Relationship between changes in platelet reactivity and changes in platelet receptor expression induced by physical exercise

Introduction: In previous studies we have consistently shown a significant increase of platelet reactivity after exercise in patients with obstructive coronary artery disease (CAD). We also observed a significant individual variability in the response to exercise of platelet reactivity in these patients. Whether exercise-induced changes in platelet reactivity correlate with changes in platelet membrane receptors in patients with CAD is unknown. Methods: We studied 26 patients with stable CAD and 10 matched healthy controls who underwent a symptom-limited treadmill exercise stress test. Venous blood samples were collected at rest and within 5 min of peak exercise. Platelet reactivity was measured by the PFA-100 method as time to occlude (closure time, CT) a ring coated with collagen/adenosine diphosphate (C/ADP). Platelet expression of glycoprotein (GP) IIb/IIIa, in both global (CD41) and active form (PAC-1), and P-selectin (CD62P) and formation of leukocyte-platelet aggregates were assessed by flow cytometry. Results: After exercise CT did not change in controls (85.4 ± 12 to 84.0 ± 9 s, p = 0.37), whereas it decreased in CAD patients (98.8 ± 24 to 91.4 ± 25 s, p <0.001). After exercise, CD41 and PAC-1 platelet expression increased significantly in CAD patients (p = 0.04 for both), but not in controls (p = 0.39 and p = 0.98, respectively). To evaluate the relationship between the response to exercise of platelet reactivity and of platelet receptor expression, CAD patients were divided into two groups: CAD group 1 (16 patients, decrease in CT > 5 s after exercise) and CAD group 2 (10 patients no increase in platelet reactivity after exercise). CD41 and PAC-1 expression increased in CAD group 1 (p = 0.008 and p = 0.026, respectively) but not in CAD group 2 (p = 0.39 and p = 0.50, respectively). No significant differences were observed between the 2 groups for changes in CD62P and leukocyte-platelet aggregates. Conclusions: Our data show that, in patients with stable CAD, an increased platelet reactivity to C/ADP stimulation after exercise, as assessed by the PFA-100 method, is specifically associated with an increased expression of platelet GP IIb/IIIa receptor.