Search

Izo Helber,1 Claudia Maria Rodrigues Alves,1 Stela Maris Grespan,1 Eduardo CA Veiga,2 Pedro IM Moraes,1 José Marconi Souza,1 Adriano H Barbosa,1 Iran Gonçalves Jr,1 Francisco AH Fonseca,1 Antônio Carlos C Carvalho1,†, Adriano Caixeta1,3 1Department of Medicine, Discipline of Cardiology, Escola Paulista de Medicina, Universidade Federal São Paulo, São Paulo, Brazil; 2Department of Gynecology and Obstetrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; 3Department of Cardiology, Hospital Israelita Albert Einstein, São Paulo, Brazil†Dr Antonio Carlos De Camargo Carvalho passed away on January 8, 2019Correspondence: Adriano CaixetaEscola Paulista de Medicina, Universidade Federal São Paulo, Av. Napoleão de Barros, 715, São Paulo, CEP: 04024002, BrazilTel +55 11- 5576-4000Email adriano.caixeta@einstein.br Twitter @adrianocaixetaBackground: There is little research in the efficacy and safety of a pharmaco-invasive strategy (PIS) in patients ≥ 75 years versus < 75 years of age. We aimed to evaluate and compare the influence of advanced age on the risk of death and major adverse cardiac events (MACE) in patients undergoing PIS.Methods: Between January 2010 and November 2016, 14 municipal emergency rooms in São Paulo, Brazil, used full-dose tenecteplase to treat patients with STEMI as part of a pharmaco-invasive strategy for a local network implementation.Results: A total of 1852 patients undergoing PIS were evaluated, of which 160 (9%) were ≥ 75 years of age. Compared to patients < 75 years, those ≥ 75 years were more often female, had lower body mass index, higher rates of hypertension; higher incidence of hypothyroidism, chronic renal failure, prior stroke, and diabetes. Compared to patients < 75 years of age, in-hospital MACE and mortality were higher in patients with ≥ 75 years (6.5% versus 19.4%; p< 0.001; and 4.0% versus 18.2%; p< 0.001, respectively). Patients ≥ 75 years had higher rates of in-hospital major bleeding (2.7% versus 5.6%; p=0.04) and higher incidence of cardiogenic shock (7.0% versus 19.6%; p< 0.001). By multivariable analysis, age ≥ 75 years was independent predictor of MACE (OR 3.57, 95% CI 1.72 to 7.42, p=0.001) and death (OR 2.07, 95% CI 1.12– 3.82, p=0.020).Conclusion: In patients with ST-segment elevation myocardial infarction undergoing PIS, age ≥ 75 years was an independent factor that entailed a 3.5-fold higher MACE and 2-fold higher mortality rate compared to patients < 75 years of age.Keywords: acute myocardial infarction, elderly, fibrinolysis, primary percutaneous coronary intervention, pharmaco-invasive strategy

Since its inception in the 80's, capillary electrophoresis has matured into a well-established separation technique, actually encompassing a family of electrodriven techniques with distinct separation mechanisms and selectivity, performed in a single capillary column. In this work, the versatility of capillary electrophoresis in handling materials from a diversity of chemical classes and complex sample matrices is illustrated by representative applications in the clinical, forensic, cosmetological, environmental, nutritional and pharmaceutical areas, grouping together our own research interests and results.

Abstract Background Yersinia pestis is the causative agent of plague and a potential agent of bioterrorism and biowarfare. The plague biothreat and the emergence of multidrug-resistant plague underscore the need to increase our understanding of the intrinsic potential of Y. pestis for developing antimicrobial resistance and to anticipate the mechanisms of resistance that may emerge in Y. pestis. Identification of Y. pestis genes that, when overexpressed, are capable of reducing antibiotic susceptibility is a useful strategy to expose genes that this pathogen may rely upon to evolve antibiotic resistance via a vertical modality. In this study, we explored the use of a multicopy suppressor, Escherichia coli host-based screening approach as a means to expose antibiotic resistance determinant candidates in Y. pestis. Results We constructed a multicopy plasmid-based, Y. pestis genome-wide expression library of nearly 16,000 clones in E. coli and screened the library for suppressors of the antimicrobial activity of ofloxacin, a fluoroquinolone antibiotic. The screen permitted the identification of a transcriptional regulator-encoding gene (robAYp) that increased the MIC99 of ofloxacin by 23-fold when overexpressed from a multicopy plasmid in Y. pestis. Additionally, we found that robAYp overexpression in Y. pestis conferred low-level resistance to many other antibiotics and increased organic solvent tolerance. Overexpression of robAYp also upregulated the expression of several efflux pumps in Y. pestis. Conclusion Our study provides proof of principle for the use of multicopy suppressor screening based on the tractable and easy-to-manipulate E. coli host as a means to identify antibiotic resistance determinant candidates of Y. pestis.

Phytosterols are natural components of plant-based foods used as supplements because of their known cholesterol-lowering effect. However, their effects on lipoprotein subfractions and the quality of the LDL particle have not been studied in greater detail. We aimed to evaluate the effects of phytosterols supplements on lipids, lipoproteins subfractions, and on the quality of LDL. A prospective, pilot-type, open label, cross-over study, randomized 23 males in primary prevention of hypercholesterolemia to receive diet or diet plus phytosterol (2.6 g in 2 doses, with meals) for 12 weeks, when treatments were switched for another 12 weeks. Lipoprotein subfractions were analyzed by electrophoresis in polyacrylamide gel (Lipoprint System®). The Sampson equation estimated the small and dense (sd) and large and buoyant (lb) LDL subfractions from the lipid profile. Quality of LDL particle was analyzed by Z-scan and UV-vis spectroscopy. Primary outcome was the comparison of diet vs. diet plus phytosterols. Secondary outcomes assessed differences between baseline, diet and diet plus phytosterol. Non-parametric statistics were performed with p < 0.05. There was a trend to reduction on HDL-7 (p = 0.05) in diet plus phytosterol arm, with no effects on the quality of LDL particles. Heatmap showed strong correlations (ρ > 0.7) between particle size by different methods with both interventions. Diet plus phytosterol reduced TC, increased HDL-c, and reduced IDL-B, whereas diet increased HDL7, and reduced IDL-B vs. baseline (p < 0.05, for all). Phytosterol supplementation demonstrated small beneficial effects on HDL-7 subfraction, compared with diet alone, without effects on the quality of LDL particles.This trial is registered in Clinical Trials (NCT06127732) and can be accessed at https://clinicaltrials.gov ., (© 2024. The Author(s).)

