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{{Atherosclerosis}}
{{Atherosclerosis}}
{{CMG}}
'''For patient information, click [[Atherosclerosis (patient information)|here]]'''


==Atherogenesis==<!-- This section is linked from [[Antioxidant]] -->
{{CMG}} {{AOEIC}} [[User:Maheep Sangha|Maheep Singh Sangha, M.B.B.S.]]{{NE}}
''Atherogenesis'' is the developmental process of atheromatous plaques. It is characterized by a remodeling of [[artery|arteries]] involving the concomitant accumulation of fatty substances called plaques. One recent theory suggests that for unknown reasons, [[leukocytes]] such as [[monocytes]] or [[basophils]] begin to attack the [[endothelium]] of the artery lumen in cardiac muscle. The ensuing [[inflammation]] leads to formation of  ''atheromatous plaques'' in the arterial [[tunica intima]], a region of the vessel wall located between the [[endothelium]] and the [[tunica media]] and [[tunica adventitia]]. The bulk of these lesions are made of excess fat, [[collagen]], and [[elastin]]. Initially, as the plaques grow only [[intima-media thickness|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 the just atherosclerosis process by itself.


===Cellular===
{{SK}} Plaque buildup - arteries; hardening of the arteries
The first step of atherogenesis is the development of [[fatty streak]]s, small subendothelial deposits of lipid. 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 [[oxidize]]d.  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.
==[[Atherosclerosis overview|Overview]]==
==[[Historical Perspective]]==


The initial damage to the blood vessel wall results in a "call for help," an [[inflammation]] response. [[Monocyte]]s (a type of [[white blood cell]]) enter the artery wall from the bloodstream, with platelets adhering to the area of insult. This may be promoted by [[redox signaling]] induction of factors such as [[VCAM-1]], which recruit circulating monocytes. The [[monocyte]]s differentiate into [[macrophage]]s, which ingest [[oxidize]]d [[LDL]], slowly turning into large "foam cells" &ndash; so-described because of their changed appearance resulting from the numerous internal cytoplasmic [[vesicle (biology)|vesicle]]s and resulting high [[lipid]] content. Under the microscope, the lesion now appears as a fatty streak. Foam cells eventually die, and further propagate the inflammatory process.
==[[Atherosclerosis classification|Classification]]==
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===
==[[Atherosclerosis pathophysiology|Pathophysiology]]==
Intracellular [[calcification|microcalcifications]] form within [[vascular smooth muscle]] cells of the surrounding muscular layer, specifically in the muscle cells adjacent to the atheromas. In time, as cells die, this leads to extracellular calcium deposits between the muscular wall and outer portion of the atheromatous plaques.


Cholesterol is delivered into the vessel wall by cholesterol-containing [[low-density lipoprotein]] (LDL) particles. To attract and stimulate macrophages, the cholesterol must be released from the LDL particles and oxidized, a key step in the ongoing inflammatory process. The process is worsened if there is insufficient [[high-density lipoprotein]] (HDL), the lipoprotein particle that removes cholesterol from tissues and carries it back to the liver.
==[[Atherosclerosis causes|Causes]]==


The foam cells and platelets encourage the migration and proliferation of [[smooth muscle]] cells, which in turn ingest lipids, become replaced by collagen and transform into foam cells themselves. A protective fibrous cap normally forms between the fatty deposits and the artery lining (the [[endothelium|intima]]).
==[[Atherosclerosis differential diagnosis|Differentiating Atherosclerosis from other Diseases]]==


These capped fatty deposits (now called ''atheromas'') produce enzymes that cause the artery to enlarge over time. As long as the artery enlarges sufficiently to compensate for the extra thickness of the atheroma, then no narrowing, [[stenosis]], of the opening, lumen, occurs. The artery becomes expanded with an egg-shaped cross-section, still with a circular opening. If the enlargement is beyond proportion to the atheroma thickness, then an [[aneurysm]] is created.<ref name="Glagov">Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. ''[[New England Journal of Medicine|N Engl J Med]]'' 1987;316:131-1375. PMID</ref>
==[[Atherosclerosis epidemiology and demographics|Epidemiology and Demographics]]==


===Visible features===
==[[Atherosclerosis risk factors|Risk Factors]]==  


Although arteries are not typically studied microscopically, two plaque types can be distinguished[http://www.pathologyatlas.ro/Coronary%20ATS%20Calcification.html]:
==[[Atherosclerosis screening]]==
# ''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.
==Overview==
# ''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 fibres (eosinophilic), precipitates of calcium (hematoxylinophilic) and, rarely, lipid-laden cells.


