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CLINICAL STUDY: ACUTE CORONARY SYNDROME

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

^a Department of Cardiology, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia

Manuscript received September 20, 2000; revised manuscript received February 7, 2001, accepted February 15, 2001.

Reprint requests and correspondence: Prof. John D. Horowitz, Department of Cardiology, The Queen Elizabeth Hospital, Woodville 5011, S.A., Australia
john.horowitz{at}adelaide.edu.au

OBJECTIVES

The study examined possible clinical determinants of platelet resistance to nitric oxide (NO) donors in patients with stable angina pectoris (SAP) and acute coronary syndromes (ACS), relative to nonischemic patients and normal subjects.

BACKGROUND

We have shown previously that platelets from patients with SAP are resistant to the antiaggregating effects of nitroglycerin (NTG) and sodium nitroprusside (SNP).

METHODS

Extent of adenosine diphosphate (1 µmol/liter)-induced platelet aggregation (impedance aggregometry in whole blood) and inhibition of aggregation by NTG (100 µmol/liter) and SNP (10 µmol/liter) were compared in normal subjects (n = 43), nonischemic patients (those with chest pain but no 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 examined 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 more 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 angina and coronary risk factors were not associated with variability in platelet responsiveness to NO donor.

CONCLUSIONS

Patients with symptomatic ischemic heart disease, especially ACS, exhibit increased platelet aggregability and decreased platelet responsiveness to the antiaggregatory effects of NO donors. The extent of NO resistance in platelets is not correlated with coronary risk factors. Pharmacotherapy with perhexiline and/or statins may improve platelet responsiveness to NO.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ACS = acute coronary syndromes   ADP = adenosine diphosphate   ANOVA = analysis of variance   cGMP = cyclic guanosine-3',5'-monophosphate   NO = nitric oxide   NTG = nitroglycerin   OR = odds ratio   SAP = stable angina pectoris   SNP = sodium nitroprusside

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