Microparticles as Potential Biomarkers of Cardiovascular Disease

Primary prevention of cardiovascular disease is a choice of great relevance because of its impact on health. Some biomarkers, such as microparticles derived from different cell populations, have been considered useful in the assessment of cardiovascular disease. Microparticles are released by the membrane structures of different cell types upon activation or apoptosis, and are present in the plasma of healthy individuals (in levels considered physiological) and in patients with different pathologies. Many studies have suggested an association between microparticles and different pathological conditions, mainly the relationship with the development of cardiovascular diseases. Moreover, the effects of different lipid-lowering therapies have been described in regard to measurement of microparticles. The studies are still controversial regarding the levels of microparticles that can be considered pathological. In addition, the methodologies used still vary, suggesting the need for standardization of the different protocols applied, aiming at using microparticles as biomarkers in clinical practice.

Association between LDL-C, Non HDL-C, and Apolipoprotein B Levels with Coronary Plaque Regression

Background:Previous reports have inferred a linear relationship between LDL-C and changes in coronary plaque volume (CPV) measured by intravascular ultrasound. However, these publications included a small number of studies and did not explore other lipid markers.Objective:To assess the association between changes in lipid markers and regression of CPV using published data.Methods:We collected data from the control, placebo and intervention arms in studies that compared the effect of lipidlowering treatments on CPV, and from the placebo and control arms in studies that tested drugs that did not affect lipids. Baseline and final measurements of plaque volume, expressed in mm3, were extracted and the percentage changes after the interventions were calculated. Performing three linear regression analyses, we assessed the relationship between percentage and absolute changes in lipid markers and percentage variations in CPV.Results:Twenty-seven studies were selected. Correlations between percentage changes in LDL-C, non-HDL-C, and apolipoprotein B (ApoB) and percentage changes in CPV were moderate (r = 0.48, r = 0.47, and r = 0.44, respectively). Correlations between absolute differences in LDL-C, non‑HDL-C, and ApoB with percentage differences in CPV were stronger (r = 0.57, r = 0.52, and r = 0.79). The linear regression model showed a statistically significant association between a reduction in lipid markers and regression of plaque volume.Conclusion:A significant association between changes in different atherogenic particles and regression of CPV was observed. The absolute reduction in ApoB showed the strongest correlation with coronary plaque regression.

Reduced Progression of Cardiac Allograft Vasculopathy with Routine Use of Induction Therapy with Basiliximab

AbstractIntroduction:Cardiac allograft vasculopathy (CAV) is a major limitation for long-term survival of patients undergoing heart transplantation (HT). Some immunosuppressants can reduce the risk of CAV.Objectives:The primary objective was to evaluate the variation in the volumetric growth of the intimal layer measured by intracoronary ultrasound (IVUS) after 1 year in patients who received basiliximab compared with that in a control group.Methods:Thirteen patients treated at a single center between 2007 and 2009 were analyzed retrospectively. Evaluations were performed with IVUS, measuring the volume of a coronary segment within the first 30 days and 1 year after HT. Vasculopathy was characterized by the volume of the intima of the vessel.Results:Thirteen patients included (7 in the basiliximab group and 6 in the control group). On IVUS assessment, the control group was found to have greater vessel volume (120–185.43 mm3 vs. 127.77–131.32 mm3; p = 0.051). Intimal layer growth (i.e., CAV) was also higher in the control group (27.30–49.15 mm3 [∆80%] vs. 20.23–26.69 mm3[∆33%]; p = 0.015). Univariate regression analysis revealed that plaque volume and prior atherosclerosis of the donor were not related to intima growth (r = 0.15, p = 0.96), whereas positive remodeling was directly proportional to the volumetric growth of the intima (r = 0.85, p < 0.001).Conclusion:Routine induction therapy with basiliximab was associated with reduced growth of the intima of the vessel during the first year after HT.

