Interleukin-8 as an independent predictor of long-term clinical outcome in patients with coronary artery disease.
BACKGROUND
Accumulating evidence suggests that inflammation plays an essential role in the pathogenesis of atherosclerosis and that circulating inflammatory markers predict future cardiovascular events. However, previous studies evaluated the predictive value of only a single cytokine at a time.


OBJECTIVE
This study was designed to simultaneously measure plasma levels of multiple cytokines in patients with coronary artery disease and to evaluate their ability to predict long-term prognosis.


METHODS
The study enrolled 158 consecutive patients with angiographically identified stable coronary artery disease. Using the Luminex micro-beads array system, we simultaneously measured plasma levels of the following 10 cytokines: interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, granulocyte-macrophage colony stimulating factor (GM-CSF) and gamma-interferon (IFN-gamma).


RESULTS
None of the 10 cytokine levels as well as high-sensitive C reactive protein (hs-CRP) was correlated with the severity of coronary artery disease. During a 7-year follow-up period, cardiovascular events occurred in 56 patients (35%). Multi-vessel disease, diabetes, and high levels of all of the 10 measured cytokines and hs-CRP were significant predictors of cardiovascular events in univariate analysis. However, multivariate analysis using multi-vessel disease, diabetes and the levels of all of 10 cytokines and hs-CRP showed that the only independent predictor was IL-8 (RR, 2.98; 95%CI, 1.64-7.24; P=0.0001).


CONCLUSIONS
IL-8 was the only cytokine that predicted cardiovascular events independent of the other 9 cytokines and hs-CRP. Since IL-8 is a neutrophil chemokine, these results suggest that neutrophil activation may be related to the occurrence of cardiovascular events.
Inoue
Teruo
T
Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan. inouete@med.saga-u.ac.jp
Komoda
Hiroshi
H
Nonaka
Masako
M
Kameda
Miho
M
Uchida
Toshihiko
T
Node
Koichi
K
D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000401:mortality; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009391:Nephelometry and Turbidimetry; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors
D015415:Biomarkers; D016209:Interleukin-8; D002097:C-Reactive Protein