Comparative prognostic value of simple, formula-derived, and biomarker-based adiposity indices for cardiovascular disease and mortality: a UK Biobank cohort study

Abstract

Abstract Background Whether differences in adiposity–outcome associations translate into better prediction remains uncertain. We primarily compared the strength and patterns of associations of 12 adiposity-related indices with cardiovascular and mortality outcomes, and secondarily evaluated their discriminatory and incremental predictive performance. Methods We analysed a complete-case sample of 278,695 UK Biobank participants without baseline coronary heart disease (CHD) or stroke. Multivariable Cox models, restricted cubic splines, and time-varying analyses associations. The primary outcome was incident cardiovascular disease (CVD; CHD or stroke); component outcomes and all-cause and broadly defined CVD mortality were also examined. Discrimination was compared using five-fold cross-validated integrated time-dependent areas under the curve (iAUCs) over 1–17 years, with alternative indices evaluated in place of body mass index (BMI) within a common covariate framework. Incremental prediction was assessed using 10-year truncated Harrell’s C-index, integrated discrimination improvement (IDI), and continuous net reclassification improvement (NRI) after adding non-BMI indices to a Framingham risk-factor benchmark containing BMI and conventional cardiovascular risk factors. Results During a median 15.6 years, 27,947 incident CVD events and 24,464 deaths occurred. Waist-to-hip ratio (WHR) was positively associated with CVD, CHD, and stroke, with adjusted hazard ratios per standard deviation of 1.11 (95% CI 1.09–1.13), 1.12 (1.10–1.14), and 1.07 (1.03–1.10), respectively. Association patterns varied by outcome, and several CVD and CHD associations attenuated over follow-up. The highest observed iAUC gains over BMI ranged from 0.0001 to 0.0025 across outcomes. Weight-adjusted waist index yielded the highest observed total NRI for CVD and CHD, WHR for broadly defined CVD mortality, and A Body Shape Index for all-cause mortality. For CVD, adding weight-adjusted waist index yielded an NRI of 0.077 (95% CI 0.063–0.093), primarily attributable to the non-event component, with small changes in C-index (0.00076) and IDI (0.000455). Conclusions Association differences did not consistently translate into substantial discrimination gains, and no index was uniformly superior across outcomes. Selected non-BMI indices provided modest, outcome-specific incremental information, based on apparent performance within this cohort. External validation and assessment of calibration and clinical utility are needed before these findings can support clinical recommendations.

The authors' abstract, as published at the source. BMC Public Health, 2026 · DOI ↗