Total NT-proBNP, a novel biomarker in atrial fibrillation. A mechanistic analysis of the GISSI-AF trial.

Objective (1) to test the association with prevalent and incident atrial fibrillation (AF), and prognosis of total N-terminal pro-B type natriuretic peptide (total NT-proBNP) and of a panel of biomarkers; (2) to assess iwhether the extent of glycosylation affects the relation of NT-proBNP with AF. Methods In a sub-study of the GISSI-AF trial on 382 patients in sinus rhythm with a history of AF, echocardiographic variables and eight circulating biomarkers were serially assayed over one year. The relations between circulating baseline biomarkers and AF and the risk of CV events, were assessed by Cox-analysis models adjusting the first by clinical variables, the second by clinical variables and the echocardiographic left-atrial-minimum-volume-index (LAVImin) . Results Over a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for cardiovascular (CV) reasons. Total NT-proBNP, NT-proBNP, angiopoietin 2 (Ang2), myosin binding protein (MyBPC3) and bone morphogenic protein-10 (BMP-10) were strongly associated to ongoing AF. Natriuretic peptides and MyBPC3 predicted recurrent AF but this lost significance after adjustment for LAVImin. NT-proBNP and Ang2 predicted CV hospitalization even after adjustment for LAVImin, HR95%CI: 2.20 [1.02-4.80] and 5.26 [1.16-23.79]. Conclusions The association of AF recurrence with the novel biomarker total NT-proBNP, is similar to that of NT-proBNP, suggesting no influence of glycosylation. Ang2, MyBPC3 and BMP10 were strongly associated with AF, indicating a possible role of extracellular matrix and myocardial injury.