Coronary heart disease
Encyclopedia
Coronary artery disease (CAD; also atherosclerotic
heart disease
) is the end result of the accumulation of atheromatous plaques
within the walls of the coronary arteries
that supply the myocardium (the muscle of the heart
) with oxygen and nutrients. It is sometimes also called coronary heart disease
(CHD). Although CAD is the most common cause of CHD, it is not the only one.
CAD is the leading cause of death worldwide. While the symptoms and signs of coronary artery disease are noted in the advanced state of disease, most individuals with coronary artery disease show no evidence of disease for decades as the disease progresses before the first onset of symptoms, often a "sudden" heart attack
, finally arises. After decades of progression, some of these atheromatous plaques
may rupture and (along with the activation of the blood clotting system) start limiting blood flow
to the heart muscle
. The disease is the most common cause of sudden death
, and is also the most common reason for death of men and women over 20 years of age.
According to present trends in the United States, half of healthy 40-year-old males will develop CAD in the future, and one in three healthy 40-year-old women. According to the Guinness Book of Records, Northern Ireland
is the country with the most occurrences of CAD. By contrast, the Maasai of Africa have almost no heart disease.
As the degree of coronary artery disease progresses, there may be near-complete obstruction of the lumen
of the coronary artery, severely restricting the flow of oxygen-carrying blood to the myocardium. Individuals with this degree of coronary artery disease typically have suffered from one or more myocardial infarction
s (heart attacks), and may have signs and symptoms of chronic coronary ischemia
, including symptoms of angina at rest and flash pulmonary edema
.
A distinction should be made between myocardial ischemia and myocardial infarction. Ischemia means that the amount of blood supplied to the tissue is inadequate to supply the needs of the tissue. When the myocardium becomes ischemic, it does not function optimally. When large areas of the myocardium becomes ischemic, there can be impairment in the relaxation and contraction of the myocardium. If the blood flow to the tissue is improved, myocardial ischemia can be reversed. Infarction means that the tissue has undergone irreversible death due to lack of sufficient oxygen-rich blood.
An individual may develop a rupture of an atheromatous plaque at any stage of the spectrum of coronary artery disease. The acute rupture of a plaque may lead to an acute myocardial infarction
(heart attack).
(cell starvation secondary to a lack of oxygen) of the myocardial cells. Myocardial cells may die from lack of oxygen
and this is called a myocardial infarction
(commonly called a heart attack). It leads to heart muscle
damage, heart muscle
death and later myocardial scarring
without heart muscle
regrowth. Chronic high-grade stenosis of the coronary arteries can induce transient ischemia which leads to the induction of a ventricular arrhythmia, which may terminate into ventricular fibrillation leading to death.
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.
of the heart
arteries
. The symptoms of angina are often treated with betablocker therapy such as metoprolol or atenolol. Nitrate preparations such as nitroglycerin, which come in short-acting and long-acting forms are also effective in relieving symptoms but are not known to reduce the chances of future heart attacks. Many other more effective treatments, especially of the underlying atheroma
tous disease, have been developed.
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.
. 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, hormone
s 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.
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:
s, calcium channel antagonists, ACE-inhibitors, statin
s, imipramine
(for 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.
Significant, but indirect risk factors include:
Risk factors can be classified as
There are various risk assessment systems for determining the risk of coronary artery disease, with various emphasis on different variables above. A notable example is Framingham Score, used in the Framingham Heart Study
. It is mainly based on age, gender, diabetes, total cholesterol, HDL cholesterol, tobacco smoking and systolic blood pressure.
levels, addressing obesity
and hypertension
, avoiding a sedentary lifestyle
, making healthy dietary choices, and stopping smoking
. There is some evidence that lowering homocysteine
levels may contribute to more heart attacks (NORVIT trial). In diabetes mellitus
, there is little evidence that very tight blood sugar
control actually improves cardiac risk although improved sugar control appears to decrease other undesirable problems like kidney failure and blindness. Some recommend a diet rich in omega-3 fatty acids and vitamin C
. The World Health Organization
(WHO) recommends "low to moderate alcohol intake" to reduce risk of coronary artery disease although this remains without scientific cause and effect proof.
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., trans-fats), limit carbohydrates and processed sugars to reduce production of Low density lipoprotein
s (LDLs), triacylglycerol and apolipoprotein-B.
It is also important to keep blood pressure
normal, exercise and stop smoking. These measures reduce 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.
