Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen deficiency in the postmenopausal woman results in numerous symptomatic and asymptomatic manifestations, including vasomotor symptoms, osteoporosis, heart disease, bladder and vaginal symptoms, and cardiovascular disease. Estrogen replacement therapy is associated with amelioration of these problems but has attendant risks. A newer class of drugs, the selective estrogen receptor modulators, provides both estrogen agonist and antagonist properties, depending on the target tissue. This article discusses the mechanism by which selective estrogen receptor modulators may vary in their end-organ effects and reviews the clinical studies associated with these compounds. Phytoestrogens are widely used in the United States, but little information is available regarding their potential long-term effects.
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PMID:Selective estrogen receptor modulators and phytoestrogens: new therapies for the postmenopausal women. 1037 37

Several studies have reported an association between hormone replacement therapy (HRT) in postmenopausal women and increased risk of idiopathic venous thromboembolic events (VTEs). Given the widespread use of HRT, it is important to identify factors that may predispose women on HRT to VTEs. To address this concern, we examined potential risk factors for VTEs in women assigned to HRT in the Postmenopausal Estrogen/Progestin Interventions (PEPI) study, a three-year, double-blinded, placebo-controlled trial of 875 postmenopausal women designed to assess the effects of HRT on heart disease risk factors (HDL cholesterol, fibrinogen, blood pressure, and insulin). Women with a history of estrogen-associated VTEs were excluded from the trial. Ten women, all assigned to HRT, had a VTE during PEPI. Only baseline fibrinogen varied significantly between those who did (mean = 249.0 mg/dl) and did not (mean = 280.8 mg/dl) have a VTE while assigned to HRT (P < 0.03). Adjusting for covariates including age, smoking, body mass index, lipid levels, blood pressure, alcohol, exercise, and prior HRT or oral contraceptive use did not affect this finding. The significantly lower fibrinogen levels seen among women subsequently reporting VTEs may be a marker for a specific, but as yet undefined, coagulopathy that is magnified in the presence of exogenous hormones. However, larger studies are needed to confirm this finding.
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PMID:Low fibrinogen level: A predisposing factor for venous thromboembolic events with hormone replacement therapy. 1044 Sep 16

The isoprenoid metabolic pathway is mainly regulated at the level of conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) to mevalonate, catalyzed by HMG CoA reductase. As estrogens are known to influence cholesterol metabolism, we have explored the potential regulation of the HMG CoA reductase gene promoter by estrogens. The promoter contains an estrogen-responsive element-like sequence at position -93 (termed Red-ERE), which differs from the ERE consensus by one mismatch in each half of the palindrome. A Red-ERE oligonucleotide specifically bound estrogen receptor in vitro and conferred receptor-dependent estrogen responsiveness to a heterologous promoter in all cell lines tested. However, expression of a reporter driven by the rat HMG CoA reductase promoter was induced by estrogen treatment after transient transfection into the breast cancer cell line MCF-7 cells but not in hepatic cell lines expressing estrogen receptor. Estrogen induction in MCF-7 cells was dependent on the Red-ERE and was strongly inhibited by the antiestrogen ICI 164,384. A functional cAMP-responsive element is located immediately upstream of the Red-ERE, but cAMP and estrogens inhibit each other in terms of transactivation of the promoter. Similarly, induction by estrogens was inhibited by micromolar concentrations of cholesterol, likely acting via changes in occupancy of the sterol-responsive element located 70 bp upstream of the Red-ERE. Thus, within its natural context, Red-ERE is able to mediate hormonal regulation of the HMG CoA reductase gene in tissues that respond to estrogens with enhanced cell proliferation, while it is not operative in liver cells. We postulate that this tissue-specific regulation of HMG CoA reductase by estrogens could partially explain the protective effect of estrogens against heart disease.
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PMID:The promoter of the rat 3-hydroxy-3-methylglutaryl coenzyme A reductase gene contains a tissue-specific estrogen-responsive region. 1044 99

The Heart and Estrogen/progestin Replacement Study (HERS) found no overall effect of 4.1 years of therapy with estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. However, within the overall null effect, a 50% increase in cardiovascular events was seen in the first year, followed by fewer events after 2 years of treatment in the hormone therapy group than in the placebo group. Understanding the cause of this pattern of early increase and late reduction in risk is key to interpreting the HERS results and reconciling them with the large number of observational and other studies of the cardiovascular effects of estrogen. There are two possibilities. One is that the HERS regimen of estrogen plus progestin has no effect on risk for heart disease, and the pattern of changing risk over time is simply the result of chance or confounding. The other is that the pattern of early increase and late reduction in risk is due to real but opposing effects of this regimen. Several lines of evidence support each possibility. Attrition of a susceptible cohort of women uniquely at risk for a cardiovascular complication from hormone therapy coupled with a gradually progressive beneficial effect due to lipid lowering and other factors is a promising potential explanation. The HERS results remind us of the need for clinical trials to evaluate both the benefits and risks of new therapies. They also illustrate how much more we need to know about the cardiovascular effects of hormone replacement therapy.
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PMID:The HERS trial results: paradigms lost? Heart and Estrogen/progestin Replacement Study. 1049 64

