Varo, N., de Lemos, J. A., Libby, P., Morrow, D. A., Murphy, S. A., Nuzzo, R., Gibson, C. M., Cannon, C. P., Braunwald, E., Schonbeck, U. Soluble CD40L: risk prediction after acute coronary syndromes Circulation. 2003;108(9):1049-52.

BACKGROUND: Elevated plasma concentrations of soluble CD40 ligand (sCD40L) indicate increased risk for future cardiovascular events in apparently healthy women. This study tested the hypothesis that plasma sCD40L, alone or in combination with troponin (cTnI) or C-reactive protein (CRP), may identify patients with acute coronary syndromes at heightened risk for recurrent cardiac events.

METHODS AND RESULTS: In a nested case-control study (cases, n=195; controls, n=195) within the OPUS-TIMI16 trial, patients with the prespecified study end points death, myocardial infarction (MI), or congestive heart failure (CHF) within 10 months had significantly higher median (25th, 75th percentiles) sCD40L plasma levels than did controls (0.78 [0.34, 1.73] ng/mL versus 0.52 [0.16, 1.42] ng/mL, P<0.002). After adjustment for other risk predictors and levels of cTnI and CRP, sCD40L levels above median were associated with higher risk for death, MI, and the composite death/MI or death/MI/CHF (adjusted hazard ratios, 1.9 [P<0.05], 1.9 [P<0.001], 1.9 [P<0.001], and 1.8 [P<0.01], respectively). Interestingly, patients with elevated plasma levels of sCD40L and cTnI showed a markedly increased risk of death, MI, or death/MI/CHF compared with patients with the lowest levels of both markers (adjusted hazard ratios, 12.1, 7.2, and 4.3, respectively; all P<0.01).

CONCLUSIONS: Elevated plasma levels of sCD40L identify patients with acute coronary syndromes at heightened risk of death and recurrent MI independent of other predictive variables, including cTnI and CRP. Notably, combined assessment of sCD40L with cTnI complements prognostic information for death and MI.

Trial: OPUS-TIMI 16