Coronary heart disease in women

Until menopause, female hormones reduce cardiovascular risk. But the lack of awareness among women that they too can develop CHD is dangerous.

Cardiovascular disease remains the leading cause of death among women in both developed and developing countries, despite considerable medical advances in recent decades.

A lower awareness of heart disease among women and the frequent absence of typical symptoms, especially in coronary heart disease (CHD), often lead to delayed diagnosis and thus delayed therapy or treatment. “Undertreatment” of women with CHD.

Gender specifics in terms of risk factors

Risk factors for cardiovascular events exist equally for men and women, but their weighting is different. Elevated blood pressure, obesity, and pathological lipid status contribute to cardiac complications to a comparable extent in men and women, whereas smoking practiced over many years and diabetes mellitus are much more relevant risk factors in women (Fig. 1).

Female hormones have a protective effect until menopause is reached, which is why the time of manifestation for cardiovascular disease in women occurs on average ten years later. At this age, more risk factors are also present, resulting in a higher complication rate associated with the cardiovascular event.

Increased attention is being paid to familial hypercholesterolemia (FH), which is characterized by elevated LDL cholesterol levels and, if it occurs in childhood, can lead to premature infarction (20% of myocardial infarctions before the age of 45 are due to FH). Men fall ill earlier, postmenopausal women then very quickly; i.e. many women suffer their infarction around the age of 50 or even already in the third and fourth decade of life.

Several data indicate that smoking is associated with a significantly increased risk constellation, especially in younger women, compared with male smokers. In a Scandinavian study, the relative risk (RR) for a first myocardial infarction was 9.4 in women compared with men (RR: 2.9). Explanations for this were found in a markedly altered lipid metabolism or in the antiestrogenic effect of cigarette smoking in smoking women.

Differences in epidemiology, clinical presentation, and diagnosis.

Coronary artery disease manifests more frequently in men than in women at any age, although mortality is higher in women than in the male population – due to older age. Again and again, gender-specific differences in the clinical picture are reported: In women, angina pectoris symptoms are much less typical and are therefore often not recognized as CHD-associated. However, several studies show that in acute coronary syndrome/myocardial infarction, ischemia-specific symptoms are as typically present in more than 70% of women as in male patients. In the stable CHD stage, the main symptoms in women are shortness of breath, chest tightness, nausea, and general fatigue.

As a noninvasive diagnostic method for the detection or recording of the dimension of a CHD, the stress ECG is the first choice. The mean specificity is 70% in women (77% in men), which conversely means that false-positive results after exercise ECG measurement are present in 30% of those examined; the positive predictive value is 50% for women and 70% for men. Thoracic pain is not very predictive as a symptom in the female population. However, there are parameters such as the duration of exercise or exercise capacity or the speed of heart rate recovery 1-2 minutes after the end of exercise, which allow valid statements regarding further action and general prognosis. Imaging procedures during stress (e.g., echocardiography), nuclear medicine procedures such as myocardial perfusion scintigraphy using SPECT or positron emission tomography (PET) subsequently increase the informative value.

If there is evidence of CHD, especially against the background of a corresponding risk profile, an invasive work-up by coronary angiography should be performed quickly. Recent data show that the path to definitive proof or exclusion of obstructive CAD by cardiac catheterization is much longer (and more arduous) for women than for male sufferers.

Although coronary artery obstruction is also the most common cause of CHD in women, nonobstructive CHD is more common in female patients than in males (Fig. 2). In this context, various mechanisms of action are discussed, among them esp. Microvascular coronary dysfunction with impaired dilatory capacity. The calculation of the so-called coronary flow reserve is performed using non-invasive methods such as PET. Resulting pathological findings are clearly associated with a worse prognosis. These associations between coronary vasomotor dysfunction and comorbidities such as insulin resistance may initiate the development of new therapeutic strategies for revascularization rather than just anatomic improvement. Entirely new perspectives could be opened up by the use of potent lipid-lowering substances (PCSK9 inhibitors), anti-inflammatory agents (e.g., interleukin 1 inhibitors), or neurohumoral modulating substances.

In addition, clinical situations with chest pain and myocardial ischemia are more frequent in women, although rare, as in the case of Tako Tsubo cardiomyopathy (TCM) or coronary artery dissections, especially in the peripartum phase. TCM is a rare but dramatic presentation: in acute myocardial infarction, it manifests as “apical ballooning” on echocardiography or laevocardiography; it occurs predominantly in postmenopausal women and often due to emotional stress associated with a “dramatic” event, and is therefore also called broken heart syndrome. Prognosis is generally very good, and detectable residual myocardium is rare.

Management of acute coronary syndrome/myocardial infarction

Percutaneous interventions (PCI) are the treatment of choice in a majority of patients to minimize left ventricular dysfunction. The motto “time is muscle” therefore means keeping the time span between the onset of infarct-typical symptoms and the reopening of the coronary vessel as short as possible. This is now being achieved satisfactorily in well-organized cities and regions. Nevertheless, international registries or the Vienna Infarction Network show relevant time differences of up to one hour: Women contact the emergency services significantly later than male infarct patients, which leads to a longer prehospital time overall. Again, as with other aspects of the topic of women and CHD, educate and buy time!

The higher hospital mortality from acute myocardial infarction in women is mainly due to older age and thus greater extent of multimorbidity. For cardiogenic shock, female sex is considered an independent predictor of significantly worse survival, regardless of concomitant comorbidities.

Cardiovascular implications of cancers in women.

Cardiovascular disease is the leading cause of death in women, followed by carcinoma. On the one hand, there are some common risk factors for both disease entities, and on the other hand, carcinoma therapies such as cardiotoxic chemotherapies can lead to an aggravation of heart disease.

Common risk factors are obesity and the metabolic syndrome that builds on it, diabetes mellitus per se, and overall health-damaging behaviors such as lack of physical activity, nutrient-poor foods, and often associated low social status. In breast cancer, the most common form of female carcinoma, various potentially cardiotoxic substances are used, such as anthracyclines, taxanes, or trastuzumab, with varying cardiac toxicity depending, among other things, on the substances administered in combination.

Outlook

Awareness of gender medicine developed in the 1970/80s on the basis of gender-specific differences in the perception, diagnosis and treatment of heart disease (Fig. 3) . In the meantime, intensive research has been conducted in this field, which is reflected in the further development of diagnostic and therapeutic procedures. Possibly, for all the academic interest in differences, one major risk factor remains: the lack of awareness among women as well as within the medical community that cardiovascular disease based on the risk factors of hypertension, obesity, smoking, and metabolic syndrome poses a significantly higher risk to women in terms of morbidity and mortality.

Take-Home Messages

Naturally acting female hormones reduce cardiovascular risk.
After menopause, the risk of CHD in women reaches the same magnitude as in men.
The risk factors for developing CHD are identical in men and women, but some (e.g., smoking) imply a much higher cardiovascular risk for women compared with male smokers.
The lack of awareness among women that they too can develop CHD is one of the biggest risk factors.
In stable CHD, symptoms are often less typical in women and are sometimes misinterpreted. In acute coronary syndrome/myocardial infarction, women and men show comparable typical symptoms.

Literature:

Kannel WB: Clinical Misconceptions Dispelled by Epidemiological Research. Circulation 1995; 92(11): 3350-3360.
Jespersen L, et al: Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major cardiovascular events. Eur Heart J 2012; 33(6): 734-744.
Mosca L, et al: Fifteen-year trends in awareness of heart disease in women. Results of a 2012 American Heart Association national survey. Ciruclation 2013; 127(11): 1254-1263.