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Abstract 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.

BackgroundWarfarin is the most common oral anticoagulant drug, especially in low-income and emerging countries, because of the high cost of direct oral anticoagulant (DOACs), or when warfarin is the only proven therapy (mechanical prosthetic valve and kidney dysfunction). The quality of warfarin therapy is directly associated with dose management. Evidence shows that pharmaceutical care achieves a better quality of therapy with warfarin. However, there are no studies showing this intervention in a specific patient group with poor quality of anticoagulation in a long period after the end of the follow-up by a pharmacist. Thus, the aim of this study was to evaluate whether the quality of warfarin therapy driven by a pharmacist remains stable in the long term after the end of follow up with a pharmacist, in AF patients with poor quality of anticoagulation.MethodsThis is a prospective study, which evaluated about 2,620 patients and selected 262 patients with AF and poor quality of anticoagulation therapy with warfarin (TTR

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.

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.

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.

The myocardial infarction (MI) types 4a and 5 guidelines recommend cardiac troponin (cTn) diagnostic decision limits of 5 and 10 times the 99th percentile, respectively. Different cTn kits elicit different responses, so the MI diagnosis is still challenging. The study aimed to establish the cutoff values and the accuracy of three different cTnI kits in the diagnosis of post-procedural MI. We analyzed 115 patients with multivessel stable chronic coronary artery disease; 26 underwent percutaneous coronary intervention, and 89 underwent coronary artery bypass graft. Delayed-enhancement magnetic resonance imaging was performed before and after each intervention for definitive MI diagnoses. Two contemporary and one high-sensitivity cTnI immunoassays were used. ROC curves determined the accuracy of each assay. Low accuracy was observed after applying the current guidelines recommendations. The three cTnI assays accuracies improved when adjusted by the new ROC cutoffs, reaching 82% for MI type 5 for all assays, and 78%, 88%, and 87% for MI type 4 for Siemens, Beckman, and Abbott, respectively. The ultrasensitive and contemporary tests’ accuracy for MI types 4a and 5 diagnoses are equivalent when adjusted for these new cutoffs. The hs-cTnI assays had lower accuracy than contemporary tests for MI types 4a and 5 diagnoses.

Introduction: HDL function has gained prominence in the literature as there is a greater predictive capacity for risk in early coronary artery disease when compared to the traditional parameters. However, it is unclear how dietary energy restriction and atorvastatin influence HDL function. Methods: A randomized controlled trial with 39 women with early CAD divided into three groups (n = 13): energy restriction (30% of VET), atorvastatin (80 mg), and control. Analyses of traditional biochemical markers (lipid and glucose profile), circulating Sirt-1, and HDL function (lipid composition, lipid transfer, and antioxidant capacity). Results: Participants’ mean age was 50.5 ± 3.8 years. Energy restriction increased Sirt-1 by 63.6 pg/mL (95%CI: 1.5–125.7; p = 0.045) and reduced BMI by 0.8 kg/m2 (95%CI: −1.349–−0.273; p = 0.004) in a manner independent of other cardiometabolic factors. Atorvastatin reduced LDL-c by 40.0 mg/dL (95%CI: −69.910–−10.1; p = 0.010). Increased Sirt-1 and reduced BMI were independently associated with reduced phospholipid composition of HDL (respectively, β = −0.071; CI95%:−0.136–−0.006; p = 0.033; β = 7.486; CI95%:0.350–14.622; p = 0.040). Reduction in BMI was associated with lower HDL-free cholesterol (β = 0.818; CI95%:0.044–1.593; p = 0.039). LDL-c reduction by statins was associated with reduced maximal lipid peroxide production rate of HDL (β = 0.002; CI95%:0.000–0.003; p = 0.022) and total conjugated diene generation (β = 0.001; CI95%:0.000–0.001; p = 0.029). Conclusion: This study showed that energy restriction and atorvastatin administration were associated with changes in lipid profile, serum Sirt-1 concentrations, and HDL function.

