期刊
EUROPEAN HEART JOURNAL
卷 40, 期 42, 页码 3459-3470出版社
OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/ehz646
关键词
Hypertension; Periodontitis; Inflammation; Vascular function; Genetics; Treatment
资金
- European Research Council [ERC]
- European Research Council [InflammaTENSION] [ERC-CoG-726318]
- National Science Centre of Poland [2997/B/P01/2009/36]
- British Heart Foundation [RE/13/5/30177]
- MRC [MC_PC_14089, G9521010, MR/M009203/1, MC_EX_MR/M009203/1] Funding Source: UKRI
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 similar to 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 2months, compared to CPT. This was accompanied by a substantial reduction in mean SBP in IPT compared to the CPT (mean difference of -11.1mmHg; 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-gamma 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.
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