IMPAIRED PLATELET PRODUCTION OF NITRIC-OXIDE PREDICTS PRESENCE OF ACUTE CORONARY SYNDROMES

Background - Thrombus formation within a coronary vessel is the acute precipitating event in most acute coronary syndromes. Recently, consti tutive nitric oxide synthase (cNOS) has been identified in human plate lets, and platelet-derived nitric oxide has been shown to inhibit plat elet recruitment after aggregation. However, its role in regulating pl atelet responses under normal or pathologic conditions has not yet bee n elucidated. Methods and Results - We examined nitric oxide (NO) prod uction by platelets isolated from 87 patients undergoing coronary angi ography, 37 with stable angina and 50 with unstable angina or a myocar dial infarction within 2 weeks. After stimulation with 5 mu mol/L ADP, platelet aggregation and NO production were simultaneously measured w ith an NO-selective microelectrode adapted for use in a standard plate let aggregometer. Mean (+/- SEM) platelet-derived NO production was 1. 78 +/- 0.36 pmol/10(8) and 0.26 +/- 0.05 pmol/10(8) platelets in coron ary patients with stable angina and acute coronary syndromes, respecti vely (P = 0.0001). By logistic regression analysis, heparin treatment (odds ratio 6.6, CI 1.9 to 22.8, P = 0.003), lower platelet-NO product ion (odds ratio 4.0, CI 1.3 to 11.5, P = 0.01), and extent of atherosc lerosis (odds ratio 1.5, CI 1.1 to 2.0, P = 0.02) were independent pre dictors of an acute coronary syndrome. In the subset of patients with angiographic evidence of atherosclerosis (n = 83), logistic regression demonstrated that platelet NO production (odds ratio 3.9, CI 1.3 to 1 1.1, P = 0.01) and heparin treatment (odds ratio 6.3, CI 1.9 to 22.0, P = 0.004) were independent predictors of an acute coronary syndrome, whereas extent of atherosclerosis was not. Conclusions - In summary, a ggregating platelets from patients with acute coronary syndromes produ ce less NO. Since platelet aggregation and thrombus formation are impl icated in unstable angina and myocardial infarction, impaired platelet -derived NO production may contribute to the development of acute coro nary syndromes.