Jefferson Luís Vieira

Role of vascular inflammation in coronary artery disease: potential of anti-inflammatory drugs in the prevention of atherothrombosis. Inflammation and anti-inflammatory drugs in coronary artery disease.

AbstractCoronary artery disease (CAD) and acute myocardial infarction (AMI) are inflammatory pathologies, involving interleukins (ILs), such as IL-1β, IL-6 and tumor necrosis factor (TNF)-α, and acute phase proteins production, such as for C reactive protein (CRP). The process begins with retention of low-density lipoprotein (LDL) and its oxidation inside the intima, with the formation of the “foam cells.” Toll-like receptors and inflamassomes participate in atherosclerosis formation, as well as in the activation of the complement system. In addition to innate immunity, adaptive immunity is also associated with atherosclerosis through antigen-presenting cells, T and B lymphocytes. AMI also increases the expression of some ILs and promotes macrophage and lymphocyte accumulation. Reperfusion increases the expression of anti-inflammatory ILs (such as IL-10) and generates oxygen free radicals. Although CAD and AMI are inflammatory disorders, the only drugs with anti-inflammatory effect so far widely used in ischemic heart disease are aspirin and statins. Some immunomodulatory or immunosuppressive promising therapies, such as cyclosporine and colchicine, may have benefits in CAD. Methotrexate also has potential cardioprotective anti-inflammatory effects, through increased adenosine levels. The TETHYS trial (The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS trial) will evaluate low-dose methotrexate in ST elevation AMI. The CIRT (Cardiovascular Inflammation Reduction Trial), in turn, will evaluate low-dose methotrexate in patients with a high prevalence of subclinical vascular inflammation. The CANTOS (The Canakinumab Antiinflammatory Thrombosis Outcomes Study) will evaluate canakinumab in patients with CAD and persistently elevated CRP. The blockage of other potential targets, such as the IL-6 receptor, CC2 chemokine receptor and CD20, could bring benefits in CAD.

Systemic effects of controlled exposure to diesel exhaust: a meta-analysis from randomized controlled trials

Abstract Introduction: Ambient air pollution is associated with adverse cardiovascular events. This meta-analysis aimed to investigate the short-term association between air pollution and cardiovascular effects on healthy volunteers. Methods: We searched databases to identify randomized trials with controlled human exposures to either of two models for studying ambient particulate matter: diesel-exhaust or concentrated ambient particles. Estimates of size effect were performed using standardized mean difference (SMD). Heterogeneity was assessed with I2 statistics. Outcomes were vascular function estimated by forearm blood flow (FBF), blood pressure, heart rate, and blood analysis. Results: Database searches yielded 17 articles (n = 342) with sufficient information for meta-analyses. High levels of heterogeneity for the some outcomes were analyzed using random-effects model. The pooled effect estimate showed that short-term exposure to air pollution impaired FBF response from 2.7 to 2.5 mL/100 mL tissue/min (SMD 0.404; p = .006). There was an increase in 5000 platelet/mm3 following pollution exposure (SMD 0.390; p = .050) but no significant differences for other outcomes. Conclusion: Controlled human exposures to air pollution are associated with the surrogates of vascular dysfunction and increase in platelet count, which might be related to adverse cardiovascular events. Given the worldwide prevalence of exposure to air pollution, these findings are relevant for public health. KEY MESSAGES Controlled exposure to air pollution impairs vasomotor response, which is a surrogate for adverse cardiovascular events. This is the first meta-analysis from randomized clinical trials showing short-term association between air pollution and cardiovascular effects on healthy volunteers. Given the worldwide prevalence of exposure to air pollution, this finding is important for public health.

Effects of reducing exposure to air pollution on submaximal cardiopulmonary test in patients with heart failure: Analysis of the randomized, double-blind and controlled FILTER-HF trial

BACKGROUND Air pollution exposure could mitigate the health benefits of exercise in patients with heart failure (HF). We tested the effects of a respiratory filter on HF patients exposed to air pollution during exercise. METHODS AND RESULTS Ancillary analysis of the FILTER-HF trial, focused on the exercise outcomes. In a randomized, double-blind, 3-way crossover design, 26 HF patients and 15 control volunteers were exposed to clean air, unfiltered dilute diesel engine exhaust (DE), or filtered DE for 6min during a submaximal cardiopulmonary testing in a controlled-exposure facility. Prospectively collected data included six-minute walking test [6mwt], VO2, VE/VCO2 Slope, O2Pulse, pulmonary ventilation [VE], tidal volume, VD/Vt, oxyhemoglobin saturation and CO2-rebreathing. Compared to clean air, DE adversely affected VO2 (11.0±3.9 vs. 8.4±2.8ml/kg/min; p<0.001); 6mwt (243.3±13.0 vs. 220.8±13.7m; p=0.030); and O2Pulse (8.9±1.0 vs. 7.8±0.7ml/beat; p<0.001) in HF patients. Compared to DE, filtration reduced the particulate concentration from 325±31 to 25±6μg/m(3), and was associated with an increase in VO2 (10.4±3.8ml/kg/min; p<0.001 vs. DE) and O2Pulse (9.7±1.1ml/beat; p<0.001 vs. DE) in patients with HF. Filtration was associated with higher VE and CO2-rebreathing in both groups. VE/VCO2 Slope was higher among patients with HF. CONCLUSION DE adversely affects exercise capacity in patients with HF. A simple respiratory filter can reduce the adverse effects of pollution on VO2 and O2Pulse. Given the worldwide prevalence of exposure to traffic-related air pollution, these findings are relevant for public health especially in this highly susceptible population. The filter intervention holds great promise that needs to be tested in future studies.

ACUTE CARDIOVASCULAR CHANGES TO CONTROLLED DIESEL EXHAUST EXPOSURE IN HEALTH SUBJECTS: A POOLED SYSTEMATIC REVIEW AND META-ANALYSIS OF 373 PARTICIPANTS FROM RANDOMIZED CONTROLLED TRIALS

Ambient particulate matter (PM) is associated with adverse cardiovascular events. To review the evidence from Randomized Controlled Trials (RCT) for the short-term association between PM and acute cardiovascular consequences. A systematic review and meta-analysis of RCT was performed using PubMed