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Background Increased aortic stiffness has been associated with cognitive decline and dementia, but the results are inconsistent. This study investigated the longitudinal association of aortic stiffness and age with decreased cognitive performance in 3 cognitive tests. Methods and Results This study included 6927 participants, with a mean age of 58.8 years at baseline (2008-2010), who participated in the second wave (2012-2014) of the ELSA-Brasil (Brazilian Longitudinal Study of Adult Health) (interval between visits ranging from 2-6 years). Cognitive performance was evaluated by Memory, Phonemic, and Semantic Verbal Fluency and Trail B Tests, applied at both cohort visits. Associations with the carotid-femoral pulse wave velocity and age at baseline were investigated using linear models with mixed effects after adjusting for confounders. After all the adjustments, including for systolic blood pressure, the interaction term carotid-femoral pulse wave velocity×time proved to be statistically significant for Memory and Verbal Fluency Tests, indicating that the higher carotid-femoral pulse wave velocity at baseline was associated with a faster decline in cognitive performance in these tests between waves. The interaction term age×time was statistically significant for all cognitive tests, suggesting that increasing age at baseline was also associated with a faster decline in cognitive performance between waves. Conclusions In this relatively young cohort, and after a relatively short interval, an increased aortic stiffness at baseline was associated with a sharper decline in cognitive performances in memory and verbal fluency, regardless of systolic blood pressure levels. This study also showed that the decline in cognitive performance was faster among older individuals than among younger ones at baseline.

The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P =1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01643434., (© 2018 American Heart Association, Inc.)

Background: Black people have a higher risk of developing hypertension and presenting higher vascular stiffening. Our aim was to investigate whether the association between race and aortic stiffness could be explained by differences in the primary risk factors., Methods and Results: We analyzed data from 11 472 adults (mean age, 51.9±8.9; 53.8% female) self-reported as white (n=6173), brown (n=3364), or black (n=1935). Their carotid-to-femoral pulse wave velocity (cf-PWV) as well as clinical and anthropometric parameters were measured. cf-PWV was higher in blacks than in whites or browns (men: white, 9.63±1.81; brown, 9.63±1.88; black, 9.98±1.99; women: white, 8.84±1.64; brown, 9.02±1.68; black, 9.34±1.91; P <0.05). However, this difference disappeared after adjustments for age, mean arterial pressure, heart rate, waist circumference, fasting glucose, and glomerular filtration rate (men: white, 9.68±1.54; brown, 9.68±1.50; black, 9.73±1.52; women: white, 8.93±1.32; brown, 8.98±1.29; black, 9.02±1.32; P >0.05). The association between race and arterial stiffness was significant for brown and black women in the highest cf-PWV quartile, even after controlling for covariates. There were no differences in the age-related increase in cf-PWV among the racial groups after adjustment, confirming the strong effect of age and mean arterial pressure on cf-PWV revealed by the multiple linear regression., Conclusions: Racial differences in cf-PWV were mainly attributed to differences in mean arterial pressure and age, although they cannot fully explain the association between race and cf-PWV in women in the highest cf-PWV values. This suggests that therapeutic approaches to overcome the effects of aging on the vascular system should focus on blood pressure control, especially in the black population., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: The six-minute walk test (6MWT) is a simple, low cost, reliable, and valid method for evaluating the functional capacity of cardiac patients. However, its early use and safety following acute myocardial infarction (AMI) is recent and has been little investigated., Objective: To evaluate and to compare the safety and the cardiac behavior of early performance of the 6MWT in patients following uncomplicated AMI up to 4 days or more than 4 days after the event., Methods: Following discharge from the Coronary Care Unit, 152 stable asymptomatic patients diagnosed with uncomplicated AMI performed the 6MWT. During the test, in addition to the distance walked, heart rate (HR), blood pressure (BP), and adverse events were also recorded. Electrocardiography was recorded using a Holter monitor in 105 patients. Patients were allocated considering two groups according to the number of days since AMI: Up to 4 Days Group and After 4 Days Group., Results: All patients completed the 6MWT, 66 in the Up to 4 Days Group and 86 in the After 4 Days Group. The walking distance was similar in both groups (85% of the predicted value), as well as the physiological responses (increase in systolic BP and HR), reaching 63% (median) of maximum HR. Only 3.9% of patients had major complications (angina, drop in BP, or ventricular tachycardia), with no difference between the groups. None of the complications regarded as severe led to truly significant complications or death., Conclusion: The 6MWT was proven to be safe and feasible for early functional evaluation following uncomplicated AMI., (Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Objectives: We aimed to assess the accuracy of the simple, contemporary and well-designed Toronto PCI mortality risk score in ICP-BR registry, the first Brazilian PCI multicenter registry with follow-up information., Background: Estimating percutaneous coronary intervention (PCI) mortality risk by a clinical prediction model is imperative to help physicians, patients and family members make informed clinical decisions and optimize participation in the consent process, reducing anxiety and improving quality of care. At a healthcare system level, risk prediction scores are essential to measure and benchmark performance., Methods: Between 2009 and 2013, a cohort of 4,806 patients from the ICP-BR registry, treated with PCI in eight tertiary referral medical centers, was included in the analysis. This population was compared to 10,694 patients of the derivation dataset from the Toronto study. To assess predictive performance, an update of the model was performed by three different methods, which were compared by discrimination, calculating the area under the receiver operating characteristic curve (AUC), and by calibration, assessed through Hosmer-Lemeshow (H-L) test and graphical analysis., Results: Death occurred in 2.6% of patients in the ICP-BR registry and in 1.3% in the Toronto cohort. The median age was 64 and 63 years, 23.8 and 32.8% were female, 28.6 and 32.3% were diabetics, respectively. Through recalibration of intercept and slope (AUC = 0.8790; H-L P value = 0.3132), we achieved a well-calibrated and well-discriminative model., Conclusions: After updating to our dataset, we demonstrated that the Toronto PCI in-hospital mortality risk score performed well in Brazilian hospitals., (© 2015 Wiley Periodicals, Inc.)

