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. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings I00-I99 - Diseases of the Circulatory system (I00-I02 Acute rheumatic fever ( Rheumatic fever without mention of Heart The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books A disease is an abnormal condition of an organism that impairs bodily functions and can be deadly Arteries are Blood vessels that carry blood away from the Heart. The blood vessels are part of the Circulatory system and function to transport Blood throughout the body 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). Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that A lipoprotein is a biochemical assembly that contains both Proteins and Lipids The lipids or their derivatives may be covalently or non-covalently bound (more properly known as, TAG or triacylglyceride) is Glyceride in which the Glycerol is Esterified with three Fatty acids It is the High-density lipoproteins ( HDL) is one of the 5 major groups of Lipoproteins ( Chylomicrons, VLDL, IDL, LDL, HDL 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. In Pathology, an atheroma (plural atheromata is an accumulation and swelling (-oma in Artery walls that is made up of cells (mostly Macrophage cells Arteries are Blood vessels that carry blood away from the Heart. ^[1]

The atheromatous plaque is divided into three distinct components:

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. In Pathology, an atheroma (plural atheromata is an accumulation and swelling (-oma in Artery walls that is made up of cells (mostly Macrophage cells In Pathology, an atheroma (plural atheromata is an accumulation and swelling (-oma in Artery walls that is made up of cells (mostly Macrophage cells Porridge, or porage, is a simple dish made by boiling Oats (normally crushed oats occasionally Oatmeal) or another cereal in Water Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that A lumen (Lat lūmen, an opening or light (pl lumina is the inside space or lining of a tubular structure such as an artery or intestine Cholesterol is a Lipid found in the Cell membranes and transported in the Blood plasma of all Animals It is an essential component of mammalian

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. An arteriole is a small diameter Blood vessel that extends and branches out from an Artery and leads to capillaries. Therefore, atherosclerosis is a form of arteriosclerosis.

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. In Pathology, an atheroma (plural atheromata is an accumulation and swelling (-oma in Artery walls that is made up of cells (mostly Macrophage cells Intima-media thickness (IMT also called intimal medial thickness is a measurement of the thickness of Artery walls, usually by external ultrasound occasionally by internal A stenosis ( Plural: stenoses; from Ancient Greek στένωσις "narrowing" is an abnormal narrowing in a Blood vessel If the compensating artery enlargement process is excessive, then a net aneurysm results. An aneurysm (or aneurism) is a localized blood-filled dilation (balloon-like bulge of a blood vessel caused by disease or weakening of the vessel wall

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. A vulnerable plaque is an Atheromatous plaque an unstable collection of White blood cells (primarily Macrophages and Lipids (including A thrombus, or blood clot, is the final product of the Blood coagulation step in Hemostasis. This catastrophic event is called an infarction. In Medicine, an infarction is the process resulting in a Macroscopic area of necrotic tissue in some organ caused by loss of adequate Blood supply One of the most common recognized scenarios is called coronary thrombosis of a coronary artery, causing myocardial infarction (a heart attack). Coronary thrombosis is a form of Thrombosis affecting the Coronary circulation. Coronary circulation is the circulation of blood in the Blood vessels that supply Blood to and from the Heart muscle Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply 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. Claudication, literally ' Limping ( Latin) is used as a Medical term in various contexts A thrombus, or blood clot, is the final product of the Blood coagulation step in Hemostasis. Since atherosclerosis is a body-wide process, similar events occur also in the arteries to the brain, intestines, kidneys, legs, etc.

Contents 1 Causes 2 Symptoms 3 Atherogenesis 3.1 Cellular 3.2 Calcification and lipids 3.3 Visible features 3.4 Rupture and stenosis 4 Diagnosis of plaque-related disease 5 Physiologic factors that increase risk 5.1 Dietary risk factors 6 Prognosis 7 Treatment 7.1 Statins 7.1.1 Primary and Secondary Prevention—Studies 7.2 Diet and dietary supplements 7.3 Surgical intervention 7.4 Prophylaxis 8 Recent research 9 French Paradox and Red Wine 10 References 10.1 General references 11 External links 12 See also

Causes

Atherosclerosis develops from low-density lipoprotein cholesterol (LDL), colloquially called "bad cholesterol". Many believe that, when this lipoprotein gets through the wall of an artery, oxygen free radicals react with it to form oxidized-LDL. A lipoprotein is a biochemical assembly that contains both Proteins and Lipids The lipids or their derivatives may be covalently or non-covalently bound Arteries are Blood vessels that carry blood away from the Heart. In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell ^[2] The body's immune system responds by sending specialised white blood cells (macrophages and T-lymphocytes) to absorb the oxidised-LDL. Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. 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.

