Treatment of periodontitis ameliorates the severity and extent of psoriasis-A randomized clinical trial.

AIM: To assess the impact of non-surgical periodontitis treatment over conventional dermatological treatment on the severity and extent of psoriasis in patients affected by comorbid psoriasis and periodontitis. METHODS: Seventy-four patients affected by both psoriasis and Stages I-IV periodontitis were randomized to receive either Steps 1-2 (non-surgical) of periodontal therapy (test group; n = 37) or no treatment (control group; n = 37). The two groups were balanced in terms of psoriasis medications, with the majority of the included patients undergoing biologics (74.0%) as monotherapy, while minor proportions were under systemic medications (13.7%) or none/topical/phototherapy (12.3%). The psoriasis area severity index (PASI) was regarded as the primary outcome. The body surface area (BSA) and the dermatology life quality index (DLQI) were additionally considered as dermatological outcomes. Probing pocket depth, recession depth, clinical attachment level periodontal inflamed surface area, and [full mouth plaque score] etc, periodontal inflamed surface area, and full-mouth plaque and bleeding scores (FMPS/FMBS) were also measured. RESULTS: Periodontal therapy in the test group led to statistically significant lower PASI scores at 10 weeks (mean = 3.15; standard deviation [SD] = 3.78) compared to the control group (mean = 7.11; SD = 6.09) (mean difference [MD] = -4.0; 95% confidence interval [CI]: -6.3, -1.6; p = .001). The test group also showed improvements in BSA (MD = -4.3) and periodontal parameters compared to the control group. DLQI only showed a non-statistically significant tendency (MD = -2.0). CONCLUSION: Steps 1-2 of periodontal therapy showed an additional effect over conventional dermatological treatment in reducing the severity and extent of psoriasis (Clinicaltrials.gov: NCT05311501).

Are periodontitis and psoriasis associated? A pre-clinical murine model.

AIM: To investigate the bidirectional influence between periodontitis and psoriasis, using the respective experimental models of ligature- and imiquimod-induced diseases on murine models. MATERIALS AND METHODS: Thirty-two C57/BL6J mice were randomly allocated to four experimental groups: control (P- Pso-), ligature-induced periodontitis (P+ Pso-), imiquimod-induced psoriasis (P- Pso+) and periodontitis and psoriasis (P+ Pso+). Samples (maxilla, dorsal skin and blood) were harvested immediately after death. Measures of periodontitis (distance between the cemento-enamel junction and alveolar bone crest [CEJ-ABC] and the number of osteoclasts) and psoriasis (epidermal thickness and infiltrate cell [/0.03mm2]) severity as well as systemic inflammation (IL-6, IL-17A, TNF-α) were collected. RESULTS: The P+ Pso+ group exhibited the most severe experimental periodontitis and psoriasis, with the highest values of CEJ-ABC, number of osteoclasts, epidermal thickness and infiltrate cells in the dorsal skin, as well as the highest blood cytokine concentration. The P+ Pso- group presented with higher cell infiltrate (/0.03mm2) compared to the control group (p <.05), while the P- Pso+ group showed substantially higher alveolar bone loss (CEJ-ABC) than the control group (p <.05). CONCLUSIONS: Experimental periodontitis may initiate and maintain psoriasiform skin inflammation and, vice versa, experimental psoriasis may contribute to the onset of periodontitis. In a combined model of the diseases, we propose a bidirectional association between periodontitis and psoriasis via systemic inflammation.

Association between toothbrushing and cardiovascular risk factors: a cross-sectional study using Korean National Health and Nutrition Examination Survey 2015-2017.

