Causal association between periodontitis and hypertension: evidence from Mendelian randomization and a randomized controlled trial of non-surgical periodontal therapy.
Genetics
Hypertension
Inflammation
Periodontitis
Treatment
Vascular function
Journal
European heart journal
ISSN: 1522-9645
Titre abrégé: Eur Heart J
Pays: England
ID NLM: 8006263
Informations de publication
Date de publication:
01 11 2019
01 11 2019
Historique:
received:
04
07
2019
revised:
25
07
2019
accepted:
21
08
2019
pubmed:
11
9
2019
medline:
21
10
2020
entrez:
11
9
2019
Statut:
ppublish
Résumé
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. 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. 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.
Identifiants
pubmed: 31504461
pii: 5556904
doi: 10.1093/eurheartj/ehz646
pmc: PMC6837161
doi:
Banques de données
ClinicalTrials.gov
['NCT02131922']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3459-3470Subventions
Organisme : British Heart Foundation
ID : FS/12/82/29736
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RE/13/5/30177
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_EX_MR/M009203/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9521010
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M009203/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_14089
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.
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