CAD has always been a tough disease to diagnose without the use of invasive or stressful activities. The development of the Multifunction Cardiogram (MCG)
has changed the way CAD is diagnosed. The MCG consists of a 2 lead resting EKG signal is transformed into a mathematical model and compared against tens of thousands of clinical trials to diagnose a patient with an objective severity score, as well as secondary and tertiary results about the patients condition. The results from MCG tests have been validated in 8 clinical trials which resulted in a database of over 50,000 patients where the system has demonstrated accuracy comparable to coronary angiography (90% overall sensitivity, 85% specificity).
This level of accuracy comes from the application of advanced techniques in signal processing and systems analysis combined with a large scale clinical database which allows MCG to provide quantitative, evidence-based results to assist physicians in reaching a diagnosis. The MCG has also been awarded a Category III CPT code by the American Medical Association
in the July 2009 CPT update.
of randomized controlled trials, found 'insufficient evidence' to recommend that doctors counsel patients on exercise, but "it did not review the evidence for the effectiveness of physical activity to reduce chronic disease, morbidity and mortality", it only examined the effectiveness of the counseling itself. However, the American Heart Association
, based on a non-systematic review, recommends that doctors counsel patients on exercise.
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
, saponin
s, or lecithin
are said to lower cholesterol levels. Foods high in grease
, salt
, trans fat
, or saturated fat
are said to raise cholesterol levels.
Regarding healthy women, the more recent Women's Health Study randomized controlled trial
found insignificant
benefit from aspirin in the reduction of cardiac events; however there was a significant
reduction in stroke
. Subgroup analysis
showed that all benefit was confined to women over 65 years old. In spite of the insignificant
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'.
on studies using traditional omega-3 products of randomized controlled trials by the international Cochrane Collaboration
and a partially positive systematic review
AHRQ Evidence reports and summaries 94. Effects of Omega-3 Fatty Acids on Cardiovascular Disease by the Agency for Healthcare Research and Quality
. Since these two reviews, a randomized controlled trial
reported a remarkable reduction on coronary events in Japanese hypercholesterolemic patients, and a later subanalysis suggested that the protective effect of highly purified EPA (E-EPA
) is even more pronounced in Japanese diabetics even though their intake of fish is high.
Omega-3 fatty acids are also found in some plant sources including flax seed oil, hemp seed oil, and walnut
s. The plant omega-3 (ALA) is biologically inferior to marine omega-3, as ALA needs to be converted in the liver to EPA, but only about five per cent is converted.
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.".
Recent research efforts focus on new angiogenic treatment modalities (angiogenesis
) and various (adult) stem cell
therapies.
found a region on Chromosome 17 was confined to families with multiple cases of myocardial infarction.
A more controversial link is that between Chlamydophila pneumoniae
infection and atherosclerosis. While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor. Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.
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.
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
heart disease
Heart disease
Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...
) is the end result of the accumulation of atheromatous plaques
Atheroma
In pathology, an atheroma is an accumulation and swelling in artery walls that is made up of macrophage cells, or debris, that contain lipids , calcium and a variable amount of fibrous connective tissue...
within the walls of the coronary arteries
Coronary circulation
Coronary circulation is the circulation of blood in the blood vessels of the heart muscle . The vessels that deliver oxygen-rich blood to the myocardium are known as coronary arteries...
that supply the myocardium (the muscle of the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
) with oxygen and nutrients. It is sometimes also called coronary heart disease
Coronary heart disease
Coronary artery disease is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium with oxygen and nutrients. It is sometimes also called coronary heart disease...
(CHD). Although CAD is the most common cause of CHD, it is not the only one.
CAD is the leading cause of death worldwide. While the symptoms and signs of coronary artery disease are noted in the advanced state of disease, most individuals with coronary artery disease show no evidence of disease for decades as the disease progresses before the first onset of symptoms, often a "sudden" heart attack
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
, finally arises. After decades of progression, some of these atheromatous plaques
Atheroma
In pathology, an atheroma is an accumulation and swelling in artery walls that is made up of macrophage cells, or debris, that contain lipids , calcium and a variable amount of fibrous connective tissue...
may rupture and (along with the activation of the blood clotting system) start limiting blood flow
Blood flow
Blood flow is the continuous running of blood in the cardiovascular system.The human body is made up of several processes all carrying out various functions. We have the gastrointestinal system which aids the digestion and the absorption of food...
to the heart muscle
Cardiac muscle
Cardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
. The disease is the most common cause of sudden death
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
, and is also the most common reason for death of men and women over 20 years of age.
According to present trends in the United States, half of healthy 40-year-old males will develop CAD in the future, and one in three healthy 40-year-old women. According to the Guinness Book of Records, Northern Ireland
Northern Ireland
Northern Ireland is one of the four countries of the United Kingdom. Situated in the north-east of the island of Ireland, it shares a border with the Republic of Ireland to the south and west...
is the country with the most occurrences of CAD. By contrast, the Maasai of Africa have almost no heart disease.
