Publications by authors named "Maria Cristina Izar"

54 Publications

Performance of the Electrocardiogram in the Diagnosis of Left Ventricular Hypertrophy in Older and Very Older Hypertensive Patients.

Arq Bras Cardiol 2021 Aug 6. Epub 2021 Aug 6.

Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, SP - Brasil.

Background: Left ventricular hypertrophy (LVH) is an important cardiovascular risk factor, regardless of arterial hypertension. Despite the evolution of imaging tests, the electrocardiogram (ECG) is still the most used in the initial evaluation, however, with low sensitivity.

Objective: To evaluate the performance of the main electrocardiographic criteria for LVH in elderly and very elderly hypertensive individuals.

Methods: In a cohort of hypertensive patients, ECGs and doppler echocardiographies (ECHO) were performed and separated into three age groups: <60 years, Group I; 60-79 years Group II; and ≥80 years, Group III. The most used electrocardiographic criteria were applied for the diagnosis of LVH: Perugia; Pegaro-Lo Presti; Gubner-Ungerleider; Narita; (Rm+Sm) x duration; Cornell voltage; Cornell voltage duration; Sokolow-Lyon voltage; R of aVL ≥11 mm; RaVL duration. In evaluating the performance of these criteria, in addition to sensitivity (Sen) and specificity (Esp), the "Diagnostic Odds Ratios" (DOR) were analyzed. We considered p-value <0.05 for the analyses, with two-tailed tests.

Results: In 2,458 patients, LVH was present by ECHO in 781 (31.7%). In Groups I and II, the best performances were for the criteria of Narita, Perugia, (Rm+Sm) x duration, with no statistical differences between them. In Group III (very elderly) the Perugia criteria and (Rm+Sm) x duration had the best performances: Perugia [44,7/89.3; (Sen/Esp)] and (Rm+Sm) duration [39.4%/91.3%; (Sen/Esp), p<0.05)], with the best PAIN results:6.8. This suggests that in this very elderly population, these criteria have greater discriminatory power to separate patients with LVH.

Conclusion: In very elderly hypertensive patients, the Perugia electrocardiographic criteria and (Rm+Sm) x duration showed the best diagnostic performance for LVH.
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http://dx.doi.org/10.36660/abc.20200600DOI Listing
August 2021

Evaluation of two highly effective lipid-lowering therapies in subjects with acute myocardial infarction.

Sci Rep 2021 Aug 5;11(1):15973. Epub 2021 Aug 5.

Division of Cardiology, Department of Medicine, Federal University of Sao Paulo (UNIFESP), Rua Loefgren 1350, São Paulo, SP, CEP 04040-001, Brazil.

For cardiovascular disease prevention, statins alone or combined with ezetimibe have been recommended to achieve low-density lipoprotein cholesterol targets, but their effects on other lipids are less reported. This study was designed to examine lipid changes in subjects with ST-segment elevation myocardial infarction (STEMI) after two highly effective lipid-lowering therapies. Twenty patients with STEMI were randomized to be treated with rosuvastatin 20 mg QD or simvastatin 40 mg combined with ezetimibe 10 mg QD for 30 days. Fasting blood samples were collected on the first day (D1) and after 30 days (D30). Lipidomic analysis was performed using the Lipidyzer platform. Similar classic lipid profile was obtained in both groups of lipid-lowering therapies. However, differences with the lipidomic analysis were observed between D30 and D1 for most of the analyzed classes. Differences were noted with lipid-lowering therapies for lipids such as FA, LPC, PC, PE, CE, Cer, and SM, notably in patients treated with rosuvastatin. Correlation studies between classic lipid profiles and lipidomic results showed different information. These findings seem relevant, due to the involvement of these lipid classes in crucial mechanisms of atherosclerosis, and may account for residual cardiovascular risk.Randomized clinical trial: ClinicalTrials.gov, NCT02428374, registered on 28/09/2014.
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http://dx.doi.org/10.1038/s41598-021-95455-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342504PMC
August 2021

Accuracy of Post-thrombolysis ST-segment Reduction as an Adequate Reperfusion Predictor in the Pharmaco-Invasive Approach.

Arq Bras Cardiol 2021 07;117(1):15-25

Universidade Federal de Sao Paulo, São Paulo, SP - Brasil.

Background: Primary percutaneous coronary intervention is considered the "gold standard" for coronary reperfusion. However, when not available, the drug-invasive strategy is an alternative method and the electrocardiogram (ECG) has been used to identify reperfusion success.

Objectives: Our study aimed to assess ST-Segment changes in post-thrombolysis and their power to predict recanalization and using the angiographic scores TIMI-flow and Myocardial Blush Grade (MBG) as an ideal reperfusion criterion.

Methods: 2,215 patients with ST-Segment Elevation Myocardial Infarction (STEMI) undergoing fibrinolysis [(Tenecteplase)-TNK] and referred to coronary angiography within 24 h post-fibrinolysis or immediately referred to rescue therapy were studied. The ECG was performed pre- and 60 min-post-TNK. The patients were categorized into 2 groups: those with ideal reperfusion (TIMI-3 and MBG-3) and those with inadequate reperfusion (TIMI and MBG <3). The ECG reperfusion criterion was defined by the reduction of the ST-Segment >50%. A p-value <0.05 was considered for the analyses, with bicaudal tests.