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. Marek's disease is a highly contagious viral neoplastic disease in Chickens Occasionally misdiagnosed as an Abtissue pathology it is caused ^[3] Herpesvirus infection of arterial smooth muscle cells has been shown to cause cholesteryl ester (CE) accumulation. The Herpesviridae are a large family of DNA viruses that cause diseases in animals including humans Smooth muscle is a type of non- Striated muscle, found within the Tunica media layer of large and small Arteries and Veins, the bladder ^[4] Cholesteryl ester accumulation is associated with atherosclerosis. 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. Arteries are Blood vessels that carry blood away from the Heart. 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. Coronary circulation is the circulation of blood in the Blood vessels that supply Blood to and from the Heart muscle The heart is a muscular organ in all Vertebrates responsible for pumping Blood through the Blood vessels by repeated rhythmic Cerebral circulation refers to the movement of Blood through the network of Blood vessels supplying the Brain. The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply Heart disease is an Umbrella term for a variety for different diseases affecting the Heart. Heart failure is a Cardiac condition that occurs when a problem with the structure or function of the Heart impairs its ability to supply Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and Atheroma in arm, or more often in leg arteries, which produces decreased blood flow is called Peripheral artery occlusive disease (PAOD). Peripheral vascular disease (PVD also known as peripheral artery disease (PAD or peripheral artery occlusive disease (PAOD is a collator for all Diseases

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' (from Greek σύμπτωμα, "accident misfortune that which befalls" from συμπίπτω, "I befall" from Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply The term sudden cardiac death refers to Natural death from cardiac causes heralded by abrupt loss of Consciousness within one hour of the onset of acute symptoms

Most artery flow disrupting events occur at locations with less than 50% lumen narrowing (~20% stenosis is average). A lumen (Lat lūmen, an opening or light (pl lumina is the inside space or lining of a tubular structure such as an artery or intestine A stenosis ( Plural: stenoses; from Ancient Greek στένωσις "narrowing" is an abnormal narrowing in a Blood vessel [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. Intravascular ultrasound ( IVUS) is a Medical imaging methodology using a specially designed Catheter with a miniaturized Ultrasound probe attached The relative geometry error within the illustration is common to many older illustrations, an error slowly being more commonly recognized within the last decade. ]

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 that indirectly reflects arterial Blood flow to the Heart during Physical exercise A lumen (Lat lūmen, an opening or light (pl lumina is the inside space or lining of a tubular structure such as an artery or intestine

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. Arteries are Blood vessels that carry blood away from the Heart. 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. Monocyte is a type of Leukocyte, part of the Human body 's Immune system. The endothelium is the thin layer of cells that line the interior surface of Blood vessels forming an interface between circulating Blood in the The cardiac muscle is a type of involuntary striated Muscle found in the walls of the Heart. 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. Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens The tunica intima (or just intima) is the innermost layer of an Artery or Vein. The endothelium is the thin layer of cells that line the interior surface of Blood vessels forming an interface between circulating Blood in the The tunica media (or just media) ( middle coat) is the middle layer of an Artery or Vein. The bulk of these lesions is made of excess fat, collagen, and elastin. Collagen is the main Protein of Connective tissue in Animals and the most abundant protein in Mammals making up about 50% of the whole-body protein 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 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. Intima-media thickness (IMT also called intimal medial thickness is a measurement of the thickness of Artery walls, usually by external ultrasound occasionally by internal A stenosis ( Plural: stenoses; from Ancient Greek στένωσις "narrowing" is an abnormal narrowing in a Blood vessel

Cellular

The first step of atherogenesis is the development of fatty streaks, which are small subendothelial deposits of oxidized cholesterol and monocyte-derived macrophages. Fatty streak, though composed of macrophage white blood cells not fat is the term generally given to the earliest stages of Atheroma, as viewed at autopsy looking at The exact cause for this process is unknown, and fatty streaks may appear and disappear.

