Antonio Casella-Filho

Increased circulating levels of matrix metalloproteinase (MMP)-8, MMP-9, and pro-inflammatory markers in patients with metabolic syndrome

BACKGROUND Metabolic syndrome (MetS) predisposes to cardiovascular complications. Increased concentrations of pro-inflammatory mediators and imbalanced concentrations of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) may reflect the pathophysiology of MetS. We compared the circulating levels of MMPs, TIMPs, and inflammatory mediators in MetS patients with those found in healthy controls. METHODS We studied 25 healthy subjects and 25 MetS patients. The plasma levels of pro-MMP-2 and pro-MMP-9 were determined by gelatin zymography. The plasma concentrations of MMP-8, MMP-3, TIMP-1, TIMP-2, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), intercellular adhesion molecule (sICAM-1), and sP-selectin were measured by ELISA kits. RESULTS We found higher sP-selectin, sICAM-1, MCP-1, and IL-6 (all P<0.05) concentrations in MetS patients compared with healthy controls. No differences in pro-MMP-2, MMP-3, and TIMP-2 levels were found (all P>0.05). However, we found higher pro-MMP-9, MMP-8, and TIMP-1 levels in MetS patients compared with healthy controls (all P<0.05). CONCLUSIONS Patients with MetS have increased circulating concentrations of pro-MMP-9, MMP-8, and TIMP-1 that are associated with increased concentrations of pro-inflammatory mediators and adhesion molecules. These findings suggest that MMPs may have a role in the increased cardiovascular risk of MetS patients. Pharmacological interventions targeting MMPs, especially MMP-9 and MMP-8 deserve further investigation in MetS patients.

Enhanced concentrations of relevant markers of nitric oxide formation after exercise training in patients with metabolic syndrome.

Metabolic syndrome (MetS) denotes a clustering of risk factors that may affect nitric oxide (NO) bioavailability and predispose to cardiovascular diseases, which are delayed by exercise training. However, no previous study has examined how MetS affects markers of NO formation, and whether exercise training increases NO formation in MetS patients. Here, we tested these two hypotheses. We studied 48 sedentary individuals: 20 healthy controls and 28 MetS patients. Eighteen MetS patients were subjected to a 3-month exercise training (E+group), while the remaining 10 MetS patients remained sedentary (E-group). The plasma concentrations of nitrite, cGMP, and ADMA (asymmetrical dimethylarginine; an endogenous nitric oxide synthase inhibitor), and the whole blood nitrite concentrations were determined at baseline and after exercise training using an ozone-based chemiluminescence assay, and commercial enzyme immunoassays. Thiobarbituric acid reactive species (TBA-RS) were measured in the plasma to assess oxidative stress using a fluorometric method. We found that, compared with healthy subjects, patients with MetS have lower concentrations of markers of NO formation, including whole blood nitrite, plasma nitrite, and plasma cGMP, and increased oxidative stress (all P<0.05). Exercise training increased the concentrations of whole blood nitrite and cGMP, and decreased both oxidative stress and the circulating concentrations of ADMA (both P<0.05). These findings show clinical evidence for lower endogenous NO formation in patients with MetS, and for improvements in NO formation associated with exercise training in MetS patients.

Endothelial Nitric Oxide Synthase Polymorphisms and Susceptibility to Hypertension: Genotype Versus Haplotype Analysis

To the Editor: Zintzaras et al reported interesting results of a meta-analysis of all the available studies on the possible association between endothelial NO synthase ( eNOS ) polymorphisms and hypertension.1 They concluded that there is evidence for significant association between the 4b/4a variable number of tandem repeats polymorphism in intron 4 of the eNOS gene and susceptibility to …

Abdominal Obesity and Association With Atherosclerosis Risk Factors: The Uberlândia Heart Study

AbstractEctopic visceral fat (VF) and subcutaneous fat (SCF) are associated with cardiovascular risk factors. Gender differences in the correlations of cardiovascular disease risk factors and ectopic fat in the Brazilian population still lacking.Cross-sectional study with 101 volunteers (50.49% men; mean age 56.5 ± 18, range 19–74 years) drawn from the Uberlândia Heart Study underwent ultrasonography assessment of abdominal visceral adipose tissue with convex transducer of 3.5 MHz of frequency. The thickness of VF was ultrasonographically measured by the distance between the inner face of the abdominal muscle and the posterior face of abdominal aorta, 1 cm above the umbilicus. The SCF thickness was measured with a 7.5 MHz linear transducer transversely positioned 1 cm above the umbilical scar. The exams were always performed by the same examiner. Ectopic fat volumes were examined in relation to waist circumference, blood pressure, and metabolic risk factors.The VF was significantly associated with the levels of triglycerides (P < 0.01, r = 0.10), HDL cholesterol (P < 0.005, r = 0.15), total cholesterol (P < 0.01, r = 0.10), waist circumference (P < 0.0001, r = 0.43), systolic blood pressure (P < 0.001, r = 0.41), and diastolic blood pressure (P < 0.001, r = 0.32) in women, and with the levels of triglycerides (P < 0.002, r = 0,14), HDL cholesterol (P < 0.032, r = 0.07), glucose (P < 0.001, r = 0.15), alanine aminotransferase (ALT) (P < 0.008, r = 0.12), gamma-GT (P < 0.001, r = 0.30), waist circumference (P < 0.001, r = 0.52), systolic blood pressure (P < 0.001, r = 0.32), and diastolic blood pressure (P < 0.001, r = 0.26) in men. SCF was significantly associated with the levels of triglycerides (P < 0.01, r = 0.34), LDL cholesterol (P < 0.001, r = 0.36), total cholesterol (P < 0.05, r = 0.36), waist circumference (P < 0.0001, r = 0.62), systolic and diastolic blood pressure (P < 0.05, r = 0.34) in women, and with the waist circumference (P < 0.001, r = 0.065)), and MetS (P < 0.05, r = 0.11) in men.The VF and SCF were correlated with most cardiovascular risk factors in both genders but our findings support the idea that there are gender differences in the correlations between ectopic fat deposition and the cardiovascular risk factors.

