Dynamic interplay of atherogenic index and body roundness in cardio-renal-metabolic disease: a multi-state analysis

Type 2 diabetes mellitus (T2DM), atherosclerotic cardiovascular disease (CVD) and chronic kidney disease (CKD) are closely linked at epidemiological, pathophysiological, and molecular levels, forming cardio-renal-metabolic (CRM) disease. Their multimorbidity leads to multi-organ dysfunction and increased cardiovascular risk, making prevention and management crucial in clinical and public health practice. We included 398,689 participants from UK Biobank free of CRM diseases at baseline. We used both traditional and multi-state regression model to assess the relationships between AIP-BRI —defined as the product of the atherogenic index of plasma (AIP) and the body roundness index (BRI) —and CRM diseases. Besides, we employed the restricted cubic spline (RCS) approach to visualize the dose-response relationship between AIP-BRI values and three main transition stages (baseline→first CRM diseases (FCRM), FCRM disease→ double CRM (DCRM) diseases, and DCRM diseases→triple CRM (TCRM) disease). Over a a median follow-up period of 12.7 years, 61,539 individuals developed FCRM disease. Among these, 10,714 further developed DCRM diseases, while 1,332 advanced to TCRM diseases. According to our study, AIP-BRI was significantly associated with the progression of CRM diseases in fully adjusted model (HR [95% CI]: 1.248 [1.241–1.255] for FCRM; 1.180 [1.167–1.193] for DCRM; 1.120 [1.086–1.155] for TCRM). Our findings highlight AIP-BRI as a potentially useful composite biomarker for predicting and monitoring CRM disease progression. Its sensitivity enables early risk stratification, supporting targeted interventions to mitigate disease burden. a. Employing a multi-state model, this study presents a comprehensive map of how a combined dyslipidemia-visceral adiposity risk score influences the entire trajectory of CRM disease progression. b. The dynamic progression of CRM diseases is significantly driven by the AIP-BRI score, with mediation analyses unveiling glycemic status as a key underlying mechanism. c. This study provides insights for clinical risk stratification, supporting the early prevention and diagnosis of CRM multimorbidity.