Atheroma
Encyclopedia
In pathology
, an atheroma (from ἀθήρωμα (athērōma)=“tumor full gruel-like matter”) is an accumulation and swelling in artery
walls that is made up of (mostly) macrophage
cells
, or debris, that contain lipids (cholesterol
and fatty acids), calcium and a variable amount of fibrous connective tissue
. Atheroma occurs in atherosclerosis
, which is one of the three subtypes of arteriosclerosis
; atherosclerosis, Monckeberg's arteriosclerosis
and arteriolosclerosis
.
In the context of heart or artery matters, atheromata are commonly referred to as atheromatous plaques. It is an unhealthy condition, but is found in most humans.
These anatomic lesions usually begin in some children younger than age 1 year and all children older than age 10 regardless of geography, race, sex, or environment. Vein
s do not develop atheromata, unless surgically moved to function as an artery, as in bypass
surgery. The accumulation (swelling) is always between the endothelium
lining and the smooth muscle wall central region (media) of the arterial tube (see IMT
). While the early stages, based on gross appearance, have traditionally been termed fatty streaks by pathologists, they are not composed of fat cells, i.e. adipose cells, but of accumulations of white blood cells, especially macrophages that have taken up oxidized low-density lipoprotein (LDL). After they accumulate large amounts of cytoplasmic membranes (with associated high cholesterol content) they are called foam cells. When foam cells die, their contents are released, which attracts more macrophages and creates an extracellular lipid core near the center to inner surface of each atherosclerotic plaque. Conversely, the outer, older portions of the plaque become more calcific, less metabolically active and more physically stiff over time.
and ensuing debility. However, the heart arteries, because (a) they are small (from about 5 mm down to microscopic), (b) they are hidden deep within the chest and (c) they never stop moving, have been a difficult target organ to track, especially clinically in individuals who are still asymptomatic. Additionally, all mass-applied clinical strategies focus on both (a) minimal cost and (b) the overall safety of the procedure. Therefore, existing diagnostic strategies for detecting atheroma and tracking response to treatment have been extremely limited. The methods most commonly relied upon, patient symptoms and cardiac stress testing, do not detect any symptoms of the problem until atheromatous disease is very advanced.
, infection control and increasing life spans, atheroma processes have become an increasingly important problem and burden for society.
Atheroma continue to be the number one underlying basis for disability
and death
, despite a trend for gradual improvement since the early 1960s (adjusted for patient age). Thus, increasing efforts towards better understanding, treating and preventing the problem are continuing to evolve.
According to United States data, 2004, for about 65% of men and 47% of women, the first symptom
of cardiovascular disease is heart attack
or sudden death (death within one hour of symptom onset.)
Most artery flow disrupting events occur at locations with less than 50% lumen
narrowing. From clinical studies published in the late 1990s to IVUS (in-the-artery-ultrasound) to visualize disease status, the typical heart attack occurs at locations with about 20% stenosis (narrowing), prior to sudden lumen closure and resulting heart attack
. Cardiac stress test
ing, traditionally the most commonly performed non-invasive testing method for blood flow limitations generally only detects lumen narrowing of ~75% or greater, although some physicians advocate that nuclear stress methods can sometimes detect as little as 50%.
s (enlargements) just large enough to compensate for the extra wall thickness with no change in the lumen diameter. However, eventually, typically as a result of rupture of vulnerable plaque
s and clots within the lumen over the plaque, stenosis
(narrowing) of the vessel develops in some areas. Less frequently, the artery enlarges so much that a gross aneurysm
al enlargement of the artery results. All three results are often observed, at different locations, within the same individual.
to stretch out, termed remodeling, typically just enough to compensate for their size such that the caliber
of the artery
opening (lumen) remains unchanged until typically over 50% of the artery wall cross-sectional area consists of atheromatous tissue (see: Glagov, below).
If the muscular wall enlargement eventually fails to keep up with the enlargement of the atheroma volume, or a clot forms and organizes over the plaque, then the lumen of the artery begins to narrow, commonly as a result of repeated ruptures of the covering tissues separating the atheroma from the blood stream. This becomes a more common event after decades of living, increasingly more common after people are in their 30s to 40s.
The endothelium
(the cell monolayer on the inside of the vessel) and covering tissue, termed fibrous cap
, separate atheroma from the blood in the lumen. If a rupture occurs of the endothelium and fibrous cap, then a platelet and clotting response over the rupture rapidly develops. Additionally, the rupture may result in a shower of debris. Platelet
and clot accumulation over the rupture may produce narrowing/closure of the lumen and tissue damage may occur due to either closure of the lumen and loss of blood flow beyond the ruptured atheroma and/or by occlusion of smaller downstream vessels by debris. See vulnerable plaque
.
This is the principal mechanism of heart attack
, stroke
or other related cardiovascular disease
problems. As research has shown, this process is not a result of stenosis
. Prior to the rupture, there may have been no lumen narrowing, even aneurysmal enlargement, at the atheroma. On average, by clinical research using IVUS, there is a minor stenosis, about 20%, present over those unstable atheroma which rupture and result in major disability or death. Comparatively, stenoses of about 75% are required to produce detectable abnormalities during cardiac stress test
s.
of the artery results, usually over decades of living. This is a less common outcome. Atheroma within aneurysmal enlargement (vessel bulging) can also rupture and shower debris of atheroma and clot downstream. If the arterial enlargement
continues to 2 to 3 times the usual diameter, the walls often become weak enough that with just the stress of the pulse, a loss of wall integrity may occur leading to sudden hemorrhage (bleeding), major symptoms and debility; often rapid death. The main stimulus for aneurysm formation is pressure atrophy of the structural support of the muscle layers. The main structural proteins are collagen
and elastin
. This causes thinning and the wall balloons allowing gross enlargement to occur, as is common in the abdominal region of the aorta.
