doi: 10.1161/hc4401.98414
(Circulation. 2001;104:2300.)
© 2001 American Heart Association, Inc.
Clinical Investigations and Reports |
Hormone Therapy and In-Hospital Survival After Myocardial Infarction in Postmenopausal Women
From the General Internal Medicine Section, Veterans Affairs Medical Center (M.G.S., D.G.), and the Department of Medicine, University of California (M.G.S., B.G.A., A.S.G., D.G.), San Francisco; the Northern California Kaiser Division of Research (A.S.G.), Oakland, Calif; Ovation Research Group (P.D.F.), Chicago, Ill; and the University of Alabama Medical Center (J.G.C.), Birmingham, Ala.
Correspondence and reprint requests to Dr Michael G. Shlipak, General Internal Medicine Section, Veterans Affairs Medical Center (111A1), San Francisco, CA 94121. E-mail shlip{at}itsa.ucsf.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background— Although postmenopausal hormone therapy (HRT) commonly is used in hope of preventing coronary heart disease, the effect of HRT on case fatality of myocardial infarction has never been studied. We evaluated HRT as a predictor of survival after MI in postmenopausal women.
Methods and Results— The present study was performed with 114 724 women of age 
55 years with confirmed myocardial infarction who presented between April 1998 and January 2000 to 1 of 1674 hospitals participating in the National Registry of Myocardial Infarction-3. Presenting characteristics, treatment, and clinical outcome data were obtained by chart review. At time of hospitalization, 7353 (6.4%) women reported current use of HRT, defined as use of estrogen, progestin, or estrogen/progestin for reasons other than contraception. Unadjusted mortality was 7.4% in users of HRT and 16.2% in nonusers (odds ratio 0.41, 95% confidence interval 0.36 to 0.43). After adjustments were made for prior medical history, clinical characteristics, treatments received in-hospital, and likelihood of receiving HRT, HRT remained associated with an improved rate of survival (odds ratio 0.65, 95% confidence interval 0.59 to 0.72). Significant association of HRT with decreased mortality after myocardial infarction was observed in all age strata.
Conclusions— Postmenopausal HRT appears to be associated with reduced mortality after myocardial infarction. This finding could be caused by therapeutic effect of HRT, selection and adherence bias, or some combination of both.
Key Words: women • hormones • myocardial infarction • survival
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Postmenopausal hormone therapy (HRT) with estrogens is commonly used for coronary heart disease prevention in women.1 Numerous observational studies have found an association of HRT with decreased incidence of myocardial infarction (MI) and coronary death in women without known coronary heart disease.2 However, the one randomized trial to test the effect of HRT on coronary heart disease events in postmenopausal women, the Heart and Estrogen/progestin Replacement Study (HERS), found no beneficial effect of HRT for reduction of incidence of MI among women with prior coronary disease.3 Also, no significant difference occurred in the rate of fatal cardiovascular events, but the number of fatal events was relatively small (n=129).3
See p 2256
Prior observational studies have found that HRT was associated with favorable outcomes after coronary angioplasty and coronary artery bypass graft surgery.4–6 In addition, estrogen therapy has multiple physiological effects that might limit ischemia and reduce reperfusion injury in acute MI.7–11 We hypothesized that use of HRT before hospitalization would be associated with decreased in-hospital mortality among postmenopausal women with acute MI.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Design and Data Collection
We designed a retrospective cohort study that used data from the National Registry of Myocardial Infarction-3 (NRMI-3), which includes information collected during hospitalization on patients discharged with confirmed MI at 1674 participating hospitals. Diagnosis of MI required a principal discharge diagnosis of MI (410.X, International Classification of Diseases, Ninth Revision, Clinical Modification) and presentation consistent with MI and
1 of the following: (1) total creatine kinase or creatine kinase myocardial isoenzymes 2x upper limit of normal range, (2) ECG evidence of MI, or (3) alternative enzymatic, scintigraphic, or autopsy evidence of MI. Each hospital is encouraged to enroll data on a consecutive sample of patients (if not all patients), to maintain generalizability of the NRMI-3 sample. Data on each patient were entered onto a 2-page case report form by trained chart abstractors. Double-key data entry and electronic data checks were performed routinely by the data collection center (Statprobe) to ensure accuracy, consistency, and completeness of data.
