Association of estimated plasma volume status with progression from stage 2 to stage 4 cardiovascular–kidney–metabolic syndrome: a cohort from the Tianjin region of China

Introduction Cardiovascular-kidney-metabolic syndrome (CKM) is a systemicdisorder linked to insulin resistance. The association between estimated plasmavolume status (ePVS) and progression from CKM stage 2 (CKM2) to stage 4(CKM4) remains poorly understood. This study assessed the association betweenePVS and CKM2-to-CKM4 progression. Methods A total of 36,505 hospitalized CKM2 patients from the TJHFIT cohortwere followed for 10 years, with 15,495 incident CKM4 events. Cox proportionalhazards models, restricted cubic splines, and SHAP analyses were applied toestimate hazard ratios, nonlinear associations, and variable importance, adjustedfor demographics, medical history, laboratory parameters, and medications. Results CKM4 patients had significantly higher admission and discharge ePVS thancontrols (all P < 0.05). In quartile-stratified analyses, elevated risk of CKM4progression was independently observed only in the upper admission ePVS strata(Q3 and Q4), with no significant risk in the moderate stratum (Q2). For dischargeePVS, a significant risk signal emerged starting from Q2. The highest admission ePVSquartile was associated with 43%, 88%, and 76% higher risks of CKM4, CKM4b, andheart failure versus Q1. Restricted cubic spline analysis revealed a spoon-shapednonlinear association between admission ePVS and CKM4, with an inflection point atapproximately 5.14. The association was stronger in patients aged >60 years. Discussion Higher admission ePVS (Q3/Q4) is independently associated with CKM2-to-CKM4 progression and may serve as a noninvasive risk biomarker particularly in older high-risk populations. External cohort validation is requiredbefore clinical application. Trial registration The research has been registered (ChiCTR2300077220) with ethics approval (TYLL2023-K-016).