Results: The ECG reperfusion criterion showed a positive predictive value of 56%; negative predictive value of 66%; sensitivity of 79%; and specificity of 40%. There was a weak positive correlation between ST-Segment reduction and ideal reperfusion angiographic data (r = 0.21; p <0.001) and low diagnostic accuracy, with an AUC of 0.60 (95%CI: 0.57-0.62).

Conclusion: The ST-Segment reduction was not able to accurately identify patients with adequate angiographic reperfusion. Therefore, even patients with apparently successful reperfusion should be referred to angiography soon, to ensure adequate macro and microvascular coronary flow.
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http://dx.doi.org/10.36660/abc.20200241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294746PMC
July 2021

Phytosterol consumption and markers of subclinical atherosclerosis: Cross-sectional results from ELSA-Brasil.

Nutr Metab Cardiovasc Dis 2021 06 20;31(6):1756-1766. Epub 2021 Mar 20.

Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil. Electronic address:

Background And Aims: Phytosterol (PS) consumption is associated with lower total and LDL-cholesterol (LDL-c) concentrations, but its impact on cardiovascular risk is unclear. This study assessed the effect of usual intake of PS on markers of subclinical atherosclerosis in the Longitudinal Study of Adult Health (ELSA-Brasil).

Methods And Results: This cross-sectional study included 2560 participants of ELSA-Brasil, aged 48 (43-54) years, with available food frequency questionnaires (FFQ), coronary artery calcium (CAC) scores, carotid intima media thickness (cIMT), and carotid-femoral pulse wave velocity (cf-PWV), at baseline. Several logistic and linear regression models were used, and significance level was set at a P < 0.05. Mean values (SD) for PS consumption were 256 (198) mg/day, CAC 22.78 (110.54) Agatston Units, cf-PWV 9.07 (1.60) m/s and cIMT 0.57 (0.12) mm. PS consumption in Q4 was associated with lower total- and LDL-c levels, and with higher percentiles of cf-PWV (P < 0.001). Proportion of subjects in Q4 of PS consumption was 1.5 times higher among individuals in cf-PWV Q4, than in Q1 (P = 0.002, for comparisons among quartiles). There was a trend (P = 0.003) for higher cf-PWV with higher PS intake. In crude logistic and linear regressions, PS intake was associated with cf-PWV. In the adjusted models, these associations disappeared. No associations were found between PS and cIMT or CAC.

Conclusions: In this large and apparently healthy cross-sectional sample from ELSA-Brasil, usual PS consumption was associated with lower total- and LDL-cholesterol, but not with markers of subclinical atherosclerosis.
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http://dx.doi.org/10.1016/j.numecd.2021.02.031DOI Listing
June 2021

HIV-Infected Naïve Patients Exhibit Endothelial Dysfunction Concomitant with Decreased Natural Antibodies Against Defined Apolipoprotein B Autoantigens.

Arq Bras Cardiol 2021 04;116(4):844-849

Universidade Federal de São Paulo Escola Paulista de Medicina, São Paulo, SP - Brasil.

Backgorund: Traditional and HIV-defined risk factors may be associated with an increase in cardiovascular events. Recent studies have suggested that the humoral immune response to modified LDL may be associated with the process of atherosclerosis.

Objectives: To evaluate the presence of anti-oxLDL and apolipoprotein B-derived peptides in the blood, and their association with the endothelial function in HIV-infection.

Methods: This study consecutively included subjects matched for age, gender, and demographic data in two groups: (1) HIV-infected and naïve for antiviral therapy and (2) uninfected individuals. Subclinical atherosclerosis was assessed by intimal-media thickness, using ultrasonography of the carotid arteries. Endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery by ultrasonography. Autoantibodies (IgM, IgG) anti-oxidized low-density lipoprotein (oxLDL), anti-apolipoprotein B-peptide fragments (ApoB-D and 0033G-Cys peptides), and cytokine levels were evaluated by ELISA.

Results: This study's results showed no difference in subclinical atherosclerosis between groups; however, HIV-infected subjects showed a lower FMD, when compared to non-infected subjects. Therefore, HIV-infected subjects showed higher levels of inflammatory cytokines, titers of IgG anti-oxLDL, and IgG anti-ApoB-D. In contrast, titers of IgM anti-ApoB-D were lower in HIV-infected individuals and associated with reduced endothelial functions.

Conclusions: This study's results show that HIV infection, in naïve subjects, is associated with endothelial dysfunction and a decline of natural antibodies to apo-B antigens.
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http://dx.doi.org/10.36660/abc.20200062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121411PMC
April 2021

Can we improve accuracy in LDL-cholesterol estimation in chronic kidney disease?

Eur J Prev Cardiol 2020 Nov 4. Epub 2020 Nov 4.

