In the 78-week study of 968 heart patients already on optimum statin therapy, Repatha lowered the percentage of atheroma volume in coronary arteries and demonstrated some plaque regression.
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Illustration comparing a normal blood vessel and partially blocked vessel due to atherosclerotic plaque. Notice the enlargement & absence of much luminal narrowing. Because artery walls enlarge at locations with atheroma, detecting atheroma before death and autopsy has long been problematic at best. Most methods have focused on the openings of arteries; highly relevant, yet totally miss the atheroma within artery walls.
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If the enlargement is beyond proportion to the atheroma thickness, then an aneurysm is created.
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Repeated atheroma rupture and healing is one of the mechanisms, perhaps the dominant one, that creates artery stenosis.
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IVUS is the current most sensitive method detecting and measuring more advanced atheroma within living individuals, though it is typically not used until decades after atheroma begin forming due to cost and body invasiveness. CT scans using state of the art higher resolution spiral, or the higher speed EBT, machines have been the most effective method for detecting calcification present in plaque. However, the atheroma have to be advanced enough to have relatively large areas of calcification within them to create large enough regions of ~130 Hounsfield units which a CT scanner's software can recognize as distinct from the other surrounding tissues. Typically, such regions start occurring within the heart arteries about 2–3 decades after atheroma start developing.
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Pain; suture extrusion; infection; rare suture granuloma or atheroma; slight, harmless post-operative bleeding; relapse(recurrence of protruding ear).
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The National Institute of Health did a five-year $5 million study, headed by medical researcher Kenneth Ouriel, to study intravascular ultrasound techniques regarding atherosclerotic plaque. More progressive clinicians have begun using IMT measurement as a way to quantify and track disease progression or stability within individual patients. Angiography, since the 1960s, has been the traditional way of evaluating for atheroma. However, angiography is only motion or still images of dye mixed with the blood with the arterial lumen and never show atheroma; the wall of arteries, including atheroma with the arterial wall remain invisible.
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Furthermore, a bulge of atheroma may be the cause of turbulent flow, where audible turbulence may be detected with a stethoscope.
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These junctions are called anastomoses. If one coronary artery is obstructed by an atheroma, the second artery is still able to supply oxygenated blood to the myocardium. However, this can only occur if the atheroma progresses slowly, giving the anastomoses a chance to proliferate. Under the most common configuration of coronary arteries, there are three areas of anastomoses.
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Progression of atherosclerosis to late complications. Although the disease process tends to be slowly progressive over decades, it usually remains asymptomatic until an atheroma ulcerates, which leads to immediate blood clotting at the site of atheroma ulcer. This triggers a cascade of events that leads to clot enlargement, which may quickly obstruct the flow of blood. A complete blockage leads to ischemia of the myocardial (heart) muscle and damage.
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More recently, some of the complex immune system patterns that promote, or inhibit, the inherent inflammatory macrophage triggering processes involved in atheroma progression are slowly being better elucidated in animal models of atherosclerosis.
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Coronary heart disease, also known as coronary artery disease, is one of the most common causes of myocardial damage, affecting over three million people in the United States. In Coronary heart disease the coronary arteries narrow due to the buildup of atheroma or fatty deposits on the vessel walls. The atheroma causes the blood flow of the arteries to be restricted. By restricting the blood flow, the tissue is still receiving some oxygen, but not enough to sustain the tissue over time.
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An atheroma, or atheromatous plaque ("plaque"), is an abnormal accumulation of material in the inner layer of the wall of an artery. The material consists of mostly macrophage cells, or debris, containing lipids, calcium and a variable amount of fibrous connective tissue. The accumulated material forms a swelling in the artery wall, which may intrude into the lumen of the artery, narrowing it and restricting blood flow. Atheroma is the pathological basis for the disease entity atherosclerosis, a subtype of arteriosclerosis.
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One way to see atheroma is the very invasive and costly IVUS ultrasound technology; it gives us the precise volume of the inside intima plus the central media layers of about of artery length. Unfortunately, it gives no information about the structural strength of the artery. Angiography does not visualize atheroma; it only makes the blood flow within blood vessels visible. Alternative methods that are non or less physically invasive and less expensive per individual test have been used and are continuing to be developed, such as those using computed tomography (CT; led by the electron beam tomography form, given its greater speed) and magnetic resonance imaging (MRI). The most promising since the early 1990s has been EBT, detecting calcification within the atheroma before most individuals start having clinically recognized symptoms and debility.
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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. These 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.
