Blood pressure control and hormone replacement therapy in postmenopausal women at risk for coronary heart disease

doi:10.1067/mhj.2002.121262

American Heart Journal

Volume 143, Issue 4, April 2002, Pages 711-717

https://doi.org/10.1067/mhj.2002.121262 Get rights and content

Abstract

Background Coronary heart disease (CHD) in women is strongly associated with estrogen deprivation. For example, risk for CHD increases dramatically after menopause. However, the role of hormone replacement therapy (HRT) in CHD prevention currently is unresolved. To better understand CHD in women, the precise mechanisms by which estrogen affects circulatory function require clarification. Evidence suggests that exogenous estrogen may affect blood pressure (BP) control, but its interaction with other CHD risk factors has not been systematically characterized. The present study examines the role of mildly elevated resting BP, family history of CHD, and HRT on BP responses to stress in postmenopausal women. Methods Postmenopausal women on long-term HRT were recruited along with a control group of postmenopausal women not on HRT. These women were divided into higher versus lower risk for CHD on the basis of resting BP and family history of CHD. BP control mechanisms were assessed before, during, and after a computer-controlled laboratory stressor. Results Results indicate that women with elevated resting BP and positive family history of CHD have exaggerated BP reactivity to stress and that HRT inhibits this effect. Conclusions This study suggests that unmedicated postmenopausal women with mildly elevated resting BP and positive family history of CHD have altered BP control as indicated by exaggerated BP responses to stress. HRT eliminates the cumulative effect of resting BP and family history on BP reactivity, suggesting that the circulatory effects of estrogen replacement may operate, at least in part, through normalization of BP reactivity in higher-risk postmenopausal women. (Am Heart J 2002;143:711-7.)

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Cited by (21)