As the degree of coronary artery disease progresses, there may be near-complete obstruction of the lumen
Lumen (anatomy)
A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
of the coronary artery, severely restricting the flow of oxygen-carrying blood to the myocardium. Individuals with this degree of coronary artery disease typically have suffered from one or more myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
s (heart attacks), and may have signs and symptoms of chronic coronary ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
, including symptoms of angina at rest and flash pulmonary edema
Pulmonary edema
Pulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...
.
A distinction should be made between myocardial ischemia and myocardial infarction. Ischemia means that the amount of blood supplied to the tissue is inadequate to supply the needs of the tissue. When the myocardium becomes ischemic, it does not function optimally. When large areas of the myocardium becomes ischemic, there can be impairment in the relaxation and contraction of the myocardium. If the blood flow to the tissue is improved, myocardial ischemia can be reversed. Infarction means that the tissue has undergone irreversible death due to lack of sufficient oxygen-rich blood.
An individual may develop a rupture of an atheromatous plaque at any stage of the spectrum of coronary artery disease. The acute rupture of a plaque may lead to an acute myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
(heart attack).
Pathophysiology
Limitation of blood flow to the heart causes ischemiaIschemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
(cell starvation secondary to a lack of oxygen) of the myocardial cells. Myocardial cells may die from lack of oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
and this is called a myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
(commonly called a heart attack). It leads to heart muscle
Cardiac muscle
Cardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
damage, heart muscle
Cardiac muscle
Cardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
death and later myocardial scarring
Myocardial scarring
Myocardial scarring is fibrous tissue that replaces normal tissue destroyed by injury or disease pertaining to the muscular tissue of the heart....
without heart muscle
Cardiac muscle
Cardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
regrowth. Chronic high-grade stenosis of the coronary arteries can induce transient ischemia which leads to the induction of a ventricular arrhythmia, which may terminate into ventricular fibrillation leading to death.
CAD is associated with smoking
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
, diabetes, and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
. 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
High density lipoprotein
High-density lipoprotein is one of the five major groups of lipoproteins, which, in order of sizes, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, which enable lipids like cholesterol and triglycerides to be transported within the water-based bloodstream...
and low-density lipoprotein
Low density lipoprotein
Low-density lipoprotein is one of the five major groups of lipoproteins, which in order of size, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, that enable transport of cholesterol within the water-based bloodstream...
(cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
) levels and triglyceride
Triglyceride
A triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....
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
Angina (chest pain) that occurs regularly with activity, after heavy meals, or at other predictable times is termed stable angina and is associated with high grade narrowingsStenosis
A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure.It is also sometimes called a stricture ....
of the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
arteries
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
. The symptoms of angina are often treated with betablocker therapy such as metoprolol or atenolol. Nitrate preparations such as nitroglycerin, which come in short-acting and long-acting forms are also effective in relieving symptoms but are not known to reduce the chances of future heart attacks. Many other more effective treatments, especially of the underlying atheroma
Atheroma
In pathology, an atheroma is an accumulation and swelling in artery walls that is made up of macrophage cells, or debris, that contain lipids , calcium and a variable amount of fibrous connective tissue...
tous disease, have been developed.
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
Angioplasty
Angioplasty is the technique of mechanically widening a narrowed or obstructed blood vessel, the latter typically being a result of atherosclerosis. An empty and collapsed balloon on a guide wire, known as a balloon catheter, is passed into the narrowed locations and then inflated to a fixed size...
may be done.
Special Pathophysiology
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 atherosclerosisAtherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
. 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
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
- 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
Arteriosclerosis
Arteriosclerosis refers to a stiffening of arteries.Arteriosclerosis is a general term describing any hardening of medium or large arteries It should not be confused with "arteriolosclerosis" or "atherosclerosis".Also known by the name "myoconditis" which is...
. 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
Angiogram
Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins and the heart chambers...
(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
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
. Studies have also shown that people with “Cardiac Syndrome X” have enhanced pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
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
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
becomes thickened throughout, making the plaques flush with the wall of the artery
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
without any scientific proof. On cardiac catheterization
Cardiac catheterization
Cardiac catheterization is the insertion of a catheter into a chamber or vessel of the heart. This is done for both investigational and interventional purposes...
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.
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
) 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, hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s 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
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
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
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
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
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, hypercholesterolemia
Hypercholesterolemia
Hypercholesterolemia is the presence of high levels of cholesterol in the blood. It is not a disease but a metabolic derangement that can be caused by many diseases, notably cardiovascular disease...
, diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
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.
Symptoms
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 pectoris with physical stress; the painPainPain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
may spread to the left arm or the neck, back, throat, or jaw. There might be present a numbness (paresthesiaParesthesiaParesthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...
) 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 epicardialEpicardialEpicardial is a term used by some cardiac surgeons meaning "on the outside of the cardiac muscle". Epicardial fat or Epicardial adipose tissue is one of the most important parts of pericardium.See also epicardium....
vessels - No inducible coronary artery spasmSpasmIn medicine a spasm is a sudden, involuntary contraction of a muscle, a group of muscles, or a hollow organ, or a similarly sudden contraction of an orifice. It is sometimes accompanied by a sudden burst of pain, but is usually harmless and ceases after a few minutes...
present during cardiac catheterizationCardiac catheterizationCardiac catheterization is the insertion of a catheter into a chamber or vessel of the heart. This is done for both investigational and interventional purposes... - Characteristic ischemic ECG changes during exercise testing
- ST segmentST segmentIn electrocardiography, the ST segment connects the QRS complex and the T wave and has a duration of 0.08 to 0.12 sec .It starts at the J point and ends at the beginning of the T wave...
depression and angina in the presence of left ventricular wall perfusion abnormalities during thallium or other stress perfusion test - Consistent response to sublingual nitrateNitrateThe nitrate ion is a polyatomic ion with the molecular formula NO and a molecular mass of 62.0049 g/mol. It is the conjugate base of nitric acid, consisting of one central nitrogen atom surrounded by three identically-bonded oxygen atoms in a trigonal planar arrangement. The nitrate ion carries a...
s. - Postmenopausal or menopausalMenopauseMenopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
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:
- BaselineBaseline (medicine)A baseline in medicine is information found at the beginning of a study or other initial known value which is used for comparison with later data. The concept of a baseline is essential to the daily practice of medicine in order to establish a relative rather than absolute meaning to data...
electrocardiography (ECG) - Exercise ECG – Stress testCardiac stress testCardiac stress test is a test used in medicine and cardiology to measure the heart's ability to respond to external stress in a controlled clinical environment....
- Exercise radioisotope test (nuclear stress test, myocardial scintigraphyScintigraphyScintigraphy is a form of diagnostic test used in nuclear medicine, wherein radioisotopes are taken internally, and the emitted radiation is captured by external detectors to form two-dimensional images...
) - EchocardiographyEchocardiographyAn echocardiogram, often referred to in the medical community as a cardiac ECHO or simply an ECHO, is a sonogram of the heart . Also known as a cardiac ultrasound, it uses standard ultrasound techniques to image two-dimensional slices of the heart...
(including stress echocardiography) - Coronary angiography
- Intravascular ultrasoundIntravascular ultrasoundIntravascular ultrasound is a medical imaging methodology using a specially designed catheter with a miniaturized ultrasound probe attached to the distal end of the catheter. The proximal end of the catheter is attached to computerized ultrasound equipment...
- Magnetic resonance imagingMagnetic resonance imagingMagnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI)
Therapy
A variety of drugs are used in the attempt to treat the Syndrome-X coronary artery disease: nitrateNitrate
The nitrate ion is a polyatomic ion with the molecular formula NO and a molecular mass of 62.0049 g/mol. It is the conjugate base of nitric acid, consisting of one central nitrogen atom surrounded by three identically-bonded oxygen atoms in a trigonal planar arrangement. The nitrate ion carries a...
s, calcium channel antagonists, ACE-inhibitors, statin
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
s, imipramine
Imipramine
Imipramine , also known as melipramine, is an antidepressant medication, a tricyclic antidepressant of the dibenzazepine group...
(for analgesia), aminophylline
Aminophylline
Aminophylline is a bronchodilator. It is a compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate-Properties:...
, 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
Preventive medicine
Preventive medicine or preventive care refers to measures taken to prevent diseases, rather than curing them or treating their symptoms...
techniques, adopting heart-healthy habits can be a good start. These include monitoring cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
and blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
levels, maintaining a low-fat diet
Diet (nutrition)
In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...
, 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
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
. This new protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
-based angiogenic therapy - using fibroblast growth factor
Fibroblast growth factor
Fibroblast growth factors, or FGFs, are a family of growth factors involved in angiogenesis, wound healing, and embryonic development. The FGFs are heparin-binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans have been shown to be essential for FGF signal...
