Department of Periodontology and Oral Sciences Research Group, University of Glasgow Dental School, Glasgow, UK.
Department of Dental Prophylaxis and Experimental Dentistry, Jagiellonian University Medical College, Krakow, 31-107 Poland.
Eur Heart J. 2019 Nov 1;40(42):3459-3470. doi: 10.1093/eurheartj/ehz646.
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.
炎症是高血压的一个重要驱动因素。牙周炎是一种慢性炎症性疾病，它可能为促高血压的免疫激活提供一种机制，但在人类中因果关系的证据很少。我们旨在研究牙周炎与高血压之间的关联性质。
我们在 UK-Biobank/国际血压基因组关联研究联盟的约 75 万参与者中进行了两样本孟德尔随机化分析，使用与牙周炎相关的单核苷酸多态性（SNP）SIGLEC5、DEFA1A3、MTND1P5 和 LOC107984137 位点中的 SNP，以确定它们对血压（BP）估计的影响。这表明牙周炎相关 SNP 与 BP 表型之间存在显著关系。然后，我们对牙周炎治疗对 BP 的影响进行了随机干预试验。101 名患有中度/重度牙周炎的高血压患者被随机分为强化牙周治疗（IPT；龈下和龈上刮治/洗必泰；n=50）或对照牙周治疗（CPT；龈上刮治；n=51），以动态血压监测 24 小时收缩压（ABPM）作为主要结果。与 CPT 相比，强化牙周治疗在 2 个月时改善了牙周状况。与 CPT 相比，IPT 使平均收缩压显著降低（平均差异为-11.1mmHg；95%CI 6.5-15.8；P<0.001）。收缩压降低与牙周状况改善相关。IPT 还改善了舒张压和内皮功能（血流介导的扩张）。这些心血管变化伴随着循环 IFN-γ 和 IL-6 以及激活（CD38+）和免疫衰老（CD57+CD28null）CD8+T 细胞的减少，这些细胞先前与高血压有关。
观察到牙周炎与 BP 之间存在因果关系，为在一大群高血压患者中开展临床试验提供了概念验证。ClinicalTrials.gov：NCT02131922。
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