) as a surrogate endpoint for evaluating the regression and/or progression of atherosclerotic cardiovascular disease. Many studies have documented the relation between the carotid intima-media thickness and the presence and severity of atherosclerosis. In 2003 the European Society of Hypertension-European Society of Cardiology recommended the use of IMT measurements in high-risk patients to help identify target organ damage not revealed by other exams such as the electrocardiogram.
Though it seems clear that carotid intima-media thickness is strongly associated with atherosclerosis
, it is worth noting that not all the processes of thickening of the intima-media are due to atherosclerosis. Intimal thickening is in fact a complex process, depending on a variety of factors, not necessarily related to atherosclerosis. Local hemodynamics
plays an important role, higher blood pressure and changes in shear stress being potential causes of intimal thickening. Changes in shear stress and blood pressure may cause a local delay in lumen transportation of potentially atherogenic particles, which favors the penetration of particles into the arterial wall and consequent plaque formation. However non-atherosclerotic reactions may also exist, as in intimal hyperplasia and intimal fibrocellular hypertrophy, two different compensatory reactions of the arterial wall to changes in shear stress, which also consist in thickening of the arterial wall. In some cases, more than one of these reactions may be present, and indeed as all of these are associated to particular flow conditions, they are often found in common areas, such as the inflow side of branches, the inner curvature at bends and opposite the flow divider at bifurcations. However, changes in the IMT above thresholds of around 900 μm almost certainly are indicative of an atherosclerotic pathology.
Mechanisms such as these may explain, at least in part, why the carotid artery seems to be a preferential site for analyzing the relation between wall thickness and atherosclerosis. In general, wall thickening may be in the intimal layer or in the muscular, medial, layer. As the carotid artery is an elastic artery, the muscular media is relatively small. Hence, thickening of the carotid arterial wall is due essentially to intimal thickening. In muscular arteries wall thickening may imply instead (or also) a thickening of the medial wall. Whether or not wall thickening in the carotid artery and the femoral artery (or other muscular arteries) have the same meaning is as yet uncertain. Several studies seem to suggest that the mechanisms underlying their evolution may at least in part differ, with consequently possibly different clinical implications.
Another issue to consider, once the choice to examine the carotid artery has been defined, is on which segment of the carotid artery to perform the measurement. Often, the measurement of the IMT is measured in three tracts: in the common carotid, at one or two cms from the flow divider, at the bifurcation and in the internal carotid artery.
From an academic standpoint, the region to select for IMT measurement is still an object of study. IMT measurements of the deep wall, by ultrasound, are generally more reliable than measurements performed on the outer wall. This difference in the accuracy of near and far wall measurements may be a problem, as some studies have used both measurements to quantify the IMT.
A practical approach to tracking disease presence and progression on any given individual is to select and track those regions with the greatest thickness, i.e. greatest disease burden, as opposed to arbitrarily selecting a particular segment in which the individual may not have much pathology.
(non-occlusive or soft plaque), have led, since the 1950s, to the development of intensive care units and complex medical and surgical interventions. Angiography and later cardiac stress testing was begun to either visualize or indirectly detect stenosis
. Next came bypass
surgery, to plumb transplanted vein
s, sometimes arteries, around the stenoses
and more recently angioplasty
, now including stent
s, most recently drug coated stent
s, to stretch the stenoses
more open.
Yet despite these medical advances, with success in reducing the symptoms of angina and reduced blood flow
, atheroma rupture events remain the major problem and still sometimes result in sudden disability and death despite even the most rapid, massive and skilled medical and surgical intervention available anywhere today. According to some clinical trials, bypass surgery
and angioplasty
procedures have had at best a minimal effect, if any, on improving overall survival. Typically mortality of by-pass operations is from 1–4%, of angioplasty about 1–1.5%.
Additionally, these vascular interventions are often done only after an individual is symptomatic, often already partially disabled, as a result of the disease. It is also clear that both angioplasty and by-pass interventions do not prevent future heart attack
.
The older methods for understanding atheroma, dating to before World War II
, relied on autopsy data. Autopsy data has long shown initiation of fatty streaks in later childhood with slow asymptomatic progression over decades.
One way to see atheroma is the very invasive and costly IVUS ultrasound technology; it gives us the precise volume of the inside intima plus the central media
layers of about 2.5 cm (0.984251968503937 in) of artery length. Unfortunately, it gives no information about the structural strength of the artery. Angiography does not visualize atheroma; it only makes the blood flow
within blood vessels visible. Alternative methods that are non or less physically invasive and less expensive per individual test have been used and are continuing to be developed, such as those using computed tomography
(CT; led by the Electron Beam Tomography
form, given its greater speed) and magnetic resonance imaging
(MRI). The most promising since the early 1990s has been EBT, detecting calcification within the atheroma before most individuals start having clinically recognized symptoms and debility. Interestingly, statin therapy (to lower cholesterol) does not slow the speed of calcification as determined by CT scan. MRI coronary vessel wall imaging, although currently limited to research studies, has demonstrated the ability to detect vessel wall thickening in asymptomatic high risk individuals (reference - Kim 2002, Circulation). As a non-invasive, ionising radiation free technique, MRI based techniques could have future uses in monitoring disease progression and regression. Most visualization techniques are used in research, they are not widely available to most patients, have significant technical limitations, have not been widely accepted and generally are not covered by medical insurance carriers.