Anxiety, Depression, and General Psychological Distress in Patients with Coronary Slow Flow

AbstractBackground:The relationship between psychiatric illness and heart disease has been frequently discussed in the literature. The aim of the present study was to investigate the relationship between anxiety, depression and overall psychological distress, and coronary slow flow (CSF).Methods:In total, 44 patients with CSF and a control group of 50 patients with normal coronary arteries (NCA) were prospectively recruited. Clinical data, admission laboratory parameters, and echocardiographic and angiographic characteristics were recorded. Symptom Checklist 90 Revised (SCL-90-R), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) scales were administered to each patient.Results:The groups were comparable with respect to age, sex, and atherosclerotic risk factors. In the CSF group, BAI score, BDI score, and general symptom index were significantly higher than controls (13 [18.7] vs. 7.5 [7], p = 0.01; 11 [14.7] vs. 6.5 [7], p = 0.01; 1.76 [0.81] vs. 1.1[0.24], p = 0.01; respectively). Patients with CSF in more than one vessel had the highest test scores. In univariate correlation analysis, mean thrombolysis in myocardial infarction (TIMI) frame counts were positively correlated with BAI (r = 0.56, p = 0.01), BDI (r = 0.47, p = 0.01), and general symptom index (r = 0.65, p = 0.01). The psychiatric tests were not correlated with risk factors for atherosclerosis.Conclusion:Our study revealed higher rates of depression, anxiety, and overall psychological distress in patients with CSF. This conclusion warrants further studies.

A Novel Algorithm to Quantify Coronary Remodeling Using Inferred Normal Dimensions

Background:Vascular remodeling, the dynamic dimensional change in face of stress, can assume different directions as well as magnitudes in atherosclerotic disease. Classical measurements rely on reference to segments at a distance, risking inappropriate comparison between dislike vessel portions.Objective:to explore a new method for quantifying vessel remodeling, based on the comparison between a given target segment and its inferred normal dimensions.Methods:Geometric parameters and plaque composition were determined in 67 patients using three-vessel intravascular ultrasound with virtual histology (IVUS-VH). Coronary vessel remodeling at cross-section (n = 27.639) and lesion (n = 618) levels was assessed using classical metrics and a novel analytic algorithm based on the fractional vessel remodeling index (FVRI), which quantifies the total change in arterial wall dimensions related to the estimated normal dimension of the vessel. A prediction model was built to estimate the normal dimension of the vessel for calculation of FVRI.Results:According to the new algorithm, “Ectatic” remodeling pattern was least common, “Complete compensatory” remodeling was present in approximately half of the instances, and “Negative” and “Incomplete compensatory” remodeling types were detected in the remaining. Compared to a traditional diagnostic scheme, FVRI-based classification seemed to better discriminate plaque composition by IVUS-VH.Conclusion:Quantitative assessment of coronary remodeling using target segment dimensions offers a promising approach to evaluate the vessel response to plaque growth/regression.

Changes in Medical Management after Coronary CT Angiography

AbstractIntroduction:Coronary computed tomography angiography (CCTA) allows for non-invasive coronary artery disease (CAD) phenotyping. There are still some uncertainties regarding the impact this knowledge has on the clinical care of patients.Objective:To determine whether CAD phenotyping by CCTA influences clinical decision making by the prescription of cardiovascular drugs and their impact on non-LDL cholesterol (NLDLC) levels.Methods:We analysed consecutive patients from 2008 to 2011 submitted to CCTA without previous diagnosis of CAD that had two serial measures of NLDLC, one up to 3 months before CCTA and the second from 3 to 6 months after.Results:A total of 97 patients were included, of which 69% were men, mean age 64 ± 12 years. CCTA revealed that 18 (18%) patients had no CAD, 38 (39%) had non-obstructive (< 50%) lesions and 41 (42%) had at least one obstructive ≥ 50% lesion. NLDLC was similar at baseline between the grups (138 ± 52 mg/dL vs. 135 ± 42 mg/dL vs. 131 ± 44 mg/dL, respectively, p = 0.32). We found significative reduction in NLDLC among patients with obstrctive lesions (-18%, p = 0.001). We also found a positive relationship between clinical treatment intensification with aspirin and cholesterol reducing drugs and the severity of CAD.Conclusion:Our data suggest that CCTA results were used for cardiovascular clinical treatment titration, with especial intensification seen in patients with obstructive ≥50% CAD.

