Atherosclerosis Classification and external resources
Changes in endothelial dysfunction in atherosclerosis (note text comments about geometry error)
ICD-10	I70.
ICD-9	440
DiseasesDB	1039
MedlinePlus	000171
eMedicine	med/182
MeSH	D050197

Atherosclerosis is a disease affecting arterial blood vessels. It is a chronic inflammatory response in the walls of arteries, in large part due to the accumulation of macrophage white blood cells and promoted by low density (especially small particle) lipoproteins (plasma proteins that carry cholesterol and triglycerides) without adequate removal of fats and cholesterol from the macrophages by functional high density lipoproteins (HDL), (see apoA-1 Milano). It is commonly referred to as a "hardening" or "furring" of the arteries. It is caused by the formation of multiple plaques within the arteries.^[1] Image File history File links Download high resolution version (602x673, 342 KB) Summary Stages of endothelial dysfunction in atheroscerosis Licensing Permission is granted to copy, distribute and/or modify this document under the terms of the GNU Free Documentation License, Version 1. ... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // I00-I99 - Diseases of the circulatory system (I00-I02) Acute rheumatic fever (I00) Rheumatic fever without mention of heart involvement (I01) Rheumatic fever with heart involvement (I02) Rheumatic chorea (I05-I09) Chronic rheumatic heart diseases (I05) Rheumatic mitral valve diseases (I050) Mitral stenosis (I051) Rheumatic mitral insufficiency (I06) Rheumatic aortic... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... MedlinePlus (medlineplus. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... This article is about the medical term. ... For other uses, see Artery (disambiguation). ... f you all The blood vessels are part of the circulatory system and function to transport blood throughout the body. ... A macrophage of a mouse stretching its arms to engulf two particles, possibly pathogens Macrophages (Greek: big eaters, from makros large + phagein eat) are cells within the tissues that originate from specific white blood cells called monocytes. ... White Blood Cells is also the name of a White Stripes album. ... A lipoprotein is a biochemical assembly that contains both proteins and lipids and may be structural or catalytic in function. ... Triglyceride (blue: fatty acid; red: glycerol backbone) Triglycerides are glycerides in which the glycerol is esterified with three fatty acids. ... High-density lipoproteins (HDL) form a class of lipoproteins, varying somewhat in their size (8–11 nm in diameter), that carry cholesterol from the bodys tissues to the liver. ... There are very few or no other articles that link to this one. ... In pathology, an atheroma (plural: atheromata) is an accumulation and swelling (-oma) in artery walls that is made up of cells, or cell debris, that contain lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue. ... Section of an artery An artery or arterial is also a class of highway. ...

The atheromatous plaque is divided into three distinct components: In pathology, an atheroma (plural: atheromata) is an accumulation and swelling (-oma) in artery walls that is made up of cells, or cell debris, that contain lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue. ...

1. The atheroma ("lump of porridge", from Athera, porridge in Greek,), which is the nodular accumulation of a soft, flaky, yellowish material at the center of large plaques, composed of macrophages nearest the lumen of the artery
2. Underlying areas of cholesterol crystals
3. Calcification at the outer base of older/more advanced lesions.

The following terms are similar, yet distinct, in both spelling and meaning, and can be easily confused: arteriosclerosis, arteriolosclerosis, and atherosclerosis. Arteriosclerosis is a general term describing any hardening (and loss of elasticity) of medium or large arteries (from the Greek Arterio, meaning artery, and sclerosis, meaning hardening), arteriolosclerosis is any hardening (and loss of elasticity) of arterioles (small arteries), atherosclerosis is a hardening of an artery specifically due to an atheromatous plaque. Therefore, atherosclerosis is a form of arteriosclerosis. In pathology, an atheroma (plural: atheromata) is an accumulation and swelling (-oma) in artery walls that is made up of cells, or cell debris, that contain lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue. ... ‹ The template below is being considered for deletion. ... A macrophage of a mouse stretching its arms to engulf two particles, possibly pathogens Macrophages (Greek: big eaters, from makros large + phagein eat) are cells within the tissues that originate from specific white blood cells called monocytes. ... artery anatomy, showing lumen The lumen (pl. ... Cholesterol is a sterol (a combination steroid and alcohol). ... An arteriole is a small diameter blood vessel that extends and branches out from an artery and leads to capillaries. ...

Atherosclerosis causes two main problems. First, the atheromatous plaques, though long compensated for by artery enlargement (see IMT), eventually lead to plaque ruptures and stenosis (narrowing) of the artery and, therefore, an insufficient blood supply to the organ it feeds. Second, if the compensating artery enlargement process is excessive, then a net aneurysm results. In pathology, an atheroma (plural: atheromata) is an accumulation and swelling (-oma) in artery walls that is made up of cells, or cell debris, that contain lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue. ... It has been suggested that this article or section be merged with Intima media thickness. ... A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure. ... Post surgical photo of brain aneurysm survivor. ...

These complications are chronic, slowly progressing and cumulative. Most commonly, soft plaque suddenly ruptures (see vulnerable plaque), causing the formation of a thrombus that will rapidly slow or stop blood flow, leading to death of the tissues fed by the artery in approximately 5 minutes. This catastrophic event is called an infarction. One of the most common recognized scenarios is called coronary thrombosis of a coronary artery, causing myocardial infarction (a heart attack). Another common scenario in very advanced disease is claudication from insufficient blood supply to the legs, typically due to a combination of both stenosis and aneurysmal segments narrowed with clots. Since atherosclerosis is a body-wide process, similar events occur also in the arteries to the brain, intestines, kidneys, legs, etc. A vulnerable plaque is an atheromatous plaque which is particularly prone to produce sudden major problems, such as a heart attack or stroke. ... For Trombe wall (used in solar homes), see Trombe wall. ... Look up Infarction in Wiktionary, the free dictionary. ... Thrombosis is the formation of a clot or thrombus inside a blood vessel, obstructing the flow of blood through the circulatory system. ... The coronary circulation consists of the blood vessels that supply blood to, and remove blood from, the heart. ... Heart attack redirects here. ... Claudication, literally limping, is used as a medical term in various contexts. ... For Trombe wall (used in solar homes), see Trombe wall. ...

Causes

Atherosclerosis develops from low-density lipoprotein cholesterol (LDL), colloquially called "bad cholesterol". When this lipoprotein gets through the wall of an artery, oxygen free radicals react with it to form oxidized-LDL. ^[2] The body's immune system responds by sending specialised white blood cells (macrophages and T-lymphocytes) to absorb the oxidised-LDL. Unfortunately, these white blood cells are not able to process the oxidised-LDL, and ultimately grow then rupture, depositing a greater amount of oxidised cholesterol into the artery wall. This triggers more white blood cells, continuing the cycle. A lipoprotein is a biochemical assembly that contains both proteins and lipids. ... For other uses, see Artery (disambiguation). ... In chemistry free radicals are uncharged atomic or molecular species with unpaired electrons or an otherwise open shell configuration. ... Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ... T cells are a subset of lymphocytes that play a large role in the immune response. ...

Eventually, the artery becomes inflamed. The cholesterol plaque causes the muscle cells to enlarge and form a hard cover over the affected area. This hard cover is what causes a narrowing of the artery, reduces the blood flow and increases blood pressure.