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Autonomic nervous system (ANS) and neuroendocrine (NE) responses to stress were introduced as one of the first biologically plausible mechanisms to explain how exposure to environmental stress increases risk for cardiovascular disease (CVD). Various patterns of ANS and NE responses to stress have been examined with respect to onset of CVD, including exaggerated response magnitudes, delayed recovery of responses, and the relative lack of responding. Although exposure to environmental stress has been associated with all of these types of allostatic load, only exaggerated response to stress and delayed response recoveries have been shown to be associated with CVD. Blunted cardiovascular responses to stress are not commonly associated with CVD, but are linked to several behavioral risk factors for CVD, including certain health behaviors and depression. In sum, considerable evidence supports the roles of ANS and NE responding to stress as potential physiologic mechanisms involved in the bodies translation of environmental stress to disease processes like atherosclerosis.
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Citation Excerpt :
Blood pressure (BP) is a major factor in inducing endothelial injury and plays a role in arterial smooth muscle proliferation and thus arterial wall thickening. Oral MHT has been reported to increase BP in younger but not older menopausal women (34) as well as to have neutral effects or even to improve BP (35–37). In one study, transdermal MHT decreased BP in postmenopausal women without altering angiotensin II, and oral HRT increased angiotensin II but did not affect BP (38).
Cardiovascular disease (CVD) is the most common cause of death in women. Before the Women's Health Initiative (WHI) hormone trials, evidence favored the concept that menopausal hormone treatment (MHT) protects against CVD. WHI studies failed to demonstrate CVD benefit, with worse net outcomes for MHT versus placebo in the population studied. We review evidence regarding the relationship between MHT and CVD with consideration of mechanisms and risk factors for atherogenesis and cardiac events, results of observational case-control and cohort studies, and outcomes of randomized trials. Estrogen effects on CVD risk factors favor delay or amelioration of atherosclerotic plaque development but may increase risk of acute events when at-risk plaque is present. Long-term observational studies have shown ∼40% reductions in risk of myocardial infarction and all-cause mortality. Analyses of data from randomized control trials other than the WHI show a ∼30% cardioprotective effect in recently menopausal women. Review of the literature as well as WHI data suggests that younger and/or more recently menopausal women may have a better risk-benefit ratio than older or remotely menopausal women and that CVD protection may only occur after >5 years; WHI women averaged 63 years of age (12 years postmenopausal) and few were studied for >6 years. Thus, a beneficial effect of long-term MHT on CVD and mortality is still an open question and is likely to remain controversial for the foreseeable future.
Timing and duration of menopausal hormone treatment may affect cardiovascular outcomes
2011, American Journal of Medicine
Citation Excerpt :
Because atherogenesis is a gradual process, progressing from fatty streaks to advanced plaques over a number of years, an intervention whose beneficial effects are confined to halting or slowing progression would not be expected to show benefit until sufficient time had elapsed to reduce the number of at-risk plaques. Menopausal hormone treatment reduces low-density lipoprotein cholesterol and lipoprotein(a), and increases high-density lipoprotein cholesterol,52-56 lowers fibrinogen levels,52 improves responsiveness of the arterial endothelium to vasodilatory stimuli,54,57 decreases expression of certain endothelial adhesion factors,58-60 reduces blood pressure,61-63 and acts as an antioxidant.64-68 All of these actions would be expected to inhibit initiation of atherosclerosis and slow progression of early atherosclerotic lesions.
Largely on the basis of the first publication of findings of net harm with menopausal hormone treatment in the Women's Health Initiative (WHI) hormone trials, current Food and Drug Administration recommendations limit menopausal hormone treatment to the “… shortest duration consistent with treatment goals …,” with goals generally taken to mean relief of menopausal symptoms and maximal duration as approximately 5 years. The WHI finding of net harm was due largely to the absence of beneficial effects on coronary heart disease incidence rates. Published analyses of WHI data by age or time since menopause find that excess coronary heart disease risk with menopausal hormone treatment is confined to more remotely menopausal or older women, with younger women showing nonsignificant trends toward benefit (the “timing hypothesis”). Moreover, a recently published reexamination of data from the WHI Estrogen plus Progestin trial suggests that reduced coronary heart disease risk may appear only after 5 to 6 years of treatment. Consistent with this finding, risk ratios for coronary heart disease were calculated as 1.08 (95% confidence interval, 0.86-1.36) in years 1 to 6 and as 0.46 (confidence interval, 0.28-0.78) in years 7 to 8+ in the WHI Estrogen Alone trial. Previous studies also support the beneficial effects of menopausal hormone treatment after prolonged exposure. Thus, current analyses do not support a generalized recommendation for short duration of menopausal hormone treatment. Rather, they suggest that current Food and Drug Administration practice guidelines should be reconsidered to allow individualized care based on risk:benefit considerations. New research is urgently needed evaluating influences of timing, duration, dose, route of administration, and agents on menopausal hormone treatment-related risks and benefits to better understand how to optimize recommendations for individual patients.
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The Women's Health Initiative (WHI) study and its ancillary Memory Study (WHIMS) revealed increased rates of cardiovascular risk, cognitive decline and dementia with opposed conjugated equine estrogens (CEE). As a result, previously accepted observational data suggesting cardiovascular and cognitive benefits and reduced risk for dementia with hormone therapy (HT) were largely attributed to ‘healthy-user’ bias. The present observational, community-based, case-controlled study examined the ‘healthy-user’ bias theory by comparing cognitive task performance in two groups of postmenopausal women, who were either HT users or non-users.
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Although independent samples t-tests revealed no statistically significant differences in the CVRF composite and its individual components between the two groups, HT users tended to possess fewer CVRF than non-users. Conversely, HT users were younger and more educated than non-users. HT users outperformed non-users on 7/9 cognitive variables. The full regression model controlling for CVRF, demographic variables, and mood showed HT users outperformed non-users on measures of verbal memory and abstract reasoning.
While there is some evidence HT users possess fewer preexisting CVRF than non-users, the observed positive association between HT and cognition is not completely explained by this trend.
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^☆: Supported by National Institutes of Health Research Award R01 HL32738 to (J. A. M.) and NRSA Postdoctoral Fellowship F32 HL10227 to (S. G. F.).

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Acute Ischemic Heart DiseaseBlood pressure control and hormone replacement therapy in postmenopausal women at risk for coronary heart disease☆

Abstract

Acute Ischemic Heart Disease
Blood pressure control and hormone replacement therapy in postmenopausal women at risk for coronary heart disease☆