"On average, these women are probably told their symptoms are not coming from their heart," because their large arteries appear clear, says Bairey Merz.

That may mean lead to misdiagnosis and patients being sent home with no treatment, says Dr. Martha Gulati, associate director of the Center for Women's Cardiovascular Health at Northwestern Memorial Hospital in Chicago.

"We need to give a different message. I'd say to women and their doctors, ‘Don't stop there,' " she says, but instead look for signs of microvessel disease as well. Tests for microvessel disease do exist at some research hospitals, but they are not standard clinical practice.

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At Mayo, Lerman does what he calls a "functional angiogram" — in addition to a traditional angiogram — to measure whether the microvessels are responding to stress appropriately in men and women. The test starts the same as the imaging angiogram, with a catheterization, but then the doctor gives a drug that raises the heartbeat to simulate stress. Next, a Doppler radar probe measures the change in the speed of the blood flowing to the heart.

At Cedars-Sinai, Bairey Merz tests patients similarly using cardiac magnetic resonance imaging (MRI) to visualize changes in blood flow to the inner heart.

Neither diagnostic test is considered standard protocol, and each is being evaluated for how effectively it detects microvessel disease.

Lerman says that among patients he's studied who have no signs of blocked large arteries but who have microvessel disease, 30% to 40% are men.

Some get no therapy

Currently, says Bairey Merz, too many patients who most likely have microvessel disease "are not put on the lifesaving therapies that help with ischemia," such as low-dose aspirin and other drugs known to help improve blood flow in the heart.

She and other cardiologists who study microvessel disease think that these patients should be offered the same drug treatments used for coronary artery blockages until more specific treatments are developed for this problem. The drugs used to treat blockages include statins to lower so-called bad, or LDL, cholesterol and prevent more plaque buildup and medicines such as aspirin, ACE inhibitors, beta blockers and nitroglycerin to improve blood flow around the blockages.

If blockages are severe, they may also be treated with interventions such as a balloon angioplasty to open up a blockage, a wire mesh stent to hold a blockage open or bypass surgery to create a new route for the blood to take.

Many questions remain about this different form of heart disease. Key among them: What causes the small vessels to react improperly? And what is the best way to treat it? Answering these questions will be expensive; not doing so will be even more expensive, Bairey Merz says. Not only would too many human lives be lost to missed heart disease, but the costs would add up in terms of repeat hospital and doctors visits and repeat angiograms of patients whose symptoms persist.

Bairey Merz and her collaborators are testing drugs that lower blood pressure and cause vessels to open up in women with microvessel disease. She and Lerman are also investigating Viagra-like drugs, which also cause vessels to dilate.

Why men appear to be more susceptible to coronary artery disease and why women appear to fall prey more often to microvessel disease also remains a mystery. Some researchers believe it could be related to hormonal differences or to the fact that women are more prone to chronic inflammation.

Regardless, some cardiologists are reluctant to classify women and men as suffering from different types of heart disease. "The danger of reclassifying the condition for women is that one would tend to forget or discount the fact that a great deal of [heart disease] in women is very similar if not identical to men," says Dr. Marian Limacher, a cardiologist at that University of Florida in Gainesville.

She's cautious because it's unclear whether microvessel problems are a spectrum of the same disease that leads to coronary artery blockages or represents another disorder altogether. Any physician evaluating a patient with cardiac symptoms should first rule out traditional coronary obstruction, which would benefit from proven treatments, she says.

Even symptoms do not fall along clear gender lines, she notes, with atypical symptoms increasing with age for men and women. "Symptoms span a spectrum for both men and women. The real message is that anytime your body is telling you something is wrong, pay attention to it."