Effect of long-term therapy with ramipril in high-risk women

Lonn, Eva; Roccaforte, Rosa; Yi, Qilong; Dagenais, Gilles R.; Sleight, Peter; Bosch, Jackie; Suhan, Pamela S.; Micks, Mary; Probstfield, Jeffrey L.; Bernstein, Victoria; Yusuf, Salim

doi:10.1016/s0735-1097(02)02035-1

Cited by 46 publications

(21 citation statements)

References 19 publications

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“…These data are relevant to recent clinical trials 35,36 examining the cardioprotective effects of ACE inhibitors within gender groups. The current study provides one mechanistic rationale for further studies examining the interactive effects of ACE inhibition and hormone replacement therapy on thrombotic outcomes in women.…”

Section: Pretorius Et Al Ace Inhibition Increases T-pa In Women 2439mentioning

confidence: 92%

Angiotensin-Converting Enzyme Inhibition Increases Basal Vascular Tissue Plasminogen Activator Release in Women But Not in Men

Pretorius

Luther

Murphey

et al. 2005

ATVB

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Objective-Angiotensin-converting enzyme inhibition (ACEI) increases vascular tissue plasminogen activator (t-PA) release through endogenous bradykinin (BK). We tested the hypothesis that gender influences the effect of ACEI on t-PA release. Methods and Results-We measured the effect of intra-arterial enalaprilat (0.33 g/min per 100 mL forearm volume) on forearm blood flow (FBF) and net t-PA release before and during BK (25 to 400 ng/min) and methacholine (3.2 to 12.8 g/min) in premenopausal women, postmenopausal women not using hormone replacement, young men, and older men. Baseline net t-PA release was similar among groups. Enalaprilat increased basal t-PA release in premenopausal (from 0.9Ϯ1.0 to 5.1Ϯ1.7 ng/min per 100 mL, Pϭ0.023) and postmenopausal women (from Ϫ3.9Ϯ2.2 to 3.9Ϯ1.1 ng/min per 100 mL, Pϭ0.010) but not in young or older men (Pϭ0.028 men versus women). Enalaprilat potentiated the effect of exogenous BK on FBF similarly in all groups. However, during enalaprilat, BK-stimulated t-PA release was greatest in premenopausal women (339.9Ϯ86.4 ng/min per 100 mL at the 100 ng/min dose, PϽ0.05 versus any other group), intermediate in postmenopausal women (243.8Ϯ51.1 ng/min per 100 mL, PϽ0.05 versus either male group), and least in young (111.9Ϯ19.2 ng/min/100 mL) and older men (103.4Ϯ27.6 ng/min/100 mL). Conclusion-ACEI enhances basal t-PA release in women, independent of menopausal status, but not in men. During ACEI, both gender and menopausal status affect BK stimulated t-PA release. (Arterioscler Thromb Vasc Biol. 2005;25:2435-2440.)Key Words: angiotensin Ⅲ inhibitors Ⅲ plasminogen activators Ⅲ women A ngiotensin-converting enzyme (ACE) inhibition improves endothelial function 1 and favorably alters fibrinolytic balance by decreasing angiotensin II (Ang II), a potent stimulus to plasminogen activator inhibitor-1 (PAI-1) synthesis 2-4 and by increasing bradykinin (BK), a potent stimulus to tissue plasminogen activator (t-PA) secretion. 5,6 For example, a recent study from this group using the specific BK B 2 receptor antagonist HOE 140 indicates that ACE inhibition increases baseline vascular t-PA release in humans through endogenous BK. 7 Unexpectedly, ACE inhibition increased basal t-PA release only in the female subjects studied. Moreover, ACE inhibition did not increase basal t-PA release in 2 earlier studies in predominantly male populations. 5,8 Coronary BK concentrations increase during myocardial ischemia 9 and ACE inhibitors potentiate BK-stimulated coronary 8 as well as forearm t-PA release. 5 Thus BK-stimulated t-PA release may be important in limiting thrombosis during myocardial infarction. Whereas the previous data of Pretorius et al 7 suggested that gender influences the effect of ACE inhibition on basal t-PA release, that study was not designed to test such a hypothesis. Study groups were not prospectively matched for gender. More importantly, the dose of enalaprilat was not normalized per forearm volume. Thus women, who have a smaller forearm volume than men, were given a higher effecti...

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Section: Pretorius Et Al Ace Inhibition Increases T-pa In Women 2439mentioning

confidence: 92%

Angiotensin-Converting Enzyme Inhibition Increases Basal Vascular Tissue Plasminogen Activator Release in Women But Not in Men

Pretorius

Luther

Murphey

et al. 2005

ATVB

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“…ACE inhibitors decrease mortality attributable to CHD in both men and women. 37 Previous studies indicate that ACE inhibition increases basal and bradykinin-stimulated t-PA antigen release in pre-and postmenopausal women compared with age-matched men, but enhances bradykinin-stimulated t-PA release to a greater extent in premenopausal women compared with postmenopausal women. 23 The present study confirms that ACE inhibition enhances basal t-PA antigen release in postmenopausal women but suggests that released antigen is rapidly inactivated.…”

