Among the most serious clinical events are fatal myocardial infarction, sudden cardiac death due to cardiac dysrhythmia and unstable angina pectoris. The latter may develop into an impending myocardial infarction. Clinical cardiac events depend, at least partly, upon the severity and hazards of the underlying coronary disease. In sudden cardiac death there is a high risk of an immediately lethal event, with an instantaneous cardiac death.

In these cases the disease is severe and may represent a serious threat to health and welfare and even to life of the patient. In fact sudden cardiac death in men makes out about half of the deaths in men under age 65, whereas only 20 % of women under 65 years suffer sudden cardiac death (Crawford et al. 2004).

Alternatively, coronary heart disease can be manifest as stable angina pectoris, which is usually clinically interpreted as less ominous, less potentially serious, and not necessarily caused by an ischemic damage of the heart muscle. In fact, stable angina pectoris is a diagnosis, which is based on clinical symptoms only. The underlying CAD is confirmed by submaximal exercise ECG. Intensity of pain, however, is not only related to ischemia, but also to psychosocial factors, such as depression and anxiety.

There is a range of differential diagnostic alternatives, from gastrointestinal disorders, to muscular tension and pain, due to cervical rhizopathologic processes. Therefore in patients with stable angina pectoris it cannot be said with absolute certainty that the patient has a diseased heart or that there will be a pathological finding of the coronary arteries. Actually, the reverse is more common: pathological findings of the coronary arteries—without typical angina symptoms. In the Korean War autopsies were systematically performed in young American soldiers who died in combat. Many young men were found to have atherosclerotic disease of their coronary arteries. In most of the cases of advanced coronary disease however, they had been asymptomatic and clinically silent (Stamler 1980).

Silent ischemic heart disease, with typical pathological changes on the ECG, but no symptoms of ischemia, is also more common in men than in women. Conversely, angina pectoris, as the first symptom of ischemic heart disease, is more common in women than in men.

Since about two decades, the coronary arteries in women have become the focus of an increasing research interest. Previously, although as many women as men died from coronary disease, nearly every research article was based on the study of men. In those studies in which women were included, the numbers of women were often so small, that gender differences could not be evaluated. But it did not matter, because men were the norm. Findings in women were of little interest, as they were said and thought to be the same as those in men.

In 1991 Bernadine Healy, the first woman director of the National Institutes of Health, Washington, wrote an editorial, “The Yentl Syndrome” for the New England Journal of Medicine, which became frequently cited. A young Jewish girl Yentl wanted to study and read the Talmud. In order to be accepted she had to dress and behave like a boy, which she did. Women cardiac patients were advised to do the same in order to enjoy all those diagnostic and therapeutic cardiologic technologies, which were available to men.

The course of the clinical ischemic event is a process, which leads to impaired blood flow and inadequate oxygen saturation of the myocardial tissue. If the lack of oxygen—with its metabolic consequences—is longstanding, it will damage the muscular tissue and lead to an AMI.

The standard clinical picture of an AMI is “more than fifteen minutes duration of intense pain in the center of the chest, irradiating to the left arm, the left jaw or the left side of the back.” This classical symptomatic combination has been found to be virtually the same in men as in women patients (Crawford et al. 2004). The underlying cause of the intense pain is the obstructed coronary artery and its impaired blood flow. It is the result of lifelong atherosclerotic processes, which are influenced by humoral factors, such as an elevated lipid profile and by tissue factors, such as endothelial dysfunction of the coronary arteries.

As our knowledge base around women’s heart disease was poor, and gender differences became ever more evident, we initiated, in 1991, a population-based study of Stockholm women with heart disease. In Stockholm we examined all women, aged 65 or younger, who had been hospitalized in intensive care for an acute cardiac event. They had noticed their symptoms in average 2 years before having an acute event, which took them to the hospital. A majority of the women had anginal pain as their first warning of heart disease (Orth-Gomer 1998; Orth-Gomer et al. 2004).

The main disease underlying the cardiac damage is coronary atherosclerosis. To evaluate extent of arteriosclerosis, the coronary arteries need to be visualized. This is done with angiography, qualitatively for clinical examination and quantitatively for research purposes.