Some researchers believe that atherosclerosis may be caused by an infection of the vascular smooth muscle cells. Chickens, for example, develop atherosclerosis when infected with the Marek's disease herpesvirus. ^[3] Herpesvirus infection of arterial smooth muscle cells has been shown to cause cholesteryl ester (CE) accumulation. ^[4] Cholesteryl ester accumulation is associated with atherosclerosis. Mareks disease is a highly contagious viral neoplastic disease in chickens and sheep. ... Genera Subfamily Alphaherpesvirinae    Simplexvirus    Varicellovirus    Mardivirus    Iltovirus Subfamily Betaherpesvirinae    Cytomegalovirus    Muromegalovirus    Roseolovirus Subfamily Gammaherpesvirinae    Lymphocryptovirus    Rhadinovirus Unassigned    Ictalurivirus The Herpesviridae are a family of DNA viruses that cause diseases in humans and animals. ... Smooth muscle Layers of Esophageal Wall: 1. ... A cholesteryl ester is, as its name would imply, an ester of cholesterol. ...

Symptoms

Atherosclerosis typically begins in early adolescence, and is usually found in most major arteries, yet is asymptomatic and not detected by most diagnostic methods during life. The stage immediately prior to actual atherosclerosis is known as subclinical atherosclerosis. The majority of the process leading to subclinical atherosclerosis can happen without our knowing it, especially given the large variety of risk factors. ^[5]. Autopsies of healthy young men that died during the Korean and Vietnam Wars showed evidence of the disease.^{[6] [7]} It most commonly becomes seriously symptomatic when interfering with the coronary circulation supplying the heart or cerebral circulation supplying the brain, and is considered the most important underlying cause of strokes, heart attacks, various heart diseases including congestive heart failure, and most cardiovascular diseases, in general. Atheroma in arm, or more often in leg arteries, which produces decreased blood flow is called Peripheral artery occlusive disease (PAOD). For other uses, see Artery (disambiguation). ... The coronary circulation consists of the blood vessels that supply blood to and from the heart muscle itself. ... The heart and lungs, from an older edition of Grays Anatomy. ... Cerebral circulation refers to the blood vessels, arteries and veins, carrying blood to and away from the brain, respectively. ... For other uses, see Brain (disambiguation). ... A stroke or cerebrovascular accident (CVA) occurs when the blood supply to a part of the brain is suddenly interrupted by occlusion (an ischemic stroke- approximately 90% of strokes), by hemorrhage (a hemorrhagic stroke - less than 10% of strokes) or other causes. ... Heart attack redirects here. ... Heart disease is an umbrella term for a number of different diseases which affect the heart and as of 2007 it is the leading cause of death in the United States,[1] and England and Wales. ... Congestive heart failure (CHF), also called congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. ... Cardiovascular disease refers to the class of diseases that involve the heart or blood vessels (arteries and veins). ... In medicine, peripheral artery occlusive disease (PAOD), also known as peripheral vascular disease (PVD) and peripheral artery disease (PAD) is a collator for all diseases caused by the obstruction of large peripheral arteries, which can result from atherosclerosis, inflammatory processes leading to stenosis, an embolism or thrombus formation. ...

According to United States data for the year 2004, for about 65% of men and 47% of women, the first symptom of atherosclerotic cardiovascular disease is heart attack or sudden cardiac death (death within one hour of onset of the symptom). A symptom is a manifestation of a disease, indicating the nature of the disease, which is noticed by the patient. ... Cardiovascular disease refers to the class of diseases that involve the heart or blood vessels (arteries and veins). ... Heart attack redirects here. ... A cardiac arrest is the cessation of normal circulation of the blood due to failure of the ventricles of the heart to contract effectively during systole. ...

Most artery flow disrupting events occur at locations with less than 50% lumen narrowing (~20% stenosis is average). [The reader might reflect that the illustration above, like most illustrations of arterial disease, overemphasizes lumen narrowing, as opposed to compensatory external diameter enlargement (at least within smaller arteries, e.g., heart arteries) typical of the atherosclerosis process as it progresses, see Glagov^[8] and the ASTEROID trial,^[9] the IVUS photographs on page 8, as examples for a more accurate understanding. The relative geometry error within the illustration is common to many older illustrations, an error slowly being more commonly recognized within the last decade.] artery anatomy, showing lumen The lumen (pl. ... A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure. ... Intravascular ultrasound (IVUS) is an medical imaging methodology using (a) specially designed long thin complex manufactured catheters attached to (b) computerized ultrasound equipment. ...

Cardiac stress testing, traditionally the most commonly performed non-invasive testing method for blood flow limitations, in general, detects only lumen narrowing of ~75% or greater, although some physicians claim that nuclear stress methods can detect as little as 50%. A cardiac stress test is a medical test performed to evaluate relative arterial blood flow increases to the left ventricular heart muscle during exercise, as compared to resting blood flow rates (i. ... artery anatomy, showing lumen The lumen (pl. ...

Atherogenesis

Atherogenesis is the developmental process of atheromatous plaques. It is characterized by a remodeling of arteries involving the concomitant accumulation of fatty substances called plaques. One recent theory suggests that, for unknown reasons, leukocytes, such as monocytes or basophils, begin to attack the endothelium of the artery lumen in cardiac muscle. The ensuing inflammation leads to formation of atheromatous plaques in the arterial tunica intima, a region of the vessel wall located between the endothelium and the tunica media. The bulk of these lesions is made of excess fat, collagen, and elastin. At first, as the plaques grow, only wall thickening occurs without any narrowing, stenosis of the artery opening, called the lumen; stenosis is a late event, which may never occur and is often the result of repeated plaque rupture and healing responses, not just the atherosclerosis process by itself. For other uses, see Artery (disambiguation). ... White Blood Cells is also the name of a White Stripes album. ... MONOCYTES: Plural of monocyte. ... This article needs to be cleaned up to conform to a higher standard of quality. ... The endothelium is the layer of thin, flat 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. ... Cardiac muscle is a type of involuntary striated muscle found within the heart. ... An abscess on the skin, showing the redness and swelling characteristic of inflammation. ... The tunica intima (or just intima) is the innermost layer of an artery. ... The endothelium is the layer of thin, flat 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. ... The tunica media (or just media) is the middle layer of an artery. ... Tropocollagen triple helix. ... 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. ... It has been suggested that this article or section be merged with Intima media thickness. ... A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure. ...

Cellular

The first step of atherogenesis is the development of fatty streaks, which are small subendothelial deposits of oxidized cholesterol and monocyte-derived macrophages. The exact cause for this process is unknown, and fatty streaks may appear and disappear. Fatty streak is the term generally given to the earliest stages of atheroma, as viewed at autopsy, looking at the inner surface of arteries, without magnification. ...

LDL in blood plasma poses a risk for cardiovascular disease when it invades the endothelium and becomes oxidized. A complex set of biochemical reactions regulates the oxidation of LDL, chiefly stimulated by presence of free radicals in the endothelium or blood vessel lining. Cardiovascular disease refers to the class of diseases that involve the heart or blood vessels (arteries and veins). ... The endothelium is the layer of thin, flat 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. ... To oxidize an element or a compound is to increase its oxidation number. ... In chemistry free radicals are uncharged atomic or molecular species with unpaired electrons or an otherwise open shell configuration. ... The endothelium is the layer of thin, flat 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. ...

