Is systemic inflammation a missing link between periodontitis and hypertension? Results from two largepopulation-based surveys

Abstract

Objective: The primary objective was to investigate the relationship between periodontitis and hypertension in two independent large surveys. The secondary objective was to ascertain whether systemic inflammation had a mediation effect in the association. Methods: This cross-sectional study analysed representative samples of the US (n = 3460; NHANES 2009/10) and Korean (n = 4539; 2015 KNHANES VI-3) populations. The association between periodontitis (exposure), hypertension (outcome) and inflammatory markers [C-reactive protein (CRP) and white blood cell counts (WBC)] (mediators) was assessed using multivariate linear and logistic regression models and mediation analysis. Results: Participants with periodontitis were more likely to have hypertension (NHANES: OR = 1.3, 95% CI: 1.0–1.6, P = 0.025; KNHANES: OR = 1.2, 95% CI: 1.0–1.4, P = 0.041) and actual systolic blood pressure ≥ 140 mmHg (NHANES: OR = 1.6, 95% CI: 1.1–2.3, P < 0.001; KNHANES: OR = 1.3, 95% CI :1.0–1.6, P < 0.031) than those without the disease. These associations were independent of age, gender, BMI, education level, smoking, alcohol consumption, creatinine, physical activity, presence of other comorbidities and confirmed in participants not taking antihypertensive medications. Diagnosis of periodontitis was directly associated with WBC (in both surveys: NHANES: β ± SE = 0.3 ± 0.1, P < 0.004; KNHANES: β ± SE = 0.3 ± 0.1, P < 0.001) and with CRP levels (in one survey: NHANES: β ± SE = 0.1 ± 0.03, P < 0.007; KNHANES: β ± SE = 0.1 ± 0.04, P > 0.213). Mediation analyses confirmed that CRP acted as a mediator in the association between periodontitis and hypertension in both populations (mediated effect: NHANES: β ± SE = 0.010 ± 0.003, P < 0.001; KNHANES: β ± SE = 0.003 ± 0.001, P = 0.015). WBC acted as a mediator in the KNHANES (mediated effect: β ± SE = 0.004 ± 0.001, P = 0.004) whilst in the NHANES, its effect was dependent of CRP inclusion in the model (mediated effect WBC + CRP: β ± SE = 0.002 ± 0.001, P = 0.001). Conclusions: These findings suggest that periodontitis is closely linked to hypertension and systemic inflammation is, in part, a mediator of this association.