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Cardiovascular disease is the major cause of morbidity and mortality in breast cancer survivors. Chemotherapy contributes to this risk. We aimed to define the mechanisms of long-term vascular dysfunction caused by neoadjuvant chemotherapy (NACT) and identify novel therapeutic targets. We studied arteries from postmenopausal women who had undergone breast cancer treatment using docetaxel, doxorubicin, and cyclophosphamide (NACT) and from women with no history of such treatment matched for key clinical parameters. We explored mechanisms in WT and Nox4-/- mice and in human microvascular endothelial cells. Endothelium-dependent, NO-mediated vasodilatation was severely impaired in patients after NACT, while endothelium-independent responses remained normal. This was mimicked by a 24-hour exposure of arteries to NACT agents ex vivo. When applied individually, only docetaxel impaired endothelial function in human vessels. Mechanistic studies showed that NACT increased inhibitory eNOS phosphorylation of threonine 495 in a Rho-associated protein kinase-dependent (ROCK-dependent) manner and augmented vascular superoxide and hydrogen peroxide production and NADPH oxidase activity. Docetaxel increased expression of the NADPH oxidase NOX4 in endothelial and smooth muscle cells and NOX2 in the endothelium. A NOX4 increase in human arteries may be mediated epigenetically by diminished DNA methylation of the NOX4 promoter. Docetaxel induced endothelial dysfunction and hypertension in mice, and these were prevented in Nox4-/- mice and by pharmacological inhibition of Nox4 or Rock. Commonly used chemotherapeutic agents and, in particular, docetaxel alter vascular function by promoting the inhibitory phosphorylation of eNOS and enhancing ROS production by NADPH oxidases.

Background: Reduced access to dental care may increase cardiovascular risk; however, socioeconomic factors are believed to confound the associations. We hypothesized that the relation persists despite economic wellness and high education, with reduced access to dental care affecting cardiovascular risk at least in part through its effect on blood pressure (BP), possibly mediated by systemic inflammation.Methods: We first assessed the sociodemographic and clinical characteristics related to last dental visit timing (≤ or >6 months; self-reported) using national representative cross-sectional data. Then, the association of last dental visit timing with clinic BP was selectively investigated in highly educated, high income participants, further matched for residual demographic and clinical confounders using propensity score matching (PSM). The mediating effect of systemic inflammation was formally tested. Machine learning was implemented to investigate the added value of dental visits in predicting high BP over the variables included in the Framingham Hypertension Risk Score among individuals without an established diagnosis of hypertension.Results: Of 27,725 participants included in the population analysis, 46% attended a dental visit ≤6 months. In the PSM cohort (n = 2350), last dental visit attendance >6 months was consistently associated with 2 mmHg higher systolic BP (P = 0.001) and with 23 to 35% higher odds of high/uncontrolled BP compared with attendance ≤6 months. Inflammation mildly mediated the association. Access to dental care improved the prediction of high BP by 2%.Conclusions: Dental care use impacts on BP profiles independent of socioeconomic confounders, possibly through systemic inflammation. Regular dental visits may contribute to preventive medicine. [ABSTRACT FROM AUTHOR]

Recent evidence suggests a link between periodontitis (PD) and hypertension, but the nature of this association remains unclear. The overall aim of this review was to critically appraise the evidence linking these two common disorders. Systematic search was conducted for studies published up to December 2018. Prevalence of hypertension in patients with PD (moderate/severe groups) vs. those without PD (non-PD) was the primary outcome. Additional outcomes included adjusted mean difference in systolic (SBP) and diastolic (DBP) blood pressure (BP) levels in PD vs. non-PD, assessment of biomarkers in PD and hypertension, and BP changes after periodontal therapy. From 81 studies selected, 40 were included in quantitative meta-analyses. Diagnoses of moderate-severe PD [odds ratio (OR) = 1.22; 95% confidence interval (CI): 1.10–1.35] and severe PD (OR = 1.49; 95% CI: 1.09–2.05) were associated with hypertension. Prospective studies confirmed PD diagnosis increased likelihood of hypertension occurrence (OR = 1.68; 95% CI: 0.85–3.35). Patients with PD exhibited higher mean SBP [weighted mean difference (WMD) of 4.49 mmHg; 95% CI: 2.88–6.11] and DBP (2.03 mmHg; 95% CI: 1.25–2.81) when compared with non-PD. Lastly, only 5 out of 12 interventional studies confirmed a reduction in BP following periodontal therapy, ranging from 3 to 12.5 mmHg of SBP and from 0 to 10 mmHg of DBP. PD is associated with increased odds of hypertension (SORT C) and higher SBP/DBP levels. The evidence suggesting that PD therapy could reduce BP is inconclusive. Although additional research is warranted on this association, these results suggest that oral health assessment and management of PD could not only improve oral/overall health and quality of life but also be of relevance in the management of patients with hypertension. [ABSTRACT FROM AUTHOR]