Subjects
From April 1, 1998, through January 31, 2000, a total of 404 106 men and women with MI were enrolled in NRMI-3. We excluded patients who were transferred to another hospital because we lacked information on their vital status at hospital discharge (n=86 205). Because NRMI-3 does not collect information on menopausal status, we limited the present study to women of age 55 years, which resulted in a cohort of 114 724 women with documented MI.
Measurements
Primary predictor variable was use of HRT before hospital admission. HRT is defined in the NRMI-3 as "the use of estrogen, progestin, or estrogen/progestin for reasons other than contraception." Women are coded as current users or nonusers, but no record is made of past use. No information on dose, preparation, or cyclic or noncyclic administration or other details were recorded. Information also was collected on patient demographic characteristics (age, race, and region of residence in the United States), past medical history (diabetes, hypertension, stroke, MI, heart failure, PTCA, CABG, hypercholesterolemia, and family history of coronary artery disease), clinical presentation characteristics (presence of chest pain, systolic and diastolic BPs, heart rate, Killip class at initial evaluation, ECG findings, and location of infarct) and treatments during index hospitalization (medications and procedures).
Primary outcome of the present study was in-hospital mortality. Secondary outcomes were MI complications during hospitalization: heart failure, hypotension, recurrent ischemia, ventricular arrhythmia, cardiogenic shock, recurrent infarction, stroke, and cardiac rupture.
Statistical Analysis
We compared admission characteristics and in-hospital treatment of users and nonusers of HRT with the t test for continuous variables and the 
2 test for categorical variables. To determine association of HRT use with MI complications and in-hospital mortality, initially we made unadjusted comparisons with the 2 test. We used multivariate logistic regression to adjust for differences in baseline characteristics, severity of presentation, and treatments received in hospital. We used a forward stepwise procedure with P<0.05 to select variables for inclusion into the multivariate model. We repeated these multivariate models evaluating association of HRT with in-hospital survival within age strata.
In addition, we used propensity score methods to adjust for residual selection bias.12 First, we constructed a multivariate logistic regression model with HRT use (yes/no) as the outcome variable, and admission characteristics (demographics, medical history, and clinical presentation) as predictor variables. Coefficients from this analysis were used to calculate likelihood of receiving HRT for each patient in our sample, regardless of whether the patient actually received HRT. This "propensity to receive HRT" was entered as a predictor variable in the multivariate logistic model, with in-hospital mortality as the outcome. Thus, we attempted to adjust association of HRT with in-hospital survival for differences between patient groups and for propensity to receive HRT.
Potential Interactions
Because prior heart failure was more common among nonusers of HRT, we compared association of HRT with heart failure complications after MI separately for women with versus without prior diagnosis of heart failure. We also determined adjusted association of HRT with in-hospital mortality separately for women with versus without prior heart failure.
We hypothesized that the effect of HRT on in-hospital survival would differ for women receiving thrombolytic therapy. We evaluated presence of thrombolytic therapy/HRT interaction among women who were ideal candidates for thrombolytic therapy (patients who had ST-segment elevation or left bundle-branch block on initial ECG, presented within 12 hours of symptom onset, and had no contraindications to thrombolytic therapy).
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patient Characteristics
Among the 114 724 women with MI in the NRMI-3 of age
55 years, 7353 (6.4%) were current users of HRT at time of hospital admission. Hormone users were younger; more likely to be white; and less likely to have a history of diabetes, heart failure, prior MI, and prior stroke than nonusers but were more likely to have hypercholesterolemia and family history of premature coronary artery disease and to use tobacco (Table 1).
|
At initial presentation, women who were hormone users had slightly higher systolic BP and lower heart rates and were more likely to complain of chest discomfort than nonusers (Table 1). At first clinical assessment, signs of heart failure (Killip class 2 to 4) were observed in 21% of HRT users versus 36% of nonusers. However, women on HRT were slightly more likely to have ST-segment elevation or left bundle-branch block on first ECG and anterior MI and to be admitted with a diagnosis of MI.