1 (FGF-1) - might be used as sole therapy as well as adjunct to bypass surgery
Coronary artery bypass surgery
Coronary artery bypass surgery, also coronary artery bypass graft surgery, and colloquially heart bypass or bypass surgery is a surgical procedure performed to relieve angina and reduce the risk of death from coronary artery disease...
– thus overcoming the limitations of conventional bypass surgery.
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
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:- HypercholesterolemiaHypercholesterolemiaHypercholesterolemia is the presence of high levels of cholesterol in the blood. It is not a disease but a metabolic derangement that can be caused by many diseases, notably cardiovascular disease...
(specifically, serum LDL concentrations) - SmokingTobacco smokingTobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
- HypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
(high systolic pressure seems to be most significant in this regard) - HyperglycemiaHyperglycemiaHyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
(due to diabetes mellitus or otherwise) - Type A Behavioural Patterns, TABPType A personalityOriginally published in the 1950s, the Type A and Type B personality theory is a theory which describes two common, contrasting personality types—the high-strung Type A and the easy-going Type B—as patterns of behavior that could either raise or lower, respectively, one's chances of developing...
. 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 as any other personality type. - 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.
- Hereditary differences/genetic polymorphismsPolymorphism (biology)Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
in such diverse aspects as lipoprotein structure and that of their associated receptors, enzymes of lipoprotein metabolism such as cholesteryl ester transfer protein (CETP) and hepatic lipaseHepatic lipaseHepatic lipase is a form of lipase. It is expressed in the liver and adrenal glands.One of the principal functions of hepatic lipase is to convert IDL to LDL.-Clinical significance:...
(HL), homocysteine processing/metabolism, etc. - High levels of Lipoprotein(a)Lipoprotein(a)Lipoprotein is a lipoprotein subclass. Studies have identified Lp as a putative risk factor for atherosclerotic diseases such as coronary heart disease and stroke....
, a compound formed when LDL cholesterol combines with a substance known as Apoliprotein (a).
Significant, but indirect risk factors include:
- Lack of exercise
- Consumption of alcohol
- Stress
- Diet rich in saturated fatSaturated fatSaturated fat is fat that consists of triglycerides containing only saturated fatty acids. Saturated fatty acids have no double bonds between the individual carbon atoms of the fatty acid chain. That is, the chain of carbon atoms is fully "saturated" with hydrogen atoms...
s - Diet low in antioxidantAntioxidantAn antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
s - ObesityObesityObesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
- Men over 60; Women over 65
- A recent study done in India (puducherry)shows its association with hemoglobin
Risk factors can be classified as
- Fixed: age, sex, family history
- Modifiable: smoking, hypertension, diabetes mellitus, obesity, etc.
There are various risk assessment systems for determining the risk of coronary artery disease, with various emphasis on different variables above. A notable example is Framingham Score, used in the Framingham Heart Study
Framingham Heart Study
The Framingham Heart Study is a long-term, ongoing cardiovascular study on residents of the town of Framingham, Massachusetts. The study began in 1948 with 5,209 adult subjects from Framingham, and is now on its third generation of participants...
. It is mainly based on age, gender, diabetes, total cholesterol, HDL cholesterol, tobacco smoking and systolic blood pressure.
Prevention
Coronary artery disease is the most common form of heart disease in the Western world. Prevention centers on the modifiable risk factors, which include decreasing cholesterolCholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
levels, addressing obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, avoiding a sedentary lifestyle
Sedentary lifestyle
Sedentary lifestyle is a medical term used to denote a type of lifestyle with no or irregular physical activity. A person who lives a sedentary lifestyle may colloquially be known as a couch potato. It is commonly found in both the developed and developing world...
, making healthy dietary choices, and stopping smoking
Smoking cessation
Smoking cessation is the process of discontinuing the practice of inhaling a smoked substance. This article focuses exclusively on cessation of tobacco smoking; however, the methods described may apply to cessation of smoking other substances that can be difficult to stop using due to the...
. There is some evidence that lowering homocysteine
Homocysteine
Homocysteine is a non-protein amino acid with the formula HSCH2CH2CHCO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene group. It is biosynthesized from methionine by the removal of its terminal Cε methyl group...
levels may contribute to more heart attacks (NORVIT trial). In diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
, there is little evidence that very tight blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
control actually improves cardiac risk although improved sugar control appears to decrease other undesirable problems like kidney failure and blindness. Some recommend a diet rich in omega-3 fatty acids and vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
. The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) recommends "low to moderate alcohol intake" to reduce risk of coronary artery disease although this remains without scientific cause and effect proof.
