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Moderate daily consumption of alcohol (MDCA) is associated with cardiovascular risk (CVR) reduction in observational studies. Some researches have suggested that this benefit may be associated not only with red wine consumption but also with other beverages. However, there are no clinical trials evaluating the possible CVR benefit of Brazilian spirit (cachaça) in humans.This is a prospective, randomized, crossover study including healthy individuals initially assigned to a MDCA of cachaça or red wine for a period of 4 weeks. After a one-week abstinence period, the type of drink was changed for another 4 weeks of intervention. The MDCA for both beverages was determined as a dose equivalent to 28 g of ethanol per day for men and 14 g for women. CVR biomarkers analyses were performed before and after each intervention to assess the serologic status of C-reactive protein, lipid profile, platelet aggregation and glycemic profile. This study is registered on the ISRCTN platform under number 15978506.Of the 42 subjects initially randomized, 2 refused to continue in the study. The median age was 44.3 ± 10.3 years and 19 were male (47.5%). Adherence to the protocol was considered ideal with 100% regular use in both interventions and only 3 individuals in each intervention group reported alcohol abuse. There was no significant variation in anthropometric measurements during the study, except for weight gain (0.7 kg) in the red wine group (p = 0.005). The median of the delta of platelet aggregation for MDCA of cachaça was 1.2% (-1.1 to 5.3) and the median of the delta to the MDCA of wine was -1.6% (-4.5 to 2) (p = 0.02). The other biomarkers didn't show any statistically significant variation.Moderate consumption of wine and cachaça was related to variation in laboratory biomarkers of CVR related to atherosclerosis. There was significant weight gain during the period of wine consumption and there was observed a difference between platelet aggregation values after both interventions.

Introduction Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease (CAD). To the best of our knowledge, this is the first study addressing the relationship between Lp(a) and platelet reactivity in primary and secondary prevention. Methods Lp(a) was evaluated in 396 individuals with (82.3%) and without (17.7%) obstructive CAD. The population was divided into two groups according to Lp(a) concentrations with a cutoff value of 50 mg/dL. The primary objective was to evaluate the association between Lp(a) and adenosine diphosphate (ADP)-induced platelet reactivity using the VerifyNow™ P2Y12 assay. Platelet reactivity was also induced by arachidonic acid and collagen–epinephrine (C-EPI) and assessed by Multiplate™, platelet function analyzer™ 100 (PFA-100), and light transmission aggregometry (LTA) assays. Secondary objectives included the assessment of the primary endpoint in individuals with or without CAD. Results Overall, 294 (74.2%) individuals had Lp(a) 0.05). Finally, multivariable analysis did not show a significant association between ADP-induced platelet reactivity and Lp(a) ≥ 50 mg/dL [adjusted OR = 1.00 [(95% CI 0.99–1.01), P = 0.590]. Conclusion In individuals with or without CAD, Lp(a) ≥ 50 mg/dL was not associated with higher platelet reactivity. Electronic supplementary material The online version of this article (10.1007/s12325-020-01483-y) contains supplementary material, which is available to authorized users.

Increased levels of periodontal pathogens disrupt the homeostasis between the host and its microbiota and increase susceptibility to periodontal diseases. Periodontitis increases the serum concentration of mannose-binding lectin (MBL), which exacerbates local inflammatory processes. In animal studies, sirtuin 1 (SIRT1) was associated with protection against inflammation. This study analyzed the influence of non-surgical periodontal treatment on serum levels of MBL and SIRT1.Forty patients with periodontitis and 38 periodontally healthy individuals (aged 45 to 79 years) were included. Periodontitis patients received scaling and root planing using machine driven and hand instruments. Clinical parameters, inflammatory biomarkers, MBL, and SIRT1 levels were measured at baseline and at post-treatment.For all patients, an inverse correlation was observed between serum concentrations of MBL and SIRT1 (r = -0.30; P = 0.006). Periodontal treatment reduced serum concentrations of MBL (1,099.35 ± 916.59 to 861.42 ± 724.82 ng/mL; P 0.001) and C-reactive protein (6.05 ± 8.99 to 2.49 ± 2.89 mg/L; P = 0.009). By contrast, SIRT1 serum levels increased (1.06 ± 1.03 to 1.66 ± 1.64 ng/mL; P 0.001) following periodontal treatment.Periodontal treatment was associated with decreased serum concentrations of MBL and CRP and increased serum levels of SIRT1. Prospective studies are needed to assess the impact of these biomarkers on pathophysiology of periodontitis.

Background Patients with coronary artery disease (CAD) and previous ischemic cerebrovascular events (ICVE, ischemic stroke, or transitory ischemic attack) constitute a high‐risk subgroup for cardiovascular outcomes. High‐density lipoprotein cholesterol (HDL‐C) levels are correlated with cardiovascular events. Lipid transfer to HDL affects structure size and HDL subclass profile. Impairment of this transfer could influence ischemic risk seen in patients with CAD + ICVE. The objective was to evaluate the HDL ability to receive the lipids in patients with CAD with or without ICVE. Methods Patients with CAD + ICVE (n = 60) and patients with CAD only (n = 60) were matched by age, sex, acute coronary syndromes (ACS) event type, and time elapsed between the ACS event and inclusion in the study. Lipid transfer to HDL was evaluated by incubating donor lipid nanoparticles labeled with radioactive unesterified cholesterol (UC) and esterified cholesterol (EC), phospholipid (PL), and triglyceride (TG) with whole plasma. After the chemical precipitation of non‐HDL fractions and nanoparticles, the supernatant was counted for HDL radioactivity. Results CAD + ICVE group presented with impaired lipid transfer to HDL for PL (CAD + ICVE: 21.14 ± 2.7% vs CAD: 21.67 ± 3.1%, P = .03), TG (CAD + ICVE: 4.88 ± 0.97% vs CAD: 5.63 ± 0.92%, P = .002), and UC (CAD + ICVE: 5.55 ± 1.19% vs CAD: 6.16 ± 1.14%, P = .009). Lipid transfer to HDL was similar in both groups for EC. Adjusted models showed similar results. Conclusion Patients with CAD and ICVE have reduced lipid transfer to HDL compared to those with CAD only. Dysfunctional HDL may account for the higher incidence of ischemic outcomes observed in this population.

Introduction: Arterial filter is the part of the cardiopulmonary bypass circuit where blood cells are exposed to high mechanical stress and where cellular aggregates may fasten in large quantities. The aim of this study was to analyse blood cell adhesiveness in the arterial filter through scanning electron microscopy and real-time PCR assay. Methods: Prospective, clinical and observational study performed on 28 patients undergoing cardiac surgery with cardiopulmonary bypass. Arterial filters were analysed by scanning electron microscopy. Real-time PCR assay was performed in extracted material from the arterial filters for analysis of platelet GPIb and CD45 leucocyte gene expression. Blood coagulation was analysed during cardiopulmonary bypass. Patients were followed until hospital discharge or 28 days after surgery. Results: All studied arterial filters used in the subject patients showed a degree of adhesion from blood elements at scanning electron microscopy. All studied filters were positive for platelets GPIb gene expression and 15% had CD45 leucocyte gene expression. The GPIb platelet gene expression in blood lowered at the end of cardiopulmonary bypass ( p = 0.019). There was negative correlation between blood GPIb platelet gene expression and Clot SR (HEPSCREEN2 ReoRox®) (rho = 0.635; p = 0.027). The filter fields count was correlated to the D-dimer dosage (rho = 0.828; p Conclusion: There was adhesion of blood elements, especially nucleated platelets, on all arterial filters studied. Although the arterial filter worked as a safety device, that possibly prevented arterial embolisation, it may also have caused greater hyperfibrinolysis during cardiopulmonary bypass.