From human clinical trials, it has become increasingly evident that a more effective focus of treatment is slowing, stopping and even partially reversing the atheroma growth process. There are several prospective epidemiologic studies including the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS), which have supported a direct correlation of CIMT with myocardial infarction and stroke risk in patients without cardiovascular disease history. The ARIC Study was conducted in 15,792 individuals between 5 and 65 years of age in 4 different regions of the USA between 1987 and 1989. The baseline CIMT was measured and measurements were repeated at 4–7 year intervals by carotid B mode ultrasonography in this study. An increase in CIMT was correlated with an increased risk for CAD. The CHS was initiated in 1988, and the relationship of CIMT with risk of myocardial infarction and stroke was investigated in 4,476 subjects ≤65 years of age. At the end of approximately 6 years of follow-up, CIMT measurements were correlated with cardiovascular events.
Paroi artérielle et Risque Cardiovasculaire in Asia Africa/Middle East and Latin America (PARC-AALA) is another important large-scale study, in which 79 centers from countries in Asia, Africa, the Middle East, and Latin America participated, and the distribution of CIMT according to different ethnic groups and its association with the Framingham cardiovascular score was investigated. Multi-linear regression analysis revealed that an increased Framingham cardiovascular score was associated with CIMT, and carotid plaque independent of geographic differences.
Cahn et al. prospectively followed-up 152 patients with coronary artery disease for 6–11 months by carotid artery ultrasonography and noted 22 vascular events (myocardial infarction, transient ischemic attack, stroke, and coronary angioplasty) within this time period. They concluded that carotid atherosclerosis measured by this non-interventional method has prognostic significance in coronary artery patients.
In the Rotterdam Study
, Bots et al. followed 7,983 patients >55 years of age for a mean period of 4.6 years, and reported 194 incident myocardial infarctions within this period. CIMT was significantly higher in the myocardial infarction group compared to the other group. Demircan et al. found that the CIMT of patients with acute coronary syndrome were significantly increased compared to patients with stable angina pectoris.
It has been reported in another study that a maximal CIMT value of 0.956 mm had 85.7% sensitivity and 85.1% specificity to predict angiographic CAD. The study group consisted of patients admitted to the cardiology outpatient clinic with symptoms of stable angina pectoris. The study showed CIMT was higher in patients with significant CAD than in patients with non-critical coronary lesions. Regression analysis revealed that thickening of the mean intima-media complex more than 1.0 was predictive of significant CAD our patients. There was incremental significant increase in CIMT with the number coronary vessel involved. In accordance with the literature, it was found that CIMT was significantly higher in the presence of CAD. Furthermore, CIMT was increased as the number of involved vessels increased and the highest CIMT values were noted in patients with left main coronary involvement. However, human clinical trials have been slow to provide clinical & medical evidence, partly because the asymptomatic nature of atheromata make them especially difficult to study. Promising results are found using Carotid Intima Media Thickness Scanning (CIMT can be measured by B-mode ultrasonography), B-vitamins that reduce a protein corrosive, homocysteine
and that reduce neck carotid artery plaque volume and thickness, and stroke, even in late-stage disease.
Additionally, understanding what drives atheroma development is complex with multiple factors involved, only some of which, such as lipoprotein
s, more importantly lipoprotein subclass analysis, blood sugar
levels and hypertension
are best known and researched. More recently, some of the complex immune system
patterns that promote, or inhibit, the inherent inflammatory macrophage triggering processes involved in atheroma progression are slowly being better elucidated in animal models of atherosclerosis.
A 4 minute animation of the atherosclerosis process, entitled "Pathogenesis of Acute MI", commissioned by Paul M. Ridker, MD, MPH, FACC, FAHA, at the Harvard Medical School, can be viewed at pri-med.com http://www.pri-med.com/pmo/Home.aspx. While the animation contains a few technical errors, partly due to the great difficulty/complexity of making a truly accurate presentation, it correctly illustrates the principal issues.
CIMT (carotid IMT) as mentioned in the Evolution of Strategies and Changing Focus section, Interventional and non-interventional methods to detect atherosclerosis, specifically vulnerable plaque
(non-occlusive or soft plaque), are widely used in research and clinical practice today; Carotid Intima-media thickness
Scan (CIMT can be measured by B-mode ultrasonography) measurement has been recommended by the American Heart Association
as the most useful method to identify atherosclerosis and may now very well be the gold standard for detection.
IVUS is the current most sensitive method detecting and measuring more advanced atheroma within living individuals, though it is typically not used until decades after atheroma begin forming due to cost and body invasiveness.
CT Scans using state of the art higher resolution spiral, or the higher speed EBT
, machines have been the most effective method for detecting calcification present in plaque. However, the atheroma have to be advanced enough to have relatively large areas of calcification within them to create large enough regions of ~130 Hounsfield units
which the CT scanner software can recognize as distinct from the other surrounding tissues. Typically, such regions start occurring within the heart arteries about 2–3 decades after atheroma start developing. Hence the detection of much smaller plaques then previously possible is being developed by some companies, such as Image Analysis. The presence of smaller, spotty plaques may actually be the more dangerous culprit for progressing to acute myocardial infarction
.
