WEDNESDAY, Oct. 1 (HealthDay News) -- The largest observational study of hormone replacement therapy since the landmark Women's Health Initiative finds that how and when women take hormone replacement therapy affects their heart attack risk.

Younger women had a higher risk of heart attacks, especially younger women who took hormone replacement therapy (HRT) for a long time, Danish researchers found. Certain formulations also lead to different results.

"For women with an intact uterus, cyclic combined therapy (causing menstrual bleedings) should be preferred instead of continuous combined therapy (not causing menstrual bleedings)," said Dr. Ellen Lokkegaard, lead author of the study published online Oct. 1 in the European Heart Journal. "And for women without a uterus, dermal application via gel or patch is associated with a lower risk."

"The regimen and route of administration should be considered carefully when HRT is administered," concluded Lokkegaard, who is a gynecologist at the Rigshospitalet in Copenhagen, Denmark.

A section of the U.S. government-sponsored Women's Health Initiative (WHI), which was designed to look at health issues in postmenopausal women, was halted in 2002, when U.S. researchers found that HRT led to an increased risk of adverse events that included heart attack, stroke, breast cancer and blood clots. The risk depended on whether the woman was taking estrogen alone or estrogen plus progesterone, another female hormone.

Since that time, however, a more complex picture has emerged with various factors, including amount of hormone as well as timing of use, determining the exact nature of risks and benefits.

Previous research indicated that HRT might have a negative effect on cardiovascular health in women who started therapy long after menopause, versus women taking it sooner after menopause.

Before the WHI, many women took HRT in the belief that it would reduce their risk for heart disease.

These researchers looked at almost 700,000 healthy Danish women aged 51 to 69 who were followed for six years. There was no information on whether the women were postmenopausal or not, although the authors stated that most of even the younger women participating were probably postmenopausal given the age range.

Overall, there was no increased risk of a heart attack in women who were currently using HRT compared with women who had never used HRT. There was, however, a 24 percent increased risk in younger women (aged 51 to 54) and a heightened risk in younger women taking the prescribed medications for a longer period of time.

There was no correlation between long-term use of HRT in older women and an elevated heart attack risk. Nor was there an increased risk with estrogen alone.

A combination of estrogen and progesterone administered continuously resulted in a 35 percent increased risk of heart attack compared with women who had never used HRT. But estrogen taken alone, followed by estrogen plus progesterone (a cyclical regimen) actually resulted in a reduced risk of heart attack as compared to women who had never taken HRT. The same reduced risk was also seen with the synthetic hormone tibolone.

Estrogen taken via patch (on the skin) or gel (in the vagina) reduced the risk of heart attack by 38 percent and 44 percent, respectively.

"Overall biological evidence suggests the findings are plausible," Lokkegaard said. "But the finding of significant lower risk among women using vaginal estrogen was very surprising and needs to be investigated further before clinical recommendations can be given."

The results were essentially similar to those from the Women's Health Initiative.

However, one expert added a caveat.

"We have learned from observational data in the past that it is not an appropriate scientific approach to draw conclusions about the benefits or risks of hormone therapy in women," said Dr. Lori Mosca, director of preventive cardiology at New York-Presbyterian Hospital/Columbia University Medical Center and founder and director of the Columbia Center for Heart Disease Prevention in New York City. "These data are interesting, but in no way definitive," Mosca said.

More information

The National Heart, Lung, and Blood Institute has more on the original findings of the Women's Health Initiative.

WEDNESDAY, Oct. 1 (HealthDay News) -- A new statement from the American Heart Association (AHA) emphasizes the need to screen heart patients for depression.

Depressed people with heart disease have at least twice the risk of second cardiac events in the one to two years following a heart attack. And more severe depression is associated with more severe second events.

The new statement, published in the current issue of Circulation, includes the following recommendations, which are endorsed by the American Psychiatric Association:

• Early and repeated screening for depression in heart patients.
• Follow-up for both heart disease and depressive symptoms in patients who have both.
• Professional evaluation in heart patients who have depressive symptoms.
• Screening for other psychiatric disorders, such as anxiety, in heart patients who have depressive symptoms.
• Treatment options such as cognitive behavioral therapy, physical activity, cardiac rehabilitation and antidepressants.
• Screening of heart patients for depression in multiple settings, including the hospital, physician's office, clinic and cardiac rehabilitation center.
• Coordination of care between health providers.

"The statement was prompted by the growing body of evidence that shows a link between depression in cardiac patients and a poorer long-term outlook," Erika Froelicher, a professor at the University of California, San Francisco, School of Nursing and Medicine and co-chair of the writing group, said in an AHA news release.

The statement, which was the first to specifically focus on depression and heart disease, is important, since depression is a common problem in heart patients.

One study found that 15 percent to 20 percent of hospitalized heart attack patients met the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for major depression. And an even greater proportion of the patients showed more depressive symptoms than the general population, though they did not meet the diagnostic criteria for depression.

Depressed heart patients are less likely to take their medicines as directed, improve their diets, exercise, and attend cardiac rehabilitation sessions.

"There is no direct evidence yet that treating depression improves coronary heart disease outcomes, but plenty of evidence shows that having depression worsens those outcomes," said Judith H. Lichtman, co-chair of the statement and an associate professor of epidemiology at Yale University School of Medicine, said in the news release. "By understanding the prevalence of depression and learning more about the subgroups of heart patients at particular risk of depression, we can begin to understand the best ways to recognize and treat it."

