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

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

This study compared the effects of tibolone, a tissue-specific compound for the treatment of climacteric symptoms and the prevention of osteoporosis, with those of conjugated equine estrogens (CEE) with and without medroxyprogesterone (MPA) on bone mineral density and coronary atherosclerosis (CAA) of postmenopausal cynomolgus monkeys. The groups were tibolone [two doses were used, 0.05 mg/kg (LoTib) and 0.2 mg/kg (HiTib)], CEE (0.042 mg/kg), CEE (0.042 mg/kg) plus MPA (0.167 mg/kg given continuously), and a control group given no treatment for 2 yr. Compared with no treatment, bone mineral density was higher by 6.3% (P = 0.0004) in the LoTib group and by 9.5% (P = 0.02) in the HiTib group compared with 4.3% (P = 0.12) for CEE and 4.5% (P = 0.10) for CEE+MPA. Plasma high density lipoprotein cholesterol was reduced by 49% with HiTib and by 34% with LoTib. There were no differences in CAA between control and HiTib (P = 0.60) or LoTib (P = 0.58). CEE and CEE+MPA both reduced CAA by about 62% (CEE vs. control, P = 0.02; CEE+MPA vs. control, P = 0.01). Despite adverse effects of tibolone on plasma lipoprotein concentrations, there was no increase in CAA, suggesting that tibolone is a cardiovascular-safe treatment for climacteric symptoms and the prevention of osteoporosis.
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PMID:A comparison of tibolone and conjugated equine estrogens effects on coronary artery atherosclerosis and bone density of postmenopausal monkeys. 1170 13

An impressive body of evidence has suggested that estrogen therapy should be helpful to slow the pathogenesis or progression of atherosclerosis. Estrogen's favorable effects on lipids and endothelial function, coupled with extensive observational epidemiology and data from animal models of atherosclerosis, persuaded many that hormone replacement therapy (HRT) would be helpful for both primary and secondary prevention of coronary disease. Recently, several randomized clinical trials of HRT have been completed, and several more are currently under way. These trials include both primary and secondary prevention cohorts and use clinical as well as anatomic manifestations of atherosclerosis as outcomes. These trials are producing surprising and controversial results that will radically alter contemporary understanding of the role of HRT for cardiovascular disease prevention. This review briefly describes the findings of the Heart and Estrogen/Progestin Replacement Study, the Estrogen Replacement and Atherosclerosis Trial, and other recently completed clinical trials. Trials that are under way are also described and discussed.
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PMID:Cardiovascular trials of estrogen replacement therapy. 1179 47

Numerous observational studies have previously shown that estrogen therapy (ERT) or estrogen/progestin hormone replacement therapy (HRT) can significantly reduce the risk of Coronary Artery Disease (CAD) in healthy postmenopausal women by up to 50%. However, due to statistical limitations inherent in these earlier studies, several large randomised trials are now under way. The results from some of these randomised trials are expected sometime in 2005 and will certainly help confirm or refute the present perceived cardio-protective effects of ERT/HRT in healthy menopausal women. On the other hand, the role of hormonal therapy in menopausal women with established CAD is more controversial. Although results from earlier observational trials have been encouraging, more recent randomised controlled data from the Heart and Estrogen/Progestin Replacement (HER) study and the Estrogen Replacement and Atherosclerosis (ERA) study have been more sober. In fact, both have generally reported on the failure of ERT/HRT to reduce the overall rate of ischaemic cardiovascular events or to halt the progression of coronary atherosclerosis in menopausal women with established CAD. However, these studies are not without their own limitations. As such, more future trials will be needed before the role of postmenopausal hormone therapy in the secondary prevention of CAD can be firmly established.
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PMID:Hormone replacement therapy (HRT) and ischaemic heart disease: getting to the heart of the matter. 1200 77

Oral contraceptive use in women with factor V Leiden is associated with increased rates of venous thromboembolic events (VTEs). However, the effects of hormone replacement therapy (HRT) in postmenopausal women with factor V Leiden are not known. A nested case-control study was conducted among women with established coronary disease enrolled in 2 randomized clinical trials of HRT, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Estrogen Replacement and Atherosclerosis (ERA) trial. The Leiden mutation was present in 8 (16.7%) of 48 cases with VTE compared with only 7 (6.3%) of 112 controls (odds ratio [OR](Leiden) 3.3, 95% CI 1.1 to 9.8; P=0.03). In women without the factor V Leiden mutation, risk associated with HRT use was significantly increased (OR(HRT) 3.7, 95% CI 1.4 to 9.4; P<0.01). On the other hand, in women with the factor V Leiden mutation, the estimated risk associated with HRT was increased nearly 6-fold, although the CIs were wide and included unity (OR(HRT) 5.7, 95% CI 0.6 to 53.9; P=0.13). The OR for women with the Leiden mutation who were also assigned to HRT compared with wild-type women assigned to placebo was 14.1 (95% CI 2.7 to 72.4, P=0.0015). In women with the factor V Leiden mutation who were treated with HRT, the estimated absolute incidence of VTE was 15.4 of 1000 per year compared with 2.0 of 1000 per year in women without the mutation who were taking a placebo (P=0.0015). On the basis of these data, in women with coronary disease, the estimated number needed to screen for factor V Leiden to avoid an HRT-associated VTE during 5 years of treatment is 376. If factor V Leiden genotyping becomes less expensive, it could be cost effective to screen for the presence of the mutation before instituting HRT in women with coronary disease.
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PMID:Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic events in women with coronary disease. 1206 91