Objective: Robust scientific and clinical evidence of how to appropriately manage denture plaque is lacking. This two-part study (i) developed an in vitro model of denture plaque removal, and (ii) assessed effectiveness of these approaches in a randomised clinical trial. Method: (i) a complex denture plaque model was developed using the dominant microbial genera from a recent microbiome analyses. Biofilms formed on polymethylmethacrylate were brushed daily with a wet toothbrush, then either treated daily for 5 days or only on Days 1 and 5 with Polident® denture cleanser tablets (3 min soaking). Quantitative and qualitative microbiological assessments were performed. (ii), an examiner-blind, randomised, crossover study of complete maxillary denture wearers was performed (n = 19). Either once-daily for 7 days or on Day 7 only, participants soaked dentures for 15 min using Corega® denture cleansing tables, then brushed. Denture plaque microbiological assessment used sterilized filter paper discs. Results: The in vitro model showed daily cleaning with denture cleanser plus brushing significantly reduced microbial numbers compared to intermittent denture cleaning with daily brushing (p < 0.001). The clinical component of the study showed a statistically significant reduction in denture plaque microbial numbers in favour of daily versus weekly treatment (aerobic bacteria p = 0.0144). Both in vitro and in vivo studies showed that denture plaque biofilm composition were affected by different treatment arms. Conclusions: This study demonstrated that daily denture cleansing regimens are superior to intermittent denture cleansing, and that cleansing regimens can induce denture plaque compositional changes. Clinicaltrials.gov registration: NCT02780661. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis affects 10-30 % of the global population and this number is likely to increase in the forthcoming years. Moreover, it commonly co-exists with allergic asthma as a chronic allergic respiratory syndrome. While the involvement of Th2 cells in allergy is well understood, alterations of pro-inflammatory Th17 responses remain poorly characterized. The aim of our study was to determine whether natural seasonal allergen exposure causes changes in T cell subset characteristics in patients with allergic rhinitis and asthma. Methods: Sixteen patients with allergic rhinitis/atopic asthma (9M, 7F; age 31.8 ± 12.1) and 16 healthy controls were recruited into the study (9M, 7F; age 31.2 ± 5.3). Blood samples were collected from the patients 1-3 months before pollen season (visit 1), within 7 days of the appearance of pollen/initiation of allergic symptoms (visit 2) and 2 weeks after visit 2 following the introduction of symptomatic treatment with antihistamines (visit 3). Flow cytometry was used to assess major T cell subsets (naïve, central memory, effector memory and CD45RA+ effector) and key T cell cytokine production (IFNγ, IL-17A, TNF and IL-4) using intracellular staining. Data were analyzed using repeated measures ANOVA and paired t test. Results: As expected, an increase in the percentage of IL-4+ CD4+ cells was observed during natural pollen exposure in patients with allergic respiratory syndrome. No significant changes were observed in the production of other cytokines, including Th17 cells, which tended to be lower than in the control population but unchanged during pollen exposure. Introduction of antihistamine treatment led to only moderate changes in cytokine production from CD4 and CD8 T cells. Selective changes in CD8+ T cells were observed during natural pollen exposure including a decrease in transient cells (with features of CD45RA+ and CD45RO+ cells) and a decrease in the percentage of central memory cells in the peripheral circulation. Within the CD4 cell group the total percentage of CD45RA positive CD4 cells was increased during pollen exposure. Conclusions: Th1 and Th17 responses are not altered during pollen season but allergen exposure affects T cell activation and memory cell status in patients with allergic respiratory syndrome. [ABSTRACT FROM AUTHOR]

