Christopher Heeschen, M.D., Stefanie Dimmeler, Ph.D., Christian W. Hamm, M.D., Marcel J. van den Brand, M.D., Eric Boersma, Ph.D., Andreas M. Zeiher, M.D., Maarten L. Simoons, M.D., for the CAPTURE Study Investigators
Background CD40 ligand is expressed on platelets and releasedfrom them on activation. We investigated the predictive valueof soluble CD40 ligand as a marker for clinical outcome andthe therapeutic effect of glycoprotein IIb/IIIa receptor inhibitionin patients with acute coronary syndromes.
Methods Serum levels of soluble CD40 ligand were measured in1088 patients with acute coronary syndromes who had previouslybeen enrolled in a randomized trial comparing abciximab withplacebo before coronary angioplasty and in 626 patients withacute chest pain.
Results The levels of soluble CD40 ligand were elevated (above5.0 µg per liter) in 221 patients with acute coronarysyndromes (40.6 percent). Among patients receiving placebo,elevated soluble CD40 ligand levels indicated a significantlyincreased risk of death or nonfatal myocardial infarction duringsix months of follow-up (adjusted hazard ratio as compared withpatients with low levels of the ligand [5.0 µg per liter],2.71; 95 percent confidence interval, 1.51 to 5.35; P=0.001).The prognostic value of this marker was validated in the patientswith chest pain, among whom elevated soluble CD40 ligand levelsidentified those with acute coronary syndromes who were at highrisk for death or nonfatal myocardial infarction (adjusted hazardratio as compared with those with low levels of the ligand,6.65; 95 percent confidence interval, 3.18 to 13.89; P<0.001).The increased risk in patients with elevated soluble CD40 ligandlevels was significantly reduced by treatment with abciximab(adjusted hazard ratio as compared with those receiving placebo,0.37; 95 percent confidence interval, 0.20 to 0.68; P=0.001),whereas there was no significant treatment effect of abciximabin patients with low levels of soluble CD40 ligand.
Conclusions In patients with unstable coronary artery disease,elevation of soluble CD40 ligand levels indicated an increasedrisk of cardiovascular events. Elevation of soluble CD40 ligandidentifies a subgroup of patients at high risk who are likelyto benefit from antiplatelet treatment with abciximab.
Source Information
From the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study (C.H., S.D., C.W.H., M.J.B., E.B., A.M.Z., M.L.S.); Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany (C.H., S.D., A.M.Z.); the Kerckhoff Heart Center, Bad Nauheim, Germany (C.W.H.); and the Thoraxcentre, Erasmus University, Rotterdam, the Netherlands (M.J.B., E.B., M.L.S.).
Address reprint requests to Dr. Heeschen at the Department of Molecular Cardiology, Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany, or at c.heeschen{at}em.uni-frankfurt.de.
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