Women with chest pain risk serious complications even in absence of blockages

November 14, 2006

GAINESVILLE, Fla. — Women who have chest pain but no evidence of clogged arteries on conventional imaging tests are nonetheless four times more likely to eventually be hospitalized for heart failure, suffer a heart attack or stroke, or die than women without heart disease symptoms, University of Florida researchers report.

The findings, described at this week’s meeting of the American Heart Association’s 2006 Scientific Sessions in Chicago, stem from the National Institutes of Health-sponsored Women’s Ischemia Syndrome Evaluation and the St. James Women Take Heart study and add to a growing body of evidence that suggests while heart disease is an equal opportunity killer, it frequently manifests itself much differently in women than in men.

“There are reasons to worry,” said Rhonda Cooper-DeHoff, a research assistant professor and associate director of the clinical research program in cardiovascular medicine at UF’s College of Medicine. “The message here is you do not want to tell a woman who comes to you and says ‘I have chest pain’ not to worry. Often when women present with chest pain or atypical signs of reduced blood flow to the heart they are told it’s probably heartburn and they should go home and lie down and it’ll go away. What our data show is that although women who present with different signs and symptoms don’t always have obstructive disease, they do have increased risk compared with women who do not have these signs and symptoms.

“Also, our data suggest that these women should be aggressively treated to manage diabetes and lower cholesterol and blood pressure, and should be told to exercise and lose weight when appropriate, because having these risk factors significantly increases the risk in these women,” Cooper-DeHoff said.

The multicenter WISE study seeks to define the prevalence, extent, severity and complexity of heart disease in women and aims to identify ways to predict heart disease, which according to the American Heart Association kills nearly half a million women each year.

Researchers studied 564 women with chest pain who underwent coronary angiography to track blood flow through key arteries and were found to have no visible obstructive coronary artery disease. They compared them with 1,000 Chicago-area women of similar age and race who were free of documented heart disease and were participating in the St. James Women Take Heart Project.

Women enrolled in WISE had a four-fold increased risk of developing serious cardiac complications or dying within the study’s five-year follow-up period, independent of the influence of age, race, history of hypertension or diabetes, and other factors. Nearly 12 percent experienced problems, compared with nearly 3 percent in the Women Take Heart study.

“You can’t explain the differences (in the two study groups) by their baseline risk factors. Something else is going on that’s increasing their risk and we think it’s at the microvascular level,” Cooper-DeHoff said. “Future studies are warranted to further assess what to do with these women.”

Physicians suspect smaller arteries become glazed with plaque, triggering symptoms. But because these vessels are much tinier than the heart’s major arteries, the build-up is not detectable using standard coronary angiography. The phenomenon, coined coronary microvascular syndrome, is thought to be much more common in women than in men, and it is raising questions about how best to diagnose and treat these patients.

“Typically when men present with chest pain and typical signs and symptoms of cardiovascular disease and we take them to the (cardiac catheterization) lab they end up having some sort of obstruction in a major cardiac vessel,” Cooper-DeHoff said. “However, in these women who have similar signs and symptoms of ischemic disease, the majority do not have obstruction. And so what do you do with these women? Do you send them home and do nothing? Do you treat their risk factors more aggressively? Do you do additional testing to look for other signs or signals of disease? It’s kind of a dilemma.”

UF researchers are pursuing additional studies to find ways to better identify women at increased risk and to better understand how to treat these women to reduce future risk of adverse outcomes.

“Cardiac catheterization is fairly invasive, and what we’d like to do is determine whether other testing can be used that is more noninvasive,” Cooper-DeHoff said.

One possibility may be to test whether blood vessels inappropriately constrict when they should dilate in response to certain medications, which has been linked to poor prognosis in both men and women. In addition, UF cardiologists have been involved in the development of a new risk assessment score designed to pinpoint the likelihood a woman with early signs of heart disease will eventually experience a bad outcome such as heart attack, stroke or death. The approach — called the WISE score — appears to determine a patient’s prognosis more effectively than standard methods alone, they have reported.

The WISE score takes into account 10 factors, traditional ones such as age, smoking, diabetes and hypertension and those increasingly recognized as playing a role in heart disease development and progression. These include elevated levels of inflammatory markers and low levels of the oxygen-carrying molecule hemoglobin. Other aspects are blood vessels that malfunction in response to exercise or blood flow-regulating chemicals in the body, and the presence of metabolic syndrome, characterized by a constellation of symptoms, including obesity.

Data suggest women may have more inflammation as the underlying root of their coronary disease, one reason why the WISE score may be useful.