Effect of oral aminophylline in patients with angina and normal coronary arteriograms (cardiac syndrome X).

BACKGROUND: Patients with syndrome X (exertional angina, positive exercise test, normal coronary arteriogram) have an altered perception of cardiac pain. This symptom may arise from increased sensitivity to adenosine. Previous studies suggest that intravenous aminophylline (an adenosine receptor blocker) improves exercise tolerance in patients with this disorder. OBJECTIVE: To examine the efficacy of oral aminophylline in syndrome X. METHODS: 13 patients (11 women and two men, mean (SD) 54 (6) years) with syndrome X were studied. Patients were randomised in a double blind crossover study to receive either oral aminophylline or placebo for three weeks. All patients underwent symptom limited exercise testing and ambulatory electrocardiography at the end of each three week period. RESULTS: 10 patients completed the study. The time to angina during exercise testing in patients who were given aminophylline was longer than for the placebo group (mean (SD) 632 (202) seconds v 522 (264) seconds, P = 0.004). Peak exercise ST depression did not differ significantly between patients who received aminophylline and those administered placebo (mean (SD) -1.9 (0.7) mm v -1.5 (0.8) mm). Six patients taking aminophylline reported a reduction in the total number of episodes of chest pain during the three weeks, but the frequency and duration of ST segment depression during Holter monitoring was unchanged. CONCLUSION: Oral aminophylline has a favourable effect on exercise induced chest pain threshold in patients with syndrome X. The disparate effects on symptoms and ST segment changes are intriguing and further study is warranted.     

Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women

OBJECTIVES

We sought to compare the effects of estrogen/transvaginal progesterone gel with estrogen/medroxyprogesterone acetate (MPA) on exercise-induced myocardial ischemia in postmenopausal women with coronary artery disease or previous myocardial infarction, or both.

BACKGROUND

Estrogen therapy beneficially affects exercise-induced myocardial ischemia in postmenopausal women; however, women with an intact uterus also take progestin to protect against uterine malignancies. The effects of combination estrogen/progestin therapy on myocardial ischemia are unknown.

METHODS

Eighteen postmenopausal women (mean ± SD age 59 ± 7 years) were given 17-beta-estradiol in single-blinded manner for four weeks (1 mg/day for three weeks then 2 mg/day for one week). Estradiol (2 mg/day) was then continued, and the patients were randomized (double-blind) for 12 days to either transvaginal progesterone gel (90 mg on alternate days) and oral MPA placebo (10 mg/day), or vice versa. After another two weeks on estradiol alone, the patients crossed over to progestin treatment and repeated the protocol on the opposite treatment. Patients underwent treadmill exercise testing after each estradiol phase and at day 10 of each progestin phase.

RESULTS

Exercise time to myocardial ischemia increased after the first estrogen phase as compared with baseline (mean difference with 95% confidence interval [CI]: 72 s [34 to 110], P = 0.001), and was increased by combination estradiol/progesterone therapy as compared with estradiol/MPA therapy (92 s [35 to 149], P = 0.001)). Two patients (11%) were withdrawn while taking estradiol/MPA owing to unstable angina.

CONCLUSIONS

Combination estrogen/transvaginal progesterone gel increases exercise time to myocardial ischemia, as compared with estrogen/MPA. These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration.     

The effects of transdermal estradiol on the response to mental stress in postmenopausal women: a randomized trial

PURPOSE: Estrogens inhibit adrenomedullary catecholamine release and catecholamine-mediated responses to stress. We examined whether estrogen supplementation reduces the sympathoadrenal response to mental stress in postmenopausal women. MATERIALS AND METHODS: We compared the effects of 3-week treatment with transdermal 17-beta-estradiol and placebo in 10 postmenopausal women using a randomized, blinded, crossover design. We measured plasma catecholamine levels and the cardiovascular and metabolic responses to a 15-minute stress with mental arithmetic. Treatments were compared using repeated measures analysis of variance. RESULTS: During placebo treatment, mean (+/- SD) epinephrine levels reached a peak of 431 +/- 135 pmol/liter after 15 minutes of stress; the epinephrine response was blunted during estradiol treatment, with a peak of 357 +/- 77 pmol/liter (P <0.05). Estradiol also blunted the diastolic blood pressure response to stress (baseline levels of 78 +/- 15 mm Hg vs peak of 90 +/- 6 mm Hg during placebo; baseline of 80 +/- 8 mm Hg vs peak of 84 +/- 6 mm Hg during estradiol; P <0.05). Estradiol treatment also blunted the decrease in the standard deviation of the mean of the electrocardiographic RR intervals and the increase in the ratio between the low-frequency and high-frequency bandwidths. CONCLUSION: We observed a moderate, although significant, reduction in markers of the stress response to mental arithmetic in postmenopausal women treated with transdermal 17-beta-estradiol.     