Introduction: Although intravascular ultrasound minimal luminal area (IVUS-MLA) is one of many anatomic determinants of lesion severity, it has been proposed as an alternative to fractional flow reserve (FFR) to assess severity of coronary artery disease., Objective: Pool the diagnostic performance of IVUS-MLA and determine its overall accuracy to predict the functional significance of coronary disease using FFR (0.75 or 0.80) as the gold standard., Methods: Studies comparing IVUS and FFR to establish the best MLA cutoff value that correlates with significant coronary stenosis were reviewed from a Medline search using the terms "fractional flow reserve" and "ultrasound." DerSimonian Laird method was applied to obtain pooled accuracy., Results: Eleven clinical trials, including two left main (LM) trials (total N = 1,759 patients, 1,953 lesions) were included. The weighted overall mean MLA cutoff was 2.61 mm(2) in non-LM trials and 5.35 mm(2) in LM trials. For non-LM lesions, the pooled sensitivity of MLA was 0.79 (95% CI = 0.76-0.83) and specificity was 0.65 (95% CI = 0.62-0.67). Positive likelihood ratio (LR) was 2.26 (95% CI = 1.98-2.57) and LR- was 0.32 (95% CI = 0.24-0.44). Area under the summary receiver operator curve for all trials was 0.848. Pooled LM trials had better accuracy: sensitivity = 0.90, specificity = 0.90, LR+ = 8.79, and LR- = 0.120., Conclusion: Given its limited pooled accuracy, IVUS-MLA's impact on clinical decision in this scenario is low and may lead to misclassification in up to 20% of the lesions. Pooled analysis points toward lower MLA cutoffs than the ones used in current practice., (© 2013 Wiley Periodicals, Inc.)

Objectives: Endothelial dysfunction is associated to cardiovascular risk factors and predicts cardiovascular events. Peripheral arterial tonometry (PAT) is a novel noninvasive method to assess endothelial function. However, there is a paucity of data about its reproducibility. The aim of this study was to assess the feasibility and reproducibility of PAT in adults., Methods: PAT exams were performed twice in the same day in 123 participants of a cohort about the determinants of diabetes and cardiovascular diseases (Brazilian Longitudinal Study of Adult Health--ELSA-Brasil). The interval between the exams was 2-6 h (mean=4 h). Endothelial function in PAT method is measured by reactive hyperemia index (RHI), which evaluates arterial pulsatile volume changes in response to hyperemia. Agreement of RHI values was compared by Bland-Altman method, coefficient of variation and coefficient of repeatability. Reliability was assessed by intraclass correlation coefficient (ICC)., Results: Mean values of RHI did not differ significantly between the exams of each participant (1.92±0.56 vs. 1.96±0.58, P=0.48). There were no systematic errors between the exams (mean of differences=-0.03±0.5). Measurement error was 0.35, coefficient of variation was 18.0% and ICC was 0.61. Sex, age or the presence of obesity did not have a considerable influence on the reproducibility of PAT., Conclusion: PAT exam is feasible and has acceptable reproducibility in adults when compared with other noninvasive methods for endothelial function assessment. This performance makes PAT a promising method for future clinical and epidemiological studies.