In this study, we aimed to examine the impact of high endurance training on vascular health parameters and immune-endocrine responses against modified low-density lipoprotein (LDL) particles. This observational, cross-sectional study included high endurance-trained and healthy non-trained subjects. Vascular ultrasound was used to assess vascular health parameters based on carotid intima-media thickness and endothelial function (flow-mediated dilation). Enzyme-linked immunosorbent assays were used to measure interleukin (IL)-8 and IL-10, autoantibody isotypes anti-oxidized LDL (oxLDL) and anti-apolipoprotein B (ApoB-D) peptide. Plasma levels of the corticosterone and 17 α-hydroxyprogesterone hormones were analyzed by mass spectrometry. This study enrolled 96 subjects, of whom 44 were high endurance trained and 52 were healthy non-trained individuals. Smaller carotid intima-media thickness values were observed in the high-endurance trained than in the healthy non-trained males, while no differences were observed between female groups. Flow-mediated dilation measurements did not differ by training or sex. The humoral immune responses to IgG anti-oxLDL and IgM anti-ApoB-D autoantibodies showed an isotype imbalance between the high-endurance trained and the non-trained groups. Immunoendocrine parameters showed inverse correlations between 17 α-hydroxyprogesterone concentrations and carotid intima-media thickness measurements. Direct correlations were found between IL-10 concentrations and flow-mediated dilation measurements. Chronic high-endurance exercise modulates immune-endocrine and vascular health parameters, in a sex-dependent manner., Competing Interests: The authors declare no conflict of interest., (Thieme. All rights reserved.)

Background: Primary prevention of cardiovascular disease (CVD) remains a major challenge, especially in communities of low- and middle-income countries with poor medical assistance influenced by distinct local, financial, infrastructural, and resource-related factors., Objective: This a community-based study aimed to determine the proportion and prevalence of uncontrolled cardiovascular risk factors (CRF) in Brazilian communities., Methods: The EPICO study was an observational, cross-sectional, and community clinic-based study. Subjects were living in Brazilian communities and were of both sexes and ≥18 years old, without a history of a stroke or myocardial infarction but presenting at least one of the following cardiovascular risk factors: hypertension, diabetes mellitus and hypercholesterolemia. The study was carried out in Brazil, including 322 basic health units (BHU) in 32 cities., Results: A total of 7,724 subjects with at least one CRF were evaluated, and one clinical visit was performed. Mean age was 59.2 years-old (53.7% were >60 years old). A total of 66.7% were women. Of the total, 96.2% had hypertension, 78.8% had diabetes mellitus type II, 71.1% had dyslipidemia, and 76.6% of patients were overweight/obese. Controlled hypertension (defined by <130/80 mmHg or <140/90 mmHg) was observed in 34.9% and 55.5% patients among respective criteria, the rates of controlled blood glucose in patients taking antidiabetic medications was 29.5%, and among those with documented dyslipidemia who received any lipid-lowering medication, only 13.9% had LDL-c on target. For patients presenting three CRF less than 1.9% had LDL-c < 100 mg/dL once their BP and blood glucose were on target. High education level as associated with blood pressure (BP) target of less than 130 / 80mm Hg. The glucose and LDL-c levels on target were associated with the presence of hypertension and diabetes mellitus., Conclusion: In Brazilian community clinics, regarding most patients in primary prevention, the CRF such as BP, blood glucose, and lipid levels are poorly controlled, with a majority of patients not achieving guidelines/recommendations., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

Black soldier fly (BSF, Hermetia illucens ) larvae is a prominent ingredient in aquafeeds due to its high protein and energy contents. This study evaluated the digestibility of full-fat BSF larvae meal (FF-BSFL) and its inclusion in diets for tambaqui, Colossoma macropomum . The apparent digestibility coefficient of FF-BSFL for protein and energy was around of 88%, corresponding to 33.55% and 21.61 MJ kg -1 of digestible protein and energy, respectively. For the feeding trial, tambaqui juveniles (53.23 ± 1.07 g) were distributed in a completely randomized experimental design (n = 4; 150 L tanks; 10 fish per tank). Fish were fed diets including 0%, 5.25%, 10.50%, and 15.75% FF-BSFL to apparent satiation for 60 days. Fish fed 10.50% FF-BSFL dietary inclusion showed higher weight gain, feed intake, final biomass, and relative growth rate. The 10.50% FF-BSFL diet presented the highest index of economic profitability. Weight gain fitted a third-degree equation and the optimum FF-BSFL inclusion level was estimated at 11.6%. However, FF-BSFL dietary inclusion up to 15.75% did not impair growth fish performance. FF-BSFL seems to be a promising source of protein and energy for omnivorous fish aquafeed.

Atherosclerosis is defined as an inflammatory disease. Low-grade inflammation is present in all phases of the cardiovascular continuum , since the establishment of cardiovascular risk factors and ischemic heart disease until cardiovascular events, such as myocardial infarction, heart failure and death. Not all inflammatory pathways are linked to cardiovascular outcomes, and thus, not all anti-inflammatory approaches decrease cardiovascular events. The most common cause of ventricular remodeling and heart failure is ischemic heart disease. Biomarkers such as high-sensitivity C-reactive protein can identify individuals at risk of major cardiovascular complications, but this biomarker has no causal effect on cardiovascular disease. On the other hand, interleukin 6 appears to be causally associated with cardiovascular disease. CANTOS was the first proof of concept study showing that anti-inflammatory therapy reduces major cardiovascular outcomes. Based on many anti-inflammatory trials, only therapies acting on the NLRP3 inflammasome, or interleukin 1beta, showed benefits on cardiovascular disease. Ventricular remodeling, particularly after myocardial infarction seems also influenced by the intensity of inflammatory responses, suggesting that anti-inflammatory therapies may reduce the residual cardiovascular risk. Inflammasome (NLRP3) activation, subtypes of lymphocytes, interleukin 6, and some inflammatory biomarkers, are associated with larger infarct size and impaired ventricular function after myocardial infarction. Cardiovascular risk factors commonly present in patients with myocardial infarction, and advanced age are associated with higher inflammatory activity., Competing Interests: FF has served as a steering committee member in JUPITER and CANTOS trials, declares an investigator-initiated study with Astra Zeneca, and has served as a speaker for Astra Zeneca, Novo Nordisk, Boehringer, Lilly, Biolab, Libbs, Ache, and Novartis; MI has served as a speaker for PTC, Novartis, Ache, Amgen, Sanofi-Aventis, Abbott, and Amrit, and declares an investigator-initiated study with PTC., (Copyright © 2022 Fonseca and Izar.)