Lipids, Atherosclerosis and Vascular Biology Section, Cardiology Division, Department of Medicine, Universidade Federal de Sao Paulo, Rua Loefgren, 1350-Vila Clementino, Sao Paulo, SP 04040-001, Brazil.

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http://dx.doi.org/10.1093/eurjpc/zwaa048DOI Listing
November 2020

Early Changes in Circulating Interleukins and Residual Inflammatory Risk After Acute Myocardial Infarction.

Arq Bras Cardiol 2020 12;115(6):1104-1111

Universidade Federal de São Paulo, São Paulo, SP - Brasil.

Background: Patients with acute myocardial infarction may have a large infarcted area and ventricular dysfunction despite early thrombolysis and revascularization.

Objective: To investigate the behavior of circulating cytokines in patients with ST-segment elevation myocardial infarction (STEMI) and their relationship with ventricular function.

Methods: In the BATTLE-AMI (B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction) trial, patients with STEMI were treated with a pharmacoinvasive strategy. The plasma levels of cytokines (IL-1 β , IL-4, IL-6, IL-10, and IL-18) were tested using enzyme-linked immunosorbent assay (ELISA) at baseline and after 30 days. Infarcted mass and left ventricular ejection fraction (LVEF) were examined by 3-T cardiac magnetic resonance imaging. All p-values < 0.05 were considered statistically significant.

Results: Compared to baseline, lower levels were detected for IL-1 β (p = 0.028) and IL-18 (p < 0.0001) 30 days after STEMI, whereas higher levels were observed for IL-4 (p = 0.001) and IL-10 (p < 0.0001) at that time point. Conversely, no changes were detected for IL-6 levels (p = 0.63). The levels of high-sensitivity C-reactive protein and IL-6 correlated at baseline (rho = 0.45, p < 0.0001) and 30 days after STEMI (rho = 0.29, p = 0.009). At baseline, correlation between IL-6 levels and LVEF was also observed (rho = -0.50, p = 0.004).

Conclusions: During the first month post-MI, we observed a marked improvement in the balance of pro- and anti-inflammatory cytokines, except for IL-6. These findings suggest residual inflammatory risk. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).
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http://dx.doi.org/10.36660/abc.20190567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133737PMC
December 2020

Advanced chronic kidney disease is associated with higher serum concentration of monocyte microparticles.

Life Sci 2020 Nov 18;260:118295. Epub 2020 Aug 18.

Santo Amaro University, São Paulo, SP, Brazil. Electronic address:

Advanced chronic kidney disease is associated with high rates of cardiovascular disease. Considering the crucial role of capillaries in renal function, our study aimed to evaluate microparticles related to vascular physiology examining the link between stages of chronic kidney disease with circulating endothelial (EMP), platelet (PMP) and monocytic (MMP) microparticles. Cross-sectional study with blinded endpoints included subjects of both sexes, aged 40-75 years (n = 247), with established cardiovascular disease (coronary heart disease, ischemic stroke, or peripheral artery disease). They were stratified 1:1 by the presence or absence of decreased glomerular filtration rate (GFR < 60 mL/min/1.73 m) estimated by the CKD-EPI criteria, and according to the stages of CKD. Microparticles were quantified by flow-cytometry using specific antibodies to identify endothelial, platelet, and monocytic derived microparticles. Higher percentages of circulating MMP (p = 0.036), but not for EMP or PMP, were observed in subjects with reduced GFR. Circulating MMP were also related to the stages of chronic kidney disease (trend analysis across renal stages, p = 0.038). Higher percentages of circulating MMP were found in subjects with reduced GFR, and their percentages were progressively higher according to the stage of chronic renal function.
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http://dx.doi.org/10.1016/j.lfs.2020.118295DOI Listing
November 2020

Green-banana biomass consumption by diabetic patients improves plasma low-density lipoprotein particle functionality.

Sci Rep 2020 07 23;10(1):12269. Epub 2020 Jul 23.

Complex Fluids Group, Instituto de Física, Universidade de São Paulo, Rua Do Matão, 1371, Butantã, São Paulo, SP, CEP: 05508-090, Brazil.

The aim of this study was to investigate the effects of 6-months consumption of green-banana biomass on the LDL particle functionality in subjects with type 2 diabetes. Subjects (n = 39, mean age 65 years old) of both sexes with diabetes (HbA1c ≥ 6·5%) were randomized to receive nutritional support plus green-banana biomass (40 g) (n = 21) or diet alone (n = 18) for 6-months. Non-linear optical responses of LDL solutions from these participants were studied by Z-scan technique. UV-visible spectrophotometer was used to measure the absorbance of the LDL samples. Small Angle X-ray Scattering and Dynamic Light Scattering experiments were used to look for any structural changes in LDL samples and to determine their size distribution. The Lipoprint test was used to determine the LDL sub-fractions in terms of distribution and size. Consumption of green-banana biomass, reduced total- (p = 0.010), non-HDL-cholesterol (p = 0.043), glucose (p = 0.028) and HbA1c (p = 0.0007), and also improved the protection of the LDL particle against oxidation, by the increase in carotenoids content in the particles (p = 0.007). This higher protection against modifications may decrease the risk of developing cardiovascular disease. These benefits of the green-banana biomass encourage the use of resistant starches with potential clinical applications in individuals with pre-diabetes and diabetes.
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http://dx.doi.org/10.1038/s41598-020-69288-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378544PMC
July 2020

Absence of Nocturnal Fall in Blood Pressure Detected by Ambulatory Blood Pressure Monitoring in Acute Chagas Disease Patients with Oral Infection.

