Data-independent acquisition mass spectrometry in severe rheumatic heart disease (RHD) identifies a proteomic signature showing ongoing inflammation and effectively classifying RHD cases.

BACKGROUND: Rheumatic heart disease (RHD) remains a major source of morbidity and mortality in developing countries. A deeper insight into the pathogenetic mechanisms underlying RHD could provide opportunities for drug repurposing, guide recommendations for secondary penicillin prophylaxis, and/or inform development of near-patient diagnostics. METHODS: We performed quantitative proteomics using Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectrometry (SWATH-MS) to screen protein expression in 215 African patients with severe RHD, and 230 controls. We applied a machine learning (ML) approach to feature selection among the 366 proteins quantifiable in at least 40% of samples, using the Boruta wrapper algorithm. The case-control differences and contribution to Area Under the Receiver Operating Curve (AUC) for each of the 56 proteins identified by the Boruta algorithm were calculated by Logistic Regression adjusted for age, sex and BMI. Biological pathways and functions enriched for proteins were identified using ClueGo pathway analyses. RESULTS: Adiponectin, complement component C7 and fibulin-1, a component of heart valve matrix, were significantly higher in cases when compared with controls. Ficolin-3, a protein with calcium-independent lectin activity that activates the complement pathway, was lower in cases than controls. The top six biomarkers from the Boruta analyses conferred an AUC of 0.90 indicating excellent discriminatory capacity between RHD cases and controls. CONCLUSIONS: These results support the presence of an ongoing inflammatory response in RHD, at a time when severe valve disease has developed, and distant from previous episodes of acute rheumatic fever. This biomarker signature could have potential utility in recognizing different degrees of ongoing inflammation in RHD patients, which may, in turn, be related to prognostic severity.

Clinical Outcomes in 3343 Children and Adults With Rheumatic Heart Disease From 14 Low- and Middle-Income Countries: Two-Year Follow-Up of the Global Rheumatic Heart Disease Registry (the REMEDY Study).

BACKGROUND: There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease or information on their predictors. We report the 2-year follow-up of individuals with rheumatic heart disease from 14 low- and middle-income countries in Africa and Asia. METHODS: Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for 2 years to assess mortality, congestive heart failure, stroke or transient ischemic attack, recurrent acute rheumatic fever, and infective endocarditis. RESULTS: Vital status at 24 months was known for 2960 (88.5%) patients. Two-thirds were female. Although patients were young (median age, 28 years; interquartile range, 18-40), the 2-year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.80-3.11), congestive heart failure (HR, 2.16; 95% CI, 1.70-2.72), New York Heart Association functional class III/IV (HR, 1.67; 95% CI, 1.32-2.10), atrial fibrillation (HR, 1.40; 95% CI, 1.10-1.78), and older age (HR, 1.02; 95% CI, 1.01-1.02 per year increase) at enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54-0.85) and female sex (HR, 0.65; 95% CI, 0.52-0.80) were associated with lower risk of death. Two hundred and four (6.9%) patients had new congestive heart failure (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/transient ischemic attack or systemic embolism. Patients from low- and lower-middle-income countries had significantly higher age- and sex-adjusted mortality than patients from upper-middle-income countries. Valve surgery was significantly more common in upper-middle-income than in lower-middle- or low-income countries. CONCLUSIONS: Patients with clinical rheumatic heart disease have high mortality and morbidity despite being young; those from low- and lower-middle-income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and the treatment of clinical rheumatic heart disease are required to improve outcomes.

Secondhand smoke exposure is independently associated with stroke among non-smoking adults in West Africa.

BACKGROUND: Stroke is a leading cause of disability and mortality worldwide, but little is known about the contribution of secondhand smoke exposure (SHSE) to stroke epidemiology among indigenous Africans. OBJECTIVE: To evaluate the association of SHSE with stroke among indigenous Africans. METHODS: We analyzed the relationship of SHSE with stroke among 2990 case-control pairs of adults who had never smoked (identified in the SIREN study) using conditional logistic regression at a two-sided P < 0.05. RESULTS: Multivariable-adjusted odds ratio and 95% confidence interval; 1.25 (1.04, 1.50; P = 0.02) revealed SHSE was positively associated with stroke independent of stroke subtypes. CONCLUSION: Culturally relevant primary prevention strategies targeted at SHSE might be promising in preventing stroke among Africans.

Domestic solid fuel combustion in an adult population in Nigeria: A cross sectional analysis of association with respiratory symptoms, quality of life and lung function.

BACKGROUND AND OBJECTIVES: We examined the association of respiratory symptoms, health status, and lung function with the use of solid fuel (wood, charcoal, coal or crop residue) for cooking or heating in a predominantly non-smoking population. METHODS: Using the protocol of the Burden of Obstructive Lung Diseases (BOLD) initiative, we collected representative population data using questionnaires and spirometry tests. We categorized solid fuel use into 'never user', 'ex user' and 'current user' based on responses to the survey. We developed regression models to evaluate the relation between use of solid fuel and the prevalence of respiratory symptoms, quality of life and lung function adjusting for confounding variables. RESULTS: Out of 1147 respondents with complete information on domestic fuel type, 33% were 'never-users', 19% were 'ex-users' while 48% reported current use of solid fuel for domestic cooking and/or indoor heating. Compared with never-users, current solid fuel users were more likely to report cough (OR: 1.7, 95% CI: 1.0, 2.9), cough or phlegm (OR: 1.6, 95% CI: 1.0, 2.5) and the association was stronger among women (OR: 3.0, 95% CI: 1.3, 7.1 and OR: 2.3, 95% CI: 1.1, 5.2, respectively). Current solid fuel users also had lower mental health status (coefficient: ?1.5, 95% CI: ?2.8, - 0.2) compared with the group of never-users. Current or previous domestic use of solid fuels for cooking or heating was not associated with higher prevalence of chronic airflow obstruction (FEV1/FVC < LLN). CONCLUSIONS: Using solid fuel for domestic cooking or heating was associated with a higher risk of cough or phlegm and a lower mental quality of life. However we found no significant effect in the prevalence of chronic airflow obstruction in Ife, Nigeria.

Aortic aneurysm with valvular insufficiency: is it due to Marfan syndrome or hypertension? A case report and review of literature.

Aortic aneurysm can result from both Marfan syndrome (MFS) and hypertension. Hypertension is more easily detected by the use of ubiquitous sphygmomanometer but MFS diagnosis requires a summation of a set of clinical features, including increased cardiac output from aortic regurgitation. A common complication of aortic aneurysm may result in apparent elevation in systolic pressure in a MFS patient with aortic root dilatation and regurgitation. Thus a patient with MFS presenting with aortic regurgitation may be misdiagnosed as having hypertensive heart disease. Clinical case presentation of a 47-year-old woman referred to the cardiology unit with the diagnosis of aortic aneurysm with regurgitation secondary to hypertension was found to have MFS. Relevant literature on diagnostic criteria of MFS and differences in aortic root disease secondary to MFS and that secondary to hypertension was reviewed. Physicians should have a high index of suspicion and consider MFS as a differential diagnosis of aortic aneurysm, especially in younger patients.