Vulnerable plaque
Encyclopedia
A vulnerable plaque is a kind of atheromatous plaque – a collection of white blood cell
s (primarily macrophage
s) and lipids (including cholesterol
) in the wall of an artery
- that is particularly unstable and prone to produce sudden major problems, such as a heart attack
or stroke.
In many cases, a vulnerable plaque has a thin fibrous cap
and a large and soft lipid pool underlying the cap. These characteristics together with the usual hemodynamic pulsating expansion during systole
and elastic recoil contraction during diastole
contribute to a high mechanical stress zone on the fibrous cap
of the atheroma
, making it prone to rupture. Increased hemodynamic stress correlates with increased rates of major cardiovascular events associated with exercise, especially exercise beyond levels the individual does routinely. This video http://www.youtube.com/watch?v=F0Y5hss1tZQ, examining autopsy specimens from an actual heart attack resulting in sudden death, shows the sequence. These videos, http://www.youtube.com/watch?v=XLLBlBiboJI&NR=1 and http://www.youtube.com/watch?v=w8wXdtoW-HQ&feature=related, illustrate the sequence of events and why, though the underlying process develops over decades, the symptoms are often of sudden onset.
Generally an atheroma
becomes vulnerable if it grows more rapidly and has a thin cover separating it from the bloodstream inside the arterial lumen
. Tearing of the cover is called plaque rupture.
Repeated atheroma
rupture and healing is one of the mechanisms, perhaps the dominant one, which creates artery
stenosis
.
, in the walls of the arteries leads to the development of "soft" or vulnerable plaque, which when released aggressively promotes blood clotting.
Researchers now think that vulnerable plaque, (see atherosclerosis
) is formed in the following way:
When this inflammation is combined with other stresses, such as high blood pressure (increased mechanical stretching and contraction of the arteries with each heart beat), it can cause the thin covering over the plaque to split, spilling the contents of the vulnerable plaque into the bloodstream. The sticky cytokines on the artery wall capture blood cells (mainly platelet
s) that accumulate at the site of injury. When these cells clump together, they form a clot, sometimes large enough to block the artery.
The most frequent cause of a cardiac event following rupture of a vulnerable plaque is blood clotting
on top of the site of the ruptured plaque that blocks the lumen of the artery
, thereby stopping blood flow to the tissues the artery
supplies.
Upon rupture, atheroma tissue debris may spill into the blood stream; this debris is often too large (over 5 micrometers) to pass on through the capillaries
downstream. In this, the usual situation, the debris obstruct smaller downstream branches of the artery resulting in temporary to permanent end artery/capillary closure with loss of blood supply to, and death of the previously supplied tissues. A severe case of this can be seen during angioplasty
in the slow clearance of injected contrast down the artery lumen. This situation is often termed non-reflow.
Additionally, atheroma
rupture may allow bleeding from the lumen into the inner tissue of the atheroma
making the atheroma size suddenly increase and protrude into the lumen of the artery producing lumen narrowing
or even total obstruction.
Because artery walls typically enlarge in response to enlarging plaques, these plaques do not usually produce much stenosis
of the artery lumen. Therefore, they are not detected by cardiac stress tests or angiography, the tests most commonly performed clinically with the goal of predicting susceptibility to future heart attack. Additionally, because these lesions do not produce significant stenoses, they are typically not considered "critical" and/or interventionable by interventional cardiologists, even though research indicates that they are the more important lesions for producing heart attacks.
The tests most commonly performed clinically with the goal of testing susceptibility to future heart attack include several medical research efforts, starting in the early to mid-1990s, using intravascular ultrasound (IVUS), thermography
, near-infrared spectroscopy, careful clinical follow-up and other methods, to predict these lesions and the individuals most prone to future heart attacks. These efforts remain largely research with no useful clinical methods to date (2006).
Another approach to detecting and understanding plaque behavior, used in research and by a few clinicians, is to use ultrasound to non-invasively measure wall thickness
(usually abbreviated IMT
) in portions of larger arteries closest to the skin, such as the carotid or femoral arteries. While stability vs. vulnerability cannot be readily distinguished in this way, quantitative baseline measurements of the thickest portions of the arterial wall (locations with the most plaque accumulation). Documenting the IMT, location of each measurement and plaque size, a basis for tracking and partially verifying the effects of medical treatments on the progression, stability or potential regression of plaque, within a given individual over time, may be achieved.
patterns, keep blood glucose levels low normal (see HbA1c), stay slender, take aspirin, eat a proper diet, quit smoking, and maintain a regular exercise program. Researchers also think that obesity and diabetes may be tied to high levels of C-reactive protein.
