Aims: Recent studies hypothesized a role of gut microbiota favoring atherosclerosis via an increased oxidative stress, but data in peripheral artery disease (PAD) have not been provided yet. The aim of this study was to assess serum lipopolysaccharide (LPS) as well as oxidative stress in PAD patients and controls (CT). Furthermore, we wanted to analyze the relationship between LPS and the severity of atherosclerosis in the lower limb arteries. Results: Eighty consecutive subjects, including 40 PAD patients and 40 CT were recruited. A cross-sectional study was performed to compare serum LPS, soluble Nox2-derived peptide (sNox2-dp), hydrogen peroxide (H₂O₂), H₂O₂ breakdown activity (HBA) and ankle brachial index (ABI) in these two groups. Serum zonulin was used to assess gut permeability. Compared with CT, PAD patients had significant higher values of LPS, zonulin, sNox2-dp, and H₂O₂; conversely ABI and HBA were significantly lower in PAD patients. LPS serum levels were associated with atherosclerotic burden as depicted by the inverse correlation with ABI. LPS was also associated with oxidative stress as shown by its direct correlation with markers of oxidative stress such as sNox2-dp, serum H₂O₂, and HBA. Finally, we found a significant correlation between LPS and zonulin. A multiple linear regression analysis showed that LPS was significantly associated only with ABI. Innovation and Conclusion: These findings suggest that LPS is elevated in PAD patients with a close association with the atherosclerotic burden and oxidative stress. The correlation between LPS and zonulin suggests that changes in gut permeability could be a potential trigger of LPS translocation in the peripheral circulation.

Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC. This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects. Seventy-eight children (2-18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed). Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H₂O₂) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis. Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT. Multivariable regression linked sNOX2 (standardized coefficient β: 0.284; SE: 0.040; p = 0.01) and H₂O₂ (standardized coefficient β: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient β:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient β:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels. Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure.

The thrombotic physiopathology of antiphospholipid syndrome (APS) is complex, heterogeneous, and dynamic. While venous thromboembolism (VTE) is the most common initial presentation, arterial thrombotic events (ATE) become more frequent in advanced stages and are associated with high morbidity and mortality. Despite the use of oral anticoagulants (OACs), thrombotic APS remains associated with a high risk of recurrent thrombosis. Given their potential antithrombotic effects capable of reducing the risk of both VTE and ATE, statins have been proposed as an adjunctive therapy to OACs for patients with APS and recurrent thrombosis. However, this recommendation is primarily based on studies not specifically conducted in APS populations, with only preclinical data or evidence from retrospective observational studies available from APS patients cohorts. For these reasons, this narrative review aims to synthesise the studies evaluating the potential antithrombotic effects of statins in patients with APS, highlighting the progress made and identifying areas for future research.

Background and aims: Offspring of patients with early myocardial infarction are at higher cardiovascular risk, but the underlying physio-pathological mechanism is unclear. NADPH oxidase-type 2 (NOX-2) plays a pivotal role as mediator of oxidative stress and could be involved in activating platelets in these patients. Furthermore, altered intestinal permeability and serum lipopolysaccharide (LPS) could be a trigger to promote NOX-2 activation and platelet aggregation. This study aims to evaluate the behavior of low grade endotoxemia, oxidative stress and platelet activation in offspring of patients with early myocardial infarction. Methods: We enrolled, in a cross-sectional study, 46 offspring of patients with early myocardial infarction and 86 healthy subjects (HS). LPS levels and gut permeability (assessed by zonulin), oxidative stress (assessed by serum NOX-2-derived peptide (sNOX2-dp) release, hydrogen peroxide (H₂O₂) production and isoprostanes), serum nitric oxide (NO) bioavailability and platelet activation (by serum thromboxane B2 (TXB2) and soluble P-Selectin (sP-Selectin)) were analyzed. Results: Compared to HS, offspring of patients with early myocardial infarction had higher values of LPS, zonulin, serum isoprostanes, sNOX2-dp H₂O₂, TXB2, p-selectin and lower NO bioavailability. Logistic regression analysis showed that the variables associated with offspring of patients with early myocardial infarction were LPS, TXB2 and isoprostanes. The multiple linear regression analysis confirmed that serum NOX-2, isoprostanes, p-selectin and H₂O₂ levels were significantly associated to LPS. Furthermore, serum LPS, isoprostanes and TXB2 levels were significantly associated with sNOX-2-dp. Conclusions: Offspring of patients with early myocardial infarction have a low grade endotoxemia that could generate oxidative stress and platelet activation increasing their cardiovascular risk. Future studies are needed to understand the role of dysbiosis in this population.