The initial damage to the blood vessel wall results in a "call for help," an inflammatory response. Monocytes (a type of white blood cell) enter the artery wall from the bloodstream, with platelets adhering to the area of insult. This may be promoted by redox signaling induction of factors such as VCAM-1, which recruit circulating monocytes. The monocytes differentiate macrophages, which ingest oxidized LDL, slowly turning into large "foam cells" – so-described because of their changed appearance resulting from the numerous internal cytoplasmic vesicles and resulting high lipid content. Under the microscope, the lesion now appears as a fatty streak. Foam cells eventually die, and further propagate the inflammatory process. There is also smooth muscle proliferation and migration from tunica media to intima responding to cytokines secreted by damaged endothelial cells. This would cause the formation of a fibrous capsule covering the fatty streak. Monocyte A monocyte is a leukocyte, part of the human bodys immune system that protects against blood-borne pathogens and moves quickly (aprox. ... White Blood Cells redirects here. ... Redox signaling is the concept that free radicals, reactive oxygen species (ROS), and other electronically-activated species act as messengers in biological systems. ... VCAM-1 (vascular cell adhesion molecule-1), also known as CD106, is a molecule with a considerable role in the human immune system. ... Monocyte A monocyte is a leukocyte, part of the human bodys immune system that protects against blood-borne pathogens and moves quickly (aprox. ... A macrophage of a mouse stretching its arms to engulf two particles, possibly pathogens Macrophages (Greek: big eaters, from makros large + phagein eat) are cells within the tissues that originate from specific white blood cells called monocytes. ... To oxidize an element or a compound is to increase its oxidation number. ... Low-density lipoprotein (LDL) refers to a class and range of lipoprotein particles, varying somewhat in their size and contents, which carry cholesterol in the blood and around the body, for use by various cells. ... In cell biology, a vesicle is a relatively small and enclosed compartment, separated from the cytosol by at least one lipid bilayer. ... Some common lipids. ...

Calcification and lipids

Intracellular microcalcifications form within vascular smooth muscle cells of the surrounding muscular layer, specifically in the muscle cells adjacent to the atheromas. In time, as cells die, this leads to extracellular calcium deposits between the muscular wall and outer portion of the atheromatous plaques. A similar form of an intramural calcification, presenting the picture of an early phase of arteriosclerosis, appears to be induced by a number of drugs that have an antiproliferative mechanism of action (Rainer Liedtke 2008). Dystrophic calcification is the mineralization of soft tissue without a systemic mineral imbalance. ... Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood vessels. ...

Cholesterol is delivered into the vessel wall by cholesterol-containing low-density lipoprotein (LDL) particles. To attract and stimulate macrophages, the cholesterol must be released from the LDL particles and oxidized, a key step in the ongoing inflammatory process. The process is worsened if there is insufficient high-density lipoprotein (HDL), the lipoprotein particle that removes cholesterol from tissues and carries it back to the liver. Low-density lipoprotein (LDL) refers to a class and range of lipoprotein particles, varying somewhat in their size and contents, which carry cholesterol in the blood and around the body, for use by various cells. ... High density lipoproteins (HDL) form a class of lipoproteins, varying somewhat in their size and contents, that carry cholesterol from the bodys tissues to the liver. ...

The foam cells and platelets encourage the migration and proliferation of smooth muscle cells, which in turn ingest lipids, become replaced by collagen and transform into foam cells themselves. A protective fibrous cap normally forms between the fatty deposits and the artery lining (the intima). Smooth muscle Layers of Esophageal Wall: 1. ... The endothelium is the layer of thin, flat 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 capped fatty deposits (now called 'atheromas') produce enzymes that cause the artery to enlarge over time. As long as the artery enlarges sufficiently to compensate for the extra thickness of the atheroma, then no narrowing ("stenosis") of the opening ("lumen") occurs. The artery becomes expanded with an egg-shaped cross-section, still with a circular opening. If the enlargement is beyond proportion to the atheroma thickness, then an aneurysm is created.^[8] A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure. ... Post surgical photo of brain aneurysm survivor. ...

Visible features

Severe atherosclerosis of the aorta. Autopsy specimen.

Although arteries are not typically studied microscopically, two plaque types can be distinguished[1]: Image File history File links Download high-resolution version (700x1090, 78 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Atherosclerosis ... Image File history File links Download high-resolution version (700x1090, 78 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Atherosclerosis ... The aorta (generally pronounced [eɪˈɔːtə] or ay-orta) is the largest artery in the human body, originating from the left ventricle of the heart and bringing oxygenated blood to all parts of the body in the systemic circulation. ... This article is about the medical procedure. ...

1. The fibro-lipid (fibro-fatty) plaque is characterized by an accumulation of lipid-laden cells underneath the intima of the arteries, typically without narrowing the lumen due to compensatory expansion of the bounding muscular layer of the artery wall. Beneath the endothelium there is a "fibrous cap" covering the atheromatous "core" of the plaque. The core consists of lipid-laden cells (macrophages and smooth muscle cells) with elevated tissue cholesterol and cholesterol ester content, fibrin, proteoglycans, collagen, elastin, and cellular debris. In advanced plaques, the central core of the plaque usually contains extracellular cholesterol deposits (released from dead cells), which form areas of cholesterol crystals with empty, needle-like clefts. At the periphery of the plaque are younger "foamy" cells and capillaries. These plaques usually produce the most damage to the individual when they rupture.
2. The fibrous plaque is also localized under the intima, within the wall of the artery resulting in thickening and expansion of the wall and, sometimes, spotty localized narrowing of the lumen with some atrophy of the muscular layer. The fibrous plaque contains collagen fibers (eosinophilic), precipitates of calcium (hematoxylinophilic) and, rarely, lipid-laden cells.

In effect, the muscular portion of the artery wall forms small aneurysms just large enough to hold the atheroma that are present. The muscular portion of artery walls usually remain strong, even after they have remodeled to compensate for the atheromatous plaques. Post surgical photo of brain aneurysm survivor. ... In pathology, an atheroma (plural: atheromata) is an accumulation and swelling (-oma) in artery walls that is made up of cells, or cell debris, that contain lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue. ... In pathology, an atheroma (plural: atheromata) is an accumulation and swelling (-oma) in artery walls that is made up of cells, or cell debris, that contain lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue. ...

However, atheromas within the vessel wall are soft and fragile with little elasticity. Arteries constantly expand and contract with each heartbeat, i.e., the pulse. In addition, the calcification deposits between the outer portion of the atheroma and the muscular wall, as they progress, lead to a loss of elasticity and stiffening of the artery as a whole. In pathology, an atheroma (plural: atheromata) is an accumulation and swelling (-oma) in artery walls that is made up of cells, or cell debris, that contain lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue. ...

The calcification deposits, after they have become sufficiently advanced, are partially visible on coronary artery computed tomography or electron beam tomography (EBT) as rings of increased radiographic density, forming halos around the outer edges of the atheromatous plaques, within the artery wall. On CT, >130 units on the Hounsfield scale {some argue for 90 units) has been the radiographic density usually accepted as clearly representing tissue calcification within arteries. These deposits demonstrate unequivocal evidence of the disease, relatively advanced, even though the lumen of the artery is often still normal by angiographic or intravascular ultrasound. negron305 Cat scan redirects here. ... Patent illustration showing a cutaway view of an electron beam computerized tomography system. ... The Hounsfield scale is a quantitative scale for describing radiodensity. ... Intravascular ultrasound (IVUS) is an medical imaging methodology using (a) specially designed long thin complex manufactured catheters attached to (b) computerized ultrasound equipment. ...

Rupture and stenosis

Although the disease process tends to be slowly progressive over decades, it usually remains asymptomatic until an atheroma obstructs the bloodstream in the artery. This is typically by rupture of an atheroma, clotting and fibrous organization of the clot within the lumen, covering the rupture but also producing stenosis, or over time and after repeated ruptures, resulting in a persistent, usually localized stenosis. Stenoses can be slowly progressive, whereas plaque rupture is a sudden event that occurs specifically in atheromas with thinner/weaker fibrous caps that have become "unstable." A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure. ...

