title: Interleukin-6 and the risk of future cardiovascular events in patients with angina pectoris and/or healed myocardial infarction.
abstract: The aim of this study was to evaluate the prognostic value of interleukin-6 (IL-6) for myocardial infarction (MI) and mortality in a population with stable coronary artery disease (CAD) during a mean period of 6.3 years. IL-6 is a major proinflammatory cytokine of acute phase response; elevated levels are associated with worse prognosis in unstable angina and after acute MI. However, data regarding its long-term prognostic value in stable CAD are limited and controversial. A nested case-control study design was used. Of 3,090 patients with stable CAD, 129 with an adequate blood sample for IL-6 and who reached the end points (MI or sudden death) were randomly selected. Each case was 1:1 matched with 129 controls (alive at the end of the study and free of cardiovascular events) according to age, gender, and treatment. Of the 129 cases, 113 had a MI as the initial event, and for the other 16 the initial event was sudden death. There were 8 patients who first had a MI and later died suddenly. IL-6 was significantly higher in cases (2.34 pg/ml) than in controls (1.65 pg/ml) (p = 0.0004). IL-6 was significantly correlated with C-reactive protein (r = 0.2, p = 0.002); a borderline significance was also found for fibrinogen (r = 0.11, p = 0.07). Each increase of 1 pg/ml in IL-6 was associated with a 1.70 (range 1.23 to 2.45) increased relative odds of subsequent MI or sudden death. Events rate per 1,000 patients-years for the 5 quintiles of IL-6 were 72.26, 89.61, 79.76, 142.53, and 181.08, respectively (p <0.0001). A significantly higher risk in the upper quintile was found (odds ratio, 3.44; 95% confidence interval 1.57 to 8.13). In conclusion, elevated IL-6 levels are strongly associated with future cardiac events and mortality in a population with stable CAD during a long-term follow-up.
authors.affiliation: Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. zfisman@post.tau.ac.il
authors.forename: Enrique Z
authors.initials: EZ
authors.lastname: Fisman
authors.forename: Michal
authors.initials: M
authors.lastname: Benderly
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Esper
authors.forename: Solomon
authors.initials: S
authors.lastname: Behar
authors.forename: Valentina
authors.initials: V
authors.lastname: Boyko
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Adler
authors.forename: David
authors.initials: D
authors.lastname: Tanne
authors.forename: Zipora
authors.initials: Z
authors.lastname: Matas
authors.forename: Alexander
authors.initials: A
authors.lastname: Tenenbaum
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000097:blood* / Q000150:complications; D001786:Blood Glucose; D015992:Body Mass Index; D016022:Case-Control Studies; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000209:etiology / Q000401:mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking
chemical_list: D001786:Blood Glucose; D015850:Interleukin-6; D005340:Fibrinogen