Acute effect of oestrogen replacement therapy on treadmill performance in postmenopausal women with coronary artery disease

The significant reduction in cardiovascular morbidity and mortalityfollowing oestrogen replacement therapy in postmenopausal womenis only partly explained by an improved lipid profile. Givenacutely, oestradiol causes vasodilatation and increases coronaryblood flow and, in large doses, improves treadmill performancein postmenopausal women with coronary artery disease. However,the significance of oestrogen-mediated vasodilatation is unknownsince the acute effects of oestradiol in doses and preparationscommonly used clinically have not been tested. The aim of thisstudy was to evaluate the acute effects of conventional replacementtherapy with 17 ß-oestradiol on treadmill performancein 16 postmenopausal women with angina in a randomized, double-blind,placebo-controlled cross-over trial. Following baseline treadmill testing a transdermal oestrogenpatch releasing 50 µg oestradiol. 24 h^–1 or matchingplacebo was applied and the exercise test repeated 24 h later.The patch was then removed. Seven to 14 days later the sequencewas repeated using the alternative patch. The changes in timeto angina, time to 1 mm ST segment depression and total exercisetime for each treatment compared with the corresponding baselinetest were calculated. Plasma 17 ß-oestradiol increased with active therapyfrom 56±30pmol. l^–1 to 204±90pmol. l^–1,indicating adequate replacement. Compared with their respectivebaseline exercise tests there were no differences between activeand placebo patches for time to angina (active: 13±55s vs placebo: 10±47 s), time to 1 mm ST segment depression(active: –30 ±52 s vs placebo: 24±71 s)or total exercise time (active: 14±45 s vs placebo: 13±35s). Despite the recognized acute vasodilator action of larger dosesof oestrogen, doses conventionally used in hormone replacementtherapy had no acute effect on treadmill performance in thisgroup of postmenopausal women with coronary artery disease.     

Estradiol-17β reduces blood pressure and restores the normal amplitude of the circadian blood pressure rhythm in postmenopausal hypertension

After menopause, both systolic (SBP) and diastolic (DBP) blood pressure (BP) become higher in women than in men of the same age, suggesting that estrogen deficiency may influence the age-related increase in BP. We studied 30 postmenopausal women (mean age, 55 ± 5.7 years; time from menopause, 2–5 years) affected by mild hypertension with no target-organ complications by means of 24-h BP monitoring. None of the group were undergoing estrogen replacement therapy or taking antihypertensive drugs. According to a randomized, double-blind protocol, subjects received patches of transdermal estradiol-17β (E₂) or a matched placebo, with crossover after a 7-day washout period. In 12 patients the 24-h peak-to-trough variation in SBP and DBP amounted to less than 10% (nondippers). Administration of E₂ significantly decreased 24-h SBP and DBP in the whole cohort (P < .05). Furthermore, E₂ restored the expected reduction in BP during nighttime in the nondipper subgroup. It is well known that estrogen replacement therapy protects against the development of both cardiovascular diseases and stroke. Our data suggest that this activity could be attributed, at least in part, to the activity of E₂ in preserving physiologic circadian fluctuation of BP.     

Heart rate-independent prolongation of QTc interval in women with syndrome X

Background: Cardiac syndrome X is usually diagnosed in the presence of typical exertional chest pain, a positive response to exercise testing, and normal coronary angiograms. The underlying pathogenic mechanisms are speculative, but myocardial ischemia and increased sympathetic activity have been implicated. Hypothesis: The present study examined whether QTc interval is prolonged in women with syndrome X when confounding factors such as heart rate, gender, and environmental conditions are accounted for. Methods: Maximum QTc interval and its relationship to clinical and exercise variables were evaluated in 32 women with syndrome X (exertional chest pain, positive exercise testing, and completely normal coronary arteries) and 34 normal controls. Results: Patients with syndrome X had significantly longer QTc interval (440 ± 24 ms) than normal subjects (410 ± 26 ms, p<0.004). However, this QTc prolongation appears to be heart rate-independent as patients with syndrome X showed longer QT and QTc intervals than controls despite an identical heart rate. No relation was found between QTc prolongation and clinical or exercise test variables in patients with syndrome X. Conclusion: Although increased sympathetic drive is present in syndrome X, and this variable is likely to modulate QTc duration, the mechanism and clinical implications of QTc interval prolongation in syndrome X remain speculative.     