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For most people, the first symptoms result from atheroma progression within the heart arteries, most commonly resulting in a heart attack and ensuing debility. The heart arteries are difficult to track because (a) they are small (from about 5 mm down to microscopic), (b) they are hidden deep within the chest and (c) they never stop moving. Additionally, all mass- applied clinical strategies focus on both (a) minimal cost and (b) the overall safety of the procedure. Therefore, existing diagnostic strategies for detecting atheroma and tracking response to treatment have been extremely limited.
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If the muscular wall enlargement is overdone over time, then a gross enlargement of the artery results, usually over decades of living. This is a less common outcome. Atheroma within aneurysmal enlargement (vessel bulging) can also rupture and shower debris of atheroma and clot downstream. If the arterial enlargement continues to 2 to 3 times the usual diameter, the walls often become weak enough that with just the stress of the pulse, a loss of wall integrity may occur leading to sudden hemorrhage (bleeding), major symptoms and debility; often rapid death.
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Whilst atherosclerosis of spinal arteries is rare, necrosis (death of tissue) in the anterior artery can be caused by disease in vessels originating from the segmental arteries such as atheroma (arterial wall swelling) or aortic dissection (a tear in the aorta).
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Atheroma) plaques as well as inflamed tonsils. CYP2S1 is expressed in macrophages, liver, lung, intestine, and spleen; is abundant in human and mouse atherosclerosis (i.e. Atheroma) plaques as well as inflamed tonsils; and, in addition to forming epoxides of arachidonic acid (and other polyunsaturated fatty acids), CYP2S1 metabolizes prostaglandin G2 and Prostaglandin H2 to 12-Hydroxyheptadecatrienoic acid. Possibly because of metabolizing and thereby inactivating the prostaglandins and/or because forming the bioactive metabolite, 12-hyddroxyheptadecatrienoic acid, rather than EETs, CYP2S1 may act to inhibit the function of monocytes and thereby limit inflammation as well as other immune responses.
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The concentration of these other components, which may cause atheroma, is known as the non-HDL-C. This is now preferred to LDL-C as a secondary marker as it has been shown to be a better predictor and it is more easily calculated.
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In those who have ACS, atheroma rupture is most commonly found 60% when compared to atheroma erosion (30%), thus causes the formation of thrombus which block the coronary arteries. Plaque rupture is responsible for 60% in ST elevated myocardial infarction (STEMI) while plaque erosion is responsible for 30% if the STEMI and vice versa for Non ST elevated myocardial infarction (NSTEMI). In plaque rupture, the content of the plaque are lipid rich, collagen poor, with abundant inflammation which is macrophage predominant, and covered with a thin fibrous cap. Meanwhile, in plaque erosion, the plaque is rich with extracellular matrix, proteoglycan, glycoaminoglycan, but without fibrous caps, no inflammatory cells, and no large lipid core.
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Glycated hemoglobin causes an increase of highly reactive free radicals inside blood cells. Radicals alter blood cell membrane properties. This leads to blood cell aggregation and increased blood viscosity, which results in impaired blood flow. Another way glycated hemoglobin causes damage is via inflammation, which results in atherosclerotic plaque (atheroma) formation.
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Huntford, p. 690. The death certificate, signed by Macklin, gave the cause as "Atheroma of the Coronary arteries and Heart failure"—in modern terms, coronary thrombosis. Later that morning, Wild, now in command, gave the news to the shocked crew, and told them that the expedition would carry on.Wild, p. 66.
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Its biosynthesis requires vitamin B6. Hardening of fats reduces EFAs and changing to low-extraction flour diminishes the vitamin B6 content. Improvers, such as chlorine dioxide, destroy any EFA present, as well as vitamin E, which would protect it. The cholesterol thus esterified with abnormal fatty acids is less easily eliminated and so leads to atheroma.
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In 2006, Nissen and his co-investigators reported on The ASTEROID trial (A Study to Evaluate the Effect of Rosuvastatin On Intravascular Ultrasound-Derived Coronary Atheroma Burden). The study concluded that intensive use of statins resulting in a decreased LDL and increased HDL can reverse the build-up of plaque in coronary arteries, as measured by IVUS.
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The phenomenon of embolisation of cholesterol was first recognized by the Danish pathologist Dr. Peter Ludvig Panum and published in 1862. Further evidence that eroded atheroma was the source of emboli came from American pathologist Dr. Curtis M. Flory, who in 1945 reported the phenomenon in 3.4% of a large autopsy series of older individuals with severe atherosclerosis of the aorta.
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The limited exception to this rule is that with very advanced atheroma, with extensive calcification within the wall, a halo-like ring of radiodensity can be seen in most older humans, especially when arterial lumens are visualized end-on. On cine-floro, cardiologists and radiologists typically look for these calcification shadows to recognize arteries before they inject any contrast agent during angiograms.
