Angiography, the gold standard for detecting blocked arteries, does not work in about one in every six women with chest pain, leading doctors to send many sick women home with a clean bill of health, researchers reported Tuesday.
Although high cholesterol levels in men generally lead to the buildup of obstructions that can be seen in the X-ray images of an angiogram, the same conditions in women lead to a general narrowing of the arteries that does not show up, leading physicians to believe that the vessels are clear.
The results appear in a series of papers to be published in a supplement to the Feb. 7 issue of the Journal of the American College of Cardiology.
Most previous studies of heart disease have been conducted in men, said Dr. C. Noel Bairey Merz of Cedars-Sinai Medical Center in Los Angeles, who led the study, "so we weren't aware of the magnitude of the problem."
She added: "One of the biggest take-home messages from this study is that we must stop falsely reassuring women when their arteries are open."
The findings represent "a shift in the paradigm" for diagnosing heart disease, said Dr. George Sopko of the National Heart, Lung and Blood Institute at the National Institutes of Health. "We have to stop thinking that if there is no significant blockage, you are OK."
The number of cases of the newly recognized disorder, called coronary microvascular syndrome, accounts for about 15% of all coronary artery disease in women, Bairey Merz said.
Overall, about 480,000 American women die of heart disease each year, the American Heart Assn. says. Failure to recognize the microvascular syndrome in women may be one reason that 60,000 more women than men die of heart disease each year.
The new findings come from the Women's Ischemia Syndrome Evaluation, an eight-year study tracking nearly 1,000 women in Florida, Pennsylvania and Alabama who had chest pains and other cardiovascular symptoms but showed no evidence of a blockage by angiography.
Ischemia is an inadequate flow of blood to the heart, restricting the amount of oxygen that can be used by the organ for pumping blood. It is characterized by chest and, sometimes, arm pains during periods of physical or psychological stress.
The team found that half the women in the study were not getting enough blood to their hearts and that a third were likely to have a heart attack or some other serious problem -- more than three times the normal risk.
In men, and in the majority of women, high cholesterol levels in the blood can lead to the formation of localized buildups of plaque that impede blood flow.
Such buildups can be readily seen on an angiogram, which is performed by inserting a catheter through an artery in the groin and threading it up to the heart, where it is used to inject a dye that shows the blockage in an X-ray. The blockage is often immediately cleared by compressing it into the side of the artery, a procedure called balloon angioplasty.
But in some women, and a much smaller percentage of men, the cholesterol is deposited much more evenly, coating the entire interior of the vessel with no obvious lumps or protrusions. It is similarly deposited on the interior of smaller blood vessels -- microvasculature -- diffusing blood into heart muscles.
The layer of new fat narrows the vessels, restricting blood flow, but is generally not seen by physicians who do not know to look for it.
But it can be detected with alternative techniques, the study found. Nuclear SPECT (single-photon emission compute tomography) tests, for example, identify about a third of the victims. A better test is the so-called provocative coronary testing, a stress test in which an adenosine injection mimics the effects of exercising on a treadmill. This is a much more effective test than the treadmill test itself, Bairey Merz said. Neither test has been routinely administered in the past.
Once coronary microvascular syndrome is detected, it is generally treated with drugs such as beta blockers and ACE inhibitors to lower blood pressure and statins to lower cholesterol levels and the dietary supplement L-arginine, which is a modest vessel dilator.
But the recognition of the syndrome is so recent, Bairey Merz said, that "we haven't had time to do trials of the treatments. We need more data."
Researchers are not sure why the cholesterol deposition pattern is so different in the women of the Women's Ischemia Syndrome Evaluation study.
Dr. Carl J. Pepine of the University of Florida College of Medicine speculates that women's bodies remodel the arteries to incorporate the cholesterol, narrowing the arteries. Such remodeling is common to increase blood supply during pregnancy.
Estrogen also clearly plays a role because it helps in the regulation of nitric oxide, which controls blood vessel dilation. Higher than normal levels before menopause, for example, might smooth the deposition of cholesterol.
In light of the study results, cardiologists should be more reluctant to dismiss the concerns of women with chest pains and no apparent blockages and more willing to order additional tests, said Dr. Elizabeth G. Nabel, director of the National Heart, Lung and Blood Institute.
"We must think outside the box when it comes to the evaluation and diagnosis of heart disease in women," Nabel said.