Association between Plasma Interleukin-27 Levels and Cardiovascular Events in Patients Undergoing Coronary Angiography

Abstract

Atherosclerotic disease, including coronary heart disease (CHD), is one of the chronic inflammatory conditions, and an imbalance between pro-inflammatory and anti-inflammatory cytokines plays a role in the process of atherosclerosis. Interleukin (IL)-27, one of the IL-12 family members, is recognized to play a dual role in regulating immune responses with both pro-inflammatory and anti-inflammatory properties. IL-27 is secreted from monocytes, T cells, and endothelial cells, and its expression is upregulated in atherosclerotic plaques. We previously reported that no significant difference was observed in plasma IL-27 levels between patients with stable CHD and those without it. However, the prognostic value of IL-27 levels has not been fully elucidated. We studied the relation of plasma IL-27 levels to cardiovascular events in 402 patients undergoing elective coronary angiography for suspected CHD. We defined cardiovascular events as cardiovascular death, myocardial infarction, unstable angina, stroke, or coronary revascularization. Of the 402 study patients, CHD was present in 209 (52%) patients. Plasma IL-27 levels were not markedly different between patients with CHD and those without it (median 0.23 vs. 0.23 ng/mL). During a follow-up of 7.6 ± 4.5 years, cardiovascular events were observed in 70 patients (17%). In comparison to the 332 patients with no event, the 70 patients who had cardiovascular events showed significantly higher IL-27 levels (median 0.29 vs. 0.22 ng/mL) and more frequently had an IL-27 level of >0.25 ng/mL (59% vs. 40%) (p < 0.01). The Kaplan–Meier analysis demonstrated a lower event-free survival rate in patients with an IL-27 level >0.25 ng/mL than in those with an IL-27 level ≤0.25 ng/mL (p < 0.02). The multivariate Cox proportional hazards regression analysis showed that IL-27 level (>0.25 ng/mL) was a significant predictor for cardiovascular events (hazard ratio: 1.82; 95%CI: 1.13–2.93, p < 0.02), independent of CHD. Thus, high IL-27 levels in plasma were related to an increased risk of further cardiovascular events in patients who underwent elective coronary angiography.