In women, serum lipid levels and the incidence of myocardial ischemia increase after menopause. Deficiency of estrogen is believed to be the cause of these epidemiological phenomena. On the other hand, hormone replacement therapy(HRT), has prevailed in developed countries. Estrogen is replaced to ease climacteric disorders, and retard bone loss. Many clinical studies cleared the effect of HRT on lipids, in which total and LDL-C (cholesterol) decreased, and HDL-C increased. TG increased by conjugated equilin estrogen but not by transdermal estradiol. In our study, hepatic triglyceride lipase(HTGL) was suppressed by HRT, but lipoprotein lipase(LpL) was not suppressed. HRT decreases coronary artery diseases, but it is still controversial whether HRT is efficient in patients who already have heart disease.
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PMID:[Efficacy of hormone replacement therapy on hyperlipidemia]. 1063 24

The Heart and Estrogen/Progestin Replacement Study (HERS) was the first randomised, double-blind, placebo-controlled study to evaluate the outcome of hormone replacement therapy (HRT) on subsequent cardiac events in postmenopausal women with established coronary heart disease (CHD). Of the 2763 women enrolled, 1380 were randomised to receive 0.625mg of conjugated equine estrogens plus 2.5mg of medroxyprogesterone daily (Prempro) and 1383 were randomised to receive a placebo. The results were surprising: 179 women in the hormone group and 182 women in the placebo group experienced either a nonfatal myocardial infarction or CHD death (relative hazard 0.99, 95% confidence interval 0.81 to 1.22). This occurred despite a net 11% reduction in low density lipoprotein (LDL) and a net 10% increase in high density lipoprotein (HDL) after 1 year of follow-up (p < 0.001 for LDL and HDL). Also, there were no differences between the 2 treatment groups in any secondary cardiovascular outcomes. The overall null effect may have been the result of an unexpected early adverse effect of the HRT regimen that offset a later reduction in risk. Clearly, the use of HRT for secondary prevention of heart disease is more complex than was initially believed. More data are needed from other clinical trials concerning the risks and benefits of HRT to confirm or refute the puzzling HERS results. HERS also underscores the need for trials with clinical end-points to evaluate both the safety and efficacy of drug therapy. Although observational studies are useful, they cannot provide definitive answers regarding treatment recommendations. Until further data are available, clinicians should not use estrogen plus medroxyprogesterone for the sole purpose of secondary prevention of CHD.
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PMID:The Heart and Estrogen/Progestin Replacement Study: what have we learned and what questions remain? 1064 52

In the premenopausal period, the risk of heart disease is considerably lower in women than in men; however, in the postmenopausal period, when estrogen levels are considerably lower, women's risk of heart disease increases dramatically and approaches that of men. Numerous animal studies, using a variety of models, also confirm estrogen's cardioprotective effect. Although the results of numerous population-based, observational studies have demonstrated a lower risk of heart disease in women who receive estrogen replacement therapy, evidence from prospective, randomized clinical trials is scant. The Postmenopausal Estrogen/Progestin Intervention (PEPI) trial evaluated cardiovascular risk factors, not events, in a large, prospective, randomized trial and found that estrogen improved lipid profiles and other known risk factors. In addition, the PEPI trial compared several estrogen/progestogen treatment regimens, including both medroxyprogesterone acetate (MPA) and micronized progesterone (MP), and found that combined hormone replacement therapy regimens including MP attenuated the beneficial effects of estrogen less than those containing MPA. In the Heart and Estrogen/Progestin Replacement Study (HERS), however, which prospectively evaluated whether estrogen and MPA use reduced the number of nonfatal myocardial infarctions and cardiovascular events, no effect was seen. Although HERS was a null trial, the vast literature base showing a cardioprotective effect should not be discounted. Further research will be required before blanket recommendations on the cardioprotective effects of hormone therapy can be made.
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PMID:Preserving cardiovascular benefits of hormone replacement therapy. 1075 7

