyses using alternative risk prediction models or expanded CVD definitions yielded similar results.
Conclusion: The CKM staging system effectively stratifies cardiovascular risk in cancer patients, with higher stages predicting significantly worse outcomes. These findings advocate for integrating CKM assessment into onco-cardiologic practice to guide early intervention and improve patient outcomes.
Keywords: Cancer; Cardiovascular disease; Cardiovascular-kidney-metabolic syndrome; Risk stratification.
© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.