Hormone replacement therapy, inflammation, and hemostasis in elderly women

Lipid-lowering by postmenopausal hormone therapy (HRT) explains only partly the assumed coronary risk reduction associated with therapy. To explore ot her possible mechanisms, we studied associations of HRT use with inflammati on and hemostasis risk markers in women greater than or equal to 65 years o f age. Subjects were selected from 3393 participants in the fourth year exa mination of the Cardiovascular Health Study, an observational study of vasc ular disease risk factors. After excluding women with vascular disease, we compared levels of inflammation and hemostasis variables in the 230 women u sing unopposed estrogen and 60 using estrogen/progestin, with those of 196 nonusers selected as controls. Compared with nonusers, unopposed estrogen u se was associated with 59% higher mean C-reactive protein (P<0.001), but wi th modestly lower levels of other inflammation indicators, fibrinogen, and alpha-1 acid glycoprotein (P<0.001). Factor VIIc was 16% higher among estro gen users (P<0.001), but this was not associated with higher thrombin produ ction (prothrombin fragment 1-2), or increased fibrin breakdown (D-dimer). Concentration of plasminogen activator inhibitor-1 was 50% lower in both us ing groups (P<0.001) compared with nonusers, and this was associated with h igher plasmin-antiplasmin complex: 8% higher in estrogen and 18% higher in estrogen/progestin users (P<0.05). Relationships between the markers and ho rmone use were less pronounced in estrogen/progestin users, with no associa tion for C-reactive protein except in women in upper 2 tertiles of body mas s index (P for interaction, 0.02). The direction and strength of the associ ations of HRT use with inflammation markers differed depending on the prote in, so it is not clear whether HRT confers coronary risk reduction through an inflammation-sensitive mechanism. Associations with hemostasis markers i ndicated no association with evidence of procoagulation and a possible asso ciation with increased fibrinolytic activity.