Abstract Background Stages of cardiovascular-kidney-metabolic (CKM) syndrome as per the 2023 American Heart Association (AHA) statement and their associations with mortality have not yet been widely explored in large cohorts. Methods UK Biobank recruited over 500,000 individuals from the UK population aged 40-69 years in 2007-2010. Participants underwent baseline assessments and outcome data were derived from medical records. Participants were followed until the earliest of 30 November 2022, death or withdrawal of consent. CKM stages 0-4 were defined according to the AHA statement with adaptation for UK Biobank data (stage 3 was defined by the very high-risk CKD and/or high predicted 10-year CVD "risk equivalents" only due to data availability). The PREVENT score was used to predict 10-year CVD risk. Outcomes were death from any cause and cardiovascular death (ICD10 codes for ischaemic heart disease, heart failure, stroke and non-specific cardiovascular disease). Cox regression models were used to estimate the association between CKM stage and mortality, adjusted for age and sex. Results After exclusion of individuals with missing data required for classification of CKM stage and those who withdrew consent, 404,202 individuals were analysed. Mean±SD age was 57±8 years, 54% were female and 95% white. Mean±SD body mass index was 27±5 kg/m2, mean±SD systolic blood pressure 138±19 mmHg and 5% self-reported diabetes at baseline. Only 9% of the analysed cohort had no CKM health risk factors (CKM stage 0) and 6% had excess and/or dysfunctional adiposity (CKM stage 1). The majority of participants (71%) had metabolic risk factors or CKD (CKM stage 2). Risk equivalents of subclinical CVD (CKM stage 3) were present in 1% and 13% of included individuals had clinical CVD in CKM (CKM stage 4). There were 35,401 deaths in total (9% of population) over median (Q1-Q3) 13.7 (13.0-14.5) years’ follow-up, of which 5406 were cardiovascular. Hazards of mortality for CKM stage 1 were not significantly different to stage 0. Relative to stage 0, stages 2, 3 and 4 were associated with increased hazards of all-cause and cardiovascular death, particularly for stage 3 (Figure). Adjusted hazard ratios (and 95% confidence intervals) for all-cause mortality for stages 1, 2, 3 and 4 vs stage 0 were 1.02 (0.94-1.10), 1.26 (1.19-1.33), 2.98 (2.77-3.21) and 2.32 (2.18-2.46); with corresponding hazards for cardiovascular mortality of 1.10 (0.81-1.49), 2.15 (1.74-2.65), 7.05 (5.56-8.93) and 6.99 (5.65-8.65)(Table). Conclusions CKM syndrome is prevalent in the "healthy" UK Biobank cohort and strongly associated with mortality. Although incompletely characterised in this analysis, stage 3 (those at high CVD risk) confers higher mortality risk than stage 4 (established CVD) which may plausibly be explained by secondary prevention and risk factor modification in stage 4. Individuals with stage 3 CKM particularly require prioritised identification of risk factors to improve prognosis.
Mayne et al. (Sat,) studied this question.