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Age related diseases like atherosclerosis, hypertension accounts many deaths in elderly people. Accumulation of lipid droplets induce the modification of macrophages to foam cells. Lysis of foam cells resulted in Atherosclerotic plaques and such plaques rupture and blocked the thrombotic vessel. Perlipin 2 protein around the macrophages and foam cells was found to play important role in formation of atheroma.
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In 1958 he moved to Montreal as assistant pathologist in the Jewish General Hospital. In 1960 he moved to the Caribbean as senior lecturer at the University of the West Indies. In 1964 he returned to Britain with his young family to teach at the Atheroma Resident Unit in Glasgow. In 1966 he became senior lecturer in pathology at Glasgow University.
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Over time, atheromata usually progress in size and thickness and induce the surrounding muscular central region (the media) of the artery to stretch out, termed remodeling, typically just enough to compensate for their size such that the calibre of the artery opening (lumen) remains unchanged until typically over 50% of the artery wall cross- sectional area consists of atheromatous tissue. Narrowed arterial blood vessel blocked with an anteroma. If the muscular wall enlargement eventually fails to keep up with the enlargement of the atheroma volume, or a clot forms and organizes over the plaque, then the lumen of the artery becomes narrowed as a result of repeated ruptures, clots & fibrosis over the tissues separating the atheroma from the blood stream. This narrowing becomes more common after decades of living, increasingly more common after people are in their 30s to 40s.
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Studies show that 64% of all unstable anginas occur between 22:00 and 08:00 when patients are at rest. In stable angina, the developing atheroma is protected with a fibrous cap. This cap may rupture in unstable angina, allowing blood clots to precipitate and further decrease the area of the coronary vessel's lumen. This explains why, in many cases, unstable angina develops independently of activity.
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Because the glycocalyx is so prominent throughout the cardiovascular system, disruption to this structure has detrimental effects that can cause disease. Certain stimuli that cause atheroma may lead to enhanced sensitivity of vasculature. Initial dysfunction of the glycocalyx can be caused by hyperglycemia or oxidized low-density lipoproteins (LDLs), which then causes atherothrombosis. In microvasculature, dysfunction of the glycocalyx leads to internal fluid imbalance, and potentially edema.
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Overview of main complications of persistent high blood pressure Arterial hypertension can be an indicator of other problems and may have long- term adverse effects. Sometimes it can be an acute problem, for example hypertensive emergency. Levels of arterial pressure put mechanical stress on the arterial walls. Higher pressures increase heart workload and progression of unhealthy tissue growth (atheroma) that develops within the walls of arteries.
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Very advanced luminal occlusion usually produces a heart attack. However, it has been increasingly recognized, since the late 1980s, that coronary catheterization does not allow the recognition of the presence or absence of coronary atherosclerosis itself, only significant luminal changes which have occurred as a result of end stage complications of the atherosclerotic process. See IVUS and atheroma for a better understanding of this issue.
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In 1858 doctor Thomas Inman described four of thirty discovered cases with cerebral softening. Each case was similar to the previous article. There was some atheroma in the internal brain arteries that led to the cerebral softening of the left side of the brain around the left lateral ventricle, thalamus and corpus striatum. There were similar right sided numbness in some patients, coldness of the extremities, and impairments in vision.
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Coleman moved to the Mornington Peninsula, buying a rural property at Arthurs Seat and running the Dromana Hotel. In the early hours of 5 April 1973, he died suddenly of coronary atheroma. The public was stunned and saddened. On Saturday 7 April 1973, the opening round of the VFL season included a match held at Windy Hill between Essendon and Richmond, which became in effect a John Coleman memorial.
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Ranke, whose father was the psychiatrist Karl Ranke (1861–1951), graduated after completing his study of medicine at the Universities of Munich and Freiburg. In Freiburg Ranke received a medical doctorate under Ludwig Aschoff with a dissertation entitled "On the change of the elastic resistance of the aortic intima and resulting formation of atheroma." Rudolf Vierhaus (Hrsg.): Deutsche biographische Enzyklopädie. 2. Auflage. Band 8, Saur, München 2007, , S. 177.
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The physician controls both the contrast injection, fluoroscopy and cine application timing so as to minimize the total amount of radiocontrast injected and times the X-ray to the injection so as to minimize the total amount of X-ray used. Doses of radiocontrast agents and X-ray exposure times are routinely recorded in an effort to maximize safety. Though not the focus of the test, calcification within the artery walls, located in the outer edges of atheroma within the artery walls, is sometimes recognizable on fluoroscopy (without contrast injection) as radiodense halo rings partially encircling, and separated from the blood filled lumen by the interceding radiolucent atheroma tissue and endothelial lining. Calcification, even though usually present, is usually only visible when quite advanced and calcified sections of the artery wall happen to be viewed on end tangentially through multiple rings of calcification, so as to create enough radiodensity to be visible on fluoroscopy.