Complete and selective estrogenic effects on lipids and cardiovascular disease

Observational studies have shown a protective effect of estrogen replacement on risk of cardiovascular disease in postmenopausal women. The estrogen protection is thought to be mediated by mechanisms acting at different levels, including a beneficial effect on plasma lipid concentrations. Selective estrogen receptor modulators (SERM) share with estrogen the ability to reduce plasma levels of atherogenic lipoproteins like low-density lipoproteins and lipoprotein(a). The recent publication of the first randomized, placebo-controlled trial of estrogen/progestin replacement (HERS), which failed to show a reduced number of cardiovascular events in women randomized to estrogen treatment as compared with placebo, has cast some doubts on the protective role of estrogen. Other large randomized studies on the effect of estrogen and other compounds with estrogenic activity (eg, SERM) on cardiovascular disease risk are currently underway and will provide more definite answers to both clinicians and postmenopausal women.     

X综合征女性患者电子束CT测定冠状动脉钙化的临床特点

为探讨X综合征女性患者冠状动脉钙化及临床情况 ,利用电子束CT对 2 6例X综合征女性患者和 2 2例冠状动脉造影及运动试验均正常的女性胸痛者冠状动脉进行检测 ,同时对其冠心病危险因子进行评估 ,测定血脂和血浆氧化型低密度脂蛋白水平 ,对比不同病例的冠状动脉钙化积分及病变血管支数。结果发现 ,有 19例(73% )X综合征女性患者存在冠状动脉钙化 ,而正常组中仅 4例 (18% )存在冠状动脉钙化 ;有冠状动脉钙化的X综合征女性患者冠心病危险因子明显高于正常组 (1.8± 1.3比 1.1± 0 .9,P <0 .0 5 ) ,前者的血浆氧化型低密度脂蛋白浓度也明显高于后者 (5 2 .38± 6 .89比 39.92± 7.87,P <0 .0 5 ) ;其中 13例为绝经期患者。绝经后X综合征患者冠状动脉钙化积分和有冠状动脉钙化的血管支数与非绝经期者相比无明显差异 ,但这两组均较正常组明显增高 (P<0 .0 5 )。结果提示 ,有相当数量的X综合征女性患者存在冠状动脉钙化 ,这种钙化似乎与绝经与否无关 ,有必要对这类患者的临床资料进行评估并作相应治疗     

The effect of estrogen plus progestin on knee symptoms and related disability in postmenopausal women: The heart and estrogen/progestin replacement study,a randomized,double‐blind,placebo‐controlled trial

Objective

Most observational studies suggest that postmenopausal women taking hormone replacement therapy have a reduced risk of radiographic knee and hip osteoarthritis (OA). There are no randomized trial data on the association of hormone treatment with knee or hip OA, and no studies have been published regarding the relationship of hormone treatment to knee or hip symptoms. This study examined the association of hormone treatment with prevalent knee symptoms and disability related to knee pain as assessed at the final visit of the Heart and Estrogen/Progestin Replacement Study (HERS).

Methods

The HERS was a 4‐year randomized, double‐blind, placebo‐controlled trial of estrogen plus medroxy progesterone acetate for prevention of coronary heart disease in postmenopausal women with documented coronary disease. Participants in this substudy on knee pain were 969 postmenopausal women, with a mean age of 66 years and mean body mass index of 28.6 kg/m², attending the final visit at 9 clinical centers. Frequent knee symptoms were assessed by interview and the severity of knee pain and disability related to knee pain were determined using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Knee symptoms and disability were compared between women assigned to receive hormones and those assigned to receive placebo.

Results

Frequent knee pain was reported in 24.1% of women assigned to receive hormone therapy versus 26.1% of those assigned to the placebo group, a difference of −2.0% (95% confidence interval [95% CI] −7.4% to 3.5%). Among women with knee pain, there were no differences in the severity of pain (score difference −0.2, 95% CI −1.2 to 0.8) or disability (score difference −0.7, 95% CI −3.8 to 2.4) as assessed on the WOMAC. All results were similar for women whose body mass index was either above or below the median.