LDL in blood plasma poses a risk for cardiovascular disease when it invades the endothelium and becomes oxidized. Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and The endothelium is the thin layer of cells that line the interior surface of Blood vessels forming an interface between circulating Blood in the Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state 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. In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell The endothelium is the thin layer of cells that line the interior surface of Blood vessels forming an interface between circulating Blood in the

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. Monocyte is a type of Leukocyte, part of the Human body 's Immune system. This may be promoted by redox signaling induction of factors such as VCAM-1, which recruit circulating monocytes. Redox signaling is the process wherein Free radicals, Reactive oxygen species (ROS and other electronically-activated species act as messengers in biological systems Vascular cell adhesion molecule 1, also known as VCAM1, is a human Gene. 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. Monocyte is a type of Leukocyte, part of the Human body 's Immune system. Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state Low-density lipoprotein ( LDL) is a type of Lipoprotein that transports Cholesterol and Triglycerides from the Liver to peripheral A vesicle is a small bubble of liquid within a cell A more formal definition in Cell biology, would be that a vesicle is a relatively small intracellular membrane-enclosed Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble 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.

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. Calcification is the process in which the mineral calcium builds up in soft tissue causing it to harden Vascular smooth muscle refers to the particular type of Smooth muscle found within and composing the majority of the wall of Blood vessels Vascular smooth muscle 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). Rainer K Liedtke (*1943 Königsberg East Prussia) is a German physician scientist and entrepreneur

Cholesterol is delivered into the vessel wall by cholesterol-containing low-density lipoprotein (LDL) particles. Low-density lipoprotein ( LDL) is a type of Lipoprotein that transports Cholesterol and Triglycerides from the Liver to peripheral 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. High-density lipoproteins ( HDL) is one of the 5 major groups of Lipoproteins ( Chylomicrons, VLDL, IDL, LDL, HDL

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. Smooth muscle is a type of non- Striated muscle, found within the Tunica media layer of large and small Arteries and Veins, the bladder A protective fibrous cap normally forms between the fatty deposits and the artery lining (the intima). The endothelium is the thin layer of cells that line the interior surface of Blood vessels forming an interface between circulating Blood in the

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. A stenosis ( Plural: stenoses; from Ancient Greek στένωσις "narrowing" is an abnormal narrowing in a Blood vessel 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. An aneurysm (or aneurism) is a localized blood-filled dilation (balloon-like bulge of a blood vessel caused by disease or weakening of the vessel wall ^[8]

Visible features

Although arteries are not typically studied microscopically, two plaque types can be distinguished[1]:

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. An aneurysm (or aneurism) is a localized blood-filled dilation (balloon-like bulge of a blood vessel caused by disease or weakening of the vessel wall In Pathology, an atheroma (plural atheromata is an accumulation and swelling (-oma in Artery walls that is made up of cells (mostly Macrophage cells The muscular portion of artery walls usually remain strong, even after they have remodeled to compensate for the atheromatous plaques. In Pathology, an atheroma (plural atheromata is an accumulation and swelling (-oma in Artery walls that is made up of cells (mostly Macrophage cells

However, atheromas within the vessel wall are soft and fragile with little elasticity. In Pathology, an atheroma (plural atheromata is an accumulation and swelling (-oma in Artery walls that is made up of cells (mostly Macrophage cells 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.

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. Computed tomography (CT is a Medical imaging method employing Tomography. Electron beam tomography (EBT is a specific form of Computed axial tomography (CAT or CT in which the X-ray tube is not mechanically spun in order to rotate the 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. The Hounsfield scale is a quantitative scale for describing Radiodensity. 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. Intravascular ultrasound ( IVUS) is a Medical imaging methodology using a specially designed Catheter with a miniaturized Ultrasound probe attached

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. A stenosis ( Plural: stenoses; from Ancient Greek στένωσις "narrowing" is an abnormal narrowing in a Blood vessel 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. "

