Abstract
BackgroundType 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.MethodsWe 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).ResultsOver 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).ConclusionOur 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.Graphical Abstract