Clinical Presentation

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Whereas almost two-thirds of men with coronary heart disease present with myocardial infarction or sudden death as the initial manifestation of disease, over 50% of women may have angina pectoris as their first symptom (Fig. 3) (16), yet establishing the diagnosis of ischemic heart disease in women remains problematic. This is, in part, due to the relatively high prevalence in women of chest pain in the absence of significant epicardial coronary artery stenoses.

To address this issue, several studies have examined the predictive value of chest pain utilizing angiographic assessment of coronary anatomy and determined that there is a poor correlation between chest pain symptoms and angiographic evidence of coronary disease (17). At best, a clinical history of angina correlated with angiographic disease only one-half of the time in women. Even when unstable symptoms were present, the correlation was no better than 59%. The best correlation occurred in women thought not

□ Chest pressure

□ Chest pressure

Fig. 3. Clinical presentation differs between women and men. Women who present for evaluation of an acute coronary syndrome complain of chest pain or pressure more frequently than men, and, in fact, 60% of women compared to 50% of men report chest pain symptoms on initial presentation (20).

Women Men

Fig. 3. Clinical presentation differs between women and men. Women who present for evaluation of an acute coronary syndrome complain of chest pain or pressure more frequently than men, and, in fact, 60% of women compared to 50% of men report chest pain symptoms on initial presentation (20).

to have angina by history in which coronary artery disease was absent 95% of the time. Some added predictive value occurred when women were stratified by presence of coronary heart disease risk factors. For example, significant coronary artery disease was found in 55% of women with two or more risk factors, but only 7% of women with fewer than two risk factors (18).

One of the initial studies to recognize the diagnostic value of chest pain in women was the Coronary Artery Surgery Study (CASS) (19). In this study, definite angina, probable angina, probably not angina, and definitely not angina were carefully defined. Over 20,000 patients, of whom 4000 were women, were prospectively enrolled in this study, and all underwent coronary angiography to define coronary disease prevalence. Significant coronary disease, defined as at least 70% coronary artery stenosis, was found in 72% of the women with definite angina and 36% of the women with probable angina. The other two categories, probably not angina and definitely not angina, were combined under a category of nonspecific chest pain, and only 6% of the women so classified had significant coronary artery disease. In men, a similar classification resulted in significantly different prevalence rates of 93, 66, and 14%, respectively (19).

Therefore, chest pain in women is neither sensitive nor specific in predicting the presence of underlying coronary artery disease. The highest sensitivity is found in women presenting with symptoms of typical angina pectoris, whereas the highest specificity is found in women presenting with nonspecific symptoms of chest pain.

In fact, women with acute coronary syndromes often present with symptom patterns that differ from their male counterparts. In a recent study of patients presenting to the emergency department, who subsequently had the diagnosis of acute coronary syndrome confirmed during hospitalization, chest pain was the most frequently reported symptom in both men and women; however, women were more likely than men to present with mid-back pain, nausea and/or vomiting, dyspnea, palpitations, and indigestion

(20,21). Similarly, in patients presenting with an acute myocardial infarction, men were significantly less likely to complain of neck pain, back pain, jaw pain, and nausea, than women (22).

The magnitude and frequency of anginal-type chest pain, as well as nonspecific chest pain, in the absence of significant epicardial coronary stenoses is of practical importance but remains largely unexplained. This phenomenon has been attributed to mitral valve prolapse, vasospastic angina, and microvascular endothelial dysfunction (23). Reduction of circulating estrogen following menopause is associated with profound impairment of endothelial vasodilator function and has been suggested to contribute to chest pain syndromes (24). In fact, recent studies demonstrate that coronary microvascular dysfunction is present in approximately one-half of women who present with chest pain in the absence of obstructive epicardial coronary disease and cannot be predicted by risk factors for atherosclerosis and hormone levels (25).

In women, studies of the control of blood flow in angiographically normal coronary vessels suggest that endothelial vasomotor dysfunction may mediate myocardial ischemia by contributing to pathologic coronary constriction or failure to dilate appropriately under conditions of increased demand (26). This phenomenon was demonstrated by measuring coronary vasodilator reserve in patients with chest pain but angiographically normal coronary arteries using a doppler-tipped flow wire. Interestingly, there was a trend for a higher coronary vasodilatory reserve in men compared to women (27).

Therefore, endothelial microvascular dysfunction may play a more important role in the production of ischemia in women than in men, and coronary angiography alone may fail to diagnose the etiology of chest pain. These observations suggest further, that in the setting of chest pain and angiographically normal or insignificant epicardial coronary artery disease, hemodynamic analysis of the coronary vasculature may be warranted.

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