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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen deficiency is the major determinant of bone loss, not only in the first years postmenopause, but also throughout the entire life and in the elderly. Major progress in the knowledge of cellular actions of estrogens has been made leading to a better understanding of the underlying mechanisms of different estrogen-deficiency related diseases such as osteoporosis, atherosclerosis and also maybe cerebral aging. Estrogen replacement therapy remains the first choice treatment in the prevention of postmenopausal osteoporosis, but the continuous aging process of the female population raises the question of a better strategy of action in a more efficient prevention of hip fractures. Moreover, the potential gynecological effects of estrogens are likely to limit their indications or long-term use. The development of new compounds, called SERMs (selective estrogen receptor modulators), with both agonist and antagonist estrogen actions, in particular with no negative effects on the uterus and the breast opens new therapeutical insights into the prevention of postmenopausal osteoporosis.
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PMID:[Estrogens and selective estrogen receptor modulators in the treatment of osteoporosis]. 1110 29

The aim of the present study was to investigate anti-proliferative and anti-atherogenic properties of 17beta-estradiol in balloon injured female and male rabbit aortae. Thirty-two female and 32 male New Zealand White rabbits where gonadectomised. Vascular injury was performed with a balloon catheter in the lower abdominal aorta. Male and female rabbits were randomised into four groups of eight animals each. Only two of four groups received a 0.5% cholesterol-enriched diet. One cholesterol-diet group and one normal-diet group received intramuscular injections of estradiol valerate (1 mg/kg body weight/week). After 28 days, the denuded part of the abdominal aorta was excised and analysed by morphometry and immunohistochemistry. Estrogen treatment did not show an inhibitory effect on neointimal proliferation in normo-cholesterolemic male or female rabbits. A gender independent inhibitory effect of 17beta-estradiol was seen on atheroma development in cholesterol-fed female and male rabbits, while plasma total cholesterol levels were significantly reduced in male rabbits only. The 17beta-estradiol treatment was associated with a significantly decreased number of luminal endothelial cells in normo and hyper-cholesterolemic female rabbits, as evaluated by immunohistochemical staining for 'von Willebrand factor'. Staining for Ki-67-positive proliferating cells after 28 days showed a statistically significant increased proliferative activity in the neointima of hyper-cholesterolemic female rabbits. The neointimal content of macrophages increased significantly in all hyper-cholesterolemic rabbits. Under 17beta-estradiol treatment, the number of macrophages was increased in female and decreased in male rabbits by tendency. Additionally, the 'classical' vascular estrogen receptor was present in both female and male rabbit aortae without statistically significant differences. In conclusion, 17beta-estradiol did not reduce post-injury neointima formation in normo-cholesterolemic rabbits. However, in hyper-cholesterolemic rabbits, 17beta-estradiol reduced atheroma development gender independently. This effect cannot be explained by lowering of plasma cholesterol levels or endothelium-mediated pathways, and requires further investigation on, for example, antioxidative, antiproliferative or estrogen receptor mediated effects.
Atherosclerosis 2001 Jan
PMID:17beta-estradiol, gender independently, reduces atheroma development but not neointimal proliferation after balloon injury in the rabbit aorta. 1113 81

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

The clinical relevance of estrogen's multiple acute and more delayed effects on vascular wall structure and function is incompletely understood. This review attempts to reevaluate epidemiological findings and clinical studies concerning the vascular actions of estrogens and gives implications for strategies in postmenopausal hormone replacement therapy (HRT). There is large evidence from observational studies that HRT reduces the risk of cardiovascular mortality and morbidity in postmenopausal women. However, according to the only large randomized, placebo-controlled, secondary prevention Heart and Estrogen/progestin Replacement Study (HERS), women with prevalent cardiovascular disease (CVD) have increased CVD events within the first year after onset of HRT. The net effects of HRT on atherosclerosis, coagulation, fibrinolysis or the inflammatory response are unproven. Randomized trials of intermediate outcomes reveal that HRT has favorable effects on isolated cardiovascular risk factors, e.g. lipoproteins, carbohydrate metabolism and vasodilatation, but the impact of this effects on clinical endpoints is still not clear. The basis of "evidenced based medicine" is currently not sufficient to provide exact recommendation who will benefit from HRT and who might not. Therefore, the decision about hormone use should consider individual benefit-risk profiles.
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PMID:Postmenopausal hormone replacement therapy and the vascular wall: epidemiology and clinical studies. 1114 46