Introduction: It is well established that moderate consumption of red wine is associated with reduced risk of cardiovascular (CV) events. Many observational studies have shown that this same benefit could be seen with other alcohol beverages different from wine. However, the correlation between the Brazilian sugarcane liquor (“cachaca”) and CV benefit has not been demonstrated in human trials. Hypothesis: Cachaca causes changes in biomarkers of CV risk in the same proportion as wine. Methods: In this crossover randomized study, healthy individuals were initially designated to have daily moderate alcohol consumption (MAC) of either cachaca or red wine for a period of 4 weeks. MAC, for both drinks, was denoted as a daily dose equivalent of 28g of alcohol for men and 14g for women. Then, after an abstinence period of 7 days, drink types were switched for more 4 weeks. Analysis of CV risk biomarkers were determined before and after each intervention, and consisted of C-reactive protein, lipid profile, platelet aggregability and glycid profile. (This research was funded by FAPESP 2018/09675-4). Results: Of the 37 individuals originally enrolled, 2 refused to continue the study. The average age of the individuals was 41.7 (±15.3 years) and 43.2% were men. Adherence to the protocol was considered essentially ideal, with 100% of regular use in both interventions and only 3 individuals reporting abuse during the study period. There was no significant variation in anthropometric measurements during the study, except for a weight gain (0.6kg) with red wine (p = 0.011). As seen in the table, no significant changes were noted in the inflammatory markers, lipid profile, platelet aggregability nor glycid profile before and after each intervention. Conclusions: This study shows that in healthy individuals, neither red wine nor cachaca changed CV biomarkers related to atherosclerotic progression after 4 weeks of MAC. However, there was a marked weight gain with daily wine consumption.

Background To evaluate the effect of nicotinamide prior to streptozotocin-induced (STZ) diabetes in baroreflex sensitivity and cardiovascular autonomic modulation, and its association with hemodynamics and metabolic parameters. Methods Methods: Male Wistar rats were divided into control (Cont) and STZ-induced diabetes (Diab). Half of the rats from each group received a single dose of nicotinamide (100 mg/Kg) before STZ injection (Cont+NicA and Diab+NicA). All groups were followed-up for 5 weeks. Results Body weight loss of more than 40% was observed in Diab throughout the period (Diab: 271.00 ± 12.74 g; Diab+NicA: 344.62 ± 17.82). Increased glycemia was seen in Diab rats (541.28 ± 18.68 mg/dl) while Diab+NicA group had a slight decrease (440.87 ± 20.96 mg/dl). However, insulin resistance was observed only in Diab. In relation to Cont, heart rate, mean blood pressure and diastolic function were reduced when compared to Diab, together with parasympathetic modulation and baroreflex sensitivity. All of these parameters were improved in Diab+NicA when compared to Diab. Improved baroreflex sensitivity and parasympathetic modulation were correlated with glycemia, insulin resistance, and body weight mass. Additionally, Diab+NicA group increased survival rate. Conclusions Results suggest that the association of nicotinamide in STZ-induced diabetic rats prevents most of the expected derangements mainly by preserving parasympathetic and baroreflex parameters.

Background Dual antiplatelet therapy is recommended for patients with acute coronary syndromes (ACS). Approximately 10% to 15% of these patients will undergo coronary artery bypass graft (CABG) surgery for index events, and current guidelines recommend stopping clopidogrel at least 5 days before CABG. This waiting time has clinical and economic implications. Objectives This study aimed to evaluate if a platelet reactivity-based strategy is noninferior to standard of care for 24-h post-CABG bleeding. Methods In this randomized, open label noninferiority trial, 190 patients admitted with ACS with indications for CABG and on aspirin and P2Y12 receptor inhibitors, were assigned to either control group, P2Y12 receptor inhibitor withdrawn 5 to 7 days before CABG, or intervention group, daily measurements of platelet reactivity by Multiplate analyzer (Roche Diagnostics GmbH, Vienna, Austria) with CABG planned the next working day after platelet reactivity normalization (pre-defined as ≥46 aggregation units). Results Within the first 24 h of CABG, the median chest tube drainage was 350 ml (interquartile range [IQR]: 250 to 475 ml) and 350 ml (IQR: 255 to 500 ml) in the intervention and control groups, respectively (p for noninferiority Conclusions A strategy based on platelet reactivity-guided is noninferior to the standard of care in patients with ACS awaiting CABG regarding peri-operative bleeding, significantly shortens the waiting time to CABG, and decreases hospital expenses. (Evaluation of Platelet Aggregability in the Release of CABG in Patients With ACS With DAPT; NCT02516267 )

This study investigated the relationship between angiographic complexities of coronary artery disease (CAD) assessed by SYNTAX Score synergy between percutaneous coronary intervention with taxus and cardiac surgery score (SYNTAX Score) and cardiac biomarker elevation after revascularization procedures. This is a post-hoc analysis of the medicine, angioplasty or surgery study V study of patients with stable CAD. High-sensitivity troponin 1 (hs-TnI) and creatinine kinase-muscle/brain (CK-MB) were assessed before and after cardiovascular procedures. Baselines SYNTAX Scores (SXScores) were calculated by blinded investigators to patient characteristics. Of the 202 patients studied, the mean SXScore was 21.25 ± 9.24; 40.10 ± 7.09 in the high SXScore group and 19.06 ± 6.61 in low/mid SXscore group (P

Background: Evidence regarding biomarkers for risk prediction in patients with infective endocarditis (IE) is limited. We aimed to investigate the value of a panel of biomarkers for the prediction of in-hospital mortality in patients with IE. Methods: Between 2016 and 2018, consecutive IE patients admitted to the emergency department were prospectively included. Blood concentrations of nine biomarkers were measured at admission (D0) and on the seventh day (D7) of antibiotic therapy: C-reactive protein (CRP), sensitive troponin I (s-cTnI), procalcitonin, B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL6), tumor necrosis factor α (TNF-α), proadrenomedullin, alpha-1-acid glycoprotein, and galectin 3. The primary endpoint was in-hospital mortality. Results: Among 97 patients, 56% underwent cardiac surgery, and in-hospital mortality was 27%. At admission, six biomarkers were independent predictors of in-hospital mortality: s-cTnI (OR 3.4; 95%CI 1.8–6.4; P

Background: Chronic sympathetic nervous system activation is associated with endothelial dysfunction and cardiometabolic disease, which may be modulated by resveratrol (RSV) and energy restriction (ER). This study aimed to examine the effects of RSV and ER on plasma noradrenaline (NA), flow-mediated vasodilation (ed-FMD), and endothelium-independent nitrate-mediated vasodilation (ei-NMD). Methods: The study included 48 healthy adults randomized to 30-days intervention of RSV or ER. Results: Waist circumference, total cholesterol, HDL-c, LDL-c, apoA-I, and plasma NA decreased in the ER group, whilst RSV increased apoB and total cholesterol, without changing plasma NA. No effects on vascular reactivity were observed in both groups. Plasma NA change was positively correlated with total cholesterol (r = 0.443, p = 0.002), triglycerides (r = 0.438, p = 0.002), apoA-I (r = 0.467, p = 0.001), apoB (r = 0.318, p = 0.032) changes, and ei-NMD (OR = 1.294, 95%CI: 1.021–1.640). Conclusions: RSV does not improve cardiometabolic risk factors, sympathetic activity, and endothelial function. ER decreases plasma NA and waist circumference as well as improves blood lipids, but does not modify endothelial function. Finally, plasma NA was associated with ei-NMD, which could be attributed to a higher response to nitrate in patients with greater resting sympathetic vasoconstriction.