Repeated plaque ruptures, ones not resulting in total lumen closure, combined with the clot patch over the rupture and healing response to stabilize the clot, is the process that produces most stenoses over time. The stenotic areas tend to become more stable, despite increased flow velocities at these narrowings. Most major blood-flow-stopping events occur at large plaques, which, prior to their rupture, produced very little if any stenosis.

From clinical trials, 20% is the average stenosis at plaques that subsequently rupture with resulting complete artery closure. Most severe clinical events do not occur at plaques that produce high-grade stenosis. From clinical trials, only 14% of heart attacks occur from artery closure at plaques producing a 75% or greater stenosis prior to the vessel closing.

If the fibrous cap separating a soft atheroma from the bloodstream within the artery ruptures, tissue fragments are exposed and released, and blood enters the atheroma within the wall and sometimes results in a sudden expansion of the atheroma size. Tissue fragments are very clot-promoting, containing collagen and tissue factor; they activate platelets and activate the system of coagulation. The result is the formation of a thrombus (blood clot) overlying the atheroma, which obstructs blood flow acutely. With the obstruction of blood flow, downstream tissues are starved of oxygen and nutrients. If this is the myocardium (heart muscle), angina (cardiac chest pain) or myocardial infarction (heart attack) develops. Tropocollagen triple helix. ... Thromboplastin is a substance present in tissues, platelets, and leukocytes necessary for the coagulation of blood; in the presence of calcium ions thromboplastin is necessary for the conversion of prothrombin to thrombin, an important step in coagulation of blood. ... A 250 ml bag of newly collected platelets. ... This article is about the clotting of blood. ... For Trombe wall (used in solar homes), see Trombe wall. ... This article is about the chemical element and its most stable form, or dioxygen. ... Myocardium is the muscular tissue of the heart. ... angina tonsillaris see tonsillitis. ... Heart attack redirects here. ...

Diagnosis of plaque-related disease

Microphotography of arterial wall with calcified (violet colour) atherosclerotic plaque (haematoxillin & eosin stain)

Areas of severe narrowing, stenosis, detectable by angiography, and to a lesser extent "stress testing" have long been the focus of human diagnostic techniques for cardiovascular disease, in general. However, these methods focus on detecting only severe narrowing, not the underlying atherosclerosis disease. As demonstrated by human clinical studies, most severe events occur in locations with heavy plaque, yet little or no lumen narrowing present before debilitating events suddenly occur. Plaque rupture can lead to artery lumen occlusion within seconds to minutes, and potential permanent debility and sometimes sudden death. Image File history File links Calcificatio_atherosclerotica. ... Image File history File links Calcificatio_atherosclerotica. ... A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure. ... Stress testing is a form of testing that is used to determine the stability of a given system or entity. ... Cardiovascular disease refers to the class of diseases that involve the heart or blood vessels (arteries and veins). ... A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure. ... A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure. ...

Plaques that have ruptured are called complicated plaques. The lipid matrix breaks through the thinning collagen gap and when the lipids come in contact with the blood, clotting occurs. After rupture the platelet adhesion causes the clotting cascade to contact with the lipid pool causing a thrombus to form. This thrombus will eventually grow and travel throughout the body. The thrombus will travel through different arteries and veins and eventually become lodged in an area that narrows. Once the area is blocked, blood and oxygen will not be able to supply the vessels and will cause death of cells and lead to necrosis and poisoning. Serious complicated plaques can cause death of organ tissues, causing serious complications to that organ system. Tropocollagen triple helix. ... For Trombe wall (used in solar homes), see Trombe wall. ... For Trombe wall (used in solar homes), see Trombe wall. ... This article is about the chemical element and its most stable form, or dioxygen. ... Necrosis (in Greek Νεκρός = Dead) is the name given to accidental death of cells and living tissue. ...

Greater than 75% lumen stenosis used to be considered by cardiologists as the hallmark of clinically significant disease because it is typically only at this severity of narrowing of the larger heart arteries that recurring episodes of angina and detectable abnormalities by stress testing methods are seen. However, clinical trials have shown that only about 14% of clinically-debilitating events occur at locations with this, or greater severity of narrowing. The majority of events occur due to atheroma plaque rupture at areas without narrowing sufficient enough to produce any angina or stress test abnormalities. Thus, since the later-1990s, greater attention is being focused on the "vulnerable plaque."^[10] A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure. ... angina tonsillaris see tonsillitis. ... Stress testing is a form of testing which is used to determine the stability of a given system or entity. ... A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure. ... A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure. ... angina tonsillaris see tonsillitis. ... Stress testing is a form of testing which is used to determine the stability of a given system or entity. ...

Though any artery in the body can be involved, usually only severe narrowing or obstruction of some arteries, those that supply more critically-important organs are recognized. Obstruction of arteries supplying the heart muscle result in a heart attack. Obstruction of arteries supplying the brain result in a stroke. These events are life-changing, and often result in irreversible loss of function because lost heart muscle and brain cells do not grow back to any significant extent, typically less than 2%. A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure. ... Heart attack redirects here. ... For other uses, see Stroke (disambiguation). ...

Over the last couple of decades, methods other than angiography and stress-testing have been increasingly developed as ways to better detect atherosclerotic disease before it becomes symptomatic. These have included both (a) anatomic detection methods and (b) physiologic measurement methods.

Examples of anatomic methods include: (1) coronary calcium scoring by CT, (2) carotid IMT (intimal media thickness) measurement by ultrasound, and (3) IVUS. It has been suggested that this article or section be merged with Intima media thickness. ...

Examples of physiologic methods include: (1) lipoprotein subclass analysis, (2) HbA1c, (3) hs-CRP, and (4) homocysteine. Glycosylated (or glycated) hemoglobin (hemoglobin A1c, Hb1c , HbA1c or HgA1c) is a form of hemoglobin used primarily to identify the plasma glucose concentration over time. ... C-reactive protein (CRP) is a plasma protein, an acute phase protein produced by the liver. ... Homocysteine is a chemical compound with the formula HSCH2CH2CH(NH2)CO2H. It is a homologue of the naturally-occurring amino acid cysteine, differing in that its side-chain contains an additional methylene (-CH2-) group before the thiol (-SH) group. ...

The example of the metabolic syndrome combines both anatomic (abdominal girth) and physiologic (blood pressure, elevated blood glucose) methods.

Advantages of these two approaches: The anatomic methods directly measure some aspect of the actual atherosclerotic disease process itself, thus offer potential for earlier detection, including before symptoms start, disease staging and tracking of disease progression. The physiologic methods are often less expensive and safer and changing them for the better may slow disease progression, in some cases with marked improvement.

Disadvantages of these two approaches: The anatomic methods are generally more expensive and several are invasive, such as IVUS. The physiologic methods do not quantify the current state of the disease or directly track progression. For both, clinicians and third party payers have been slow to accept the usefulness of these newer approaches.

Physiologic factors that increase risk

Various anatomic, physiological & behavioral risk factors for atherosclerosis are known.^[11] These can be divided into various categories: congenital vs acquired, modifiable or not, classical or non-classical. The points labelled '+' in the following list form the core components of "metabolic syndrome": Metabolic syndrome is a combination of medical disorders that increase ones risk for cardiovascular disease and diabetes. ...