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: Quantitative comparison of the effects of intensive (IPT) or conventional (CPT) periodontal treatment on arterial blood pressure, endothelial function and inflammatory/metabolic biomarkers., Materials and Methods: A systematic search was conducted to identify randomized controlled trials (RCT) of IPT (supra and subgingival instrumentation). Eight RCTs were included in the meta-analysis. Difference in change of systolic blood pressure (SBP) and diastolic blood pressure (DBP) before and after IPT or CPT were the primary outcomes. The secondary outcomes included: endothelial function and selected inflammatory/anti-inflammatory (CRP, IL-6, IL-10, IFN-γ) and metabolic biomarkers (HDL, LDL, TGs)., Results: The overall effect estimates (pooled Weighted Mean Difference (WMD)) of the primary outcome for SBP and DBP was -4.3 mmHg [95%CI: -9.10-0.48], p = 0.08 and -3.16 mmHg [95%CI: -6.51-0.19], p = 0.06 respectively. These studies were characterized by high heterogeneity. Therefore, random effects model for meta-analysis was performed. Sub-group analyses confirmed statistically significant reduction in SBP [WMD = -11.41 mmHg (95%CI: -13.66, -9.15) P < 0.00001] and DBP [WMD = -8.43 mmHg (95%CI: -10.96,-5.91)P < 0.00001] after IPT vs CPT among prehypertensive/hypertensive patients, while this was not observed in normotensive individuals. The meta-analyses showed significant reductions in CRP and improvement of endothelial function following IPT at all analysed timepoints., Conclusions: IPT leads to improvement of the cardiovascular health in hypertensive and prehypertensive individuals., (Copyright © 2021. Published by Elsevier Ltd.)

Recent evidence suggests a link between periodontitis (PD) and hypertension, but the nature of this association remains unclear. The overall aim of this review was to critically appraise the evidence linking these two common disorders. Systematic search was conducted for studies published up to December 2018. Prevalence of hypertension in patients with PD (moderate/severe groups) vs. those without PD (non-PD) was the primary outcome. Additional outcomes included adjusted mean difference in systolic (SBP) and diastolic (DBP) blood pressure (BP) levels in PD vs. non-PD, assessment of biomarkers in PD and hypertension, and BP changes after periodontal therapy. From 81 studies selected, 40 were included in quantitative meta-analyses. Diagnoses of moderate-severe PD [odds ratio (OR) = 1.22; 95% confidence interval (CI): 1.10-1.35] and severe PD (OR = 1.49; 95% CI: 1.09-2.05) were associated with hypertension. Prospective studies confirmed PD diagnosis increased likelihood of hypertension occurrence (OR = 1.68; 95% CI: 0.85-3.35). Patients with PD exhibited higher mean SBP [weighted mean difference (WMD) of 4.49 mmHg; 95% CI: 2.88-6.11] and DBP (2.03 mmHg; 95% CI: 1.25-2.81) when compared with non-PD. Lastly, only 5 out of 12 interventional studies confirmed a reduction in BP following periodontal therapy, ranging from 3 to 12.5 mmHg of SBP and from 0 to 10 mmHg of DBP. PD is associated with increased odds of hypertension (SORT C) and higher SBP/DBP levels. The evidence suggesting that PD therapy could reduce BP is inconclusive. Although additional research is warranted on this association, these results suggest that oral health assessment and management of PD could not only improve oral/overall health and quality of life but also be of relevance in the management of patients with hypertension., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background and Purpose: Emerging evidence indicates that hypertension is mediated by immune mechanisms. We hypothesized that exposure to Porphyromonas gingivalis antigens, commonly encountered in periodontal disease, can enhance immune activation in hypertension and exacerbate the elevation in BP, vascular inflammation and vascular dysfunction., Experimental Approach: Th1 immune responses were elicited through immunizations using P. gingivalis lysate antigens (10 μg) conjugated with aluminium oxide (50 μg) and IL-12 (1 μg). The hypertension and vascular endothelial dysfunction evoked by subpressor doses of angiotensin II (0.25 mg·kg -1 ·day -1 ) were studied, and vascular inflammation was quantified by flow cytometry and real-time PCR., Key Results: Systemic T-cell activation, a characteristic of hypertension, was exacerbated by P. gingivalis antigen stimulation. This translated into increased aortic vascular inflammation with enhanced leukocyte, in particular, T-cell and macrophage infiltration. The expression of the Th1 cytokines, IFN-γ and TNF-α, and the transcription factor, TBX21, was increased in aortas of P. gingivalis/IL-12/aluminium oxide-immunized mice, while IL-4 and TGF-β were unchanged. These immune changes in mice with induced T-helper-type 1 immune responses were associated with an enhanced elevation of BP and endothelial dysfunction compared with control mice in response to 2 week infusion of a subpressor dose of angiotensin II., Conclusions and Implications: These results support the concept that Th1 immune responses induced by bacterial antigens such as P. gingivalis can increase sensitivity to subpressor pro-hypertensive insults such as low-dose angiotensin II, thus providing a mechanistic link between chronic infection, such as periodontitis, and hypertension., Linked Articles: This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc., (© 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)