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

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) (P <= 0.001) 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.