Luisa Campos Caldeira Brant

Cardiovascular Health in Brazil Trends and Perspectives

Brazil is a large country, with an evolving economy, but marked social inequalities. The population is formed by an admixture of native Brazilians, Europeans, and Africans; is predominantly urban; and faces rapid aging. Time trends related to health behaviors show a substantial reduction in smoking rates, but a rising prevalence of overweight and obesity, unhealthy eating habits, and insufficient physical activity. The high prevalence of hypertension and the increasing prevalence of diabetes mellitus are also causes for concern. Cardiovascular disease (CVD) has been the leading cause of mortality since the 1960s and has accounted for a substantial percentage of all hospitalizations. In 2011, CVD was responsible for 31% of all deaths, with ischemic heart disease (31%) and cerebrovascular diseases (30%) being the leading CVD causes. Despite an increase in the overall number of CVD deaths, the age-adjusted mortality rates for CVD declined 24% between 2000 and 2011. Health care delivered by Brazils universal public health system, which focuses on primary prevention, has contributed to this achievement. However, the decline in age-adjusted mortality differs according to race, sex, and socioeconomic status with black individuals and lower-income populations sustaining the greatest impact of CVD, especially at younger ages. With one of the worlds largest public health systems in terms of population coverage, Brazil has the means to implement actions to confront the high burden of CVD, focusing on health promotion and comprehensive care. Insufficient funding, low education levels, and social inequalities remain as the main barriers to be overcome.

Reproducibility of peripheral arterial tonometry for the assessment of endothelial function in adults.

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.

Reduced protective effect of Plasmodium berghei immunization by concurrent Schistosoma mansoni infection

Studies on concomitant schistosomiasis and human and experimental malaria have shown a variation in the immunospecific response, as well as an increase in the severity of both parasitoses. In the present study, a murine co-infection model was used to determine the effects of a co-infection with Schistosoma mansoni and Plasmodium berghei on the protective immunity acquired by repeated malarial infections and subsequent curative treatment with chloroquine. Our results have demonstrated that, compared to an infection with P. berghei only, the co-infection increases the malarial parasitaemia and decreases the survival rate. Indeed, mice that were immunized by infection and treatment with drug displayed no mortality whereas co-infected mice showed a reduced protective efficacy of immunization against P. berghei (mortality > 60%). Interestingly, this high mortality rate was not associated with high levels of parasitaemia. Our findings support the idea of a suppressive effect of a Schistosoma co-infection on the anti-malarial protection by immunization. This result reveals a possible drawback of the development of anti-malarial vaccines, especially considering the wide endemic areas for both parasitoses.

Endomyocardial fibrosis associated with mansoni schistosomiasis

Endomyocardial fibrosis (EMF) is a neglected tropical disease that affects millions of people worldwide. EMF is the most common cause of restrictive cardiomyopathy, caused by deposition of fibrous tissue on endocardial surfaces. EMF is a major cause of death in areas where it is endemic, but the pathogenesis of the disease is poorly understood. Schistosomiasis mansoni is a parasitic disease endemic in Brazil, where EMF has also been described. The association between EMF and schistosomiasis has been suggested in various publications, seeking a possible correlation between endocardial and periportal fibroses. This report describes a case of EMF associated with schistosomiasis.

Global health and cardiovascular disease

The modern definition of Global Health has expanded its scope beyond neglected diseases and low-income and underdeveloped countries. The current initiatives focus on improvement of health, reduction of disparities and protection against global threats, seeking for interaction with health practices, policies and systems. There has been a growing interest on Global Health research, given the epidemiological transition currently underway in low and mid-income countries and the increasing epidemiological importance of cardiovascular and other non-communicable diseases, to the detriment of infectious diseases and nutritional deficiencies. Various aspects—formerly neglected—of these diseases, such as epidemiology, prevention, diagnosis and therapy, have been addressed in Global Health publications, leading to a better understanding of the importance of health as a public good, beyond borders. Scientific evidence supports broader initiatives in which governments, foundations and the civil society must share responsibilities and funding to achieve health equity, the main goal of Global Health.

Relations of digital vascular function, cardiovascular risk factors, and arterial stiffness: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort study.