In-Hospital Therapy
HRT users received more-aggressive in-hospital care than women who were nonusers (Table 2) and were more likely to receive reperfusion therapy, acetylsalicylic acid (aspirin), heparin, ß-blockers, and nitrates. Before discharge, HRT users were more likely to undergo coronary angiography, PTCA, and CABG than nonusers.
|
Adverse Events and Mortality
Complication rates were similar among HRT users and nonusers. Nonusers were more likely to develop heart failure or cardiogenic shock but less likely to have recurrent ischemia while in hospital (Table 3). Proportion of women who experienced hypotension, ventricular arrhythmia, recurrent MI, stroke, and cardiac rupture was similar among users and nonusers of HRT. However, risk of in-hospital mortality for women who used HRT was less than half that of women who did not use HRT (unadjusted odds ratio [OR] 0.40, 95% confidence interval [CI] 0.36 to 0.43).
|
Multivariate Analysis
After adjustment for patient characteristics, treatment in-hospital, and likelihood of receiving HRT, use of HRT remained associated with reduced odds of in-hospital mortality (OR 0.65; 95% CI 0.59 to 0.72). (Table 4) Reduction in odds for mortality after adjustment varied from 28% to 46%, with association being strongest for the youngest group of women (age 55 to 64 years).
|
Potential Interactions With Prior Heart Failure and Thrombolytic Therapy
Use of HRT was associated with decreased heart failure complications among women with a prior diagnosis of heart failure (44% versus 48%, P=0.02) and without a prior diagnosis of heart failure (17% versus 25%, P<0.0001). Adjusted association of HRT with decreased in-hospital mortality was similar among women with prior heart failure (OR 0.62, 95% CI 0.50 to 0.77) and without prior heart failure (OR 0.66, 95% CI 0.59 to 0.74).
We repeated multivariate analysis among women who received thrombolytic therapy (n=13 482). Use of HRT was associated with reduced mortality risk in this subgroup (OR 0.65, 95% CI 0.51 to 0.84). We detected no statistical interaction between HRT and thrombolytic therapy among women who were ideal candidates for thrombolysis (n=20 856).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Many observational studies and 1 clinical trial have evaluated association between postmenopausal HRT and risk of incident MI.2,3,13–15 To our knowledge, no large study to date has evaluated effect of HRT on case fatality of MI. We found that 7% of women with MI were current users of HRT, and these women were somewhat younger and healthier than nonusers. In-hospital treatment for MI was more aggressive for women who used HRT. However, after adjustment for these differences, HRT remained associated with 35% reduced odds of in-hospital mortality overall and significantly reduced odds in each age category.
Because these results are observational, interpret them with caution. The only clinical trial to evaluate the effect of HRT on coronary risk, the HERS trial, found no benefit from an estrogen/progestin combination in women with documented coronary artery disease.3 Participants in the present study may have differed from HERS participants because less than half the women in the present study had prior coronary heart disease events and HRT users may have undergone HRT for decades. However, benefit of HRT for cardiovascular prevention in observational studies also could be explained by differences between users and nonusers of HRT, despite multivariable adjustments.2
Similar bias could explain all or part of the association observed in our present study. Users of HRT in the present cohort generally were younger and had less comorbidity than nonusers. We controlled for these differences in our multivariable analysis, but the healthier profile that decreased mortality risk also may have increased their likelihood of taking HRT, in which case the association between HRT and lower mortality may not be causative. Users of HRT might have been expected to have healthier lifestyles than nonusers, but greater use of tobacco among HRT users is inconsistent with this hypothesis. Because HRT users received more treatment interventions during hospitalization, they may have received care at hospitals with greater experience with MI care, which would be an additional potential confounder. To account for these and other unmeasured differences between HRT users and nonusers, we calculated a propensity score for likelihood of receiving HRT based on measured characteristics. Selection bias should have been minimized by this extensive multivariate adjustment.12
Adherence bias refers to the favorable characteristics of patients who are willing to take a daily medication for prevention. This bias could be more important than selection bias for explaining disparate results between observational and randomized trials that evaluate such therapies as HRT, beta carotene, and vitamin E.3,16–18 Simply complying with assigned treatment, even a placebo, has been associated with decreased mortality risk.19–21 In the present study, users and nonusers of HRT may have differed in important characteristics related to treatment compliance for which we were unable to control.
