Causal association between periodontitis and hypertension: evidence from Mendelian randomization and a randomized controlled trial of non-surgical periodontal therapy

• Published in: European heart journal Vol. 40; no. 42; pp. 3459 - 3470
• Main Authors: Czesnikiewicz-Guzik, Marta, Osmenda, Grzegorz, Siedlinski, Mateusz, Nosalski, Richard, Pelka, Piotr, Nowakowski, Daniel, Wilk, Grzegorz, Mikolajczyk, Tomasz P, Schramm-Luc, Agata, Furtak, Aneta, Matusik, Pawel, Koziol, Joanna, Drozdz, Miroslaw, Munoz-Aguilera, Eva, Tomaszewski, Maciej, Evangelou, Evangelos, Caulfield, Mark, Grodzicki, Tomasz, D'Aiuto, Francesco, Guzik, Tomasz J
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.11.2019
• Subjects: Editor's Choice; Fast Track Clinical Research; Female; Humans; Hypertension - complications; Hypertension - epidemiology; Hypertension - genetics; Inflammation; Male; Mendelian Randomization Analysis; Middle Aged; Periodontitis - complications; Periodontitis - epidemiology; Periodontitis - genetics; Vasodilation - physiology; Hypertension; Genetics; Inflammation; Treatment; Periodontitis; Vascular function
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehz646

Abstract Aims Inflammation is an important driver of hypertension. Periodontitis is a chronic inflammatory disease, which could provide a mechanism for pro-hypertensive immune activation, but evidence of a causal relationship in humans is scarce. We aimed to investigate the nature of the association between periodontitis and hypertension. Methods and results We performed a two-sample Mendelian randomization analysis in the ∼750 000 UK-Biobank/International Consortium of Blood Pressure-Genome-Wide Association Studies participants using single nucleotide polymorphisms (SNPs) in SIGLEC5, DEFA1A3, MTND1P5, and LOC107984137 loci GWAS-linked to periodontitis, to ascertain their effect on blood pressure (BP) estimates. This demonstrated a significant relationship between periodontitis-linked SNPs and BP phenotypes. We then performed a randomized intervention trial on the effects of treatment of periodontitis on BP. One hundred and one hypertensive patients with moderate/severe periodontitis were randomized to intensive periodontal treatment (IPT; sub- and supragingival scaling/chlorhexidine; n = 50) or control periodontal treatment (CPT; supragingival scaling; n = 51) with mean ambulatory 24-h (ABPM) systolic BP (SBP) as primary outcome. Intensive periodontal treatment improved periodontal status at 2 months, compared to CPT. This was accompanied by a substantial reduction in mean SBP in IPT compared to the CPT (mean difference of −11.1 mmHg; 95% CI 6.5–15.8; P < 0.001). Systolic BP reduction was correlated to periodontal status improvement. Diastolic BP and endothelial function (flow-mediated dilatation) were also improved by IPT. These cardiovascular changes were accompanied by reductions in circulating IFN-γ and IL-6 as well as activated (CD38+) and immunosenescent (CD57+CD28null) CD8+T cells, previously implicated in hypertension. Conclusion A causal relationship between periodontitis and BP was observed providing proof of concept for development of clinical trial in a large cohort of hypertensive patients. ClinicalTrials.gov: NCT02131922.