Biomarkers of structural remodelling and endothelial dysfunction for prediction of cardiovascular events or death in patients with atrial fibrillation

Abstract

Atrial fibrillation (AF) is associated not only with inflammation but also with structural remodelling and altered endothelial activation which may contribute to clot formation, embolization and mortality. We aimed to determine the predictive value of single-time biomarker analysis for prediction of outcome in patients with AF. We conducted a prospective study to evaluate if biomarkers of structural, electrical or endothelial remodelling are predictive of cardiovascular events (composite primary endpoint of myocardial infarction, stroke, peripheral embolism or death). Secondary endpoint was all-cause mortality. Patients with any type of AF and without active inflammatory conditions were eligible. Plasma samples were collected for ELISA analysis of biomarkers (inflammation [hsCRP, sCD40L], structural [MMP-2] and endothelial remodelling [vWF, sVCAM-1]) at enrolment. Patients (n = 278) were followed for 28 ± 12 (median 32) months. Eighty-eight individuals (32%) experienced a primary outcome event, including 8 (2.9%) with myocardial infarction, 13 (4.8%) with stroke and 4 (1.5%) with peripheral embolism. Predictors of the primary endpoint were age >75 years, CHADS(2)-score >2, LVEF <35%, diabetes, presence of an ICD/pacemaker, elevated vWF, sVCAM-1 and MMP-2 levels. On multivariate regression analysis, only age >75 years, sVCAM-1 and MMP-2 levels remained independently associated with the endpoint. There were 75 deaths during follow-up. Age >75 years, reduced LVEF, elevated sVCAM-1 and MMP-2 levels were predictors of all-cause mortality. In this cohort of AF patients, old age, elevated sVCAM-1 and MMP-2 levels were associated with cardiovascular events. Our data indicate that single-time biomarker assessment may be a useful tool to improve risk stratification schemes.