Arterial ultrasound, especially of the carotid arteries, with measurement of the thickness of the artery wall, offers a way to partially track the disease progression. As of 2006, the thickness, commonly referred to as IMT for intimal-medial thickness, is not measured clinically though it has used by some researchers since the mid 1990s to track changes in arterial walls. Traditionally, clinical carotid ultrasounds have only estimated the degree of blood lumen restriction, stenosis
, a result of very advanced disease. The National Institute of Health did a five–year $5 million study, headed by medical researcher Kenneth Ouriel
, to study intravascular ultrasound techniques regarding atherosclerotic plaque. More progressive clinicians have begun using IMT measurement as a way to quantify and track disease progression or stability within individual patients.
Angiography, since the 1960s, has been the traditional way of evaluating for atheroma. However, angiography is only motion or still images of dye mixed with the blood with the arterial lumen and never show atheroma; the wall of arteries, including atheroma with the arterial wall remain invisible. The limited exception to this rule is that with very advance atheroma, with extensive calcification within the wall, a halo-like ring of radiodensity can be seen in most older humans, especially when arterial lumens are visualized end-on. On cine-floro, cardiologists and radiologists typically look for these calcification shadows to recognize arteries before they inject any contrast agent during angiograms.
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
, an atheroma (from ἀθήρωμα (athērōma)=“tumor full gruel-like matter”) is an accumulation and swelling in 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....
walls that is made up of (mostly) 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...
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....
, or debris, that contain lipids (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 fatty acids), calcium and a variable amount of fibrous connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
. Atheroma occurs in atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
, which is one of the three subtypes of 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...
; atherosclerosis, Monckeberg's arteriosclerosis
Monckeberg's arteriosclerosis
Monckeberg's arteriosclerosis, also called medial calcific sclerosis, is a form of arteriosclerosis or vessel hardening, where calcium deposits form in the middle layer of the walls of medium sized vessels...
and arteriolosclerosis
Arteriolosclerosis
Arteriolosclerosis is a form of cardiovascular disease affecting the small arteries and arterioles.Types include hyaline arteriolosclerosis and hyperplastic arteriolosclerosis, both associated with vessel wall thickening and luminal narrowing that may cause downstream ischemic injury...
.
In the context of heart or artery matters, atheromata are commonly referred to as atheromatous plaques. It is an unhealthy condition, but is found in most humans.
These anatomic lesions usually begin in some children younger than age 1 year and all children older than age 10 regardless of geography, race, sex, or environment. Vein
Vein
In the circulatory system, veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated blood to the heart...
s do not develop atheromata, unless surgically moved to function as an artery, as in bypass
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...
surgery. The accumulation (swelling) is always between the endothelium
Endothelium
The 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 and the smooth muscle wall central region (media) of the arterial tube (see 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...
). While the early stages, based on gross appearance, have traditionally been termed fatty streaks by pathologists, they are not composed of fat cells, i.e. adipose cells, but of accumulations of white blood cells, especially macrophages that have taken up oxidized low-density lipoprotein (LDL). After they accumulate large amounts of cytoplasmic membranes (with associated high cholesterol content) they are called foam cells. When foam cells die, their contents are released, which attracts more macrophages and creates an extracellular lipid core near the center to inner surface of each atherosclerotic plaque. Conversely, the outer, older portions of the plaque become more calcific, less metabolically active and more physically stiff over time.
Difficulty of tracking and researching atheroma
For most people the first clinical symptoms result from atheroma progression within the heart arteries, most commonly resulting in a heart attackMyocardial 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...
and ensuing debility. However, the heart arteries, because (a) they are small (from about 5 mm down to microscopic), (b) they are hidden deep within the chest and (c) they never stop moving, have been a difficult target organ to track, especially clinically in individuals who are still asymptomatic. Additionally, all mass-applied clinical strategies focus on both (a) minimal cost and (b) the overall safety of the procedure. Therefore, existing diagnostic strategies for detecting atheroma and tracking response to treatment have been extremely limited. The methods most commonly relied upon, patient symptoms and cardiac stress testing, do not detect any symptoms of the problem until atheromatous disease is very advanced.
History of research
In developed countries, with improved public healthPublic health
Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals" . It is concerned with threats to health based on population health...
, infection control and increasing life spans, atheroma processes have become an increasingly important problem and burden for society.
Atheroma continue to be the number one underlying basis for disability
Disability
A disability may be physical, cognitive, mental, sensory, emotional, developmental or some combination of these.Many people would rather be referred to as a person with a disability instead of handicapped...
and death
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....
, despite a trend for gradual improvement since the early 1960s (adjusted for patient age). Thus, increasing efforts towards better understanding, treating and preventing the problem are continuing to evolve.
According to United States data, 2004, for about 65% of men and 47% of women, the first symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
of cardiovascular disease is 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 sudden death (death within one hour of symptom onset.)
Most artery flow disrupting events occur at locations with less than 50% lumen
Lumen (anatomy)
A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
narrowing. From clinical studies published in the late 1990s to IVUS (in-the-artery-ultrasound) to visualize disease status, the typical heart attack occurs at locations with about 20% stenosis (narrowing), prior to sudden lumen closure and resulting 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...