Background: Rifampicin remains one of the first-line drugs used in tuberculosis therapy. This drug's potential to induce the hepatic cytochrome P450 oxidative enzyme system increases the risk of drug-drug interactions. Thus, although the presence of comorbidities typically necessitates the use of multiple drugs, the co-administration of rifampicin and warfarin may lead to adverse drug events. We report a bleeding episode after termination of the co-administration of rifampicin and warfarin and detail the challenges related to international normalized ratio (INR) monitoring., Case Presentation: A 59-year-old Brazilian woman chronically treated with warfarin for atrial fibrillation (therapeutic INR range: 2.0-3.0) was referred to a multidisciplinary anticoagulation clinic at a university hospital. She showed anticoagulation resistance at the beginning of rifampicin therapy, as demonstrated by repeated subtherapeutic INR values. Three months of sequential increases in the warfarin dosage were necessary to reach a therapeutic INR, and frequent visits to the anticoagulation clinic were needed to educate the patient about her pharmacotherapy and to perform the warfarin dosage adjustments. The warfarin dosage also had to be doubled at the beginning of rifampicin therapy. However, four weeks after rifampicin discontinuation, an excessively high INR was observed (7.22), with three-day macroscopic hematuria and the need for an immediate reduction in the warfarin dosage. A therapeutic and stable INR was eventually attained at 50% of the warfarin dosage used by the patient during tuberculosis therapy., Conclusions: The present case exemplifies the influence of rifampicin therapy on warfarin dosage requirements and the increased risk of bleeding after rifampicin discontinuation. Additionally, this case highlights the need for warfarin weekly monitoring after stopping rifampicin until the maintenance dose of warfarin has decreased to the amount administered before rifampicin use. In particular, patients with cardiovascular diseases and active tuberculosis represent a group with a substantial risk of drug-drug interactions. Learning how to predict and monitor drug-drug interactions may help reduce the incidence of clinically significant adverse drug events.

This work investigated if methods used to produce a uniformly sampled heart rate variability (HRV) time series significantly change the deterministic signature underlying the dynamics of such signals and some nonlinear measures of HRV. Two methods of preprocessing were used: the convolution of inverse interval function values with a rectangular window and the cubic polynomial interpolation. The HRV time series were obtained from 33 Wistar rats submitted to autonomic blockade protocols and from 17 healthy adults. The analysis of determinism was carried out by the method of surrogate data sets and nonlinear autoregressive moving average modelling and prediction. The scaling exponents alpha, alpha(1) and alpha(2) derived from the detrended fluctuation analysis were calculated from raw HRV time series and respective preprocessed signals. It was shown that the technique of cubic interpolation of HRV time series did not significantly change any nonlinear characteristic studied in this work, while the method of convolution only affected the alpha(1) index. The results suggested that preprocessed time series may be used to study HRV in the field of nonlinear dynamics.

We report a case of acute myocardial infarction in a nephrotic child. A 7-year-old boy with a 4-year history of steroid-unresponsive nephrotic syndrome due to mesangial proliferation disease presented with acute vomiting and chest pain. An electrocardiogram showed ST elevation and pathological Q waves in leads consistent with anterior and septal myocardial infarction. Subsequent cardiac catheterization showed no evidence of atherosclerotic coronary artery disease, and thrombotic occlusion of the anterior descending coronary artery was the likely cause of the event. Myocardial scintigraphy showed extensive myocardial damage. The child had no long history of extreme hypercholesterolemia or hypertriglyceridemia. The case suggests that children with long-lasting nephrotic syndrome may be at increased risk for ischemic cardiovascular events, due to hyperlipidemia as well as a hypercoagulability state. The literature is reviewed regarding the relationship between nephrotic syndrome and the incidence of ischemic heart disease.