The Association of Blood Cobalt Levels with Cardiovascular and Chronic Kidney Diseases: Mediating Role of Inflammatory Indicators (SII, NLR, PLR, NMLR, and LMR)

Abstract

Cobalt is a prevalent environmental metal with known toxicological potential. Inflammation plays a key role in the pathophysiology of cardiovascular disease (CVD) and chronic kidney disease (CKD). However, the relationships between blood cobalt concentrations, inflammatory indicators, and their roles in CVD and CKD remain inadequately characterized. This study aimed to evaluate the associations between blood cobalt concentrations and the prevalence of CVD and CKD and to explore the mediating role of inflammatory indicators in these associations. Data from 6689 participants were obtained from the National Health and Nutrition Examination Survey 2015-2018. Restricted cubic splines and multivariate logistic regression models were used to assess the associations between blood cobalt exposure, CVD, CKD, and inflammatory markers. Generalized additive models were applied to investigate potential nonlinear relationships. The receiver operating characteristic analysis assessed the discriminatory ability of blood cobalt levels for CVD and CKD. Mediation analysis was conducted to examine whether inflammatory indicators mediate the association between blood cobalt and CVD/CKD. Multivariate logistic regression analysis showed that higher blood cobalt levels (OR = 1.50, 95% CI 1.22-1.85, P < 0.001) and NMLR (OR = 1.34, 95% CI 1.07-1.68, P = 0.010) were significantly associated with a higher prevalence of CVD. For CKD, blood cobalt (OR = 1.74, 95% CI 1.44-2.11, P < 0.001), SII (OR = 1.43, 95% CI 1.18-1.73, P < 0.001), NLR (OR = 1.73, 95% CI 1.42-2.10, P < 0.001), and NMLR (OR = 1.63, 95% CI 1.33-2.00, P < 0.001) were all significantly associated with a higher prevalence of CKD. Blood cobalt levels showed significant positive correlations with SII, NLR, PLR, and NMLR. Specifically, SII (β = 49.93, 95% CI 26.91-72.94, P < 0.001), NLR (β = 0.21, 95% CI 0.13-0.30, P < 0.001), and NMLR (β = 0.20, 95% CI 0.13-0.27, P < 0.001) exhibited significant increases. Mediation analysis indicated that SII, NLR, NMLR, and LMR significantly mediated the association between log_BCo and both CVD and CKD (P < 0.05). Notably, NMLR had the strongest mediating effect in both CVD and CKD, with a mediation effect percentage: 13.42% (P < 0.001) in CVD and 11.76% (P < 0.001) in CKD. Blood cobalt concentrations are significantly associated with the prevalence of cardiovascular disease and chronic kidney disease. Inflammation may play a mediating role in these associations. These findings highlight the potential contribution of inflammation to cobalt-related cardiovascular and kidney disease risks.

Keywords: Blood cobalt; Cardiovascular disease; Chronic kidney disease; Inflammation.