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., trans-fats), limit carbohydrates and processed sugars to reduce production of Low density lipoprotein
Low density lipoprotein
Low-density lipoprotein is one of the five major groups of lipoproteins, which in order of size, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, that enable transport of cholesterol within the water-based bloodstream...
s (LDLs), triacylglycerol and apolipoprotein-B.
It is also important to keep blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
normal, exercise and stop smoking. These measures reduce 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
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
), but not phylloquinone (Vitamin K1
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
), intake is associated with reduced risk of CAD mortality
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
, all-cause mortality and severe aortic calcification.
CAD has always been a tough disease to diagnose without the use of invasive or stressful activities. The development of the Multifunction Cardiogram (MCG)
Multifunction cardiogram
Multifunction CardioGramTM is an FDA and AMA approved diagnostic tool used to diagnose myocardial ischemia due to Coronary Artery Disease...
has changed the way CAD is diagnosed. The MCG consists of a 2 lead resting EKG signal is transformed into a mathematical model and compared against tens of thousands of clinical trials to diagnose a patient with an objective severity score, as well as secondary and tertiary results about the patients condition. The results from MCG tests have been validated in 8 clinical trials which resulted in a database of over 50,000 patients where the system has demonstrated accuracy comparable to coronary angiography (90% overall sensitivity, 85% specificity).
This level of accuracy comes from the application of advanced techniques in signal processing and systems analysis combined with a large scale clinical database which allows MCG to provide quantitative, evidence-based results to assist physicians in reaching a diagnosis. The MCG has also been awarded a Category III CPT code by the American Medical Association
American Medical Association
The American Medical Association , founded in 1847 and incorporated in 1897, is the largest association of medical doctors and medical students in the United States.-Scope and operations:...
in the July 2009 CPT update.
Exercise
Separate to the question of the benefits of exercise; it is unclear whether doctors should spend time counseling patients to exercise. The U.S. Preventive Services Task Force (USPSTF), based on a systematic reviewSystematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
of randomized controlled trials, found 'insufficient evidence' to recommend that doctors counsel patients on exercise, but "it did not review the evidence for the effectiveness of physical activity to reduce chronic disease, morbidity and mortality", it only examined the effectiveness of the counseling itself. However, the American Heart Association
American Heart Association
The American Heart Association is a non-profit organization in the United States that fosters appropriate cardiac care in an effort to reduce disability and deaths caused by cardiovascular disease and stroke. It is headquartered in Dallas, Texas...
, based on a non-systematic review, recommends that doctors counsel patients on exercise.
Preventive diets
It has been suggested that coronary artery disease is partially reversible using an intense dietary regimen coupled with regular cardio exercise.- Vegetarian diet: VegetariansVegetarianismVegetarianism encompasses the practice of following plant-based diets , with or without the inclusion of dairy products or eggs, and with the exclusion of meat...
have been shown to have a 24% reduced risk of dying of heart disease. - Cretan Mediterranean dietMediterranean dietThe Mediterranean diet is a modern nutritional recommendation inspired by the traditional dietary patterns of southern Italy, Crete and much of the rest of Greece in the 1960s....
: The Seven Countries StudySeven Countries StudyThe Seven Countries Study is an important epidemiological study. It is a large longitudinal study. It was the first study to systematically examine the relationships between lifestyle, diet, coronary heart disease and stroke in different populations from different regions of the world...
found that Cretan men had exceptionally low death rates from heart disease, despite moderate to high intake of fat. The Cretan dietCretan dietCretan cuisine is the traditional cuisine of the Mediterranean island of Crete.The core of the cuisine consists of food derived from natural sources, whereas food of animal origin was more peripheral in nature. In general, people consumed seasonal products, available in the wider local area, which...
is similar to other traditional Mediterranean diets: consisting mostly of olive oilOlive oilOlive oil is an oil obtained from the olive , a traditional tree crop of the Mediterranean Basin. It is commonly used in cooking, cosmetics, pharmaceuticals, and soaps and as a fuel for traditional oil lamps...
, bread, abundant fruit and vegetables, a moderate amount of wine and fat-rich animal products such as lamb, and goat cheese. However, the Cretan dietCretan dietCretan cuisine is the traditional cuisine of the Mediterranean island of Crete.The core of the cuisine consists of food derived from natural sources, whereas food of animal origin was more peripheral in nature. In general, people consumed seasonal products, available in the wider local area, which...
consisted of less fish and wine consumption than some other Mediterranean-style diets, such as the diet in CorfuCorfuCorfu is a Greek island in the Ionian Sea. It is the second largest of the Ionian Islands, and, including its small satellite islands, forms the edge of the northwestern frontier of Greece. The island is part of the Corfu regional unit, and is administered as a single municipality. The...
