coronary-artery disease

coronary heart disease

or ischemic heart disease


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Limitation of blood flow to the heart causes ischemia (cell starvation secondary to a lack of oxygen) of the myocardial cells. When myocardial cells die from lack of oxygen, this is called a myocardial infarction (commonly called a heart attack). It leads to heart muscle damage, heart muscle death and later scarring without heart muscle regrowth.

Myocardial infarction usually results from the sudden occlusion of a coronary artery when a plaque ruptures, activating the clotting system and atheroma-clot interaction fills the lumen of the artery to the point of sudden closure. The narrowing of the lumen of the heart artery before sudden closure is often not severe, according to clinical research completed in the late 1990s and using IVUS examinations within 6 months prior to a heart attack. High grade stenoses as such exceeding 75% blockage, such as detected by stress testing while carrying much higher individual risk for sudden closure, were found to be responsible for only 14% of acute heart attacks because they are rarer compared to less severe narrowings. The events leading up to plaque rupture are not understood despite many theories. Myocardial infarction is almost never caused by temporary spasm of the artery wall occluding the lumen, a condition also associated with atheromatous plaque and CAD.

CAD is associated with smoking, diabetes, and hypertension. A family history of early CAD is one of the less important predictors of CAD. Most of the familial association of coronary artery disease are related to common dietary habits. Screening for CAD includes evaluating high-density and low-density lipoprotein (cholesterol) levels and triglyceride levels. Despite much press, most of the alternative risk factors including homocysteine, C-reactive protein (CRP), Lipoprotein (a), coronary calcium and more sophisticated lipid analysis have added little if any additional value to the conventional risk factors of smoking, diabetes and hypertension.



Angina that changes in intensity, character or frequency is termed unstable. Unstable angina may precede myocardial infarction, and requires urgent medical attention. It may be treated with oxygen, intravenous nitroglycerin, and aspirin. Interventional procedures such as angioplasty may be done.

Sex characteristics of coronary artery disease

Special Pathophysiology


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.
  • 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:


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.

Risk factors

The following are confirmed independent risk factors for the development of CAD:

  1. Hypercholesterolemia (specifically, serum LDL concentrations)
  2. Smoking
  3. Hypertension (high systolic pressure seems to be most significant in this regard)
  4. Hyperglycemia (due to diabetes mellitus or otherwise)
  5. Type A Behavioural Patterns, TABP. Added in 1981 as an independent risk factor after a majority of research into the field discovered that TABP's were twice as likely to exhibit CAD than any other personality type.
  6. Hemostatic Factors: High levels of fibrinogen and coagulation factor VII are associated with an increased risk of CAD. Factor VII levels are higher in individuals with a high intake of dietary fat. Decreased fibrinolytic activity has been reported in patients with coronary atherosclerosis.

Significant, but indirect risk factors include:

Risk factors can be classified as

  1. Fixed: age, sex, family history
  2. Modifiable: smoking, hypertension, diabetes mellitus, obesity, etc.



An increasingly growing number of other physiological markers and homeostatic mechanisms are currently under scientific investigation. Patients with CAD and those trying to prevent CAD are advised to avoid fats that are readily oxidized (e.g., saturated fats and trans-fats), limit carbohydrates and processed sugars to reduce production of Low density lipoproteins, triacylglycerol and apolipoprotein-B. It is also important to keep blood pressure normal, exercise and stop smoking. These measures reduces the development of heart attacks. Recent studies have shown that dramatic reduction in LDL levels can cause regression of coronary artery disease in as many as 2/3 of patients after just one year of sustained treatment.

Menaquinone (Vitamin K2), but not phylloquinone (Vitamin K1), intake is associated with reduced risk of CAD mortality, all-cause mortality and severe aortic calcification.



Preventive diets

It has been suggested that coronary artery disease is partially reversible using an intense dietary regimen coupled with regular cardio exercise.

