Stroke Correlates in Chagasic and Non-Chagasic Cardiomyopathies

BACKGROUND: Aging and migration have brought changes to the epidemiology and stroke has been shown to be independently associated with Chagas disease. We studied stroke correlates in cardiomyopathy patients with focus on the chagasic etiology. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional review of medical records of 790 patients with a cardiomyopathy. Patients with chagasic (329) and non-chagasic (461) cardiomyopathies were compared. There were 108 stroke cases, significantly more frequent in the Chagas group (17.3% versus 11.1%; p<0.01). Chagasic etiology (odds ratio [OR], 1.79), pacemaker (OR, 2.49), atrial fibrillation (OR, 3.03) and coronary artery disease (OR, 1.92) were stroke predictors in a multivariable analysis of the entire cohort. In a second step, the population was split into those with or without a Chagas-related cardiomyopathy. Univariable post-stratification stroke predictors in the Chagas cohort were pacemaker (OR, 2.73), and coronary artery disease (CAD) (OR, 2.58); while atrial fibrillation (OR, 2.98), age over 55 (OR, 2.92), hypertension (OR, 2.62) and coronary artery disease (OR, 1.94) did so in the non-Chagas cohort. Chagasic stroke patients presented a very high frequency of individuals without any vascular risk factors (40.4%; OR, 4.8). In a post-stratification logistic regression model, stroke remained associated with pacemaker (OR, 2.72) and coronary artery disease (OR, 2.60) in 322 chagasic patients, and with age over 55 (OR, 2.38), atrial fibrillation (OR 3.25) and hypertension (OR 2.12; p = 0.052) in 444 non-chagasic patients. CONCLUSIONS/SIGNIFICANCE: Chagas cardiomyopathy presented both a higher frequency of stroke and an independent association with it. There was a high frequency of strokes without any vascular risk factors in the Chagas as opposed to the non-Chagas cohort. Pacemaker rhythm and CAD were independently associated with stroke in the Chagas group while age over 55 years, hypertension and atrial fibrillation did so in the non-Chagas cardiomyopathies

Chagas Cardiomyopathy in the Context of the Chronic Disease Transition

Latin America is undergoing a transition from disease patterns characteristic of developing countries with high rates of infectious disease and premature deaths to a pattern more like industrialized countries, in which chronic conditions such as obesity, hypertension and diabetes are more common. Many rural residents with Chagas disease have now migrated to cities, taken on new habits and may suffer from both types of disease. We studied heart disease among 394 adults seen by cardiologists in a public hospital in the city of Santa Cruz, Bolivia; 64% were infected with T. cruzi, the parasite that causes Chagas disease. Both T. cruzi infected and uninfected patients had a high rate of hypertension (64%) and overweight (67%), with no difference by infection status. Nearly 60% of symptomatic congestive heart failure was due to Chagas disease; mortality was also higher for infected than uninfected patients. Males and older patients had more severe Chagas heart disease. Chagas heart disease remains an important cause of congestive heart failure in this hospital population, but often occurs in patients who also have obesity, hypertension and/or other cardiac risk factors

2 nd Brazilian Consensus on Chagas Disease, 2015

Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research

Lysosomal storage disease-associated neuropathy: Targeting stable nucleic acid lipid particle (snalp)-formulated sirnas to the brain as a therapeutic approach

More than two thirds of Lysosomal Storage Diseases (LSDs) present central nervous system involvement. Nevertheless, only one of the currently approved therapies has an impact on neuropathology. Therefore, alternative approaches are under development, either addressing the underlying enzymatic defect or its downstream consequences. Also under study is the possibility to block substrate accumulation upstream, by promoting a decrease of its synthesis. This concept is known as substrate reduction therapy and may be triggered by several molecules, such as small interfering RNAs (siRNAs). siRNAs promote RNA interference, a naturally occurring sequence-specific post-transcriptional gene-silencing mechanism, and may target virtually any gene of interest, inhibiting its expression. Still, naked siRNAs have limited cellular uptake, low biological stability, and unfavorable pharmacokinetics. Thus, their translation into clinics requires proper delivery methods. One promising platform is a special class of liposomes called stable nucleic acid lipid particles (SNALPs), which are characterized by high cargo encapsulation efficiency and may be engineered to promote targeted delivery to specific receptors. Here, we review the concept of SNALPs, presenting a series of examples on their efficacy as siRNA nanodelivery systems. By doing so, we hope to unveil the therapeutic potential of these nanosystems for targeted brain delivery of siRNAs in LSDs.This work was supported by the Portuguese Society for Metabolic Disorders (Sociedade Portuguesa de Doenças Metabólicas, SPDM—Bolsa SPDM de apoio à investigação Dr. Aguinaldo Cabral 2018; 2019DGH1629/SPDM2018I&D) and Sanfilippo Children's Foundation (SCF Incubator Grant 2019; 2019DGH1656/SCF2019I&D). Additional support came from the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme (project CENTRO-01-0145-FEDER-000008: BrainHealth 2020), and the COMPETE 2020—Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT—Fundação para a Ciência e a Tecnologia (projects POCI-01-0145-FEDER-016390: CANCEL STEM and POCI-01-0145-FEDER-007440; UIDB/04539/2020). L.S.M. is funded by FCT/MCTES National Funds under project CEECIND/04242/2017

Genomic African and Native American Ancestry and Chagas Disease: The Bambui (Brazil) Epigen Cohort Study of Aging

The influence of genetic ancestry on Trypanosoma cruzi infection and Chagas disease outcomes is unknown.We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual proportions of African, European and Native American genomic ancestry with T. cruzi infection and related outcomes in 1,341 participants (aged ≥ 60 years) of the Bambui (Brazil) population-based cohort study of aging. Potential confounding variables included sociodemographic characteristics and an array of health measures. The prevalence of T. cruzi infection was 37.5% and 56.3% of those infected had a major ECG abnormality. Baseline T. cruzi infection was correlated with higher levels of African and Native American ancestry, which in turn were strongly associated with poor socioeconomic circumstances. Cardiomyopathy in infected persons was not significantly associated with African or Native American ancestry levels. Infected persons with a major ECG abnormality were at increased risk of 15-year mortality relative to their counterparts with no such abnormalities (adjusted hazard ratio = 1.80; 95% 1.41, 2.32). African and Native American ancestry levels had no significant effect modifying this association.Our findings indicate that African and Native American ancestry have no influence on the presence of major ECG abnormalities and had no influence on the ability of an ECG abnormality to predict mortality in older people infected with T. cruzi. In contrast, our results revealed a strong and independent association between prevalent T. cruzi infection and higher levels of African and Native American ancestry. Whether this association is a consequence of genetic background or differential exposure to infection remains to be determined