BACKGROUND: Previous studies have suggested that frequent toothbrushing is associated with a lower risk of future cardiovascular events. We sought to investigate further the relationship between toothbrushing, cardiovascular risk factors, and lifestyle behaviours. METHODS: We analysed a cross-sectional survey including 13,761 adults aged 30 years or older without a history of cardiovascular diseases from the Korean National Health and Nutritional Examination Survey. Conventional cardiovascular risk factors (blood pressure, lipid profiles, and fasting glucose), and inflammatory markers (high-sensitivity C-reactive protein [hsCRP], and white blood cell counts [WBC]) were investigated in relation to the frequency of toothbrushing. RESULTS: The estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk, calculated using the pooled cohort equations was 13.7%, 9.1%, and 7.3% for participants who reported toothbrushing 0-1, 2, and ≥ 3 times a day, respectively. Both conventional risk factors and inflammatory markers were significantly associated with frequent toothbrushing. However, after adjusting potential confounding factors such as age, sex, comorbidities, and lifestyle behaviours, only inflammatory markers were remained as significant factors. CONCLUSIONS: Oral hygiene behaviours are closely linked to cardiovascular risk factors. This study suggests that reduced systemic inflammatory burden may explain the benefit of improved oral hygiene in terms of cardiovascular risk.

Local delivery of nitric oxide prevents endothelial dysfunction in periodontitis.

AIMS: Increased cardiovascular disease risk underlies elevated rates of mortality in individuals with periodontitis. A key characteristic of those with increased cardiovascular risk is endothelial dysfunction, a phenomenon synonymous with deficiencies of bioavailable nitric oxide (NO), and prominently expressed in patients with periodontitis. Also, inorganic nitrate can be reduced to NO in vivo to restore NO levels, leading us to hypothesise that its use may be beneficial in reducing periodontitis-associated endothelial dysfunction. Herein we sought to determine whether inorganic nitrate improves endothelial function in the setting of periodontitis and if so to determine the mechanisms underpinning any responses seen. METHODS AND RESULTS: Periodontitis was induced in mice by placement of a ligature for 14 days around the second molar. Treatment in vivo with potassium nitrate, either prior to or following establishment of experimental periodontitis, attenuated endothelial dysfunction, as determined by assessment of acetylcholine-induced relaxation of aortic rings, compared to control (potassium chloride treatment). These beneficial effects were associated with a suppression of vascular wall inflammatory pathways (assessed by quantitative-PCR), increases in the anti-inflammatory cytokine interleukin (IL)-10 and reduced tissue oxidative stress due to attenuation of xanthine oxidoreductase-dependent superoxide generation. In patients with periodontitis, plasma nitrite levels were not associated with endothelial function indicating dysfunction. CONCLUSION: Our results suggest that inorganic nitrate protects against, and can partially reverse pre-existing, periodontitis-induced endothelial dysfunction through restoration of nitrite and thus NO levels. This research highlights the potential of dietary nitrate as adjunct therapy to target the associated negative cardiovascular outcomes in patients with periodontitis.

Periodontitis and metabolic diseases (diabetes and obesity): Tackling multimorbidity.

Noncommunicable diseases (NCDs) are multifactorial, long-term, chronic conditions that represent a burden to health-care systems worldwide as they can only be controlled rather than cured; hence, they require long-term care. With the exponential increase in NCDs, the occurrence of individuals presenting with more than one chronic disease is also rapidly rising. "Multimorbidity," defined as the presence of two or more long-term physical or mental disorders, is now considered a worldwide epidemic, affecting around 20% of the adult population. Periodontitis, diabetes, and obesity, all chronic inflammatory diseases, are an example of multimorbidity highly relevant to dental practitioners. Over the last three decades, the three-way relationship among the diseases has been vastly researched and accepted, with important contributions by European researchers. The interplay among periodontitis, diabetes, and obesity is sustained by shared biological mechanisms, such as systemic inflammation, insulin resistance, and metabolic dysfunction, as well as common lifestyle-related risk factors. As such, unhealthy lifestyles were found to generally increase systemic inflammation and insulin resistance and decrease immune function, hence, eventually increasing the risk of NCDs onset and the development of multimorbidity. This narrative review of the evidence supports the need for a paradigm shift from a "single-disease" to a "multiple-disease" framework, characterized by an integrated multidisciplinary approach, which should include lifestyle modification interventions to successfully tackle multimorbid periodontitis and metabolic diseases (diabetes and obesity). A multidisciplinary integrated care pathway in both dental and medical settings should be considered to further tackle the global health challenge of multimorbidity.