Conclusion

In a group of older, postmenopausal women with cardiac disease, we found no significant effect of 4 years of estrogen plus progestin therapy compared with placebo on knee pain and related disability. Our findings may not apply to other groups of women or to the effect of hormone therapy on the structural changes of knee OA.

     

Effect of raloxifene on activated protein C (APC) resistance in postmenopausal women and on APC resistance and homocysteine levels in elderly men: two randomized placebo-controlled studies.

Raloxifene, a selective estrogen receptor modulator, like hormonal replacement therapy increases the risk of venous thromboembolism in postmenopausal women. A possible explanation for the increased thrombotic risk could be an increase in acquired resistance to activated protein C (APC). In two randomized, placebo-controlled, double-blind studies we determined the effect of raloxifene on the normalized APC sensitivity ratios (nAPCsr). The nAPCsr were determined with the thrombin generation-based APC resistance test. In the first study 83 postmenopausal women (age, 51.1 +/- 2.7 years) randomly received daily 0.625 mg conjugated equine estrogen and 2.5 mg medroxyprogesterone acetate (n=17), 60 mg raloxifene (n=23), 150 mg raloxifene (n=20) or placebo (n=23) for 24 months. At baseline and after 6, 12 and 24 months the nAPCsr were measured. In the second study 30 elderly men (age, 64.4 +/- 2.4 years) randomly received 120 mg raloxifene (n=15) or placebo (n=15) for 3 months. At baseline and after 3 months the nAPCsr and fasting homocysteine levels were measured. In postmenopausal women conjugated equine estrogen/medroxyprogesterone acetate significantly increased the nAPCsr from 1.26 +/- 0.82 to 2.87 +/- 0.86 at 24 months (P <0.0005 compared with placebo). Raloxifene had no significant effect on nAPCsr compared with placebo in both women and men. The results did not change after excluding carriers of factor V Leiden. Also fasting homocysteine levels were not affected by raloxifene in the aging men. It is concluded that raloxifene, in contrast to combined hormonal replacement therapy, does not increase APC resistance.     

运动试验对有胸痛发作女性的冠心病预测价值

目的:探讨运动试验对绝经期前、后具有胸痛发作的女性是否有冠心病预测价值。方法:30例绝经期前和43例绝经期后女性进行平板运动试验,并与冠状动脉造影的结果相比较。结果:30例绝经期前女性中18例运动试验阴性,其中17例冠状动脉造影阴性,阴性预测价值94％;43例绝经期后女性中22例运动试验阳性,其中17例冠状动脉造影阳性,阳性预测价值77％。绝经后妇女阳性预测值显著高于绝经前妇女(P<0.01)。结论:对具有胸痛症状女性而言,运动试验对绝经期前女性的阴性预测价值较高,对绝经期后女性的阳性预测价值提高。     

Overview of gender aspects of cardiac syndrome X

Cardiac syndrome X, a condition defined by the presence of angina-like chest pain, a positive response to stress testing and normal coronary arteriograms, has been shown to occur in approximately 20--30% of angina patients undergoing coronary arteriography. The prevalence of syndrome X is significantly higher in women compared to men. In the majority of patients with chest pain and normal coronary arteriograms, symptoms are likely to be non-cardiac in origin. However, myocardial ischaemia may be the pathogenic mechanism in a proportion of syndrome X patients. Indeed, the clinical characteristics, the ischaemic electrocardiographic findings and the presence of myocardial perfusion defects during stress testing are similar in syndrome X and coronary artery disease patients. Moreover, coronary sinus oxygen saturation abnormalities and pH changes, as well as myocardial lactate production and alterations of cardiac high energy phosphate are seen during stress testing in patients with syndrome X and appear to endorse an ischaemic origin of symptoms in at least a proportion of these individuals. Patients with chest pain and normal coronary arteries have abnormal vasodilatory coronary blood flow responses and an increased sensitivity of the coronary microcirculation to vasoconstrictor stimuli (microvascular angina). Microvascular endothelial dysfunction appears to be responsible for these coronary microcirculation abnormalities. Given the high prevalence of peri- and post-menopausal women in cardiac syndrome X, it has been hypothesized that oestrogen deficiency may play a major role in the pathogenesis of this condition. Oestrogen vasoactive properties involve endothelium-dependent effects and, in postmenopausal women, forearm vasodilatation induced by acetylcholine is potentiated by the acute local administration of intravenous oestradiol. This suggests that endothelium-dependent responses in the peripheral circulation may be modulated by steroid hormones. Impairment of endothelial function in post-menopausal women with syndrome X has been reported by various groups and it could be hypothesized that oestrogen deficiency may contribute to the development of microvascular angina through endothelial dysfunction and that exogenous oestrogen administration may have a beneficial effect in syndrome X patients. This article reviews current knowledge regarding the role of oestrogen deficiency in the pathogenesis of syndrome X and the potential therapeutic role of oestrogen replacement therapy in women with chest pain and normal coronary arteriograms     

