Abstract：
Certain heavy metals have been correlated to an elevated risk of inflammation-related diseases and mortality. Nevertheless, the intricate relationships between metal exposure, inflammation and mortality remain unknown. We included 3741 adults with measurements of ten urinary heavy metals in the National Health and Nutritional Examination Survey (NHANES) 2005-2010, followed up to December 31, 2019. Low-grade systemic inflammation was evaluated by various markers, including C-reactive protein (CRP) and ratios derived from regular blood tests. We assessed associations between heavy metal and all-cause mortality using multivariate COX regressions. Then we assessed the mediation effect of low-grade systemic inflammation on the associations via Sobel Test. To gauge the systemic inflammatory potential of the multi-metal mixture and its correlation with all-cause mortality, a Metal Mixture Inflammatory Index (MMII) was developed using reduced rank regression (RRR) models. The association between MMII and all-cause mortality was explored via multivariate COX regressions. Cadmium, antimony and uranium displayed positive associations with mortality, with hazard ratios (HR) ranging from 1.18 to 1.46 (all P-FDR < 0.05). Mediation analyses revealed that the associations between specific heavy metals (cadmium and antimony) and mortality risk were slightly mediated by the low-grade systemic inflammation markers, with mediation proportions ranging from 3.11 % to 5.38 % (all P < 0.05). MMII, the weighted sum of 9 heavy metals, significantly predicted platelet-to-lymphocyte ratio (PLR) and CRP (β = 0.10 and 1.16, all P < 0.05), was positively associated with mortality risk (HR 1.28, 95 % CI 1.14 to 1.43). Exposure to heavy metals might increase all-cause mortality, partly mediated by low-grade systemic inflammation. MMII, designed to assess the potential systemic inflammatory effects of exposure to multiple heavy metals, was closely related to the all-cause mortality risk. This study introduces MMII as an approach to evaluating co-exposure and its potential health effects comprehensively.
摘要：
某些重金属与炎症相关疾病和死亡的风险升高相关。然而，金属暴露之间错综复杂的关系，炎症和死亡率仍然未知。我们在2005-2010年全国健康和营养检查调查（NHANES）中纳入了3741名成年人，对10种尿重金属进行了测量，随访至2019年12月31日。通过各种标记物评估低度全身性炎症，包括C反应蛋白（CRP）和来自常规血液检查的比率。我们使用多变量COX回归评估了重金属和全因死亡率之间的关联。然后，我们通过Sobel测试评估了低度全身炎症对关联的调解作用。为了评估多金属混合物的全身炎症潜能及其与全因死亡率的相关性，a金属混合物炎症指数(MMII)采用降阶回归(RRR)模型建立.通过多变量COX回归探讨MMII与全因死亡率之间的关联。镉,锑和铀与死亡率呈正相关，风险比（HR）范围为1.18至1.46（所有P-FDR<0.05）。中介分析显示，特定重金属（镉和锑）与死亡风险之间的关联是由低度全身性炎症标志物介导的，调解比例为3.11%~5.38%(均P<0.05)。MMII,9种重金属的加权总和，显著预测血小板与淋巴细胞比值(PLR)和CRP(β=0.10和1.16,均P<0.05),与死亡风险呈正相关(HR1.28，95%CI1.14至1.43)。接触重金属可能会增加全因死亡率，部分由低度全身性炎症介导。MMII,旨在评估暴露于多种重金属的潜在全身炎症效应，与全因死亡风险密切相关。本研究引入MMII作为一种全面评估共同暴露及其潜在健康影响的方法。