More information

The National Heart, Lung, and Blood Institute has more about heart attack.

FRIDAY, Sept. 26 (HealthDay News) -- A physical exam and patient history may still be one of the most accurate and cost-effective ways of assessing patients with congestive heart failure, even though doctors have come to rely on high-tech diagnostic methods such as imaging and measuring biomarkers, a new study says.

"There has been a shift away from the use of the history and physical examination in patient care. The key objective of this study was to uncover whether the history and physical examination remains useful in the modern era," lead author Dr. Mark Drazner, medical director of the Heart Failure and Cardiac Transplantation Program at the University of Texas Southwestern Medical Center at Dallas, said in a school news release.

History and physical examinations were performed for 388 congestive heart failure patients. About half of them also underwent invasive right-heart catheterization to measure how much fluid they had in their body.

The history and physical exam-based estimates of the amount of fluid in the body compared favorably to the results of the invasive procedure. The study also found that patients estimated to have extra fluid after collection of histories and physical exams were more likely to be hospitalized or die within six months.

The findings were published in the journal Circulation: Heart Failure.

"Our study touches upon an important clinical question: If physicians were more adept at performing histories and physicals, would they rely less on more costly diagnostic tests?" Drazner said.

"Hopefully, this study might shift the pendulum back just a bit toward using the history and physical examination in patient care. It might even get trainees more interested in learning about the history and physical examinations so that this important art can be perpetuated in future generations of physicians," he added.

More information

The American Heart Association has more about heart failure  .

FRIDAY, Sept. 26 (HealthDay News) -- Preliminary results from a German study suggest that stroke patients' use of anti-anemia drugs such as Aranesp, Procrit and Epogen might end up boosting their risk for death, the U.S. Food and Drug Administration (FDA) warned on Friday.

The goal of the study was to see if high doses of the anti-anemia drug epoetin alfa could improve the ability of stroke patients to take care of themselves after recovering from a stroke.

The hope was that the drug would be neuroprotective, but use of epoetin alfa now appears linked to a near-doubling of mortality.

This is not the first time that these drugs have come under scrutiny. In the United States, medications like Procrit were marketed heavily as anemia treatments, particularly for cancer patients and those with kidney failure.

However, in July of this year, the FDA called on manufacturers of Aranesp and Procrit to add a warning label that could limit their use for cancer patients.

These changes were spurred by studies that showed these types of medications might cause tumors to spread and also raise patients' risks for bleeding. These findings resulted in an FDA advisory committee recommending in June that while the drugs should remain on the market, they should not be used in patients whose cancer is curable.

The committee also voted to recommend against the drugs' use in patients with breast or head and neck cancer.

The new German study looked at the use of epoetin alfa as an aid to stroke recovery.

"These drugs are not licensed in the United States for this particular use," noted Dr. Kathy Robie-Suh, a team leader in the division of medical imaging and hematology at the Center for Drug Evaluation and Research, part of the FDA's Office of New Drugs and Office of Drug Safety.

"The drug has been approved for about 19 years for treating anemia in patients with acute renal [kidney] failure and in other settings," Robie-Suh said. "Today's warning doesn't have any bearing on the particular label uses of the product in the United States," she said.

The FDA will continue to look into the results of this study, Robie-Suh said. "We have asked for more information about the study. We would certainly like to receive the data, but those data are not in our hands or under our control," she said.

For the trial, 522 stroke patients were randomly assigned to receive relatively high doses of epoetin alfa or a placebo. Some patients were also given R-tPA, a powerful clot-busting drug.

Three months after the start of the trial, 16 percent of the patients who received high doses of the drug epoetin alfa died, compared with 9 percent of patients who were not given the drug, according to the U.S. Food and Drug Administration (FDA).

Among the deaths in the German trial, about 50 percent occurred within the first week after the drug was started. Among those receiving the drug, 4 percent died from bleeding within the brain compared with 1 percent of the patients who were not given the drug.

The FDA said that it expects to receive more data on the study "within the next several weeks," and when the agency's analysis is complete, it will "communicate our conclusions and recommendations to the public."

Friday's FDA notice was issued after Ortho Biotech -- the division of the pharmaceutical giant Johnson and Johnson, which makes Procrit -- alerted the agency to the results of the German trial.

"Ortho Biotech has become aware of preliminary data from an investigator-initiated experimental study of the effects of Epoetin alfa in patients with acute ischemic stroke," the company said in a Sept. 17 statement. "Ortho Biotech has reported this information to the U.S. Food and Drug Administration and to European regulatory authorities. Additional analyses are under way to better understand these preliminary results."

"This study is interesting, because people were looking at potential neuroprotective effects of erythropoiesis-stimulating agents (ESAs)," said Dr. Samuel M. Silver, a spokesman for the American Society of Hematology.

These patients were not anemic, Silver noted. "They were also receiving very powerful clot-busting drugs at the same time as relatively high doses of ESAs. These are not the typical patients in any way shape or form that usually receive these drugs," he said.

Silver doesn't think further action by the FDA is needed. "I don't think the drug needs to be looked at for patients who are currently being treated in this country, but it certainly will give pause to the way studies are being designed to look at the neuroprotective effects of these drugs," he said.

More information

For more information on ESA's, visit the U.S. Food and Drug Administration.