Improved exercise capacity with acute aminophylline administration in patients with syndrome X

The efficacy of the adenosine receptor blocker aminophylline on exercise capacity in patients with effort ischemia and documented coronary artery disease has been previously documented. In this study the effect of aminophylline on effort electrocardiographic (ECG) alterations and chest pain was tested in eight patients with syndrome X (anginal chest pain on effort, ischemic ECG changes during exercise, positive dipyridamole test, normal epicardial coronary arteries on angiography and absence of coronary spasm after ergonovine). After double-blind, randomized intravenous infusion of aminophylline (6 mg/kg body weight over 15 min) or placebo (20 ml of saline solution over 15 min), the eight patients with syndrome X underwent an upright bicycle exercise stress test on 2 consecutive days. After aminophylline, there was an increase in effort tolerance (aminophylline 7.7 +/- 1.2 min of exercise versus placebo 5.6 +/- 0.9, p less than 0.01) paralleled by an increase of the rate-pressure product (mm Hg x beats/min x 1/100) at 0.1 mV of ST segment depression or at peak exercise (aminophylline 278 +/- 55 versus placebo 230 +/- 24, p less than 0.05). Aminophylline provoked the abolition of ECG signs of ischemia in all eight patients. Thus, at a dosage that should effectively inhibit adenosine receptors, aminophylline infusion exerts a beneficial effect on exercise-induced chest pain and ischemia-like ECG changes in syndrome X. This effect occurs possibly through the prevention of myocardial flow maldistribution elicited by inappropriate adenosine release during effort in the presence of increased coronary resistance at the level of small intramural coronary arteries. This study, however, does not document the ischemic nature of effort-induced pain and ECG alterations in syndrome X.     

Effects of oral and transdermal 17 beta-estradiol combined with progesterone on homocysteine metabolism in postmenopausal women: a randomised placebo-controlled trial

Mild hyperhomocysteinemia is a risk factor for both ischaemic heart disease and venous thromboembolism. The effects of transdermal estrogen replacement therapy (ERT) on homocysteine metabolism in postmenopausal women have scarcely been investigated. This clinical trial aimed to estimate the effects of combined hormone replacement therapy on the fasting total homocysteine levels according to the estrogen route of administration. We enrolled 196 postmenopausal women, who were randomly allocated to receive on a continuous basis either 1mg of 17 beta-estradiol orally (n = 63) or 50 microg transdermally (n = 68) per day, both combined with a daily intake of 100 mg progesterone, or placebo (n = 65) over a period of 6 months. Neither oral nor transdermal ERT significantly affected total plasma homocysteine levels or red-blood cell folate levels. However, oral ERT significantly decreased plasma vitamin B12 levels compared to placebo (mean relative variation difference over 6 months between oral ERT and placebo: -11.7% (95%CI, -21 to -2%) whereas transdermal ERT did not display any significant effects. Our data show that transdermal ERT as well as low dose of oral ERT does not significantly affect the homocysteine metabolism. This finding does not support a role for transdermal estrogen in the prevention of ischaemic heart disease in postmenopausal women.     

Venous thromboembolism and hormone replacement therapy

There is evidence that postmenopausal women who take hormone replacement therapy develop biochemical hypercoagulability, expressed by increased activity of coagulation enzymes. Such effects are observed whether estrogen is given alone or in combination with progestogens, orally or transdermally. Two recent randomized, double-blind clinical trials have shown that hormone replacement therapy leads to an increased risk of venous thromboembolism (VTE) in postmenopausal women. Generally, in women with no additional risk factors for VTE, the excess risk due to hormone replacement therapy is rather small. However, women with a history of VTE should not be prescribed hormone replacement therapy.     