  • Cretan Mediterranean diet: The Seven Country Study found that Cretan men had exceptionally low death rates from heart disease, despite moderate to high intake of fat. The Cretan diet is similar to other traditional Mediterranean diets: consisting mostly of olive oil, bread, abundant fruit and vegetables, a moderate amount of wine and fat-rich animal products such as lamb, sausage and goat cheese. However, the Cretan diet consisted of less fish and wine consumption than some other Mediterranean-style diets, such as the diet in Corfu, another region of Greece, which had higher death rates.

The consumption of trans fat (commonly found in hydrogenated products such as margarine) has been shown to cause the development of endothelial dysfunction, a precursor to atherosclerosis.The consumption of trans fatty acids has been shown to increase the risk of coronary artery disease

Foods containing fiber, potassium, nitric oxide (in green leafy vegetables), monounsaturated fat, polyunsaturated fat, saponins, or lecithin are said to lower cholesterol levels. Foods high in grease, salt, trans fat, or saturated fat are said to raise cholesterol levels.


Aspirin, in doses of less than 75 to 81 mg/d, can reduce the incidence of cardiovascular events. The U.S. Preventive Services Task Force 'strongly recommends that clinicians discuss aspirin chemoprevention with adults who are at increased risk for coronary artery disease'. The Task Force defines increased risk as 'Men older than 40 years of age, postmenopausal women, and younger persons with risk factors for coronary artery disease (for example, hypertension, diabetes, or smoking) are at increased risk for heart disease and may wish to consider aspirin therapy'. More specifically, high-risk persons are 'those with a 5-year risk ≥ 3%'. A risk calculator is available.

Regarding healthy women, the more recent Women's Health Study randomized controlled trial found insignficant benefit from aspirin in the reduction of cardiac events; however there was a signficant reduction in stroke. Subgroup analysis showed that all benefit was confined to women over 65 years old. In spite of the insignficant benefit for women < 65 years old, recent practice guidelines by the American Heart Association recommend to 'consider' aspirin in 'healthy women' <65 years of age 'when benefit for ischemic stroke prevention is likely to outweigh adverse effects of therapy'.

Omega-3 fatty acids

The benefit of fish oil is controversial with conflicting conclusions reached by a negative meta-analysis of randomized controlled trials by the international Cochrane Collaboration and a partially positive systematic review by the Agency for Healthcare Research and Quality. Since these two reviews, a randomized controlled trial reported a reduction on coronary events in Japanese hypercholesterolemic patients.

Omega-3 fatty acids are also found in some plant sources including flax seed oil, hemp seed oil, and walnuts. Plant sources may be safer as fish products have been shown to contain heavy metals and other fat soluble pollutants.

Secondary prevention


Anti-platelet therapy

A meta-analysis of randomized controlled trials by the international Cochrane Collaboration found "that the use of clopidogrel plus aspirin is associated with a reduction in the risk of cardiovascular events compared with aspirin alone in patients with acute non-ST coronary syndrome. In patients at high risk of cardiovascular disease but not presenting acutely, there is only weak evidence of benefit and hazards of treatment almost match any benefit obtained.".

Therapy - Principles of Treatment

Therapeutic options for coronary artery disease today are based on three principles:

  • 2. Coronary interventions as angioplasty and coronary stent-implantation;
  • 3. Coronary artery bypass grafting (CABG - coronary artery bypass surgery).


Recent research

A 2006 study by the Cleveland Clinic found a region on Chromosome 17 was confined to families with multiple cases of myocardial infarction.


Since the 1990s the search for new treatment options for coronary artery disease patients, particularly for so called "no-option" coronary patients, focused on usage of angiogenesis and (adult) stem cell therapies. Numerous clinical trials were performed, either applying protein (angiogenic growth factor) therapies, such as FGF-1 or VEGF, or cell therapies using different kinds of adult stem cell populations. Research is still going on - with first promising results particularly for FGF-1 and utilization of endothelial progenitor cells.


See also

External links

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