Hormone replacement therapy and associated risk of stroke in postmenopausal women

BACKGROUND: There is little information about the risk of stroke in relation to time since initiation of hormone therapy and in relation to estrogen dose. METHODS: We conducted a population-based case-control study at Group Health Cooperative (GHC), a health maintenance organization in the greater Seattle (Wash) area, to assess the association of hormone replacement therapy with the risks of incident ischemic and hemorrhagic stroke. Cases were all postmenopausal women with incident stroke at GHC during July 1989 through December 1998 (726 ischemic strokes and 213 hemorrhagic strokes). Controls were randomly selected from GHC enrollees and frequency matched to cases on age and calendar year (n = 2525). Hormone use was assessed from computerized pharmacy data. We reviewed the medical record to confirm eligibility and assess other risk factors. RESULTS: After risk factor adjustment, ischemic stroke was not associated with current use of estrogen with progestin (odds ratio [95% confidence interval]: 0.97 [0.69-1.37]) or without (0.94 [0.72-1.23]) compared with never use. Similarly, hemorrhagic stroke was not associated with current use of estrogen with progestin (0.74 [0.43-1.28]) or without (1.06 [0.71-1.56]). However, the risks of ischemic stroke and hemorrhagic stroke were increased 2-fold during the first 6 months of hormone use (ischemic stroke: 2.16 [1.04-4.49], hemorrhagic stroke: 2.20 [0.83-5.81]). Risk of ischemic stroke also increased with estrogen dose (P for trend =.03). CONCLUSION: The transitory increase in risks of ischemic stroke and hemorrhagic stroke associated with initiation of hormone replacement therapy merits further investigation.     

Medical therapy after acute myocardial infarction.

Several therapeutic agents have been tested for secondary prevention after acute myocardial infarction. Each patient presents a clinical challenge and gives the physician an opportunity to use the tests and therapy most likely to benefit the clinical course. The presence of other associated medical conditions, the type of myocardial infarction, the presence or absence of accompanying ischemia, left ventricular dysfunction, intracardiac thrombus, or ventricular arrhythmias dictate the choices that are to be made. It is apparent from this review that no single class of agents can be considered a cure, although beta-adrenergic blocking agents come the closest to this role. Analysis of these drugs helps individualize drug therapy and provides a physiologic probe to understanding the pathophysiologic processes that characterize the period after myocardial infarction. To address the impact of developing technology and drug availability on the practice and cost of medical care, the American College of Cardiology and the American Heart Association have developed guidelines for the management of patients with myocardial infarction. The clinical trial remains the best test for the assessment of therapeutic choices and can also expand our knowledge of the natural history of the disease process. Nevertheless, the issue of appropriate therapy is ever-changing, affected by the explosion of new technology and the continued investigation into the pathophysiology of coronary artery disease.     

Hormone replacement therapy in postmenopausal women

From the endocrine point of view, menopause is considered a deficiency state and menopausal hormone replacement therapy (HRT) regarded as restoring the premenopausal endocrine milieu. Millions of healthy postmenopausal women were taking HRT in late 1990's many in the absence of menopausal symptoms. The major benefit from HRT was considered to be cardiovascular protection and also protection against osteoporosis and Alzheimer's Disease. The Women's Health Initiative (WHI) trial and other studies published since 2002 fundamentally changed our understanding of risks and benefits associated with HRT. This review discusses the effects of HRT on menopausal symptoms, cognitive function, cardiovascular disease, osteoporosis and also breast and bowel cancer.     

Anticoagulant therapy after acute myocardial infarction

The use of anticoagulant therapy for patients who have had an acute myocardial infarction is still controversial, mainly because early major studies had conflicting findings, but reanalysis of the data did produce evidence that anticoagulation had clinically and statistically significant benefits. Now more evidence, including the results of a 10-day in-hospital study of low- and high-dose calcium heparin, has been gathered to support using anticoagulants for these patients. The study used the development of left ventricular mural thrombosis, a frequent complication of acute myocardial infarction that carries a high risk for systemic embolic complications, to assess clinical outcome: A reduced incidence of mural thrombosis would be taken to indicate reduced chances that patients would have major systemic emboli. Two-dimensional echocardiography was used to detect thrombi. In the study, the incidence of left ventricular mural thrombosis was significantly lower in the high--than in the low-dose group. Among patients in the high-dose group in whom a mural thrombosis did develop, plasma heparin concentrations were significantly lower and activated partial thromboplastin times were shorter. These data suggest that monitoring plasma heparin levels and anticoagulant response can ensure maximal treatment effectiveness. No significant differences in other outcomes--such as bleeding complications, nonhemorrhagic strokes and mortality--were found between the high- and low-dose treatment groups.     