Effects of angiotensin-converting enzyme inhibition on exercise-induced angina and ST segment depression in patients with microvascular angina

Objectives. This study was conducted to test the hypothesis that angiotensin-converting enzyme inhibition may lessen myocardial ischemia in patients with microvascular angina.Background. Patients with syndrome X (angina pectoris, positive findings on exercise testing and normal coronary arteriogram) have reduced coronary vasodilator reserve (“microvascular angina”, and may show an increased sympathetic drive. Angiotensin-converting enzyme inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease.Methods. Ten patients (seven women and three men, mean age [±SD] 53 ± 6 years) with syndrome X and a reduced coronary flow reserve underwent a randomized, single-blind, crossover, placebo-controlled study of the effects of the angiotensin-converting enzyme inhibitor enalapril on angina and exercise-induced ST segment depression. Assessment was by symptom-limited treadmill exercise testing after 2 weeks of treatment with 10 mg/day of enalapril and after 2 weeks of placebo administration.Results. All patients had positive findings on exercise testing (≥1 mm ST segment depression and angina) white taking placebo, whereas six patients had a positive test results (four with angina) during enalapril therapy. Total exercise duration and time to 1 mm of ST segment depression were prolonged by enalapril over those obtained with placebo (mean 779 ± 141 vs. 690 ± 148s, p = 0.006 and 690 ± 204 vs. 485 ± 241 s, p = 0.007, respectively). The magnitude of ST segment depression was also less with enalapril than with placebo (mean 1.1 ± 0.4 vs. 1.5 ± 0.2 mm, p = 0.004). Heart rate and blood pressure at peak exercise and at 1 mm of ST depression were not significantly different during placebo and enalapril treatment.Conclusions. Angiotensin-converting enzyme inhibition lessens exercise-induced ischemia in patients with syndrome X and microvascular angina, probably by a direct modulation of coronary microvascular tone, which results in an increased myocardial oxygen supply.     

17-beta-estradiol increases cardiac remodeling and mortality in mice with myocardial infarction

OBJECTIVES: This study was designed to examine the effects of estrogen replacement on infarct size, ventricular remodeling, and mortality after myocardial infarction (MI) in mice. BACKGROUND: Observational and clinical studies suggest that the cardiovascular effects of hormone replacement therapy can differ depending on the patient population studied. No prospective studies have examined the effect of estrogen on outcomes following MI. We now examine the effects of estrogen replacement on infarct size, ventricular remodeling, and mortality after MI in mice. METHODS: Myocardial infarction was induced by left coronary artery ligation in ovariectomized female mice treated with 17-beta-estradiol (E2) or placebo. At either one day or six weeks after MI, hemodynamic function was assessed, animals were euthanized, and infarct size was determined. RESULTS: 17-beta-estradiol-treated mice had smaller infarcts than placebo-treated animals both one day (18% decrease; p < 0.01), and six weeks (14% decrease; p < 0.05) following MI. E2 reduced cardiomyocyte apoptosis as assessed by the terminal deoxynucleotidyl transferase uridine nucleotide end-labeling method (50% reduction, p < 0.05) and caspase 3 activation (33% reduction, p < 0.05). Despite having smaller infarcts, however, left ventricular mass increased more in the E2-treated animals (16% greater; p < 0.01). Left ventricular weight was positively correlated with infarct size in the estrogen-treated animals (R2 = 0.79, p = 0.0001). 17-beta-estradiol treatment also significantly increased mortality in the infarcted animals (relative risk of death = 2.4; 95% confidence interval 1.2 to 5.3). CONCLUSIONS: Estrogen replacement therapy reduces infarct size and cardiomyocyte apoptosis in mice. However, estrogen increased post-MI ventricular remodeling and mortality. Further studies will be necessary to elucidate the mechanisms underlying the complex effects of estrogen observed in the present study.     

