Platelet aggregability in syndrome X: a role for adenosine

Patients with syndrome X, defined as angina without demonstrable obstructive epicardial coronary artery disease, have been the subject of multiple investigations evaluating the pathophysiology of this syndrome. Multiple aetiologies have been proposed to explain the mechanism of ischaemia including endothelial dysfunction, microvascular hyperresponsiveness, and hyperadrenergic state. Interestingly, although platelets have been shown to play a central role in acute coronary syndromes, and changes in platelet aggregability following exercise have been demonstrated in patients with significant coronary artery disease, the role of platelets in syndrome X has been little studied. In this issue Lanza and colleagues report the results of an evaluation of platelet function in patients with syndrome X, and compare this to a normal control group as well as a group of patients with chronic ischaemic coronary disease. The investigators make the novel observation that ADP stimulated collagen and platelet aggregation was substantially increased at rest in patients with syndrome X compared to patients with chronic ischaemic coronary disease and healthy controls. Additionally, following exercise, platelet aggregability substantially decreased in patients with syndrome X, in contradistinction to patients with chronic ischaemic coronary disease in whom platelet aggregability increased. Moreover, the investigators evaluated the effect of theophylline, a non-specific adenosine receptor antagonist, on platelet function before and during peak exercise in patients with syndrome X and a group of healthy controls. While platelet aggregability did not substantially change in the control group during exercise with or without theophylline, the decrease in platelet aggregability observed in the patients with syndrome X was abolished by the administration of theophylline. These findings are provocative, and suggest that altered platelet responsiveness exists in patients with syndrome X, as well as implicating adenosine in mediating these changes. In the design of the study the investigators chose not to evaluate the role of theophylline in patients