Adjunctive therapy after reperfusion therapy in acute myocardial infarction

The current era has witnessed dramatic improvement in the treatment of acute myocardial infarction, due in large part to the more widespread use of thrombolytic therapy aimed at quickly restoring perfusion in the infarct-related artery. This review addresses the role of adjunctive pharmacologic therapy in the thrombolytic era, recognizing that much of the available clinical trial data supporting the role of adjunctive pharmacologic treatment strategies was conducted in patient populations not widely exposed to reperfusion therapy. This review, therefore, explores the data supporting the incremental benefit of therapy with beta blockers, nitrates, angiotensin-converting enzyme inhibitors, or magnesium in addition to thrombolytic therapy. Heparin and aspirin will not be discussed.     

Fibrinolytic therapy in young women with acute myocardial infarction

STUDY OBJECTIVE: Previous studies found that women with acute myocardial infarction (AMI) receive less aggressive therapy compared with men. We sought to determine the percentage of young women (12 hours after symptom onset) were the most common reasons for ineligibility.     

Obesity and the risk of death after acute myocardial infarction

Background

In the general population, obesity is associated with an increased risk of all-cause death. However, the importance of obesity in patients with established coronary heart disease is less well defined.

Methods

As part of the Determinants of Myocardial Infarction Onset Study, we performed a prospective cohort study of 1898 patients hospitalized with confirmed acute myocardial infarction between 1989 and 1994, with a median follow-up of 3.8 years. We assessed all-cause death through December 1995, using the National Death Index. We categorized patients according to WHO criteria for body mass index (BMI). We compared long-term death according to BMI (kg/m²) by using Cox proportional hazards regression.

Results

Of the 1898 eligible patients, 607 (32%) were normal weight (18.5 to 24.9 kg/m²), 832 (44%) were overweight (25.0 to 29.9 kg/m²), 331 (17%) were class I obese (30.0 to 34.9 kg/m²), and 128 (7%) were class II or more obese (≥35.0 kg/m²). A total of 311 patients died during follow-up. After adjustment for potentially confounding risk factors and excluding patients with noncardiac comorbidity, the risk for death appeared to increase linearly, with increasing BMI across all categories (P for trend = .08). The relative risk of death in all obese patients (≥30 kg/m²) was 1.46, compared with those with normal weight (95% CI, 0.98 to 2.17).

Conclusions

We found that BMI appeared to have a positive, graded relation with post-myocardial infarction death. Whether weight reduction and secondary prevention strategies would reverse this effect in obese population remains to be seen.     

Outcomes of thrombolytic therapy for acute myocardial infarction in women

Coronary artery disease is the leading cause of mortality in women older than 50 years of age. Thrombolytic therapy substantially reduces mortality in both women and men with ST-elevation acute myocardial infarction. However, the mortality risk reduction is somewhat lower in women, in spite of similar rates of successful coronary reperfusion after thrombolytic therapy in women and men. Hemorrhagic complications including stroke and other major bleeding appear to be more common in women, particularly elderly women. The risk of reinfarction after thrombolytic therapy also is greater in women compared with men. Because of the higher complication rates, women should be monitored closely after thrombolytic therapy. However, this lifesaving treatment should not be withheld or delayed in women when indicated.     

Noninvasive risk stratification in women with uncomplicated acute myocardial infarction

The aim of our study was to compare the prognostic value of stress echocardiography and exercise electrocardiography after uncomplicated non-Q-wave acute myocardial infarction in a series of 89 female patients. Our data show that stress echocardiography has independent predictive value in a female patient population recovering from uncomplicated acute myocardial infarction.     

Hormone replacement therapy and ischaemic heart disease among postmenopausal women.

The beneficial effect of hormone replacement treatment (HRT) on osteoporosis and menopausal symptoms has been well documented in randomised trials, but the impact of oestrogen-mediated metabolic changes on the risk of ischaemic heart disease (IHD) is still debated. Randomised studies have shown that HRT increases levels of high-density lipoprotein cholesterol while causing a reduction in the levels of low-density lipoprotein cholesterol, serum fibrinogen, plasminogen activator inhibitor and homocysteine. In addition, HRT increases insulin sensitivity in both normoglycaemic and diabetic women. Unlike oral contraceptives, HRT has not been associated with an increase in arterial blood pressure, whereas a small increase in the risk of breast cancer and of venous thromboembolism appears to occur with both treatments. Interestingly, some data suggest that oestrogen preparations may have different effects on lipids. For instance, the beneficial effect on cholesterol metabolism observed with oral conjugated oestrogen does not occur with transdermal oestradiol, suggesting that the first-pass effect through the portal circulation may be necessary to achieve the full metabolic effect of oestrogen treatment. Nevertheless, although a wealth of observational studies show that HRT is associated with a significant reduction in morbidity and mortality from IHD, the only randomised data available to date do not support these findings in postmenopausal women with established coronary artery disease.