Effect of physician gender on the prescription of estrogen replacement therapy

OBJECTIVE: To determine if women cared for by female physicians are more likely to receive postmenopausal estrogen replacement therapy than women cared for by male physicians. DESIGN: Case-control study with follow-up telephone survey. SETTING: An outpatient practice at an urban teaching hospital in Boston, Massachusetts. PARTICIPANTS: Subjects were women begun on estrogen replacement therapy during an 18-month period; controls were matched on age and month of visit. Seventy-one cases (mean age 60 years, 41% nonwhite) and 142 controls (mean age 60 years, 48% nonwhite) were identified. Fifty-two (82%) of 64 eligible case patients and 89 (80%) of 111 eligible control patients completed a follow-up telephone interview assessing their preferences for female physicians and interest in estrogen replacement therapy. MAIN RESULTS: After adjusting for potential confounders using conditional logistic regression, patients with female physicians were more likely to begin estrogen replacement therapy than those seen by male physicians (odds ratio [OR] 5.4; 95% confidence interval [CIJ 1.8, 15.3). Case patients selected their primary care physician more often than control patients and were more interested in estrogen replacement therapy. After adjusting for potential confounders including patients’ preferences to select their physician and their interest in estrogen replacement therapy, patients with female physicians were still more likely to begin estrogen replacement therapy than those seen by male physicians (OR 11.4, 95% CI 1.1, 113.6). CONCLUSIONS: We conclude that female patients are more likely to be prescribed estrogen replacement therapy if they are cared for by female physicians rather than male physicians even after accounting for patient preferences. Further research is required to determine whether these differences reflect differences in physicians’ knowledge or attitudes regarding estrogen replacement therapy or reflect gender differences in how physicians discuss estrogen replacement therapy with their patients.     

Are the acute effects of transdermal estradiol in postmenopausal women with coronary disease related to changes of the autonomic tone?

The single application of estradiol in postmenopausal women with symptomatic coronary heart disease has an antiischemic effect, which seems to be mainly related to the relaxation of the vascular smooth muscle. Longterm replacement with estrogen in postmenopausal women reduces their increased sympathetic activity. The aim of the double-blinded study was to assess whether a single transdermal estradiol administration also has an effect on the sympathovagal balance and may additionally explain the acute effects of estradiol. Methods Fifteen women with symptomatic and angiographically proven coronary artery disease were cross-over randomized to two 100-microgram patches of estradiol or identical placebo. After one week the women received the opposite treatment. One day after patch application a 24-hour Holter-ECG recording was performed to assess the mean heart rate over 24 hours as well as time domain and frequency domain indices of the heart rate variability. Results The estradiol plasma concentration rose significantly from 354 +/- 176 pmol/l after placebo to 800 +/- 260 pmol/l after estradiol application. Heart rate during placebo was 74 +/- 15 bpm and during therapy 74 +/- 15 bpm. Heart rate variability was not different for time domain indices such as SDNN (estradiol: 64 +/- 31 ms; placebo: 65 +/- 33 ms) or for frequency domain indices such as LF (estradiol: 15.8 +/- 8.0 ms; placebo: 15.3 +/- 9.4 ms) and HF (estradiol: 12.1 +/- 8.5 ms; placebo: 12.9 +/- 9.9 ms). Conclusion A single transdermal application of estradiol did not modify heart rate or heart rate variability of women with coronary artery disease. The modulation of the autonomic tone does not seem to be a relevant mechanism of short-term estradiol effects.     

无冠状动脉病变女性胸痛患者血流动力学改变与运动试验结果的关系及临床意义

目的探讨无冠状动脉病变女性胸痛患者血流动力学改变与运动试验结果的关系,以及心脏X综合征的可能病理生理机制。方法选取因发作性心绞痛样胸痛症状疑诊冠心病(CHD)女性患者,选择性冠状动脉造影(SCAG)检查正常,左室射血分数(LVEF)>55%的患者65例,根据次极量踏车运动试验(SBET)Bruce方案结果,分为运动试验阳性组39例与阴性组26例,对比分析两组间升主动脉脉压(PP)与脉压指数(PPI)、左心室舒张末压(LVEDP)及左心室舒张末压指数(LVEDPI)等血流动力学指标变化。结果①阳性组平均年龄及绝经患者数高于阴性组(P<0.05);但CHD危险因素两组间差异无统计学意义(P>0.05)。②升主动脉PP与PPI在两组间差异无统计学意义(P>0.05)。③阳性组LVEDP显著高于阴性组(P=0.008),而LVEDPI显著低于后者(P=0.0001)。结论SCAG正常的女性胸痛患者,PP或PPI指标并不能反映其对运动反应的冠脉血流储备,女性心脏X综合征可能与雌激素水平下降有关。此类患者LVEDP增加和LVEDPI降低可能与心内膜下心肌缺血或冠脉血流储备下降有关,指标LVEDPI较LVEDP反应可能更为敏感。