Although these systematic biases may explain the association of HRT with survival after acute MI, several mechanisms by which HRT could benefit women in the setting of an acute coronary event have been described.22 Estrogen has favorable effects on vasomotor tone, blunting vasoconstrictor response to prostaglandin-F223; histamine, serotonin, and angiotensin II24; and norepinephrine.25 Such effects appear to be mediated by nitric oxide synthase and free-radical scavenging.26,27 In addition, women on HRT have been shown to have lower levels of plasminogen activator inhibitor8 and higher D-dimer levels, which suggests greater endogenous fibrinolysis.9 HRT may also moderate reperfusion injury in acute MI. In animal models, estrogens decrease mediators of inflammation within the infarct zone,10 abolish the burst of OH radicals on reperfusion,11 and increase serum glutathione levels.28 In the short term, estrogen speeds endothelial repair after mechanical injury is simulated with a balloon or scraper and neointimal thickening is blunted.7
These mechanisms may translate into clinical benefits. In a retrospective analysis of postmenopausal women undergoing PTCA, patients taking HRT had fewer cardiovascular events (12% versus 35%) and better survival (93% versus 75%) than matched controls over 7 years of follow-up.4 In a similar study, in-hospital and long-term (22-month) survival was better among women taking HRT at the time of PTCA.5 Among women undergoing coronary artery bypass graft surgery, HRT was associated with a 62% improvement in the odds of 5-year survival,6 although a subsequent study found no significant association.29 Each of these studies was observational and thus subject to the same potential biases as the present study.
Our data do not support any specific physiological mechanism of HRT to explain the observed mortality difference. Unadjusted rates of in-hospital adverse events were similar among users and nonusers of HRT. Of note, no differential effect of HRT was seen among patients who did or did not receive thrombolysis, which argues against any enhancement of this therapy. Similarity in complication rates implies that women on HRT were more likely to survive for reasons other than reduced complications, which may or may not be related to a beneficial effect of HRT itself. For comparison, a recent study by Alexander and colleagues30 in 1857 women who survived MI also found HRT users to have lower mortality risk but increased risk of unstable angina admissions.
Among the limitations of the present study is that we do not have information on duration of use, type of hormones taken, or dosage level of HRT, such that the treatment association observed could represent a rough average of many therapies. Also, because the data collection process in NRMI-3 is conducted separately at each hospital, misclassification of HRT status may have occurred. However, accuracy of NRMI data has been favorably compared with the rigorously validated Cooperative Cardiovascular Project database.31 NRMI-3 includes outcomes only until hospital discharge; thus, any effect on long-term mortality cannot be assessed from this data set.
In conclusion, we found that among postmenopausal women who presented with acute MI, women undergoing HRT were younger and healthier than women not undergoing HRT and were treated more aggressively during hospitalization. Nonetheless, after controlling for these differences, HRT was associated with a substantially lower risk of in-hospital mortality. This association of HRT with improved survival may be explained by a therapeutic effect of HRT, by selection and adherence bias, or by some combination of both.
|
Acknowledgments |
|---|
Dr Shlipak is supported by a Research Career Development Award from the Health Services Research and Development Division of the Veterans Administration.
|
Footnotes |
|---|
Presented in part at the 73rd Scientific Sessions of the American Heart Association, New Orleans, La, November 12–15, 2000, and published in abstract form (Circulation. 2000;102[suppl II]:II-837).
Received June 20, 2001; revision received August 22, 2001; accepted August 22, 2001.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Keating NL Cleary PD Rossi AS et al. Use of hormone replacement therapy by postmenopausal women in the United States. Ann Intern Med. 1999; 130: 545–553.
2. Grady D Rubin SM Petitti DB et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med. 1992; 117: 1016–1037.
3.
Hulley S Grady D Bush T et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women: Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA. 1998; 280: 605–613.
4. O. Keefe JH Jr Kim SC Hall RR et al. Estrogen replacement therapy after coronary angioplasty in women. J Am Coll Cardiol. 1997; 29: 1–5.[Abstract]
5. Abu-Halawa SA Thompson K Kirkeeide RL et al. Estrogen replacement therapy and outcome of coronary balloon angioplasty in postmenopausal women. Am J Cardiol. 1998; 82: 409–413.[Medline] [Order article via Infotrieve]
6. Sullivan JM El-Zeky F Vander Zwaag R et al. Effect on survival of estrogen replacement therapy after coronary artery bypass grafting. Am J Cardiol. 1997; 79: 847–850.[Medline] [Order article via Infotrieve]
7.
Krasinski K Spyridopoulos I Asahara T et al. Estradiol accelerates functional endothelial recovery after arterial injury. Circulation. 1997; 95: 1768–1772.
8.