Background The lack of a correlation between myocardial necrosis biomarkers and electrocardiographic abnormalities after revascularization procedures has resulted in a change in the myocardial infarction (MI) definition. Methods Patients with stable multivessel disease who underwent percutaneous or surgical revascularization were included. Electrocardiograms and concentrations of high-sensitive cardiac troponin I (cTnI) and creatine kinase (CK)-MB were assessed before and after procedures. Cardiac magnetic resonance and late gadolinium enhancement were performed before and after procedures. MI was defined as more than five times the 99th percentile upper reference limit for cTnI and 10 times for CK-MB in percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), respectively, and new late gadolinium enhancement for cardiac magnetic resonance. Results Of the 202 patients studied, 69 (34.1%) underwent on-pump CABG, 67 (33.2%) off-pump CABG, and 66 (32.7%) PCI. The receiver operating characteristic curve showed the accuracy of cTnI for on-pump CABG, off-pump CABG, and PCI patients was 21.7%, 28.3%, and 52.4% and for CK-MB was 72.5%, 81.2%, and 90.5%, respectively. The specificity of cTnI was 3.6%, 9.4%, and 42.1% and of CK-MB was 73.2%, 86.8%, and 96.4%, respectively. Sensitivity of cTnI was 100%, 100%, and 100% and of CK-MB was 69.2%, 64.3%, and 44.4%, respectively. The best cutoff of cTnI for on-pump CABG, off-pump CABG, and PCI was 6.5 ng/mL, 4.5 ng/mL, and 4.5 ng/mL (162.5, 112.5, and 112.5 times the 99th percentile upper reference limit) and of CK-MB was 37.5 ng/mL, 22.5 ng/mL, and 11.5 ng/mL (8.5, 5.1, and 2.6 times the 99th percentile upper reference limit), respectively. Conclusions Compared with cardiac magnetic resonance, CK-MB was more accurate than cTnI for diagnosing MI. These data suggest a higher troponin cutoff for the diagnosis of procedure-related MI.

High lipoprotein(a) [Lp(a)] in plasma is an important coronary artery disease (CAD) risk factor and different mechanisms for Lp(a) atherogenicity have been postulated such as interference in coagulation cascade; however, if platelet aggregability may be involved remain uncertain. We investigated

Thromboembolic events are associated with high mortality and morbidity indexes. In this context, warfarin is the most widely prescribed oral anticoagulant agent for preventing and treating these events. This medication has a narrow therapeutic range and, consequently, patients usually have difficulty in achieving and maintaining stable target therapeutics. Some studies on the literature about oral anticoagulant management showed that pharmacists could improve the efficiency of anticoagulant therapy. However, the majority of these studies included general patients retrospectively. The aim of this study was to prospectively evaluate a pharmacist’s warfarin management in patients with poor quality of anticoagulation therapy (Time in the Therapeutic Range- TTR < 50%). We included 268 patients with atrial fibrillation (AF) and without stable dose of warfarin (TTR < 50%, based on the last three values of International Normalized Ratio-INR). We followed them up for 12 weeks, INR values were evaluated and, when necessary, the dose adjustments were performed. During the first four visits, patient’s INR was measured every 7 days. Then, if INR was within the target therapeutic range (INR: 2–3), the patient was asked to return in 30 days. However, if INR was out the therapeutic target, the patient was asked to return in 7 days. Adherence evaluation was measured through questionnaires and by counting the pills taken. Comparison between basal TTR (which was calculated based on the three last INR values before prospective phase) and TTR of 4 weeks (calculated by considering the INR tests from visits 0 to 4, in the prospective phase of the study) and basal TTR and TTR of 12 weeks (calculated based on the INR tests from visits 0 to 12, in the prospective phase of the study) revealed significant statistical differences (0.144 ± 0.010 vs. 0.382 ± 0.016; and 0.144 ± 0.010 vs. 0.543 ± 0.014, p < 0.001, respectively). We also observed that the mean TTR of 1 year before (retrospective phase) was lower than TTR value after 12 weeks of pharmacist-driven treatment (prospective phase) (0.320 ± 0.015; 0.540 ± 0.015, p < 0.001). In conclusion, pharmaceutical care was able to improve TTR values in patients with AF and poor quality of anticoagulation with warfarin.

Background Cirrhotic cardiomyopathy is characterized by an attenuated contractile response to stress. Long-term exposure of β-adrenergic receptors to persistently high levels of catecholamines has been implicated in its pathogenesis. We hypothesized that β-blockade with metoprolol could reverse the changes in heart function and morphology in cirrhotic cardiomyopathy. Patients and methods In this prospective randomized trial, we included 78 patients aged between 18 and 60 years with abnormal cardiac output response under dobutamine stress echocardiography, without primary cardiac disease or a history of alcohol intake. Patients were assigned randomly to receive metoprolol or placebo for 6 months. The primary endpoint was the improvement in cardiac output response to stress, measured by an increase in the left ventricle stroke volume more than 30%. Results Three (7.3%) patients in the metoprolol group and nine (24.3%) patients in the placebo group showed improved stroke volume (P=0.057). Diastolic dysfunction was found in two (4.8%) patients before and in five (15.6%) patients after therapy in the metoprolol group, and in 10 (27%) patients before and nine (31%) patients after therapy in the placebo group (P=0.67). After treatment, no echocardiography parameter of morphology was significantly different between metoprolol or placebo groups. No significant differences were observed in noradrenaline, plasma renin activity, and troponin levels between groups. Cirrhosis-related clinical events, including hospitalizations and mortality, were not significantly different between the two groups. Six months of therapy with β-blocker did not ameliorate heart function and morphology in patients with cirrhotic cardiomyopathy.

OBJECTIVE Evaluate if statin therapy prior to elective coronary stent implantation (CSI) reduces the plasma levels of markers of inflammation and of myocardial necrosis in low-risk stable coronary artery disease patients (CAD). BACKGROUND The elevation of markers of inflammation and of myocardial necrosis after percutaneous coronary intervention may interfere with clinical outcome. Among acute coronary syndrome patients, statins improve clinical outcomes when used before CSI-mostly due to reduction of CSI-related myocardial infarction. However, little is known concerning preprocedural statin therapy on the reduction of these markers in stable patients at low-risk. METHODS In this prospective, observational study, 100 patients (n = 50 on statin therapy vs. n = 50 not on statin) with stable coronary artery disease underwent elective CSI. Inflammatory (C-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor-α and matrix metalloproteinase-9) and myocardial necrosis markers (troponin I and CK-MB) were determined before and 24 hr after CSI. RESULTS All patients presented a significant increase of CRP and IL-6 after CSI. However, this increase was attenuated in patients on statin therapy prior to CSI than those without statin therapy: 75% vs. 150% (P < 0.001) and 192% vs. 300% (P < 0.01). The other pro-inflammatory markers were similar for both sets of patients. Troponin I and CK-MB did not change after CSI regardless of previous statin therapy or not. CONCLUSIONS Pretreatment with statin attenuates procedural inflammation, denoted by markedly lower increases of CRP and IL-6 levels, in elective CSI within low-risk stable CAD patients. Periprocedural myocardial injury was irrelevant and was not affected by preprocedural statin therapy in this population.