Methodological Gaps in Left Atrial Function Assessment by 2D Speckle Tracking Echocardiography

Abstract The assessment of left atrial (LA) function is used in various cardiovascular diseases. LA plays a complementary role in cardiac performance by modulating left ventricular (LV) function. Transthoracic two-dimensional (2D) phasic volumes and Doppler echocardiography can measure LA function non‑invasively. However, evaluation of LA deformation derived from 2D speckle tracking echocardiography (STE) is a new feasible and promising approach for assessment of LA mechanics. These parameters are able to detect subclinical LA dysfunction in different pathological condition. Normal ranges for LA deformation and cut-off values to diagnose LA dysfunction with different diseases have been reported, but data are still conflicting, probably because of some methodological and technical issues. This review highlights the importance of an unique standardized technique to assess the LA phasic functions by STE, and discusses recent studies on the most important clinical applications of this technique.

Hemorheological and Glycemic Parameters and HDL Cholesterol for the Prediction of Cardiovascular Events

Abstract Background: Hemorheological and glycemic parameters and high density lipoprotein (HDL) cholesterol are used as biomarkers of atherosclerosis and thrombosis. Objective: To investigate the association and clinical relevance of erythrocyte sedimentation rate (ESR), fibrinogen, fasting glucose, glycated hemoglobin (HbA1c), and HDL cholesterol in the prediction of major adverse cardiovascular events (MACE) and coronary heart disease (CHD) in an outpatient population. Methods: 708 stable patients who visited the outpatient department were enrolled and followed for a mean period of 28.5 months. Patients were divided into two groups, patients without MACE and patients with MACE, which included cardiac death, acute myocardial infarction, newly diagnosed CHD, and cerebral vascular accident. We compared hemorheological and glycemic parameters and lipid profiles between the groups. Results: Patients with MACE had significantly higher ESR, fibrinogen, fasting glucose, and HbA1c, while lower HDL cholesterol compared with patients without MACE. High ESR and fibrinogen and low HDL cholesterol significantly increased the risk of MACE in multivariate regression analysis. In patients with MACE, high fibrinogen and HbA1c levels increased the risk of multivessel CHD. Furthermore, ESR and fibrinogen were significantly positively correlated with HbA1c and negatively correlated with HDL cholesterol, however not correlated with fasting glucose. Conclusion: Hemorheological abnormalities, poor glycemic control, and low HDL cholesterol are correlated with each other and could serve as simple and useful surrogate markers and predictors for MACE and CHD in outpatients.

Genetic and Environmental Effects on the Abdominal Aortic Diameter Development

Abstract Background: Configuration of the abdominal aorta is related to healthy aging and a variety of disorders. Objectives: We aimed to assess heritable and environmental effects on the abdominal aortic diameter. Methods: 114 adult (69 monozygotic, 45 same-sex dizygotic) twin pairs (mean age 43.6 ± 16.3 years) underwent abdominal ultrasound with Esaote MyLab 70X ultrasound machine to visualize the abdominal aorta below the level of the origin of the renal arteries and 1-3 cm above the bifurcation. Results: Age- and sex-adjusted heritability of the abdominal aortic diameter below the level of the origin of the renal arteries was 40% [95% confidence interval (CI), 14 to 67%] and 55% above the aortic bifurcation (95% CI, 45 to 70%). None of the aortic diameters showed common environmental effects, but unshared environmental effects were responsible for 60% and 45% of the traits, respectively. Conclusions: Our analysis documents the moderate heritability and its segment-specific difference of the abdominal aortic diameter. The moderate part of variance was explained by unshared environmental components, emphasizing the importance of lifestyle factors in primary prevention. Further studies in this field may guide future gene-mapping efforts and investigate specific lifestyle factors to prevent abdominal aortic dilatation and its complications.