Complications and treatment errors in periodontal therapy in medically compromised patients.

Patients who are medically compromised may be at an increased risk of complications and treatment errors following periodontal therapy. A review of the evidence on the topic is presented, in relation to the type of complication reported, of periodontal treatment, and of patients' medical status. Further, a framework for risk assessment and appropriate treatment modifications is introduced, with the aim of facilitating the management of patients with existing comorbidities and reducing the incidence of treatment complications.

Comparative evidence of different surgical techniques for the management of vertical alveolar ridge defects in terms of complications and efficacy: A systematic review and network meta-analysis.

AIM: To systematically appraise the available evidence on vertical ridge augmentation (VRA) techniques and estimate a treatment-based ranking on the incidence of complications as well as their clinical effectiveness. MATERIALS AND METHODS: Searches were conducted in six databases to identify randomized clinical trials comparing VRA techniques up to November 2022. The incidence of complications (primary) and of early, major, surgical and intra-operative complications, vertical bone gain (VBG), marginal bone loss, need for additional grafting, implant success/survival, and patient-reported outcome measures (secondary) were chosen as outcomes. Direct and indirect effects and treatment ranking were estimated using Bayesian pair-wise and network meta-analysis (NMA) models. RESULTS: Thirty-two trials (761 participants and 943 defects) were included. Five NMA models involving nine treatment groups were created: onlay, inlay, dense-polytetrafluoroethylene, expanded-polytetrafluoroethylene, titanium, resorbable membranes, distraction osteogenesis, tissue expansion and short implants. Compared with short implants, statistically significant higher odds ratios of healing complications were confirmed for all groups except those with resorbable membranes (odds ratio 5.4, 95% credible interval 0.92-29.14). The latter group, however, ranked last in clinical VBG. CONCLUSIONS: VRA techniques achieving greater VBG are also associated with higher incidence of healing complications. Guided bone regeneration techniques using non-resorbable membranes yield the most favourable results in relation to VBG and complications.

Treatment of periodontitis and C-reactive protein: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Systemic inflammation is implicated in the onset and progression of several chronic diseases. Periodontitis is a potential trigger of systemic inflammation. PURPOSE: To comprehensively appraise all the evidence on the effects of the treatment of periodontitis on systemic inflammation assessed by serum C-reactive protein (CRP) levels. DATA SOURCES: Six electronic databases were searched up to 10 February 2022 to identify and select articles in English language only. STUDY SELECTION: Twenty-six randomized controlled clinical trials reporting changes amongst 2579 participants about CRP levels at 6 months or more after treatment. DATA EXTRACTION: Two reviewers independently extracted data and rated the quality of studies. Meta-analyses were performed using random and fixed effect models. RISK OF BIAS: Risk of bias (RoB 2.0 tool) and quality of evidence (GRADEpro GDT tool) analyses were completed. DATA SYNTHESIS: Treatment of periodontitis reduced CRP levels by 0.69 mg/L (95% confidence interval: -0.97 to -0.40) after 6 months, but limited evidence was retrieved from studies with longer follow-ups. Similar findings were observed in participants with other co-morbidities in addition to periodontitis. Greatest reductions were observed in participants with concentrations of CRP >3 mg/L at baseline. LIMITATIONS: High level of heterogeneity. CONCLUSIONS: Treatment of periodontitis reduces serum CRP levels (up to 6 months follow-up) to a degree equivalent to that observed after traditional lifestyle or drug interventions. This evidence supports a causal association between periodontitis and systemic inflammation.

