Cumulative inflammatory burden of metal mixtures is associated with central obesity, cardiovascular disease, and mortality: findings from NHANES.

Background: The exposure of heavy metals is a serious environmental risk factor for cardiometabolic health. However, the association of cumulative inflammatory load of metal mixtures with cardiovascular disease (CVD) and mortality remain incompletely characterized. This study aimed to evaluate the associations of a metal mixture inflammatory index (MMII) with CVD and mortality, and to examine whether central obesity measured by weight-adjusted waist index WWI statistically mediates the association of MMII with CVD in an exploratory cross-sectional study. Methods: Data were obtained from 7 cycles of the National Health and Nutrition Examination Survey (NHANES 2005-2018) with mortality follow-up through 2019. A total of 11,577 adults aged ≥20 years with complete urinary metal, inflammatory markers, CVD, and WWI data were included. Using inductively coupled plasma mass spectrometry (ICP-MS), nine metals' urinary concentrations were measured. MMII was calculated using reduced rank and stepwise regression based on inflammation biomarkers. Linear association of MMII with CVD was examined using logistic regression and Cox proportional hazards models, along with RCS and exploratory mediation analyses for associations with prevalence and mortality. Results: Elevated MMII levels were noticeably associated with increased odds of CVD (OR = 2.79, 95% CI: 1.81-4.29). Estimates from mediation analyses further indicated that WWI statistically explained 11.4% of the effect observed. Elevated MMII was associated with a higher risk of all-cause mortality (HR = 2.39, 95% CI: 1.69-3.38), without significant association with cardiovascular mortality. Conclusion: Elevated levels of MMII reflect the burden of metal mixtures and are linked to central obesity, cardiovascular disease (CVD), and all-cause mortality.