This study aimed to evaluate the effects of carvedilol treatment and a regimen of supervised aerobic exercise training on quality of life and other clinical, echocardiographic, and biochemical variables in a group of client-owned dogs with chronic mitral valve disease (CMVD). Ten healthy dogs (control) and 36 CMVD dogs were studied, with the latter group divided into 3 subgroups. In addition to conventional treatment (benazepril, 0.3-0.5 mg/kg once a day, and digoxin, 0.0055 mg/kg twice daily), 13 dogs received exercise training (subgroup I; 10.3 ± 2.1 years), 10 dogs received carvedilol (0.3 mg/kg twice daily) and exercise training (subgroup II; 10.8 ± 1.7 years), and 13 dogs received only carvedilol (subgroup III; 10.9 ± 2.1 years). All drugs were administered orally. Clinical, laboratory, and Doppler echocardiographic variables were evaluated at baseline and after 3 and 6 months. Exercise training was conducted from months 3-6. The mean speed rate during training increased for both subgroups I and II (ANOVA, P0.001), indicating improvement in physical conditioning at the end of the exercise period. Quality of life and functional class was improved for all subgroups at the end of the study. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level increased in subgroup I from baseline to 3 months, but remained stable after training introduction (from 3 to 6 months). For subgroups II and III, NT-proBNP levels remained stable during the entire study. No difference was observed for the other variables between the three evaluation periods. The combination of carvedilol or exercise training with conventional treatment in CMVD dogs led to improvements in quality of life and functional class. Therefore, light walking in CMVD dogs must be encouraged.

We aimed to directly compare preoperative high-sensitivity cardiac troponin (hs-cTn) I and T concentration for the prediction of major cardiac complications after non-cardiac surgery.We measured hs-cTnI and hs-cTnT preoperatively in a blinded fashion in 1022 patients undergoing non-cardiac surgery. The primary endpoint was a composite of major cardiac complications including cardiac death, cardiac arrest, myocardial infarction, clinically relevant arrhythmias, and acute heart failure within 30 days. We hypothesized that the type of surgery may impact on the predictive accuracy of hs-cTnI/T and stratified all analyses according to the type of surgery.Major cardiac complications occurred in 108 (11%) patients, 58/243 (24%) patients undergoing vascular surgery and 50/779 (6%, P .001) patients undergoing non-vascular surgery. Using regulatory-approved 99th percentile cut-off concentrations, preoperative hs-cTnI elevations were less than one-fifth as common as preoperative hs-cTnT elevations (P .001). Among patients undergoing vascular surgery, preoperative hs-cTnI concentrations, but not hs-cTnT, was an independent predictor of cardiac complications (adjusted odds ratio (aOR) 1.5, 95% confidence interval (95% CI) 1.0-2.1). The area under the receiver-operating characteristics curve (AUC) was 0.67 (95% CI, 0.59-0.75) for hs-cTnI versus 0.59 (95% CI 0.51-0.67, P = .012) for hs-cTnT. In contrast, among patients undergoing non-vascular surgery both preoperative hs-cTnI and hs-cTnT were independent predictors of the primary endpoint (aOR 1.6, 95% CI 1.3-2.0, and aOR 3.0, 95% CI 2.0-4.6, respectively) and showed higher predictive accuracy (AUC 0.77, 95% CI, 0.71-0.83, and 0.79, 95% CI 0.73-0.85, P = ns).Preoperative hs-cTnI and hs-cTnT concentrations predict major cardiac complications after non-vascular surgery, while, in patients undergoing vascular surgery, hs-cTnI may have better accuracy.

Drug interaction studies selecting patients in a real-life setting are scarce, and most studies to date are characterized by a small sample size.To evaluate the effect of amiodarone on warfarin maintenance dose and adverse events in an anticoagulation cohort from a tertiary cardiovascular service.This study recruited 866 patients, and oral anticoagulant therapy was monitored by the prothrombin time expressed as the international normalized ratio (INR). Genotyping of CYP2C9*2, CYP2C9*3, and VKORC1 3673 polymorphisms was performed.Of the 866 patients, 111 (12.8%) were taking amiodarone and warfarin simultaneously, and 514 (59.4%) reached the therapeutic target dose. The warfarin maintenance dose was significantly lower in patients simultaneously using amiodarone (23.8 ± 11.3 mg/wk) compared with other patients (29.5 ± 14.3 mg/wk; P0.001). Patients taking amiodarone had higher INR/current dose ratios (0.83 ± 0.04 per mg) compared with patients not using amiodarone (0.71 ± 0.02 per mg, P = 0.001). Adverse event frequency was not different between the groups (P = 0.40). No genotype effect was noted on the odds of bleeding associated with amiodarone use.Simultaneous use of amiodarone influences warfarin maintenance dose, but is not associated with adverse events.

Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats. Diabetes was induced experimentally by the injection of streptozotocin and nicotinamide, and the rats were treated with resveratrol for 6 weeks. According to our results, there is an up-regulation of the expression of genes and/or proteins of Glypican-1, Syndecan-4, FGF2, peroxisome proliferator-activated receptor gamma and AMP-activated protein kinase in diabetic rats. On the other hand, resveratrol treatment promoted the attenuation of left ventricular diastolic dysfunction and the down-regulation of the expression of all proteins under study. The trigger for the changes in gene expression and protein synthesis promoted by resveratrol was the presence of diabetes. The negative modulation conducted by resveratrol on FGF2 and HSPGs expression, which are involved in cardiac remodeling, underlies the amelioration of cardiac function.

Sirtuin 1 (Sirt1) plays an important role in vascular biology, and influences aspects of age-dependent atherosclerosis. In animals, the sirtuin system is strongly influenced by resveratrol and caloric restriction, but its expression in humans is controversial. This study investigated the effects of resveratrol and caloric restriction on Sirt1 serum concentrations and vascular biomarkers in a healthy human population.Forty-eight healthy participants (24 women) aged 55-65years were randomized to either 30days of resveratrol administration (500mg/day) or caloric restriction (1000cal/day). Blood was collected at baseline and day 30. Laboratory data analyzed were triglycerides, total cholesterol, HDL, VLDL, LDL, apolipoprotein A1, apolipoprotein B, lipoprotein (a), non-esterified fatty acids (NEFA), glucose, insulin, oxidative stress, C-reactive protein, and Sirt1. Expression of the Sirt1 gene was analyzed using real-time PCR. Caloric restriction diminished the abdominal circumference and improved the lipid profile, but not resveratrol intervention. Resveratrol and caloric restriction increased serum concentrations of Sirt1, from 1.06±0.71 to 5.75±2.98ng/mL; p0.0001, and from 1.65±1.81 to 5.80±2.23ng/mL; p0.0001, respectively. Sirt1 increased in women and men in both interventions. On the other hand expression of Sirt1 mRNA was not different after caloric restriction and resveratrol treatment.Caloric restriction and resveratrol significantly increased plasma concentrations of Sirt1. The long-term impact of these interventions on atherosclerosis should be assessed.