In the clinical situation the evaluation of angiographic films for clinical purposes is usually done by a trained angiographer/cardiologist, who estimates the width and the shape of the coronary arteries, as they are visualized. Concerns have been expressed about the precision and accuracy of estimates that indicate, for example, a 50 % narrowing of the coronary segment. This is an important evaluation, as it is often the basis for decisions about cardiological interventions such as stents.

Standardization of angiographic procedures has been described in detail in a previous publication (Orth-Gomer et al. 1998). In our patients, selective coronary arteriography was performed at the Karolinska University Hospital using the Judkins’ technique and a standard clinical angiographic procedure. Before and after intracoronary injection of nitroglycerine, identical angiographic projections were obtained. After engaging the coronary segment under study with the injection catheter, the angiographic view was optimized with short test injections. During a breath hold, filming was started before contrast injection, to show the catheter. Dye was injected to view the segments of interest for at least three cardiac cycles.

For research purposes, imaging conditions (angiographic view angles, catheter size, and field size) were recorded in an arteriography procedure log. Angiograms were recorded as cine films with a frame rate of 25 frames/s.

Evaluations were carried out at the Angiographic Image Processing Laboratory of the Division of Cardiology, University of Texas (Gould et al. 1992; Büchi et al. 1997). To ensure complete comparability between first and second angiographic examinations, a detailed study protocol was followed and experts visited the angio lab several times per year. For each angiogram, absolute luminal diameter (mm) was measured in ten predefined coronary segments (Brunt et al. 1995). Mean segment diameter was calculated as the mean of all diameters (up to 50 measurements) along a given segment. Special procedures were undertaken to replicate the biologic and imaging conditions of the original angiogram at the 3-year follow-up. The evaluation procedure was blinded to the patient’s identity and the order of examinations. The progression of atherosclerosis was evaluated using the mean luminal diameter change over time by subtracting the first from the second measurement (Ornish et al. 1998; Seiler et al. 1992). In conclusion, as a substudy to the Stockholm Female Coronary Risk Study we evaluated by means of this computer-aided system, the atherosclerosis progression in 103 Stockholm women patients. The evaluation was carried out by the team in Houston, Texas. The patients were angiographed twice with 3 years in between, the order of films and the characteristic and identity of patients were unknown to the team in Houston.

Educational level was divided into two categories: mandatory level (corresponding to 9 years of school education) or higher education (completion of high school, college, or university). Smoking status was categorized as nonsmokers, former smokers or current smokers, ever (current or former smokers) versus never. Alcohol consumption was reported as the habitual weekly intake of beer, wine, strong spirits and calculated as average daily consumption of absolute alcohol in grams. Physical exercise was assessed according to the World Health Organization questionnaire and categorized as sedentary or active lifestyle. Body mass index (BMI) and blood pressure were assessed using standard methods. Menopause was defined as cessation of menses since 6 months and women’s menopausal status was classified as premenopausal status, postmenopausal status with and postmenopausal status without hormone replacement therapy. Family history of CHD was defined as having at least one close family member diagnosed with AMI.

Severity of angina pectoris symptoms was graded as: I no angina, II mild angina, III moderately severe angina, and IV very severe angina, by the Canadian Cardiovascular Society Scale for Angina Pectoris. Patients were categorized as either having severe angina or mild (III + IV), or no angina (I + II). Severity of heart failure was estimated using the Killip classification (NYHA). For our analysis, subjects were dichotomized according to the presence (Killip class >1) or absence of symptoms of heart failure. Left ventricular function was visually classified as normal or dysfunctional by left ventriculography as described elsewhere (Al-Khalili et al. 2000).

A full history of current medication intake was abstracted from the hospital charts and verified by interviewing the patients. Medications were classified as: aspirin, beta-blockers, ACE inhibitors, calcium antagonists, and lipid-lowering medications including statins as well as medications for diabetes, including insulin (Orth-Gomér et al. 1997). Several characteristic psychosocial features were hypothesised to predict progression of CAD in these women. The negative emotions associated with vital exhaustion was the most prominent factor, but also marital stress, social isolation, and poor relations to other people were risk factors for accelerated CAD (see Table 4.1) (Wang et al. 2006).