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In small vessels, the most common cause is lipohyalinosis. Lipohyalinosis is when high blood pressure and aging causes a build-up of fatty hyaline matter in blood vessels. Atheroma formation can also cause small vessel thrombotic ischemic stroke. Occlusion of blood flow generates a depolarization of neurons that generate a wave called spreading depolarization, that moves from the affected core to the penumbra and healthy brain producing further depolarization, neuronal dead and neurologic symptoms.
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A protective fibrous cap normally forms between the fatty deposits and the artery lining (the intima). 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.
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The majority of cardiovascular events that involve sudden rupture of the atheroma plaque do not display any evident narrowing of the lumen. Thus, greater attention has been focused on "vulnerable plaque" from the late 1990s onwards. Besides the traditional diagnostic methods such as angiography and stress-testing, other detection techniques have been developed in the past decades for earlier detection of atherosclerotic disease. Some of the detection approaches include anatomical detection and physiologic measurement.
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The presence or absence of atherosclerosis or atheroma within the walls of the arteries cannot be clearly determined. Coronary angiography can visualize coronary artery stenosis, or narrowing of the blood vessel. The degree of stenosis can be determined by comparing the width of the lumen of narrowed segments of blood vessel with wider segments of adjacent vessel. To detect coronary artery disease, a CT scan is more satisfactory than an MRI scan.
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After a knee injury ended his playing career at age 25, he returned to coach Essendon to premiership success. Coleman died in 1973, at the age of 44, of sudden coronary atheroma. He is the namesake of the Coleman Medal, awarded to the AFL player who kicks the most goals during the home and away season. In 1996 he was one of 12 inaugural Australian Football Hall of Fame inductees bestowed "Legend" status.
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Additionally, these vascular interventions are often done only after an individual is symptomatic, often already partially disabled, as a result of the disease. It is also clear that both angioplasty and bypass interventions do not prevent future heart attack. The older methods for understanding atheroma, dating to before World War II, relied on autopsy data. Autopsy data has long shown initiation of fatty streaks in later childhood with slow asymptomatic progression over decades.
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On the evening of 12 May 1960, in the woods around Staple Farm, the Kent farmhouse in which she and Folley were then living, Dunbar suddenly collapsed and died. A post- mortem showed coronary atheroma to have been the cause of death. At the time of her death, the storage shelves in a room adjoining the studio in Staple Farm, contained some 30–40 canvases. There were also numerous folios of drawings.
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Philadelphia: Saunders Elsevier. pp. 500–501. . Foam cells form the fatty streaks of the plaques of atheroma in the tunica intima of arteries. Foam cells are not dangerous as such, but can become a problem when they accumulate at particular foci thus creating a necrotic centre of atherosclerosis. If the fibrous cap that prevents the necrotic centre from spilling into the lumen of a vessel ruptures, a thrombus can form which can lead to emboli occluding smaller vessels.
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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 (); 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 (). The term atherogenic is used for substances or processes that cause formation of atheroma.
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Important internal heart and lung blood pressures, not measurable from outside the body, can be accurately measured during the test. The relevant problems that the test deals with most commonly occur as a result of advanced atherosclerosis – atheroma activity within the wall of the coronary arteries. Less frequently, valvular, heart muscle, or arrhythmia issues are the primary focus of the test. Coronary artery luminal narrowing reduces the flow reserve for oxygenated blood to the heart, typically producing intermittent angina.
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Hogg died on August 19, 1975, at the age of 93, from a heart attack resulting from atheroma. She had been vacationing in London at the time, but fell as she was getting into a taxi, and died a few days later in a London hospital. An autopsy report revealed that her death was not related to the earlier fall. On receiving news of her death, the University of Texas declared two days of mourning and flew the flag at half-staff.
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Cholesterol crystals may also play a role. # 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.
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The methods most commonly relied upon, patient symptoms and cardiac stress testing, do not detect any symptoms of the problem until atheromatous disease is very advanced because arteries enlarge, not constrict in response to increasing atheroma. It is plaque ruptures, producing debris and clots which obstruct blood flow downstream, sometimes also locally (as seen on angiograms), which reduce/stop blood flow. Yet these events occur suddenly and are not revealed in advance by either stress testing, stress tests or angiograms.