Background and Aims: Familial hypercholesterolemia (FH) is characterized by lifelong exposure to high LDL-c concentrations and premature atherosclerotic cardiovascular disease; nevertheless, disease severity can be heterogeneous.We aimed at evaluating if the immune-inflammatory system could modulate atherosclerosis burden in FH., Methods: From a cohort of subjects with confirmed FH (Dutch Lipid Clinic Network and genotype), 92 patients receiving high-intensity lipid-lowering therapy (statin ± ezetimibe) were included. The extension and severity of coronary atherosclerosis was assessed by standardized reporting systems (CAD-RADS) for coronary computed tomography angiography (CCTA) and coronary artery calcium (CAC) scores. Lipids, apolipoproteins, anti -oxLDL and anti-apolipoprotein B-D peptide ( anti -ApoB-D) autoantibodies (IgM and IgG), lymphocytes subtypes, platelet, monocyte and endothelial microparticles (MP), IgM levels (circulating or produced by B1 cells) and cytokines in the supernatant of cultured cells were determined. Multiple linear regression models evaluated associations of these biomarkers with CAC and CAD-RADS scores., Results: In univariate analysis CAC correlated with age, systolic blood pressure, TCD4+ cells, and titers of IgM anti -ApoB-D. In multiple linear regression [ANOVA F = 2.976; p  = 0.024; R 2  = 0.082), CD4+T lymphocytes (B = 35.289; beta = 0.277; p  = 0.010; 95%CI for B 8.727 to 61.851), was independently associated with CAC. CAD-RADS correlated with age, systolic blood pressure, titers of IgM anti -ApoB-D, and endothelial MP in univariate analysis. In multiple linear regression, [ANOVA F = 2.790; p  = 0.032; R 2  = 0.119), only age (B = 0.027; beta = 0.234; p  = 0.049; 95% CI for B 0.000 to 0.053) was independent predictor., Conclusions: In subjects with FH, under high-intensity lipid-lowering therapy, age and CD4+T cells were associated to atherosclerosis burden., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Mucopolysaccharidosis (MPS) is a heterogeneous group of rare, chronic, progressive and systemic inherited disorders resulting from deficiency or lack of lysosomal enzymes responsible for the degradation of glycosaminoglycans. Products of nitrosative stress have been previously detected in blood and urine samples of patients with MPS. However, it is unclear whether they are present in the saliva of MPS patients and also if they correlate with salivary parameters such as flow and pH. This study compared the salivary levels of NOX (NO2- + NO3-), nitrite (NO2-), protein (albumin), erythrocyte and leukocyte numbers, as well as the salivary flow rate and pH values of samples obtained from 10 MPS patients and 10 healthy subjects. MPS patients exhibited higher salivary levels of NOX and NO2- when compared to healthy subjects (p < 0.05). Albumin was only detected in six saliva samples of MPS patients and, erythrocytes and leukocytes were detected in 60% and 40% of the MPS patients, respectively. In addition, salivary flow rate and pH averages were statistically lower in this group when compared to healthy samples (p < 0.05). Overall, the data indicates that the salivary levels of NO products can be used in combination with other heath indicators to monitor MPS disorders.

Background: Large observational studies have shown that small, dense LDL subfractions are related to atherosclerotic cardiovascular disease. This study assessed the effects of two highly effective lipid-lowering therapies in the atherogenic subclasses of lipoproteins in subjects with ST-segment elevation myocardial infarction (STEMI)., Methods: Patients of both sexes admitted with their first myocardial infarction and submitted to pharmacoinvasive strategy (N = 101) were included and randomized using a central computerized system to receive a daily dose of simvastatin 40 mg plus ezetimibe 10 mg or rosuvastatin 20 mg for 30 days. Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) subfractions were analysed by polyacrylamide gel electrophoresis (Lipoprint System) on the first (D1) and 30th days (D30) of lipid-lowering therapy. Changes in LDL and IDL subfractions between D1 and D30 were compared between the lipid-lowering therapies (Mann-Whitney U test)., Results: The classic lipid profile was similar in both therapy arms at D1 and D30. At D30, the achievement of lipid goals was comparable between lipid-lowering therapies. Cholesterol content in atherogenic subclasses of LDL (p = 0.043) and IDL (p = 0.047) decreased more efficiently with simvastatin plus ezetimibe than with rosuvastatin., Conclusions: Lipid-lowering therapy with simvastatin plus ezetimibe was associated with a better pattern of lipoprotein subfractions than rosuvastatin monotherapy. This finding was noted despite similar effects in the classic lipid profile and may contribute to residual cardiovascular risk., Trial Registration: ClinicalTrials.gov , NCT02428374, registered on 28/09/2014., (© 2021. The Author(s).)

Background: Epilepsy is highly comorbid with psychiatric disorders and a significant amount of the morbidity related to epilepsy is in fact a result of psychiatric comorbidities., Objective: To investigate the frequency of different psychiatric comorbidities in children with refractory epilepsy., Methods: We present preliminary observational data from a series of patients (n=82) examined in the psychiatric branch of a tertiary epilepsy center in Rio de Janeiro, Brazil. Patients were classified as presenting autism spectrum disorders, mood disorders, anxiety disorders, disruptive disorders, attention deficit hyperactivity disorder (ADHD), intellectual development disorder, psychotic episode, dissociative/conversive disorders or others. We determined the frequency of each disorder, along with demographic data, medications prescribed, electroencephalogram findings and additional medical examinations and consultations., Results: The most common comorbidities in our sample were autism spectrum disorders and ADHD. Antipsychotics and selective serotonin uptake inhibitors were the most commonly prescribed psychiatric medications., Conclusions: Knowledge about the prevalence of such comorbidities may provide more targeted interventions in Psychiatry and Psychology services linked to epilepsy centers.