. Cardiac stress test
Cardiac stress test
Cardiac 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....
ing, traditionally the most commonly performed non-invasive testing method for blood flow limitations generally only detects lumen narrowing of ~75% or greater, although some physicians advocate that nuclear stress methods can sometimes detect as little as 50%.
Artery and atheroma behavior
The healthy epicardial coronary artery consists of 3 layers, the (1) intima, (2) media, and (3) adventitia. Atheroma and changes in the artery wall usually result in small aneurysmAneurysm
An aneurysm or aneurism is a localized, blood-filled balloon-like bulge in the wall of a blood vessel. Aneurysms can commonly occur in arteries at the base of the brain and an aortic aneurysm occurs in the main artery carrying blood from the left ventricle of the heart...
s (enlargements) just large enough to compensate for the extra wall thickness with no change in the lumen diameter. However, eventually, typically as a result of rupture of vulnerable plaque
Vulnerable plaque
A vulnerable plaque is a kind of atheromatous plaque – a collection of white blood cells and lipids 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...
s and clots within the lumen over the plaque, 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 ....
(narrowing) of the vessel develops in some areas. Less frequently, the artery enlarges so much that a gross aneurysm
Aneurysm
An aneurysm or aneurism is a localized, blood-filled balloon-like bulge in the wall of a blood vessel. Aneurysms can commonly occur in arteries at the base of the brain and an aortic aneurysm occurs in the main artery carrying blood from the left ventricle of the heart...
al enlargement of the artery results. All three results are often observed, at different locations, within the same individual.
Stenosis and closure
Over time, atheromata usually progress in size and thickness and induce the surrounding muscular central region (the media) of the arteryArtery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
to stretch out, termed remodeling, typically just enough to compensate for their size such that the caliber
Caliber
In guns including firearms, caliber or calibre is the approximate internal diameter of the barrel in relation to the diameter of the projectile used in it....
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....
opening (lumen) remains unchanged until typically over 50% of the artery wall cross-sectional area consists of atheromatous tissue (see: Glagov, below).
If the muscular wall enlargement eventually fails to keep up with the enlargement of the atheroma volume, or a clot forms and organizes over the plaque, then the lumen of the artery begins to narrow, commonly as a result of repeated ruptures of the covering tissues separating the atheroma from the blood stream. This becomes a more common event after decades of living, increasingly more common after people are in their 30s to 40s.
The endothelium
Endothelium
The 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...
(the cell monolayer on the inside of the vessel) and covering tissue, termed 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....
, separate atheroma from the blood in the lumen. If a rupture occurs of the endothelium and fibrous cap, then a platelet and clotting response over the rupture rapidly develops. Additionally, the rupture may result in a shower of debris. 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...
and clot accumulation over the rupture may produce narrowing/closure of the lumen and tissue damage may occur due to either closure of the lumen and loss of blood flow beyond the ruptured atheroma and/or by occlusion of smaller downstream vessels by debris. See vulnerable plaque
Vulnerable plaque
A vulnerable plaque is a kind of atheromatous plaque – a collection of white blood cells and lipids 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...
.
This is the principal mechanism of 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...
, 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...
or other related cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
problems. As research has shown, this process is not a result of 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 ....
. Prior to the rupture, there may have been no lumen narrowing, even aneurysmal enlargement, at the atheroma. On average, by clinical research using IVUS, there is a minor stenosis, about 20%, present over those unstable atheroma which rupture and result in major disability or death. Comparatively, stenoses of about 75% are required to produce detectable abnormalities during cardiac stress test
Cardiac stress test
Cardiac 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....
s.
Artery enlargement
If the muscular wall enlargement is overdone over time, then a gross enlargementAneurysm
An aneurysm or aneurism is a localized, blood-filled balloon-like bulge in the wall of a blood vessel. Aneurysms can commonly occur in arteries at the base of the brain and an aortic aneurysm occurs in the main artery carrying blood from the left ventricle of the heart...
of the artery results, usually over decades of living. This is a less common outcome. Atheroma within aneurysmal enlargement (vessel bulging) can also rupture and shower debris of atheroma and clot downstream. If the arterial enlargement
Aneurysm
An aneurysm or aneurism is a localized, blood-filled balloon-like bulge in the wall of a blood vessel. Aneurysms can commonly occur in arteries at the base of the brain and an aortic aneurysm occurs in the main artery carrying blood from the left ventricle of the heart...
continues to 2 to 3 times the usual diameter, the walls often become weak enough that with just the stress of the pulse, a loss of wall integrity may occur leading to sudden hemorrhage (bleeding), major symptoms and debility; often rapid death. The main stimulus for aneurysm formation is pressure atrophy of the structural support of the muscle layers. The main structural proteins are collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
and elastin
Elastin
Elastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of...
. This causes thinning and the wall balloons allowing gross enlargement to occur, as is common in the abdominal region of the aorta.
IMT measurements in the carotid artery
Since the 1990s, both small clinical and several larger scale pharmaceutical trials have used CIMT (carotid IMTIntima-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...
) as a surrogate endpoint for evaluating the regression and/or progression of atherosclerotic cardiovascular disease. Many studies have documented the relation between the carotid intima-media thickness and the presence and severity of atherosclerosis. In 2003 the European Society of Hypertension-European Society of Cardiology recommended the use of IMT measurements in high-risk patients to help identify target organ damage not revealed by other exams such as the electrocardiogram.