In effect, the muscular portion of the artery wall forms small [[aneurysm]]s just large enough to hold the [[atheroma]] that are present. The muscular portion of artery walls usually remain strong, even after they have remodeled to compensate for the [[atheroma]]tous plaques.
There is insufficient evidence to recommend routine screening for [disease/malignancy].  


However, [[atheroma]]s within the vessel wall are soft and fragile with little elasticity. Arteries constantly expand and contract with each heartbeat, i.e., the pulse. In addition, the calcification deposits between the outer portion of the atheroma and the muscular wall, as they progress, lead to a loss of elasticity and stiffening of the artery as a whole.
OR


The calcification deposits, after they have become sufficiently advanced, are partially visible on coronary artery [[computed tomography]] or [[electron beam tomography]] (EBT) as rings of increased radiographic density, forming halos around the outer edges of the atheromatous plaques, within the artery wall. On CT, >130 units on the [[Hounsfield scale]] {some argue for 90 units) has been the radiographic density usually accepted as clearly representing tissue calcification within arteries. These deposits demonstrate unequivocal evidence of the disease, relatively advanced, even though the lumen of the artery is often still normal by angiographic or intravascular ultrasound.
According to the [guideline name], screening for [disease name] is not recommended.


<gallery>
OR
Image:Atherosclerosis aorta gross pathology PHIL 846 lores.jpg|Severe atherosclerosis of the [[aorta]]. [[Autopsy]] specimen.
Image:Calcificatio atherosclerotica.jpg|Microphotography of arterial wall with calcified (violet colour) atherosclerotic plaque (haematoxillin & eosin stain)
</gallery>


===Rupture and stenosis===
According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].
Although the disease process tends to be slowly progressive over decades, it usually remains asymptomatic until an atheroma obstructs the bloodstream in the artery. This is typically by rupture of an atheroma, clotting and fibrous organization of the clot within the lumen, covering the rupture but also producing [[stenosis]], or over time and after repeated ruptures, resulting in a persistent, usually localized stenosis. Stenoses can be slowly progressive, while plaque rupture is a sudden event that occurs specifically in atheromas with thinner/weaker fibrous caps that have become "unstable".
==Screening==
There is insufficient evidence to recommend routine screening for [disease/malignancy].


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.
OR


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.
According to the [guideline name], screening for [disease name] is not recommended.


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 [[platelet]]s and activate the [[coagulation|system of coagulation]]. The result is the formation of a [[thrombus]] (blood clot) overlying the atheroma, which obstructs blood flow acutely. With the obstruction of blood flow, downstream tissues are starved of [[oxygen]] and nutrients. If this is the [[myocardium]] (heart muscle), [[Angina pectoris|angina]] (cardiac chest pain) or [[myocardial infarction]] (heart attack) develops.
OR


Rather than a single plaque rupture, atherosclerosis is the result of multiple plaque ruptures over time.  In patients with ACS, autopsy data show that there had been 5-7 ruptures before the terminal event.  These events often due to not lead to a coronary event.  Thin capped fibroatheroma (TCFA) with rupture is the most common form of plaque rupture.  A less common form is erosion of the plaque.  Intraplaque hemorrhage as a result of rupture of the vasa vasorum may also occur.  Most ACS is due to TCFA plaque rupture. Less likely there is plaque erosion in ACS.  Younger women more often have plaque erosion.  Older women more often have plaque rupture.  Plaque rupture is usually the mechanism in young men. In older men, the mechanism is similar to women.  You cannot predict what plaque is going to rupture on the angiogram.  Virtual histology and OCT may potentially predict plaque rupture, but the odds of rupture are so low that their utility is marginal.
According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with:
*[Condition 1]
*[Condition 2]
*[Condition 3]


==Diagnosis of plaque-related disease==
==References==
 
{{Reflist|2}}
Areas of severe narrowing, [[stenosis]], detectable by angiography, and to a lesser extent "stress testing" have long been the focus of human diagnostic techniques for [[cardiovascular disease]], in general. However, these methods focus on detecting only severe [[stenosis|narrowing]], not the underlying atherosclerosis disease.  As demonstrated by human clinical studies, most severe events occur in locations with heavy plaque, yet little or no lumen [[stenosis|narrowing]] present before debilitating events suddenly occur. Plaque rupture can lead to artery lumen occlusion within seconds to minutes, and potential permanent debility and sometimes sudden death.
 