Background: The knowledge of the variables predicting mortality is important in clinical practice and for therapeutic monitoring in mitral valve disease. Objectives: To determine whether a quality of life score evaluated with the Functional Evaluation of Cardiac Health questionnaire would predict mortality in dogs with degenerative mitral valve disease (DMVD). Methods: Thirty-six client-owned dogs with mitral valve disease underwent clinical, laboratory, and echocardiographic evaluations at baseline and were monitored for 6 months. Cardiovascular death was the primary outcome. Results: The 36 dogs were classified as survivors or nonsurvivors. Higher values of the following variables were obtained at baseline in the nonsurviving group (12 dogs): amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, plasma norepinephrine, heart rate, quality of life score, diastolic left ventricular internal dimension to aortic root ratio, systolic left ventricular internal dimension to aortic root ratio, and left atrium to aortic root ratio. NT-proBNP levels and quality life score were independently associated with death in the multivariable analysis. Conclusion: The quality life score was an independent variable for cardiac death in dogs with DMVD. This result is encouraging, as this score is easy to apply and does not require any technology, only a veterinarian and an observant owner. Resumo Fundamento: O conhecimento das variáveis preditoras de mortalidade é importante para a prática clínica e para o acompanhamento terapêutico na doença da valva mitral. Objetivos: Determinar se um escore de qualidade de vida avaliado com o Functional Evaluation of Cardiac Health poderia auxiliar na predição de mortalidade em cães com doença degenerativa da valva mitral (DDVM). Métodos: Trinta e seis cães de estimação com doença valvar mitral foram submetidos a avaliação clínica, laboratorial e ecocardiográfica no início do estudo e monitorizados durante 6 meses. A morte cardiovascular foi o desfecho primário. Resultados: Os 36 cães foram classificados como sobreviventes ou não sobreviventes. Os valores mais elevados das seguintes variáveis foram obtidos no início do estudo no grupo de não sobreviventes (12 cães): fragmento N-terminal do peptídeo natriurético tipo B (NT-proBNP), norepinefrina plasmática, frequência cardíaca, escore de qualidade de vida, razão da dimensão interna diastólica do ventrículo esquerdo e raiz aórtica, razão da dimensão interna sistólica do ventrículo esquerdo e raiz aórtica e a relação da dimensão do átrio esquerdo e a raiz aórtica. Concentrações de NT-proBNP e o escore de qualidade de vida foram independentemente associados com morte na análise multivariada. Conclusão: O escore de qualidade de vida foi uma variável independente para a morte por doença cardíaca em cães com DDVM. Este resultado é encorajador, pois este escore é de fácil aplicação e não requer o emprego de tecnologia, necessitando apenas de um veterinário e um dono observador.

Proton-pump inhibitors (PPIs) are often prescribed to patients receiving dual antiplatelet therapy (DAPT). However, this class of medication, especially omeprazole, has been associated with a reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine.Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine.We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily (bid) or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12™ (Accumetrics; San Diego, CA, USA), depicting aggregability as percent inhibition of platelet aggregation (IPA).We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel (from 26.3 ± 32.9 to 17.4 ± 33.1 %; p = 0.025), with no statistical significant changes observed in the ranitidine group (from 32.6 ± 28.9 to 30.1 ± 31.3 %; p = 0.310). The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance (p = 0.07, 95 % confidence interval [CI] -1.19 to 26.59); after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance (32.7 ± 30.8 vs. 17.7 ± 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04).Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel.NCT01896557.

High-density-lipoprotein (HDL) has several antiatherogenic properties and, although the concentration of HDL-cholesterol negatively correlates with incidence of coronary artery disease (CAD), this is not sufficient to evaluate the overall HDL protective role. The aim was to investigate whether precocious CAD patients show abnormalities in lipid transfers to HDL, a fundamental step in HDL metabolism and function.Thirty normocholesterolemic CAD patients aged50 y and 30 controls paired for sex, age and B.M.I. were studied. Fasting blood samples were collected for the in vitro lipid transfer assay and plasma lipid determination. A donor nanoemulsion labeled with radioactive free-cholesterol, cholesteryl esters, phospholipids and triglycerides was incubated with whole plasma and after chemical precipitation of non-HDL fractions, supernatant was counted for radioactivity in HDL.LDL and HDL-cholesterol and triglycerides were equal in both groups. Transfers of free-cholesterol (3.8±1.2%vs 7.0±3.3%,p0.0001) and triglycerides (3.7±1.7%vs 4.9±1.9%, p=0.0125) were diminished in CAD patients whereas cholesteryl ester transfer increased (6.5±1.9%vs 4.8±1.8%, p=0.0008); phospholipid transfer was equal (17.8±3.5% vs 19.5±3.9%).Alterations in the transfer of lipids to HDL may constitute a new marker for precocious CAD and relation of this metabolic alteration with HDL antiatherogenic function should be investigated in future studies.

FUNDAMENTO: A relação entre atividade inflamatória e pró-trombótica na cardiomiopatia chagásica e em outras etiologias é obscura. OBJETIVO: Estudar o perfil de marcadores pró-trombóticos e pró-inflamatórios em pacientes com insuficiência cardíaca chagásica e compará-los com os de etiologia não chagásica. MÉTODOS: Coorte transversal. Critérios de inclusão: fração de ejeção do VE (FEVE) < 45% e tempo de início de sintomas > um mês. Os pacientes foram divididos em dois grupos: grupo 1 (G1) - sorologias positivas para Chagas - e grupo 2 (G2) - sorologias negativas para Chagas. Fator pró-inflamatório: PCR ultrassensível. Fatores pró-trombóticos: fator trombina-antitrombina, fibrinogênio, antígeno do fator de von Willebrand, P-selectina plasmática e tromboelastograma. Amostra calculada para poder de 80%, assumindo-se diferença de 1/3 de desvio-padrão; p significativo se < 0,05. Análise estatística: teste exato de Fischer para variáveis categóricas; teste t de Student não pareado para variáveis contínuas paramétricas e teste de Mann-Whitney para variáveis contínuas não paramétricas. RESULTADOS: Entre janeiro e junho de 2008, foram incluídos 150 pacientes, 80 no G1 e 70 no G2. Ambos os grupos mantinham médias de PCR ultrassensível acima dos valores de referência, porém, sem diferença significativa (p=0,328). Os níveis de fibrinogênio foram maiores no G2 do que no G1 (p=0,015). Entre as variáveis do tromboelastograma, os parâmetros MA (p=0,0013), G (p=0,0012) e TG (p=0,0005) foram maiores no G2 em comparação ao G1. CONCLUSÃO: Não há indícios de maior status pró-trombótico entre chagásicos. A dosagem de fibrinogênio e dos parâmetros MA, G e TG do tromboelastograma apontam para status pró-trombótico entre não chagásicos. Ambos os grupos tinham atividade inflamatória exacerbada. BACKGROUND: The relationship between inflammatory and prothrombotic activity in chagas cardiomyopathy and in other etiologies is unclear. OBJECTIVE: To study the profile of pro-thrombotic and pro-inflammatory markers in patients with Chagas' heart failure and compare them with patients of non-chagas etiology. METHODS: Cross-sectional cohort. Inclusion criteria: left ventricle ejection fraction (LVEF) < 45% and onset time to symptoms > one month. The patients were divided into two groups: group 1 (G1) - seropositive for Chagas - and group 2 (G2) - seronegative for Chagas. Pro-inflammatory factor: Ultra-sensitive CRP. Pro-thrombotic factors: thrombin-antithrombin factor, fibrinogen, von Willebrand factor antigen, plasma P-selectin and thromboelastography. Sample calculated for 80% power, assuming a standard deviation difference of 1/3; significant p if it is < 0.05. Statistical analysis: Fisher's exact test for categorical variables; unpaired Student's t-test for parametric continuous variables and Mann-Whitney test for nonparametric continuous variables. RESULTS: Between January and June 2008, 150 patients were included, 80 in G1 and 70 in G2. Both groups maintained the averages of high sensitivity CRP above baseline values, however, there was no significant difference (p = 0.328). The fibrinogen levels were higher in G2 than in G1 (p = 0.015). Among the thromboelastography variables, the parameters MA (p=0.0013), G (p=0.0012) and TG (p =0.0005) were greater in G2 than in G1. CONCLUSION: There is no evidence of greater pro-thrombotic status among patients with Chagas disease. The levels of fibrinogen and the MA, G and TG parameters of the thromboelastography point to pro-thrombotic status among non-chagas patients. Both groups had increased inflammatory activity.

