Hyperactivity of Platelets to 5-Hydroxytryptamine in Patients With Cardiovascular Diseases

Abstract

Controversy still exists about the exact role of platelets in the pathogenesis of atherosclerosis. However, patients with cardiovascular (CV) diseases have been reported to have enhanced platelet activity and to show hyperaggregability in response to common aggregators. Very little is known on 5-hydroxytryptamine (5-HT)-induced platelet aggregation in these patients. In a previous preliminary study we observed an increased sensitivity of platelets in response to 5-HT in patients with CV diseases. We further showed that ketanserin, a selective 5-HT receptor antagonist both on platelets and vascular tissue, abolished the 5-HT dependent hyperreactivity of platelets in patients with CV diseases. In a prospective study we investigated platelet aggregation in response to 5-HT at 2 x 10-5Mol in 405 patients with various CV diseases as compared with an age-matched control group of 110 apparently healthy donors. Evaluation of the results was based on the presence of a second irreversible aggregation in response to 5-HT. The control subjects responded to 5-HT with a shape change and a weak, reversible aggregation, except for 9 of the 110 volunteers, where a second irreversible wave occurred (8%). In contrast, it was found that 119 out of 405 patients with CV diseases had a biphasic irreversible aggregation (29%) (Chi-square test : p < 0.0001). From these 405 patients 129 patients suffered from an acute myocardial infarction (AMI), between 4 and 14 days after the onset of symptoms, 78 patients suffered from ischemic heart disease (IHD), 99 patients from peripheral arterial obstructive disease (PAOD) and 99 patients from diabetes, without clinical symptoms of atherosclerosis. A secondary irreversible platelet aggregation to 5-HT was observed in 36% of patients with AMI, in 22% of patients with IHD, in 25% of patients with PAOD and in 31% of patients with diabetes, all the subgroups being significantly different from the control subjects (p <0.01). These findings suggest that platelets may play a role in the propagation and manifestations of CV diseases and that in diabetes the enhanced platelet activity may be a contributing risk factor in de development of atherosclerosis. Finally, since 5-HT is a potent mediator of vasospasm, treatment with ketanserin might be of therapeutic value in atherosclerosis, where platelet activation is thought to be involved.