This paper documents recruitment for the Estrogen Replacement and Atherosclerosis trial, a multicenter, placebo-controlled, double-blind angiographic trial of the effects of opposed and unopposed estrogen on coronary atherosclerosis in postmenopausal women (average scheduled duration of follow-up 3.2 years). We compare costs, yields, and participant characteristics between community-based and hospital-based recruitment strategies. We further compare community-based enriched sources (i.e., those that allowed self-selection or targeted women with known health characteristics) and nonenriched sources. Data gathered on potential participants include method of contact, clinical site, eligibility, completion of screening visits, and randomization rates. Demographic data on participants include age, race, education, marital status, and income. Self-reported health status, smoking status, lipid level, ejection fraction as well as history of chest pain, hypertension, and diabetes were recorded at baseline. Recruitment costs were estimated from employee salaries and costs of screening tests and procedures. Yields were compared by clinical site and by method of contact. Enriched sources of recruitment yielded higher percentages of enrolled participants than nonenriched sources. Both types of source resulted in demographically similar participants. Costs of community-based recruitment were less than hospital-based recruitment; however, screening costs were higher. Overall, screening and recruitment averaged $2508 per randomized participant. Control Clin Trials 2001;22:13-25
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PMID:Recruitment of participants for the Estrogen Replacement and Atherosclerosis (ERA) trial. a comparison of costs, yields, and participant characteristics from community- and hospital-based recruitment strategies. 1116 19

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

Interleukin-6 (IL-6) gene expressed in bone marrow-derived stromal cells and osteoblasts contributes to the state of mineralization and its control by estradiol may be involved in the development of post-menopausal osteoporosis. Since IL-6 is also expressed in the different cell populations of the arterial wall, the purpose of this study was to gain more insight into its involvement in the atherosclerotic process and the atheroprotective effect of estradiol by studying double deficient mice at the apolipoprotein E and IL-6 loci (IL-6(-/-)/E(-/-)). At 1 year of age, IL-6(-/-)/E(-/-) mice showed similar hypercholesterolemia to IL-6(+/+)/E(-/-) mice but presented significantly larger and more calcified lesions. In younger mice (sixteen weeks of age), no significant difference in fatty streaks could be detected in IL-6(+/+)/E(-/-), IL-6(+/-)/E(-/-) and IL-6(-/-)/E(-/-) mice on a normal chow diet. Estrogen supplementation at this age induced a decrease of fatty streak formation in all three genotypes. The combined data indicate that IL-6 expression is involved at the fibrous plaque stage of the atherosclerotic process but does not constitute a direct target for estradiol to prevent fatty streak formation.
Atherosclerosis 2001 Jun
PMID:Involvement of interleukin-6 in atherosclerosis but not in the prevention of fatty streak formation by 17beta-estradiol in apolipoprotein E-deficient mice. 1139 27

Despite biologically plausible mechanisms whereby estrogen may confer cardioprotection as well as observational data suggesting cardiovascular benefit, data from the sole randomized controlled clinical outcomes trial reported on the benefit of hormone use. A trend was observed in the Heart and Estrogen/progestin Replacement Study (HERS) of an early increase in coronary events with possible late benefit, and in a recent angiographic trial, the Estrogen Replacement and Atherosclerosis trial (ERA) where no benefit was seen. Furthermore, selective estrogen receptor modulators may enable dissociation of estrogen risks and benefits; the selective estrogen replacement modulator raloxifene is under study in a large randomized clinical outcomes trial entitled the Raloxifene Use for the Heart trial (RUTH). (c) 2000 by CVRR, Inc.
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PMID:Hormonal and Nonhormonal Therapies for the Postmenopausal Woman: What is the Evidence for Cardioprotection? 1141 67

