title: Interleukin-10 concentration and coronary heart disease (CHD) event risk in the estrogen replacement and atherosclerosis (ERA) study.
abstract: Interleukin-10 (IL-10) is a cytokine with pleiotropic properties. Limited biochemical and clinical evidence suggest a link between IL-10 and coronary heart disease (CHD). However, more data are needed to clarify the relationship between IL-10 and risk for CHD events.
  
  
  METHODS
  The present study was a secondary analysis of the estrogen replacement and atherosclerosis (ERA) trial, a randomized clinical trial that examined the effects of hormone replacement therapy on post-menopausal women with known coronary atherosclerosis. IL-10 concentration, measured at baseline, was treated as both a continuous and categorical variable. Cox proportional hazards models were used to compute hazard ratios as estimates of relative risk for CHD events.
  
  
  RESULTS
  There were 71 events over an average 3.2 year follow-up. Incident rates were higher for individuals with IL-10 concentrations equal to or greater than the median level (1.04 pg/mL) compared to those individuals below the median level (30% versus 18.5%, p=0.02). The cumulative incidence of CHD events was significantly greater in individuals with IL-10 concentrations >or=1.04 pg/mL (p=0.01). A one standard deviation increase in baseline IL-10 concentration was associated with a 34% greater risk of a CHD event (HR 1.34 [1.06-1.68], p=0.01). This elevated risk was not altered by interleukin-6, C-reactive protein, or additional cardiovascular risk factors. IL-10 concentration and risk for CHD events was most pronounced in diabetics (HR 2.4 [1.46-3.83], p=0.0005).
  
  
  CONCLUSIONS
  In the ERA trial, elevated IL-10 concentration was associated with an increased risk for future cardiovascular events in post-menopausal women with established coronary atherosclerosis. Further study of the relationship between IL-10 and the pathogenesis and progression of atherosclerosis and cardiovascular events is warranted.
authors: Department of Internal Medicine/Cardiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. slakoski@wfubmc.edu
authors: Susan G
authors: SG
authors: Lakoski
authors: Yongmei
authors: Y
authors: Liu
authors: K Bridget
authors: KB
authors: Brosnihan
authors: David M
authors: DM
authors: Herrington
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003327:Coronary Disease / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology; D018450:Disease Progression; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects / Q000276:immunology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D014657:Vasculitis / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control
chemical_list: D015415:Biomarkers; D004967:Estrogens; D015850:Interleukin-6; D016753:Interleukin-10; D002097:C-Reactive Protein
references: Circulation. 2004 May 4;109(17):2046-9
references: 15096450
references: Circulation. 2003 Apr 29;107(16):2109-14
references: 12668510
references: J Exp Med. 1991 Nov 1;174(5):1209-20
references: 1940799
references: Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1890-3
references: 1371884
references: J Immunol. 1993 Jun 1;150(11):4754-65
references: 7684412
references: Lymphokine Cytokine Res. 1994 Feb;13(1):47-54
references: 8186324
references: Int Immunol. 1994 Dec;6(12):1927-36
references: 7696210
references: Ann Med. 1995 Oct;27(5):537-41
references: 8541028
references: J Exp Med. 1996 Jun 1;183(6):2663-8
references: 8676087
references: J Immunol. 1998 Apr 1;160(7):3188-93
references: 9531274
references: J Immunol. 1998 Oct 15;161(8):4420-7
references: 9780221
references: Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):611-6
references: 10073964
references: J Biol Chem. 2004 Dec 3;279(49):51697-703
references: 15465816
references: Am Heart J. 2005 Sep;150(3):488-99
references: 16169330
references: Eur Heart J. 2006 Jul;27(14):1685-9
references: 16772342
references: Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2469-75
references: 16917108
references: Atherosclerosis. 2007 Aug;193(2):335-42
references: 17087966
references: Scand J Immunol. 2006 Sep;64(3):336-44
references: 16918703
references: Control Clin Trials. 2000 Jun;21(3):257-85
references: 10822123
references: N Engl J Med. 2000 Aug 24;343(8):522-9
references: 10954759
references: Circulation. 2001 Aug 14;104(7):746-9
references: 11502695
references: Am J Cardiol. 2003 Jan 15;91(2):133-6
references: 12521622
references: Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1474-8
references: 15178562