Soluble CD40 ligand in acute coronary syndromes.
BACKGROUND
CD40 ligand is expressed on platelets and released from them on activation. We investigated the predictive value of soluble CD40 ligand as a marker for clinical outcome and the therapeutic effect of glycoprotein IIb/IIIa receptor inhibition in patients with acute coronary syndromes.


METHODS
Serum levels of soluble CD40 ligand were measured in 1088 patients with acute coronary syndromes who had previously been enrolled in a randomized trial comparing abciximab with placebo before coronary angioplasty and in 626 patients with acute chest pain.


RESULTS
The levels of soluble CD40 ligand were elevated (above 5.0 microg per liter) in 221 patients with acute coronary syndromes (40.6 percent). Among patients receiving placebo, elevated soluble CD40 ligand levels indicated a significantly increased risk of death or nonfatal myocardial infarction during six months of follow-up (adjusted hazard ratio as compared with patients with low levels of the ligand [< or =5.0 microg 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 patients with chest pain, among whom elevated soluble CD40 ligand levels identified those with acute coronary syndromes who were at high risk for death or nonfatal myocardial infarction (adjusted hazard ratio 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 ligand levels 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 abciximab in patients with low levels of soluble CD40 ligand.


CONCLUSIONS
In patients with unstable coronary artery disease, elevation of soluble CD40 ligand levels indicated an increased risk of cardiovascular events. Elevation of soluble CD40 ligand identifies a subgroup of patients at high risk who are likely to benefit from antiplatelet treatment with abciximab.
Heeschen
Christopher
C
c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany. c.heeschen@em.uni-frankfurt.de
Dimmeler
Stefanie
S
Hamm
Christian W
CW
van den Brand
Marcel J
MJ
Boersma
Eric
E
Zeiher
Andreas M
AM
Simoons
Maarten L
ML
D000077284:Abciximab; D000208:Acute Disease; D000787:Angina Pectoris / Q000097:blood* / Q000188:drug therapy; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D023201:CD40 Ligand; D000077284:Abciximab