The incidence of coronary heart disease (CHD) is lower in premenopausal women than in men and post-menopausal women of the same age. The higher CHD rate after menopause is currently attributed to estrogen deficiency: many epidemiological (case-control and prospective) studies have reported a reduced risk (0.5-0.63) of CHD in post-menopausal women receiving hormone replacement therapy (HRT). Moreover, estrogens have multiple effects that would be expected to be cardioprotective, including favorable changes in lipids, endothelial function, vascular reactivity and blood flow. However, the observational studies are subject to several biases that could falsely elevate the apparent benefit of estrogens: women taking estrogens tend to be wealthier, more educated and healthier than untreated women. The american HERS (Heart and Estrogen-progestin Replacement Study; 2.763 women) is a large multicenter randomized study of secondary prevention, designed to evaluate the efficacy of HRT. Results are disappointing, since no reduced risk was observed, and the risk of CHD was even higher in women receiving HRT during the first year: 1.52 (CI 95%: 1.01-2.29). In HERS study, the treatments consisted of conjugated equine estrogens and the synthetic progestin medroxyprogesterone acetate (MPA) which are rarely used in Europe. Indeed, the effects of HRT are not equivalent depending on the dose, the route of administration, the type of progestogen. It should be emphasized that MPA, contrarily to progesterone, inhibits the beneficial effect of estrogens on lipids and experimental atherosclerosis. The route of administration of estrogens is also involved: estrogens alter hemostasis factors, and when orally administered, they have a first pass liver effect, which favors hypercoagulability. It is therefore urgent that Europeans undertake a European "HERS study" in order to investigate the possible beneficial effect of non oral estrogens (gel or patch) associated with natural progesterone.
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PMID:[Hormone replacement therapy of menopause, heart and blood vessels]. 1149 29

The endothelium is thought to play an important role in the genesis of atherosclerosis, and several lines of evidence suggest that the effect of an intervention on endothelial function might predict its involvement in coronary disease progression and in the rate of cardiovascular events. Estrogen has direct effects on the blood vessel wall, indicating that vascular endothelium may play a key role in the cardiovascular protective effects of hormone replacement therapy (HRT). Raloxifene relaxes coronary arteries in vitro by an estrogen receptor-dependent and NO-dependent mechanism, thus suggesting that this selective estrogen receptor modulator could also have beneficial effects on endothelial function. This study compared the effects of HRT and raloxifene on NO products, endothelin-1 plasma levels, and endothelium-dependent vasodilatation in postmenopausal women. Healthy postmenopausal women (n=90) were enrolled in a double-blind, randomized, placebo-controlled, 6-month trial. Women were randomly assigned to receive continuous HRT (1 mg 17beta-estradiol combined with 0.5 mg norethisterone acetate), raloxifene (60 mg/d), or placebo for 6 months. Flow-mediated endothelium-dependent vasodilation of the brachial artery, plasma NO concentrations, and endothelin levels were measured at baseline and after 6 months of therapy. The mean baseline level of NO breakdown products was 26.5+/-10.7 micromol/L and increased to 36.3+/-11.4 micromol/L after 6 months of treatment with raloxifene. The mean baseline plasma endothelin level was 17.3+/-8.9 pg/mL and decreased to 11.5+/-2.1 pg/mL after 6 months of treatment with the selective estrogen receptor modulator. The mean baseline ratio of NO (breakdown products) to endothelin was also significantly increased at the end of treatment with raloxifene. Postmenopausal women treated with HRT had similar changes in plasma nitrites/nitrates and endothelin levels as well as in the ratio of NO to endothelin. In contrast, these markers of endothelial function did not change in the placebo-treated women. Flow-mediated endothelium-dependent vasodilation of the brachial artery was 8.3+/-2.1% at baseline and increased to 12.3+/-2.1% after 6 months of treatment with raloxifene. HRT also caused a significant and similar increase in flow-mediated endothelium-dependent vasodilation. No change in flow-mediated vasodilation was observed in the participants treated with placebo. We conclude that raloxifene therapy and HRT influence endothelial function and improve flow-mediated endothelium-dependent vasodilation to a comparable extent in healthy postmenopausal women at least after a 6-month treatment period. However, further investigation is warranted to enhance our understanding of the mechanisms of the effect of raloxifene on vascular function and to determine whether its effect on endothelial function may contribute to the reduction in cardiovascular-related morbidity and mortality.
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PMID:Randomized, double-blind, placebo-controlled study on effects of raloxifene and hormone replacement therapy on plasma no concentrations, endothelin-1 levels, and endothelium-dependent vasodilation in postmenopausal women. 1155 81


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