Innate immunity and chronic inflammation are involved in atherosclerosis and atherothrombosis, leading to target organ damage in essential hypertension (EH). However, the role of neutrophils in EH is still elusive. We investigated the association between angiotensin II (Ang II) and neutrophil extracellular traps (NETs) in pathogenesis of EH. Plasma samples, kidney biopsies, and surgical specimens of abdominal aortic aneurysms (AAAs) from patients with EH were used. Cell-based assays, NETs/human aortic endothelial cell cocultures, and in situ studies were performed. Increased plasma levels of NETs and tissue factor (TF) activity were detected in untreated, newly diagnosed patients with EH. Stimulation of control neutrophils with plasma from patients with untreated EH generated TF-enriched NETs promoting endothelial collagen production. Ang II induced NETosis in vitro via an ROS/peptidylarginine deiminase type 4 and autophagy-dependent pathway. Circulating NETs and thrombin generation levels were reduced substantially in patients with EH starting treatment with Ang II receptor blockers, whereas their plasma was unable to trigger procoagulant NETs. Moreover, TF-bearing NETotic neutrophils/remnants accumulated in sites of interstitial renal fibrosis and in the subendothelial layer of AAAs. These data reveal the important pathogenic role of an Ang II/ROS/NET/TF axis in EH, linking thromboinflammation with endothelial dysfunction and fibrosis.

The objective of this systematic review and meta‐analysis is to determine whether nocturnal blood pressure fall, expressed by dipping patterns according to ambulatory blood pressure monitoring (ABPM), is a risk factor for cardiovascular events (CVEs) in untreated hypertensives. Α thorough systematic literature search at MEDLINE, Embase, Cochrane Library, and gray literature was conducted through March 2020. Two reviewers screened studies and assessed dipping patterns of untreated hypertensives using ABPM with a follow‐up >6 months. Newcastle‐Ottawa scale was used for risk of bias assessment. We initially identified 463 reports; of which, seven cohort studies were eligible for meta‐analysis enrolling 10 438 untreated hypertensives. Untreated patients classified as dippers at baseline (n = 7081) had significant lower risk of CVEs and total mortality compared to non‐dippers (n = 3,357) [RR = 0.67, 95% CI (0.49, 0.92); RR = 0.71, 95% CI (0.59, 0.86)]. However, when patients were further classified into four dipping groups, only reverse dippers, yet not extreme dippers or non‐dippers, were at increased risk for CVEs compared to dippers [RR = 0.47, 95% CI (0.33, 0.66)]. Likewise, only reverse dippers had a higher stroke risk than dippers [RR = 0.39, 95% CI (0.22, 0.72)]. When compared with the whole group of dippers (including extreme dippers), non‐dipping alone (excluding reverse dipping) was not a significant risk factor for CVEs [RR = 0.84, 95% CI (0.61, 1.16)] or total mortality [RR = 0.84, 95% CI (0.61, 1.16); RR = 0.78, 95% CI (0.53, 1.13), respectively]. Untreated hypertensives may benefit more from the evaluation of reverse dipping rather than the non‐dipping phenomenon in general.

Rheumatoid arthritis is characterized by early and accelerated atherosclerosis leading to increased cardiovascular morbidity and mortality. Beyond traditional cardiovascular risk factors, several pathogenetic mechanisms have been proposed, including emerging inflammatory and autoimmune mechanisms. Inflammatory stimuli are now believed to cause vascular damage, which can be estimated by well-established noninvasive techniques. Carotid intima-media thickness, pulse-wave velocity and flow-mediated dilatation, markers of subclinical atherosclerosis, arterial stiffness, and endothelial function, respectively, have been recently used to detect vascular dysfunction in the wide spectrum of autoimmune diseases. The role of anti-tumor necrosis factor α and novel biologic agents remains unclear, although early control of the inflammatory process seems crucial for reducing cardiovascular risk. Considering the importance of cardiovascular risk management, further well-designed studies are warranted to clarify the potential benefits and harms of anti-inflammatory treatment.

Background: Galectin‐3 has emerged as a promising novel biomarker of cardiovascular fibrosis in patients with cardiovascular diseases.Hypothesis: We investigated whether galectin‐3 correlates with markers of vascular fibrosis, subclinical atherosclerosis, and cardiac function in patients with rheumatoid arthritis (RA), a disease accompanied by high cardiovascular risk.Methods: RA and non‐RA individuals underwent applanation tonometry, carotid ultrasound, and impedance cardiography, to obtain markers of arterial stiffness, subclinical atherosclerosis, and myocardial function, respectively. Cardiovascular risk was estimated from the Framingham Heart Study. Serum levels of galectin‐3 were determined by enzyme‐linked immunosorbent assay.Results: Galectin‐3 was elevated in RA patients (n = 85) compared to controls (n = 39), but this difference was no longer significant after adjustment for the presence of cardiovascular comorbidities. In the univariate analysis, galectin‐3 significantly correlated with markers of vascular stiffness (including pulse wave velocity, central blood pressure, central and peripheral pulse pressure, and total arterial compliance); atherosclerosis (carotid intima‐media thickness); myocardial blood flow (cardiac output, stroke volume) and contractibility (acceleration and velocity index); systemic vascular resistance, and estimated cardiovascular risk. Multivariate analysis models revealed an independent association between galectin‐3 and both cardiac output (β = −0.274, P = 0.039), as well as systemic vascular resistance (β = 0.266, P = 0.039).Conclusions: In a relatively well‐controlled cohort of RA patients with low‐grade systemic inflammation and long‐standing disease, serum galectin‐3 might be useful as a marker of cardiac function and cardiovascular fibrosis.

Background: The objective of this systematic review and meta-analysis is to investigate whether nocturnal blood pressure fall, expressed by dipping patterns according to 24 h ambulatory blood pressure monitoring (ABPM), is associated with abnormal cognitive function (cognitive impairment or dementia).Methods: We systematically searched PubMed, Embase, and Cochrane databases to identify original articles through December 2022. We included any study with at least ten participants reporting on all-cause dementia or cognitive impairment incidence (primary outcome) or validated cognitive tests (secondary outcome) among ABPM patterns. We assessed risk of bias using Newcastle–Ottawa Quality Assessment Scale. We pooled odds ratios (OR) and standardized mean differences (SMD) using random-effect models for primary and secondary outcome, respectively.Results: In the qualitative synthesis, 28 studies examining 7595 patients were included. The pooled analysis of 18 studies showed that dippers had a 51% [OR 0.49(0.35–0.69)] lower risk of abnormal cognitive function and a 63% [OR 0.37(0.23–0.61)] lower risk of dementia alone, compared to non-dippers. Reverse dippers presented an up to sixfold higher risk [OR 6.06(3.15–11.64)] of abnormal cognitive function compared to dippers and an almost twofold higher risk [OR 1.81(1.26–2.6)] compared to non-dippers. Reverse dippers performed worse in global function neuropsychological tests compared with both dippers [SMD − 0.66(− 0.93 to − 0.39)] and non-dippers [SMD − 0.35(− 0.53 to − 0.16)].Conclusion: Dysregulation of the normal circadian BP rhythm, specifically non-dipping and reverse dipping is associated with abnormal cognitive function. Further studies are required to determine potential underlying mechanisms and possible prognostic or therapeutic implications.Protocol registration: PROSPERO database (ID: CRD42022310384).