Elevated NT-proBNP is associated with unfavorably altered plasma fibrin clot properties in atrial fibrillation

Abstract

BackgroundDense fibrin clot formation and hypofibrinolysis have been reported in atrial fibrillation (AF). It is unclear which factors affect fibrin clot properties in AF. Methods and resultsWe investigated plasma fibrin clot permeability (Ks), clot lysis time (CLT), endogenous thrombin potential (ETP) as well as other coagulation and fibrinolysis parameters along with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in 160 AF patients (median age, 70.5years). Previous stroke (n=15; 9.4%) was associated with decreased Ks (P=0.04) and longer CLT (P=0.005), together with higher antiplasmin (P=0.03) and lower tissue-type plasminogen activator (P=0.01). Lower Ks (P=0.04) and tendency towards longer CLT (P=0.10) were observed in patients with a left atrium diameter>40mm. Patients with a CHA2DS2-VASc score of 3 or more (82.5%) were characterized by higher thrombin-activatable fibrinolysis inhibitor antigen (P=0.009). Ks was inversely correlated with log NT-proBNP (r=−0.34, P<0.0001), plasminogen activator inhibitor-1 (PAI-1) antigen (r=−0.24, P=0.002) and C-reactive protein (r=−0.18, P=0.02), while CLT was positively correlated with log NT-proBNP (R=0.61, P<0.0001) and ETP (r=0.37, P<0.0001), which were interrelated (r=0.59, P<0.0001). After adjustment for potential confounders, PAI-1 (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.02–1.26) was the only independent predictor of low Ks (the lowest quartile,≤6×10−9cm2), while NT-proBNP (OR: 1.21; 95% CI: 1.12–1.31) and PAI-1 (OR: 1.30; 95% CI: 1.12–1.51) both predicted prolonged CLT (the top quartile,≥109min). ConclusionIn AF patients prothrombotic fibrin clot properties assessed ex vivo are determined by PAI-1 and NT-proBNP and this phenotype is associated with prior ischemic stroke.