Is interleukin-18 correlated with endothelial dysfunction and platelet activation in patients with unstable angina?

The aim of the study was to assess the interaction between interleukin-18 (IL-18, a cytokine with a central role in the inflammatory cascade) and the presence of endothelial dysfunction and prothrombotic profile in patients with unstable angina and proven coronary artery disease.

The study EDIT-ACS (Endothelial Dysfunction, Inflammation and Thrombosis in Acute Coronary Syndromes) was set in the Cardiology Department of our Institute, and inclusions were performed between June-November 2004. We included 40 consecutive patients with unstable angina hospitalized in our Department (mean age = 60.2 +/- 8.8 years, 57.5% male), as well as 20 normal pts as a control population,matched for age and sex (mean age = 61.9 +/- 8.6 years, 58.3% male). All pts had the following biological studies performed: interleukin-18 (IL-18), C-reactive protein (CRP), fibrinogen, leukocyte count, and Von Willebrand factor, as well as platelet activity parameters (mean platelet volume, MPV and platelet distribution width, PDW). All pts had echographic studies of flow mediated dilatation (FMD) and measurement of carotid intima-media thickness (C-IMT), and underwent coronary angiography as well.

We found that patients in the highest quartile of IL-18 had higher levels of CRP (11.9 +/- 4.2 vs 6.8 +/- 3.4 mg/l, p<0.01), von Willebrand factor (166% vs 150%, p=0.08), PDW (14.5 vs 13.2, p=0.04), MPV (11.2 vs 10.2, p=0.02), as well as a higher number of coronary stenoses (mean no. of affected vessels 2.5 vs 1.1, p<0.001), trend towards higher carotid IMT (0.92 mm vs 0.81 mm, p=0.06). They also have significant endothelial dysfunction (FMD of 5 % vs 8.5% for 4th quartile and 1st quartile respectively). Pts with higher levels of IL-18 associated a worse short term (in hospital prognosis) with 60% of pts in the 4th quartile having adverse events, versus 22% in the lowest quartile.

High levels of interkleukin-18 are associated with endothelial dysfunction (high von Willebrand factor and low brachial FMD) and platelet activation (high MPV and PDW values), in pts with a higher number of affected coronary arteries but similar global atherosclerotic burden. This could explain the association between high levels of IL-18 and worse short-term prognosis in pts with unstable angina.