GAINESVILLE---Early findings from a national study of women with chest pain suggest that many are being declared free of heart disease when they actually have minor blockages developing in their coronary arteries, University of Florida and Brown University researchers say.
Furthermore, while the overall risk was small, these women were almost twice as likely as those whose arteries were truly healthy to be hospitalized with recurrent chest pain, heart attack, heart failure or stroke in the two years following their initial evaluation.
The findings underscore the difficulties doctors face in determining which women have heart disease, and in those who do, what their prognosis is.
"The problem of how to evaluate women with chest discomfort is tremendous," said Dr. Richard Kerensky, director of interventional cardiology at UF. "The best way to assess these patients is currently not known. There are many questions to be answered."
Of 322 women evaluated recently as part of the National Institutes of Health-sponsored Women's Ischemia Syndrome Evaluation (WISE) study, nearly one-fourth whose coronary arteries traditionally would be considered "normal" in fact had minimal heart disease that might have contributed to their symptoms, Kerensky said.
Doctors were able to identify minor blockages in their arteries using coronary angiography, which enables them to view vessels on X-ray films. The angiograms were reviewed at a central core laboratory, where physicians used sophisticated electronic calipers or computer- based techniques to actually measure arteries to detect small differences in vessel size suggestive of minor blockages, said Dr. Barry L. Sharaf. An associate professor of medicine at Brown
University's School of Medicine and director of the WISE study's Coronary Angiography Core Laboratory, Sharaf presented the pilot data Nov. 8 at the American Heart Association's annual meeting in Atlanta.
In contrast, many cardiologists follow common practice and visually inspect the films for signs of atherosclerosis. But narrowings of the arteries can be subtle, and some coronary angiograms interpreted as normal may not be, Kerensky said.
Previously, only blockages that appeared severe on angiograms were thought to limit blood flow. But more recently it has been recognized that blockages that appear less severe are those most often responsible for heart attacks and also may be associated with abnormalities of the heart's microvasculature vessels too small to be seen by angiography.
In addition, nearly half the study participants had heart disease that was fairly advanced, suggesting they were identified relatively late in the progression of their disease. They were at greatest risk of a poor outcome.
Of all patients who visit a doctor for chest pain, women are much more likely than men to have "normal" coronary arteries and yet still have symptoms and/or abnormal stress tests that suggest heart disease or reduced blood flow to the heart, Sharaf said.
"It's unclear whether these women have the wrong diagnosis, whether their chest pain and other findings are from something else or whether there is more to the 'normal' coronary angiogram," Sharaf said. "What we found when we looked hard at many of these angiograms from women with so-called normal coronary arteries is that in many cases there is some detectable or measurable coronary disease. It may not be severe, but we can see these arteries are not really normal."
Researchers have only recently begun to debate the effects of gender, age, hormones and other factors on heart disease. In fact, for years it was not recognized that heart disease was a major cause of death in women, who have been notoriously understudied in clinical trials of the condition.
The multicenter trial, sponsored by the National Heart, Lung, and Blood Institute, is evaluating more than 900 women with chest pain who are 18 to 75 years old in an effort to define the prevalence, extent, severity and complexity of heart disease in women. It also seeks to identify ways of predicting heart disease and is correlating findings from angiograms with patient outcome.
In the pilot phase, only 34 percent of those studied had no detectable blockage. The data highlight the need for improved non-invasive ways of screening women for reduced blood flow to the heart so that they don't undergo invasive tests needlessly, said Kerensky, an associate professor of medicine at UF's College of Medicine. In comparison to the exercise stress test, angiography is an invasive test that involves inserting a thin, flexible plastic tube into an artery in the groin, then threading it up to the heart. Doctors inject a contrast dye into the blood, which allows them to detect arterial blockages on X-ray films.
"This study shows that if you look at a lot of women with chest pain, a high percentage of them will not have obvious high-grade obstructions in their arteries, a simple explanation for the chest pain," Kerensky said. "It's been conventional wisdom that women have a lot of false positives on non-invasive tests, but it might not be that simple. Just because the angiogram didn't show blockages in many of these women doesn't mean that their chest pain is not caused by reduced blood flow to the heart, too."
While the angiogram has been the "gold standard" for evaluating chest pain, Kerensky said, researchers plan to evaluate other ways of assessing the health of coronary arteries, using new tests to identify abnormalities that occur before obstructions form.
The next step is to see whether the findings hold true for the entire study group, Sharaf said.
"In addition, we will continue to follow these women to see what happens over time," he said. "Overall, these are a fairly stable population of women and we would expect relatively few serious events such as heart attack or death, but we will follow them longer to detect true differences between those with normal, minimal or significant disease."