The bulk of the experimental data suggest beneficial effects of estrogen (both premenopausal use of OCs and postmenopausal use of ERT-HRT). An intriguing finding from the monkey studies is that social subordination, which induces estrogen deficiency in female monkeys, accelerates atherosclerosis premenopausally and predicts extent of postmenopausal atherosclerosis. This effect can be inhibited by exogenous estrogen, premenopausally. The results suggest that more effort on detecting and regulating premenopausal ovarian dysfunction may be justified. A complication in understanding estrogen action may be the result of varying extents of arterial damage. For example, primary prevention studies in both postmenopausal animals and women have provided strong evidence of atheroprotection with a variety of estrogens. In contrast, the results of secondary prevention studies [10,12] have in general suggested little cardioprotection with either ERT or HRT. Studies in rabbits suggest the antiatherogenic effect of estrogen may not be present when the endothelium is damaged [64]. The state of the endothelium may be critical for some estrogen actions. For those effects of estrogen that require the ER, be it ERalpha or ERbeta, the presence of the receptor may vary with age, disease state, or type of hormone therapy. If continuous combined HRT therapy decreases ER in the artery as it does in the uterus, this may eliminate those estrogen actions requiring the ER, but not others. Older women who have not been exposed to estrogens for many years may be more sensitive to some estrogen effects, and may need lower doses of ERT-HRT. Recent reports suggest that lower doses of estrogens maintain beneficial effects on lipoproteins and coagulation factors [95], while also requiring lower doses of progestogens to protect the uterus [96]. These beneficial findings are very promising in light of the improvements in CHD risk and decreased stroke risk reported with low-dose estrogens [5]. It ill be interesting to see if CRP is increased with lower doses of estrogens and whether these changes are associated with increased early risk of CHD. Perhaps older women with CHD are also more obese, may have diabetes, and may be more susceptible to inflammatory and thrombotic effects of higher doses of estrogens. There are many questions left unanswered. It is hoped that some of the answers may come from the WHI, which is a large prospective trial assessing ERT and HRT. The age range is also relatively large and may be able to determine if older women respond differently than younger women. Some initial data from the WHI have been made available suggesting a small increased risk in the first 2 years and a trend for decreasing risk in the last months of the first 2 years [34]. Just recently, the CEE + MPA arm of the study was stopped early by the data and-safety monitoring board as the overall health risks exceeded benefits with increases in both breast cancer and CVD [97]. The remainder of the study groups including an estrogen-only arm, are expected to continue until 2005.
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PMID:Reproductive hormones and cardiovascular disease mechanism of action and clinical implications. 1235 69

Cardiovascular disease (CVD) is increasingly being recognised as having a profound effect on women, especially after menopause. Lack of oestrogen has been targeted as one of the reasons for increased incidence of CVD in postmenopausal women. Oestrogen has been found to have favourable effects on lipid profile, tone of vascular smooth muscle cells and fibrinogen levels. Several observational studies have supported these experimental findings, consistently demonstrating reduced cardiovascular risks in users of hormone replacement therapy (HRT). However, evidence from recent clinical trials has challenged this widespread belief. Heart and Estrogen/Progesterone Replacement Study II, Estrogen Replacement and Atherosclerosis trial and more recently, Women's Health Initiative, have shown that HRT has no role in primary and secondary prevention of CVD and most authorities currently do not advocate HRT for the prevention of CVD.
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PMID:Effect of hormone replacement therapy on cardiovascular disease: current opinion. 1273 92