Despite early reperfusion, patients with ST segment elevation myocardial infarction (STEMI) may present large myocardial necrosis and significant impairment of ventricular function. The present study aimed to evaluate the role of subtypes of B lymphocytes and related cytokines in the infarcted mass and left ventricular ejection fraction obtained by cardiac magnetic resonance imaging performed after 30 days of STEMI. This prospective study included 120 subjects with STEMI submitted to pharmacoinvasive strategy. Blood samples were collected in subjects in the first (D1) and 30th (D30) days post STEMI. The amount of CD11b+ B1 lymphocytes (cells/ml) at D1 were related to the infarcted mass (rho = 0.43; P=0.033), measured by cardiac MRI at D30. These B1 cells were associated with CD4+ T lymphocytes at D1 and D30, while B2 classic lymphocytes at day 30 were related to left ventricular ejection fraction (LVEF). Higher titers of circulating IL-4 and IL-10 were observed at D30 versus D1 (P=0.013 and P<0.001, respectively). Titers of IL-6 at D1 were associated with infarcted mass (rho = 0.41, P<0.001) and inversely related to LVEF (rho = -0.38, P<0.001). After multiple linear regression analysis, high-sensitivity troponin T and IL-6 collected at day 1 were independent predictors of infarcted mass and, at day 30, only HDL-C. Regarding LVEF, high-sensitivity troponin T and high-sensitivity C-reactive protein were independent predictors at day 1, and B2 classic lymphocytes, at day 30. In subjects with STEMI, despite early reperfusion, the amount of infarcted mass and ventricular performance were related to inflammatory responses triggered by circulating B lymphocytes., (© 2021 The Author(s).)

Introduction and Objectives: Cow's milk allergy (CMA) is common, especially in children. The treatment is based on the exclusion of milk and dairy products and guidance regarding the exclusion diet. This study aimed to compare the anthropometric measurements and food intake of children with CMA with those of healthy controls, and to evaluate the serum concentrations of Vitamin A and 25(OH)D in children with CMA., Methods: This is a cross-sectional study with 27 children in the CMA group and 30 in the control group. z-Scores of body mass index and height, skinfolds, food intake and serum concentrations of retinol, beta-carotene, lycopene, 25(OH)D, parathyroid hormone and high sensitivity C-reactive protein were evaluated., Results: Mean age was four years (±1.9). The CMA group evidenced a lower height compared to those from the control group (p=0.0043). The CMA group showed a lower intake of calcium (p=0.0033) and lipids (p=0.0123). Low serum concentrations of retinol, beta-carotene, lycopene, 25(OH)D were found in 25.9%, 59.3%, 48.1% and 70.3% of the CMA group, respectively., Conclusions: Children with CMA consume smaller amounts of calcium and lipids and have shorter height compared to healthy controls. Insufficient levels of vitamins A and D were frequent in the CMA group, emphasizing the need for nutritional guidance and monitoring., (Copyright © 2019 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Age, smoking, hypercholesterolemia, and hypertension are major risk factors for atherosclerotic cardiovascular disease., Objective: We examined whether the effects of alirocumab on low-density lipoprotein cholesterol (LDL-C) differed according to age, hypertension, or smoking status., Methods: Data were pooled from 10 Phase 3 ODYSSEY randomized trials (24-104 weeks' duration) in 4983 people with heterozygous familial hypercholesterolemia (FH) or non-familial hypercholesterolemia (3188 on alirocumab, 1795 on control [620 on ezetimibe and 1175 on placebo]). Most participants received concomitant maximum tolerated statin therapy. In 8 trials, the alirocumab dose was increased from 75 mg every 2 weeks (Q2W) to 150 mg Q2W at Week 12 if predefined risk-based LDL-C goals were not achieved at Week 8 (≥70 mg/dL in very high cardiovascular risk; ≥100 mg/dL in moderate or high cardiovascular risk). Two trials compared alirocumab 150 mg Q2W vs placebo. The efficacy and safety of alirocumab were assessed post hoc in subgroups stratified by age (<65, ≥65 to <75, ≥75 years) and baseline hypertension or smoking status., Results: Alirocumab reduced LDL-C by 23.7% (75/150 mg vs ezetimibe + statin) to 65.4% (150 mg vs placebo + statin) from baseline to Week 24 vs control. Subgroup analyses confirmed no significant interactions in response to alirocumab between age group, hypertension, or smoking status. Overall rates of treatment-emergent adverse events were similar between alirocumab and control groups., Conclusions: In this pooled analysis from 10 trials, alirocumab led to substantial LDL-C reductions vs control in every age group and regardless of hypertension or smoking status. Alirocumab was well tolerated in all subgroups., (Copyright © 2019 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: This is an overview of the mechanisms of obesity and its relation to cardiovascular risks, describing the available treatment options to manage this condition., Main Body: The pathogenesis of obesity includes the balance between calories consumed and energy expenditure followed by the maintenance of body weight. Diet, physical activity, environmental, behavioral and physiological factors are part of the complex process of weight loss, since there are several hormones and peptides involved in regulation of appetite, eating behavior and energy expenditure. The cardiovascular complications associated to obesity are also driven by processes involving hormones and peptides and which include inflammation, insulin resistance, endothelial dysfunction, coronary calcification, activation of coagulation, renin angiotensin or the sympathetic nervous systems. Pharmacological treatments are often needed to insure weight loss and weight maintenance as adjuncts to diet and physical activity in people with obesity and overweight patients., Conclusion: To accomplish satisfactory goals, patients and physicians seek for weight loss, weight maintenance and improvement of the risk factors associated to this condition, especially cardiovascular risk., Competing Interests: Competing interestsFF has served as steering committee member for Novartis and Astra Zeneca, and reports having received research grants, lecture fees, and consulting fees from AstraZeneca, Bayer, Sanofi-Aventis, Novo Nordisk, Novartis, Takeda, Amgen, Biolab, Ache, EMS, and Merck. CC has served as advisory board for Eurofarma and Novo NordisK, and reports having received research grants from AstraZeneca, Sanofi-Aventis, Novo Nordisk, Eurofarma, Fractyl, Lilly, Boehringer Ingelheim, and Abbvie. The authors declare that they have no competing interests.