• Advanced age
• Having Diabetes or Impaired glucose tolerance (IGT) +
• Dyslipoproteinemia (unhealthy patterns of serum proteins carrying fats & cholesterol): +
  • High serum concentration of low-density lipoprotein (LDL, "bad if elevated concentrations and small"), and / or very low density lipoprotein (VLDL) particles, i.e., "lipoprotein subclass analysis"
  • Low serum concentration of functioning high density lipoprotein (HDL "protective if large and high enough" particles), i.e., "lipoprotein subclass analysis"
  • An LDL:HDL ratio greater than 3:1
• Male sex
• Tobacco smoking
• Having high blood pressure +
• Being obese (in particular central obesity, also referred to as abdominal or male-type obesity) +
• A sedentary lifestyle
• Having close relatives who have had some complication of atherosclerosis (eg. coronary heart disease or stroke)
• Elevated serum levels of triglycerides +
• Elevated serum levels of homocysteine
• Elevated serum levels of uric acid (also responsible for gout)
• Elevated serum fibrinogen concentrations
• Elevated serum lipoprotein(a) concentrations
• Elevated serum C-reactive protein concentrations
• Elevated serum insulin levels + ^[12]
  • Chronic systemic inflammation as reflected by upper normal WBC concentrations, elevated hs-CRP and many other blood chemistry markers, most only research level at present, not clinically done.^[13]
• Stress or symptoms of clinical depression
• Hyperthyroidism (an over-active thyroid)

In biology, senescence is the combination of processes of deterioration which follow the period of development of an organism. ... This article is about the disease that features high blood sugar. ... Impaired Glucose Tolerance (IGT) is a pre-diabetic state of dysglycemia, that is associated with insulin resistance and increased risk of cardiovascular pathology. ... A lipoprotein is a biochemical assembly that contains both proteins and lipids. ... Cholesterol is a sterol (a combination steroid and alcohol). ... Low-density lipoprotein (LDL) refers to a class and range of lipoprotein particles, varying somewhat in their size and contents, which carry cholesterol in the blood and around the body, for use by various cells. ... Very Low Density Lipoprotein (VLDL) is a lipoprotein subclass. ... High-density lipoproteins (HDL) form a class of lipoproteins, varying somewhat in their size (8–11 nm in diameter), that carry cholesterol from the bodys tissues to the liver. ... This article is about the Male sex. ... The cigarette is the most common method of smoking tobacco. ... For other forms of hypertension, see Hypertension (disambiguation). ... A sphygmomanometer, a device used for measuring arterial pressure. ... Obesity is a condition in which the natural energy reserve, stored in the fatty tissue of humans and other mammals, is increased to a point where it is associated with certain health conditions or increased mortality. ... Central obesity (or apple-shaped or masculine obesity) occurs when the main deposits of body fat are localised around the abdomen and the upper body. ... The term sedentary in biology and anthropology applies to organisms and species that are not migratory but rather remain at a single location (permanently fixed or otherwise). ... Coronary heart disease (CHD), also called coronary artery disease (CAD), ischaemic heart disease, atherosclerotic heart disease, is the end result of the accumulation of atheromatous plaques within the walls of the arteries that supply the myocardium (the muscle of the heart) with oxygen and nutrients. ... For other uses, see Stroke (disambiguation). ... Triglyceride (blue: fatty acid; red: glycerol backbone) Triglycerides are glycerides in which the glycerol is esterified with three fatty acids. ... Homocysteine is a chemical compound with the formula HSCH2CH2CH(NH2)CO2H. It is a homologue of the naturally-occurring amino acid cysteine, differing in that its side-chain contains an additional methylene (-CH2-) group before the thiol (-SH) group. ... Uric acid (or urate) is an organic compound of carbon, nitrogen, oxygen and hydrogen with the formula C5H4N4O3. ... Fibrin is a protein involved in the clotting of blood. ... Lipoprotein(a) (also called LP(a) and Lp-a) is a lipoprotein subclass. ... C-reactive protein (CRP) is a plasma protein, an acute phase protein produced by the liver. ... An abscess on the skin, showing the redness and swelling characteristic of inflammation. ... C-reactive protein (CRP) is a plasma protein, an acute phase protein produced by the liver. ... In medical terms, stress is the disruption of homeostasis through physical or psychological stimuli. ... On the Threshold of Eternity. ... Hyperthyroidism (or overactive thyroid gland) is the clinical syndrome caused by an excess of circulating free thyroxine (T4) or free triiodothyronine (T3), or both. ...

Dietary risk factors

The relation between dietary fat and atherosclerosis is a contentious field. The USDA, in its food pyramid, promotes a low-fat diet, based largely on its view that fat in the diet is atherogenic. The American Heart Association, the American Diabetes Association and the National Cholesterol Education Program make similar recommendations. In contrast, Prof Walter Willett (Harvard School of Public Health, PI of the second Nurses' Health Study) recommends much higher levels, especially of monounsaturated and polyunsaturated fat.^[14] Writing in Science, Gary Taubes detailed that political considerations played into the recommendations of government bodies.^[15] These differing views reach a consensus, though, against consumption of trans fats. USDA redirects here. ... This Food Pyramid diagram can be found on much of the food packaging in the United States The food guide pyramid, informally known as the food pyramid, is a nutrition guide created by the USDA. Released in 1992, it suggests how much of each food category one should eat each... The American Heart Association (AHA) 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 American Stroke Association Web site. ... The American Diabetes Association, or the ADA, is an American health organization providing diabetes research, information and advocacy. ... The National Cholesterol Education Program is a program managed by the National Heart, Lung and Blood Institute, a division of the National Institutes of Health. ... Dr. Walter Willett, MD, DrPH., (born in 1945 in Hart, Michigan[5]) is an American physician and nutrition researcher. ... A principal investigator (PI) is the lead scientist for a particular well-defined science project, such as an astronomical observing campaign, laboratory study or clinical trial. ... The Nurses Health Study, established in 1976 by Dr. Frank Speizer, and the Nurses Health Study II, established in 1989 by Dr. Walter Willett, are the most definitive long-term epidemiological studies conducted to date on older womens health. ... For discussion how dietary fats affect cardiovascular health, see Diet and heart disease. ... // In nutrition, polyunsaturated fat is an abbreviation of polyunsaturated fatty acid. ... A magnet levitating above a high-temperature superconductor demonstrates the Meissner effect. ... Gary Taubes is a science writer. ... A trans fatty acid (commonly shortened to trans fat) is an unsaturated fatty acid molecule that contains a trans double bond between carbon atoms, which makes the molecule less kinked compared to cis fat. Research suggests a correlation between diets high in trans fats and diseases like atherosclerosis and coronary...

The role of dietary oxidized fats / lipid peroxidation (rancid fats) in humans is not clear. Laboratory animals fed rancid fats develop atherosclerosis. Rats fed DHA-containing oils experienced marked disruptions to their antioxidant systems, as well as accumulated significant amounts of peroxide in their blood, livers and kidneys.^[16] In another study, rabbits fed atherogenic diets containing various oils were found to undergo the greatest amount of oxidative susceptibility of LDL via polyunsaturated oils.^[17] In a study involving rabbits fed heated soybean oil, "grossly induced atherosclerosis and marked liver damage were histologically and clinically demonstrated".^[18] Mechanism of lipid peroxidation. ... Rancidification is the decomposition of fats and other lipids by hydrolysis and/or oxidation. ... Docosahexaenoic acid (commonly known as DHA; 22:6(ω-3), all-cis-docosa-4,7,10,13,16,19-hexaenoic acid; trivial name cervonic acid) is an omega-3 essential fatty acid. ... Space-filling model of the antioxidant metabolite glutathione. ...

Rancid fats and oils taste very bad even in small amounts; people avoid eating them.^[19] It is very difficult to measure or estimate the actual human consumption of these substances.^[20] In addition, the majority of oils consumed in the United States are refined, bleached, deodorized and degummed by manufacturers. The resultant oils are colorless, odorless, tasteless and have a longer shelf life than their unrefined counterparts.^[21] This extensive processing serves to make peroxidated, rancid oils much more elusive to detection via the various human senses than the unprocessed alternatives.