Arq Bras Cardiol 2020 04 29;114(4):711-715. Epub 2020 May 29.

Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.

Background The involvement of the autonomic nervous system is one of the mechanisms proposed to explain the progression of myocardial lesion in Chagas disease. Evidences have shown changes in sympathetic and parasympathetic nervous system since the acute phase of the disease, and studies to clarify the pathophysiological and prognostic value of these changes are needed. Objetives To assess blood pressure profile by ambulatory blood pressure monitoring (ABPM) in normotensive patients with acute Chagas disease (ACD) without apparent cardiac damage, and the influence of the infection on nocturnal blood pressure fall. Methods ABPM was performed with 54 patients with ACD and a control group composed of 54 age- and sex-matched normotensive individuals. The alpha level of significance (type I error rate) was set at 5%. Results In the total of 54 patients, 74.0% did not show nocturnal fall in systolic blood pressure, 53.7% did not show nocturnal fall in diastolic blood pressure, and lack of both nocturnal fall in SBP and DBP was observed in 51.8% (*p<0.05). In 12.9% of patients, there was an increase in SBP and in 18.5% increase in DBP (p<0.05). Conclusions In patients with acute Chagas disease, a significant absence of the physiological fall in both systolic and diastolic blood pressure was observed during sleep, and some of the patients showed nocturnal increase in these parameters. These findings suggest autonomic changes in the acute phase of Chagas disease. (Arq Bras Cardiol. 2020; 114(4):711-715).
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http://dx.doi.org/10.36660/abc.20190143DOI Listing
April 2020

Circulating microparticles and central blood pressure according to antihypertensive strategy.

Clinics (Sao Paulo) 2019 11;74:e1234. Epub 2019 Nov 11.

Departamento de Medicina, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, SP, BR.

Objectives: This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients.

Methods: The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period.

Results: No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm.

Conclusions: Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm.
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http://dx.doi.org/10.6061/clinics/2019/e1234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827330PMC
April 2020

Physical Activity and Healthy Eating Patterns in Public Schools in Brazil: A Strategy to Avert Risk Factors in Adulthood.

Arq Bras Cardiol 2019 07 15;112(6):782-783. Epub 2019 Jul 15.

Escola Paulista de Medicina da Universidade Federal de São Paulo, São Paulo, SP - Brazil.

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http://dx.doi.org/10.5935/abc.20190099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636374PMC
July 2019

Effect of a Multifaceted Quality Improvement Intervention on the Prescription of Evidence-Based Treatment in Patients at High Cardiovascular Risk in Brazil: The BRIDGE Cardiovascular Prevention Cluster Randomized Clinical Trial.

JAMA Cardiol 2019 05;4(5):408-417

HCor Research Institute, Hospital do Coração, São Paulo, São Paulo, Brazil.

Importance: Studies have found that patients at high cardiovascular risk often fail to receive evidence-based therapies in community practice.

Objective: To evaluate whether a multifaceted quality improvement intervention can improve the prescription of evidence-based therapies.

Design, Setting, And Participants: In this 2-arm cluster randomized clinical trial, patients with established atherothrombotic disease from 40 public and private outpatient clinics (clusters) in Brazil were studied. Patients were recruited from August 2016 to August 2017, with follow-up to August 2018. Data were analyzed in September 2018.

Interventions: Case management, audit and feedback reports, and distribution of educational materials (to health care professionals and patients) vs routine practice.

Main Outcomes And Measures: The primary end point was prescription of evidence-based therapies (ie, statins, antiplatelet therapy, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) using the all-or-none approach at 12 months after the intervention period in patients without contraindications.

Results: Of the 1619 included patients, 1029 (63.6%) were male, 1327 (82.0%) had coronary artery disease (843 [52.1%] with prior acute myocardial infarction), 355 (21.9%) had prior ischemic stroke or transient ischemic attack, and 197 (12.2%) had peripheral vascular disease, and the mean (SD) age was 65.6 (10.5) years. Among randomized clusters, 30 (75%) were cardiology sites, 6 (15%) were primary care units, and 26 (65%) were teaching institutions. Among eligible patients, those in intervention clusters were more likely to receive a prescription of evidence-based therapies than those in control clusters (73.5% [515 of 701] vs 58.7% [493 of 840]; odds ratio, 2.30; 95% CI, 1.14-4.65). There were no differences between the intervention and control groups with regards to risk factor control (ie, hyperlipidemia, hypertension, or diabetes). Rates of education for smoking cessation were higher among current smokers in the intervention group than in the control group (51.9% [364 of 701] vs 18.2% [153 of 840]; odds ratio, 11.24; 95% CI, 2.20-57.43). The rate of cardiovascular mortality, acute myocardial infarction, and stroke was 2.6% for patients from intervention clusters and 3.4% for those in the control group (hazard ratio, 0.76; 95% CI, 0.43-1.34).

