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

Cześnikiewicz-Guzik, Marta; Osmenda, Grzegorz; Siedliński, Mateusz; Nosalski, Ryszard; Pełka, Piotr; Nowakowski, Daniel; Wilk, G.; Mikołajczyk, T.; Schramm‐Luc, Agata; Furtak, Aneta; Matusik, Paweł T.; Kozioł, Joanna; Dróźdź, M; Munoz-Aguilera, Eva; Tomaszewski, Maciej; Εvangelou, Εvangelos; Caulfield, Mark J.; Grodzicki, Tomasz; D’Aiuto, Francesco; Guzik, Tomasz J.

doi:10.1093/eurheartj/ehz646

Cited by 191 publications

(195 citation statements)

References 50 publications

Supporting

Mentioning

177

Contrasting

Unclassified

Order By: Relevance

“…The results of this study confirmed an association between high BP and periodontitis, analyzing periodontal clinical parameters and traditional cardiovascular risk factors in a well-characterized representative adult population in Portugal. These effects on BP were confounded by the age factor as previously highlighted [43,44], and also a major covariate for periodontal status previously reported in this population [28].…”

Section: Discussionmentioning

confidence: 60%

Association between Periodontitis and High Blood Pressure: Results from the Study of Periodontal Health in Almada-Seixal (SoPHiAS)

Machado

Aguilera

Botelho

et al. 2020

JCM

Self Cite

View full text Add to dashboard Cite

Periodontitis is a common chronic inflammatory disease which could have an important impact on blood pressure (BP). This study aimed to explore (a) the association between periodontal health and BP in a large representative cohort, (b) the predictive value of diagnosis of periodontitis in undiagnosed raised BP and (c) whether age is a mediator of this relationship. In total, 1057 randomly recruited individuals (mean age, 60.9 ± 16.3 years, 57.7% women) underwent periodontal clinical assessment and one-single BP measurement using an automated sphygmomanometer device. Logistic and linear regression models were used to estimate the odds of hypertension based on periodontitis case definitions. Mediation analysis was performed to understand the effect of age on the association of periodontitis with hypertension. Adjusted logistic model for gender, smoking habits and body mass index confirmed the association between high BP and periodontitis (OR = 2.31, 95%CI: 1.75–3.04, p < 0.001). Among 168 participants with undiagnosed high BP (15.9% of the study sample), 62.5% had periodontitis (n = 105). In this study, the association between periodontitis with both systolic blood pressure (SBP) (77.6%, p < 0.001) and diastolic blood pressure (DBP) (66.0%, p < 0.001) was mediated by age. Periodontitis is closely linked to BP in a representative Portuguese population.

show abstract

Section: Discussionmentioning

confidence: 60%

Association between Periodontitis and High Blood Pressure: Results from the Study of Periodontal Health in Almada-Seixal (SoPHiAS)

Machado

Aguilera

Botelho

et al. 2020

JCM

Self Cite

View full text Add to dashboard Cite

show abstract

“…Statistical analysis was performed using t-test ( Translational study was performed on 51 hypertensive and 49 normotensive subjects (Clinical Characteristics-Online Table I) and included analysis of miR-214 in plasma, PWV, and flow-mediated dilatation studies as described previuosly. 19,21 Study was performed according to the Declaration of Helsinki and was approved by the Ethics Committee of Jagiellonian University. All participants gave written informed consent.…”

