Stable angina and acute coronary syndromes are associated with nitric oxide resistance in platelets

OBJECTIVES The study examined possible clinical determinants of platelet re sistance to nitric oxide (NO) donors in patients with stable angina pectori s (SAP) and acute coronary syndromes (ACS), relative to nonischemic patient s and normal subjects. BACKGROUND We have shown previously that platelets from patients with SAP a re resistant to the antiaggregating effects of nitroglycerin (NTG) and sodi um nitroprusside (SNP). METHODS Extent of adenosine diphosphate (1 mu mol/liter)-induced platelet a ggregation (impedance aggregometry in whole blood) and inhibition of aggreg ation by NTG (100 mu mol/liter) and SNP (10 mu mol/liter) were compared in normal subjects (n = 43), nonischemic patients (those with chest pain but n o fixed coronary disease, (n = 35) and patients with SAP (n = 82) or ACS (n = 153). Association of NO resistance with coronary risk factors, coronary artery disease (CAD), intensity of angina and current medication was examin ed by univariate and multivariate analyses. RESULTS In patients with SAP and ACS as distinct from nonischemic patients and normal subjects, platelet aggregability was increased (both p < 0.01), and inhibition of aggregation by NTG and SNP was decreased (both p < 0.01). Multivariate analysis revealed that NO resistance occurred significantly m ore frequently with ACS than with SAP (odds ratio [OR] 2.3:1), and was less common among patients treated with perhexiline (OR 0.3:1) or statins (OR 0 .45:1). Therapy with other antianginal drugs, extent of CAD, intensity of a ngina and coronary risk factors were not associated with variability in pla telet responsiveness to NO donor. CONCLUSIONS Patients with symptomatic ischemic heart disease, especially AC S, exhibit increased platelet aggregability and decreased platelet responsi veness to the antiaggregatory effects of NO donors. The extent of NO resist ance in platelets is not correlated with coronary risk factors. Pharmacothe rapy with perhexiline and/or statins may improve platelet responsiveness to NO. (J Am Coll Cardiol 2001;37:1851-7) (C) 2001 by the American College of Cardiology.