Gebara OC Mittleman MA Sutherland P et al. Association between increased estrogen status and increased fibrinolytic potential in the Framingham Offspring Study. Circulation. 1995; 91: 1952–1958.
9.
Koh KK Mincemoyer R Bui MN et al. Effects of hormone-replacement therapy on fibrinolysis in postmenopausal women. N Engl J Med. 1997; 336: 683–690.
10. Squadrito F Altavilla D Squadrito G et al. 17ß-oestradiol reduces cardiac leukocyte accumulation in myocardial ischaemia reperfusion injury in rat. Eur J Pharmacol. 1997; 335: 185–192.[Medline] [Order article via Infotrieve]
11. McHugh NA Merrill GF Powell SR Estrogen diminishes postischemic hydroxyl radical production. Am J Physiol. 1998; 274(pt 2): H-1950–H-1954.
12. D’Agostino RB Jr Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998; 17: 2265–2281.[Medline] [Order article via Infotrieve]
13.
Grodstein F Stampfer MJ Manson JE et al. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med. 1996; 335: 453–461.
14. Grodstein F Stampfer MJ Falkeborn M et al. Postmenopausal hormone therapy and risk of cardiovascular disease and hip fracture in a cohort of Swedish women. Epidemiology. 1999; 10: 476–480.[Medline] [Order article via Infotrieve]
15.
Newton KM LaCroix AZ McKnight B et al. Estrogen replacement therapy and prognosis after first myocardial infarction. Am J Epidemiol. 1997; 145: 269–277.
16.
Omenn GS Goodman GE Thornquist MD et al. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst. 1996; 88: 1550–1559.
17.
Yusuf S Dagenais G Pogue J et al. Vitamin E supplementation and cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000; 342: 154–160.
18.
Barrett-Connor E Khaw KT Cigarette smoking and increased endogenous estrogen levels in men. Am J Epidemiol. 1987; 126: 187–192.
19. Influence of adherence to treatment and response of cholesterol on mortality in the coronary drug project. N Engl J Med. 1980; 303: 1038–1041.[Abstract]
20. Horwitz RI Viscoli CM Berkman L et al. Treatment adherence and risk of death after a myocardial infarction. Lancet. 1990; 336: 542–545.[Medline] [Order article via Infotrieve]
21.
Gallagher EJ Viscoli CM Horwitz RI The relationship of treatment adherence to the risk of death after myocardial infarction in women. JAMA. 1993; 270: 742–744.
22.
Mendelsohn ME Karas RH The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999; 340: 1801–1811.
23. Mugge A Riedel M Barton M et al. Endothelium independent relaxation of human coronary arteries by 17ß-oestradiol in vitro. Cardiovasc Res. 1993; 27: 1939–1942.[Medline] [Order article via Infotrieve]
24. Mugge A Barton M Fieguth HG et al. Contractile responses to histamine, serotonin, and angiotensin II are impaired by 17 beta-estradiol in human internal mammary arteries in vitro. Pharmacology. 1997; 54: 162–168.[Medline] [Order article via Infotrieve]
25.
Sudhir K Elser MD Jennings GL et al. Estrogen supplementation decreases norepinephrine-induced vasoconstriction and total body norepinephrine spillover in perimenopausal women. Hypertension. 1997; 30: 1538–1543.
26.
Guetta V Quyyumi AA Prasad A et al. The role of nitric oxide in coronary vascular effects of estrogen in postmenopausal women. Circulation. 1997; 96: 2795–2801.
27.
Best PJ Berger PB Miller VM et al. The effect of estrogen replacement therapy on plasma nitric oxide and endothelin-1 levels in postmenopausal women. Ann Intern Med. 1998; 128: 285–288.
28. Kim YD Farhat MY Myers AK et al. 17-beta estradiol regulation of myocardial glutathione and its role in protection against myocardial stunning in dogs. J Cardiovasc Pharmacol. 1998; 32: 457–465.[Medline] [Order article via Infotrieve]
29. Shackelford DP Daniels S Hoffman MK et al. Estrogen therapy in women undergoing coronary artery bypass grafting: effect on surgical complications. Obstet Gynecol. 2000; 95: 732–735.[Medline] [Order article via Infotrieve]
30.
Alexander KP Newby LK Hellkamp AS et al. Initiation of hormone replacement therapy after acute myocardial infarction is associated with more cardiac events during follow-up. J Am Coll Cardiol. 2001; 38: 1–7.
