Mortality Risks Linked to Cardiovascular-Kidney-Metabolic Syndrome in UK Biobank

Overview

This prospective UK Biobank study demonstrates that cardiovascular-kidney-metabolic (CKM) syndrome stages 2 and above are strongly associated with increased all-cause and cardiovascular mortality over nearly 14 years of follow-up. Mortality risk increases with CKM stage in both sexes, with relative risks higher in females but absolute risk increments greater in males.

Background

The American Heart Association recently defined CKM syndrome to capture the interconnected pathophysiology of metabolic risk factors, diabetes, cardiovascular disease, and chronic kidney disease. Prior studies from the US and China have linked CKM syndrome stages with mortality, but data from large UK or European populations were lacking. The UK Biobank cohort provides a unique opportunity to characterize CKM syndrome prevalence and prognostic implications in a predominantly White, middle-aged UK population.

Data Highlights

Over a median 13.7 years follow-up, 35,401 deaths occurred (9%), including 5,406 cardiovascular deaths.

Key Findings

• CKM Stages 2 and combined 3–4 were significantly associated with increased hazards of all-cause and cardiovascular mortality compared to Stage 0 in both sexes.
• Stage 1 CKM (excess adiposity without metabolic sequelae) was not associated with increased mortality risk relative to Stage 0.
• Relative mortality risks were higher in females across CKM stages, but absolute risk increases were greater in males due to higher baseline risk.
• CKM syndrome prevalence was high, with 85% of the cohort classified as Stage 1 or higher.
• CKM stage correlated with established risk factors including age, BMI, blood pressure, glycated hemoglobin, triglycerides, diabetes, hypertension, smoking, and predicted 10-year CVD risk.

Clinical Implications

CKM syndrome staging can identify individuals at elevated mortality risk, particularly from Stage 2 onwards, underscoring the importance of early detection and management of metabolic and kidney dysfunction to prevent cardiovascular outcomes. The lack of increased mortality risk at Stage 1 highlights that obesity alone may not confer risk without metabolic complications, emphasizing targeted intervention on cardiometabolic sequelae. Sex differences in relative and absolute risk suggest tailored risk communication and management strategies may be warranted.

Conclusion

In this large UK cohort, CKM syndrome stages 2 and above are common and strongly linked to increased mortality risk, reinforcing the clinical relevance of integrated cardiovascular, kidney, and metabolic risk assessment. Further research is needed to optimize CKM syndrome classification and its utility in routine care.

References

1. American Heart Association 2023 -- Definition of Cardiovascular-Kidney-Metabolic Syndrome
2. UK Biobank 2007-2010 -- Cohort Recruitment and Baseline Assessment
3. KDIGO 2012 -- Chronic Kidney Disease Risk Classification
4. PREVENT Score Study -- Cardiovascular Risk Prediction