, another region of Greece, which had higher death rates.
The consumption of trans fat
Trans fat
Trans fat is the common name for unsaturated fat with trans-isomer fatty acid. Because the term refers to the configuration of a double carbon-carbon bond, trans fats are sometimes monounsaturated or polyunsaturated, but never saturated....
(commonly found in hydrogenated products such as margarine
Margarine
Margarine , as a generic term, can indicate any of a wide range of butter substitutes, typically composed of vegetable oils. In many parts of the world, the market share of margarine and spreads has overtaken that of butter...
) has been shown to cause the development of endothelial dysfunction
Endothelial dysfunction
Endothelial dysfunction is a systemic pathological state of the endothelium and can be broadly defined as an imbalance between vasodilating and vasoconstricting substances produced by the endothelium...
, a precursor to atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
. The consumption of trans fatty acids has been shown to increase the risk of coronary artery disease
Foods containing fiber
Fiber
Fiber is a class of materials that are continuous filaments or are in discrete elongated pieces, similar to lengths of thread.They are very important in the biology of both plants and animals, for holding tissues together....
, potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
, nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
(in green leafy vegetables), monounsaturated fat
Monounsaturated fat
In biochemistry and nutrition, monounsaturated fats or MUFA are fatty acids that have one double bond in the fatty acid chain and all of the remainder of the carbon atoms in the chain are single-bonded...
, polyunsaturated fat
Polyunsaturated fat
In nutrition, polyunsaturated fat, or polyunsaturated fatty acid, are fatty acids in which more than one carbon–carbon double bond exists within the representative molecule. That is, the molecule has two or more points on its structure capable of supporting hydrogen atoms not currently part of the...
, saponin
Saponin
Saponins are a class of chemical compounds, one of many secondary metabolites found in natural sources, with saponins found in particular abundance in various plant species...
s, or lecithin
Lecithin
Lecithin is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues, and in egg yolk, composed of phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides, and phospholipids .The word lecithin was originally coined in 1847 by...
are said to lower cholesterol levels. Foods high in grease
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
, salt
Salt
In chemistry, salts are ionic compounds that result from the neutralization reaction of an acid and a base. They are composed of cations and anions so that the product is electrically neutral...
, trans fat
Trans fat
Trans fat is the common name for unsaturated fat with trans-isomer fatty acid. Because the term refers to the configuration of a double carbon-carbon bond, trans fats are sometimes monounsaturated or polyunsaturated, but never saturated....
, or saturated fat
Saturated fat
Saturated fat is fat that consists of triglycerides containing only saturated fatty acids. Saturated fatty acids have no double bonds between the individual carbon atoms of the fatty acid chain. That is, the chain of carbon atoms is fully "saturated" with hydrogen atoms...
are said to raise cholesterol levels.
Aspirin
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 90 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
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
found insignificant
Statistical significance
In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....
benefit from aspirin in the reduction of cardiac events; however there was a significant
Statistical significance
In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....
reduction in stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
. Subgroup analysis
Subgroup analysis
Subgroup analysis, in the context of design and analysis of experiments, refers to looking for pattern in a subset of the subjects....
showed that all benefit was confined to women over 65 years old. In spite of the insignificant
Statistical significance
In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....
benefit for women <65 years old, recent practice guidelines by the American Heart Association
American Heart Association
The American Heart Association is a non-profit organization in the United States that fosters appropriate cardiac care in an effort to reduce disability and deaths caused by cardiovascular disease and stroke. It is headquartered in Dallas, Texas...
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-analysisMeta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
on studies using traditional omega-3 products of randomized controlled trials by the international Cochrane Collaboration
Cochrane Collaboration
The Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
and a partially positive systematic review
Systematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
AHRQ Evidence reports and summaries 94. Effects of Omega-3 Fatty Acids on Cardiovascular Disease by the Agency for Healthcare Research and Quality
Agency for Healthcare Research and Quality
The Agency for Healthcare Research and Quality is a part of the United States Department of Health and Human Services, which supports research designed to improve the outcomes and quality of health care, reduce its costs, address patient safety and medical errors, and broaden access to effective...
. Since these two reviews, a randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
reported a remarkable reduction on coronary events in Japanese hypercholesterolemic patients, and a later subanalysis suggested that the protective effect of highly purified EPA (E-EPA
E-EPA
Ethyl eicosapentaenoic acid is a highly purified, vacuum distilled derivate of the omega-3 fatty acid eicosapentaenoic acid . In Japan E-EPA is often called EPA-E.Only EPA is considered to exihibit antipsychotic and antidepressive effects...