Conclusions And Relevance: Among Brazilian patients at high cardiovascular risk, a quality improvement intervention resulted in improved prescription of evidence-based therapies.

Trial Registration: ClinicalTrials.gov identifier: NCT02851732.
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http://dx.doi.org/10.1001/jamacardio.2019.0649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537802PMC
May 2019

Beneficial effects of green banana biomass consumption in patients with pre-diabetes and type 2 diabetes: a randomised controlled trial.

Br J Nutr 2019 06 19;121(12):1365-1375. Epub 2019 Mar 19.

Department of Medicine,Universidade Federal de São Paulo,UNIFESP, São Paulo, SP,Brazil.

Diabetes mellitus is a global epidemic, characterised as a heterogeneous group of metabolic disorders associated with high risk of CVD. Green banana biomass, which is composed of resistant starches (RS) and cannot be hydrolysed by amylases, delays gastric emptying and modulates insulin sensitivity, thus contributing to improve metabolic disorders. The aim of the present study was to investigate the effects of consumption of RS from green banana biomass on body composition, fasting plasma glucose, glycated Hb (HbA1c) and homeostasis model assessment of insulin resistance in subjects with pre-diabetes or type 2 diabetes on top of treatment. Middle-aged subjects (n 113) of both sexes with pre-diabetes (HbA1c: 5·7-6·4 %) or diabetes (HbA1c ≥ 6·5 %) were randomised to receive nutritional support plus green banana biomass (40 g) (RS: approximately 4·5 g, G1, n 62) or diet alone (G2, n 51) for 24 weeks. Body composition, biochemical analyses and dietary intake were evaluated at the beginning and end of the study. In the experimental group (G1), consumption of RS was associated with reduction in HbA1c (P = 0·0001), fasting glucose (P = 0·021), diastolic blood pressure (P = 0·010), body weight (P = 0·002), BMI (P = 0·006), waist and hip circumferences (P < 0·01), fat mass percentage (P = 0·001) and increase in lean mass percentage (P = 0·011). In controls (G2), reductions were observed in waist and hip circumferences (P < 0·01), HbA1c (P = 0·002) and high-density lipoprotein-cholesterol (P = 0·020). In pre-diabetes or diabetes, non-significant differences were observed in the percentage reduction in HbA1c and fasting glucose in exploratory analyses. Our results indicate that the consumption of bioactive starches is a good dietary strategy to improve metabolic control and body composition.
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http://dx.doi.org/10.1017/S0007114519000576DOI Listing
June 2019

Regional QT Interval Dispersion as an Early Predictor of Reperfusion in Patients with Acute Myocardial Infarction after Fibrinolytic Therapy.

Arq Bras Cardiol 2019 01 17;112(1):20-29. Epub 2018 Dec 17.

Universidade Federal de São Paulo, São Paulo, SP - Brazil.

Background: Patients with ST-elevation acute myocardial infarction attending primary care centers, treated with pharmaco-invasive strategy, are submitted to coronary angiography within 2-24 hours of fibrinolytic treatment. In this context, the knowledge about biomarkers of reperfusion, such as 50% ST-segment resolution is crucial.

Objective: To evaluate the performance of QT interval dispersion in addition to other classical criteria, as an early marker of reperfusion after thrombolytic therapy.

Methods: Observational study including 104 patients treated with tenecteplase (TNK), referred for a tertiary hospital. Electrocardiographic analysis consisted of measurements of the QT interval and QT dispersion in the 12 leads or in the ST-segment elevation area prior to and 60 minutes after TNK administration. All patients underwent angiography, with determination of TIMI flow and Blush grade in the culprit artery. P-values < 0.05 were considered statistically significant.

Results: We found an increase in regional dispersion of the QT interval, corrected for heart rate (regional QTcD) 60 minutes after thrombolysis (p = 0.06) in anterior wall infarction in patients with TIMI flow 3 and Blush grade 3 [T3B3(+)]. When regional QTcD was added to the electrocardiographic criteria for reperfusion (i.e., > 50% ST-segment resolution), the area under the curve increased to 0.87 [(0.78-0.96). 95% IC. p < 0.001] in patients with coronary flow of T3B3(+). In patients with ST-segment resolution >50% and regional QTcD > 13 ms, we found a 93% sensitivity and 71% specificity for reperfusion in T3B3(+), and 6% of patients with successful reperfusion were reclassified.

Conclusion: Our data suggest that regional QTcD is a promising non-invasive instrument for detection of reperfusion in the culprit artery 60 minutes after thrombolysis.
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http://dx.doi.org/10.5935/abc.20180239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317627PMC
January 2019

Capillary electrophoresis with dual diode array detection and tandem mass spectrometry to access cardiovascular biomarkers candidates in human urine: Trimethylamine-N-Oxide and l-carnitine.

