Association between body roundness index and progression of cardio-renal-metabolic diseases using multistate models.

To investigate associations between body roundness index (BRI) and progression of cardio-renal-metabolic diseases (CRMDs). This study included 442,489 UK Biobank participants aged ≥ 40 years without CRMDs at baseline. BRI was analyzed continuously and by tertiles. Primary outcomes were first CRMD (FCRMD), cardio-renal-metabolic multimorbidity (CRMM), and all-cause mortality. Hazard ratios (HRs) and population attributable fractions (PAFs) were estimated using Cox and multistate models. Higher BRI was consistently associated with increased risks of CRMD onset and all-cause mortality, with strongest associations in the highest tertile for T2D (HR 6.94, 95% CI 6.57-7.33) and CRMM (HR 3.25[3.05-3.46]). In multistate analyses, the highest BRI tertile showed significantly higher risks for transitioning from baseline to FCRMD (HR 2.24[2.19-2.29], PAF 26.22%), from FCRMD to CRMM (HR 1.58[1.47-1.69], PAF 21.21%), and from baseline to death (HR 1.05[1.02-1.09], PAF 2.06%). Participants with higher BRI combined with high genetic risk or unhealthy lifestyle had a greater risk of CRMD onset and progression along the cardio-renal-metabolic continuum. Elevated BRI was associated with increased risks of incident CRMDs and progression to multimorbidity, supporting its potential value for early risk identification.