Background: Atherosclerosis and periodontal disease (PD) are inflammatory diseases that have been shown in studies to have a direct association. Mannose-binding lectin (MBL) is an immune system protein that binds to periodontal pathogens favoring phagocytosis. Conversely, increased serum sirtuin-1 (SIRT1) concentration reduces the inflammatory process. Methods: This was a prospective, case-controlled study that analyzed serum concentration of biomarkers in patients with or without coronary artery disease (CAD) and PD. A total of 78 patients were evaluated: 20 healthy individuals, 18 patients with CAD, 20 patients with PD, and 20 patients with both PD and CAD. Clinical and laboratory characteristics were analyzed before and after nonsurgical treatment of PD and also at two equivalent times in patients without PD. Serum MBL and SIRT1 concentration were analyzed by enzyme-linked immunosorbent assay. Results: A negative correlation was observed between changes in serum concentration of MBL and SIRT1 ( r = −0.30; p = 0.006). Comparison between pre- and post-treatment of PD showed a reduction in MBL levels (886.27 ± 906.72 versus 689.94 ± 808.36; p = 0.002) and an increase in SIRT1 values (0.80 ± 1.01 versus 1.49 ± 1.55; p = 0.005) in patients with PD and without CAD. The same result was observed in patients with PD and CAD for MBL and SIRT1, respectively, of 1312.43 ± 898.21 versus 1032.90 ± 602.52 ( p = 0.010) and 1.32 ± 1.0 versus 1.82 ± 1.75 ( p = 0.044). Conclusion: PD treatment reduced MBL serum concentration and increased SIRT1 serum concentration in patients with and without CAD.

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: High sensitivity C-reactive protein (hs-CRP) is commonly used in clinical practice to assess cardiovascular risk. However, a correlation has not yet been established between the absolute levels of peripheral and central hs-CRP. Objective: To assess the correlation between serum hs-CRP levels (mg/L) in a peripheral vein in the left forearm (LFPV) with those in the coronary sinus (CS) of patients with coronary artery disease (CAD) and a diagnosis of stable angina (SA) or unstable angina (UA). Methods: This observational, descriptive, and cross-sectional study was conducted at the Instituto do Coração, Hospital das Clinicas, Faculdade de Medicina, Universidade de São Paulo, and at the Hospital Beneficência Portuguesa de Sao Paulo, where CAD patients referred to the hospital for coronary angiography were evaluated. Results: Forty patients with CAD (20 with SA and 20 with UA) were included in the study. Blood samples from LFPV and CS were collected before coronary angiography. Furthermore, analysis of the correlation between serum levels of hs-CRP in LFPV versus CS showed a strong linear correlation for both SA (r = 0.993, p < 0.001) and UA (r = 0.976, p < 0.001) and for the entire sample (r = 0.985, p < 0.001). Conclusion: Our data suggest a strong linear correlation between hs-CRP levels in LFPV versus CS in patients with SA and UA.

