Women with Nonobstructive Coronary Artery Disease Are Not Necessarily Healthy

Women and men differ when it comes to heart disease. Years ago women with typical anginal chest pain and a “normal” coronary angiography were discharged from the cardiac care unit and told that they did not have heart disease and that their prognosis was good. Nowadays we know that a number of these women are at risk for future cardiovascular events and in fact face a prognosis worse than that of breast cancer. ¹

In a Swedish registry study in 12,200 patients undergoing coronary angiography for the investigation of stable chest pain, normal or nonobstructive coronary artery disease (CAD) was found in 79% of women compared with 42% of men below 60 years of age. ² Similarly normal or nonsignificant CAD is much more common for women than for men among myocardial infarction (MI) patients. The not-so-benign prognosis in these patients is supported by another Swedish registry study in which 8% of ST-elevation myocardial infarction (STEMI) and 5% of non-ST-elevation myocardial infarction (NSTEMI) patients with nonsignificant CAD died during a median follow-up time of 2.6 years. ³

These two studies and many others suggest gender differences in pathophysiological mechanisms of CAD. The present study by Eskerud et al. published in this issue ⁴ is an attempt to further define the etiology of CAD among patients with nonobstructive CAD. In this study, myocardial perfusion using contrast echocardiography was assessed in relation to the degree of significant CAD, plaque area, and coronary artery tortuosity. CAD was assessed by conventional coronary angiography and plaque area by quantitative coronary angiography. Tortuosity was defined as ≥3 curves >45 degrees in the same vessel. Significant CAD was more common among men, whereas plaque area was similar between men and women. Tortuosity was more common among women.

In adjusted analyses, myocardial hypoperfusion was associated with plaque area independent of significant coronary artery stenosis. Many different mechanisms have been proposed to explain MI in the setting of nonobstructive disease, such as plaque erosion, endothelial dysfunction, vasospasm, and microvessel disease. ⁵ All of these mechanisms are associated with atherosclerosis, which may go undetected by conventional coronary angiography. Cholesterol plaque deposition in the vessel wall is more diffuse in women compared with men, as is remodeling, which maintains the lumen diameter. In this study, the authors also investigated the relation of vessel tortuosity with myocardial perfusion. Tortuosity can result in a reduction in coronary perfusion pressure through a disruption of laminar flow. Recent studies have found tortuosity to be much more common among women suffering from spontaneous coronary artery dissections. ⁶ The lack of association with decreased myocardial perfusion in this study may be due to the small sample size and definition of tortuosity.

In conclusion, the findings from this study support the need for diagnostic investigation beyond coronary angiography in patients with chest pain and/or MI with “normal” coronary arteries to help identify those patients at risk of future cardiovascular events. This is especially important in women who comprise the majority of these patients. In light of the growing scientific evidence, we can no longer accept dismissal of these patients as “heart healthy” and continue to undertreat them.