BACKGROUND:Traditional strategies for primary cardiovascular prevention have been insufficient in reducing the high rates of coronary ischemic events in women, probably because these women are often stratified into low-risk groups. However, cardiovascular diseases continue to be the main cause of morbidity and mortality in women worldwide. We hypothesized that carotid atherosclerosis (CA) is common in middle-aged women. METHODS:We prospectively evaluated asymptomatic peri- and post-menopausal women with no cardiovascular diseases or the use of hormone therapy from two gynecologic clinics. All the patients underwent full clinical and laboratory evaluation and underwent a B-mode ultrasound for carotid evaluations. The presence of CA was defined as the presence of plaque and/or carotid intima-media thickness (CIMT)>1.00 mm. We performed logistic regression to evaluate independent predictors of CA. RESULTS:We studied 823 women (age: 54.4±5.4 years; body mass index-BMI: 28.5±4.9 kg/m2; diabetes:10%; hypertension: 58%). The prevalence of CA was 12.7% for the entire population and 11% for the low-risk sub-group as defined by a Framingham risk score

The authors evaluated levels of inflammatory markers in 34 chronic heart failure (CHF) out-patients age 65 years and over, with (N=18) and without (N=16) major depressive disorder (MDD), and healthy-control subjects (N=13). Patients with CHF had left-ventricular ejection fractions0.40 and were in the New York Heart Association functional class II or III. The authors used the SCID DSM-IV to diagnosis MDD. High-sensitivity C-reactive protein levels were significantly higher in patients with CHF and MDD as compared with healthy-control subjects. No differences regarding tumor necrosis factor(alpha) or interleukin(6) were found among the three groups.

Background Cardiac-specific troponin detected with the new high-sensitivity assays can be chronically elevated in response to cardiovascular comorbidities and confer important prognostic information, in the absence of unstable coronary syndromes. Both diabetes mellitus and coronary artery disease are known predictors of troponin elevation. It is not known whether diabetic patients with coronary artery disease have different levels of troponin compared with diabetic patients with normal coronary arteries. To investigate this question, we determined the concentrations of a level 1 troponin assay in two groups of diabetic patients: those with multivessel coronary artery disease and those with angiographically normal coronary arteries. Methods We studied 95 diabetic patients and compared troponin in serum samples from 50 patients with coronary artery disease (mean age = 63.7, 58 % male) with 45 controls with angiographically normal coronary arteries. Brain natriuretic peptide and the oxidative stress biomarkers myeloperoxidase, nitrotyrosine and oxidized LDL were also determined. Results Diabetic patients with coronary artery disease had higher levels of troponin than did controls (median values, 12.0 pg/mL (95 % CI:10–16) vs 7.0 pg/mL (95 % CI: 5.9-8.5), respectively; p = 0.0001). The area under the ROC curve for the diagnosis of CAD was 0.712 with a sensitivity of 70 % and a specificity of 66 %. Plasma BNP levels and oxidative stress variables (myeloperoxidase, nitrotyrosine, and oxidized LDL) were not different between the two groups. In a multivariate analysis, gender (p = 0.04), serum glucose (0.03) and Troponin I (p = 0.01) had independent statistical significance. Conclusion Troponin elevation is related to the presence of chronic coronary artery disease in diabetic patients with multiple associated cardiovascular risk factors. Troponin may serve as a biomarker in this high-risk population. Trial registration http://www.controlled-trials.com Registration number:ISRCTN26970041

Background: The main aims of the present study were to develop a pharmacogenetic-based warfarin dosing algorithm and to validate it in a highly admixed population. Materials & methods: We included two patient cohorts treated with warfarin (first cohort, n = 832; and second cohort, n = 133). Results: Our algorithm achieved a determination coefficient of 40% including the variables age, gender, weight, height, self-declared race, amiodarone use, enzyme inducers use, VKORC1 genotypes and predicted phenotypes according to CYP2C9 polymorphisms. Conclusion: Data suggest that our developed algorithm is more accurate than the IWPC algorithm when the application is focused on patients from the Brazilian population. Population-specific derivation and/or calibration of warfarin dosing algorithms may lead to improved performance compared with general use dosing algorithms currently available. Original submitted 26 November 2014; Revision submitted 9 April 2015

Background: Lipoprotein lipase catalyzes the hydrolysis of the triglycerides contained in both very-low-density lipoproteins and chylomicrons for storage in the adipose tissue and muscle of fats of both hepatic and dietary origin. The S447X-Stop lipoprotein lipase is the most common polymorphism of the enzyme, affecting roughly 20% of the population and is accompanied by normal or diminished fasting triglycerides and perhaps lower incidence of coronary artery disease (CAD). Delay in the removal of chylomicron and remnant is now an established risk factor for CAD. Methods: Currently, the chylomicron metabolism has been evaluated in 12 normolipidemic subjects with the S447X-Stop and in 13 age- and sex-paired control subjects with no mutation. The doubly labeled chylomicron-like emulsion method was used to evaluate chylomicron metabolism. The emulsions labeled with cholesteryl-oleate (14C-CE) and tri[9,10-3H]oleate (3H-Tg) were injected intravenously and the decay curves of the labels were determined by blood sampling over 60 min followed by radioactive counting. Results: The fractional clearance rate (FCR, min−1) of the labels was not different in the S447X carriers compared with the noncarriers (FCR 3H-Tg 0.035±0.019 and 0.030±0.009 ; FCR 14C-CE 0.008±0.007 and 0.009±0.007, respectively). Conclusions: The chylomicron intravascular lipolysis monitored by the 3H-Tg emulsion and the remnant removal monitored by the 14C-CE emulsion were not altered by the presence of this polymorphism of great populational impact.

The aim of this study was to assess the influence of anxiety and plasma catecholamines on the pharmaco-induced erection of psychogenic erectile dysfunction (ED) patients. A total of 23 patients with psychogenic ED aged from 19 to 43 y were submitted to: (1) anxiety evaluation by the Spielberger's State and Trait Anxiety Inventory-STAI; (2) intracavernous injection of PGE1 10 microg+phentolamine 1 mg with the response monitored by Rigiscan; (3) blood sampling from cavernous bodies and cubital vein for adrenaline and noradrenaline levels determination by high performance liquid chromatography. The whole procedure was done in a single clinical setting at the same day. We found no significant correlation between the erection rigidity and the cavernous or peripheral catecholamines or between erection rigidity and anxiety scores. Some patients showed rigid erections despite high anxiety scores or penile catecholamine levels while others, with incomplete erections, had much smaller levels. These results are suggestive of a more complex mechanism controlling the penile sympathetic responsiveness in psychogenic ED patients.