Metabolic Syndrome Patient Compliance with Drug Treatment

OBJECTIVES 1) To evaluate the compliance with drug treatment in patients with metabolic syndrome. 2) To determine association between access to and use of medicines, as well as the level of knowledge of cardiovascular risk factors and compliance. INTRODUCTION Low compliance has been one of the greatest challenges for the successful treatment of chronic diseases. Although this issue has been widely studied in patients with isolated hypertension, diabetes and dyslipidemia, compliance studies involving patients with these concomitant diseases or with metabolic syndrome diagnosis are scarce. METHODS This was a cross-sectional study involving patients who have been diagnosed with metabolic syndrome according to the IDF criteria. Patients were being treated in a Health-Medical School Center bound to the Public Brazilian Healthcare System. This study was conducted in two phases. Phase I was characterized by analyzing medical records and Phase II involved interviewing the patients. A variation of the Morisky-Green Test was used to evaluate compliance. Compliance was the dependent variable and the independent variables included access to medicines, the use of medicines and the level of knowledge concerning cardiovascular risk factors. RESULTS Two hundred and forty-three patients were identified as being eligible for Phase II, and 75 were included in the study. The average level of compliance was 5.44 points (standard deviation of 0.68), on a scale ranging from 1.00 to 6.00 points. There was no statistically meaningful association between independent variables and compliance. The level of patient knowledge of diet and dyslipidemia was considered to be low. CONCLUSIONS Patients involved in this study exhibited a high level of compliance with drug treatment. Further research is needed to better elucidate the compliance behavior of patients who have been diagnosed with metabolic syndrome.

High plasma concentrations of asymmetric dimethylarginine inhibit ischemic cardioprotection in hypercholesterolemic rats

A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs 0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats.

Cardiac Tumors: A Brief Commentary

Patients with cardiac tumors may present with cardiovascular related or constitutional symptoms, but more often than not a cardiac mass is discovered incidentally during an imaging examination performed for an unrelated indication. Cardiac myxoma is generally considered to be a surgical emergency. Echocardiography, including the transesophageal approach, is the most important means of diagnosis; computed tomography and magnetic resonance imaging. The clinical presentation has changed, and the management of cardiac myxoma now needs to be reviewed.

Efficacy and safety of pharmacological interventions in metabolic syndrome: protocol for systematic review and network meta-analysis

Introduction: The prevalence of metabolic syndrome (MetS) and MetS-related stroke is set to increase dramatically in coming decades. MetS is a complex disease that includes endothelial dysfunction, insulin resistance, diabetes, hypertension, ectopic obesity, and dyslipidaemia and an increased risk of cardiovascular events.This study aims to fill this gap of research by conducting a Bayesian network meta-analysis to compare major drugs to treat MetS. Methods and analysis: We will search the PubMed, EMBASE, Cochrane Library, Web of Science, Embase, google scholar, clinical trials registry (ClinicalTrials. gov) for unpublished or undergoing research listed in registry platforms. Randomized controlled trials (RCTs) on the drug therapy of MetS with outcome measures including diagnostic criteria of MetS will be included. The quality of included RTCs will be evaluated according to the Cochrane Collaboration’s risk of bias tool. Traditional pairwise meta-analysis and Bayesian network meta-analysis will be conducted to compare the efficacies of antidiabetic drugs. Sensitivity analysis on the sample size of RCTs, meta-regression analysis on the follow-up periods, dosages and baselines of outcome measure, contradiction analysis between pairwise and network meta-analyses, and publication bias analysis, will be performed. Randomized controlled trials (RCTs) on the drug therapy of MetS with outcome measures criteria of MetS diagnostic will be included. The quality of included RTCs will be evaluated according to the Cochrane Collaboration’s risk of bias tool. Traditional pairwise meta-analysis and Bayesian network meta-analysis will be conducted to compare the efficacies of drugs. Sensitivity analysis on the sample size of RCTs, meta-regression analysis on the follow-up periods, dosages and baselines of outcome measure, contradiction analysis between pairwise and network meta-analyses, and publication bias analysis, will be performed. Ethics and dissemination Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. Trial registration number: PROSPERO (CRD42018083468). *Correspondence to: Leonardo Roever, MHS, Federal University of Uberlândia, Department of Clinical Research, Brazil, Email: leonardoroever@hotmail.com

HIGH SENSITIVITY CARDIAC TROPONIN I AS A DIAGNOSTIC TOOL FOR THE PRESENCE OF CORONARY ARTERY DISEASE IN STABLE DIABETIC PATIENTS

The recent emergence of several high sensitivity troponin (hsTroponin) assays has shown that cardiac troponins can be chronically elevated in response to cardiovascular comorbidities and that they confer important prognostic information. In the absence of unstable coronary artery disease,

EVOLUTION OF VENTRICULAR FUNCTION IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE SUBMITTED TO ON-PUMP OR OFF-PUMP CORONARY ARTERY BYPASS GRAFT IN MASS III TRIAL

Ventricular function is a major determinant of prognosis in patients with coronary artery disease (CAD). Few data are available to assess the evolution of ventricular function among patients submitted to off-pump coronary artery bypass graft surgery (OPCAB). To compare the evolution of ventricular