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s (primarily macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s) and lipids (including 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...
) in the wall of an 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....
- that is particularly unstable and prone to produce sudden major problems, such as a 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...
or stroke.
In many cases, a vulnerable plaque has a thin fibrous cap
Fibrous cap
The fibrous cap is a layer of fibrous connective tissue, which is thicker and less cellular than the normal intima. The fibrous cap contains macrophages and smooth muscle cells....
and a large and soft lipid pool underlying the cap. These characteristics together with the usual hemodynamic pulsating expansion during systole
Systole (medicine)
Systole is the contraction of the heart. Used alone, it usually means the contraction of the left ventricle.In all mammals, the heart has 4 chambers. The left and right ventricles pump together. The atria and ventricles pump in sequence...
and elastic recoil contraction during diastole
Diastole
Diastole is the period of time when the heart fills with blood after systole . Ventricular diastole is the period during which the ventricles are relaxing, while atrial diastole is the period during which the atria are relaxing...
contribute to a high mechanical stress zone on the fibrous cap
Fibrous cap
The fibrous cap is a layer of fibrous connective tissue, which is thicker and less cellular than the normal intima. The fibrous cap contains macrophages and smooth muscle cells....
of the 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...
, making it prone to rupture. Increased hemodynamic stress correlates with increased rates of major cardiovascular events associated with exercise, especially exercise beyond levels the individual does routinely. This video http://www.youtube.com/watch?v=F0Y5hss1tZQ, examining autopsy specimens from an actual heart attack resulting in sudden death, shows the sequence. These videos, http://www.youtube.com/watch?v=XLLBlBiboJI&NR=1 and http://www.youtube.com/watch?v=w8wXdtoW-HQ&feature=related, illustrate the sequence of events and why, though the underlying process develops over decades, the symptoms are often of sudden onset.
Generally an 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...
becomes vulnerable if it grows more rapidly and has a thin cover separating it from the bloodstream inside the arterial lumen
Lumen (anatomy)
A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
. Tearing of the cover is called plaque rupture.
Repeated 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...
rupture and healing is one of the mechanisms, perhaps the dominant one, which creates 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....
stenosis
Stenosis
A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure.It is also sometimes called a stricture ....
.
Causes
Researchers have found that accumulation of white blood cells, especially macrophages, termed inflammationAtherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
, in the walls of the arteries leads to the development of "soft" or vulnerable plaque, which when released aggressively promotes blood clotting.
Researchers now think that vulnerable plaque, (see atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
) is formed in the following way:
- LipoproteinLipoproteinA lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
LDL particles, which carry fats (including the fat cholesterolCholesterolCholesterol 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...
) within the water/plasmaPlasmaPlasma may refer to:* Blood plasma, the yellow-colored liquid component of blood, in which blood cells are suspended* Plasma , an ionized state of matter similar to a gas...
portion of the blood stream, are absorbed into the artery wall, past the endotheliumEndotheliumThe endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
lining, some of the LDL-lipoprotein particles become oxidized and this attracts macrophages which eat the particles. This process typically starts in childhood. Specifically: - oxidized lipoprotein particles in the artery wall are an irritant which causes the release of proteins (called cytokineCytokineCytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s) which attract monocyte white blood cells (white blood cells are the inflammatory cells within the body). - The cytokines induce the endothelial cells lining the artery wall to display adhesion molecules which attract immune-system white blood cells (specifically monocytes).
- The monocytes squeeze into the artery wall. Once inside, they transform into eating cells called macrophages and ingest the oxidized lipoprotein particles.
- The macrophages sometimes become so overloaded with oxidized lipoprotein particles, the cholesterol contained therein and membrane laden that they are called foam cells. Some of these cells die in place, releasing their fat and cholesterol laden membranes into the intracellular space. This attracts more macrophages.
- In some regions of increased macrophage activity, macrophage-induced-enzymes erode away the fibrous membrane beneath the endothelium so that the cover separating the plaque from blood flow in the lumenLumen (anatomy)A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
becomes thin and fragile. - Mechanical stretching and contraction of the artery, with each heart beat, i.e. the pulse, results in rupture of the thin covering membrane spewing clot-promoting plaque contents into the blood stream.
- The clotting system reacts and forms clots both on the particles shed into the blood stream and locally over the rupture. The clot, if large enough, can block all blood flow. Since all the blood, within seconds, passes through 5 micrometre capillaries, any particles much larger than 5 micrometres block blood flow. (most of the occlusions are too small to see by angiography).
