Patients with acute coronary syndromes express enhanced CD40 ligand/CD154 on platelets

Abstract

Objective: To investigate whether CD40L/CD154 on platelets and soluble CD40L/CD154 may play a role in the inflammatory process of acute coronary syndromes.

Design and setting: Observational study in a university hospital.

Patients: 15 patients with acute myocardial infarction, 25 patients with unstable angina, 15 patients with stable angina, and 12 controls.

Main outcome measures: CD40L/CD154 on platelets, P-selectin/CD62P on platelets, soluble CD40L/CD154 serum concentrations.

Results: Mean (SD) CD40L/CD154 expression on platelets was 6.2 (2.8) MFI (mean fluorescence intensity) in the infarct group, 11 (3.3) MFI in the unstable angina group (p < 0.001 v infarction), 3.6 (0.9) MFI in the stable angina group (p < 0.01 v infarction; p < 0.001 v unstable angina), and 3.2 (1.0) MFI in the controls (p < 0.01 v infarction; p < 0.001 v unstable angina; NS v stable angina). Soluble CD40L/CD154 concentration was 5.2 (1.1) ng/ml in the infarct group, 4.2 (0.7) ng/ml in the unstable angina group (p < 0.001 v infarction), 2.9 (1.0) ng/ml in stable angina group (p < 0.001 v infarction and unstable angina), and 3.0 (0.5) ng/ml in the controls (p < 0.001 v infarction and unstable angina; NS v stable angina). At a six months follow up, there was lower expression of CD40L/CD154 on platelets in patients with unstable angina (12.3 (3.6) v 3.8 (1.2) MFI, p < 0.0001) and acute myocardial infarction (6.2 (2.8) v 3.5 (0.8) MFI, p < 0.01) compared with their admission values six months earlier. Patients with unstable angina who needed redo coronary angioplasty (PTCA) or who had recurrence of angina were characterised by increased CD40L/CD154 expression on platelets compared with the remainder of the study group (recurrence of angina: 12.7 (3.2) v 9.7 (1.6) MFI, p < 0.05; re-do PTCA: 14.3 (4.2) v 10.3 (2.1) MFI, p < 0.05).

Conclusions: Both CD40L/CD154 on platelets and soluble CD40L/CD154 are raised in patients with unstable angina and myocardial infarction. These findings suggest that CD40-CD40L/CD154 interactions may play a pathogenic role in triggering and propagation of acute coronary syndromes.

Figure 1

CD40L/CD154 on platelets in 12 controls (C), 15 patients with stable (SAP), 25 patients with unstable angina (UAP), and 15 patients with acute myocardial infarction (AMI). Symbols represent individual measurements (mean fluorescence intensity ((MFI)), the dotted line the mean value of each group (ns, non-significant).

Figure 2

CD40L/CD154 expression on platelets from 10 patients with unstable angina at admission and at six months follow up (p < 0.001). Symbols represent individual measurements (mean fluorescence intensity ((MFI)).

Figure 3

Serum concentrations of soluble CD40L/CD154 from 12 controls (C), 15 patients with stable (SAP), 25 patients with unstable angina pectoris (UAP), and 15 patients with acute myocardial infarction (AMI). Symbols represent individual measurements (ng/ml), the dotted line the mean value of each group (ns, non significant).

Figure 4

P-selectin/CD62P expression on platelets in 12 controls (C), 15 patients with stable (SAP), 25 patients with unstable angina (UAP), and 15 patients with acute myocardial infarction (AMI). Symbols represent individual measurements (mean fluorescence intensity ((MFI)), the dotted line the mean value of each group (ns, non-significant).

Figure 5

Mean CD40L/CD154 expression on platelets (mean fluorescence intensity ((MFI)) in relation to major cardiac events within 30 days (30 days MACE), recurrence of angina, need for repeated PTCA of target lesion, or death. Fourteen of 23 patients with unstable angina fulfilled criteria for 30 days combined end points (white bar), nine patients did not (black bar). Nine patients with unstable angina suffered from recurrence of angina (white bar), whereas 14 patients remained free of symptoms (black bar). Four patients with unstable angina needed repeated PTCA (white bar), the remaining 19 patients with unstable angina did not. Two patients died within 30 days after admission for unstable angina; * CD40L/CD154 on platelets of those who died were within interquartile range of survivors (black bar): both values of those who died (each represented by +) are placed between the median and third quartile of survivors.