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. Collagen is the main Protein of Connective tissue in Animals and the most abundant protein in Mammals making up about 50% of the whole-body protein Tissue factor, also called thromboplastin, factor III or CD142 is a Protein present in subendothelial tissue, Platelets Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby The result is the formation of a thrombus (blood clot) overlying the atheroma, which obstructs blood flow acutely. A thrombus, or blood clot, is the final product of the Blood coagulation step in Hemostasis. With the obstruction of blood flow, downstream tissues are starved of oxygen and nutrients. Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the If this is the myocardium (heart muscle), angina (cardiac chest pain) or myocardial infarction (heart attack) develops. Myocardium is the muscular tissue of the Heart. Relationship to other layers The other tissues of the heart are the Endocardium Angina pectoris, commonly known as angina, is severe Chest pain due to Ischemia (a lack of blood and hence Oxygen supply of the heart Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply

Diagnosis of plaque-related disease

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. A stenosis ( Plural: stenoses; from Ancient Greek στένωσις "narrowing" is an abnormal narrowing in a Blood vessel Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and However, these methods focus on detecting only severe narrowing, not the underlying atherosclerosis disease. A stenosis ( Plural: stenoses; from Ancient Greek στένωσις "narrowing" is an abnormal narrowing in a Blood vessel 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. A stenosis ( Plural: stenoses; from Ancient Greek στένωσις "narrowing" is an abnormal narrowing in a Blood vessel Plaque rupture can lead to artery lumen occlusion within seconds to minutes, and potential permanent debility and sometimes sudden death.

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. Collagen is the main Protein of Connective tissue in Animals and the most abundant protein in Mammals making up about 50% of the whole-body protein After rupture the platelet adhesion causes the clotting cascade to contact with the lipid pool causing a thrombus to form. A thrombus, or blood clot, is the final product of the Blood coagulation step in Hemostasis. 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. A thrombus, or blood clot, is the final product of the Blood coagulation step in Hemostasis. 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. Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the Necrosis (in Greek Νεκρός = "dead" is the name given to unnatural Death of cells and living tissue. Serious complicated plaques can cause death of organ tissues, causing serious complications to that organ system.

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. A stenosis ( Plural: stenoses; from Ancient Greek στένωσις "narrowing" is an abnormal narrowing in a Blood vessel Angina pectoris, commonly known as angina, is severe Chest pain due to Ischemia (a lack of blood and hence Oxygen supply of the heart However, clinical trials have shown that only about 14% of clinically-debilitating events occur at locations with this, or greater severity of narrowing. A stenosis ( Plural: stenoses; from Ancient Greek στένωσις "narrowing" is an abnormal narrowing in a Blood vessel The majority of events occur due to atheroma plaque rupture at areas without narrowing sufficient enough to produce any angina or stress test abnormalities. A stenosis ( Plural: stenoses; from Ancient Greek στένωσις "narrowing" is an abnormal narrowing in a Blood vessel Angina pectoris, commonly known as angina, is severe Chest pain due to Ischemia (a lack of blood and hence Oxygen supply of the heart Thus, since the later-1990s, greater attention is being focused on the "vulnerable plaque. "^[10]

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. A stenosis ( Plural: stenoses; from Ancient Greek στένωσις "narrowing" is an abnormal narrowing in a Blood vessel Obstruction of arteries supplying the heart muscle result in a heart attack. Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply Obstruction of arteries supplying the brain result in a stroke. A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain 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%.

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. Intima-media thickness (IMT also called intimal medial thickness is a measurement of the thickness of Artery walls, usually by external ultrasound occasionally by internal

Examples of physiologic methods include: (1) lipoprotein subclass analysis, (2) HbA1c, (3) hs-CRP, and (4) homocysteine. Glycosylated (or glycated hemoglobin ( hemoglobin A1c Hb1c, or HbA1c) is a form of Hemoglobin used primarily to identify the average C-reactive protein ( CRP) is a Plasma protein, an Acute phase protein produced by the Liver and by Adipocytes. Homocysteine is a Chemical compound with the formula HSCH2CH2CH(NH2CO2H

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":

