Background:

OxPL-apoB, which is bound to lipoprotein(a), has been established in several studies as a risk factor for cardiovascular events. Higher levels of OxPL-plasminogen (OxPL bound to plasminogen) have been associated with a protective effect in patients with acute myocardial infarction, probably due to its impact on fibrinolysis. It has been shown in vitro that OxPL binds to and activates the CD36 receptor of platelets. However, data on the influence of OxPL-apoB and OxPL-plasminogen on platelet aggregation are not available so far. This secondary analysis of the EXCELSIOR study sought to evaluate the clinical impact of OxPL-apoB and OxPL-plasminogen on platelet function.

Methods:

2040 patients scheduled for coronary angiography in our heart centre could be included in this first analysis. All patients received a loading dose of 600 mg clopidogrel p.o. followed by a maintenance dose of 75mg p.o. daily as well as a loading dose of 400 mg ASA p.o. if they were not on a long-term therapy with 100 mg ASA p.o. daily. Blood samples were taken before the loading dose and 2-4 hours after the first maintenance dose on day 1 after coronary angiography. Platelet function was analyzed using light transmission aggregometry (LTA, stimulation with collagen and ADP) and flow cytometry (FACS, measuring CD62P, CD41 and PAC-1). For the evaluation, the patients were divided into quintiles based on the OxPL-apoB concentrations and the OxPL-plasminogen concentrations.

Results:

Patients with higher levels of OxPL-apoB had more frequently a history of PCI (p = 0.006), CABG (p = <0.001), or myocardial infarction (p = 0.007) as well as more extensive coronary heart disease at time of angiography (p = 0.001) as more frequently an indication for PCI (p = <0.001). In contrast, patients with  higher levels of OxPL-plasminogen had less frequently a history of CABG (p = 0.002), as well as less extensive coronary heart disease at time of angiography (p = 0.02) and less frequently an indication for PCI (p = 0.008). Platelet function testing with LTA showed a reduced intrinsic aggregation with ADP for increasing OxPL-plasminogen concentrations. FACS analyses showed similar results (figure 1). For low OxPL-apoB concentrations, there was a reduced intrinsic CD41 expression after stimulation with ADP and increased expression of PAC-1 on DAPT.

Conclusion:

High concentrations of OxPL-plasminogen are associated to reduced platelet aggregation and might therefore be protective for cardiovascular events. Further clinical studies are needed to proof this association.

Figure 1:

Shown is the intrinsic and on-dual antiplatelet therapy (DAPT) platelet reactivity tested by light transmission aggregometry and the expression of CD62P, CD41 amd PAC-1 measured by flow cytometry. Test were performed before and 24h following loading with clopidogrel.