title: Divergent effects of hormone therapy on serum markers of inflammation in postmenopausal women with coronary artery disease on appropriate medical management.
abstract: OBJECTIVE
  The goal of our study was to determine whether hormone therapy alters markers of inflammation in postmenopausal women with chronic stable coronary artery disease (CAD) on appropriate medical management.
  
  
  BACKGROUND
  Hormone therapy reduces some markers of inflammation associated with atherosclerosis risk (cell adhesion molecules) but increases levels of another marker of inflammation--C-reactive protein-in healthy postmenopausal women.
  
  
  METHODS
  Ten women (average age 66 years; range 59 to 76 years) with CAD on medical management (including aspirin [9], statin lipid-lowering therapy [7], angiotensin-converting enzyme inhibitors [3]) were randomly assigned to conjugated equine estrogens 0.625 mg (combined with medroxyprogesterone acetate 2.5 mg daily in five women with uterus intact) or placebo(s) daily for one month with crossover to the alternate therapy after one month off of hormone treatment in a double-blind study. At the end of each treatment phase, the following markers of inflammation were measured in serum: interleukin-6, C-reactive protein, E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and matrix metalloproteinase-9.
  
  
  RESULTS
  Hormone therapy significantly lowered serum levels of cell adhesion molecules E-selectin (46.9+/-18.3 vs. 56.3+/-20.6 ng/mL, p = 0.006), intercellular adhesion molecule-1 (282+/-74 vs. 304+/-78 ng/mL, p = 0.013) and vascular cell adhesion molecule-1 (605+/-218 vs. 657+/-214 ng/mL, p = 0.01) but increased levels of matrix metalloproteinase-9 (648+/-349 vs. 501+/-285 ng/mL, p = 0.02). Interleukin-6 (4.33+/-4.78 vs. 3.04+/-1.47 pg/mL, p = 0.283) and C-reactive protein (0.88+/-1.13 vs. 0.61+/-0.50 mg/dL, p = 0.358) were not significantly elevated on hormone therapy compared with placebo values.
  
  
  CONCLUSIONS
  Hormone therapy has divergent effects on serum markers of inflammation in women with CAD. Reduction in levels of cell adhesion molecules may reduce attachment of white blood cells to the vessel wall, but increases in matrix metalloproteinase-9 within the vessel wall could digest and weaken fibrous caps of vulnerable plaques, thus provoking thrombosis.
authors.affiliation: Cardiology Branch and the Office of Biostatistics Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: D
authors.initials: D
authors.lastname: Zanger
authors.forename: B K
authors.initials: BK
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Ardans
authors.forename: M A
authors.initials: MA
authors.lastname: Waclawiw
authors.forename: G
authors.initials: G
authors.lastname: Csako
authors.forename: L M
authors.initials: LM
authors.lastname: Wahl
authors.forename: R O
authors.initials: RO
authors.lastname: Cannon
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis*; D015815:Cell Adhesion Molecules / Q000097:blood*; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy; D018592:Cross-Over Studies; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D004966:Estrogens, Conjugated (USP); D015850:Interleukin-6; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9