Section: Perspectivesmentioning

confidence: 94%

17β-Estradiol Increases Basal but Not Bradykinin-Stimulated Release of Active t-PA in Young Postmenopausal Women

et al. 2008

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Abstract-Angiotensin-converting enzyme inhibition potentiates basal and bradykinin-stimulated tissue-type plasminogen activator (t-PA) release to a greater extent in women than in men. This study tested the hypothesis that 17␤-estradiol enhances the effect of angiotensin-converting enzyme inhibition on t-PA release in young postmenopausal women. We conducted a double-blind, prospective, crossover study in 14 young postmenopausal women (mean age 48.2Ϯ2.3 years) who were randomized to receive 17␤-estradiol (1 mg/d) or matching placebo for 4 weeks. At the end of each treatment period, we measured the effect of intraarterial infusion of bradykinin, methacholine, and nitroprusside on forearm blood flow and net t-PA release, before and during intraarterial enalaprilat (0.33 g/min/100 mL forearm volume Key Words: estradiol Ⅲ angiotensin-converting enzyme inhibition Ⅲ postmenopausal women Ⅲ plasminogen activator Ⅲ bradykinin E strogen deficiency of menopause causes vascular and metabolic changes that increase the risk for cardiovascular disease. 1,2 In contrast to observational studies that suggest that hormone replacement therapy (HRT) reduces the risk of coronary heart disease (CHD), 3-5 recent randomized controlled trials indicate that treatment with conjugated estrogen plus progestin increases the risk of pulmonary emboli, CHD, and stroke, whereas treatment with conjugated estrogen alone increases risk of stroke without affecting embolic events or risk of CHD. 6 -8 This discrepancy in results has been attributed to the type of HRT used, the timing of intervention of HRT after menopause, 9,10 or the route of administration. 11 For example, the Heart and Estrogen/progestin Replacement Study (HERS) 8 and the Women's Health Initiative (WHI) 6,7 study assessed the effect of treatment with conjugated equine estrogens, a mixture of estrogens extracted from horse urine that also contains progestins and androgens, whereas estradiol is the major endogenous estrogen. 12 Differences in the outcomes of epidemiological studies and clinical trials are best interpreted in the context of an understanding of the biological effects of estrogen. On the one hand, oral HRT increases circulating fibrin split products (FSP), concentrations of inflammatory cytokines, and C-reactive protein. [13][14][15] On the other, estradiol exerts many salutary effects on the vasculature, including improving endothelial-dependent vasodilation, 16 decreasing fibrinogen and plasminogen activator inhibitor (PAI)-1 (PAI-1), [17][18][19] increasing the secretion of nitric oxide from intact platelets, 20 and attenuating platelet-derived growth factor (PDGF) receptor-activated smooth muscle cell migration and proliferation. 21 HRT decreases circulating t-PA antigen in parallel with PAI-1 antigen, to which it is complexed. Circulating t-PA antigen does not reflect the capacity of the vasculature to release t-PA, however, and the effect of HRT or estrogen on endothelial fibrinolytic function has not been studied exten-

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“…Another explanation can be the well-known fact that women display more side effects on ACE inhibitors. 17 The highest persistence has been shown in patients using ARBs. 8 In our study the use of ARBs was unusually high and it cannot be ruled out that this could have contributed to the high rate of patients reaching target blood pressure.…”

Section: Discussionmentioning

confidence: 99%

Swedish Hypertension Open care retrospective study in men and Women (SHOW)

Ljungman

Manhem

2010

J Hum Hypertens

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The aim of this retrospective study in primary health care was to study gender differences in blood pressure levels in response to treatment of new onset hypertension. Gender difference in blood pressure control and pharmacological treatment was also recorded. A total of 334 women and 332 men aged X50 years and o80 years at baseline, with blood pressure X140 mm Hg systolic and/or X90 mm Hg were included. Men were younger, had a higher frequency of type II diabetes mellitus and a higher body mass index compared with women at baseline. There was no difference between women and men in systolic blood pressure (SBP) before or after treatment. Women however had a lower diastolic blood pressure (DBP) before and after intervention and as a result a higher pulse pressure (PP). Approximately 50% of the patients reached target blood pressure (p140/ 90 mm Hg) in both women and men. Beta blocker was the most commonly used antihypertensive treatment in both genders, whereas diuretics were predominately used in women. In conclusion; women and men reached target blood pressure to the same extent but with different antihypertensive treatment strategies. Differences at baseline in risk factor pattern may explain the finding.

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Effect of long-term therapy with ramipril in high-risk women

Abstract: Treatment with ramipril reduces the CV risk in high-risk women without heart failure and with preserved LV systolic function.

Cited by 46 publications

References 19 publications

Angiotensin-Converting Enzyme Inhibition Increases Basal Vascular Tissue Plasminogen Activator Release in Women But Not in Men

Angiotensin-Converting Enzyme Inhibition Increases Basal Vascular Tissue Plasminogen Activator Release in Women But Not in Men

17β-Estradiol Increases Basal but Not Bradykinin-Stimulated Release of Active t-PA in Young Postmenopausal Women

Swedish Hypertension Open care retrospective study in men and Women (SHOW)

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