Though it seems clear that carotid intima-media thickness is strongly associated with atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
, it is worth noting that not all the processes of thickening of the intima-media are due to atherosclerosis. Intimal thickening is in fact a complex process, depending on a variety of factors, not necessarily related to atherosclerosis. Local hemodynamics
Hemodynamics
Hemodynamics, meaning literally "blood movement" is the study of blood flow or the circulation.All animal cells require oxygen for the conversion of carbohydrates, fats and proteins into carbon dioxide , water and energy in a process known as aerobic respiration...
plays an important role, higher blood pressure and changes in shear stress being potential causes of intimal thickening. Changes in shear stress and blood pressure may cause a local delay in lumen transportation of potentially atherogenic particles, which favors the penetration of particles into the arterial wall and consequent plaque formation. However non-atherosclerotic reactions may also exist, as in intimal hyperplasia and intimal fibrocellular hypertrophy, two different compensatory reactions of the arterial wall to changes in shear stress, which also consist in thickening of the arterial wall. In some cases, more than one of these reactions may be present, and indeed as all of these are associated to particular flow conditions, they are often found in common areas, such as the inflow side of branches, the inner curvature at bends and opposite the flow divider at bifurcations. However, changes in the IMT above thresholds of around 900 μm almost certainly are indicative of an atherosclerotic pathology.
Mechanisms such as these may explain, at least in part, why the carotid artery seems to be a preferential site for analyzing the relation between wall thickness and atherosclerosis. In general, wall thickening may be in the intimal layer or in the muscular, medial, layer. As the carotid artery is an elastic artery, the muscular media is relatively small. Hence, thickening of the carotid arterial wall is due essentially to intimal thickening. In muscular arteries wall thickening may imply instead (or also) a thickening of the medial wall. Whether or not wall thickening in the carotid artery and the femoral artery (or other muscular arteries) have the same meaning is as yet uncertain. Several studies seem to suggest that the mechanisms underlying their evolution may at least in part differ, with consequently possibly different clinical implications.
Another issue to consider, once the choice to examine the carotid artery has been defined, is on which segment of the carotid artery to perform the measurement. Often, the measurement of the IMT is measured in three tracts: in the common carotid, at one or two cms from the flow divider, at the bifurcation and in the internal carotid artery.
From an academic standpoint, the region to select for IMT measurement is still an object of study. IMT measurements of the deep wall, by ultrasound, are generally more reliable than measurements performed on the outer wall. This difference in the accuracy of near and far wall measurements may be a problem, as some studies have used both measurements to quantify the IMT.
A practical approach to tracking disease presence and progression on any given individual is to select and track those regions with the greatest thickness, i.e. greatest disease burden, as opposed to arbitrarily selecting a particular segment in which the individual may not have much pathology.
Evolution of strategies and changing focus
The sudden nature of the complications of pre-existing atheroma, vulnerable plaqueVulnerable plaque
A vulnerable plaque is a kind of atheromatous plaque – a collection of white blood cells and lipids 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...
(non-occlusive or soft plaque), have led, since the 1950s, to the development of intensive care units and complex medical and surgical interventions. Angiography and later cardiac stress testing was begun to either visualize or indirectly detect 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 ....
. Next came bypass
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...
surgery, to plumb transplanted vein
Vein
In the circulatory system, veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated blood to the heart...
s, sometimes arteries, around the stenoses
Stenosis
A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure.It is also sometimes called a stricture ....
and more recently 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...
, now including stent
Stent
In the technical vocabulary of medicine, a stent is an artificial 'tube' inserted into a natural passage/conduit in the body to prevent, or counteract, a disease-induced, localized flow constriction. The term may also refer to a tube used to temporarily hold such a natural conduit open to allow...
s, most recently drug coated stent
Stent
In the technical vocabulary of medicine, a stent is an artificial 'tube' inserted into a natural passage/conduit in the body to prevent, or counteract, a disease-induced, localized flow constriction. The term may also refer to a tube used to temporarily hold such a natural conduit open to allow...
s, to stretch the stenoses
Stenosis
A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure.It is also sometimes called a stricture ....
more open.
Yet despite these medical advances, with success in reducing the symptoms of angina and reduced 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...
, atheroma rupture events remain the major problem and still sometimes result in sudden disability and death despite even the most rapid, massive and skilled medical and surgical intervention available anywhere today. According to some clinical trials, 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...
and 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...
procedures have had at best a minimal effect, if any, on improving overall survival. Typically mortality of by-pass operations is from 1–4%, of angioplasty about 1–1.5%.
Additionally, these vascular interventions are often done only after an individual is symptomatic, often already partially disabled, as a result of the disease. It is also clear that both angioplasty and by-pass interventions do not prevent future 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...
.
The older methods for understanding atheroma, dating to before World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
, relied on autopsy data. Autopsy data has long shown initiation of fatty streaks in later childhood with slow asymptomatic progression over decades.
