10/25/2010 06:19 pm ET | Updated May 25, 2011

Gender Differences in Heart Disease: Nation's No. 1 Killer Kills Differently

Heart disease is the nation's No. 1 killer of both men and women. However, it can present warning signs that are so different in women than in men that heart disease in women may be misdiagnosed or missed entirely. In fact, the death rate from ischemic heart disease in women is higher than in men.

One study, adjusted for age, size and other factors, put the death risk for woman at 1.7 times greater than that for men. Even when heart disease is recognized in women, they have a higher rate of death after a heart attack and a higher rate of adverse events following treatment than men. This has lead some physicians to now view coronary artery disease as a gender-specific condition that requires different testing and treatment plans, rather than the traditional uniform approach.

Unfortunately, the process of raising awareness about this problem has been slow. Significant research into gender differences in coronary artery disease has been underway only in the past 10 years. The good news is that because of this research, heart disease in women is starting to be addressed more effectively and in a timely manner. But I want to stress, "starting to be addressed more effectively," because there's still a long way to go. Most of the risk stratification tools that physicians use for estimating risk of heart disease and recommendations for therapy were developed in studies on men. Indeed, many of the clinical trials that have examined the effects of various heart drugs did not have an adequate representation of women to even see if there are gender differences in the response to the medications.

For men, heart disease is generally experienced as chest pain on exertion due to a severe narrowing of the large arteries of the heart by atherosclerotic plaques, or as an acute onset of severe chest pain if the artery is acutely blocked. While 80 percent of women with coronary artery disease do have plaque buildup in their major arteries, this buildup often isn't visible on many standard tests because it's spread diffusely in the vessel walls. Women who exhibit symptoms, such as extreme fatigue, shortness of breath and/or chest pains, may be suffering from coronary microvascular dysfunction, which is a narrowing of the small arteries and blood vessels of the heart. Rather than a blockage, it represents a failure of the arteries to open and close properly, preventing the heart from getting enough blood. Since this kind of coronary artery disease is a departure from the norm, many of the standard tests for recognizing it are ineffective.

Better Thinking for More Effective Tests

Treadmill stress tests and CT scans can show a normal result for a woman who, in fact, has heart disease because they don't focus on the small arteries and blood vessels. The same can be true in the case of standard angiography, an imaging technique long considered the gold standard for detecting heart disease. While a regular angiogram does enable the study of veins and arteries -- via a catheter that is threaded into the heart through a vein followed by an injection of contrast dye in order to determine whether blood vessels are blocked, damaged or malformed -- the small arteries of the heart are not seen. Consequently, up to two thirds of women exhibiting chest pain appear to be healthy on an angiogram when they turn out to have heart disease. A stress test combined with an echocardiogram that uses sound waves or with nuclear imaging to look at how the muscular walls of the heart respond to exercise is superior to the standard stress test.

Computed axial tomography (CAT or CT) angiography may provide the correct diagnosis. In this test, no tube is necessary and the dye can be placed with a simple injection in the arm. A CAT angiogram delivers a highly detailed image of blood vessels, and causes less discomfort than a traditional angiogram. Recent studies using magnetic resonance imaging (MRI) following dye injections have shown great promise in demonstrating both large vessel and microvascular disease.

The current gold standard for diagnosing coronary microvascular dysfunction in woman is the coronary reactivity test, also called provocative coronary angiography. This is a special kind of angiography procedure that's specifically designed to examine the blood vessels in the heart and how they respond to different medications.

New Studies on Gender Distinctions

Research is continually showing us the differences between men and women in heart disease, especially in the area of underlying causes. One study looked at two common medications for hypertension (high blood pressure), losartan and atenolol, in the treatment of left-ventricular hypertrophy (LVH). LVH is a thickening and enlargement of muscle of the left ventricle of the heart. The study showed that even though the drugs seemed to be working equally for both men and women because the blood pressure levels were lowered to a similar level in both sexes, men had a greater reduction in LVH than did women, who, thus, were at greater risk for heart disease later in life.

Another important study that's changing the way women's heart disease is being detected and treated is the WISE (Women's Ischemic Syndrome Evaluation) initiative, under the leadership of my colleague at Cedars-Sinai, Dr. Noel Bairey Merz and her team at the Women's Heart Center. Dr. Bairey Merz's research has not only had a major impact on bringing to light the shortcomings of traditional testing methods in detecting heart disease in women, but her studies are looking at the hormonal and genetic determinants that control arterial blood vessel construction.

Aside from the clinical advancements, however, awareness is also a key issue for physicians and patients alike. Heart disease kills more than half a million women each year, more than all cancers combined. Women have a greater chance of dying from their first heart attack. Women also tend to wait too long before they go to an emergency room. If a woman's husband or a family member is having chest pains, more likely than not she gets them right to the ER. But if she's experiencing the same thing, she might want to take care of a few things for other people first. This delay is unfortunate, because life-saving and heart-saving interventions like the administration of clot-busting medication or angioplasty have better results if used within the first few hours after the onset of chest discomfort. Women and their physicians should know that extreme fatigue and shortness of breath also are important warning signs of possible heart disease, and should prompt immediate testing for both large coronary vessel and coronary microvascular disease.