Pentraxin 3 Is an Inflammation-Related Biomarker That Distinguishes Early-Stage from Mid-Advanced Cardiovascular-Kidney-Metabolic Syndrome

Background: The cardiovascular-kidney-metabolic (CKM) syndrome represents a continuum linking metabolic dysfunction, chronic kidney disease, and cardiovascular disease, in which chronic inflammation plays a central role. However, conventional inflammatory biomarkers may not fully capture local inflammatory processes involved in CKM stage transitions. Pentraxin 3 (PTX3), a long pentraxin produced locally at sites of inflammation, may provide complementary information, yet its association with CKM staging has not been systematically evaluated. Methods: In this cross-sectional study, circulating PTX3 levels were measured in 240 adults, including healthy controls (stage 0, S0; n = 60) and individuals with stage 2 (S2; n = 60), stage 3 (S3; n = 60), and stage 4 (S4; n = 60) CKM, classified according to the CKM staging framework. Associations between PTX3 and inflammatory, metabolic, cardiac, and renal biomarkers were assessed using Spearman correlation analysis. Multivariable logistic regression models were constructed within the CKM population (S2-S4) to distinguish early-stage CKM (S2) from mid-advanced-stage CKM (S3 + S4). Model discrimination and calibration were evaluated using receiver operating characteristic (ROC) analysis and the Hosmer-Lemeshow goodness-of-fit test. Results: PTX3 levels were significantly elevated in early-stage CKM (S2) compared with healthy controls ( p  < 0.001) and showed further differentiation between S2 and S3 ( p  < 0.01). PTX3 showed moderate correlations with biomarkers reflecting inflammatory activation, metabolic dysregulation, myocardial injury, and renal dysfunction, including high-sensitivity C-reactive protein (hs-CRP; ρ = 0.361, p  < 0.001), glycated hemoglobin (HbA1c; ρ = 0.434, p  < 0.001), triglycerides (TG; ρ = 0.296, p  < 0.001), and high-sensitivity cardiac troponin T (hs-cTnT; ρ = 0.411, p  < 0.001), and was inversely correlated with estimated glomerular filtration rate (eGFR; ρ = -0.419, p  < 0.001). In multivariable logistic regression models adjusting for demographic factors, metabolic indices, and cardiorenal biomarkers, PTX3 remained independently associated with classification into mid-advanced-stage CKM (S3 + S4 vs S2; odds ratio [OR] per unit increase = 1.05, 95% confidence interval [CI]: 1.03–1.08; p  < 0.001), whereas hs-CRP and procalcitonin (PCT) showed no independent associations. Incorporation of PTX3 significantly improved model discrimination (area under the curve [AUC], 0.892 vs 0.804 for the baseline model; ΔAUC = 0.088, p  = 0.001 by DeLong test), without evidence of compromised calibration. Conclusions: Circulating PTX3 is cross-sectionally associated with CKM stage classification and demonstrates incremental discriminative value beyond conventional inflammatory markers in distinguishing early-stage from mid-advanced-stage CKM. These findings suggest that PTX3 may reflect inflammatory processes not fully captured by systemic markers, supporting its potential role in CKM risk stratification.