Mazen Ahmad Asayreh, MD
King Hussein Medical Center, Royal Medical Services, Jordan

Correspondence:
P.O. Box 11343
Amman 11123 Jordan
E-mail: asayreh@yahoo.com

Epidemiologic studies of acute myocardial infarction have described gender differences in the time of death after infarction, with greater numbers of men dying before hospitalization than women. Chest pain in women is a commonly encountered condition which accounts for an appreciable number of referrals to cardiologists for further evaluation. Psychiatric illnesses are present in up to 50% of new patients attending the cardiac clinic with chest pain. Patients with recurrent chest pain who are free of significant coronary artery disease (CAD) account for 10% to 30% of patients who undergo coronary angiography.

The accurate diagnosis of chest pain is often difficult. Myocardial ischemia, aortic dissection, pulmonary embolism, pericarditis, and gastroenterological sources of chest pain are the most common differentials. The symptom of chest pain has many causes; some of them are cardiac and others are not.

The presence of common symptoms, such as heartburn and regurgitation, usually make the diagnosis of gastroesophageal reflux disease fairly straightforward. Coronary angiography is the criterion for establishing a diagnosis of CAD. Patients with positive results on an exercise test are more likely to be further investigated, but ST segment shift with exercise is a less specific marker of CAD in women.

However, coronary angiography carries a small but well documented risk of complications and consequently should be for those patients most likely to have chest pain of cardiac origin. For many years research in CAD has been focused on men, yet CAD is also the major cause of death and an important cause of disability in women.

We studied the files of 500 women referred to the cardiac center in King Hussein Medical Center (KHMC) with chest pain for further investigation over a four year period, in addition to comparing the characteristics of women with CAD and women with normal coronary arteries.

We reviewed the files of 500 women referred to the cardiac center
with chest pain who subsequently underwent coronary angiography. Risk factors, results of exercise testing and coronary angiography, intervention, morbidity and mortality were recorded.

Patients were divided into two groups according to the presence or absence of CAD identified by coronary angiography. A diagnosis of CAD, based on the cardiologist's reports, was made if the diameter of stenosis in any coronary artery exceeded 40%.

Patients were excluded if they were found to have cardiac disease other than CAD. The presence of recognized risk factors for CAD, which included a family history (first degree relative with CAD), hypercholesterolemia (random total cholesterol more or equal to 6.5mmol/l or patient receiving lipid lowering agent), hypertension requiring specific treatment, history of smoking (current or previous cigarette smoker), and diabetes mellitus (requiring treatment by diet, oral hypoglycemic, or insulin, were recorded).

The exercise test was analyzed as positive or negative. Patient details were obtained from the clinical notes, with follow up to present day. Events during follow up including MI, hospital readmission and death were recorded. Chi -square was used for statistical analysis.

Of the 500 females who underwent coronary angiography, 305 (61%) had CAD and 195 (39%) had normal coronary arteries. Women with CAD were older than women with normal coronary arteries (mean SD 58.7(9.1) year v 53.6(9.3); P 0.001). Only diabetes mellitus was more frequently encountered in women with CAD than women with normal coronary arteries (39/305(13%) v 4/195(2%); P=0.01) (Table 1). Hypertension and positive family history for CAD were more frequently encountered in women with CAD than in those with normal coronaries (hypertension 156/305(51%) v 106/305 (35%), P=0.003; family history, 216/305 (71%) v 155/195(51%), P= 0.01.

Smoking was not a common risk factor for CAD in both groups (70/305(23%) v 33/195(17%)). Exercise test results were correlated with the presence or absence of CAD. The test was positive in 50/195 (26%) in women with normal coronary arteries and 201/305 (66%) in women with CAD. The sensitivity of exercise testing was (63%) and the specificity was (74%). In 103/305(34%) had single vessel disease, 88/305 (29%) had two vessel disease, and 118/305 (39%) had triple vessel disease .No correlation was found between the results of exercise test and numbers of diseased vessels.

Follow up details were obtained in 91% of patients. Mean follow up time was 3.6 years for patients with normal coronary arteries. Table ll shows the outcome in the 195 women with normal coronary arteries. Three women died from non-cardiac causes, and three women died suddenly of an unknown cause. Table lll shows the outcome in the 305 women found to have CAD.

There is growing interest in research into women with suspected or documented coronary artery disease, which until recently, has been little studied. Coronary artery disease is the main cause of death in women in the Western world; whether the results from these studies can be applied to all women is unknown.

Consequently, the aim of our study was to characterise women referred with chest pain to a cardiac centre since they represent an important clinical problem. Standard risk factors for coronary artery disease and the results of exercise testing were of limited value in distinguishing women with coronary artery disease from those with chest pain from non-cardiac causes. Despite a diagnosis of noncardiac chest pain, many patients continued to have symptoms and seemed to have derived little benefit from cardiac investigation. Furthermore, cardiac events were no more frequent during the follow up period. Women represented the minority of patients referred with a clinical diagnosis of angina for further investigation. 39% of women referred with chest pain for further investigation, were subsequently found to have normal coronary arteries, which is in keeping with the coronary artery surgery study, in which 46%of women referred with chest pain for angiography had normal coronary arteries.

Studies examining the importance of risk factors in the development of coronary artery disease have shown that hypertension, smoking, raised serum concentrations of lipids, diabetes mellitus and a family history of coronary artery disease are all important in predicting the development of the disease . Other than diabetes mellitus, however, risk factors for coronary artery disease in women were poor discriminators in our study. The reason(s) why only diabetes mellitus discriminated between women with and without coronary artery disease is uncertain. Smoking is not a common risk factor for coronary artery disease in Jordan because of social restrictions. In one study the relative risk of fatal coronary artery disease in diabetics compared with non-diabetic patients was 3.3 in women after adjustment for age, systolic blood pressure, cholesterol, body mass index, and cigarette smoking. Positive results on the exercise test were found in 26% women subsequently shown on angiography to have normal coronary arteries, which is comparable with other studies. Some patients may have abnormalities of coronary flow reserve, which could account for their symptoms.

Our data indicates that the vast majority of patients with normal coronary arteries continue to experience chest pain. Perhaps this is not surprising since the cause of the patient's symptoms may remain undiagnosed, despite further non-cradiological investigation. Alternatively, patients may continue to believe that their pain is cardiac in origin, a possible explanation in some, since about a third continued antianginal treatment during follow up. Although these findings are not new, the implication is that doctors communicate poorly with patients and reassurance is inadequate. Furthermore, the situation is perpetuated by the continued prescription of antianginal drugs in the knowledge that the patient does not have coronary artery disease. Perhaps cardiologists spend disproportionately little time counseling patients with normal coronary arteries compared with patients with coronary artery disease.

The results of this study indicate that chest pain in women referred for coronary angiography is often non-cardiac in origin, and standard criteria used to determine the likelihood of coronary artery disease in men are of limited value in women .Current limitations on health care resources emphasise the need for better identification of those women most likely to have coronary artery disease before referral for invasive assessment.

Although establishing a diagnosis of normal coronary arteries may be reassuring for the patient's physician, such a diagnosis does little to relieve the symptoms experienced by these patients, who, in the absence of an alternative diagnosis, continue to place a considerable drain on health care resources.

Chest pain in women is common and may or may not have a cardiac cause. In this study 39% of women referred with chest pain who subsequently underwent coronary angiography were found to have normal coronary arteries. Despite a diagnosis of normal coronary arteries morbidity was considerable; an appreciable proportion continued to have chest pain and to take anti-anginal drugs.

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