Hypertension and periodontitis: A joint report by the Italian society of hypertension (SIIA) and the Italian society of periodontology and implantology (SIdP).

An accumulating body of evidence supports an independent association between high blood pressure (BP) and periodontitis, possibly mediated by low-grade inflammation. This joint report by the Italian Society of Hypertension (SIIA) and the Italian Society of Periodontology and Implantology (SIdP) working group on Hypertension and Periodontitis (Hy-Per Group) provides a review of the evidence on this topic encompassing epidemiology, biological plausibility, relevance, magnitude, and treatment management. Consensus recommendations are provided for health professionals on how to manage BP in individuals showing signs of poor oral health. In summary, (1) large epidemiological studies highlight that individuals with periodontal diseases have increased risk for high/uncontrolled BP independent of confounders; (2) mechanistically, low-grade inflammation might have a causal role in the association; (3) BP profile and control might benefit from periodontal treatment in pre-hypertensive and hypertensive individuals; (4) oral health status should be evaluated as a potential risk factor for high/uncontrolled BP, and effective oral care should be included as an adjunct lifestyle measure during hypertension management. Further research is needed to optimize BP management in individuals with poor oral health.

Remote Ischemic Preconditioning Protects Against Endothelial Dysfunction in a Human Model of Systemic Inflammation: A Randomized Clinical Trial.

OBJECTIVE: Inflammation, oxidative stress, and endothelial dysfunction are known to contribute to ischemia-reperfusion injury. Remote ischemic preconditioning (RIPC) protects from endothelial dysfunction and the damage induced by ischemiareperfusion. Using intensive periodontal treatment (IPT), an established human model of acute systemic inflammation, we investigated whether RIPC prevents endothelial dysfunction and modulates systemic levels of inflammation and oxidative stress. APPROACH AND RESULTS: Forty-nine participants with periodontitis were randomly allocated to receive either 3 cycles of ischemia-reperfusion on the upper limb (N=24, RIPC) or a sham procedure (N=25, control) before IPT. Endothelial function assessed by flow-mediated dilatation of the brachial artery, inflammatory cytokines, markers of vascular injury, and oxidative stress were evaluated at baseline, day 1, and day 7 after IPT. Twenty-four hours post-IPT, the RIPC group had lower levels of IL-10 (interleukin-10) and IL-12 (interleukin-12) compared with the control group (P<0.05). RIPC attenuated the IPTinduced increase in IL-1ß (interleukin-1ß), E-selectin, sICAM-3 (soluble intercellular adhesion molecule 3), and sTM (soluble thrombomodulin) levels between the baseline and day 1 (P for interaction <0.1). Conversely, oxidative stress was differentially increased at day1 in the RIPC group compared with the control group (P for interaction <0.1). This was accompanied by a better flow-mediated dilatation (mean difference 1.75% [95% CI, 0.428­3.07], P=0.011). After 7 days from IPT, most of the inflammatory markers, endothelial-dependent and -independent vasodilation, were similar between groups. CONCLUSIONS: RIPC prevented acute endothelial dysfunction by modulation of inflammation and oxidation processes in patients with periodontitis following exposure to an acute inflammatory stimulus. REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT03072342; Unique identifier: NCT03072342.

Periodontitis and Systemic Lupus Erythematosus: A systematic review and meta-analysis.