Assessment of Intima-Media Thickness in Healthy Children Aged 1 to 15 Years

Abstract Background: Carotid intima-media thickness (CIMT) has been shown to be increased in children and adolescents with traditional cardiovascular risk factors such as obesity, hypertension, and chronic kidney disease, compared with those of healthy children. Objective: To assess the influence of sex, age and body mass index (BMI) on the CIMT in healthy children and adolescents aged 1 to 15 years. Methods: A total of 280 healthy children and adolescents (males, n=175; mean age, 7.49±3.57 years; mean BMI, 17.94±4.1 kg/m2) were screened for CIMT assessment. They were divided into 3 groups according to age: GI, 1 to 5 years [n=93 (33.2%); males, 57; mean BMI, 16±3 kg/m2]; GII, 6 to 10 years [n=127 (45.4%); males, 78; mean BMI, 17.9±3.7 kg/m2], and GIII, 11 to 15 years [n=60 (21.4%); males, 40; mean BMI, 20.9±4.5 kg/m2]. Results: There was no significant difference in CIMT values between male and female children and adolescents (0.43±0.06 mm vs. 0.42±0.05 mm, respectively; p=0.243). CIMT correlated with BMI neither in the total population nor in the 3 age groups according to Pearson correlation coefficient. Subjects aged 11 to 15 years had the highest CIMT values (GI vs. GII, p=0.615; GI vs. GIII, p=0.02; GII vs. GIII, p=0.004). Conclusions: CIMT is constant in healthy children younger than 10 years, regardless of sex or BMI. CIMT increases after the age of 10 years.

Early Markers of Atherosclerotic Disease in Individuals with Excess Weight and Dyslipidemia

Abstract Background: Excessive weight is a cardiovascular risk factor since it generates a chronic inflammatory process that aggravates the endothelial function. Objective: To evaluate the endothelial function in individuals with excess weight and mild dyslipidemia using brachial artery flow-mediated dilation (BAFMD), and the association of endothelial function with anthropometric and biochemical variables. Methods: Cross-sectional study that included 74 individuals and evaluated anthropometric variables (body mass index [BMI], waist-hip ratio [WHR], waist circumference [AC], and percentage of body fat [PBF]), biochemical (blood glucose, insulinemia, ultrasensitive C-reactive protein, fibrinogen, total cholesterol, HDL-cholesterol, triglycerides, and LDL-cholesterol) and endothelial function (BAFMD, evaluated by ultrasound). The statistical analysis was performed with SPSS, version 16.0. To study the association between the variables, we used chi-square, Student's t and Mann-Whitney tests, and Pearson's correlation. Logistic regression analyzed the independent influence of the factors. Values of p < 0.05 were considered significant. Results: The participants had a mean age of 50.8 years, and 57% were female. BMI, WC, WHR, and PBF showed no significant association with BAFMD. The male gender (p = 0.02) and higher serum levels of fibrinogen (p = 0.02) were significantly and independently associated with a BAFMD below 8%. Conclusions: In individuals with excess weight and mild untreated dyslipidemia, male gender and higher levels of fibrinogen were independently associated with worse BAFMD.

A water-borne hepatitis A outbreak in Rio de Janeiro

An excess of hepatitis cases, in the research center of Petrobrás located in the Fundaão Island, within the city of Rio de Janeiro, was notified during the second half of March 1980. In recent years this center has had an average of four cases per year, but between March 5th and April 25th, sixteen cases were reported. The cause and possible source of infection were investigated. A serologic diagnosis of hepatitis A was made by showing IgG serum antibodies against this virus in patients. No subclinical cases among a group of 60 healthy employees could be identified. A questionnaire was circulated to investigate a possible commom source of infection. Evaluation of the water supply system indicated that it had recently been contaminated. Information obtained from other medical services in the island failed to reveal that the episode was part of a larger outbreak.

B cell dependent T lymphocyte responses in leishmaniasis

The activation of B cell dependent T cells during Leishmania infection cannot be considered a trivial event, because their removal profoundly alters the course and outcome of infection within genetically susceptible and resistant mouse strains. The demonstration that idiotype recognizing T cells also appear within human populations sensitized to leishmanial antigens as a result of asymptomatic or subclinical infections supports a role for these cells in immunity. These cells are not demonstrable in patients with active visceral disease, so that their role in promoting specific unresponsiveness has not been extended to humans. Whether B cell dependent, idiotype specific T cells represent a functionally distinct T lymphocyte subset with unique regulatory activities remains to be determined.

IgM immunoglobulins reacting with the phenolic glycolipid-1 antigen from Mycobacterium leprae in sera of leprosy patients and their contacts

For the first time in Brazil it was investigated the occurrence of IgM anti-PGL-1 in the sera of household contacts of leprozy patients using the ELISA methodology. The sera of the multipatients. It was observed a high subclinical infection incidence among household contacts (19.4%). The percentage of leprosy development was 5% (1/21) among the seropositive contact group. This finding suggests that serology could be useful as prognostic test, but for better definition is necessary to tet a population from endemic area for long period time.