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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1667.)
© 2006 American Heart Association, Inc.

Thrombosis

Soluble CD40L Levels Are Regulated by the –3459 A>G Polymorphism and Predict Myocardial Infarction and the Efficacy of Antithrombotic Treatment in Non-ST Elevation Acute Coronary Syndrome

Anders Mälarstig; Bertil Lindahl; Lars Wallentin; Agneta Siegbahn

From the Department of Medical Sciences, Clinical Chemistry (A.M., A.S.), Cardiology, Uppsala Clinical Research Centre (B.L., L.W.), Uppsala University, Sweden.

Correspondence to Agneta Siegbahn, Department of Medical Sciences, Clinical Chemistry, Uppsala University, S-751 85 Uppsala, Sweden. E-mail agneta.siegbahn{at}akademiska.se

Objectives— Current evidence suggests the CD40–CD40L pathway as a key process in the development, progression, and outcome of acute coronary syndrome (ACS). The aim was to investigate the prognostic importance of soluble (s) CD40L levels, single nucleotide polymorphisms (SNP) in the CD40LG gene, and the relation between sCD40L and SNPs in patients with acute coronary syndromes (ACS).

Methods and Results— Samples were obtained on admission from 2359 patients with non-ST elevation ACS randomized to an early invasive versus a conservative and to placebo controlled long-term dalteparin treatment in the FRISC-II study. The –3459 A>G SNP was identified as a novel regulator of sCD40L levels (P=0.001). In the placebo-treated group, sCD40L levels above median were associated with a 2.5-fold increased risk of myocardial infarction (MI) (P0.001) but not with raised mortality. In the dalteparin treated group, sCD40L showed no association with MI (P=0.75). Consequently, dalteparin treatment was effective in reducing the risk of MI only in patients with sCD40L levels above median. A combined assessment of troponin-T and sCD40L complemented the prognostic information on risk of MI.

Conclusions— We identified a SNP in the CD40LG gene as a novel regulator of sCD40L plasma concentrations. Soluble CD40L levels above median reflect a prothrombotic state, which can be managed with the use of intense anti-thrombotic treatments.

Elevation of soluble CD40L was associated with myocardial infarction in the FRISC-II trial, which enrolled 2457 patients with acute coronary syndromes. A prolonged dalteparin treatment was more beneficial in patients with elevated sCD40L. The –3459 A>G SNP in the CD40LG gene was identified as a novel regulator of sCD40L levels.

Key Words: ACS • CD40L • myocardial infarction • outcome • SNP • thrombosis

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