In every year since 1984, cardiovascular disease has claimed the lives of more females than males. More than 450,000 women succumb to heart disease annually, and 250,000 die of coronary artery disease. Despite the proportions, most women believe they will die of breast cancer. The perception that heart disease is a man's disease and that women are more likely to die of breast cancer is alarming. Although women develop heart disease about 10 years later than men, they are likely to fare worse after a heart attack. The poorer outcomes are due, in part, to the failure to identify heart attack symptoms. Approximately 35% of heart attacks in women are believed to go unnoticed or unreported. However, because of increased age, women are more likely to have co-morbid diseases such as diabetes and hypertension. In women, not only is "tightness" or discomfort in the chest a warning sign, but in addition, nausea and dizziness are common indicators of myocardial ischemia. Other symptoms include breathlessness, perspiration, a sensation of fluttering in the heart, and fullness in the chest. In comparison to men, women are less likely to undergo tertiary care interventions such as cardiac catheterization, angioplasty, thrombolytic therapy, and bypass surgery; to participate in cardiac rehabilitation; and to return to work full-time after myocardial infarction. In the past, most research about treatments for heart disease focused on men, and gender differences have been ignored. Recent studies are enrolling enough women to test if there are differences between men and women in outcomes. One of the major areas of research relates to estrogen and hormonal replacement therapy to reduce the relative risk of heart attack and stroke. The Women's Health Initiative is a major NIH-sponsored trial that addresses the issue of primary prevention of cardiac disease by hormonal replacement therapy. The results will be available in 2004. The Heart Estrogen/Progestin Replacement Study (HERS), disappointingly, did not show a significant reduction of coronary events in women taking hormonal replacement therapy, nor did the Estrogen Replacement and Atherosclerosis (ERA) trial of 309 postmenopausal women who underwent coronary angiography. New insight into the role of vitamins, phytoestrogens and other natural sources, and selective estrogen receptor modulators may provide other options for management. Until then, modification of risk factors and healthy life style choices are recommended for reducing the risk of cardiac disease. In fact, the key to a healthy heart in the year 2000 appears closely tied to life style choices. Prevention of disease is the key, and current recommendations are simply to stop smoking, or do not start; treat and control blood pressure >140/90 mm Hg; manage elevated lipids by diet, exercise, and cholesterol-lowering medications (if necessary); treat diabetes; lose weight so that BMI is <25; walk for 20-30 minutes at least three times a week; and take an aspirin tablet daily.
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PMID:Heart disease in women. 1114 May 44

It is necessary to adopt a proactive, prevention-based strategy for addressing gynecologic and obstetric issues in the adolescent with heart disease. Pregnancy carries known cardiovascular alterations, manifestations and risks. The nature of the underlying cardiac disease needs to be considered in preconception counseling and in the prevention of pregnancy. Specific risks of oral contraceptive methods must be considered as well. Estrogen-based oral contraceptives may confer risks of thromboembolic phenomenon, whereas progesterone-based agents may be associated with increased risk of bleeding. Medical termination of pregnancy may pose risks to the young woman with cyanotic heart disease or pulmonary hypertension. Full prepregnancy evaluation helps to ensure a good outcome for both mother and baby. There are risks of continuing specific cardiovascular medications during pregnancy; however, certain medications are continued to safeguard maternal health. This is particularly problematic in the patient who must remain on anticoagulation.
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PMID:Gynecologic and obstetric issues in the adolescent with heart disease. 1122 29

Cardiovascular disease, primarily coronary heart disease (CHD), outnumbers the next 16 causes of death in women combined. However, the long-held belief that heart disease in women has a more benign prognosis than in men has resulted in less aggressive diagnosis and management patterns. Appreciation of the differences between men and women in CHD risk factors and presentation can assist in treatment decisions. Although estrogen replacement offers substantial beneficial effects on lipid levels in postmenopausal women, the first 2 randomized trials of estrogen alone and estrogen plus progestin, the Heart and Estrogen/Progestin Replacement Study and Estrogen Replacement and Atherosclerosis Study, observed no benefit in reducing risk of CHD death and nonfatal myocardial infarction and angiographic progression of CHD, respectively, in women with CHD. Available data show that lipid-lowering therapy reduces women's CHD risk and mortality but also indicate that a considerable proportion of women remains untreated or undertreated. Randomized trials of statins for primary and secondary prevention of coronary heart disease suggest that these agents are at least as effective for lowering coronary disease risk in women as in men. Therefore, statin drugs should be the drug of first choice for women with established CHD. Hypercholesterolemic postmenopausal women who require estrogen for menopausal symptoms may derive further reductions in low-density lipoprotein cholesterol and reductions in trigyceride levels with the addition of a statin drug.
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PMID:Cardiovascular disease and dyslipidemia in women. 1160 57


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