Background: Approximately 17% of pts with coronary artery disease (CAD) have previous ischemic stroke or transitory ischemic attack. (IS/TIA). This is a high risk subgroup for ischemic and bleeding events. The role of platelet aggregability, coagulation, endogenous fibrinolysis and inflammation in

A previous study demonstrated that the intrapleural injection of 2 mg/kg mitoxantrone in rabbits resulted in a degree of pleurodesis which is comparable to that seen after 35 mg/kg tetracycline but that the animals had a high mortality rate after this dose of mitoxantrone. The objective of the present study was to assess the acute pleural fluid findings, the acute gross and microscopic pleural findings, and the chronic gross and microscopic findings in rabbits that received mitoxantrone. Mitoxantrone, 1.5 mg/kg, was instilled intrapleurally in 70 lightly anesthetized male rabbits. Groups of rabbits were sacrificed 1, 2, 4, 7, 15, 28, and 60 days after the injection. The intrapleural injection of mitoxantrone resulted in an exudative effusion on day 1. The pleural fluid contained predominantly neutrophils and had a mean lactate dehydrogenase (LDH) level that exceeded 4,000 IU/liter. Over the following week the volume of fluid diminished, the predominant cell became the macrophage, and the LDH levels decreased to less than 400 IU/liter. Macroscopic examination of the pleural space revealed that the mean degree of pleurodesis increased progressively over the 60-day observation period. With microscopy, the mean degree of pleural fibrosis also increased progressively. There were also substantial fibrosis and inflammation of the underlying lung and the contralateral lung. The mortality rates were low in the first 28 days (3/70) but subsequently increased and exceeded 80% in the period between 60 and 120 days. This experimental model of pleurodesis should be useful in future studies directed toward uncovering the mechanisms of pleurodesis.

Ramires, P. R., C. L. M. Forjaz, C. M. C. Strunz, M. E. R. Silva, J. Diament, W. Nicolau, B. Liberman, and C. E. Negrão.Oral glucose ingestion increases endurance capacity in normal and diabetic (type I) humans. J. Appl. Physiol. 83(2): 608–614, 1997.—The effects of an oral glucose administration (1 g/kg) 30 min before exercise on endurance capacity and metabolic responses were studied in 21 type I diabetic patients [insulin-dependent diabetes mellitus (IDDM)] and 23 normal controls (Con). Cycle ergometer exercise (55–60% of maximal O2uptake) was performed until exhaustion. Glucose administration significantly increased endurance capacity in Con (112 ± 7 vs. 125 ± 6 min, P < 0.05) but only in IDDM patients whose blood glucose decreased during exercise (70.8 ± 8.2 vs. 82.8 ± 9.4 min, P < 0.05). Hyperglycemia was normalized at 15 min of exercise in Con (7.4 ± 0.2 vs. 4.8 ± 0.2 mM) but not in IDDM patients (12.4 ± 0.7 vs. 15.6 ± 0.9 mM). In Con, insulin and C-peptide levels were normalized during exercise. Glucose administration decreased growth hormone levels in both groups. In conclusion, oral glucose ingestion 30 min before exercise increases endurance capacity in Con and in some IDDM patients. In IDDM patients, in contrast with Con, exercise to exhaustion attenuates hyperglycemia but does not bring blood glucose levels to preglucose levels.

Heart failure (HF) is, after cirrhosis, the second-most common cause of ascites. Serum B-type natriuretic peptide (BNP) plays an important role in the diagnosis of HF. Therefore, we hypothesized that BNP would be useful in the differential diagnosis of ascites. Consecutive patients with new onset ascites were prospectively enrolled in this cross-sectional study. All patients had measurements of serum-ascites albumin gradient (SAAG), total protein concentration in ascitic fluid, serum, and ascites BNP. We enrolled 218 consecutive patients with ascites resulting from HF (n = 44), cirrhosis (n = 162), peritoneal disease (n = 10), and constrictive pericarditis (n = 2). Compared to SAAG and/or total protein concentration in ascites, the test that best discriminated HF-related ascites from other causes of ascites was serum BNP. A cutoff of >364 pg/mL (sensitivity 98%, specificity 99%, and diagnostic accuracy 99%) had the highest positive likelihood ratio (168.1); that is, it was the best to rule in HF-related ascites. Conversely, a cutoff ≤182 pg/mL had the lowest negative likelihood ratio (0.0) and was the best to rule out HF-related ascites. These findings were confirmed in a 60-patient validation cohort. Conclusions: Serum BNP is more accurate than ascites analyses in the diagnosis of HF-related ascites. The workup of patients with new onset ascites could be streamlined by obtaining serum BNP as an initial test and could forego the need for diagnostic paracentesis, particularly in cases where the cause of ascites is uncertain and/or could be the result of HF. (Hepatology 2014;59:1043–1051)

The creatine kinase-isoenzyme MB (CK-MB) mass assay is one of the laboratory tests used for the diagnosis of myocardial infarction. It is recommended, however, that reference limits should take gender and race into account. In the present study, we analyzed the plasma CK-MB mass and troponin levels of 244 healthy volunteers without a personal history of coronary artery disease and with no chronic diseases, muscular trauma or hypothyroidism, and not taking statins. The tests were performed with commercial kits, CK-MB mass turbo kit and Troponin I turbo kit, using the Immulite 1000 analyzer from Siemens Healthcare Diagnostic. The values were separated according to gender and showed significant differences by the Mann-Whitney test. Mean (± SD) CK-MB mass values were 2.55 ± 1.09 for women (N = 121; age = 41.20 ± 10.13 years) and 3.49 ± 1.41 ng/mL for men (N = 123; age = 38.16 ± 11.12 years). Gender-specific reference values at the 99th percentile level, according to the Medicalc statistical software, were 5.40 ng/mL for women and 7.13 ng/mL for men. The influence of race was not considered because of the high miscegenation of the Brazilian population. The CK-MB values obtained were higher than the 5.10 mg/mL proposed by the manufacturer of the laboratory kit. Therefore, decision limits should be related to population and gender in order to improve the specificity of this diagnostic tool, avoiding misclassification of patients.

The relationship between inflammatory and prothrombotic activity in chagas cardiomyopathy and in other etiologies is unclear.To study the profile of pro-thrombotic and pro-inflammatory markers in patients with Chagas' heart failure and compare them with patients of non-chagas etiology.Cross-sectional cohort.left ventricle ejection fraction (LVEF)45% and onset time to symptomsone month. The patients were divided into two groups: group 1 (G1) - seropositive for Chagas - and group 2 (G2) - seronegative for Chagas. Pro-inflammatory factor: Ultra-sensitive CRP. Pro-thrombotic factors: thrombin-antithrombin factor, fibrinogen, von Willebrand factor antigen, plasma P-selectin and thromboelastography. Sample calculated for 80% power, assuming a standard deviation difference of 1/3; significant p if it is0.05.Fisher's exact test for categorical variables; unpaired Student's t-test for parametric continuous variables and Mann-Whitney test for nonparametric continuous variables.Between January and June 2008, 150 patients were included, 80 in G1 and 70 in G2. Both groups maintained the averages of high sensitivity CRP above baseline values, however, there was no significant difference (p = 0.328). The fibrinogen levels were higher in G2 than in G1 (p = 0.015). Among the thromboelastography variables, the parameters MA (p=0.0013), G (p=0.0012) and TG (p =0.0005) were greater in G2 than in G1.There is no evidence of greater pro-thrombotic status among patients with Chagas disease. The levels of fibrinogen and the MA, G and TG parameters of the thromboelastography point to pro-thrombotic status among non-chagas patients. Both groups had increased inflammatory activity.