J Chromatogr A 2019 Jan 2;1583:136-142. Epub 2018 Nov 2.

Department of Chemistry, Federal University of Sao Paulo (UNIFESP), Diadema, SP, Brazil. Electronic address:

A capillary electrophoresis with diode array and tandem mass spectrometry detection (CE-UV-MS/MS) method has been developed for the targeted assessment of cardiovascular biomarkers candidates, trimethylamine-N-Oxide (TMAO) and l-carnitine, and creatinine in human urine samples. The dual detection was applied due to the high concentration of creatinine (monitored by UV detection at 200 nm) in relation to TMAO and l-carnitine (quantified by selected reaction monitoring (SRM) mass spectrometry), in human urine. All instrumental parameters, sheath liquid (SHL) and background electrolyte (BGE) compositions were optimized with a pool of urine provided by adult healthy volunteers and evaluated by signal-to-noise ratio (SNR) and peak shape of TMAO. The compositions for the optimized BGE was formic acid at concentration of 0.10 mol L, and for SHL was 70:30 MeOH:HO containing 0.05% (v/v) formic acid, delivered at a flow rate of 5 μL min. Limits of detection for TMAO, l-carnitine and creatinine were 0.76, 0.54 and 303 μmol L, respectively. Limits of quantification were 2.5, 1.8 and 1000 μmol L, respectively. Linearity was evaluated by ANOVA and presented R from 0.993 to 0.997. Precision and accuracy were evaluated at three concentration levels. Coefficients of variation (CV) from 1 to 21% were obtained for the intra-day precision evaluation and from 2 to 16% for the inter-day precision evaluation. The recovery ranged from 75 to 116%. Quantitation of TMAO and l-carnitine in infarcted patients urine in comparison to healthy individuals indicated a 2.2 fold increase of TMAO and a 7.0 fold increase of l-carnitine. These results showed the potential applicability of the proposed method for the evaluation of TMAO and l-carnitine in urine within a panel of candidate metabolites in targeted metabolomics studies of cardiovascular diseases among other conditions.
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http://dx.doi.org/10.1016/j.chroma.2018.10.005DOI Listing
January 2019

Rationale and design for a cluster randomized quality-improvement trial to increase the uptake of evidence-based therapies for patients at high cardiovascular risk: The BRIDGE-Cardiovascular Prevention trial.

Am Heart J 2019 01 17;207:40-48. Epub 2018 Oct 17.

Research Institute HCor - Hospital do Coração, São Paulo, SP, Brazil.

Background: Translating evidence into clinical practice in the management of high cardiovascular risk patients is challenging. Few quality improvement interventions have rigorously evaluated their impact on both patient care and clinical outcomes.

Objectives: The main objectives are to evaluate the impact of a multifaceted educational intervention on adherence to local guidelines for the prescription of statins, antiplatelets and angiotensin converting enzyme inhibitors or angiotensin II receptor blockers for high cardiovascular risk patients, as well as on the incidence of major cardiovascular events.

Design: We designed a pragmatic two arm cluster randomized trial involving 40 clusters. Clusters are randomized to receive a multifaceted quality improvement intervention or to routine practice (control). The multifaceted intervention includes: reminders, care algorithms, training of a case manager, audit and feedback reports, and distribution of educational materials to health care providers. The primary endpoint is the adherence to combined evidence-based therapies (statins, antiplatelet therapy and angiotensin converting enzyme inhibitors or angiotensin receptor blockers) at 12 months after the intervention period in patients without contra-indications for these medications. All analyses follow the intention-to-treat principle and take the cluster design into account using linear mixed logistic regression modeling.

Summary: If proven effective, this multifaceted intervention would have wide utility as a means of promoting optimal usage of evidence-based interventions for the management of high cardiovascular risk patients.
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http://dx.doi.org/10.1016/j.ahj.2018.10.001DOI Listing
January 2019

Predictors of Family Recruitment in a Program of Genetic Cascade Screening for Familial Hypercholesterolemia.

Arq Bras Cardiol 2018 10;111(4):585-586

Disciplina de Cardiologia - Escola Paulista de Medicina - Universidade Federal de São Paulo, São Paulo, SP - Brazil.

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http://dx.doi.org/10.5935/abc.20180193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199521PMC
October 2018

Behavior of Blood Pressure Variables in Children and Adolescents with Duchenne Muscular Dystrophy.

Arq Bras Cardiol 2018 Jun;110(6):551-557

Universidade Federal de São Paulo, São Paulo, SP - Brazil.

Background: Duchenne muscular dystrophy is an X-chromosome-linked genetic disorder (locus Xp21). Involvement of the cardiovascular system is characterized by fibrous degeneration/replacement of myocytes with consequent ventricular hypertrophy and arterial hypertension.