Prognosis

Lipoprotein imbalances, upper normal and especially elevated blood sugar, i.e., diabetes and high blood pressure are risk factors for atherosclerosis; homocysteine, stopping smoking, taking anticoagulants (anti-clotting agents), which target clotting factors, taking omega-3 oils from fatty fish or plant oils such as flax or canola oils, exercising and losing weight are the usual focus of treatments that have proven to be helpful in clinical trials. The target serum cholesterol level is ideally equal or less than 4mmol/L (160 mg/dL), and triglycerides equal or less than 2mmol/L (180 mg/dL). Dyslipidemia is a disruption in the amount of lipids in the blood. ... This article is about the disease that features high blood sugar. ... Homocysteine is a chemical compound with the formula HSCH2CH2CH(NH2)CO2H. It is a homologue of the naturally-occurring amino acid cysteine, differing in that its side-chain contains an additional methylene (-CH2-) group before the thiol (-SH) group. ... An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. ...

Evidence has increased that people with diabetes, despite their not having clinically-detectable atherosclotic disease, have more severe debility from atherosclerotic events over time than even non-diabetics that have already suffered atherosclerotic events. Thus diabetes has been upgraded to be viewed as an advanced atherosclerotic disease equivalent. This article is about the disease that features high blood sugar. ... This article is about the disease that features high blood sugar. ...

Treatment

If atherosclerosis leads to symptoms, some symptoms such as angina pectoris can be treated. Non-pharmaceutical means are usually the first method of treatment, such as cessation of smoking and practicing regular exercise. If these methods do not work, medicines are usually the next step in treating cardiovascular diseases, and, with improvements, have increasingly become the most effective method over the long term. However, medicines are criticized for their expense, patented control and occasional undesired effects.

Statins

In general, the group of medications referred to as statins has been the most popular and are widely prescribed for treating atherosclerosis. They have relatively few short-term or longer-term undesirable side-effects, and multiple comparative treatment/placebo trials have fairly consistently shown strong effects in reducing atherosclerotic disease 'events' and generally ~25% comparative mortality reduction in clinical trials, although one study design, ALLHAT.^[22] was less strongly favorable. Lovastatin, the first statin to be marketed The statins form a class of hypolipidemic agents. ...

The newest statin, rosuvastatin, has been the first to demonstrate regression of atherosclerotic plaque within the coronary arteries by IVUS (intravascular ultrasound evaluation),^[9] The study was set up to demonstrate effect primarily on atherosclerosis volume within a 2 year time-frame in people with active/symptomatic disease (angina frequency also declined markedly) but not global clinical outcomes, which was expected to require longer trial time periods; these longer trials remain in progress. Rosuvastatin is a member of the drug class of statins, used to treat hypercholesterolemia and related conditions, and to prevent cardiovascular disease. ... The coronary circulation consists of the blood vessels that supply blood to, and remove blood from, the heart. ... Intravascular ultrasound (IVUS) is an medical imaging methodology using (a) specially designed long thin complex manufactured catheters attached to (b) computerized ultrasound equipment. ...

However, for most people, changing their physiologic behaviors, from the usual high risk to greatly reduced risk, requires a combination of several compounds, taken on a daily basis and indefinitely. More and more human treatment trials have been done and are ongoing that demonstrate improved outcome for those people using more-complex and effective treatment regimens that change physiologic behaviour patterns to more closely resemble those that humans exhibit in childhood at a time before fatty streaks begin forming. Fatty streak is the term generally given to the earliest stages of atheroma, as viewed at autopsy, looking at the inner surface of arteries, without magnification. ...

The statins, and some other medications, have been shown to have antioxidant effects, possibly part of their basis for some of their therapeutic success in reducing cardiac 'events'. Lovastatin, the first statin to be marketed The statins (or HMG-CoA reductase inhibitors) form a class of hypolipidemic drugs used to lower cholesterol levels in people with or at risk of cardiovascular disease. ... Space-filling model of the antioxidant metabolite glutathione. ...

The success of statin drugs in clinical trials is based on some reductions in mortality rates, however by trial design biased toward men and middle-age, the data is as, as yet, less strongly clear for women and people over the age of 70 CMAJ. For example, in the Scandinavian Simvastatin Survival Study (4S), the first large placebo controlled, randomized clinical trial of a statin in people with advanced disease who had already suffered a heart attack, the overall mortality rate reduction for those taking the statin, vs. placebo, was 30%. For the subgroup of people in the trial that had Diabetes Mellitus, the mortality rate reduction between statin and placebo was 54%. 4S was a 5.4-year trial that started in 1989 and was published in 1995 after completion. There were 3 more dead women at trial's end on statin than in the group on placebo drug whether chance or some relation to the statin remains unclear. The ASTEROID trial has been the first to show actual disease volume regression^[9] (see page 8 of the paper, which shows cross-sectional areas of the total heart artery wall at start and 2 years of rosuvastatin 40 mg/day treatment); however, its design was not able to "prove" the mortality reduction issue since it did not include a placebo group, the individuals offered treatment within the trial had advanced disease and promoting a comparison placebo arm was judged to be unethical. The Scandinavian Simvastatin Survival Study (also known under the abbreviation 4S) is a multicenter clinical trial that was performed in 1990s in Scandinavia. ...

Primary and Secondary Prevention—Studies

Combinations of statins, niacin, intestinal cholesterol absorption-inhibiting supplements (ezetimibe and others, and to a much lesser extent fibrates) have been the most successful in changing common but sub-optimal lipoprotein patterns and group outcomes. In the many secondary prevention and several primary prevention trials, several classes of lipoprotein expression (less correctly termed "cholesterol-lowering") altering agents have consistently reduced not only heart attack, stroke and hospitalization but also all-cause mortality rates. The first of the large secondary prevention comparative statin/placebo treatment trials was the Scandinavian Simvastatin Survival Study (4S) ^[23] with over 15 more extending through the more recent ASTEROID ^[24] trial published in 2006. The first primary prevention comparative treatment trial was AFCAPS/TexCAPS ^[25] with multiple later comparative statin/placebo treatment trials including EXCEL.^[26], ASCOT ^[27] and SPARCL.^{[28] [29]} While the statin trials have all been clearly favorable for improved human outcomes, only ASTEROID showed evidence of atherosclerotic regression (slight). For both human and animal trials, those which have shown evidence of disease regression had all utilized more aggressive combination agent treatment strategies, nearly always including niacin.^[11] Lovastatin, the first statin to be marketed The statins (or HMG-CoA reductase inhibitors) form a class of hypolipidemic drugs used to lower cholesterol levels in people with or at risk of cardiovascular disease. ... Niacin, also known as nicotinic acid or vitamin B3, is a water-soluble vitamin whose derivatives such as NADH, NAD, NAD+, and NADP play essential roles in energy metabolism in the living cell and DNA repair. ... Ezetimibe (IPA: ) is an anti-hyperlipidemic medication which is used to lower cholesterol levels. ... Clofibrate Clofibride Etofibrate Aluminium clofibrate In pharmacology, the fibrates are a class of amphipathic carboxylic acids. ... A lipoprotein is a biochemical assembly that contains both proteins and lipids. ...

Diet and dietary supplements

Vitamin B3, AKA niacin, in pharmacologic doses, (generally 1,000 to 3,000 mg/day), sold in many OTC and prescription formulations, tends to improve (a) HDL levels, size and function, (b) shift LDL particle distribution to larger particle size and (c) lower lipoprotein(a), an atheroslerosis promoting genetic variant of LDL. Additionally, individual responses to daily niacin, while mostly evident after a month at effective doses, tends to continue to slowly improve further over time. (However, careful patient understanding of how to achieve this without nuisance symptoms is needed, though not often achieved.) Research work on increasing HDL particle concentration and function, beyond the usual niacin effect/response, even more important, is slowly advancing. Niacin, also known as nicotinic acid or vitamin B3, is a water-soluble vitamin whose derivatives such as NADH, NAD, NAD+, and NADP play essential roles in energy metabolism in the living cell and DNA repair. ... Lipoprotein(a) (also called LP(a) and Lp-a) is a lipoprotein subclass. ...

