雌激素与血管紧张素转换酶抑制剂对健康绝经后女性纤溶酶原激活物抑制剂-1的比较作用

Comparative effects of estrogen and angiotensin-converting enzyme inhibition on plasminogen activator inhibitor-1 in healthy postmenopausal women.

作者信息

Brown Nancy J, Abbas Amira, Byrne Daniel, Schoenhard John A, Vaughan Douglas E

机构信息

Division of Clinical Pharmacology, Department of Medicine, Vanerbilt University Medical Center, Nashville, Tennessee, USA.

出版信息

Circulation. 2002 Jan 22;105(3):304-9. doi: 10.1161/hc0302.102570.

DOI:10.1161/hc0302.102570

PMID:11804984

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.

摘要

背景

本研究比较了雌激素和血管紧张素转换酶（ACE）抑制剂对健康绝经后女性纤溶酶原激活物抑制剂-1（PAI-1）浓度的影响，这些女性针对PAI-1启动子中的4G/5G多态性进行了基因分型，该多态性已被证明会影响PAI-1浓度。方法与结果：对19名绝经后女性（5G/5G:4G/5G:4G4G分别为5:10:4）在基线时以及在随机、单盲、交叉治疗期间测量了早晨的雌二醇、PAI-1、组织纤溶酶原激活物、血浆肾素活性、血管紧张素II和醛固酮，治疗药物分别为每日口服0.625mg结合马雌激素、每日口服10mg雷米普利以及结合雌激素与雷米普利的联合用药。在使用雌激素期间，雌二醇（P<0.005）和血管紧张素II（P<0.01）显著升高。在进行ACE抑制期间，血浆肾素活性显著增加（P<0.05）。结合雌激素[PAI-1抗原从基线时的12.5（7.6，17.4）[均值（95%CI）]降至6.6（2.6，10.7）ng/mL，P<0.01]和ACE抑制[8.3（4.9，11.7）ng/mL，P<0.005]均降低了PAI-1，而未降低组织纤溶酶原激活物。联合治疗对PAI-1的影响[5.6（2.3，8.8）ng/mL]显著大于单独使用雷米普利（P<0.05）。PAI-1 4G/5G基因型对基线PAI-1浓度有显著影响（P=0.001），并且4G/5G基因型与治疗之间存在显著的交互作用，因此基因型影响雷米普利治疗期间（P=0.011）或联合治疗期间（P=0.006）PAI-1的变化，但不影响雌激素治疗期间（P=0.715）。