Objective: To assess, by using 24-hour ambulatory blood pressure monitoring, the behavior of blood pressure variables in children and adolescents with a confirmed diagnosis of Duchenne muscular dystrophy.

Methods: Prospective observational cohort study, which selected 46 patients followed up on an outpatient basis, divided according to age groups. Blood pressure was classified according to the age percentile. The monitoring interpretation includes systolic and diastolic blood pressure means, systolic and diastolic blood pressure loads, and nocturnal dipping. The blood pressure means were calculated for the 24-hour, wakefulness and sleep periods. Nocturnal dipping was defined as a drop in blood pressure means during sleep greater than 10%. The significance level adopted was p < 0.05.

Results: Nocturnal dipping for systolic blood pressure was present in 29.9% of the participants. Approximately 53% of them had attenuated nocturnal dipping, and 15%, reverse nocturnal dipping. The age groups of 9-11 years and 6-8 years had the greatest percentage of attenuation, 19.1% and 14.9%, respectively. Regarding diastolic blood pressure, nocturnal dipping was identified in 53.2% of the children, being extreme in 27.7% of those in the age group of 6-11 years.

Conclusions: The early diagnosis of blood pressure changes can allow the appropriate and specific therapy, aimed at increasing the life expectancy of patients with Duchenne muscular dystrophy.
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http://dx.doi.org/10.5935/abc.20180085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023634PMC
June 2018

Prevalence of Metabolic Syndrome and Framingham Risk Score in Vegetarian and Omnivorous Apparently Healthy Men.

Arq Bras Cardiol 2018 05;110(5):438-439

Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP - Brazil.

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http://dx.doi.org/10.5935/abc.20180083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967137PMC
May 2018

Association of Multiple Genetic Variants with the Extension and Severity of Coronary Artery Disease.

Arq Bras Cardiol 2018 Jan 1;110(1):16-23. Epub 2018 Feb 1.

Universidade Federal de São Paulo (UNIFESP), São Paulo, SP - Brazil.

Background: Metabolic syndrome (MS) is a condition that, when associated with ischemic heart disease and cardiovascular events, can be influenced by genetic variants and determine more severe coronary atherosclerosis.

Objectives: To examine the contribution of genetic polymorphisms to the extension and severity of coronary disease in subjects with MS and recent acute coronary syndrome (ACS).

Methods: Patients (n = 116, 68% males) aged 56 (9) years, with criteria for MS, were prospectively enrolled to the study during the hospitalization period after an ACS. Clinical and laboratory parameters, high-sensitivity C-reactive protein, thiobarbituric acid reactive substances, adiponectin, endothelial function, and the Gensini score were assessed. Polymorphisms of paraoxonase-1 (PON-1), methylenotetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (ENOS), angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL) were analysed by polymerase chain reaction (PCR) technique, followed by the identification of restriction fragment length polymorphisms (RFLP, and a genetic score was calculated. Parametric and non-parametric tests were used, as appropriate. Significance was set at p < 0.05.

Results: Polymorphisms of PON-1, MTHFR and ENOS were not in the Hardy-Weinberg equilibrium. The DD genotype of LPL was associated with higher severity and greater extension of coronary lesions. Genetic score tended to be higher in patients with Gensini score < P50 (13.7 ± 1.5 vs. 13.0 ± 1.6, p = 0.066), with an inverse correlation between genetic and Gensini scores (R = -0.194, p = 0.078).

Conclusions: The LPL polymorphism contributed to the severity of coronary disease in patients with MS and recent ACS. Combined polymorphisms were associated with the extension of coronary disease, and the lower the genetic score the more severe the disease.
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http://dx.doi.org/10.5935/abc.20170177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831297PMC
January 2018

Effects of four antiplatelet/statin combined strategies on immune and inflammatory responses in patients with acute myocardial infarction undergoing pharmacoinvasive strategy: Design and rationale of the B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction (BATTLE-AMI) study: study protocol for a randomized controlled trial.

Trials 2017 Dec 19;18(1):601. Epub 2017 Dec 19.

Universidade Federal de São Paulo, Rua Loefgren 1350, 04040-001, São Paulo, SP, Brazil.

Background: Early reperfusion of the occluded coronary artery during acute myocardial infarction is considered crucial for reduction of infarcted mass and recovery of ventricular function. Effective microcirculation and the balance between protective and harmful lymphocytes may have roles in reperfusion injury and may affect final ventricular remodeling.

Methods/design: BATTLE-AMI is an open-label, randomized trial comparing the effects of four therapeutic strategies (rosuvastatin/ticagrelor, rosuvastatin/clopidogrel, simvastatin plus ezetimibe/ticagrelor, or simvastatin plus ezetimibe/clopidogrel) on infarcted mass and left ventricular ejection fraction (LVEF) (blinded endpoints) in patients with ST-segment elevation myocardial infarction submitted to fibrinolytic therapy before coronary angiogram (pharmacoinvasive strategy). All patients (n = 300, 75 per arm) will be followed up for six months. The effects of treatment on subsets of B and T lymphocytes will be determined by flow-cytometry/ELISPOT and will be correlated with the infarcted mass, LVEF, and microcirculation perfusion obtained by cardiac magnetic resonance imaging. The primary hypothesis is that the combined rosuvastatin/ticagrelor therapy will be superior to other therapies (particularly for the comparison with simvastatin plus ezetimibe/clopidogrel) for the achievement of better LVEF at 30 days (primary endpoint) and smaller infarcted mass (secondary endpoint) at 30 days and six months. The trial will also evaluate the improvement in the immune/inflammatory responses mediated by B and T lymphocytes. Omics field (metabolomics and proteomics) will help to understand these responses by molecular events.

