Typically, coronary artery disease occurs when part of the smooth, elastic lining inside a coronary artery (the arteries that supply blood to the heart muscle) develops atherosclerosis. With atherosclerosis, the artery's lining becomes hardened, stiffened, and swollen with all sorts of "grunge" - including calcium deposits, fatty deposits, and abnormal inflammatory cells - to form a plaque. Deposits of calcium phosphates (hydroxyapatites) in the muscular layer of the blood vessels appear to play not only a significant role in stiffening arteries but also for the induction of an early phase of coronary arteriosclerosis. This can be seen in a so-called metatstatic mechanism of calcification as it occurs in chronic kidney disease and haemodialysis (Rainer Liedtke 2008). Although these patients suffer from a kidney dysfunction, almost fifty percent of them die due to coronary artery disease. Plaques can be thought of as large "pimples" that protrude into the channel of an artery, causing a partial obstruction to blood flow. Patients with coronary artery disease might have just one or two plaques, or might have dozens distributed throughout their coronary arteries. However, there is a term in medicine called ''“Cardiac Syndrome X”'', which describes chest pain (Angina pectoris) and chest discomfort in people who do not show signs of blockages in the larger coronary arteries of their hearts when an angiogram (coronary angiogram) is being performed.
No one knows exactly what causes “Cardiac Syndrome X” and it is unlikely to have a single cause. Today, we speculate that the major contributing factor to “Cardiac Syndrome X” is ''“microvascular dysfunction”''. The term “microvascular” refers to very small blood vessels and, in this case, very small arteries (arterioles, capillaries) of the heart. Studies have also shown that people with “Cardiac Syndrome X” have enhanced pain perception, meaning they feel chest pain more intensely than the average person.
The large majority of women have the garden variety of coronary artery disease. Rarely, women with “Cardiac Syndrome X” have typical anginal syndromes that are not associated with the presence of atherosclerotic plaques; that is, the localized blockages are absent. Scientists speculate that the blood vessels in these women are diffuse abnormal. Some have falsely claim that the entire lining of the artery becomes thickened throughout, making the plaques flush with the wall of the artery without any scientific proof. On cardiac catheterization their coronary arteries appear smooth-walled and normal, though they may look "small" in diameter. By the way: in general, female coronary arteries (like all arteries) are somewhat smaller than in males.
“Cardiac Syndrome X” have never been shown to cause acute heart attacks (myocardial infarction) despite much speculation. The prognosis with syndrome-X coronary artery disease is also known to be better than with typical coronary artery disease, but this is not a benign condition since it can be quite disabling.
It is not completely clear why women are more likely than men to suffer from "Syndrome X"; however, hormones and other risk factors unique to women may play a role. Women’s blood vessels are exposed to changing levels of oestrogen throughout their lives, first during regular menstrual cycles and later during and after menopause as oestrogen levels decline with age. Oestrogen affects how blood vessels narrow and widen and how they respond to injury, so changes in oestrogen levels mean changes in the reactivity of the blood vessels. Women’s vessels may be “programmed” for more changes than men’s vessels, which could increase the risk of having problems in the lining of the arteries (endothelial cells) and the smooth muscle cells in the walls of the arteries.
The endothelial dysfunction is likely to be multifactorial in these patients and it is conceivable that risk factors such as hypertension, hypercholesterolemia, diabetes mellitus and smoking can contribute to its development. Most patients with Syndrome X are postmenopausal women and oestrogen deficiency has been therefore proposed as a pathogenic factor in female patients. In addition to changing hormone levels, there are several other risk conditions for blood vessel problems that are unique to women, such as preeclampsia (a problem associated with high blood pressure during pregnancy) and delivering a low-birth weight baby. Of course, despite these issues women, the female gender as a whole is protective against coronary artery disease.
Cardiac Syndrome X often is a diagnosis of exclusion where the presence of typical chest pains is not accompanied by coronary artery narrowings on angiography. In considering Syndrome-X, it is important to understand that about 80% of chest pains have nothing to do with the heart. Therefore, the characteristics of typical chest pains must be carefully documented to avoid unnecessary labelling patients with heart disease:
- Chest pain or Angina with physical stress; the pain may spread to the left arm or the neck, back, throat, or jaw. There might be present a numbness (paresthesia) or a loss of feeling in the arms, shoulders, or wrists.
- Coronary angiography demonstrates “normal” coronary arteries, i. e. no blockages or stenoses can be detected in the larger epicardial vessels.
- No inducible coronary artery spasm present during cardiac catheterization.
- Characteristic ischemic ECG changes during exercise testing.
- ST segment depression and angina in the presence of left ventricular wall perfusion abnormalities during thallium or other stress perfusion test.
- Consistent response to sublingual nitrates.
- Postmenopausal or menopausal status.
The diagnosis of “Cardiac Syndrome X” - the rare coronary artery disease that is more common in women, as mentioned, an “exclusion” diagnosis. Therefore, usually the same tests are used as in any patient with the suspicion of coronary artery disease:
- Baseline ECG
- Exercise ECG – Stress test
- Exercise radioisotope test (nuclear stress test, myocardial scintigraphy).
- Echocardiography (including stress echocardiography).
- Coronary angiography.
- Intravascular ultrasound.
- MRI scan.
A variety of drugs are used in the attempt to treat the Syndrome-X coronary artery disease: nitrates, calcium channel antagonists, ACE-inhibitors, statins, imipramin (analgesia), aminophylline, hormone replacement therapy (oestrogen), even electrical spinal cord stimulation are tried to overcome the symptomatology -all with mixed results. Quite often the quality of life for these women remains poor.
While not enough is known about Syndrome-X coronary artery disease to list specific prevention techniques, adopting heart-healthy habits can be a good start. These include monitoring cholesterol and blood pressure levels, maintaining a low-fat diet, exercising regularly, quitting smoking, avoiding recreational drugs, and moderating alcohol intake. However, there might be a new option for women suffering from “Cardiac Syndrome X”: Protein based Angiogenesis. This new protein-based angiogenic therapy - using fibroblast growth factor 1 (FGF-1) - might be used as sole therapy as well as adjunct to bypass surgery – thus overcoming the limitations of conventional bypass surgery. Beyond drug therapy, interventional procedures, and coronary artery bypass grafting, angiogenesis now offers a new, specific and – so far as we know from three human clinical trials – effective treatment targeted for women’s coronary artery disease.
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