Association Between Serum Advanced Glycation End Products and Cardiovascular‐Kidney‐Metabolic (CKM) Syndrome: A 3‐Year Longitudinal Cohort Study (2019–2022)

Background Cardiovascular‐kidney‐metabolic (CKM) syndrome begins with obesity and glucose abnormalities, advancing to cardiovascular and kidney complications. This study investigates the relationship of advanced glycation end products (AGEs) with CKM syndrome staging and transition patterns. Methods This 3‐year longitudinal study (2019–2022) of 1264 adults identified five CKM trajectory groups: Group 1 (stable low‐risk, 6.7%, stage 0/1), Group 2 (fluctuating, 15.8%, stages 0/1–2), Group 3 (stable intermediate, 52.8%, stage 2), Group 4 (progressors, 8.9%, to stage 3/4), and Group 5 (stable high‐risk, 15.8%, stage 3/4), from baseline distributions of stage 0 (1.6%), 1 (12.3%), 2 (71.0%), 3 (5.8%), and 4 (9.2%). Serum AGEs were quantified by UPLC‐MS/MS. Results Higher AGEs levels showed significant associations with CKM severity, with each 1‐SD increase corresponding to a 30% greater likelihood of advanced staging (95% CI:10%–54%). Quartile analysis revealed a dose–response relationship (Q2:1.66[1.15–2.41]; Q3:1.67[1.12–2.48]; Q4:1.92[1.31–2.81]). Longitudinally, the total AGEs score was significantly associated with CKM transition patterns from 2019 to 2022. The odds ratios (ORs) for Group 2, Group 3, Group 4, and Group 5 compared to Group 1 were 1.61 (1.06–2.45), 1.64 (1.11–2.41), 1.71 (1.07–2.73), and 2.03 (1.32–3.13), respectively. Conclusions These findings suggest that serum AGEs are linked to CKM severity and progression, potentially serving as biomarkers for CKM staging and targets for intervention.