) is even more pronounced in Japanese diabetics even though their intake of fish is high.
Omega-3 fatty acids are also found in some plant sources including flax seed oil, hemp seed oil, and walnut
Walnut
Juglans is a plant genus of the family Juglandaceae, the seeds of which are known as walnuts. They are deciduous trees, 10–40 meters tall , with pinnate leaves 200–900 millimetres long , with 5–25 leaflets; the shoots have chambered pith, a character shared with the wingnuts , but not the hickories...
s. The plant omega-3 (ALA) is biologically inferior to marine omega-3, as ALA needs to be converted in the liver to EPA, but only about five per cent is converted.
Secondary prevention
Secondary prevention is preventing further sequelae of already established disease. Regarding coronary artery disease, this can mean risk factor management that is carried out during cardiac rehabilitation, a 4-phase process beginning in hospital after MI, angioplasty or heart surgery and continuing for a minimum of three months. Exercise is a main component of cardiac rehabilitation along with diet, smoking cessation, and blood pressure and cholesterol management. Beta blockers may also be used for this purpose.Anti-platelet therapy
A meta-analysisMeta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
of randomized controlled trials by the international Cochrane Collaboration
Cochrane Collaboration
The Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
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:- 1. Medical treatment - drugs (e.g. cholesterol lowering medications, beta-blockers, nitroglycerin, calcium antagonists, etc.);
- 2. Coronary interventions as angioplastyAngioplastyAngioplasty is the technique of mechanically widening a narrowed or obstructed blood vessel, the latter typically being a result of atherosclerosis. An empty and collapsed balloon on a guide wire, known as a balloon catheter, is passed into the narrowed locations and then inflated to a fixed size...
and coronary stentCoronary stentA coronary stent is a tube placed in the coronary arteries that supply the heart, to keep the arteries open in the treatment of coronary heart disease. It is used in a procedure called percutaneous coronary intervention...
-implantation; - 3. Coronary artery bypass grafting (CABG - coronary artery bypass surgeryCoronary artery bypass surgeryCoronary artery bypass surgery, also coronary artery bypass graft surgery, and colloquially heart bypass or bypass surgery is a surgical procedure performed to relieve angina and reduce the risk of death from coronary artery disease...
).
Recent research efforts focus on new angiogenic treatment modalities (angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
) and various (adult) stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
therapies.
Recent research
A 2006 study by the Cleveland ClinicCleveland Clinic
The Cleveland Clinic is a multispecialty academic medical center located in Cleveland, Ohio, United States. The Cleveland Clinic is currently regarded as one of the top 4 hospitals in the United States as rated by U.S. News & World Report...
found a region on Chromosome 17 was confined to families with multiple cases of myocardial infarction.
A more controversial link is that between Chlamydophila pneumoniae
Chlamydophila pneumoniae
Chlamydophila pneumoniae is a species of Chlamydophila, an obligate intracellular bacteria that infects humans and is a major cause of pneumonia....
infection and atherosclerosis. While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor. Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.
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
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
and (adult) stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
therapies. Numerous clinical trials were performed, either applying protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
(angiogenic growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
) therapies, such as FGF-1 or VEGF
Vascular endothelial growth factor
Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....
, or cell therapies using different kinds of adult stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
populations. Research is still going on - with first promising results particularly for FGF-1 and utilization of endothelial progenitor cells.
See also
- Diet and Heart Disease
- ApoA-1 MilanoApoA-1 MilanoApoA-1 Milano is a naturally occurring mutated variant of the apolipoprotein A1 protein found in human HDL, the lipoprotein particle that carries cholesterol from tissues to the liver and is associated with protection against cardiovascular disease. ApoA1 Milano was first identified by Dr...
- Endothelium-derived relaxing factorEndothelium-derived relaxing factorEndothelium-derived relaxing factor is produced and released by the endothelium to promote smooth muscle relaxation. The best-characterized is nitric oxide . Some sources equate EDRF and nitric oxide....
- CADgeneCADgeneCADgene is a database of genes involved in coronary artery disease ....
database
External links
- Risk Assessment of having a heart attack or dying of coronary artery disease, from the American Heart Association.
- Risk Assessment Tool for Estimating 10-year Risk of Developing Hard CHD using Framingham score
- The InVision Guide to a Healthy Heart An interactive website on the development and function of the cardiovascular system and cardiovascular diseases and consequences. The website also features treatment options and preventative measures for maintaining a healthy heart.
- A Mechanism of a Metabolic Induction of Coronary Artery Disease in Chronic Kidney Disease, Rainer K. Liedtke, MD