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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2661.)
© 2005 American Heart Association, Inc.

Thrombosis

Platelet Nitric Oxide Responsiveness

A Novel Prognostic Marker in Acute Coronary Syndromes

Scott R. Willoughby; Simon Stewart; Andrew S. Holmes; Yuliy Y. Chirkov; John D. Horowitz

From the Cardiology Unit (S.R.W., A.S.H., Y.Y.C., J.D.H.), Basil Hetzel Institute, Queen Elizabeth Hospital, Department of Medicine, University of Adelaide, and Department of Nursing and Midwifery (S.S.), University of South Australia, Adelaide.

Correspondence to John D. Horowitz, Cardiology Unit, Queen Elizabeth Hospital, 28 Woodville Rd, Woodville 5011, South Australia, Australia. E-mail john.horowitz{at}adelaide.edu.au

Objectives— Nitric oxide (NO) is critically important in the regulation of vascular tone and the inhibition of platelet aggregation. We have shown previously that patients with acute coronary syndromes (ACS) or stable angina pectoris have impaired platelet responses to NO donors when compared with normal subjects. We tested the hypotheses that platelet hyporesponsiveness to NO is a predictor of (1) cardiovascular readmission and/or death and (2) all-cause mortality in patients with ACS (unstable angina pectoris or non–Q-wave myocardial infarction).

Methods and Results— Patients (n=51) with ACS had evaluation of platelet aggregation within 24 hours of coronary care unit admission using impedance aggregometry. Patients were categorized as having "normal" (32% inhibition of ADP-induced aggregation with the NO donor sodium nitroprusside; 10 µmol/L; n=18) or "impaired" (<32% inhibition of ADP-induced aggregation; n=33) NO responses. We then compared the incidence of cardiovascular readmission and death during a median of 7 years of follow-up in these 2 groups. Using a Cox proportional hazards model adjusting for age, sex, index event, postdischarge medical treatment, revascularization status, left ventricular systolic dysfunction, concurrent disease states, and cardiac risk factors, impaired NO responsiveness was associated with an increased risk of the combination of cardiovascular readmission and/or death (relative risk, 2.7; 95% CI, 1.03 to 7.10; P=0.041) and all-cause mortality (relative risk, 6.3; 95% CI, 1.09 to 36.7; P=0.033).

Conclusions— Impaired platelet NO responsiveness is a novel, independent predictor of increased mortality and cardiovascular morbidity in patients with high-risk ACS.

We tested the hypotheses that platelet hyporesponsiveness to nitric oxide (NO) at time of admission is a predictor cardiovascular readmission and/or death and all-cause mortality in high-risk patients (n=51) with ACS. Impaired NO responsiveness was associated with an 3-fold increased risk of the combination of cardiovascular readmission and/or death and 6-fold incremental risk of all-cause mortality. Severe impairment of platelet responsiveness to NO is, thus, an independent prognostic marker in such patients and may more directly reflect risk of vascular events than measures of endothelial dysfunction.

Key Words: nitric oxide • platelets • acute coronary syndrome • nitric oxide resistance

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