- Most ruptures and clotting events are too small to produce symptoms, though they still produce heart muscle damage, a slow progressive process resulting in ischemic heart disease, the most common basis for congestive heart failureCongestive heart failureHeart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
. - The clot organizes and contracts over time, leaving behind narrowing(s) called stenoses. These narrowing(s) are responsible for both the symptoms of the disease and are identified, after the fact, by the changes seen on stress testsCardiac 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....
, angiography and treated with 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...
and/or 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...
, with or without stents.
When this inflammation is combined with other stresses, such as high blood pressure (increased mechanical stretching and contraction of the arteries with each heart beat), it can cause the thin covering over the plaque to split, spilling the contents of the vulnerable plaque into the bloodstream. The sticky cytokines on the artery wall capture blood cells (mainly platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
s) that accumulate at the site of injury. When these cells clump together, they form a clot, sometimes large enough to block the artery.
The most frequent cause of a cardiac event following rupture of a vulnerable plaque is blood clotting
Thrombus
A thrombus , or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system...
on top of the site of the ruptured plaque that blocks the lumen 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....
, thereby stopping blood flow to the tissues 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....
supplies.
Upon rupture, atheroma tissue debris may spill into the blood stream; this debris is often too large (over 5 micrometers) to pass on through the capillaries
Capillary
Capillaries are the smallest of a body's blood vessels and are parts of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...
downstream. In this, the usual situation, the debris obstruct smaller downstream branches of the artery resulting in temporary to permanent end artery/capillary closure with loss of blood supply to, and death of the previously supplied tissues. A severe case of this can be seen during 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...
in the slow clearance of injected contrast down the artery lumen. This situation is often termed non-reflow.
Additionally, 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...
rupture may allow bleeding from the lumen into the inner tissue of the 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...
making the atheroma size suddenly increase and protrude into the lumen of the artery producing lumen narrowing
Stenosis
A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure.It is also sometimes called a stricture ....
or even total obstruction.
Detection
While a single ruptured plaque can be identified during autopsy as the cause of a coronary event, there is currently no way to identify a culprit lesion before it ruptures.Because artery walls typically enlarge in response to enlarging plaques, these plaques do not usually produce much stenosis
Stenosis
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 artery lumen. Therefore, they are not detected by cardiac stress tests or angiography, the tests most commonly performed clinically with the goal of predicting susceptibility to future heart attack. Additionally, because these lesions do not produce significant stenoses, they are typically not considered "critical" and/or interventionable by interventional cardiologists, even though research indicates that they are the more important lesions for producing heart attacks.
The tests most commonly performed clinically with the goal of testing susceptibility to future heart attack include several medical research efforts, starting in the early to mid-1990s, using intravascular ultrasound (IVUS), thermography
Thermography
Infrared thermography, thermal imaging, and thermal video are examples of infrared imaging science. Thermal imaging cameras detect radiation in the infrared range of the electromagnetic spectrum and produce images of that radiation, called thermograms...
, near-infrared spectroscopy, careful clinical follow-up and other methods, to predict these lesions and the individuals most prone to future heart attacks. These efforts remain largely research with no useful clinical methods to date (2006).
Another approach to detecting and understanding plaque behavior, used in research and by a few clinicians, is to use ultrasound to non-invasively measure wall thickness
Intima-media thickness
Intima-media thickness , also called intimal medial thickness, is a measurement of the thickness of artery walls, usually by external ultrasound, occasionally by internal, invasive ultrasound catheters, see IVUS, to both detect the presence and to track the progression of atherosclerotic disease in...
(usually abbreviated IMT
Intima-media thickness
Intima-media thickness , also called intimal medial thickness, is a measurement of the thickness of artery walls, usually by external ultrasound, occasionally by internal, invasive ultrasound catheters, see IVUS, to both detect the presence and to track the progression of atherosclerotic disease in...
) in portions of larger arteries closest to the skin, such as the carotid or femoral arteries. While stability vs. vulnerability cannot be readily distinguished in this way, quantitative baseline measurements of the thickest portions of the arterial wall (locations with the most plaque accumulation). Documenting the IMT, location of each measurement and plaque size, a basis for tracking and partially verifying the effects of medical treatments on the progression, stability or potential regression of plaque, within a given individual over time, may be achieved.
Prevention
Patients can lower their risk for vulnerable plaque rupture in the same ways that they can cut their heart attack risk: optimize lipoproteinLipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
patterns, keep blood glucose levels low normal (see HbA1c), stay slender, take aspirin, eat a proper diet, quit smoking, and maintain a regular exercise program. Researchers also think that obesity and diabetes may be tied to high levels of C-reactive protein.