This systematic review and meta-analysis evaluated the association between periodontitis (PD) and systemic lupus erythematosus (SLE). A systematic search was conducted through the following electronic databases: Cochrane Library, MEDLINE, EMBASE, Scopus, LILACS, CINAHL and SIGLE (System for Information on Grey Literature in Europe) for relevant publications up to September 2020 with no language restriction. The association between PD and SLE was assessed by the prevalence of PD in SLE patients (both sex and females only) as the primary outcome. Secondary outcomes included differences in common gingival parameters including probing pocket depth (PPD), clinical attachment level (CAL), disease activity index (SLEDAI) scores of SLE patients with or without PD. A total of 1183 citations and 22 full text articles were screened. Eighteen articles were included in the qualitative synthesis, and 13 in the quantitative analysis. SLE diagnosis was associated with greater odds of PD (OR = 1.33, 95% Confidence Interval [CI]: 1.20-1.48), but these were non-significant when examined in females (OR = 3.20, 95%CI: 0.85-12.02). Patients with SLE exhibited no differences in PPD (SMD: -0.09 mm, 95%CI: -0.45-0.27) and CAL (SMD: 0.05 mm, 95%CI: -0.30-0.40) when compared with systemically healthy controls. PD diagnosis was, however, associated with higher SLEDAI scores in patients suffering from SLE (SMD: 0.68, 95% CI: 0.03-1.32). PD and SLE are both inflammatory diseases and their association could be bi-directional. This review suggested that the patients with SLE have greater odds of suffering with PD. Further investigations are required to assess the association between PD and SLE.

Invasive dental treatment and acute vascular events: A systematic review and meta-analysis.

BACKGROUND: Acute infection/inflammation increases the risk of acute vascular events (AVEs). Invasive dental treatments (IDTs) trigger short-term acute inflammation. PURPOSE: The aim of this work is to critically appraise the evidence linking IDTs and AVEs. DATA SOURCES: Six bibliographical databases were searched up to 31 August 2021. A systematic review following PRISMA guidelines was performed. STUDY SELECTION: Intervention and observational studies reporting any AVEs following IDT were included. DATA EXTRACTION: Two reviewers independently extracted data and rated the quality of studies. Data were pooled using fixed-effect, inverse variance weights analysis. RISK OF BIAS: Risk of bias was assessed by the Newcastle-Ottawa Quality Assessment Scale for observational studies and the Cochrane Handbook-Rob 2.0 for randomized controlled trials. DATA SYNTHESIS: In 3 out of 16 clinical studies, a total of 533,175 participants, 124,344 myocardial infarctions, and 327,804 ischaemic strokes were reported. Meta-analysis confirmed that IDT did not increase incidence ratios (IR) for combined vascular events either at 1-4 weeks (IR of 1.02, 95% CIs: 0.92 to 1.13) and at 5-8 weeks (IR of 1.04, 95% CIs: 0.97 to1.10) after treatment. LIMITATIONS: A high level of heterogeneity (study designs and time point assessments) was found. CONCLUSION: Patients who received IDT exhibited no substantial increase in vascular risk over 8 weeks post treatment.

Impact of the treatment of periodontitis on systemic health and quality of life: A systematic review.

AIM: To investigate the effect of treatment of periodontitis on systemic health outcomes, pregnancy complications, and associated quality of life. MATERIALS AND METHODS: Systematic electronic searches were conducted to identify randomized controlled trials with minimum 6-month follow-up and reporting on the outcomes of interest. Qualitative and quantitative analyses were performed as deemed suitable. RESULTS: Meta-analyses confirmed reductions of high-sensitivity C-reactive protein (hs-CRP) [0.56 mg/L, 95% confidence interval (CI) (-0.88, -0.25), p < .001]; interleukin (IL)-6 [0.48 pg/ml, 95% CI (-0.88, -0.08), p = .020], and plasma glucose [1.33 mmol/l, 95% CI (-2.41, -0.24), p = .016], and increase of flow-mediated dilation (FMD) [0.31%, 95% CI (0.07, 0.55), p = .012] and diastolic blood pressure [0.29 mmHg, 95% CI (0.10, 0.49), p = .003] 6 months after the treatment of periodontitis. A significant effect on preterm deliveries (<37 weeks) was observed [0.77 risk ratio, 95% CI (0.60, 0.98), p = .036]. Limited evidence was reported on quality-of-life (QoL) outcomes in the included studies. CONCLUSIONS: Treatment of periodontitis results in systemic health improvements including improvement in cardiometabolic risk, reduction in systemic inflammation and the occurrence of preterm deliveries. Further research is however warranted to confirm whether these changes are sustained over time. Further, appropriate QoL outcomes should be included in the study designs of future clinical trials.