Background: The efficacy of ticagrelor in the long-term post-ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain., Objectives: The purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy., Methods: This international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months., Results: The combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups., Conclusion: Among patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: The bleeding safety of ticagrelor in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy remains uncertain., Objective: To evaluate the short-term safety of ticagrelor when compared with clopidogrel in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy., Design, Setting and Participants: We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevation myocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%., Interventions: Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel., Main Outcomes and Measures: The primary outcome was thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days., Results: The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95% CI, -0.49% to 0.58%; P < .001 for noninferiority). Major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 23 patients (1.20%) in the ticagrelor group and in 26 patients (1.38%) in the clopidogrel group (absolute difference, -0.18%; 95% CI, -0.89% to 0.54; P = .001 for noninferiority). The rates of fatal (0.16% vs 0.11%; P = .67) and intracranial bleeding (0.42% vs 0.37%; P = .82) were similar between the ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with ticagrelor than with clopidogrel. The composite of death from vascular causes, myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95% CI, 0.67-1.25; P = .57)., Conclusions and Relevance: In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days., Trial Registration: clinicaltrials.gov Identifier: NCT02298088.

1 H HR-MAS NMR spectroscopy was used to track the metabolic changes throughout the whole development of astringent ('Giombo') and non-astringent ('Fuyu') cultivars of persimmon (Diospyros kaki). The NMR data revealed the low concentration of amino acids (threonine, alanine, citrulline and GABA) and organic acids (malic acid). In addition, the signals of carbohydrates (sucrose, glucose and fructose) seemed to play the most important role in the fruit development. In both cultivars, the growth was characterized by fluctuating sucrose concentration along with a constant increase in both glucose and fructose. In the initial growth stage, the polyphenol composition was quite different between the cultivars. Gallic acid was detected throughout the growth of 'Giombo', while for 'Fuyu', signals of polyphenols disappeared over time. Additional multivariate analysis suggested that these cultivars share many metabolic similarities during development. These findings might help the comprehension of fruit development, which in turn, impacts the quality of the fruits., (Copyright © 2017. Published by Elsevier Ltd.)

Background: A pharmacodynamic comparison between ticagrelor and prasugrel after fibrinolytic therapy has not yet been performed., Methods: In the single-center SAMPA trial, 50 consecutive STEMI patients previously treated with clopidogrel and undergoing a pharmacoinvasive strategy were randomized to either a ticagrelor (n=25) 180mg loading dose followed by 90mg bid, or a prasugrel (n=25) 60mg loading dose followed by 10mg/day, initiated after fibrinolytic therapy but before angiography. Platelet reactivity was assessed with the VerifyNow P2Y 12 assay at 0, 2, 6, and 24h after randomization., Results: Mean times from fibrinolysis to prasugrel or ticagrelor administration were 11.1±6.9 and 13.3±6.3h, respectively (p=0.24). The values of PRU decreased significantly from baseline to 2h (all p<0.001) and from 2h to 6h (all p<0.001) in both groups. There was no difference in PRU values between 6h and 24h. The mean PRU values at 0, 2, 6, and 24h were 234.9, 127.8, 45.4, and 48.0 in the prasugrel group and 233.1, 135.1, 67.7, and 56.9 in the ticagrelor group, respectively. PRU values did not significantly differ between groups at any time period of the study., Conclusions: In patients with STEMI treated with fibrinolytic therapy, platelet inhibition after clopidogrel is suboptimal and can be further increased with more potent agents. Ticagrelor and prasugrel demonstrated a similar extent of P2Y 12 receptor inhibition within 24h, although maximal platelet inhibition after these potent agents was not achieved for 6h., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

In the last two decades, statin therapy has proved to be the most potent isolated therapy for attenuation of cardiovascular risk. Its frequent use has been seen as one of the most important elements for the reduction of cardiovascular mortality in developed countries. However, the recurrent incidence of muscle symptoms in statin users raised the possibility of causal association, leading to a disease entity known as statin associated muscle symptoms (SAMS). Mechanistic studies and clinical trials, specifically designed for the study of SAMS have allowed a deeper understanding of the natural history and accurate incidence. This set of information becomes essential to avoid an unnecessary risk of severe forms of SAMS. At the same time, this concrete understanding of SAMS prevents overdiagnosis and an inadequate suspension of one of the most powerful prevention strategies of our times. In this context, the Luso-Latin American Consortium gathered all available information on the subject and presents them in detail in this document as the basis for the identification and management of SAMS.

Background: Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular events, and its detection usually begins with an electrocardiogram (ECG)., Objective: To evaluate the impact of complete left bundle branch block (CLBBB) in hypertensive patients in the diagnostic performance of LVH by ECG., Methods: A total of 2,240 hypertensive patients were studied. All of them were submitted to an ECG and an echocardiogram (ECHO). We evaluated the most frequently used electrocardiographic criteria for LVH diagnosis: Cornell voltage, Cornell voltage product, Sokolow-Lyon voltage, Sokolow-Lyon product, RaVL, RaVL+SV3, RV6/RV5 ratio, strain pattern, left atrial enlargement, and QT interval. LVH identification pattern was the left ventricular mass index (LVMI) obtained by ECHO in all participants., Results: Mean age was 11.3 years ± 58.7 years, 684 (30.5%) were male and 1,556 (69.5%) were female. In patients without CLBBB, ECG sensitivity to the presence of LVH varied between 7.6 and 40.9%, and specificity varied between 70.2% and 99.2%. In participants with CLBBB, sensitivity to LVH varied between 11.9 and 95.2%, and specificity between 6.6 and 96.6%. Among the criteria with the best performance for LVH with CLBBB, Sokolow-Lyon, for a voltage of ≥ 3,0mV, stood out with a sensitivity of 22.2% (CI 95% 15.8 - 30.8) and specificity of 88.3% (CI 95% 77.8 - 94.2)., Conclusion: In hypertensive patients with CLBBB, the most often used criteria for the detection of LVH with ECG showed significant decrease in performance with regards to sensitivity and specificity. In this scenario, Sokolow-Lyon criteria with voltage ≥3,0mV presented the best performance., Competing Interests: Potential Conflict of Interest No potential conflict of interest relevant to this article was reported.