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Since oxidative stress commonly produces both free radicals and singlet oxygen, most or all of these products may form together in tissues undergoing oxidative stress. Free radical and singlet oxygen oxidations of linoleic acid produce a similar set of 13-HODE metabolites (see 9-Hydroxyoctadecadienoic acid). Studies attribute these oxidations to be major contributors to 13-HODE production in tissues undergoing oxidative stress including in humans sites of inflammation, steatohepatitis, cardiovascular disease-related atheroma plaques, neurodegenerative disease, etc. (see oxidative stress).
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The healthy epicardial coronary artery consists of three layers, the tunica intima, media, and adventitia. Atheroma and changes in the artery wall usually result in small aneurysms (enlargements) just large enough to compensate for the extra wall thickness with no change in the lumen diameter. However, eventually, typically as a result of rupture of vulnerable plaques and clots within the lumen over the plaque, stenosis (narrowing) of the vessel develops in some areas. Less frequently, the artery enlarges so much that a gross aneurysmal enlargement of the artery results.
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The higher the pressure, the more stress that is present and the more atheroma tend to progress and the heart muscle tends to thicken, enlarge and become weaker over time. Persistent hypertension is one of the risk factors for strokes, heart attacks, heart failure, and arterial aneurysms, and is the leading cause of chronic kidney failure. Even moderate elevation of arterial pressure leads to shortened life expectancy. At severely high pressures, mean arterial pressures 50% or more above average, a person can expect to live no more than a few years unless appropriately treated.
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Arguably the most valuable use of IVUS is to visualize plaque, which cannot be seen by angiography. Over time this technique has evolved into an extremely useful research tool for modern invasive cardiology, and it has been increasingly used in research to better understand the behavior of the atherosclerosis process in living people. IVUS enables accurately visualizing not only the lumen of the coronary arteries but also the atheroma (membrane/cholesterol loaded white blood cells) "hidden" within the wall. IVUS has thus enabled advances in clinical research providing a more thorough perspective and better understanding.
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Atheroma blocking an artery lumen After 5.4 years, compared to the group that were given placebo, the simvastatin group demonstrated a 35% reduction in LDL-C and 30% reduction in overall mortality. The risk of hospital-verified non-fatal myocardial infarction reduced by 37% and fatal and non-fatal cerebrovascular events (stroke and TIA) lessened by 28%. 30 people would need to be treated with simvastatin to prevent one death; number needed to treat around 30. There were no extra deaths from other non-cardiac causes such as cancer or trauma.
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Willmott’s prodigious spending during her lifetime caused financial difficulties in later life, forcing her to sell her French and Italian properties, and eventually her personal possessions. She became increasingly eccentric and paranoid: she booby-trapped her estate to deter thieves; secretly planted seeds of the giant prickly thistle Eryngium giganteum (now known as 'Miss Willmott's Ghost') in other people's gardens; and carried a revolver in her handbag. Willmott was arrested on suspicion of shoplifting in 1928, although later acquitted. Willmott died of atheroma and embolus of the coronary artery in 1934, aged 76.
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Calcification forms among vascular smooth muscle cells of the surrounding muscular layer, specifically in the muscle cells adjacent to atheromas and on the surface of atheroma plaques and tissue. In time, as cells die, this leads to extracellular calcium deposits between the muscular wall and outer portion of the atheromatous plaques. With the atheromatous plaque interfering with the regulation of the calcium deposition, it accumulates and crystallizes. 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).
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In developed countries, with improved public health, infection control and increasing life spans, atheroma processes have become an increasingly important problem and burden for society. Atheromata continue to be the primary underlying basis for disability and death, despite a trend for gradual improvement since the early 1960s (adjusted for patient age). Thus, increasing efforts towards better understanding, treating and preventing the problem are continuing to evolve. According to United States data, 2004, for about 65% of men and 47% of women, the first symptom of cardiovascular disease is myocardial infarction (heart attack) or sudden death (death within one hour of symptom onset).
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However, animal studies on the effects of estetrol on levels of allopregnanolone and β-endorphin in various brain areas have shown weak estrogenic effects when given alone and antiestrogenic effects in the presence of estradiol, suggesting that estetrol may have SERM-like effects in some regions of the brain. Estetrol has mixed effects in the vascular system similarly. It has been found to have estrogenic effects on atheroma prevention in arteries (and hence might be expected to have beneficial effects on atherosclerosis), but has antiestrogenic effects against estradiol-induced endothelial nitric oxide synthase activation and acceleration of endothelial healing.
