Heart Disease Differs in Women

"I was one of the lucky ones. I escaped an actual heart attack," said Kathy Kastan, 41, of her initially misdiagnosed heart disease. (Troy Glasgow For The Washington Post)

"In general, people think these ladies are crazy. They are not infrequently told they are nuts," Bairey Merz said. They often are sent to stomach specialists or for psychotherapy and end up in a maddening hunt for the source of their ills until finally, weeks, months or years later, they are in an emergency room with a heart attack.

The WISE study found that in nearly half of these women, their hearts are not getting enough blood, and one-third are likely to go on to have a heart attack or other serious heart problems -- three times the usual risk.

"Women appear more likely to more diffusely lay out their plaque throughout the wall of the artery, whereas men are more likely to lay it down a lumpy-bumpy pattern," Bairey Merz said. "This could explain the delayed diagnoses, the missed diagnoses, the never diagnoses."

The reason for this difference is unclear, but it may be a result of women's unique hormonal chemistry and differences in how women's arteries respond to stress.

"What we believe is that women's bodies remodel their arteries to accommodate the . . . plaque," Pepine said. "If you think about the whole female picture, they are designed to do that. They remodel their arteries to accommodate blood flow when they are pregnant."

Detailed studies of the arteries of women who died of heart attacks have found that the disease often looks much different in women in another way.

"In men, it's like a sore, like a pimple, that breaks and leads to the formation of a blood clot, that causes a heart attack," said Renu Vermani of the Armed Forces Institute of Pathology in Washington. "In women, we don't see this pimple. We see erosion. It's a malformation -- like a scab, like a scar."

Vermani speculates that when arteries spasm, the innermost lining, called the endothelium, momentarily rubs against itself. "Over time, that causes it to erode," he said. "The endothelium is disturbed, it's eroded, which leads to clot formation."

Doctors have long known that women are prone to blood vessel spasms and the ailments they cause, such as migraine headaches. When it happens to an artery feeding the heart, it produces pain or, in severe instances, a heart attack.

"It's like putting a rubber band around the artery: It narrows so that you can't get enough blood to supply the muscle to keep it viable," said Marianne J. Legato, a women's health expert at Columbia University.

The same bad actors that cause better-known forms of heart disease -- high cholesterol, high blood pressure, smoking, obesity -- may also damage the endothelium, making arteries prone to spasms or to diffuse plaques that diminish their ability to dilate properly. But there may be other factors that are particularly dangerous for women.

Because estrogen plays a role in processing nitric oxide, which helps arteries function properly, the endothelium may suffer when estrogen levels wane due to menopause. Another key player may be inflammation -- an overreaction by the immune system.

"Let's say you have somewhat high cholesterol and just slightly high blood pressure. The likelihood would be that you should have a low risk," Sopko said. "However, if you take some of these novel risk factors, like inflammation, it is possible that they act as amplifiers . . . that are gender-specific or gender-related."

Some researchers suspect that the crucial oxygen-carrying protein in blood, hemoglobin, may also be important. Women tend to have less hemoglobin than men because of their monthly menstrual cycles, and low hemoglobin may further starve the heart muscle. Hemoglobin deficits may also reduce nitric oxide levels.