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

Czesnikiewicz-Guzik, M. et al. (2019) Causal association between periodontitis and hypertension: evidence from Mendelian randomization and a randomized controlled trial of non-surgical periodontal therapy. European Heart Journal, (doi:10.1093/eurheartj/ehz646) (Early Online Publication)

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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.

Item Type:Articles
Additional Information:This study was funded by the European Research Council [ERC and InflammaTENSION; ERC-CoG-726318; to T.J.G.] and by National Science Centre of Poland grant [2997/B/P01/2009/36] and British Heart Foundation (RE/13/5/30177).
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Nosalski, Mr Ryszard and Czesnikiewicz-Guzik, Dr Marta and Mikolajczyk, Dr Tomasz and Siedlinski, Mr Mateusz and Guzik, Professor Tomasz
Authors: Czesnikiewicz-Guzik, M., Osmenda, G., Siedlinski, M., Nosalski, R., Pelka, P., Nowakowski, D., Wilk, G., Mikolajczyk, T.P., Schramm-Luc, A., Furtak, A., Matusik, P., Koziol, J., Drozdz, M., Munoz Aguilera, E., Tomaszewski, M., Evangelou, E., Caulfield, M., Grodzicki, T., D'Aiuto, F., and Guzik, T.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:European Heart Journal
Publisher:Oxford University Press
ISSN:0195-668X
ISSN (Online):1522-9645
Published Online:01 September 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in European Heart Journal 2019
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES
3007980A study of the roles of the immune and inflammatory systems in hypertensionTomasz GuzikEuropean Research Council (ERC)N/ACAMS - Cardiovascular Science