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The amount of blood loss can be copious, can occur very rapidly, and be life-threatening. Over time, factors such as elevated arterial blood sugar (particularly as seen in diabetes mellitus), lipoprotein, cholesterol, high blood pressure, stress and smoking, are all implicated in damaging both the endothelium and walls of the arteries, resulting in atherosclerosis. Atherosclerosis is a disease marked by the hardening of arteries. This is caused by an atheroma or plaque in the artery wall and is a build-up of cell debris, that contain lipids, (cholesterol and fatty acids), calciumBertazzo, S. et al.
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A significant proportion of artery flow-disrupting events occur at locations with less than 50% lumenal narrowing. Cardiac stress testing, traditionally the most commonly performed noninvasive testing method for blood flow limitations, generally only detects lumen narrowing of ~75% or greater, although some physicians advocate nuclear stress methods that can sometimes detect as little as 50%. The sudden nature of the complications of pre-existing atheroma, vulnerable plaque (non-occlusive or soft plaque), have led, since the 1950s, to the development of intensive care units and complex medical and surgical interventions. Angiography and later cardiac stress testing was begun to either visualize or indirectly detect stenosis.
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As noted above, statins exhibit action beyond lipid-lowering activity in the prevention of atherosclerosis through so-called "pleiotropic effects of statins." The pleiotropic effects of statins remain controversial. The ASTEROID trial showed direct ultrasound evidence of atheroma regression during statin therapy. Researchers hypothesize that statins prevent cardiovascular disease via four proposed mechanisms (all subjects of a large body of biomedical research): # Improve endothelial function # Modulate inflammatory responses # Maintain plaque stability # Prevent blood clot formation In 2008, the JUPITER trial showed statins provided benefit in those who had no history of high cholesterol or heart disease, but only elevated high-sensitivity C-reactive protein (hsCRP) levels, an indicator for inflammation.
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As the plaque burden increases, the lumen size will decrease and the degree of stenosis will increase.Perhaps the greatest contribution to understanding, so far, was achieved by clinical research trials completed in the United States in the late 1990s, using combined angiography and IVUS examination, to study which coronary lesions most commonly result in a myocardial infarction. The studies revealed that most myocardial infarctions occur at areas with extensive atheroma within the artery wall, however very little stenosis of the artery opening. The range of lumen stenosis locations at which myocardial infarctions occurred ranged from areas of mild dilation all the way to areas of greater than 95% stenosis.
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Next came bypass surgery, to plumb transplanted veins, sometimes arteries, around the stenoses and more recently angioplasty, now including stents, most recently drug coated stents, to stretch the stenoses more open. Yet despite these medical advances, with success in reducing the symptoms of angina and reduced blood flow, atheroma rupture events remain the major problem and still sometimes result in sudden disability and death despite even the most rapid, massive and skilled medical and surgical intervention available anywhere today. According to some clinical trials, bypass surgery and angioplasty procedures have had at best a minimal effect, if any, on improving overall survival. Typically mortality of bypass operations is between 1 and 4%, of angioplasty between 1 and 1.5%.
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Additionally, IVUS examinations, as they were done more frequently, served to reveal and confirm the autopsy research findings of the late 1980s, showing that atheromatous plaque tends to cause expansion of the internal elastic lamina, causing the degree of plaque burden to be greatly underestimated by angiography. Angiography only reveals the edge of the atheroma that protrudes into the lumen. Intravascular ultrasound image of a coronary artery (left), with color-coding on the right, delineating the lumen (yellow), external elastic membrane (blue) and the atherosclerotic plaque burden (green). The percentage stenosis is defined as the area of the lumen (yellow) divided by the area of the external elastic membrane (blue) times 100.
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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. 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 angiography.
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A vulnerable plaque is a kind of atheromatous plaque – a collection of white blood cells (primarily macrophages) and lipids (including cholesterol) in the wall of an artery – that is particularly unstable and prone to produce sudden major problems such as a heart attack or stroke. The defining characteristics of a vulnerable plaque include but are not limited to: a thin fibrous cap, large lipid-rich necrotic core, increased plaque inflammation, positive vascular remodeling, increased vasa-vasorum neovascularization, and intra- plaque hemorrhage. These characteristics together with the usual hemodynamic pulsating expansion during systole and elastic recoil contraction during diastole contribute to a high mechanical stress zone on the fibrous cap of the atheroma, making it prone to rupture. Increased hemodynamic stress, e.g.