Background Vascular dysfunction is an early expression of atherosclerosis and predicts cardiovascular (CV) events. Peripheral arterial tonometry (PAT) evaluates basal pulse amplitude (BPA), endothelial function (PAT ratio), and wave reflection (PAT‐AIx) in the digital microvessels. In Brazilian adults, we investigated the correlations of PAT responses to CV risk factors and to carotid‐femoral pulse wave velocity (PWV), a measure of arterial stiffness. Methods and Results In a cross‐sectional study, 1535 participants of the ELSA‐Brasil cohort underwent PAT testing (52±9 years; 44% women). In multivariable analyses, more‐impaired BPA and PAT ratios were associated with male sex, higher body mass index (BMI), and total cholesterol/high‐density lipoprotein. Higher age and triglycerides were related to higher BPA, whereas lower systolic blood pressure, hypertension (HTN) treatment, and prevalent CV disease (CVD) were associated with lower PAT ratio. PAT‐AIx correlated positively with female sex, advancing age, systolic and diastolic blood pressures, and smoking and inversely to heart rate, height, BMI, and prevalent CVD. Black race was associated with lower BPA, higher PAT ratio, and PAT‐AIx. Microvessel vasodilator function was not associated with PWV. Higher PAT‐AIx was modestly correlated to higher PWV and PAT ratio and inversely correlated to BPA. Conclusion Metabolic risk factors are related to impaired microvessel vasodilator function in Brazil. However, in contrast to studies from the United States, black race was not associated with an impaired microvessel vasodilator response, implying that vascular function may vary by race across populations. PAT‐AIx relates to HTN, may be a valid measure of wave reflection, and provides distinct information from arterial stiffness.

Relations of Metabolically Healthy and Unhealthy Obesity to Digital Vascular Function in Three Community‐Based Cohorts: A Meta‐Analysis

Background Microvascular dysfunction is a marker of early vascular disease that predicts cardiovascular events. Whether metabolically healthy obese individuals have impaired microvascular function remains unclear. The aim of this study was to evaluate the relation of obesity phenotypes stratified by metabolic status to microvascular function. Methods and Results We meta‐analyzed aggregate data from 3 large cohorts (Brazilian Longitudinal Study of Adult Health, the Framingham Heart Study, and the Gutenberg Heart Study; n=16 830 participants, age range 19–90, 51.3% men). Regression slopes between cardiovascular risk factors and microvascular function, measured by peripheral arterial tonometry (PAT), were calculated. Individuals were classified as normal‐weight, overweight, or obese by body mass index (BMI) and stratified by healthy or unhealthy metabolic status based on metabolic syndrome using the ATP‐III criteria. Male sex, BMI, and metabolic risk factors were associated with higher baseline pulse amplitude and lower PAT ratio. There was stepwise impairment of vascular measures from normal weight to obesity in both metabolic status strata. Metabolically healthy obese individuals had more impaired vascular function than metabolically healthy normal‐weight individuals (baseline pulse amplitude 6.12±0.02 versus 5.61±0.01; PAT ratio 0.58±0.01 versus 0.76±0.01, all P<0.0001). Metabolically unhealthy obese individuals had more impaired vascular function than metabolically healthy obese individuals (baseline pulse amplitude 6.28±0.01 versus 6.12±0.02; PAT ratio 0.49±0.01 versus 0.58±0.01, all P<0.0001). Conclusions Metabolically healthy obese individuals have impaired microvascular function, though the degree of impairment is less marked than in metabolically unhealthy obese individuals. Our findings suggest that obesity is detrimental to vascular health irrespective of metabolic status.

Inconsistent Correlation Between Carotid Artery Intima-Media Thickness and Peripheral Arterial Tonometry: Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

