DIAGNOSTIC TESTING FOR CORONARY ARTERY DISEASE IN WOMEN AND GENDER DIFFERENCES IN REFERRAL FOR REVASCULARIZATION

Coronary artery disease (CAD) is increasingly well recognized as the number one cause of death for women in the United States. In 1993, 503,542 women died of cardiovascular disease, more than all other diseases combined. 1 In fact, the absolute number of deaths from CAD in women is rising because the age of the population is increasing. Optimal diagnostic and management strategies for CAD in women present a different set of considerations than in men. There are several challenges in designing these strategies. Many large trials of CAD diagnosis and treatment have not included women or have included women only in small numbers. Applicability of these trial results to women is controversial because CAD epidemiology, diagnostic test accuracy, test performance characteristics, and treatment efficacy differ between men and women. There are also gender differences in referral patterns: Studies suggest that CAD in women is underdiagnosed and undertreated compared to CAD in men; women are less likely than men to be referred for diagnostic tests and therapeutic interventions. 28,35,41 This article reviews the current data on accuracy, test characteristics, and cost-efficiency for the most common noninvasive testing techniques—exercise testing, pharmacologic stress, and newer radiologic imaging techniques—as well as reviewing gender differences in referral for revascularization. The first step in the diagnosis of cardiac ischemia for men and women is a careful clinical history with emphasis on delineating chest pain characteristics. Classic angina is characterized by substernal squeezing chest pain, occurring with stress and relieved with rest or nitroglycerin. It may radiate down the left arm and be associated with nausea, vomiting, or diaphoresis. Probable angina, as used in the coronary artery surgery study (CASS), had features of typical angina, with some atypical features, whereas atypical chest pain has none of the characteristics of classic angina. Although some studies suggest that women are more likely to present with atypical symptoms, such as abdominal pain, nausea, and vomiting, an analysis of the Myocardial Infarction Triage and Intervention (MITI) registry found no gender differences in presenting symptoms for myocardial infarction, with 99.6% of women presenting with chest pain. 22 The next step in diagnosis is to review the patient's risk factors, which have stronger predictive value in women than in men. 10 This information can then be used to estimate the composite likelihood of disease. Combining disease prevalence data from age, gender, risk factors, and type of chest pain and test results provides higher diagnostic certainty than relying on the test results alone. For example, a 65-year-old woman with typical angina has a 91% chance of having CAD, a 55-year-old woman with atypical angina has a 32% chance of having CAD, and a 45-year-old woman with nonanginal chest pain has a 3% chance of having CAD. 8 This estimate, also known as pretest likelihood, is helpful in deciding when to test and what test to choose. It is especially important to consider because of the lower accuracy in women of most of the available noninvasive tests. In general, testing is most useful for patients with intermediate (20% to 80%) pretest likelihood of disease. Posttest probability is changed least by testing when the pretest likelihood is low or high. Likelihood ratios, a test characteristic (see next paragraph), are the key determinants of the relationship of posttest to pretest probability. Knowing the pretest likelihood allows the clinician to apply the principle of bayesian theory to testing for CAD. The Framingham data and others showed that the prevalence of CAD in women begins to increase at age 50 and equals men when women reach their 70s. Therefore, extrapolating bayesian theory, the positive predictive value of a positive noninvasive test is lower in patients with lower pretest probability, as is often true for middle-aged women. In addition, nonbayesian factors, such as particular test artifacts, intrinsic test characteristics, altered referral patterns, hormonal interactions, and other factors such as that stress testing was developed and validated in men, affect diagnostic accuracy in women. Thus, the clinician is faced with the dilemma of diagnosing a disease that is less common in women with tests that are less accurate in women. A number of noninvasive diagnostic tests are available for diagnosis of CAD in women; the advantages and disadvantages of each are reviewed in this article (Table 1).