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Historically, arterial wall fixation, staining and thin section has been the gold standard for detection and description of atheroma, after death and autopsy. With special stains and examination, micro calcifications can be detected, typically within smooth muscle cells of the arterial media near the fatty streaks within a year or two of fatty streaks forming. Interventional and non-interventional methods to detect atherosclerosis, specifically vulnerable plaque (non-occlusive or soft plaque), are widely used in research and clinical practice today. Carotid Intima-media thickness Scan (CIMT can be measured by B-mode ultrasonography) measurement has been recommended by the American Heart Association as the most useful method to identify atherosclerosis and may now very well be the gold standard for detection.
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Furthermore, CIMT was increased as the number of involved vessels increased and the highest CIMT values were noted in patients with left main coronary involvement. However, human clinical trials have been slow to provide clinical & medical evidence, partly because the asymptomatic nature of atheromata make them especially difficult to study. Promising results are found using carotid intima-media thickness scanning (CIMT can be measured by B-mode ultrasonography), B-vitamins that reduce a protein corrosive, homocysteine and that reduce neck carotid artery plaque volume and thickness, and stroke, even in late-stage disease. Additionally, understanding what drives atheroma development is complex with multiple factors involved, only some of which, such as lipoproteins, more importantly lipoprotein subclass analysis, blood sugar levels and hypertension are best known and researched.
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HDL particles remove fats and cholesterol from cells, including within artery wall atheroma, and transport it back to the liver for excretion or re- utilization; thus the cholesterol carried within HDL particles (HDL-C) is sometimes called "good cholesterol" (despite being the same as cholesterol in LDL particles). Those with higher levels of HDL-C tend to have fewer problems with cardiovascular diseases, while those with low HDL-C cholesterol levels (especially less than 40 mg/dL or about 1 mmol/L) have increased rates for heart disease. Higher native HDL levels are correlated with better cardiovascular health, but it does not appear that further increasing one's HDL improves cardiovascular outcomes. The remainder of the serum cholesterol after subtracting the HDL is the non-HDL cholesterol.
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Most visualization techniques are used in research, they are not widely available to most patients, have significant technical limitations, have not been widely accepted and generally are not covered by medical insurance carriers. From human clinical trials, it has become increasingly evident that a more effective focus of treatment is slowing, stopping and even partially reversing the atheroma growth process. There are several prospective epidemiologic studies including the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS), which have supported a direct correlation of Carotid Intima-media thickness (CIMT) with myocardial infarction and stroke risk in patients without cardiovascular disease history. The ARIC Study was conducted in 15,792 individuals between 5 and 65 years of age in four different regions of the US between 1987 and 1989.
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Gibbons' death was recorded on 17 February 1913 at his nephew's apartment at Portman Mansions, just off Baker Street, although it was rumoured he had died in the arms of a lover at the Savoy Hotel and was subsequently transported to his nephew's house. His death certificate gives his occupation as "A retired Stamp Collector" and the cause was stated as "Coma, Haemorrhage of the Brain, secondary to Extensive Valvular Disease of the Heart with Atheroma of Endocardium and the Blood Vessels accelerated by enlarged prostate". He is buried in Twickenham cemetery. Gibbons' string of wives, all but one of whom died relatively young, his swift remarriages and his background in pharmacy has given rise to suspicions of ill-doing on his part, however there is no evidence for this.
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5,6-EEQ isomers are generally either not formed or formed in undetectable amounts while 8,9-EEQ isomers are formed in relatively small amounts by the cited CYPs. The EET-forming CYP epoxygenases often metabolize EPA to EEQs (as well as DHA to EDPs) at rates that exceed their rates in metabolizing arachidonic acid to EETs; that is, EPA (and DHA) appear to be preferred over arachidonic acid as substrates for many CYP epoxygenases. The EEQ-forming cytochromes are widely distributed in the tissues of humans and other mammals, including blood vessel endothelium, blood vessel atheroma plaques, heart muscle, kidneys, pancreas, intestine, lung, brain, monocytes, and macrophages. These tissues are known to metabolize arachidonic acid to EETs; it has been shown or is presumed that they also metabolize EPA to EEQs.
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The plaque is divided into three distinct components: # The atheroma ("lump of gruel", ), 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 # Underlying areas of cholesterol crystals # Calcification at the outer base of older or more advanced lesions. Atherosclerotic lesions, or atherosclerotic plaques, are separated into two broad categories: Stable and unstable (also called vulnerable). The pathobiology of atherosclerotic lesions is very complicated, but generally, stable atherosclerotic plaques, which tend to be asymptomatic, are rich in extracellular matrix and smooth muscle cells. On the other hand, unstable plaques are rich in macrophages and foam cells, and the extracellular matrix separating the lesion from the arterial lumen (also known as the fibrous cap) is usually weak and prone to rupture.