To evaluate the effects of long-term exposure to high-intensity training among professional runners on cardiac hypertrophy and subclinical atherosclerosis. Prospective study included runners of both sexes (n = 52) and age and gender matched controls (n = 57), without classical cardiovascular risk factors. Ventricular hypertrophy was quantified by echocardiography by linear method and carotid intima-media thickness (cIMT) by 2-D images obtained by ultrasonography. Endothelial function was evaluated by flow-mediated dilation (FMD). Steroid hormones were quantified by HPLC followed by LC-MS/MS. Higher left ventricular (LV) mass index was found in male athletes (p<0.0001 vs. other groups). When adjusted for gender, the degree of left ventricular mass index classified as mildly, moderately or severely abnormal was obtained in 26%, 35%, and 30%, respectively, of female athletes, and in 39%, 14%, and 21%, respectively, of male athletes. Higher ratio of the early (E) to late (A) ventricular filling velocities was found in athletes of both genders. Male athletes presented lower cIMT in the right (p = 0.012 vs. male controls) and left (p<0.0001 vs. male controls) common carotid arteries, without differences in cIMT between female athletes and controls. FMD results were similar among groups. Higher serum testosterone levels were found in male athletes (p<0.0001 vs. other groups) and they were correlated with LV mass (r = 0.50, p<0.0001). The chronic exposure of high-intensity training among professional runners of both genders was associated with increased ventricular mass and adaptive remodeling. Less subclinical atherosclerosis was found in male athletes. Differences in steroid hormones may account in part for these findings., Competing Interests: The authors have declared that no competing interests exist.

We investigated the association between the degree of oxidative modification of LDL particles by non-linear optical response of LDL (Z-scan technique) and the presence of subclinical atherosclerosis in different segments of the carotid artery. We recruited high-intensity athlete runners (n = 44) and controls (n = 51) to participate in the study. The carotid intima-media thickness (cIMT), interleukin 10 (IL-10), TNF-alpha, and the non-linear optical responses of LDL particle (Z-scan) were assessed. In athletes, the mean cIMT differed between genders, with higher values observed in female athletes compared to male athletes (P < 0.05). Higher mean values for cIMT were seen in the right carotid arteries of female athletes as compared to female controls (P < 0.05). Higher levels of TNF-alpha and IL-10 were found in athletes (P < 0.05). Yet, ΔΓpv (transmittance curve) of Z-scan in athletes was higher than in the non-athletes, indicating less oxidation in LDL particles of athletes (P < 0.05). There was an inverse association between the ΔΓpv and cIMT in the right internal carotid segments (β = -0.163, P < 0.05) in all subjects, and between the VO2max and the mean cIMT (β = -0.003, P < 0.05) in male subjects. The present study shows that the Z-scan technique enabled to detect less oxidative modifications in LDL particles from athletes. This effect was associated with cIMT in a gender-dependent mode.

Despite substantial differences in ethnicities, habits, cultures, the prevalence of traditional cardiovascular risk factors and affordable therapies, atherosclerosis remains the major cause of death in developing and developed countries. However, irrespective of these differences, inflammation is currently recognized as the common pathway for the major complications of atherosclerosis, stroke, and ischemic heart disease. A PubMed search was conducted for "high-sensitivity C-reactive protein" (hs-CRP) in combination with the terms race, ethnicity, gender, prevalence, geographic, epidemiology, cardiovascular, obesity, diabetes, hypertension, cholesterol, smoking, ischemic heart disease, stroke, and mortality. This review includes the articles that pertained to the topic and additional articles identified from the reference lists of relevant publications. This review describes the marked differences in cardiovascular mortality across countries and ethnicities, which may be attributed to inequalities in the prevalence of the classic risk factors and the stage of cardiovascular epidemiological transition. However, hs-CRP appears to contribute to the prognostic information regarding cardiovascular risk and mortality even after multiple adjustments. Considering the perception of cardiovascular disease as an inflammatory disease, the more widespread use of hs-CRP appears to represent a valid tool to identify people at risk, independent of their ancestry or geographic region. In conclusion, this review reports that the complications associated with vulnerable atherosclerotic plaques are triggered by the major mechanisms of dyslipidemia and inflammation; whereas both mechanisms are influenced by classic risk factors, hs-CRP contributes additional information regarding cardiovascular events and mortality.

The paper summarizes the difficulties to study the rare population of endothelial progenitor cells in clinical trials, based on the experience of our group in many publications in this area.

