COX-2 rs20417 Polymorphism Is Associated with Stroke and White Matter Disease.

BACKGROUND: To investigate the effect of COX-2 polymorphism and its product, prostaglandin E2 (PGE2), on stroke risk in an endemic area for Chagas disease. In a separate cohort, to investigate the effect of COX-2 polymorphisms on the total burden of cerebral white matter disease. METHODS: Cases were outpatients with ischemic stroke; controls were stroke-free subjects from 2 outpatient clinics (heart failure and caregivers of a movement disorders clinic). We extracted DNA from total blood to investigate the rs20417 COX-2 polymorphism. Serologic tests (Enzime-linked immunosorbent assay) were performed to confirm Trypanosoma cruzi infection and to quantify PGE2 levels. In the Boston cohort, white matter hyperintensity volume (WMHv) was quantified on the admission brain magnetic resonance images of subjects with ischemic stroke, who also donated DNA for the COX-2 gene region analysis. RESULTS: We studied 44 patients with stroke and 96 controls (46 with heart failure and 50 caregivers) in the Brazilian cohort; and 788 stroke patients (302 cardioembolic and 486 noncardioembolic) in the Boston cohort. In the Brazilian cohort, rs20417 polymorphism was associated with both stroke (P = 5 × 10(-6)) and decreased PGE2 levels (P = 4 × 10(-5)); similarly, Chagas was associated with stroke (P = 4 × 10(-3)) and decreased PGE2 levels (P = 7 × 10(-3)). In the Boston cohort, rs20417 polymorphism was associated with increased WMHv among noncardioembolic (P = .037), but not among cardioembolic stroke patients. CONCLUSIONS: Variation in COX-2 gene is associated with both symptomatic and silent brain cerebrovascular disease. This candidate gene region should be tested in population-based samples.

Influencia de la etiología sobre la mortalidad en la insuficiencia cardíaca con función sistólica preservada en una población con alta prevalencia de cardiopatía chagásica / Influence of Etiology on Heart Failure With Preserved Systolic Function Mortality in a Population With High Prevalence of Chagas Cardiomyopathy

Introducción La insuficiencia cardíaca con función sistólica preservada es un síndrome clínico con los mismos signos y síntomas de la insuficiencia cardíaca clásica. La enfermedad de Chagas es una causa importante de insuficiencia cardíaca en América Latina, que se asocia con miocardiopatía dilatada y deterioro progresivo de la función sistólica. No existen estudios previos que hayan evaluado pacientes con insuficiencia cardíaca y función sistólica preservada de una zona endémica en la cual la enfermedad de Chagas es la causa principal de insuficiencia cardíaca. Objetivo Comparar las características clínicas y la evolución de la insuficiencia cardíaca en pacientes con disfunción sistólica y con función sistólica preservada en una población con alta prevalencia de enfermedad de Chagas. Material y métodos Se realizó una evaluación prospectiva de los pacientes con diagnóstico clínico de insuficiencia cardíaca que ingresaron a un centro de referencia en Salvador, Bahía (Brasil). Se consideró función sistólica preservada a una fracción de eyección del ventrículo izquierdo mayor del 45% por ecocardiograma. Se realizó seguimiento al año a través de contacto telefónico o entrevista personal en el consultorio de insuficiencia cardíaca. Resultados Se incluyeron 383 pacientes durante un período de 16 meses; el 52,5% eran hombres y la edad media fue de 54,2 años. La función sistólica estuvo preservada en 138 pacientes (36%). La enfermedad de Chagas fue la principal etiología de ambos tipos de insuficiencia cardíaca (45,3% con disfunción sistólica y 44,2% con función sistólica preservada). El 93,5% (358) de los pacientes completaron un año de seguimiento. Los pacientes con enfermedad de Chagas y función sistólica preservada tuvieron menor mortalidad que los pacientes con disfunción sistólica (10% vs. 23,6%; p = 0,039). En los pacientes sin enfermedad de Chagas y función sistólica preservada, la mortalidad fue similar a la de aquellos con disfunción sistólica (10,4% vs. 15,8%; p = 0,307). Conclusiones La función sistólica preservada fue muy frecuente en nuestra población. La enfermedad de Chagas es la principal etiología de insuficiencia cardíaca independientemente de la fracción de eyección del ventrículo izquierdo. Los pacientes con enfermedad de Chagas y función sistólica preservada tienen mejor pronóstico que aquellos con disfunción sistólica, probablemente porque se encuentran en la fase inicial del compromiso cardíaco.

Background Heart failure with preserved systolic function is a clinical syndrome with the same signs and symptoms of classic heart failure. Chagas disease is a major cause of heart failure in Latin America, associated with dilated cardiomyopathy and progressive deterioration of systolic function. There are no previous assessment studies of patients with heart failure and preserved systolic function in an endemic area in which Chagas disease is the leading cause of heart failure. Objective The aim of this study was to compare clinical characteristics and evolution of heart failure in patients with systolic dysfunction and with preserved systolic function in a population with high prevalence of Chagas disease. Methods A prospective assessment was performed in patients with clinical diagnosis of heart failure admitted to a referral center in Salvador, Bahia (Brazil). Left ventricular ejection fraction > 45% by echocardiogram was considered as preserved systolic function. A one year follow-up was conducted through telephone or personal interview at the heart failure clinic. Results Three hundred and eighty three patients, 52.5% of whom were male, with an average age of 54.2 years, were included in this study over a period of 16 months. Systolic function was preserved in 138 patients (36%). Chagas disease was the main etiology of both types of heart failure (45.3% with systolic dysfunction and 44.2% with preserved systolic function). One year follow-up was completed by 93.5% (358) of patients. Patients with Chagas disease and preserved systolic function had lower mortality than patients with systolic dysfunction (10% vs. 23.6%; p=0.039). In patients without Chagas disease and preserved systolic function, mortality was similar to that of those with systolic dysfunction (10.4% vs. 15.8%; p=0.307). Conclusions Preserved systolic function was very common in our population. Chagas' disease is the leading cause of heart failure irrespective of left ventricular ejection fraction. Patients with Chagas disease and preserved systolic function have a better prognosis than those with systolic dysfunction, probably because they are in the initial phase of cardiac involvement.