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.

Direct and indirect links between brain regions and cardiac function have been reported. We performed a systematic literature review to summarize current knowledge regarding the associations of heart rate variability (HRV) and brain region morphology, activity and connectivity involved in autonomic control at rest in healthy subjects. Both positive and negative correlations of cortical thickness and gray matter volumes of brain structures with HRV were observed. The strongest were found for a cluster located within the cingulate cortex. A decline in HRV, as well as cortical thickness with increasing age, especially in the orbitofrontal cortex were noted. When associations of region-specific brain activity with HRV were examined, HRV correlated most strongly with activity in the insula, cingulate cortex, frontal and prefrontal cortices, hippocampus, thalamus, striatum and amygdala. Furthermore, significant correlations, largely positive, between HRV and brain region connectivity (in the amygdala, cingulate cortex and prefrontal cortex) were observed. Notably, right-sided neural structures may be preferentially involved in heart rate and HRV control. However, the evidence for left hemispheric control of cardiac vagal function has also been reported. Our findings provide support for the premise that the brain and the heart are interconnected by both structural and functional networks and indicate complex multi-level interactions. Further studies of brain–heart associations promise to yield insights into their relationship to health and disease.

Endothelial dysfunction, characterized by the loss of nitric oxide bioavailability, is a key element in the pathogenesis of atherosclerosis and an important prognostic factor in cardiovascular diseases. Therefore, the development of reliable, safe, and noninvasive methods of endothelial function assessment is important for their use in cardiovascular risk stratification. Brachial artery flow‑mediated dilation (FMD) is widely used in research but technical difficulties and problems with calibration between laboratories limit its clinical use. Reactive hyperemia-peripheral artery tonometry (RH‑PAT, EndoPAT) has been developed as a simpler, cheaper, and potentially more reproducible method. We aimed to investigate associations between RH‑PAT and FMD in relation to atherosclerotic risk factor profile. The study involved 80 subjects (52 men, 28 women) aged 43.6 ±14.8 years, with moderate‑to‑low cardiovascular risk (mean SCORE, 2.2% ±2%), in whom FMD, RH‑PAT, and intima-media thickness (IMT) were determined. The reactive hyperemia index (RHI) measured by RH‑PAT correlated with FMD (r = 0.35, P <0.01). However, no significant correlation was observed between RHI and IMT, SCORE, or the number of classical atherosclerotic risk factors (hypertension, smoking, diabetes, hypercholesterolemia), while FMD was significantly correlated with IMT (r = -0.53, P <0.001), risk factors (r = -0.55, P <0.05), and SCORE (r = -0.4, P <0.05). Despite its technical requirements, FMD is a more sensitive method than RH‑PAT in evaluating the effect of classical atherosclerotic risk factors on vascular endothelial function. Microvasculature response during RH‑PAT needs to be further studied, including the assessment of nonendothelial factors that may affect the measurements, before RH‑PAT becomes the universal tool for the evaluation of the endothelial cells.

Aims: Superior vena cava (SVC) isolation during atrial fibrillation catheter ablation is limited by the risk of collateral damage to the sinus node and/or the phrenic nerve. Due to its tissue-specificity, we hypothesized the feasibility and safety of pulsed-field ablation (PFA)–based SVC isolation. Methods and results: One hundred and five consecutive patients undergoing PFA-based AF catheter ablation were prospectively included. After pulmonary vein isolation (±posterior wall isolation and electrical cardioversion), SVC isolation was performed using a standardized workflow. Acute SVC isolation was achieved in 105/105 (100%) patients after 6 ± 1 applications. Transient phrenic nerve stunning occurred in 67/105 (64%) patients but without phrenic nerve palsy at the end of the procedure and at hospital discharge. Transient high-degree sinus node dysfunction occurred in 5/105 (4.7%) patients, with no recurrence at the end of the procedure and until discharge. At the 3-month follow-up visit, no complication occurred. Conclusion: SVC isolation using a pentaspline PFA catheter is feasible and safe.