Mechanical prosthetic heart valves (MPHVs) are commonly used for valvular heart disease in patients with a long life expectancy. Few longitudinal data on the specific causes of hospitalization in patients with MPHV are available. We investigated the risk of all-cause hospitalization and mortality in patients with MPHV. We performed a prospective, observational, ongoing study including consecutive patients with MPHVs who were referred to the atherothrombosis outpatient clinic of the Policlinico Umberto I of Rome for the vitamin K antagonist management. Study end points were all-cause, cardiovascular hospitalization, and overall mortality. We included 305 patients with MPHV (38.4% women, median age 60.2 years). The site of MPHV was aortic in 53.5%, mitral in 29.5%, and mitroaortic in 17%. During a median follow-up of 57.3 months, 142 hospitalizations occurred (8.16 per 100 person-years). The most common causes of hospitalization were cardiovascular disease (3.62 per 100 person-years), infections, surgery, and bleeding. The predictors of cardiovascular hospitalization were atrial fibrillation (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.04 to 2.95, p = 0.035), previous stroke/transient ischemic attack (HR 2.96, 95% CI 1.59 to 5.48, p = 0.001), and peripheral artery disease (HR 2.42, 95% CI 1.09 to 5.36, p = 0.030). During a median follow-up of 97.2 months, 61 deaths occurred (2.43 per 100 person-years). Age was directly associated with the risk of death (HR 1.088, 95% CI 1.054 to 1.122, p < 0.001), whereas the time in therapeutic range higher than the median was inversely associated (HR 0.436, 95% CI 0.242 to 0.786, p = 0.006). In conclusion, patients with MPHV had a high incidence of hospitalizations, especially cardiovascular-related. The incidence of death is high; however, it may be decreased by maintaining a good quality of anticoagulation. (c) 2024 The Author(s). Published by Elsevier Inc.

Background: Few data are available on the outcomes of patients with venous thromboembolism (VTE) on long-term reduced dose of direct oral anticoagulants (DOACs). We evaluated the effectiveness and safety of reduced dose of DOACs for the extended treatment of VTE. Methods: In this monocenter, ambispective cohort study, 140 patients receiving a reduced dose of DOACs for VTE were included. The primary outcomes were recurrent VTE, major bleeding and clinically relevant non-major bleeding. The secondary outcomes were arterial events and minor bleedings. The incidence of the primary outcomes was calculated. The rate for secondary outcomes was descriptively reported. Results: The mean age of the overall cohort was 72 years. Half of the patients were female, 51.4% had a persistent risk factor, 40.0% an unprovoked VTE, and 8.6% a minor transient risk factor. Most patients had lower extremity deep vein thrombosis with or without pulmonary embolism (55.0%) and received apixaban (73.6%) or rivaroxaban (14.3%) for a mean duration of 2.7 years. Regarding the primary outcomes, there was one recurrent VTE (0.7%), four major bleedings (2.9%) and two clinically relevant non-major bleedings (1.4%). Regarding the secondary outcomes, there were four acute ischemic strokes (2.9%) and two minor bleedings (1.4%). Conclusions: Reduced dose of DOACs was associated with a low rate of recurrent VTE and an acceptably low rate of bleeding complications. The rate of arterial events during follow-up suggests the need for an assessment of cardiovascular risk factors in this study population.