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 pectoris|angina]] and detectable abnormalities by stress testing methods are seen. However, clinical trials have shown that only about 14% of clinically-debilitating events occur at locations with this, or greater severity of [[stenosis|narrowing]]. The majority of events occur due to atheroma plaque rupture at areas without [[stenosis|narrowing]] sufficient enough to produce any [[Angina pectoris|angina]] or stress test abnormalities. Thus, since the later-1990s, greater attention is being focused on the "vulnerable plaque."
 
Though any artery in the body can be involved, usually only severe [[stenosis|narrowing]] or obstruction of some arteries, those that supply more critically-important organs are recognized. Obstruction of arteries supplying the heart muscle result in a [[myocardial infarction|heart attack]]. Obstruction of arteries supplying the brain result in a [[stroke]]. These events are life-changing, and often result in irreversible loss of function because lost heart muscle and brain cells do not grow back to any significant extent, typically less than 2%.
 
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 medial thickness) measurement by ultrasound, and
 
(3) IVUS.
 
'''Examples of physiologic methods include''':


(1) lipoprotein subclass analysis,
{{WH}}
{{WS}}
[[Category: (name of the system)]]


(2) HbA1c,  
==[[Atherosclerosis natural history, complications and prognosis|Natural History, Complications and Prognosis]]==


(3) hs-CRP, and
==Diagnosis==
 
[[Atherosclerosis history and symptoms|History and Symptoms]] | [[Atherosclerosis physical examination|Physical Examination]] | [[Atherosclerosis laboratory findings|Laboratory Findings]] | [[Atherosclerosis other diagnostic studies|Other Diagnostic Studies]]
(4) homocysteine.
 
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. 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]]":
 
* [[Senescence|Advanced age]]
* [[Male]] sex
* Having [[Diabetes]] or [[Impaired glucose tolerance]] (IGT) +
* [[lipoprotein|Dyslipoproteinemia]] (unhealthy patterns of serum proteins carrying fats & [[cholesterol]]): +
** High serum concentration of [[low density lipoprotein]] (LDL, "bad if elevated concentrations and small"), [[Lipoprotein(a)]] (a variant of LDL), and / or [[very low density lipoprotein]] (VLDL) particles, i.e. "lipoprotein subclass analysis"
** Low serum concentration of functioning [[high density lipoprotein]] (HDL "protective if large and high enough" particles), i.e. "lipoprotein subclass analysis"
* [[Tobacco smoking]]
* Having [[hypertension|high]] [[blood pressure]] +
* Being [[obesity|obese]] (in particular [[central obesity]], also referred to as ''abdominal'' or ''male-type'' obesity) +
* A [[sedentary lifestyle]]
* Having close relatives who have had some complication of atherosclerosis (eg. [[coronary heart disease]] or [[stroke]])
* Elevated serum levels of [[homocysteine]]
* Elevated serum levels of [[uric acid]] (also responsible for gout)
* Elevated serum [[fibrinogen]] concentrations +
* Chronic systemic [[inflammation]] as reflected by upper normal WBC concentrations, elevated [[C reactive protein|hs-CRP]] and many other blood chemistry markers, most only research level at present, not clinically done.<ref name=Bhatt> [http://circ.ahajournals.org/cgi/content/full/circulationaha;106/1/136 Deepak L. Bhatt, MD; Eric J. Topol, MD] ''Need to Test the Arterial Inflammation Hypothesis'', 2002, referenced on 4/1/06 </ref>
* [[Stress (medicine)|Stress]] or symptoms of [[clinical depression]]
* [[Hypothyroidism]] (a slow-acting [[thyroid]])
* High intake of trans-fats and saturated fats in diet