Serum levels of troponin and heart-related fraction of creatine kinase (CK-MB) mass are used as diagnostic and prognostic criteria in myocardial infarction, but the relation between those levels and the necropsy-determined size of necrosis has not been tested in human beings. In this retrospective study, 1-cm-thick transverse sections of the ventricles were cut from the base to the apex in the necropsy hearts of 27 patients aged 47 to 86 years (mean 66, median 69; 19 men). Total and necrotic areas were measured using a computer-linked image analysis system. The weights of the necrotic areas were also calculated. The correlations of the areas and weights of necrotic myocardium with the highest serum values of CK-MB mass and troponin I, which had been quantified during life by chemiluminescence immunoassays, were verified by Pearson's test; results were considered significant at p

OBJETIVO: O objetivo deste estudo foi avaliar o efeito do polimorfismo S447X sobre os lípides plasmáticos em pacientes com doença arterial coronariana (DAC) prematura. MÉTODOS: Os lípides plasmáticos e a genotipagem foram determinados em 2 grupos: 313 pacientes com DAC prematura (

e20648 Background: vein thromboembolic events (VTE) significantly affect oncological patients, leading to increased morbidity and mortality. Early diagnosis could reduce these complications. Method...

Objective—To evaluate correlations between plasma concentrations of norepinephrine and Doppler echocardiographic variables for dogs with degenerative mitral valve disease (DMVD) or dilatative cardiomyopathy (DCM) to better understand the time course and magnitude of sympathetic activation in dogs with heart failure (HF). Animals—15 healthy dogs, 15 dogs with DMVD, and 15 dogs with DCM. Procedures—Dogs were positioned in lateral recumbency with minimal restraint for at least 20 minutes. Plasma samples were obtained and assayed by use of high-performance liquid chromatography. Concentrations were correlated with HF classification and with the main Doppler echocardiographic variables for each group. Results—Mean ± SD norepinephrine concentration was significantly higher in dogs with DMVD (494.4 ± 204.8 pg/mL) or DCM (655.7 ± 652.5 pg/mL) than in healthy dogs (205.8 ± 78.9 pg/mL), but concentrations did not differ significantly between the 2 groups with HF. Correlations were not detected between norepinephrine and heart rate or any M-mode echocardiographic variables evaluated, except for fractional shortening (FS) in DCM dogs. In that group, norepinephrine was inversely correlated with FS values. In DMVD dogs, no significant correlation was found between norepinephrine and the left atrium-to-aortic root ratio or mitral regurgitation. Conclusions and Clinical Relevance—A proportional inverse correlation exists between norepinephrine and FS values in dogs with DCM. However, norepinephrine concentration was not correlated with the evaluated echocardiographic variables in dogs with DMVD. Sympathetic antagonists should be evaluated as a treatment option because of the increased plasma concentrations of norepinephrine detected in dogs with HF.

Background The effect of home-based exercise training on neurovascular control in heart failure patients is unknown. Aims To test the hypothesis that home-based training would maintain the reduction in muscle sympathetic nerve activity (MSNA) and forearm vascular resistance (FVR) acquired after supervised training. Methods and results Twenty-nine patients (54±1.9 years, EF

After injury to the adult central nervous system (CNS), numerous cytokines and growth factors are released that contribute to reactive gliosis and extracellular matrix production. In vitro examination of these cytokines revealed that the presence of transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF) greatly increased the production of several chondroitin sulfate proteoglycans (CSPG) by astrocytes. Treatment of astrocytes with other EGF-receptor (ErbB1) ligands, such as TGF-alpha and HB-EGF, produced increases in CSPG production similar to those observed with EGF. Treatment of astrocytes, however, with heregulin, which signals through other members of the EGF-receptor family (ErbB2, ErbB3, ErbB4), did not induce CSPG upregulation. The specificity of activation through the ErbB1 receptor was further verified by using a selective antagonist (AG1478) to this tyrosine kinase receptor. Western blot analysis of astrocyte supernatant pre-digested with chondroitinase ABC indicated the presence of multiple core proteins containing 4-sulfated or 6-sulfated chondroitin. To identify some of these CSPGs, Western blots were screened using antibodies to several known CSPG core proteins. These analyses showed that treatment of astrocytes with EGF increased phosphacan expression, whereas treatment with TGF-beta1 increased neurocan expression. Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of these molecules in vivo, which result in increased expression of TGF-beta1, EGF-receptor, neurocan, and phosphacan after injury to the brain. These data begin to elucidate some of the injury-induced growth factors that regulate the expression of CSPGs which could be targeted in the future to modulate CSPG production after injury to the central nervous system.

Background Estrogen protects against atherosclerosis through its genomic/nongenomic effects. Estrogen receptors (ESR) α (1) and β (2) mediate much estrogen action. Both receptors exist in the arterial wall, but the extent of their distribution in arterial layers is unknown. Allelic variants of the gene encoding ESR1 and ESR2 may alter their expression and function, resulting in genetic variability. Methods In the present age-adjusted, case-control study, the prevalence of four mutations in estrogen receptors was analyzed in patients with premature CAD and controls. Results Mutation in the ESR1 ( Pvu II) was more prevalent in the controls (18 vs. 11%; p =0.062) than in CAD patients, and the mutation identified by the Xba I enzyme in the same receptor was associated with reduced apolipoprotein B levels and low body mass index. Mutation of the ESR2 ( Alu I) was more prevalent in CAD patients (0.6 vs. 18%; p =0.008). Homozygosis for this mutation involved increased body mass index, elevated serum triglycerides and apolipoprotein B, and reduced HDL-cholesterol. Multivariate logistic regression analysis showed dyslipidemia, low serum HDL levels, and ESR2 polymorphism ( Alu I) [OR=1.89 (95% CI: 1.08–3.34); p =0.034] to be independent risk factors for CAD. Conclusions Our data suggest that mutation of the ESR2 is an independent risk marker for premature CAD.

We investigated whether 2,3-diphosphoglycer- ate (2,3-DPG) is altered in patients with low cardiac output and the influence of its concentration on the calculation of in vivo P50. Biochemical and blood gas analysis were per- formed along with the measurement of cardiac output and body temperature in 13 patients submitted to cardiopul- monary bypass surgeries without the use of donor blood. In vivo P50 was calculated using the measured (P50m) and the estimated 2,3-DPG (P50e). 2,3-DPG concentration was lower in these patients when compared to the values obtained in normal volunteers (6.9 ± 2.2 vs. 11.9 ± 2.4 mmol/gHb). P50m was lower than P50e (21.6 ± 1.1 vs. 30.1 ± 1.2 mm Hg) at all time points. Our data show that in patients with low cardiac output, 2,3-DPG concentration is reduced. Therefore, in these patients, the use of standard values for this variable may introduce an error in the cal- culation of in vivo P50. Key Words: 2,3-Diphosphoglycer- ate—In vivo P50.

In patients taking dual antiplatelet therapy with acetylsalycilic acid (ASA) and clopidogrel, proton-pump inhibitors are often utilized for gastrointestinal (GI) bleeding prophylaxis. However, this class of medication has been associated with reduction of the antiplatelet potency of clopidogrel. The