• 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. Metabolic syndrome is a combination of medical disorders that increase the risk of developing Cardiovascular disease and diabetes. Senescence refers to the biological processes of a living Organism approaching an advanced age (i Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc 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 The lipids or their derivatives may be covalently or non-covalently bound Cholesterol is a Lipid found in the Cell membranes and transported in the Blood plasma of all Animals It is an essential component of mammalian Low-density lipoprotein ( LDL) is a type of Lipoprotein that transports Cholesterol and Triglycerides from the Liver to peripheral e. , "lipoprotein subclass analysis"
  • Low serum concentration of functioning high density lipoprotein (HDL "protective if large and high enough" particles), i. High-density lipoproteins ( HDL) is one of the 5 major groups of Lipoproteins ( Chylomicrons, VLDL, IDL, LDL, HDL 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. Male (♂ refers to the sex of an organism or part of an organism which produces small mobile Gametes called spermatozoa. Tobacco Smoking is the inhalation of smoke from burned dried or cured leaves of the Tobacco plant most often in the form of a Cigarette. Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Blood pressure is also the title of a short story by Damon Runyan in Guys and Dolls and Other Stories Obesity is a condition in which excess Body fat has accumulated to such an extent that health may be negatively affected Central obesity, the "apple-shaped" Obesity commonly referred to as belly fat, is the accumulation of Visceral fat ( fat deposited Sedentary lifestyle is a medical Neologism used to denote a type of Lifestyle most commonly found in modern (particularly Western) cultures 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. Coronary disease (or coronary heart disease) refers to the failure of Coronary circulation to supply adequate circulation to Cardiac muscle and surrounding A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain (more properly known as, TAG or triacylglyceride) is Glyceride in which the Glycerol is Esterified with three Fatty acids It is the Homocysteine is a Chemical compound with the formula HSCH2CH2CH(NH2CO2H Uric acid (or urate) is an Organic compound of Carbon, Nitrogen, Oxygen and Hydrogen with the formula C5H4N4O3 Fibrin (also called Factor Ia) is a Protein involved in the clotting of blood Lipoprotein(a (also called Lp(a is a Lipoprotein subclass Studies have identified Lp(a as a putative risk factor for atherosclerotic diseases such as Coronary C-reactive protein ( CRP) is a Plasma protein, an Acute phase protein produced by the Liver and by Adipocytes. Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens C-reactive protein ( CRP) is a Plasma protein, an Acute phase protein produced by the Liver and by Adipocytes. ^[13]
• Stress or symptoms of clinical depression
• Hyperthyroidism (an over-active thyroid)

Dietary risk factors

The relation between dietary fat and atherosclerosis is a contentious field. Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression Hyperthyroidism is the term for overactive tissue within the Thyroid gland resulting in overproduction and thus an excess of circulating free thyroid hormones Thyroxine The thyroid is one of the largest Endocrine glands in the body 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. The American Heart Association (AHA is a Non-profit organization in the United States that fosters appropriate 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 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. Dr Walter Willett, MD DrPH (born in 1945 in Hart Michigan is an American physician and nutrition researcher A principal investigator ( PI) is the lead Scientist for a particular well-defined science (or other academic project such as an astronomical observing The Nurses' Health Study, established in 1976 by Dr Frank Speizer, and the Nurses' Health Study II, established in 1989 by Dr For discussion how dietary fats affect cardiovascular health see Diet and heart disease. In nutrition polyunsaturated fat is an abbreviation of polyunsaturated Fatty acid. ^[14] Writing in Science, Gary Taubes detailed that political considerations played into the recommendations of government bodies. Science (from the Latin scientia, meaning " Knowledge " or "knowing" is the effort to discover, and increase human understanding Gary Taubes (born April 30, 1956) is an American science writer ^[15] These differing views reach a consensus, though, against consumption of trans fats. Trans fat is the common name for a type of Unsaturated fat with trans - isomer Fatty acid (s

The role of dietary oxidized fats / lipid peroxidation (rancid fats) in humans is not clear. Lipid peroxidation refers to the oxidative degradation of Lipids It is the process whereby free radicals "steal" electrons from the lipids in Rancidification is the decomposition of Fats Oils and other Lipids by Hydrolysis or Oxidation, or both 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. Docosahexaenoic acid (commonly known as DHA; 226(ω-3 all-cis -docosa-4710131619-hexa- enoic acid Trivial name cervonic An antioxidant is a Molecule capable of slowing or preventing the oxidation of other molecules ^[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]

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. Dyslipidemia is a disruption in the amount of Lipids in the blood e. , diabetes, high blood pressure, 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. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Homocysteine is a Chemical compound with the formula HSCH2CH2CH(NH2CO2H An anticoagulant is a substance that prevents coagulation; that is it stops Blood from clotting 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).