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Macklin, who conducted the postmortem, concluded that the cause of death was atheroma of the coronary arteries exacerbated by "overstrain during a period of debility". Leonard Hussey, a veteran of the Imperial Trans-Antarctic expedition, offered to accompany the body back to Britain; while he was in Montevideo en route to England, a message was received from Emily Shackleton asking that her husband be buried in South Georgia. Hussey returned to South Georgia with the body on the steamer , and on 5 March 1922, Shackleton was buried in the Grytviken cemetery, South Georgia, after a short service in the Lutheran church, with Edward Binnie officiating.Sir Ernest Shackleton: Funeral Ceremony In South Georgia: Many Wreaths On Coffin, in the Barrier Miner (archived in the NLA Trove); published 5 May 1922; retrieved 25 June 2014Shackleton's Last Voyage: the Story of the Quest, by Frank Wild, published 1923 by Cassell (via archive.
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The endothelium (the cell monolayer on the inside of the vessel) and covering tissue, termed fibrous cap, separate atheroma from the blood in the lumen. If a rupture (see vulnerable plaque) of the endothelium and fibrous cap occurs, then both (a) a shower of debris from the plaque combined with (b) a platelet and clotting response (to both the debris and at the rupture site) occurs within fractions of a second. The rupture results in both (a) a shower of debris occluding smaller downstream vessels (debris larger than 5 micrometres are too large to pass through capillaries)) combined with (b) platelet and clot accumulation over the rupture (an injury/repair response) resulting in narrowing, sometimes closure, of the lumen. Downstream tissue damage occurs due to (a) closure of downstream microvascular and/or (b) closure of the lumen at the rupture, both resulting in loss of blood flow to downstream capillary microvasulature.
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If atheroma, or clots, are protruding into the lumen, producing narrowing, the narrowing may be seen instead as increased haziness within the X-ray shadow images of the blood/dye column within that portion of the artery; this is as compared to adjacent, presumed healthier, less stenotic areas. For guidance regarding catheter positions during the examination, the physician mostly relies on detailed knowledge of internal anatomy, guide wire and catheter behavior and intermittently, briefly uses fluoroscopy and a low X-ray dose to visualize when needed. This is done without saving recordings of these brief looks. When the physician is ready to record diagnostic views, which are saved and can be more carefully scrutinized later, he activates the equipment to apply a significantly higher X-ray dose, termed cine, in order to create better quality motion picture images, having sharper radiodensity contrast, typically at 30 frames per second.
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Oxidative stress in cells and tissues produces Free- radical-induced and singlet-oxygen-induced oxidations of linoleic acid to generate the various racemic mixtures of 9-HpODE and 9-HODE in non-enzymatic reactions that produce, or are suspected but not proven to produce, approximately equal amounts of their S and R stereoisomers.Prog Lipid Res. 1984;23(4):197-221Biochim Biophys Acta. 1998 May 20;1392(1):23-40Chem Res Toxicol. 2005 Feb;18(2):349-56 These oxidations are credited with being the major contributors to 9-HODE and 13-HODE isomer production in tissues undergoing oxidative stress such as occurs in any tissue suffering inadequate blood flow, inflammation, or other serious insult, in liver steatohepatitis, in the atheroma plaques of cardiovascular disease, in nerve tissues of neurodegenerative diseases, and in the various tissues compromised by diabetes (see oxidative stress). Free-radical oxidation of linoleic acid produces racemic mixtures of 9-HODE and 9-EE-HODE; singlet-oxygen attack on linoleic acid produces (presumably) racemic mixtures of 9-HODE, 10-hydroxy-8E,12Z-octadecadienoic acid, and 12-hydroxy-9Z-13-E-octadecadienoic acid.
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Arrows point to two vertical white lines which is how calcifications in the first part (proximal component) of the internal carotid artery appear on panoramic radiographs. A line drawing depicting a panoramic radiograph with an ovoid atheroma in the bifurcation region of the common carotid artery (CCA) as it bifurcates (divides) in the neck into the internal carotid artery (ICA) which supplies blood to the brain and the external carotid artery (ECA) which supplies blood to the face and mouth. Panoramic radiographs have the capability to demonstrate a portion of the neck and display atheromas (calcifications in the carotid artery) which are an indication of both local and generalized (systemic) atherosclerosis. Atherosclerosis of the coronary arteries leading to myocardial infarction (heart attack), and atherosclerosis of the carotid artery leading to stroke are the number one and number three most common causes of death in the United States.American Heart Association’s Heart Disease and Stroke Statistics—2010 Update There is interest to look at panoramic radiographs as a screening tool, however further data is needed with regards if it is able to make a meaningful difference in outcomes.
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