title: Comparative effects of estrogen and angiotensin-converting enzyme inhibition on plasminogen activator inhibitor-1 in healthy postmenopausal women.
abstract: BACKGROUND
  This study compares the effect of estrogens and ACE inhibition on plasminogen activator inhibitor-1 (PAI-1) concentrations in healthy postmenopausal women, genotyped for a 4G/5G polymorphism in the PAI-1 promoter, a polymorphism shown to influence PAI-1 concentrations. Methods and Results- Morning estradiol, PAI-1, tissue plasminogen activator, plasma renin activity, angiotensin II, and aldosterone were measured in 19 postmenopausal women (5G/5G:4G/5G:4G4G=5:10:4, respectively) at baseline and during randomized, single-blind, crossover treatment with conjugated equine estrogens 0.625 mg per os per day, ramipril 10 mg per os per day, and combination estrogens and ramipril. Estradiol (P<0.005) and angiotensin II (P<0.01) were significantly higher during estrogens. Plasma renin activity was significantly increased during ACE inhibition (P<0.05). Both conjugated estrogens [PAI-1 antigen from 12.5 (7.6, 17.4) [mean (95% CI)] baseline to 6.6 (2.6, 10.7) ng/mL, P<0.01] and ACE inhibition [8.3 (4.9, 11.7) ng/mL, P<0.005] decreased PAI-1 without decreasing tissue plasminogen activator. The effect of combined therapy on PAI-1 [5.6 (2.3, 8.8) ng/mL] was significantly greater than that of ramipril alone (P<0.05). There was a significant effect of PAI-1 4G/5G genotype on baseline PAI-1 concentrations (P=0.001) and a significant interactive effect of 4G/5G genotype and treatment, such that genotype influenced the change in PAI-1 during ramipril (P=0.011) or combined therapy (P=0.006) but not during estrogens (P=0.715).
  
  
  CONCLUSIONS
  ACE inhibition with ramipril and conjugated estrogens similarly decrease PAI-1 antigen concentrations in postmenopausal women. Larger studies that use clinical outcomes are needed to determine whether PAI-1 4G/5G genotype should influence the choice of conjugated estrogens or ACE inhibition for the treatment of healthy postmenopausal women.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanerbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
authors.forename: Amira
authors.initials: A
authors.lastname: Abbas
authors.forename: Daniel
authors.initials: D
authors.lastname: Byrne
authors.forename: John A
authors.initials: JA
authors.lastname: Schoenhard
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Vaughan
mesh_terms: D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000517:prevention & control; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000097:blood; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics; D011110:Polymorphism, Genetic; D017698:Postmenopause / Q000097:blood / Q000187:drug effects*; D017257:Ramipril / Q000008:administration & dosage / Q000494:pharmacology*; D012083:Renin / Q000097:blood; D016037:Single-Blind Method; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004966:Estrogens, Conjugated (USP); D017395:Plasminogen Activator Inhibitor 1; D000804:Angiotensin II; D000450:Aldosterone; D004958:Estradiol; D010959:Tissue Plasminogen Activator; D012083:Renin; D017257:Ramipril