New Test May Provide Answers For Women With Chest Pain

Women often seek medical help for chest pain, sometimes undergoing coronary angiography. But in almost half of all such women, there is no coronary artery disease. Now scientists suggest that blockages in the smaller, slender arteries that feed the heart muscle-blockages that cannot be spotted on standard tests-might be at fault.

"We have seen that many of these women are admitted to the hospital for chest pain, and undergo angiography to look for coronary artery disease behind the angina, yet no such disease is found," says Gerald M. Pohost, M.D., chief of the division of cardiovascular medicine at the Keck School of Medicine of the University of Southern California and corresponding and senior author on the study. "Our results indicate that in many of these women, something is keeping the heart from getting the oxygen it needs. We suspect microvascular dysfunction or disease."

Coronary artery disease, or CAD, claims more lives in the United States, Europe and other developed regions than any other disease. Prompted by symptoms such as chest pain, or angina, more than a half million U.S. women underwent coronary angiography to look for CAD in 2001. Yet nearly half of women with chest pain who undergo coronary angiography are found to have no significant CAD, posing a puzzle for physicians.

CAD is a disease of the arteries that supply blood to the heart muscle. Over time, as fatty materials collect in the vessels that supply the heart, the artery walls thicken and narrow the space where blood can flow, depriving heart tissue of oxygen.

The study was a part of the Women's Ischemia Syndrome Evaluation, or WISE, study. WISE is a four-center study of women undergoing coronary angiography for chest pain or suspected myocardial ischemia.

The researchers compared 352 women with CAD to 74 other women without it. These CAD-free women underwent an imaging scan called phosphorus-31 nuclear magnetic resonance spectroscopy, which is done completely from outside the body.

The technique simply required that women squeeze a handgrip while lying inside an MRI unit. Nuclear magnetic resonance spectroscopy technology enabled scientists to measure levels of two phosphates found in heart tissue, once while women were at rest and again while they were squeezing the handgrip (experiencing physical stress). Investigators then compared the before-and-after levels of the two phosphates.

Researchers saw that the ratio of the two phosphates, phosphocreatine and ATP- called high-energy phosphates, since they supply the energy source for heart contraction-declined significantly in 14 of the 74 CAD-free women when they squeezed the handgrip. A big drop in the ratio is abnormal and a sign that heart tissue is not getting enough blood, Pohost explains.

Investigators wanted to see whether the abnormal results were linked to women's cardiovascular health. Over the next three years, they tracked how many of the women experienced a cardiovascular event such as a heart attack, stroke or hospitalization for a blood clot or unstable angina.

They found that 87 percent of the CAD-free women with normal magnetic resonance spectroscopy results stayed free of cardiovascular events. But 57 percent of the CAD-free women with abnormal magnetic resonance spectroscopy results had no events. That is not much better than the women who had been diagnosed with CAD: 52 percent of them avoided cardiovascular events during that time period.

Most of the events were hospitalizations due to unstable angina, and many of the women with abnormal magnetic resonance spectroscopy results experienced repeated, fruitless angiography procedures to find the cause of the angina during the three-year follow-up. Health care for CAD-free women with abnormal results cost more than twice that of the other CAD-free women over the three years.

In the clinic, Pohost and fellow cardiologists use standard angina therapies to treat chest pain in these CAD-free women, he says. The study suggests that magnetic resonance spectroscopy could be widely used to evaluate women complaining of chest pain, and even may reduce the number of women undergoing repeated coronary angiography procedures.

Nuclear magnetic resonance spectroscopy is available only at a few select institutes and academic medical centers, such as USC University Hospital.

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WISE is supported by the National Heart, Lung, and Blood Institute.

B. Delia Johnson, Leslee J. Shaw, Steven D. Buchthal, C. Noel Bairey Merz, Hee-Won Kim, Katherine N. Scott, Mark Doyle, Marian B. Olson, Carl J. Pepine, Jan den Hollander, Barry Sharaf, William J. Rogers, Sunil Mankad, John R. Forder, Sheryl F. Kelsey, Gerald M. Pohost. "Prognosis in Women with Myocardial Ischemia in the Absence of Obstructive Coronary Disease," Circulation. Vol. 109, No. 154, June 22, 2004.