Journal of Thrombosis and Thrombolysis 14(2), 139–143, 2002. C  2003 Kluwer Academic Publishers, Manufactured in The Netherlands. Interleukin-1 Receptor Antagonist: A Sensitive Marker of Instability in Patients with Coronary Artery Disease Giuseppe Patti MD, 1 Andrea D’Ambrosio MD, 1 Aldo Dobrina MD, 3 Giordano Dicuonzo MD, 1 Carlo Giansante MD, 2 Nicola Fiotti MD, 2 Antonio Abbate MD, 1 Gianfranco Guarnieri MD, 2 Germano Di Sciascio MD, FACC, FESC 1 1 Department of Cardiovascular Sciences, Campus Bio-Medico University, Rome, Italy; 2 Department of Clinical Medicine, University of Trieste, Italy; 3 Department of Pathology, Campus Bio-Medico University, Rome, Italy Abstract. Background: Increased plasma levels of acute phase reactants are correlated with acute coro- nary syndromes and increased risk of in-hospital events. Interleukin-1 receptor antagonist (IL-1Ra) mod- ulates the activity of IL-1, a cytokine associated with inflammatory response; we have prospectively investi- gated whether detection of increased levels of IL-1Ra in patients may be useful in the characterization of coro- nary syndromes. Methods: Plasma levels of IL-1Ra were measured in 118 consecutive patients undergoing coronary an- giography with a clinical diagnosis of recent unstable angina ( N = 57), chronic stable angina ( N = 49) or atyp- ical chest pain ( N = 12). Results: Angiography showed significant coronary disease in the first two groups and was normal in the latter group. Patients with unstable angina had signifi- cantly higher levels of IL-1Ra than stable patients [158 (110–224) vs 108 (95–154) pg/ml, P = 0.002] and individu- als with chest pain and normal coronary angiogram [110 (97–123) pg/ml, P = 0.038]. In contrast, while C-reactive protein levels were significantly higher in patients with stable and unstable angina vs those without coronary disease (0.29 vs 0.06 mg/dl, P = 0.022), they did not dis- criminate between stable and unstable angina patients (0.22 vs 0.32 mg/dl, P = 0.66). Conclusions: These results indicate that IL-1Ra may be a sensitive marker of clinical instability in patients with coronary artery disease. Abbreviated abstract. Increased plasma levels of acute phase reactants are correlated with acute coro- nary syndromes and increased risk of in-hospital events. Interleukin-1 receptor antagonist (IL-1Ra) mod- ulates the activity of IL-1, a cytokine associated with inflammatory response; we have prospectively inves- tigated whether detection of increased levels of IL- 1Ra in patients may be useful in the characteriza- tion of coronary syndromes. Plasma levels of IL-1Ra were measured in 118 consecutive patients undergo- ing coronary angiography. Patients with recent unsta- ble angina had significantly higher levels of IL-1Ra than stable patients [158 (110–224) vs 108 (95–154) pg/ml, P = 0.002] and individuals with chest pain and nor- mal coronary angiogram [110 (97–123) pg/ml, P = 0.038]. IL-1Ra may therefore represent a sensitive marker of clinical instability in patients with coronary artery disease. Key Words. coronary disease, inflammation, interleukins Introduction Systemic markers of inflammation, such as the acute-phase reactant C-reactive protein (CRP), have been used to assess the risk of coronary events in patients with angina and in apparently healthy men [1–4]. Recently, elevated levels of interleukin-1 re- ceptor antagonist (IL-1Ra), a naturally occurring an- tagonist of the pro-inflammatory cytokine IL-1, were found in patients with unstable coronary syndromes [5]; IL-1Ra was also identified as a prognostic factor following percutaneous coronary interventions [6,7], while no previous investigation has specifically re- ported the diagnostic value of IL-1Ra in patients with chest pain syndromes. IL-1Ra competitively blocks the binding of IL-1β b to IL-1 membrane receptors [8] and counterbalances an augmented synthesis of IL-1 [9]. Goal of this study was to compare IL-1Ra plasma levels in patients with different clinical pre- sentations of coronary artery disease (CAD) and in patients without angiographic evidence of CAD in order to assess the ability of this marker to identify pts with unstable clinical syndromes; a comparison with plasma CRP levels was also performed. Methods Patient population and study design The study population consists of 118 consecutive patients undergoing coronary angiography in our Address for correspondence: Prof. Germano Di Sciascio, De- partment of Cardiovascular Sciences, Campus Bio-Medico University, Via E. Longoni, 83-00155 Rome, Italy. Tel.: +39- 06-22541523; Fax: +39-06-22541336; E-mail: g.disciascio@ unicampus.it 139