Periodontal therapy and treatment of hypertension-alternative to the pharmacological approach. A systematic review and meta-analysis.

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.

Periodontal therapy and cardiovascular risk.

Cardiovascular diseases are the worldwide leading cause of mortality. Cardiovascular diseases are noncommunicable conditions with a complex pathogenesis, and their clinical manifestations include major cardiovascular events such as myocardial infarction and stroke. Epidemiologic evidence suggests a consistent association between periodontitis and increased risk of cardiovascular diseases. Some evidence supports a beneficial effect of the treatment of periodontitis on both surrogate and hard cardiovascular outcomes. This narrative review has been conducted as an update of the most recent evidence on the effects of periodontitis treatment on cardiovascular outcomes since the last commissioned review of the European Federation of Periodontology-American Academy of Periodontology World Workshop in 2012. Newer evidence originating from published randomized controlled trials confirms a positive effect of periodontal treatment on surrogate measures of cardiovascular diseases, whereas there have been no randomized controlled trials investigating the effect of periodontal treatment on the incidence of cardiovascular disease events such as myocardial infarction and stroke. In conclusion, there is sufficient evidence from observational and experimental studies on surrogate cardiovascular measures to justify the design and conduct of appropriately powered randomized controlled trials investigating the effect of effective periodontal interventions on cardiovascular disease outcomes (ie, myocardial infarction and stroke) with adequate control of traditional cardiovascular risk factors.

Obesity as predictive factor of periodontal therapy clinical outcomes: A cohort study.

AIM: The study aim was to investigate the predictive role of obesity on clinical response following non-surgical periodontal therapy in individuals with severe periodontitis. METHODS: A total of 57 BMI obese and 58 BMI normal non-smoker adults with periodontitis (defined as probing pocket depths (PPD) of ≥5 mm and alveolar bone loss of >30% with >50% of the teeth affected) received non-surgical periodontal therapy. Periodontal status was based upon PPD, clinical attachment level (CAL) and full-mouth bleeding score (FMBS). Mean PPD, percentage sites PPD >4 mm, percentage sites PPD >5 mm and FMBS at 2 and 6 months were outcome variables. Propensity score analysis was used to assess the effect of obesity on outcome variables after adjusting for confounders. RESULTS: Statistically significant higher clinical measures (mean PPD, mean percentage of sites with PPD >4 mm, mean percentage of sites with PPD >5 mm and FMBS) were observed in the obese group than the normal group at baseline, 2 and 6 months after therapy (p < .01). At 2 and 6 months, obesity was associated with worse mean PPD (p < .05), percentage sites with PPD >4 mm (p < .05), percentage sites with PPD > 5mm (p < .05) and FMBS (p < .01), independent of age, gender, ethnicity or plaque levels. CONCLUSIONS: Obesity compared to normal BMI status was an independent predictor of poorer response following non-surgical periodontal therapy.

Periodontitis and systemic markers of neurodegeneration: A case-control study.

