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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2763.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Soluble CD40 Ligand Predicts Ischemic Stroke and Myocardial Infarction in Patients With Nonvalvular Atrial Fibrillation

Domenico Ferro; Lorenzo Loffredo; Licia Polimeni; Filippo Fimognari; Paolo Villari; Pasquale Pignatelli; Valentin Fuster; Francesco Violi

From the Department of Experimental Medicine (D.F., L.L., L.P., P.V., P.P., F.V.), University "La Sapienza," Rome, Italy; the Division of Internal Medicine (F.F.), Leopoldo Parodi-Delfino Hospital, ASL Roma G, Colleferro, Rome, Italy; and the Cardiovascular Institute (V.F.), Mount Sinai School of Medicine, New York.

Correspondence to Professor Francesco Violi, Divisione di Medicina Interna H, Viale del Policlinico 155, Roma, 00161, Italy. E-mail francesco.violi{at}uniroma1.it

Objective— Atrial fibrillation (AF) is associated with a high incidence of vascular disease that may be related to a prothrombotic and inflammatory state. Soluble CD40 ligand (sCD40L), which stems essentially from platelet activation, possesses inflammatory and prothrombotic properties. The aim of the study was to assess whether sCD40L is a predictor of stroke or myocardial infarction (MI) in patients with nonvalvular AF.

Methods and Results— Plasma levels of sCD40L were measured in 231 patients (177 [77%] had permanent or persistent AF, and 54 [23%] had paroxysmal AF). Patients were followed for a mean period of 27.8±8.8 months, and cardiovascular events such as fatal and nonfatal stroke and MI were recorded. AF population was divided in 2 groups according to sCD40L level above or below the median (4.76 ng/mL). The 2 patients’ groups had similar distribution of cardiovascular risk factors, age, gender, medications, or serum C-reactive protein levels. During the follow-up period, vascular events occurred in 6 (2 nonfatal MI and 4 nonfatal ischemic strokes) of 116 patients with low levels of sCD40L (5.1%) and in 29 (11 fatal and 3 nonfatal MI; 3 fatal and 12 nonfatal ischemic strokes) of 115 patients with high levels (25.2%) (log-rank test: P<0.001). Using the COX proportional Hazards model, patients with sCD40L above the median were 4.63 times more likely to experience a vascular event (95% C.I.: 1.92 to 11.20).

Conclusions— This study shows that enhanced soluble CD40L level is a predictor of vascular events in patients with nonvalvular AF, thus suggesting that enhanced platelet activation may play a role in its clinical progression.

This prospective study provides evidence that enhanced plasma levels of sCD40L (>4.76 ng/mL) are predictive of cardiovascular events in patients with nonvalvular atrial fibrillation, thus suggesting that enhanced platelet activation may play a pivotal role in its clinical progression.

Key Words: atrial fibrillation • sCD40L • atherosclerosis

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