A recent study entitled “Association of cardiovascular–kidney–metabolic syndrome stages with mortality and the heterogeneity of its components in relation to mortality risk: A nationwide, population-based, prospective cohort study,” published in the Chinese Medical Journal (English Edition), has garnered considerable academic interest. Utilizing data from the China Health Evaluation and Risk Reduction through Nationwide Teamwork (ChinaHEART) project, this nationwide, population-based cohort constitutes one of the largest and most comprehensive studies conducted in China to date. The research systematically investigated the associations between cardiovascular–kidney–metabolic (CKM) syndrome stages and substages and both all-cause and cause-specific mortality, highlighting the pivotal role of chronic kidney disease (CKD) as a key determinant of mortality risk.
Cardiovascular disease (CVD), CKD, and metabolic abnormalities frequently coexist and interact, creating a complex network of risk factors that significantly contribute to global morbidity and mortality. To enhance the understanding of these interconnected pathways, the American Heart Association (AHA) recently proposed the CKM syndrome framework to facilitate multisystemic risk stratification. Nevertheless, empirical evidence regarding the predictive value of CKM staging for long-term outcomes remains limited. To address this gap, the present study analyzed data from 764,856 adults aged 35 years and older, drawn from 353 counties and districts across 31 provinces in the Chinese mainland, thereby encompassing a geographically and demographically diverse population.
Based on clinical and laboratory data, participants were classified into CKM stages 0 through 4 in accordance with the AHA definition. Additionally, stages 2 to 4 were further subdivided according to the presence of CKD and its risk categories as defined by the Kidney Disease: Improving Global Outcomes guidelines, enabling a more nuanced assessment of mortality risk heterogeneity within each stage.
The findings demonstrated a clear and progressive relationship between CKM stages and mortality risk. Compared to participants at stages 0–1, individuals at stages 2, 3, and 4 exhibited 47%, 113%, and 144% increased risks of all-cause mortality, respectively, as well as 162%, 304%, and 464% elevated risks of cardiovascular mortality. Notably, substage analyses revealed considerable heterogeneity; within each CKM stage, the presence of CKD significantly heightened mortality risk, even at moderate-risk CKD levels. Among the various subcomponents of stage 2, CKD emerged as the strongest predictor of mortality, followed by the coexistence of diabetes and hypertension. In contrast, isolated hypertension, isolated diabetes, and other metabolic abnormalities (such as elevated triglycerides or low HDL-C) were associated with comparatively weaker mortality risks.
This extensive nationwide study presents the first evidence indicating that CKD is the primary determinant of mortality within the CKM framework, exceeding the prognostic significance of traditional metabolic risk factors. Further analyses revealed that mortality due to hemorrhagic stroke demonstrated the strongest correlation with advancing CKM stages, underscoring the critical importance of blood pressure management in comprehensive cardiorenal-metabolic prevention strategies. The authors suggest that future CKM risk stratification—particularly for stages 2 through 4—should emphasize CKD status and risk grading to improve the accuracy of mortality prediction and to inform personalized interventions.
The research further emphasized that maintaining renal function and early detection of CKD are critical strategies for reducing both all-cause and cardiovascular mortality. For individuals at high risk of CKD, regular monitoring of kidney function, early initiation of nephroprotective therapies, such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, along with multidisciplinary management, are recommended to prevent disease progression and enhance long-term outcomes.
This study, conducted under the leadership of Professor Xi Li and Professor Jianfang Cai at the National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, provides robust population-based evidence from China that advances the current understanding of CKM syndrome and its substage heterogeneity. The findings hold significant implications for public health policy and clinical practice, offering a scientific basis for improving the integrated management of cardiovascular, renal, and metabolic diseases both within China and internationally.
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Reference
DOI: 10.1097/CM9.0000000000003914
About Professor Xi Li from Fuwai Hospital, Chinese Academy of Medical Sciences
Professor Xi Li, MD, PhD, is Executive Deputy Director of the National Clinical Research Center for Cardiovascular Diseases at Fuwai Hospital. He also serves as Deputy Director of the Department of Preventive Medicine at the National Center for Cardiovascular Diseases and Head of the Biobank. An expert in epidemiology and biostatistics, he focuses on cardiovascular prevention, disease burden forecasting, and health equity. He has authored over 100 high-impact publications in leading journals such as The Lancet , BMJ , and JAMA Network Open , and serves on editorial boards including JACC and European Heart Journal – Quality of Care and Clinical Outcomes .
About Professor Jianfang Cai from Fuwai Hospital, Chinese Academy of Medical Sciences
Professor Jianfang Cai, MD, PhD, is Chief Physician and Graduate Supervisor, and serves as Deputy Director of the Department of Internal Medicine and Director of the Department of Nephrology at Fuwai Hospital. His clinical expertise includes acute and chronic kidney diseases and renal replacement therapies. He is actively involved in several national professional societies in nephrology and epidemiology. Professor Cai has led multiple national and provincial research projects and has extensive teaching experience in internal medicine and clinical epidemiology. His research interests focus on cardiorenal diseases, chronic kidney disease, and acute kidney injury.
About Dr. Xingyu Zhou from Peking Union Medical College, Fuwai Hospital
Dr. Xingyu Zhou, PhD, is a graduate of Peking Union Medical College, Fuwai Hospital. His research centers on cardiovascular epidemiology and prevention strategies for cardiometabolic-kidney (CKM) syndrome. He is committed to advancing population-based research and evidence-driven prevention strategies to improve cardiovascular health outcomes.
Funding information
This project was partly supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Science (No. 2021-1-I2M-011), the National High Level Hospital Clinical Research Funding (No. 2022-GSP-GG-4), the Ministry of Finance of China and National Health Commission of China, and the 111 Project from the Ministry of Education of China (No. B16005).
Chinese Medical Journal
Association of cardiovascular–kidney–metabolic syndrome stages with mortality: A nationwide, population-based, prospective cohort study
31-Dec-2025
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