31.
Every NR Frederick PD Robinson M et al. A comparison of the National Registry of Myocardial Infarction 2 with the cooperative cardiovascular project. J Am Coll Cardiol. 1999; 33: 1886–1894.
This article has been cited by other articles:
 |
|
 |
|
  E. Zhan, T. Keimig, J. Xu, E. Peterson, J. Ding, F. Wang, and X.-P. Yang Dose-dependent cardiac effect of oestrogen replacement in mice post-myocardial infarction Exp Physiol, August 1, 2008; 93(8): 982 - 993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pedram, M. Razandi, D. Lubahn, J. Liu, M. Vannan, and E. R. Levin Estrogen Inhibits Cardiac Hypertrophy: Role of Estrogen Receptor-{beta} to Inhibit Calcineurin Endocrinology, July 1, 2008; 149(7): 3361 - 3369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-M. Lee, M.-S. Lin, and N.-C. Chang Physiological Concentration of 17{beta}-Estradiol on Sympathetic Reinnervation in Ovariectomized Infarcted Rats Endocrinology, March 1, 2008; 149(3): 1205 - 1213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Collins, G. Rosano, C. Casey, C. Daly, M. Gambacciani, P. Hadji, R. Kaaja, T. Mikkola, S. Palacios, R. Preston, et al. Management of cardiovascular risk in the peri-menopausal woman: a consensus statement of European cardiologists and gynaecologists Eur. Heart J., August 2, 2007; 28(16): 2028 - 2040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Peter, G. S. Huggins, A. M. Shearman, A. Pollak, C. H. Schmid, L. A. Cupples, S. Demissie, R. D. Patten, R. H. Karas, D. E. Housman, et al. Age-Related Changes in Echocardiographic Measurements: Association With Variation in the Estrogen Receptor-{alpha} Gene Hypertension, May 1, 2007; 49(5): 1000 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Dawn and R. Bolli Increasing Evidence That Estrogen Is an Important Modulator of Bone Marrow-Mediated Cardiac Repair After Acute Infarction Circulation, November 21, 2006; 114(21): 2203 - 2205. [Full Text] [PDF]
|
|
|
|
|
|
H. Hamada, M. K. Kim, A. Iwakura, M. Ii, T. Thorne, G. Qin, J. Asai, Y. Tsutsumi, H. Sekiguchi, M. Silver, et al. Estrogen Receptors {alpha} and {beta} Mediate Contribution of Bone Marrow-Derived Endothelial Progenitor Cells to Functional Recovery After Myocardial Infarction Circulation, November 21, 2006; 114(21): 2261 - 2270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pedram, M. Razandi, M. Aitkenhead, and E. R. Levin Estrogen Inhibits Cardiomyocyte Hypertrophy in Vitro: ANTAGONISM OF CALCINEURIN-RELATED HYPERTROPHY THROUGH INDUCTION OF MCIP1 J. Biol. Chem., July 15, 2005; 280(28): 26339 - 26348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Guo, M. Razandi, A. Pedram, G. Kassab, and E. R. Levin Estrogen Induces Vascular Wall Dilation: MEDIATION THROUGH KINASE SIGNALING TO NITRIC OXIDE AND ESTROGEN RECEPTORS {alpha} AND {beta} J. Biol. Chem., May 20, 2005; 280(20): 19704 - 19710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Patten, I. Pourati, M. J. Aronovitz, J. Baur, F. Celestin, X. Chen, A. Michael, S. Haq, S. Nuedling, C. Grohe, et al. 17{beta}-Estradiol Reduces Cardiomyocyte Apoptosis In Vivo and In Vitro via Activation of Phospho-Inositide-3 Kinase/Akt Signaling Circ. Res., October 1, 2004; 95(7): 692 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xu, S. J. Armstrong, I. A. Arenas, D. J. Pehowich, and S. T. Davidge Cardioprotection by chronic estrogen or superoxide dismutase mimetic treatment in the aged female rat Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H165 - H171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Herrington Hormone Replacement Therapy and Heart Disease: Replacing Dogma With Data Circulation, January 7, 2003; 107(1): 2 - 4. [Full Text] [PDF]
|
|
|
|
 |
|
 Women on HT May Have Better Survival Rates After Acute MI Journal Watch Women's Health, January 8, 2002; 2002(108): 6 - 6. [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||