One way to see atheroma is the very invasive and costly IVUS ultrasound technology; it gives us the precise volume of the inside intima plus the central media
Tunica media
The tunica media is the middle layer of an artery or vein.-Artery:It is made up of smooth muscle cells and elastic tissue...
layers of about 2.5 cm (0.984251968503937 in) of artery length. Unfortunately, it gives no information about the structural strength of the artery. Angiography does not visualize atheroma; it only makes the 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...
within blood vessels visible. Alternative methods that are non or less physically invasive and less expensive per individual test have been used and are continuing to be developed, such as those using computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(CT; led by the Electron Beam Tomography
Electron beam tomography
Electron beam tomography , now owned by the General Electric company , is a specific form of computed tomography in which the X-ray tube is not mechanically spun in order to rotate the source of X-ray photons...
form, given its greater speed) and magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI). The most promising since the early 1990s has been EBT, detecting calcification within the atheroma before most individuals start having clinically recognized symptoms and debility. Interestingly, statin therapy (to lower cholesterol) does not slow the speed of calcification as determined by CT scan. MRI coronary vessel wall imaging, although currently limited to research studies, has demonstrated the ability to detect vessel wall thickening in asymptomatic high risk individuals (reference - Kim 2002, Circulation). As a non-invasive, ionising radiation free technique, MRI based techniques could have future uses in monitoring disease progression and regression. Most visualization techniques are used in research, they are not widely available to most patients, have significant technical limitations, have not been widely accepted and generally are not covered by medical insurance carriers.
From human clinical trials, it has become increasingly evident that a more effective focus of treatment is slowing, stopping and even partially reversing the atheroma growth process. There are several prospective epidemiologic studies including the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS), which have supported a direct correlation of CIMT with myocardial infarction and stroke risk in patients without cardiovascular disease history. The ARIC Study was conducted in 15,792 individuals between 5 and 65 years of age in 4 different regions of the USA between 1987 and 1989. The baseline CIMT was measured and measurements were repeated at 4–7 year intervals by carotid B mode ultrasonography in this study. An increase in CIMT was correlated with an increased risk for CAD. The CHS was initiated in 1988, and the relationship of CIMT with risk of myocardial infarction and stroke was investigated in 4,476 subjects ≤65 years of age. At the end of approximately 6 years of follow-up, CIMT measurements were correlated with cardiovascular events.
Paroi artérielle et Risque Cardiovasculaire in Asia Africa/Middle East and Latin America (PARC-AALA) is another important large-scale study, in which 79 centers from countries in Asia, Africa, the Middle East, and Latin America participated, and the distribution of CIMT according to different ethnic groups and its association with the Framingham cardiovascular score was investigated. Multi-linear regression analysis revealed that an increased Framingham cardiovascular score was associated with CIMT, and carotid plaque independent of geographic differences.
Cahn et al. prospectively followed-up 152 patients with coronary artery disease for 6–11 months by carotid artery ultrasonography and noted 22 vascular events (myocardial infarction, transient ischemic attack, stroke, and coronary angioplasty) within this time period. They concluded that carotid atherosclerosis measured by this non-interventional method has prognostic significance in coronary artery patients.
In the Rotterdam Study
Rotterdam Study
The Rotterdam Study is a prospective, population-based cohort study. The aim of the Rotterdam Study is to investigate factors that determine the occurrence of cardiovascular, neurological, ophthalmological, endocrinological, and psychiatric diseases in elderly people.The study was established in...
, Bots et al. followed 7,983 patients >55 years of age for a mean period of 4.6 years, and reported 194 incident myocardial infarctions within this period. CIMT was significantly higher in the myocardial infarction group compared to the other group. Demircan et al. found that the CIMT of patients with acute coronary syndrome were significantly increased compared to patients with stable angina pectoris.
It has been reported in another study that a maximal CIMT value of 0.956 mm had 85.7% sensitivity and 85.1% specificity to predict angiographic CAD. The study group consisted of patients admitted to the cardiology outpatient clinic with symptoms of stable angina pectoris. The study showed CIMT was higher in patients with significant CAD than in patients with non-critical coronary lesions. Regression analysis revealed that thickening of the mean intima-media complex more than 1.0 was predictive of significant CAD our patients. There was incremental significant increase in CIMT with the number coronary vessel involved. In accordance with the literature, it was found that CIMT was significantly higher in the presence of CAD. Furthermore, CIMT was increased as the number of involved vessels increased and the highest CIMT values were noted in patients with left main coronary involvement. However, human clinical trials have been slow to provide clinical & medical evidence, partly because the asymptomatic nature of atheromata make them especially difficult to study. Promising results are found using Carotid Intima Media Thickness Scanning (CIMT can be measured by B-mode ultrasonography), B-vitamins that reduce a protein corrosive, 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...
and that reduce neck carotid artery plaque volume and thickness, and stroke, even in late-stage disease.
Additionally, understanding what drives atheroma development is complex with multiple factors involved, only some of which, such as lipoprotein
Lipoprotein
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...
s, more importantly lipoprotein subclass analysis, 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...
levels 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...
are best known and researched. More recently, some of the complex immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
patterns that promote, or inhibit, the inherent inflammatory macrophage triggering processes involved in atheroma progression are slowly being better elucidated in animal models of atherosclerosis.
A 4 minute animation of the atherosclerosis process, entitled "Pathogenesis of Acute MI", commissioned by Paul M. Ridker, MD, MPH, FACC, FAHA, at the Harvard Medical School, can be viewed at pri-med.com http://www.pri-med.com/pmo/Home.aspx. While the animation contains a few technical errors, partly due to the great difficulty/complexity of making a truly accurate presentation, it correctly illustrates the principal issues.
Diagnosis
Arterial wall fixation, staining and thin section: historically this has been the gold standard for detection and description of atheroma, though only done after autopsy. With special stains and examination, micro calcifications can be detected, typically with smooth muscle cells of the arterial media near the fatty streaks within a year or two of fatty streaks forming.CIMT (carotid IMT) as mentioned in the Evolution of Strategies and Changing Focus section, Interventional and non-interventional methods to detect atherosclerosis, specifically vulnerable plaque
Vulnerable plaque
A vulnerable plaque is a kind of atheromatous plaque – a collection of white blood cells and lipids 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...