Aims: The aim of this work was to evaluate the effects of treatment of hypertension on the autoantibodies to apolipoprotein B-derived peptides (anti-ApoB-D peptide Abs) response, inflammation markers and vascular function., Main Methods: Eighty-eight patients with hypertension (stage 1 or 2) were recruited and advised to receive perindopril (4mg), hydrochlorothiazide (25mg), or indapamide (1.5mg) for 12weeks in a blinded fashion. Office and 24-h ambulatory blood pressure monitoring (24h ABPM), flow-mediated dilatation (FMD), nitrate-induced dilatation (NID), titers of IgG and IgM anti-ApoB-D peptide Abs, hsCRP, and interleukins (IL-8 and IL-10) were evaluated at baseline and 12weeks after therapies., Key Findings: All treatments reduced office BP, and improved FMD (P<0.05 vs. baseline). The NID was improved only in the perindopril arm (P<0.05 vs. baseline). The 24h-ABPM was reduced with perindopril and hydrochlorothiazide therapies (P<0.05 vs. baseline), but not with indapamide, and this effect was followed by increase in titers of IgM Anti-ApoB-D peptide Abs (P<0.05 vs. baseline), without modifications in titers IgG Anti-ApoB-D peptide Abs and interleukins. Multivariable regression analysis has shown that change in the titers of IgM anti-ApoB-D peptide was associated with the changes in FMD (β -0.347; P<0.05)., Significance: These findings shed light to a possible modulator effect of the antihypertensive therapy on the natural immunity responses and vascular function., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Obstructive sleep apnea (OSA) has been linked to increased oxidative stress, lipid peroxidation and worsening atherosclerosis. This study investigated oxidized low-density lipoprotein (oxLDL) as a marker of lipid peroxidation, and total LDL cholesterol (direct LDL-C), as a marker of the lipid profile among individuals with OSA, and its association with hypertension (HYP) and dyslipidemia (DYS). The impact of one year of continuous positive airway pressure (CPAP) was also assessed., Methods: Blood was collected after 12 h of fasting from 99 consecutive patients who were diagnosed with OSA via polysomnography, and were also diagnosed with both HYP and DYS via clinical and laboratory studies. The patients were classified into the following three groups: GI [OSA with comorbidities (HYP or DYS)], GII [OSA without comorbidities], and GIII [control]. Thirty-five patients with an apnea/hypopnea index >20 per hour of sleep were randomized to groups that received either Sham-CPAP or CPAP treatments over 12 months., Results: In a binary regression controlled for sex, age, body mass index, and glycemia, model 1 which analyzed direct LDL-C, demonstrated significant levels of risk in the setting of DYS but not in the settings of HYP and OSA. In model 2, which analyzed oxLDL, DYS (p = 0.01), HYP (p = 0.032), and OSA (p = 0.039) were statistically significant. Significant alterations were observed in only the sleep parameters following one year of CPAP., Conclusions: Based on the statistical regression model, only the presence of DYS (p = 0.001) was associated with the levels of direct LDL-C. The remaining comorbidities (OSA and HYP) were not significantly related to the levels of direct LDL-C. Regarding oxLDL, OSA, HYP and DYS each added significant score values to the levels of oxLDL. These findings are suggestive of the importance of assessing oxLDL among patients presenting with OSA, both with and without comorbidities., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Plant sterol (PS) supplementation has been widely used alone or combined with lipid-lowering therapies (LLTs) to reduce low-density lipoprotein (LDL) cholesterol. The effects of PS added to high-intensity LLT are less reported, especially regarding the effects on cholesterol synthesis and absorption., Methods: A prospective, randomized, open-label study, with parallel arms and blinded end points was designed to evaluate the effects of addition of PS to LLT on LDL cholesterol, markers of cholesterol synthesis, and absorption. Eighty-six patients of both genders were submitted to a 4-wk run-in period with atorvastatin 10 mg (baseline). Following, subjects received atorvastatin 40 mg, ezetimibe 10 mg, or combination of both drugs for another 4-wk period (phase I). In phase II, capsules containing 2.0 g of PSs were added to previous assigned treatments for 4 wk. Lipids, apolipoproteins, plasma campesterol, β-sitosterol, and desmosterol levels were assayed at all time points. Within and between-group analyses were performed., Results: Compared with baseline, atorvastatin 40 mg reduced total and LDL cholesterol (3% and 22%, respectively, P < .05), increased β-sitosterol, campesterol/cholesterol, and β-sitosterol/cholesterol ratios (39%, 47%, and 32%, respectively, P < .05); ezetimibe 10 mg reduced campesterol and campesterol/cholesterol ratio (67% and 70%, respectively, P < .05), and the combined therapy decreased total and LDL cholesterol (22% and 38%, respectively, P < .05), campesterol, β-sitosterol, and campesterol/cholesterol ratio (54%, 40%, and 27%, P < .05). Addition of PS further reduced total and LDL cholesterol by ∼ 7.7 and 6.5%, respectively, in the atorvastatin therapy group and 5.0 and 4.0% in the combined therapy group (P < .05, for all), with no further effects in absorption or synthesis markers., Conclusions: PS added to LLT can further improve lipid profile, without additional effects on intestinal sterol absorption or synthesis., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

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.

Background: Patients with diabetes are in extract higher risk for fatal cardiovascular events., Objective: To evaluate major predictors of mortality in subjects with type 2 diabetes., Methods: A cohort of 323 individuals with type 2 diabetes from several regions of Brazil was followed for a long period. Baseline electrocardiograms, clinical and laboratory data obtained were used to determine hazard ratios (HR) and confidence interval (CI) related to cardiovascular and total mortality., Results: After 9.2 years of follow-up (median), 33 subjects died (17 from cardiovascular causes). Cardiovascular mortality was associated with male gender; smoking; prior myocardial infarction; long QTc interval; left ventricular hypertrophy; and eGFR <60 mL/min. These factors, in addition to obesity, were predictors of total mortality. Cardiovascular mortality was adjusted for age and gender, but remained associated with: smoking (HR = 3.8; 95% CI 1.3-11.8; p = 0.019); prior myocardial infarction (HR = 8.5; 95% CI 1.8-39.9; p = 0.007); eGFR < 60 mL/min (HR = 9.5; 95% CI 2.7-33.7; p = 0.001); long QTc interval (HR = 5.1; 95% CI 1.7-15.2; p = 0.004); and left ventricular hypertrophy (HR = 3.5; 95% CI 1.3-9.7; p = 0.002). Total mortality was associated with obesity (HR = 2.3; 95% CI 1.1-5.1; p = 0.030); smoking (HR = 2.5; 95% CI 1.0-6.1; p = 0.046); prior myocardial infarction (HR = 3.1; 95% CI 1.4-6.1; p = 0.005), and long QTc interval (HR = 3.1; 95% CI 1.4-6.1; p = 0.017)., Conclusions: Biomarkers of simple measurement, particularly those related to target-organ lesions, were predictors of mortality in subjects with type 2 diabetes.