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. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Thus diabetes has been upgraded to be viewed as an advanced atherosclerotic disease equivalent. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc

Treatment

If atherosclerosis leads to symptoms, some symptoms such as angina pectoris can be treated. Angina pectoris, commonly known as angina, is severe Chest pain due to Ischemia (a lack of blood and hence Oxygen supply of the heart 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. 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 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.

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 Coronary circulation is the circulation of blood in the Blood vessels that supply Blood to and from the Heart muscle Intravascular ultrasound ( IVUS) is a Medical imaging methodology using a specially designed Catheter with a miniaturized Ultrasound probe attached

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, though composed of macrophage white blood cells not fat is the term generally given to the earliest stages of Atheroma, as viewed at autopsy looking at

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'. 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 An antioxidant is a Molecule capable of slowing or preventing the oxidation of other molecules

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. The Scandinavian Simvastatin Survival Study (also known under the abbreviation 4S) is a multicenter Clinical trial that was performed in 1990s in Scandinavia 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.

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. 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 Niacin, also known as vitamin B3, is a water-soluble vitamin which prevents the deficiency disease Pellagra. Ezetimibe (ɛˈzɛtəmɪb is an anti-hyperlipidemic medication which is used to lower cholesterol levels In Pharmacology, the fibrates are a class of amphipathic Carboxylic acids They are used for a range of metabolic disorders mainly Hypercholesterolemia A lipoprotein is a biochemical assembly that contains both Proteins and Lipids The lipids or their derivatives may be covalently or non-covalently bound 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]

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. Niacin, also known as vitamin B3, is a water-soluble vitamin which prevents the deficiency disease Pellagra. Lipoprotein(a (also called Lp(a is a Lipoprotein subclass Studies have identified Lp(a as a putative risk factor for atherosclerotic diseases such as Coronary 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.

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 the Chemical reaction that results in addition of Hydrogen (H2

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 blind method is a part of the Scientific method, used to prevent research outcomes from being influenced by either the Placebo effect or the Observer Placebo is a substance or procedure a patient accepts as medicine or therapy but which has no specific therapeutic activity Scientific controls allow Experiments to study one Variable at a time and are a vital part of the Scientific method.

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(NH2CO2H 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. Vitamin C or L-ascorbate is an Essential nutrient for a large number of higher primate species a small number of other Mammalian Hypercholesterolemia (literally high blood cholesterol is the presence of high levels of Cholesterol in the blood. ^[31] Vitamin C acts as an antioxidant in vessels. Vitamin C or L-ascorbate is an Essential nutrient for a large number of higher primate species a small number of other Mammalian An antioxidant is a Molecule capable of slowing or preventing the oxidation of other molecules ^[32]

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. See also Tocopherol, Tocotrienol Vitamin E is the collective name for a set of 8 related Tocopherols and Tocotrienols which are fat-soluble ^[33]

Menaquinone (Vitamin K2), but not phylloquinone (Vitamin K1), intake is associated with reduced risk of CHD mortality, all-cause mortality and severe aortic calcification. Vitamin K (K from "Koagulations-Vitamin" in German Danish Swedish and Norwegian denotes a group of Lipophilic, Hydrophobic Vitamins that Vitamin K (K from "Koagulations-Vitamin" in German Danish Swedish and Norwegian denotes a group of Lipophilic, Hydrophobic Vitamins that ^[34][35][36]

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. Iron (ˈаɪɚn is a Chemical element with the symbol Fe (ferrum and Atomic number 26 Peripheral vascular disease (PVD also known as peripheral artery disease (PAD or peripheral artery occlusive disease (PAOD is a collator for all Diseases ^[39] Further studies may be warranted.

