Patients with advanced stage cardiovascular-kidney-metabolic (CKM) syndrome face up to a 30% higher risk for cancer than people without CKM risk factors, according to a new retrospective cohort analysis of nearly 1.4 million participants.

While CKM shares risk factors with cancer, the link between cancer and CKM stage has been unclear, according to the study published in Circulation: Population Health and Outcomes. The findings reinforce the importance of treating patients across overlapping conditions, researchers said.

The study investigated a longitudinal association between CKM stage and the risk for incident cancer using a large-scale nationwide database, said one of the lead study authors Hidehiro Kaneko, MD, PhD, of the Department of Cardiovascular Medicine at The University of Tokyo in Tokyo, Japan.

CKM syndrome is staged from 0 to 4, which allows for stratified risk assessment and early intervention, according to the study authors. The syndrome represents a continuum of risk, starting with cardiometabolic risk factors such as hypertension, diabetes, and chronic kidney disease and progressing through subclinical organ damage to cardiovascular disease.

The analysis was adjusted for clinical, demographic, and lifestyle factors, with the primary outcome being incident cancer. Over a median follow-up of 3.4 years, higher CKM stages at baseline were linked to a higher risk for incident cancer. The stage-specific correlation was the same across cancer types and in assessments ranked by age and sex. Comparable patterns were found among subgroups.

Among men, researchers found a major link between prostate cancer and advanced CKM stages at baseline while in women, breast cancer along with cervical and uterine cancers were prevalent in those with higher baseline CKM stages.

Processes Overlap and Amplify

The key takeaway is that when compared with people without CKM risk factors, those with later-stage CKM had about a 25%-30% increased cancer risk, said Tochukwu M. Okwuosa, MD, professor of medicine and cardiology at Rush University in Chicago.

“This reinforces the idea that chronic systemic disease processes don’t occur in isolation but often overlap and amplify one another,” said Okwuosa, who was not involved in the study.

“The study team wanted to explore whether CKM syndrome stage could also provide insight into cancer risk to better understand whether the same biological and systemic processes driving CKM might also contribute to cancer development,” she said.

Addressing Modifiable Risk Factors

For clinicians, the study’s findings have practical implications, Okwuosa added.

“First, it reinforces the importance of aggressively addressing modifiable risk factors not just for cardiovascular prevention but potentially for cancer risk reduction as well,” she said. “Second, the CKM staging framework may serve as a useful clinical tool to identify higher-risk individuals, prompting more thoughtful consideration of appropriate cancer screening and surveillance. Ultimately, it encourages a more integrated, systems-based approach to patient care.”

The robustness of the authors’ findings across malignancy subtypes, subgroup analyses, and sensitivity analyses does indeed suggest that CKM syndrome may also increase the risk for cancer and not just cardiovascular disease, according to an accompanying editorial written by Caitlin F. Bell, MD, of the Division of Cardiology in the Department of Medicine at the University of Colorado Anschutz School of Medicine in Aurora, Colorado.

“Their results are notable for a clear inflection in the significance of risk when moving from CKM stage 2-3, which by the current definition means moving from the presence of metabolic risk factors to actual subclinical end organ dysfunction,” she wrote.

Bell added that more research is needed to understand how to practically factor these risks in from a broader public health and implementation perspective, “but one could imagine the potential for more personalized and effective cancer screening practices.”

For future studies, Okwuosa would like to see more diverse and representative populations involved, including those from the US, because this study was conducted solely in a Japanese population.

“Beyond that, subsequent research should focus on mechanisms — understanding why CKM syndrome is linked to cancer risk — and whether intervening in CKM risk factors can actually reduce cancer incidence,” Okwuosa said. “That would move this from association to actionable prevention.”

Kaneko reported receiving research funding and scholarship support from Medtronic Japan Co., Ltd; Boston Scientific Japan Co., Ltd; BIOTRONIK JAPAN, Inc.; SIMPLEX QUANTUM, Inc.; and UT-Heart, Inc. He reported holding shares in PrevMed Co., Ltd, and Japan Preventive Medicine Development Institute Co., Ltd.

Okwuosa and Bell reported having no financial disclosures.

Martta Kelly is a medical journalist who lives in the metropolitan New York area.