Imbalance on endothelial turnover can predict cardiovascular outcomes. We aimed at evaluating the effects of lipid-modifying therapies on circulating endothelial progenitor cells (EPCs), endothelial microparticles (EMPs), and platelet microparticles (PMPs) in high cardiovascular risk subjects with elevated C-reactive protein (CRP). Sixty-three individuals with coronary heart disease (CHD) or CHD risk equivalent on stable statin therapy, with LDL-cholesterol <100 mg/dL and CRP ≥ 2.0 mg/L were selected. After a 4-week run-in period with atorvastatin 10 mg, those with persistent CRP ≥ 2.0 mg/L were randomized to another 4-week treatment period with atorvastatin 40 mg, ezetimibe 10 mg or atorvastatin 40 mg/ezetimibe 10 mg. EPC (CD34(+)/CD133(+)/KDR(+)), EMP (CD51(+)), and PMP (CD42(+)/CD31(+)) were quantified by flow cytometry. Atorvastatin 40 mg and atorvastatin 40 mg/ezetimibe 10 mg reduced LDL-cholesterol (P < 0.001, paired T test, vs. baseline). Combined therapy, but not ezetimibe reduced CRP. CD34(+)/KDR(+) EPC were reduced after ezetimibe alone (P = 0.011 vs. baseline, Wilcoxon test) or combined with atorvastatin (P = 0.016 vs. baseline, Wilcoxon test). In addition, ezetimibe increased CD51(+) EMP (P = 0.017 vs. baseline, Wilcoxon test). No correlations between these markers and LDL-cholesterol or CRP were observed. These results contribute to understand the link between inflammation and vascular homeostasis and highlight the broader benefit of statins decreasing inflammation and preventing microparticles release, an effect not observed with ezetimibe alone.

Background: Nephropathic cystinosis is an autosomal recessive systemic severe disease characterized by intralysosomal cystine storage. Cysteamine is an essential component of treatment. There is solid evidence that cystine accumulation itself is not responsible for all abnormalities in cystinosis; there is also a deficiency of glutathione in the cytosol. Patients with cystinosis can be more susceptible to oxidative stress., Case-Diagnosis/treatment: The patient cohort comprised 23 cystinosis patients (16 males) aged <18 years (mean age 8.0 ± 3.6 years) with chronic kidney disease class I-IV with good adherence to treatment, including cysteamine. Oxidative stress was evaluated based on the levels of serum thiobarbituric acid-reactive substances (TBARS), and renal function was evaluated based on serum creatinine and cystatin C levels and creatinine clearance (Schwartz formula). N-Acetylcysteine (NAC), an antioxidant drug was given to all patients for 3 months (T1) at 25 mg/kg/day divided in three doses per day. The measured values at just before the initiation of NAC treatment (T0) served as the control for each patient., Results: Median serum TBARS levels at T0 and T1 were 6.92 (range 3.3-29.0) and 1.7 (0.6-7.2)  nmol/mL, respectively (p < 0.0001). In terms of renal function at T0 and T1, serum creatinine levels (1.1 ± 0.5 vs. 0.9 ± 0.5 mg/dL, respectively; p < 0.0001), creatinine clearance (69.7 ± 32.2 vs. T1 = 78.5 ± 33.9 mL/min/1.73 m(2), respectively; p = 0.006), and cystatin c level (1.33 ± 0.53 vs. 1.15 ± 0.54 mg/l, respectively; p = 0.0057) were all significantly different at these two time points. Serum creatinine measurements at 6 (T -6) and 3 months (T -3) before NAC initiation and at 3 (T +3) and 6 months (T +6) after NAC had been withdrawn were also evaluated., Conclusion: During the 3-month period that our 23 cystinosis patients were treated with NAC, oxidative stress was reduced and renal function significantly improved. No side-effects were detected. Larger and controlled studies are needed to confirm these findings.

Background: Obesity is associated with several cardiovascular risk factors, including nonalcoholic fatty liver disease (NAFLD). These risk factors can induce changes in the arteries such as an increase in the carotid intima-media thickness (cIMT), which contributes to the early development of atherosclerosis., Objective: To determine whether NAFLD is associated with an atherogenic lipid profile, inflammatory markers, or cIMT in obese adolescents and to compare the effects of therapeutic lifestyle changes in NAFLD and non-NAFLD groups., Methods: A total of 79 obese adolescents were divided into two groups: 33 NAFLD and 46 non-NAFLD. They were submitted to an interdisciplinary therapy involving diet exercise and psychological support during the course of 1 year. The cIMT and estimates of fat mass (liver, intra-abdominal, and subcutaneous) were determined ultrasonographically. Body composition, glucose, lipid profile, and adipokines were analyzed before and after the therapy., Results: At baseline, only in the NAFLD group was the homeostasis model assessment of insulin resistance positively correlated with cIMT and triglyceride/high-density lipoprotein cholesterol ratio. Therapy was associated with an increase in adiponectin concentrations and reduced visceral fat, cIMT, leptin, and plasminogen activator inhibitor-1 concentrations, as well as the ratios of total cholesterol/high-density lipoprotein cholesterol and triglycerides/high-density lipoprotein cholesterol in both groups. Only in the non-NAFLD group did therapy result in a reduction in the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio and increased high-density lipoprotein cholesterol concentration., Conclusions: In obese adolescents, NAFLD is associated with cardiovascular risk factors and inflammatory markers of atherosclerosis that were positively correlated with cIMT only in the NAFLD group. Nevertheless, the strength of the present study is that the interdisciplinary therapy effectively improved cIMT and other proinflammatory adipokines in both groups., (Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1

Aims: To compare the effects of two of the most effective lipid-lowering therapies with similar LDL-cholesterol reduction capacity on the innate and adaptive immune responses through the evaluation of autoantibodies anti-oxidized LDL (anti-oxLDL Abs) and electronegative LDL [LDL(-)] levels., Main Methods: We performed a prospective, randomized, open label study, with parallel arms and blinded endpoints. One hundred and twelve subjects completed the study protocol and received rosuvastatin 40 mg or ezetimibe/simvastatin 10/40 mg for 12 weeks. Lipids, apolipoproteins, LDL(-), and anti-oxLDL Abs (IgG) were assayed at baseline and end of study., Key Findings: Main clinical and laboratory characteristics were comparable at baseline. Lipid modifications were similar in both treatment arms, however, a significant raise in anti-oxLDL Abs levels was observed in subjects treated with rosuvastatin (p=0.026 vs. baseline), but not in those receiving simvastatin/ezetimibe. (p=0.233 vs. baseline), thus suggesting modulation of adaptive immunity by a potent statin. Titers of LDL(-) were not modified by the treatments., Significance: Considering atherosclerosis as an immune disease, this study adds new information, showing that under similar LDL-cholesterol reduction, the choice of lipid-lowering therapy can differently modulate adaptive immune responses., (Copyright © 2014 Elsevier Inc. All rights reserved.)