Cardio-kidney-metabolic syndrome in the general population: patterns and sex-specific trajectories
R Coenen Chelu, S J L Bakker, R T Gansevoor, K Damman, R A De Boer, N Suthahar, W C MeijersAbstract
Introduction
Cardio-kidney-metabolic (CKM) dysfunction links metabolic, renal, and cardiovascular impairment as a unified continuum of multimorbidity. Long-term changes in CKM health within the general population and possible sex-specific trajectories remain poorly defined.
Purpose
Quantifying CKM stage migration—and its sex-specific patterns—pinpoints prevention windows and guides risk-based follow-up in the general population.
Methods
Data were drawn from the population-based Prevention of Renal and Vascular ENd-stage Disease cohort. Among 3213 participants (mean age 52 ± 12 years, 51 % women) with complete data, CKM stages were assigned at two visits 5-8 years apart, using BMI, blood pressure, glucose, cholesterol, and albuminuria, supplemented by NT-proBNP and registry-confirmed cardiovascular (CVD) or heart-failure (HF) events. Stage 4 denoted clinical or advanced disease (major CVD, HF, or NT-proBNP ≥ 300 pg/mL). Stage transitions (Δstage) were visualized with alluvial plots and compared by sex using t-tests and linear regression adjusted for age and baseline stage; interaction between sex and baseline stage was assessed by ANCOVA.
Results
All baseline variables (age, sex, BMI, systolic blood pressure (BP), fasting glucose, total cholesterol, urinary albumin, NT-proBNP) differed across CKM stages (p < 0.001). CKM distribution shifted toward higher severity: stages 0–1 declined from 55 % to 46 %, while stages 2–3 increased from 31 % to 38 %. Stage 4 prevalence increased by 19 %, driven by incident CVD/HF and elevated NT-proBNP. Mean ΔCKM stage was +0.31 ± 1.09 in women and +0.36 ± 1.03 in men (p = 0.17). After adjustment, male sex was associated with a modest but significantly greater increase (β = +0.12, p < 0.001). A significant sex × baseline-stage interaction (p = 0.017) indicated that the relationship between baseline CKM stage and subsequent progression differ by sex.
Conclusions
CKM burden worsened substantially over five to eight years, reflecting the accumulation of metabolic and subclinical cardiovascular injury. Although CKM burden increased in both sexes, men tended to worsen from early, metabolic stages, whereas women progressed more steeply once intermediate CKM impairment was established.CKM sex-specific trajectoriesFor image description, please refer to the figure legend and surrounding text.