Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:893-899
© 1999 American Heart Association, Inc.
Original Contributions |
Hormone Replacement Therapy, Inflammation, and Hemostasis in Elderly Women
From the Departments of Medicine and Pathology (M.C.) and the Department of Pathology (R.P.T.), University of Vermont, Burlington; the London School of Hygiene and Tropical Medicine, Department of Public Health, London, UK (E.N.M.); the Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle (B.M.P.); the Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pa (L.H.K.) and the Department of Medicine, The Johns Hopkins University, Baltimore, Md (A.S.D.).
Correspondence to Mary Cushman, MD, MSc, Assistant Professor of Medicine, University of Vermont, 55A South Park Drive, Colchester, VT 05446. E-mail mcushman{at}salus.uvm.edu
Abstract—Lipid-lowering by
postmenopausal hormone therapy (HRT) explains only partly the assumed
coronary risk reduction associated with therapy. To explore
other possible mechanisms, we studied associations of HRT use with
inflammation and hemostasis risk markers in women 
65 years of age.
Subjects were selected from 3393 participants in the fourth year
examination of the Cardiovascular Health Study, an
observational study of vascular disease risk factors. After excluding
women with vascular disease, we compared levels of inflammation and
hemostasis variables in the 230 women using unopposed estrogen and
60 using estrogen/progestin, with those of 196 nonusers
selected as controls. Compared with nonusers, unopposed
estrogen use was associated with 59% higher mean C-reactive protein
(P<0.001), but with modestly lower levels of other
inflammation indicators, fibrinogen, and alpha-1 acid
glycoprotein (P<0.001). Factor VIIc was
16% higher among estrogen users (P<0.001), but this
was not associated with higher thrombin production (prothrombin
fragment 1-2), or increased fibrin breakdown (D-dimer). Concentration
of plasminogen activator
inhibitor-1 was 50% lower in both using groups
(P<0.001) compared with nonusers, and this was
associated with higher plasmin-antiplasmin complex: 8% higher in
estrogen and 18% higher in estrogen/progestin users
(P<0.05). Relationships between the markers and hormone
use were less pronounced in estrogen/progestin users, with no
association for C-reactive protein except in women in upper 2 tertiles
of body mass index (P for interaction, 0.02). The
direction and strength of the associations of HRT use with inflammation
markers differed depending on the protein, so it is not clear whether
HRT confers coronary risk reduction through an
inflammation-sensitive mechanism. Associations with hemostasis markers
indicated no association with evidence of procoagulation and a possible
association with increased fibrinolytic activity.
Key Words: blood coagulation • inflammation • hormone replacement therapy • elderly • women
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