Mediating role of systemic inflammation in the association between heavy metals exposure and periodontitis risk

Background: This study evaluated the mediating role of systemic inflammation in the association between exposure to heavy metals and periodontitis in a nationwide sample of adults. 

Methods: Pooled cross-sectional data from the National Health and Nutrition Examination Survey (NHANES 2009-2014) were used (n = 8993). Periodontitis was defined by a full-mouth examination and classified as no/mild and moderate/severe (mod/sev) groups. Blood and urinary heavy metal levels were investigated, including cadmium (Cd), lead (Pb), and mercury (Hg). In addition, systemic inflammation was assessed using circulatory leukocyte counts and C-reactive protein (CRP) levels. 

Results: Multivariable logistic regression analysis revealed the positive associations of blood and urinary levels of Cd and Pb with mod/sev periodontitis. In contrast,blood Hg levels did not show a significant association. The odds of having periodontitis were 1.233 and 1.311 times higher for each one-unit increment in Ln-transformed blood Cd (95% confidence interval [CI]: 1.109–1.371) and Pb (95% CI: 1.170-1.470), respectively. Mediation analysis suggested a 6.3% to 11.5% contribution of leucocyte counts in the association of blood Cd and Pb levels with periodontitis. Sensitivity analyses for urinary Cd levels yielded consistent mediating effects. However, no significant mediating effect of CRP was detected. 

Conclusion: Higher exposures to Cd and Pb were positively associated with periodontitis risk. These associations might be partially mediated by the elevated levels of leukocytes rather than CRP. Further longitudinal studies are needed to elucidate the discordant results of the systemic inflammatory biomarkers.