In This Week’s Circulation: Microcirculatory Function in Postmenopausal Women and the Effect of Long-Term and Short-Term Estrogen Administration
In this week’s issue of Circulation, researchers from the Departments of Molecular and Medical Pharmacology and Obstetrics and Gynecology at the University of California at Los Angeles describe measurements of myocardial blood flow with the positron emission tomography scanner in 54 postmenopausal women without coronary artery disease (CAD). Of these, 31 were on long-term hormone replacement therapy (HRT) and 23 were not (Circulation. 2002;105:425–430).
In their study, which measured myocardial blood flow during cold pressor testing and during dipyridamole, the researchers compared the results to those of 12 young, healthy premenopausal women. In the women not on HRT, measurements were repeated after they received 25 mg of conjugated equine estrogens intravenously.
The researchers, led by Heinrich R. Schelbert, MD, PhD, determined that menopause is associated with an abnormal cold pressor test as an indirect measure of endothelial function. The abnormal test can be reversed by long-term HRT, but only when the women have no other risk factors for cardiovascular disease, according to the researchers. They said their results indicate that “Estrogen administration may therefore be effective in primary prevention of CAD in premenopausal women without RFs [risk factors] for CAD.”
They continued, “These findings are in line with epidemiological studies where HRT reduced the risk of cardiovascular morbidity in postmenopausal women without RF when compared with those with documented CAD and suggests that estrogen replacement therapy, along with a progestin, may be useful for primary prevention of CAD in women without RF for CAD. Further studies are in progress to assess whether estrogens are beneficial after treatment of RF in women without clinical CAD.”
The role of hormone replacement therapy in cardiovascular disease prevention has been under scrutiny since the large-scale Heart and Estrogen Replacement Study (HERS) found no benefit of HRT among women with heart disease. (JAMA. 1998:280:605–613).
In September, the American Heart Association released a scientific advisory stating that HRT should not be initiated for the secondary prevention of cardiovascular disease in women already affected by it. The decision to continue or stop HRT in such women should be based on established noncoronary benefits and risks and on patient preference. If the woman develops a heart attack or stroke or other acute cardiovascular event while on HRT, “it is prudent to consider discontinuance of HRT or to consider anticoagulant prophylaxis while she is hospitalized to minimize the risk of blood clots associated with immobilization. Reinstitution of HRT should be based on established noncoronary benefits and risks, as well as patient preference.”
The value of HRT as primary prevention in women who do not have cardiovascular disease can only be determined after the conclusion of ongoing randomized, clinical trials, the AHA concluded. There currently is insufficient data to suggest initiating HRT for the sole purpose of primary prevention of cardiovascular disease (Circulation. 2001;104:1577–1579).
Aspirin Gets a Tentative Nod
A meta-analysis of studies of the effectiveness of aspirin in protecting healthy patients from heart attacks gave the nod to frank discussions between patients and physicians about the benefits and risks of the medication as primary prevention in patients with increased risks of cardiovascular problems (Ann Intern Med. 2002;136:161–172).
The study, conducted by researchers from the University of North Carolina at Chapel Hill, the Air Force Medical Operations Agency, and The University of Texas Health Science Center at San Antonio, for the US Preventive Services Task Force, looked at studies of more than a year’s duration that evaluated the use of aspirin to prevent heart attacks in previously healthy patients, as well as systematic reviews, recent trials, and observational studies examining rates of hemorrhagic strokes and gastrointestinal bleeding secondary to aspirin use.
The researchers’ analysis of the studies showed that aspirin reduced the risk of nonfatal and fatal coronary heart disease. It also showed that the medication increased the risk of hemorrhagic strokes and major gastrointestinal bleeding, although all-cause mortality was not significantly affected.
For every 1000 patients who have a 5% risk of developing coronary heart disease within 5 years, aspirin would prevent as few as 6 and as many as 20 heart attacks. In the same population, it would cause as many as 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events, according to the researchers’ analysis. When the risk of coronary heart disease drops to 1%, aspirin would prevent as few as 1 and as many as 4 heart attacks while causing as many as 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeds. In other words, the risks and benefits of aspirin differ with the class of risks patients face, or as the researchers put it, “The net benefit of aspirin increases with increasing cardiovascular risk.” When physicians and patients discuss using aspirin as primary prevention, they have to take into account the various possible outcomes in making the decision.
“It’s been pretty well recognized that aspirin is helpful to people who have had heart attacks or strokes by preventing or delaying future cardiovascular events like these,” said study leader Michael Pignone, MD, Assistant Professor of Medicine at the UNC School of Medicine. “What has been unclear, however, was whether this was true for people who hadn’t had heart problems, and now we think we know.” Dr Pignone said that the meta-analysis determined that “aspirin is probably beneficial for people who have a 3% or greater risk of suffering a heart attack over the next 5 years.”
Fortification of Food With Vitamin B12 in Addition to Folic Acid Might Reduce Cardiovascular Disease Risk
Researchers from Trinity College in Dublin, Ireland, and Ulster University at Coleraine, Northern Ireland, recommended that vitamin B12, along with folic acid, should be used to fortify food in order to reduce the concentrations of blood protein homocysteine, thereby reducing the risk of cardiovascular disease (Lancet. 2002;359:227–228).
When fortification of grain foods with folic acid was mandated in the United States in 1998, a 19% reduction in neural-tube defects resulted, said the researchers. A similar mandate is being considered in the United Kingdom, they said.
In a study led by Joe McPartlin, PhD, from Trinity College along with others at Ulster University, 30 men and 23 women received sequential supplementation with increasing doses of folic acid. They found that after the supplementation, the usual dependency of homocysteine on folic acid diminished and vitamin B12 became the main determinant of plasma-homocysteine concentration.
“The finding suggests that a fortification policy based on folic acid and vitamin B12, rather than folic acid alone, is likely to be much more effective in lowering homocysteine concentration, with potential benefits for reduction of the risk of cardiovascular disease,” said Dr McPartlin.