Dietary changes to achieve benefit have been more controversial, generally far less effective and less widely adhered to with success. One key reason for this is that most cholesterol, typically 80-90%, within the body is created and controlled by internal production by all cells in the body (true of all animals), with typically slightly greater relative production by hepatic/liver cells. (Cell structure relies on fat membranes to separate and organize intracellular water, proteins and nucleic acids and cholesterol is one of the components of all animal cell membranes.)

Caldwell B Esselstyn Jr. MD has had an article published in Preventive Cardiology 2001;4: 171-177 in which he has published angiograms showing regression of atherosclerosis brought about by a very low fat vegan diet in some cases with cholesterol lowering medications.^[30]

While the absolute production quantities vary with the individual, group averages for total human body content of cholesterol within the U.S. population commonly run about ~35,000 mg (assuming lean build; varies with body weight and build) and ~1,000 mg/day ongoing production. Dietary intake plays a smaller role, 200-300 mg/day being common values; for pure vegetarians, essentially 0 mg/day, but this typically does not change the situation very much because internal production increases to largely compensate for the reduced intake. For many, especially those with greater than optimal body mass and increased glucose levels, reducing carbohydrate (especially simple forms) intake, not fats or cholesterol, is often more effective for improving lipoprotein expression patterns, weight and blood glucose values. For this reason, medical authorities much less frequently promote the low dietary fat concepts than was commonly the case prior to about year 2005. However, evidence has increased that processed, particularly industrial non-enzymatic hydrogenation produced trans fats, as opposed to the natural cis-configured fats, which living cells primarily produce, is a significant health hazard. Hydrogenation is a class of chemical reactions which result an addition of hydrogen (H2) usually to unsaturated organic compounds. ... CIS usually refers to: Commonwealth of Independent States, a modern-day political entity consisting of 11 former Soviet Union Republics CIS is also an acronym for: Canadian Interuniversity Sport Cancer Information Service Carcinoma in situ Centre for Independent Studies Center for Immigration Studies Chinese International School Cisalpino Citizenship & Immigration Services...

Dietary supplements of Omega-3 oils, especially those from the muscle of some deep salt water living fish species, also have clinical evidence of significant protective effects as confirmed by 6 double blind placebo controlled human clinical trials. The Double blind method is an important part of the scientific method, used to prevent research outcomes from being influenced by the placebo effect or observer bias. ... For other uses, see Placebo (disambiguation). ... A scientific control augments integrity in experiments by isolating variables as dictated by the scientific method in order to make a conclusion about such variables. ...

There is also a variety of evidence, though less robust, that homocysteine and uric acid levels, including within the normal range promote atherosclerosis and that lowering these levels is helpful, up to a point. Homocysteine is a chemical compound with the formula HSCH2CH2CH(NH2)CO2H. It is a homologue of the naturally-occurring amino acid cysteine, differing in that its side-chain contains an additional methylene (-CH2-) group before the thiol (-SH) group. ... Uric acid (or urate) is an organic compound of carbon, nitrogen, oxygen and hydrogen with the formula C5H4N4O3. ...

In animals Vitamin C deficiency has been confirmed as an important role in development of hypercholesterolemia and atherosclerosis, but due to ethical reasons placebo-controlled human studies are impossible to do.^[31] Vitamin C acts as an antioxidant in vessels.^[32] This article is about the nutrient. ... Hypercholesterolemia (literally: high blood cholesterol) is the presence of high levels of cholesterol in the blood [1]. It is not a disease but a metabolic derangement that can be secondary to many diseases and can contribute to many forms of disease, most notably cardiovascular disease. ... This article is about the nutrient. ... Space-filling model of the antioxidant metabolite glutathione. ...

Trials on Vitamin E have been done, but they have failed to find a beneficial effect, for various reasons, but for some patients at high risk for atherosclerosis there may be some benefits.^[33] The α-tocopherol form of vitamin E. Main articles: tocopherol and tocotrienol Vitamin E is the collective name for a set of 8 related tocopherols and tocotrienols, which are fat-soluble vitamins with antioxidant properties. ...

Menaquinone (Vitamin K2), but not phylloquinone (Vitamin K1), intake is associated with reduced risk of CHD mortality, all-cause mortality and severe aortic calcification.^[34][35][36] Vitamin K1 (phylloquinone). ... Vitamin K1 (phylloquinone). ...

It has been suggested that excess iron may be involved in development of atherosclerosis^[37][38], but one study found reducing body iron stores in patients with symptomatic peripheral artery disease through phlebotomy did not significantly decrease all-cause mortality or death plus nonfatal myocardial infarction and stroke.^[39] Further studies may be warranted. Fe redirects here. ... In medicine, peripheral artery occlusive disease (PAOD), also known as peripheral vascular disease (PVD) and peripheral artery disease (PAD) is a collator for all diseases caused by the obstruction of large peripheral arteries, which can result from atherosclerosis, inflammatory processes leading to stenosis, an embolism or thrombus formation. ... Bloodletting (or blood-letting, in modern medicine referred to as phlebotomy) was a popular medical practice from antiquity up to the late 19th century, involving the withdrawal of often considerable quantities of blood from a patient in the belief that this would cure or prevent illness and disease. ...

Surgical intervention

Other physical treatments, helpful in the short term, include minimally invasive angioplasty procedures that may include stents to physically expand narrowed arteries^[40] and major invasive surgery, such as bypass surgery, to create additional blood supply connections that go around the more severely narrowed areas. This article does not cite any references or sources. ... In medicine, a stent is an expandable wire mesh tube that is inserted into a hollow structure of the body to keep it open. ... Early in a coronary artery bypass surgery during vein harvesting from the legs (left of image) and the establishment of bypass (placement of the aortic cannula) (bottom of image). ...

Prophylaxis

Patients at risk for atherosclerosis-related diseases are increasingly being treated prophylactically with low-dose aspirin and a statin. The high incidence of cardiovascular disease led Wald and Law^[41] to propose a Polypill, a once-daily pill containing these two types of drugs in addition to an ACE inhibitor, diuretic, beta blocker, and folic acid. They maintain that high uptake by the general population by such a Polypill would reduce cardiovascular mortality by 80%. It must be emphasized however that this is purely theoretical, as the Polypill has never been tested in a clinical trial. Prophylaxis refers to any medical or public health procedure whose purpose is to prevent, rather than treat or cure, disease. ... This article is about the drug. ... Lovastatin, the first statin to be marketed The statins (or HMG-CoA reductase inhibitors) form a class of hypolipidemic drugs used to lower cholesterol levels in people with or at risk of cardiovascular disease. ... // In medicine, the term Polypill has been coined to refer to a medication which contains a combination of active ingredients. ... Captopril, the first ACE inhibitor ACE inhibitors, or inhibitors of Angiotensin-Converting Enzyme, are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in some cases as the drugs of first choice. ... This illustration shows where some types of diuretics act, and what they do. ... Beta blockers or beta-adrenergic blocking agents are a class of drugs used to treat a variety of cardiovascular conditions and some other diseases. ... Folic acid and folate (the anion form) are forms of the water-soluble Vitamin B9. ...