Discussion: BATTLE-AMI is aimed to (1) evaluate the role of subsets of lymphocytes on microcirculation improvement and (2) show how the choice of statin/antiplatelet therapy may affect cardiac remodeling after acute myocardial infarction with ST elevation.

Trial Registration: ClinicalTrials.gov, NCT02428374 . Registered on 28 September 2014.
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http://dx.doi.org/10.1186/s13063-017-2361-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735810PMC
December 2017

Brazilian guidelines on prevention of cardiovascular disease in patients with diabetes: a position statement from the Brazilian Diabetes Society (SBD), the Brazilian Cardiology Society (SBC) and the Brazilian Endocrinology and Metabolism Society (SBEM).

Diabetol Metab Syndr 2017 14;9:53. Epub 2017 Jul 14.

Universidade de São Paulo (USP), Av. Dr. Enéas de Carvalho Aguiar, 44, São Paulo, SP 05403-000 Brazil.

Background: Since the first position statement on diabetes and cardiovascular prevention published in 2014 by the Brazilian Diabetes Society, the current view on primary and secondary prevention in diabetes has evolved as a result of new approaches on cardiovascular risk stratification, new cholesterol lowering drugs, and new anti-hyperglycemic drugs. Importantly, a pattern of risk heterogeneity has emerged, showing that not all diabetic patients are at high or very high risk. In fact, most younger patients who have no overt cardiovascular risk factors may be more adequately classified as being at intermediate or even low cardiovascular risk. Thus, there is a need for cardiovascular risk stratification in patients with diabetes. The present panel reviews the best current evidence and proposes a practical risk-based approach on treatment for patients with diabetes.

Main Body: The Brazilian Diabetes Society, the Brazilian Society of Cardiology, and the Brazilian Endocrinology and Metabolism Society gathered to form an expert panel including 28 cardiologists and endocrinologists to review the best available evidence and to draft up-to-date an evidence-based guideline with practical recommendations for risk stratification and prevention of cardiovascular disease in diabetes. The guideline includes 59 recommendations covering: (1) the impact of new anti-hyperglycemic drugs and new lipid lowering drugs on cardiovascular risk; (2) a guide to statin use, including new definitions of LDL-cholesterol and in non-HDL-cholesterol targets; (3) evaluation of silent myocardial ischemia and subclinical atherosclerosis in patients with diabetes; (4) hypertension treatment; and (5) the use of antiplatelet therapy.

Conclusions: Diabetes is a heterogeneous disease. Although cardiovascular risk is increased in most patients, those without risk factors or evidence of sub-clinical atherosclerosis are at a lower risk. Optimal management must rely on an approach that will cover both cardiovascular disease prevention in individuals in the highest risk as well as protection from overtreatment in those at lower risk. Thus, cardiovascular prevention strategies should be individualized according to cardiovascular risk while intensification of treatment should focus on those at higher risk.
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http://dx.doi.org/10.1186/s13098-017-0251-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512820PMC
July 2017

Effects of Chronic Exercise on Endothelial Progenitor Cells and Microparticles in Professional Runners.

Arq Bras Cardiol 2017 Mar;108(3):212-216

Universidade Federal de São Paulo, São Paulo, SP, Brazil.

Background: The effects of chronic exposure to exercise training on vascular biomarkers have been poorly explored.

Objective: Our study aimed to compare the amounts of endothelial progenitor cells (EPCs), and endothelial (EMP) and platelet (PMP) microparticles between professional runners and healthy controls.

Methods: Twenty-five half-marathon runners and 24 age- and gender-matched healthy controls were included in the study. EPCs (CD34+/KDR+, CD133+/KDR+, and CD34+/CD133+), EMP (CD51+) and PMP (CD42+/CD31+) were quantified by flow-cytometry. All blood samples were obtained after 12 h of fasting and the athletes were encouraged to perform their routine exercises on the day before.

Results: As compared with controls, the CD34+/KDR+ EPCs (p=0.038) and CD133+/KDR+ EPCs (p=0.018) were increased, whereas CD34+/CD133+ EPCs were not different (p=0.51) in athletes. In addition, there was no difference in MPs levels between the groups.

Conclusion: Chronic exposure to exercise in professional runners was associated with higher percentage of EPCs. Taking into account the similar number of MPs in athletes and controls, the study suggests a favorable effect of exercise on these vascular biomarkers.
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http://dx.doi.org/10.5935/abc.20170022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389870PMC
March 2017
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