(non-occlusive or soft plaque), are widely used in research and clinical practice today; Carotid Intima-media 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...
Scan (CIMT can be measured by B-mode ultrasonography) measurement has been recommended 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...
as the most useful method to identify atherosclerosis and may now very well be the gold standard for detection.
IVUS is the current most sensitive method detecting and measuring more advanced atheroma within living individuals, though it is typically not used until decades after atheroma begin forming due to cost and body invasiveness.
CT Scans using state of the art higher resolution spiral, or the higher speed EBT
Electron beam tomography
Electron beam tomography , now owned by the General Electric company , is a specific form of computed tomography in which the X-ray tube is not mechanically spun in order to rotate the source of X-ray photons...
, machines have been the most effective method for detecting calcification present in plaque. However, the atheroma have to be advanced enough to have relatively large areas of calcification within them to create large enough regions of ~130 Hounsfield units
Hounsfield scale
The Hounsfield scale, named after Sir Godfrey Newbold Hounsfield, is a quantitative scale for describing radiodensity.-Definition:The Hounsfield unit scale is a linear transformation of the original linear attenuation coefficient measurement into one in which the radiodensity of distilled water at...
which the CT scanner software can recognize as distinct from the other surrounding tissues. Typically, such regions start occurring within the heart arteries about 2–3 decades after atheroma start developing. Hence the detection of much smaller plaques then previously possible is being developed by some companies, such as Image Analysis. The presence of smaller, spotty plaques may actually be the more dangerous culprit for progressing to 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...
.
Arterial ultrasound, especially of the carotid arteries, with measurement of the thickness of the artery wall, offers a way to partially track the disease progression. As of 2006, the thickness, commonly referred to as IMT for intimal-medial thickness, is not measured clinically though it has used by some researchers since the mid 1990s to track changes in arterial walls. Traditionally, clinical carotid ultrasounds have only estimated the degree of blood lumen restriction, 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 ....
, a result of very advanced disease. The National Institute of Health did a five–year $5 million study, headed by medical researcher Kenneth Ouriel
Kenneth Ouriel
Kenneth Ouriel is a prominent vascular surgeon and medical researcher. He has published widely in scientific and medical journals. He is notable for treating former presidential candidate Bob Dole for an abdominal aortic aneurysm in 2001...
, to study intravascular ultrasound techniques regarding atherosclerotic plaque. More progressive clinicians have begun using IMT measurement as a way to quantify and track disease progression or stability within individual patients.
Angiography, since the 1960s, has been the traditional way of evaluating for atheroma. However, angiography is only motion or still images of dye mixed with the blood with the arterial lumen and never show atheroma; the wall of arteries, including atheroma with the arterial wall remain invisible. The limited exception to this rule is that with very advance atheroma, with extensive calcification within the wall, a halo-like ring of radiodensity can be seen in most older humans, especially when arterial lumens are visualized end-on. On cine-floro, cardiologists and radiologists typically look for these calcification shadows to recognize arteries before they inject any contrast agent during angiograms.
Classification
- Type I: Isolated macrophage foam cells
- Type II: Multiple foam cell layers
- Type III: Preatheroma, intermediate lesion
- Type IV: Atheroma
- Type V: Fibroatheroma
- Type VI: Fissured, ulcerated, hemorrhagic, thrombotic lesion
- Type VII: Calcific lesion
- Type VIII: Fibrotic lesion
Treatment
Many approaches have been promoted as methods to reduce atheroma progression:- reducing or eliminating one's consumption of foods which contain saturated fat and LDL cholesterol found in animal products;
- eating a diet of raw fruits, vegetables, nuts, beans, berries, and grains;
- consuming foods containing omega-3 fatty acids, such as fish, fish-derived supplements, flax seed oil, borage oil, and other non-animal-based oils;
- abdominal fat reduction;
- aerobic exercise;
- inhibitors of the 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...
synthesis (known as statins); - low normal blood glucose levels (glycosylated hemoglobinGlycosylated hemoglobinGlycated hemoglobin is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. It is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to plasma glucose...
, also called HbA1c); - micronutrient (multivitamin, potassiumPotassiumPotassium 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...
, and magnesiumMagnesiumMagnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
) consumption
See also
- AngiogramAngiogramAngiography 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...
- 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...
- AtherosclerosisAtherosclerosisAtherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
- Atherothrombosis
- Coronary circulationCoronary circulationCoronary 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...
- Coronary catheterizationCoronary catheterizationA coronary catheterization is a minimally invasive procedure to access the coronary circulation and blood filled chambers of the heart using a catheter. It is performed for both diagnostic and interventional purposes....
- EBTElectron beam tomographyElectron beam tomography , now owned by the General Electric company , is a specific form of computed tomography in which the X-ray tube is not mechanically spun in order to rotate the source of X-ray photons...
- Hemorheologic-Hemodynamic Theory of Atherosclerosis
- 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, HDLHigh density lipoproteinHigh-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...
, IDLIntermediate density lipoproteinIntermediate-density lipoproteins belong to the lipoprotein particle family and are formed from the degradation of very low-density lipoproteins. IDL is one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream...
and VLDL