Say what you will about Mars and Venus, but anatomically, male and female hearts look the same. When healthy, both should be about the size of a fist. Both have three main coronary arteries, the large blood vessels that wrap around the outside of the heart, supplying blood, oxygen and nutrients to keep each one pumping properly.

But when heart disease sets in, researchers are learning, gender can dictate major differences in how it actually develops and the parts of the heart it affects. These differences have implications for how heart disease is diagnosed — and treated. They may also change how doctors predict who is at risk for the most catastrophic of cardiac events, sudden cardiac arrest (see related story).

As is true with most gender differences, however, the issue is not as clear cut as XX versus XY, and cardiologists warn that heart disease can't be divided into male and female forms.

 

Men and women can have coronary artery disease in which those main, large arteries are plugged up by fatty, athlerosclerotic plaques. These blockages greatly increase the risk of a heart attack, sudden cardiac arrest, stroke and heart failure. But far fewer women show up with this "classic" form of heart disease.

"When it comes to acute heart attacks and sudden death [from cardiac arrest], women have these kinds of events much more often without any obstructions in their coronary arteries," says Dr. Amir Lerman, a cardiologist at the Mayo Clinic in Rochester, Minn.

Instead, it appears that a significant portion of women suffer from another form of heart disease altogether, one that affects not the superhighway coronary arteries but rather the smaller arteries, called microvessels, that deliver blood directly to the heart muscle tissue. What researchers are learning about this new form of heart disease may explain why some patients experience different heart-related symptoms and why women, as a group, have higher mortality and poorer outcomes from the suite of disorders that make up cardiovascular disease.

Cardiovascular disease kills more Americans, men and women, of all ethnicities than any other cause. Each year since 1984, more women (432,709 in 2006) have died of cardiovascular disease -- which includes not just heart disease and heart attacks but also stroke and heart failure -- than men (398,563 in 2006). But more men experience and die of coronary heart disease and heart attacks than do women each year. Men develop heart disease on average 10 years earlier than women. But women who have a heart attack seem to fare worse right after the event and also suffer a poorer quality of life.

Figuring out what underlies these gender differences has become a priority among cardiology researchers. If they succeed, doctors could predict, diagnose and treat all varieties of heart disease more effectively.

"Men and women today smoke the same, are equally obese, have the same levels of physical activity and stress, and they eat pretty much the same," says Dr. C. Noel Bairey Merz, director of the Women's Heart Center at the Cedars-Sinai Heart Institute in Los Angeles. "It doesn't look like there are gender differences in the traditional risk factor pathways." (Translation: Prevention efforts are the same for men and women.)

But Bairey Merz and other researchers around the country have found that while men predominantly suffer from coronary artery disease, women predominantly suffer from what she proposes calling ischemic heart disease. In this form, also referred to as microvessel disease or microvascular dysfunction, the smaller arteries of the heart do not function properly.

Normally, these vessels regulate the supply of blood to the heart tissue when demands are higher — at times of stress, for example, or during exercise when the heart pumps faster. But in many women (and some men), this process becomes dysfunctional, and the microvessels fail to respond properly. This can lead to ischemia, a starving of the heart tissue of oxygen and nutrients. If severe enough or prolonged, this ischemia can cause the same end result that plugged-up arteries cause — not enough blood supply when demand is high, leading to a heart attack.

Bairey Merz believes this problem, which looks very different from coronary artery disease, probably underlies the generally worse cardiac outcomes for women because it is not being recognized and treated as heart disease.

To understand why that may be the case, it helps to compare the symptoms, diagnosis and treatment of these two types of heart disease.

Symptoms versus no symptoms

Only about half of patients will have what doctors call the " Hollywood heart attack," clutching their chest, sweating, face in agony as an elephantine crushing weight attacks them. The other half will experience what are called atypical symptoms, such as fatigue, pain in their arms, shoulders, back or jaw, and shortness of breath, or they'll have no symptoms at all. Women are much more likely to fall into this group, something physicians have long known.

When patients show up in the doctor's office distressed by symptoms of potential heart disease, a majority of men and a significant portion of women will show signs of coronary artery disease in diagnostic tests. Those tests may include an electrocardiogram (EKG) and an exercise stress test on a treadmill to detect abnormal heart rhythms, and possibly an angiogram, an invasive technique that shows in real time the blood flow through coronary arteries.

In a typical angiogram, a catheter, or small plastic tube, is threaded through the femoral artery in the patient's groin to just outside the heart. A dye is then injected that shows up on a special type of X-ray — a cardiologist can then see whether any blockages prevent the dye, or blood, from flowing freely.

But some women with coronary artery disease appear to form plaques that do not create blockages but rather build up uniformly along the inside of their large arteries, narrowing them. This is difficult to see in an angiogram.

Further, the exercise stress test and angiogram will not pick up problems occurring in the microvessels. This means a majority of women, even those complaining of chest pains or fatigue, (and some portion of men too) may be given an "all clear" diagnosis simply because their coronary arteries show no signs of blockage. In fact, treadmill tests are known to give a higher rate of false positives in women.