Heart disease is no longer viewed as a man’s disease. In fact, 450,000 women die each year of cardiovascular disease, making it the leading cause of death in women in the United States. Moreover, American women are about 5 times more likely to die of heart disease than of breast cancer. The problem with reducing these frightening numbers is that much of the information on presentation and treatment of heart disease is based on studies done in men, leading to some misperceptions of heart disease in women. Fortunately, that trend is changing.
Research done specifically in women has shown that coronary artery disease (CAD) differs in men and women. Women often have angina without significant blockage (> 50%) of the coronary vessels in the heart as seen on angiography. This clinical scenario of chest pain when the coronary arteries are considered normal is called non-obstructive CAD. About half of the women who undergo coronary angiography do not have obstructed heart vessels, whereas only about 15% of men don’t have significant lesions on angiography (Circulation 2004;109:e44- e46). Nevertheless, these women who have signs and symptoms of myocardial ischemia (lack of blood flow) but no diseased vessels on angiography often continue to have symptoms that require hospitalization and repeated diagnostic testing to no avail.
The medical importance of non-obstructive CAD has been debated, with most physicians assigning it to a low-risk category. Moreover, in the past, women who sought medical care for symptoms and signs of heart disease without having angiographically proven vessel obstruction were told they didn’t have heart disease and were offered little treatment. Until recently, physicians didn’t know if women who have nonobstructive CAD were indeed at increased risk of a cardiovascular event (eg, heart attack).
However, a recent article published in the Archives of Internal Medicine (2009;169:843- 50) sheds some light on this issue. To better understand the risks women face when they have cardiac symptoms with non-obstructive CAD, the investigators compared data from 2 large studies done in women: the Women’s Ischemia Syndrome Evaluation (WISE) study (Circulation 2004;109:2993-9) and the St. James Women Take Heart (WTH) study (Circulation 2003;108;1554-9). The WISE study comprised women with symptoms of heart disease who underwent diagnostic coronary angiography; the Archive investigators created 2 groups of symptomatic patients from this study—those with normal coronary arteries (no evidence of CAD [0% stenosis]) on angiography (n=318) and those with non-obstructive CAD on angiography (n=222). Non-obstructive CAD was defined as 1% to 49% stenosis in any coronary artery, usually deemed insignificant by the medical community. The comparative group of women (n=1000) was drawn from the WTH study, which was a community-based sample of women with no history or symptoms of heart disease who were followed up for 10 years. Women from the WISE and WTH study were matched for age and race. The investigators compared outcomes between the groups in terms of cardiovascular events (heart attack, stroke, hospitalization for heart failure) and death.
In comparing the symptomatic WISE women and the asymptomatic WTH women, the Archive investigators found that CAD risk factors, such as obesity, family history of heart disease, hypertension, and diabetes, were seen less often in the WTH women than in the symptomatic women. After adjusting for these risk factors, the investigators then analyzed the 5-year rate of cardiovascular events in the three groups. The 5-year rate was highest in WISE women with non-obstructive CAD, 16% of whom experienced a cardiovascular event. The next highest rate was seen in WISE women who had normal coronary arteries (7.9%). The lowest 5-year rate of cardiovascular events was seen in the WTH women, with only 2.4% of them experiencing an event. Then, they examined the 5-year event rate by the number of cardiac risk factors each woman had. Women who had 4 or more cardiovascular risk factors (eg, smoking, diabetes) had the highest event rates in each group. Moreover, WISE women with nonobstructive CAD who had 4 or more risk factors were more than 3 times more likely to have a cardiovascular event than were WTH women who had at least 4 risk factors (25.3% vs 6.5%, respectively). Falling in between these two groups were the WISE women with normal coronary arteries and 4 or more risk factors; 13.9% of these women had a cardiovascular event within 5 years. The investigators also identified increasing age as a significant factor for cardiovascular events in women who had symptoms and non-obstructive CAD.
The take-home message from this Archive report is that women who have signs and symptoms of CAD but who do not have blocked vessels on angiography are not, as once thought, a low-risk group. In fact, these symptomatic women are at a relatively high risk of future cardiovascular events, especially women who have multiple CAD risk factors. The prognosis for symptomatic women who have normal or non-obstructed coronary arteries is not benign. Moreover, physicians should consider aggressive modification of risk factors in this group of women.
The results from the Archives study are striking and serve to remind us once again of the gender differences in heart disease. The one-size-fits-all approach will not work for heart disease. Understanding the differences in the presentation and treatment of heart disease in men and women is imperative in reducing the tremendous burden of this devastating and pervasive disease. Specifically, we are one step closer in that understanding by realizing that women who have CAD symptoms but no CAD disease on angiography are not in a low-risk category for future cardiovascular events and should be treated accordingly.