AbstractTo estimate the association between 2 markers for atherosclerosis, measurements of carotid artery intima-media thickness (IMT) and of peripheral arterial tonometry (PAT), and to evaluate the role of traditional cardiovascular risk factors in this association.We applied the 2 diagnostic tests to 588 participants from the ELSA-Brazil longitudinal study cohort. The PAT measurements, obtained with the EndoPAT2000, were the reactive hyperemia index (RHI), the Framingham RHI (F-RHI), and the mean basal pulse amplitude (BPA). We used the mean of the mean scores of carotid IMT of the distal layers of the left and right common carotids obtained by ultrasonography after 3 cardiac cycles. We used linear regression and the Spearman correlation coefficient to test the relationship between the 2 markers, and multiple linear regressions to exam the relationship between the RHI/F-RHI scores and the mean BPA and IMT scores after adjusting for cardiovascular risk factors.In the multivariate analysis, RHI (but not F-RHI) was positively correlated with the mean of the means of the IMT values after adjusting for sex and risk factors connected with both measures (&bgr; = 0.05, P = 0.02). Mean BPA did not remain significantly associated with IMT after adjusting for common risk factors.We found that the higher the IMT (or the worse the IMT), the higher the RHI (or the better the endothelial function). F-RHI was not associated with IMT. These 2 results are against the direction that one would expect and may imply that digital endothelial function (RHI and F-RHI) and IMT correspond to distinct and independent stages of the complex atherosclerosis process and represent different pathways in the diseases progression. Therefore, IMT and PAT measures may be considered complementary and not interchangeable.

Factors associated with compliance to AHA/ACC performance measures in a myocardial infarction system of care in Brazil

Objective To evaluate compliance with American Heart Association/American College of Cardiology (AHA/ACC) performance measures for adults with acute myocardial infarction (AMI) and to investigate the factors associated with compliance, in an AMI System of Care in Brazil. Design Observational longitudinal study. Setting A high-complexity University Hospital, part of the AMI System of Care implemented in Belo Horizonte, Brazil, in 2010. Participants Of note, 1129 patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) admitted to a single center over 36 months (between 2011 and 2014). Main Outcome Measures Compliance with 13 pre-specified AHA/ACC AMI performance measures was evaluated for patients with AMI, observing exclusion criteria and appropriate numerators and denominators. Median compliance was calculated and variables independently associated with compliance rates were evaluated. Results Median age was 60 (51/68) years, 67.7% male, 69.8% presented with STEMI and hospital mortality was 8.7%. Median compliance with performance measures was 83% (75/88). Among patients with STEMI, 56% received reperfusion therapy. Overall, 67.3% of patients complied with ≥80% of quality measures. Factors independently associated with better compliance were later date of presentation (semester), likely reflecting ongoing training (OR = 1.19, 95% CI: 1.10-1.28, P < 0.001), male gender (OR = 1.33, 95% CI: 1.00-1.76, P < 0.046), Killip I/II on admission (OR = 1.95, 95% CI: 1.36-2.80, P < 0.001) and diagnosis of NSTEMI (OR = 5.0, 95% CI: 3.51-7.11, P < 0.001). Conclusion Compliance with AHA/ACC AMI performance measures remains below target in Brazil, but the time trends observed suggest improvement. Continuing education, reduction of system delays and prioritizing high-risk groups are needed to optimize AMI systems of care and improve patient outcomes.

Variações e diferenciais da mortalidade por doença cardiovascular no Brasil e em seus estados, em 1990 e 2015: estimativas do Estudo Carga Global de Doença

Objective: To analyze variations and particularities in mortality due to cardiovascular disease (CVD) in Brazil and in Brazilian states, in 1990 and 2015. Methods: We used data compiled from the Global Burden of Disease (GBD) 2015, obtained from the database of the Mortality Information System (SIM) of the Brazilian Ministry of Health. Correction of the sub-registry of deaths and reclassification of the garbage codes were performed using specific algorithms. The cardiovascular causes were subdivided into 10 specific causes. Age-standardized CVD mortality rates - in 1990 and 2015 - were analyzed according to sex and Brazilian state. Results: Age-standardized CVD mortality rate decreased from 429.5 (1990) to 256.0 (2015) per 100,000 inhabitants (40.4%). The proportional decrease was similar in both sexes, but death rates in males were substantially higher. The reduction of age-standardized mortality rate was more significant for rheumatic heart disease (44.5%), ischemic cardiopathy (43.9%), and cerebrovascular disease (46.0%). The decline in mortality was markedly different across states, being more pronounced in those of the southeastern and southern regions and the Federal District, and more modest in most states in the north and northeast regions. Conclusion: Age-standardized CVD mortality has declined in Brazil in recent decades, but in a heterogeneous way across states and for different specific causes. Considering the burden magnitude and the Brazilian population aging, policies to prevent and manage CVD should continue to be prioritized.