Soluble Fibrin Monomer Complex and Prediction of Cardiovascular Events in Atrial Fibrillation: The Observational Murcia Atrial Fibrillation Project

José Miguel Rivera-Caravaca, Vanessa Roldán, Marta Romera, María Asunción Esteve-Pastor, Mariano Valdés, Gregory Y. H. Lip, Vicente Vicente, Francisco Marín

Soluble fibrin monomer complex (SFMC) is a biomarker of fibrin formation abnormally elevated in clinical situations of hypercoagulability. We investigated the association and predictive performance of SFMC for stroke, adverse cardiovascular events, cardiovascular mortality and all-cause mortality in a cohort of patients with atrial fibrillation (AF) receiving vitamin K antagonist (VKA) anticoagulant therapy. During the second semester of 2007, we included 1226 AF outpatients stable on VKAs (INR 2.0-3.0) over a period of 6 months. SFMC levels were assessed at baseline. During 6.5 (IQR 4.4-8.0) years of follow-up, we recorded all ischemic strokes, adverse cardiovascular events (composite of stroke, acute heart failure, acute coronary syndrome and cardiovascular death), cardiovascular deaths and all-cause deaths. All patients were recruited consecutively. We excluded patients with rheumatic mitral valves, prosthetic heart valves, acute coronary syndrome, stroke, hemodynamic instability, hospital admissions or surgical interventions within the preceding 6 months. SFMC levels were measured in plasma by immunoturbidimetry in an automated coagulometer (STALiatestFM, Diagnostica Stago, Asnieres, France). We recorded 121 (1.52%/year) ischemic strokes, 257 (3.23%/year) cardiovascular events, 67 (0.84%/year) cardiovascular deaths and 486 (6.10%/year) all-cause deaths. SFMC >12 μg/mL was not associated with stroke but was associated with higher risk of cardiovascular events (HR 1.72, 95% CI 1.31-2.26), cardiovascular mortality (HR 2.16, 95% CI 1.30-3.57) and all-cause mortality (HR 1.26, 95% CI 1.03-1.55). When SFMC >12 μg/mL was added to the CHA2DS2-VASc, there were significant improvements in predictive performance, sensitivity and reclassification for adverse cardiovascular events (c-index: 0.645 vs. 0.660, p = 0.010; IDI = 0.013, p < 0.001; NRI = 0.121, p < 0.001) and cardiovascular mortality (c-index: 0.661 vs. 0.691, p = 0.006; IDI = 0.009, p = 0.049; NRI = 0.217, p < 0.001), but decision curves demonstrated a similar net benefit and clinical usefulness. In AF patients taking VKAs, high SFMC levels were associated with the risk of adverse cardiovascular events, cardiovascular mortality and all-cause mortality. The addition of SFMC to the CHA2DS2-VASc score improved its predictive performance for these outcomes, but failed to show an improvement in clinical usefulness.