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. Angioplasty is the technique of mechanically widening a narrowed or totally obstructed Blood vessel; typically as a result of Atherosclerosis. In Medicine, a stent is a tube that is inserted into a natural conduit of the body to prevent or counteract a disease-induced localized flow constriction Coronary artery bypass surgery, also coronary artery bypass graft surgery, and colloquially heart bypass or bypass surgery is a surgical procedure

Prophylaxis

Patients at risk for atherosclerosis-related diseases are increasingly being treated prophylactically with low-dose aspirin and a statin. Prophylaxis ( Greek "προφυλάσσω" to guard or prevent beforehand) is any medical or Public health procedure whose purpose Aspirin, or acetylsalicylic acid (ASA (əˌsɛtɨlsælɨˌsɪlɨk ˈæsɨd is a Salicylate drug, often used as an Analgesic to relieve 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 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. In medicine the term Polypill has been coined to refer to a medication which contains a combination of active ingredients ACE inhibitors, or inhibitors of '''A'''ngiotensin-'''C'''onverting '''E'''nzyme, are a group of Pharmaceuticals that are used primarily in treatment of Hypertension A diuretic is any Drug that elevates the rate of urination ( Diuresis) Beta blockers (sometimes written as β-blocker) are a class of drugs used for various indications but particularly for the management of Cardiac arrhythmias Folic acid (also known as Vitamin M and Folacin) and Folate (the Anionic form are forms of the water-soluble Vitamin B9 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.

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

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.

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) is one of the 5 major groups of Lipoproteins ( Chylomicrons, VLDL, IDL, LDL, HDL

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. Niacin, also known as vitamin B3, is a water-soluble vitamin which prevents the deficiency disease Pellagra. 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.

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%). Torcetrapib (CP-529414 Pfizer) was a drug being developed to treat Hypercholesterolemia (elevated Cholesterol levels and prevent Cardiovascular However, in clinical trials it also raised deaths by 60%. All studies regarding this drug were halted in December 2006. ^[42]

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. Rosuvastatin is a member of the drug class of Statins used to treat Hypercholesterolemia and related conditions and to prevent Cardiovascular disease ) It found plaque (intima + media volume) reduction. ^[9] Several additional rosuvastatin treatment/placebo trials for evaluating other clinical outcomes are in progress.

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. In the field of Molecular biology, the peroxisome proliferator-activated receptors ( PPARs) are a group of Nuclear receptor Proteins that function

Some controversial research has suggested a link between atherosclerosis and the presence of several different nanobacteria in the arteries, e. Nanobacteria is the name of a possible class of living organisms specifically cell-walled Microorganisms with a size much smaller than the generally accepted 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]

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. The French paradox refers to the observation that the French suffer a relatively low incidence of Coronary heart disease, despite having a diet relatively rich in 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. Resveratrol is a Phytoalexin produced naturally by several Plants when under attack by Pathogens such as Bacteria or Fungi BBC.Why wine is good for you. Red Wine Protects The Heart [2]

References

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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15876361.  
• Mol, A (2002). The Body Multiple: Ontology in medical practice. London: Duke University Press.  

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

Monckeberg's Arteriosclerosis, also called medial calcific sclerosis, is a form of arteriosclerosis or vessel hardening where calcium deposits form in the middle Arteries are Blood vessels that carry blood away from the Heart. In Pathology, an atheroma (plural atheromata is an accumulation and swelling (-oma in Artery walls that is made up of cells (mostly Macrophage cells Fatty streak, though composed of macrophage white blood cells not fat is the term generally given to the earliest stages of Atheroma, as viewed at autopsy looking at The heart is a muscular organ in all Vertebrates responsible for pumping Blood through the Blood vessels by repeated rhythmic Coronary circulation is the circulation of blood in the Blood vessels that supply Blood to and from the Heart muscle A coronary catheterization is a Minimally invasive procedure to access the Coronary circulation and blood filled chambers of the Heart using a Catheter Angiography or arteriography is a Medical imaging technique in which an X-ray image is taken to visualize the inside or lumen, of blood vessels Intravascular ultrasound ( IVUS) is a Medical imaging methodology using a specially designed Catheter with a miniaturized Ultrasound probe attached Arteries stiffen as a consequence of age and Atherosclerosis.

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