Medical treatments often focus predominantly on the symptoms. However, over time, the treatments which focus on decreasing the underlying atherosclerosis processes, as opposed to simply treating the symptoms resulting from the atherosclerosis, have been shown by clinical trials to be more effective.

In summary, the key to the more effective approaches has been better understanding of the widespread and insidious nature of the disease and to combine multiple different treatment strategies, not rely on just one or a few approaches. In addition, for those approaches, such as lipoprotein transport behaviors, which have been shown to produce the most success, adopting more aggressive combination treatment strategies has generally produced better results, both before and especially after people are symptomatic. However, treating asymptomatic people remains controversial in the medical community.

Recent research

June 22nd http://www.news-medical.net/?id=39374. Discovery of a new protein and how immune reacts to cholesterol deposits.

An indication of the role of HDL on atherosclerosis has been with the rare Apo-A1 Milano human genetic variant of this HDL protein. A small short-term trial using bacterial synthetized human Apo-A1 Milano HDL in people with unstable angina produced fairly dramatic reduction in measured coronary plaque volume in only 6 weeks vs. the usual increase in plaque volume in those randomized to placebo. The trial was published in JAMA in early 2006. Ongoing work starting in the 1990s may lead to human clinical trials—probably by about 2008. These may use synthesized Apo-A1 Milano HDL directly. Or they may use gene-transfer methods to pass the ability to synthesize the Apo-A1 Milano HDLipoprotein. There are very few or no other articles that link to this one. ...

Methods to increase high-density lipoprotein (HDL) particle concentrations, which in some animal studies largely reverses and remove atheromas, are being developed and researched. High density lipoproteins (HDL) form a class of lipoproteins, varying somewhat in their size and contents, that carry cholesterol from the bodys tissues to the liver. ...

Niacin has HDL raising effects (by 10 - 30%) and showed clinical trial benefit in the Coronary Drug Project and is commonly used in combination with other lipoprotein agents to improve efficacy of changing lipoprotein for the better. However most individuals have nuisance symptoms with short term flushing reactions, especially initially, and so working with a physician with a history of successful experience with niacin implementation, careful selection of brand, dosing strategy, etc. are usually critical to success. Niacin, also known as nicotinic acid or vitamin B3, is a water-soluble vitamin whose derivatives such as NADH, NAD, NAD+, and NADP play essential roles in energy metabolism in the living cell and DNA repair. ...

However, increasing HDL by any means is not necessary helpful. For example, the drug torcetrapib is the most effective agent currently known for raising HDL (by up to 60%). However, in clinical trials it also raised deaths by 60%. All studies regarding this drug were halted in December 2006.^[42] Chemical structure of torcetrapib Torcetrapib (CP-529414, Pfizer) was a drug being developed to treat hypercholesterolemia (elevated cholesterol levels) and prevent cardiovascular disease. ...

The ERASE trial is a newer trial of an HDL booster which has shown promise.^[43]

The ASTEROID trial used a high-dose of rosuvastatin—the statin with typically the most potent dose/response correlation track record (both for LDLipoproteins and HDLipoproteins.) It found plaque (intima + media volume) reduction.^[9] Several additional rosuvastatin treatment/placebo trials for evaluating other clinical outcomes are in progress. Rosuvastatin is a member of the drug class of statins, used to treat hypercholesterolemia and related conditions, and to prevent cardiovascular disease. ...

The actions of macrophages drive atherosclerotic plaque progression. Immunomodulation of atherosclerosis is the term for techniques which modulate immune system function in order to suppress this macrophage action.^[44] Immunomodulation has been pursued with considerable success in both mice and rabbits since about 2002. Plans for human trials, hoped for by about 2008, are in progress.

Research on genetic expression and control mechanisms is progressing. Topics include

• PPAR, known to be important in blood sugar and variants of lipoprotein production and function;
• The multiple variants of the proteins that form the lipoprotein transport particles.

Some controversial research has suggested a link between atherosclerosis and the presence of several different nanobacteria in the arteries, e.g., Chlamydophila pneumoniae, though trials of current antibiotic treatments known to be usually effective in suppressing growth or killing these bacteria have not been successful in improving outcomes.^[45] In cell biology, peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor isoforms that exist across biology. ... Structures found on meteorite fragment ALH84001 Nanobacteria are said to be cell walled microorganisms with a diameter well below the generally accepted lower limit (about 200 nanometres) for bacteria. ... Chlamydophila pneumoniae (previously known as Chlamydia pneumoniae) is a species of chlamydiae bacteria which infects humans and is a major cause of pneumonia. ...

The immunomodulation approaches mentioned above, because they deal with innate responses of the host to promote atherosclerosis, have far greater prospects for success.

French Paradox and Red Wine

French Paradox study shows 44% lower cases of heart disease in the French even though they consume a diet rich in saturated fats. In 1999, rates of death from coronary heart disease among males aged 35–74 years was 115 per 100,000 people in the US but only 83 per 100,000 in France. Resveratrol is one of the key active antioxidants. BBC.Why wine is good for you. Red Wine Protects The Heart [2] This article or section does not cite any references or sources. ... The cis-isomer of resveratrol Resveratrol is a phytoalexin produced naturally by several plants when under attack by bacteria or fungi. ...

References

Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 306th day of the year (307th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 306th day of the year (307th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 325th day of the year (326th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 323rd day of the year (324th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Common Era (or Anno Domini), in accordance with the Gregorian calendar. ... is the 113th day of the year (114th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 329th day of the year (330th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 329th day of the year (330th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 344th day of the year (345th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 344th day of the year (345th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 344th day of the year (345th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 338th day of the year (339th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Common Era (or Anno Domini), in accordance with the Gregorian calendar. ... is the 178th day of the year (179th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 329th day of the year (330th in leap years) in the Gregorian calendar. ... Udo Erasmus is a nutritionist, lecturer, and writer specializing in fats, oils, cholesterol, and essential fatty acids. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 306th day of the year (307th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 322nd day of the year (323rd in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 325th day of the year (326th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 325th day of the year (326th in leap years) in the Gregorian calendar. ... Medscape is a free site containing peer-reviewed information written at the level of physicians and other health profesionals, but open to anyone who registers. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 323rd day of the year (324th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 323rd day of the year (324th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Common Era (or Anno Domini), in accordance with the Gregorian calendar. ... is the 178th day of the year (179th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Common Era (or Anno Domini), in accordance with the Gregorian calendar. ... is the 91st day of the year (92nd in leap years) in the Gregorian calendar. ... The British Medical Journal (BMJ) is a medical journal published weekly in the United Kingdom by the British Medical Association (BMA)which published its first issue in 1845. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 317th day of the year (318th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Common Era (or Anno Domini), in accordance with the Gregorian calendar. ... is the 177th day of the year (178th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 317th day of the year (318th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 306th day of the year (307th in leap years) in the Gregorian calendar. ...

General references

• Stevens RJ, Douglas KM, Saratzis AN, Kitas GD (2005). "Inflammation and atherosclerosis in rheumatoid arthritis". Expert reviews in molecular medicine 7 (7): 1–24. doi:10.1017/S1462399405009154. PMID 15876361. Retrieved on 2007-11-02. 
• Mol, A (2002). The Body Multiple: Ontology in medical practice. London: Duke University Press. 

A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) was a common year starting on Monday of the Gregorian calendar in the 21st century. ... is the 306th day of the year (307th in leap years) in the Gregorian calendar. ...

External links

• Atlas of Pathology
• International Atherosclerosis Society
• Arterial Vascular Effects of Non-steroidal Antiphlogistic Drugs - A Biochemical Model on an Intramural Induction of Arteriosclerosis, Rainer K Liedtke, MD

See also