OBJETIVO: Comparar os resultados do Índice de Normalização Internacional (INR) obtidos pelo teste rápido com os do método convencional nos pacientes em terapia de anticoagulação oral com varfarina sódica. MÉTODOS: Para 383 pacientes tratados com varfarina (idade média: 56,5 anos; 207 mulheres), o INR foi determinado em sangue capilar pelo equipamento Hemochron Jr. e comparado com os resultados de amostras de plasma venoso analisadas pelo teste convencional realizado em equipamento Coag-A-Mate. Foram avaliados os resultados do desempenho global das amostras e dos seguintes subgrupos: INR < 2,0, entre 2,0 a 3,5 e > 3,5. RESULTADOS: A comparação entre os valores de INR dos dois métodos resultou em um coeficiente de correlação (r) de 0,86. Entretanto, a análise das diferenças médias entre os resultados dos dois testes, considerando os três subgrupos, apresentou diferenças estatisticamente significativas (p < 0,001): 0,14 ± 0,21 (INR < 2,0); 0,54 ± 0,31 (2,0 < INR < 3,5) e 1,64 ± 1,10 (INR> 3,5). O cálculo do teste t-pareado de Student resultou em um p < 0,001 para os três subgrupos analisados. CONCLUSÃO: A adoção do teste rápido para monitoramento da anticoagulação oral apresenta restrições. Esse método subestimou a intensidade da anticoagulação nos três subgrupos estudados.OBJECTIVE: to compare the international normalized ratio (INR) measured by a point-of-care (POC) testing device with that measured by the conventional method in patients undergoing anticoagulation therapy with warfarin sodium. METHODS: The INR of 383 warfarin-treated patients (mean age: 56.5 years; 207 female) was measured in capillary blood using the Hemochron Jr. device and compared with that of venous plasma samples determined by the conventional method performed in a Coag-A-Mate analyzer. Results were evaluated globally and for the following subgroups: INR < 2.0, from 2.0 to 3.5, and > 3.5. RESULTS: Using both methods, the comparison between INR values yielded a correlation coefficient (r) of 0.86. However, mean differences in INR in both tests, considering the three subgroups, proved to be statistically significant (p 3.5). Paired Student’s t-test analysis revealed a p value < 0.001 for the three subgroups studied. CONCLUSION: The use of point-of-care testing for monitoring oral anticoagulation has some limitations. Anticoagulation intensity was underestimated by this method in the three subgroups studied.

CONTEXT AND OBJECTIVES: Glycoprotein inhibitors (abciximab, eptifibatide and tirofiban) are used in patients with unstable angina and non-ST-segment elevation myocardial infarction before percutaneous coronary intervention. Of these, tirofiban is the least effective. We hypothesized that the response to tirofiban might be associated with glycoprotein gene mutations. DESIGN AND SETTING: Prospective study at Emergency Unit, Heart Institute (InCor), University of São Paulo. METHOD: Intrahospital evolution and platelet aggregation in response to tirofiban were analyzed in relation to four glycoprotein mutations in 50 patients indicated for percutaneous coronary intervention: 17 (34%) with unstable angina and 33 (66%) with non-ST-segment elevation myocardial infarction. Platelet aggregation was analyzed using the Born method. Blood samples were obtained before and one hour after tirofiban infusion. Glycoproteins Ia (807C/T ), Ib (Thr/Met) , IIb (Ile/Ser ) and IIIa (PIA ) were the mutations selected. RESULTS: Hypertension, dyslipidemia, diabetes, smoking, previous coronary artery disease and stroke were similar between the groups. Mutant glycoprotein IIIa genotypes had lower platelet aggregation before tirofiban administration than that of the wild genotype (41.0% ± 22.1% versus 55.9% ± 20.8%; P = 0.035). Mutant glycoprotein IIIa genotypes correlated moderately with lower platelet inhibition (r = -0.31; P = 0.030). After tirofiban administration, platelet glycoprotein Ia, Ib, IIb and IIIa mutations did not influence the degree of inhibition of platelet aggregation or intrahospital mortality. CONCLUSIONS: Mutations of glycoproteins Ia, Ib, IIb and IIIa did not influence platelet aggregation in response to tirofiban in patients with unstable angina and non-ST-segment elevation myocardial infarction.

OBJECTIVES: Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 4-17% of patients with coronary artery disease (CAD). This subgroup of patients is at high risk for both ischemic and bleeding events. The aim of this study was to determine the role of platelet aggregability, coagulation and endogenous fibrinolysis in patients with CAD and previous IS or TIA. METHODS: A prospective case-control study that included 140 stable CAD patients divided into two groups: the CASE group (those with a previous IS/TIA, n=70) and the CONTROL group (those without a previous IS/TIA, n=70). Platelet aggregability (VerifyNow Aspirin® and VerifyNow P2Y12®), coagulation (fibrinogen and thromboelastography by Reorox®) and endogenous fibrinolysis (D dimer and plasminogen activator inhibitor-1) were evaluated. RESULTS: Patients in the CASE group presented significantly higher systolic blood pressure levels (135.84±16.09 vs 123.68±16.11, p