AIM: To investigate whether periodontitis is associated with amyloid beta (Aß) peptides and whether systemic inflammation could act as a potential mediator of this link. MATERIALS AND METHODS: A case-control study was designed including 75 patients with periodontitis (cases) and 75 age-balanced and gender-matched participants without periodontitis (controls). Full-mouth periodontal evaluation was performed in all participants. Demographic, clinical and behaviour data were also recorded. Fasting blood samples were collected, and serum levels of interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), Aß1-40 and Aß1-42 were determined. RESULTS: Cases showed higher levels of IL-6 (8.7 ± 3.2 vs. 4.8 ± 0.5 pg/ml), hs-CRP (3.3 ± 1.2 vs. 0.9 ± 0.7 mg/L), Aß1-40 (37.3 ± 6.0 vs. 30.3 ± 1.8 pg/ml) and Aß1-42 (54.5 ± 10.6 vs. 36.5 ± 10.0 pg/ml) when compared to controls (all p < .001). Diagnosis of periodontitis was statistically significantly associated with circulating Aß1-40 ( ßcoefficientadjusted  = 6.9, 95% CI: 5.4-8.3; p < .001) and Aß1-42 ( ßcoefficientadjusted  = 17.8, 95% CI: 14.4-21.3; p < .001). Mediation analysis confirmed hs-CRP and IL-6 as mediators of this association. CONCLUSIONS: Periodontitis is associated with increased peripheral levels of Aß. This finding could be explained by enhanced systemic inflammation that can be seen in patients with periodontitis.

Periodontitis and cardiovascular diseases: Consensus report.

BACKGROUND: In Europe cardiovascular disease (CVD) is responsible for 3.9 million deaths (45% of deaths), being ischaemic heart disease, stroke, hypertension (leading to heart failure) the major cause of these CVD related deaths. Periodontitis is also a chronic non-communicable disease (NCD) with a high prevalence, being severe periodontitis, affecting 11.2% of the world's population, the sixth most common human disease. MATERIAL AND METHODS: There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs, in particular CVD. In 2012 a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. In the last five years important new scientific information has emerged providing important emerging evidence to support these associations RESULTS AND CONCLUSIONS: The present review reports the proceedings of the workshop jointly organised by the EFP and the World Heart Federation (WHF), which has updated the existing epidemiological evidence for significant associations between periodontitis and CVD, the mechanistic links and the impact of periodontal therapy on cardiovascular and surrogate outcomes. This review has also focused on the potential risk and complications of periodontal therapy in patients on anti thrombotic therapy and has made recommendations for dentists, physicians and for patients visiting both the dental and medical practices.

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

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 ∼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. 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.

Severe periodontitis is linked with increased peripheral levels of sTWEAK and PTX3 in chronic migraineurs.

OBJECTIVES: Periodontitis (PD) and chronic migraine (CM) have been recently linked, and inflammatory processes and vascular endothelial changes are hypothesized as potential mediators of this relationship. The aim of this cross-sectional analysis was to investigate the potential association of PD with vascular systemic inflammation and complement activation in patients with CM. MATERIALS AND METHODS: Ninety-four chronic migraineurs underwent a full-mouth periodontal evaluation and a measure of PD activity and severity, namely the periodontal inflamed surface area (PISA) was calculated for each patient. We divided CM patients according to their periodontal status: mild PD (N = 14), moderate PD (N = 22), severe PD (N = 19), and non-PD (N = 39). Serum levels of C-reactive protein (CRP), pentraxin 3 (PTX3), soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), and complements C3 and C4 were measured outside of migraine attacks. RESULTS: We found that severe periodontal patients had significantly higher circulating levels of PTX3 and sTWEAK compared with those without PD (2475.3 ± 1646.8 pg/mL vs. 516.6 ± 1193.8 pg/mL, P < 0.0001 and 672.4 ± 118.2 pg/mL vs. 485.7 ± 112.2 pg/mL, P < 0.0001; respectively). For the remaining biomarkers, no significant differences were found between groups. Severe PD was independently associated with higher levels of PTX3 (ß = 1997.6, P < 0.0001) and sTWEAK (ß = 187.1, P < 0.0001) but not with CRP, C3, and C4. PISA positively correlated to PTX3 (r = 0.475, P < 0.0001) and sTWEAK (r = 0.386, P < 0.0001). CONCLUSIONS: Based on these preliminary results, severe PD was linked with vascular systemic inflammation in patients with CM. However, further longitudinal studies should be performed to confirm these findings. CLINICAL RELEVANCE: sTWEAK and PTX3 measured in serum could be used as biomarkers in the PD-CM link.