Concerns exist about the cardiovascular effects of hormone replacement therapy (HRT) in postmenopausal women because results from the Women's Health Initiative (WHI) and the Heart and Estrogen/Progestin Replacement Study (HERS) are contradictory. In both of these studies, postmenopausal conjugated equine estrogens + medroxyprogesterone acetate did not reduce risk, and somewhat increased the risk of myocardial infarction in both primary (WHI) and secondary (HERS) prevention. These results appear to contradict numerous observational clinical trials and animal studies, which reported profound beneficial effects of HRT on cardiovascular disease risk. Results of both human and monkey studies indicate that estrogen replacement therapy (ERT)/HRT is effective in inhibiting progression of early stage (fatty streak) atherosclerosis but that ERT/HRT is much less effective in inhibiting progression of more advanced (established plaque) atherosclerosis. Results of these monkey studies are consistent with those of studies in women wherein ERT/HRT was initiated in postmenopausal women with different initial amounts of atherosclerosis. Based on these findings, it is speculated that ERT/HRT may be more cardioprotective in younger postmenopausal women with less coronary artery disease, and less effective in women with established coronary artery disease. Researchers are challenged to define the relative cardiovascular risk/benefit in different populations of postmenopausal women based on differences in age, amounts of pre-existing atherosclerosis, and risk factors.
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PMID:Hormone replacement therapy and cardiovascular disease: lessons from a monkey model of postmenopausal women. 1511 33

Oxidative stress plays an important role in the pathogenesis of atherosclerosis and can be effectively influenced by radical scavenging enzymes. Estrogens exert antioxidative effects in the vasculature; however, cotreatment with progesterone may abrogate the vasoprotective effects of estrogen. Therefore, the effects of progesterone on the production of reactive oxygen species (ROS) and expression and function of antioxidant and oxidant enzymes were investigated in cultured vascular smooth muscle cells (VSMCs) and vascular tissue of mice. Progesterone time- and concentration-dependently downregulated extracellular superoxide dismutase (ecSOD) and manganese superoxide dismutase (MnSOD) expression and enzyme activity and reversed 17beta-estradiol-induced overexpression of ecSOD and MnSOD in VSMCs. Nuclear run-on assays revealed that progesterone decreases MnSOD and ecSOD transcription rates. Consequently, progesterone increased ROS release in VSMCs that was prevented by concomitant treatment with 17beta-estradiol. Estrogen deficiency in ovariectomized mice was associated with an increase in vascular superoxide release and NADPH oxidase activity. Estrogen replacement prevented this increase, whereas progesterone substitution enhanced ROS production and NADPH oxidase activity. The modulation of superoxide release coincided with decreased expression of ecSOD and MnSOD and upregulation of the p22phox and p67phox subunits of the NADPH oxidase complex in progesterone-treated animals. Furthermore, administration of progesterone to ovariectomized mice treated with 17beta-estradiol abrogated the antioxidative effects of estrogen. Progesterone antagonizes the vasoprotective effects of estrogen on ecSOD and MnSOD expression and increases NADPH oxidase activity. These findings may in part explain why hormone replacement therapy with estrogen plus progesterone displayed no beneficial effect on cardiovascular event rates in the prospective clinical trials.
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PMID:Progesterone antagonizes the vasoprotective effect of estrogen on antioxidant enzyme expression and function. 1619 79

Clinical trials indicate that hormone therapy (HT) does not decrease cardiovascular disease events or angiographic coronary disease progression. The effects of HT on SVG vessels are unknown. To determine whether postmenopausal hormone therapy started after coronary bypass surgery (CABG) decreases saphenous vein graft (SVG) disease, we conducted a multicenter randomized placebo-controlled angiographic study of estradiol+/-medroxyprogesterone started within 6 months of CABG in 83 postmenopausal women. Angiographic and intravascular ultrasound (IVUS) assessment at 6 and 42 months was planned to assess SVG disease progression. The study was stopped early following publication of the Women's Health Initiative Estrogen/Progestin study. Eighty-three subjects underwent a 6-month angiogram with 63 undergoing IVUS. Forty-five subjects completed the 42-month angiogram (20 underwent 42-month IVUS). In analysis of paired 6- and 42-month angiogram and IVUS studies, HT slowed angiographic progression of SVG disease assessed by mean percent stenosis (p<0.001), minimal lumen diameter (p=0.029), and total plaque volume (p=0.006). In contrast, HT accelerated disease progression in non-bypassed native coronary arteries (minimum lumen diameter, p=0.01). SVG disease and closure occurred in 38% subjects within 1-year post-CABG. The groups had similar frequency of cardiovascular events expect for angioplasty that occurred in eight HT compared to one placebo subject (p<0.05). In HT subjects angioplasty was indicated for native coronary arterial stenoses while in the placebo subject angioplasty was indicated for SVG stenosis. This study suggests that hormone treatment may slow SVG disease progression while accelerating atherosclerosis in non-bypassed native coronary arteries.
Atherosclerosis 2006 Dec
PMID:Randomized trial of hormone therapy in women after coronary bypass surgery. Evidence of differential effect of hormone therapy on angiographic progression of disease in saphenous vein grafts and native coronary arteries. 1644 14


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