Section: Methodsmentioning

confidence: 99%

T-Cell–Derived miRNA-214 Mediates Perivascular Fibrosis in Hypertension

Nosalski

Siedliński

Denby

et al. 2020

Circulation Research

Self Cite

View full text Add to dashboard Cite

Despite increasing understanding of the prognostic importance of vascular stiffening linked to perivascular fibrosis in hypertension, the molecular and cellular regulation of this process is poorly understood. OBJECTIVES: To study the functional role of microRNA-214 (miR-214) in the induction of perivascular fibrosis and endothelial dysfunction driving vascular stiffening. METHODS AND RESULTS: Out of 381 miRs screened in the perivascular tissues in response to Ang II (angiotensin II)-mediated hypertension, miR-214 showed the highest induction (8-fold, P=0.0001). MiR-214 induction was pronounced in perivascular and circulating T cells, but not in perivascular adipose tissue adipocytes. Global deletion of miR-214 −/− prevented Ang II-induced periaortic fibrosis, Col1a1, Col3a1, Col5a1, and Tgfb1 expression, hydroxyproline accumulation, and vascular stiffening, without difference in blood pressure. Mechanistic studies revealed that miR-214 −/− mice were protected against endothelial dysfunction, oxidative stress, and increased Nox2, all of which were induced by Ang II in WT mice. Ang IIinduced recruitment of T cells into perivascular adipose tissue was abolished in miR-214 −/− mice. Adoptive transfer of miR-214 −/− T cells into RAG1 −/− mice resulted in reduced perivascular fibrosis compared with the effect of WT T cells. Ang II induced hypertension caused significant change in the expression of 1380 T cell genes in WT, but only 51 in miR-214 −/−. T cell activation, proliferation and chemotaxis pathways were differentially affected. MiR-214 −/− prevented Ang II-induction of profibrotic T cell cytokines (IL-17, TNF-α, IL-9, and IFN-γ) and chemokine receptors (CCR1, CCR2, CCR4, CCR5, CCR6, and CXCR3). This manifested in reduced in vitro and in vivo T cell chemotaxis resulting in attenuation of profibrotic perivascular inflammation. Translationally, we show that miR-214 is increased in plasma of patients with hypertension and is directly correlated to pulse wave velocity as a measure of vascular stiffness. CONCLUSIONS: T-cell-derived miR-214 controls pathological perivascular fibrosis in hypertension mediated by T cell recruitment and local profibrotic cytokine release. VISUAL OVERVIEW: An online visual overview is available for this article.

show abstract

“…As an example, an association between periodontitis and hypertension was recently shown by using periodontal-linked single nucleotide polymorphisms (SNPs) and hypertension phenotypes. 168 This study design may be a future tool for elucidating the association between periodontitis and myocardial infarction.…”

Section: Implications and Future Researchmentioning

confidence: 99%

Invasive Dental Treatment and Risk for a First Myocardial Infarction

et al. 2018

View full text Add to dashboard Cite

Invasive dental treatment is suggested to be associated with an increased risk for the development of cardiovascular events. We tested the hypothesis that the incidence of a first myocardial infarction (MI) within 4 wk after invasive dental treatments is increased. A registry-based case-control study within nationwide health care and population registries in Sweden was performed. The case patients included 51,880 individuals with a first fatal or nonfatal MI between January 2011 and December 2013. For each case, 5 control subjects, free from prior MI and matched for age, sex, and geographic area of residence, were randomly selected from the national population registry through risk set sampling with replacement, resulting in 246,978 control subjects. Information on dental treatments was obtained from the Dental Health Register, and the procedures were categorized into invasive dental treatments or other dental treatments. Conditional logistic regression was used to estimate odds ratios (ORs) for MI with corresponding 95% confidence intervals (CIs). In addition to the matching variables, adjustments were made for the following confounders: diabetes, previous cardiovascular disease (CVD), CVD drug treatment, education, and income. The mean age for case patients and controls subjects was 72.6 ± 13.0 y and 72.3 ± 13.0 y, respectively. Case patients more often had previous CVD (49% vs. 23%; P < 0.001) and diabetes (19% vs. 11%; P < 0.001) and received more treatment with CVD drugs (68% vs. 56%; P < 0.001) than control subjects. There was no association between invasive dental treatments during the 4 wk preceding the MI index date (crude OR = 0.99; 95% CI, 0.92 to 1.06; adjusted for confounders OR = 0.98; 95% CI, 0.91 to 1.06). This study did not support the hypothesis of an increased incidence of MI after recent invasive dental treatment.

show abstract

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

Cited by 191 publications

References 50 publications

Association between Periodontitis and High Blood Pressure: Results from the Study of Periodontal Health in Almada-Seixal (SoPHiAS)

Association between Periodontitis and High Blood Pressure: Results from the Study of Periodontal Health in Almada-Seixal (SoPHiAS)

T-Cell–Derived miRNA-214 Mediates Perivascular Fibrosis in Hypertension

Invasive Dental Treatment and Risk for a First Myocardial Infarction

Contact Info

Product

Resources

About