==Treatment==
==Treatment==
If atherosclerosis leads to symptoms, some symptoms such as [[angina pectoris]] can be treated. Non-pharmaceutical means are usually the first method of treatment, such as cessation of smoking and practicing regular exercise. If these methods do not work, medicines are usually the next step in treating cardiovascular diseases, and with improvements, have increasingly become the most effective method over the long term. However, medicines are criticized for their expense, patented control and occasional undesired effects.
[[Atherosclerosis medical therapy|Medical Therapy]] | [[Atherosclerosis primary prevention|Primary Prevention]] | [[Atherosclerosis secondary prevention|Secondary Prevention]] | [[Atherosclerosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Atherosclerosis future or investigational therapies|Future or Investigational Therapies]]
 
[[dyslipidemia|Lipoprotein imbalances]], upper normal and especially elevated blood sugar, i.e. [[diabetes]], high blood pressure, [[homocysteine]], stopping smoking, taking [[anticoagulant]]s (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 which have proved to be helpful in clinical trials. The target serum cholesterol level is ideally equal or less than 4mmol/L (160 mg/dL) and triglycerides equal or less than 2mmol/L 180 (mg/dL).
 
In general, the group of medications referred to as statins has seen popularity yet they are not approved in most jurisdictions for treating atherosclerosis.  They have relatively few short-term undesirable side-effects and have shown some effect in reducing atherosclerotic disease 'events' in some but not all studies such as [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12479764&dopt=Abstract ALLHAT].
 
The newest statin, [[rosuvastatin]], has been the first to demonstrate regression of atherosclerotic plaque within the [[coronary arteries]] by [[IVUS]] evaluation,<ref name=Nissen "JAMA">[http://jama.ama-assn.org/cgi/reprint/jama;295/13/1556.pdf?ijkey=Md42dlk7z9TzyL8&keytype=finite], "Effect of Very High-Intensity Statin Therapy on Regression of Coronary Atherosclerosis".</ref> see the ''Effect of Very High-Intensity Statin Therapy'' reference below. The study was not set up to demonstrate clinical benefit or harm. 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 which demonstrate improved outcome for those people using more complex and effective treatment regimens which change physiologic behaviour patterns to more closely resemble those humans exhibit in childhood at a time before [[fatty streaks]] begin forming.
 
Lowering lipoprotein little a, a genetic variant of LDL, can be achieved with large daily doses of vitamin B3, niacin. Niacin also tends to shift LDL particle distribution to larger particle size and improve HDL functioning. Work on increasing HDL particle concentration and function, beyond the niacin effect, perhaps even more important, is slowly advancing. Combinations of [[statin]]s, [[niacin]], intestinal cholesterol absorption inhibiting supplements ([[ezetimibe]] and others, and to a much lesser extent [[fibrate]]s have been the most successful in changing [[dyslipidemia]] patterns and but, in the case of inhibitors and fibrates without improving clinical outcomes in secondary prevention. In primary prevention, cholesterol lowering agents have not reduced the mortality rates, for example the AFCAPS/TexCAPS and EXCEL trials and the 2 main trials with atorvastatin, Lipitor, as in the ASCOT and SPARCL studies.  Dietary changes to achieve benefit have been more controversial, generally far less effective and less widely adhered to with success.
 
Evidence has increased that people with [[diabetes]], despite not having clinically detectable atherosclotic disease, have more severe debility from atherosclerotic events over time than even non-diabetics who have already suffered atherosclerotic events. Thus [[diabetes]] has been upgraded to be viewed as an advanced atherosclerotic disease equivalent.
 
Lowering [[homocysteine]] levels, including within the normal range and 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]] [[scientific control|controlled]] human clinical trials.
 
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.
 
Other physical treatments, helpful in the short term, include minimally invasive [[angioplasty]] procedures to physically expand narrowed arteries and major invasive surgery, such as [[Coronary artery bypass surgery|bypass surgery]], to create additional blood supply connections which go around the more severely narrowed areas.
 
High dose supplements of vitamin E or C, with the goal of improving [[antioxidant]] protection, have failed to produce any beneficial trends in human, double blind, clinical research trials. However, these trials have consistently used lower doses than those claimed to be effective and have ignored the short half life of high intakes of [[vitamin C]] in the body.
 
On the other hand, the [[statin]]s, 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 success of statin drugs in clinical trials is based on some  reductions in mortality rates, however never in women or people over the age of 70 [http://www.cmaj.ca/cgi/content/full/173/10/1207-a CMAJ].  For example, in 4S, the first large placebo controlled, randomized clinical trial of a statin in people with advanced disease who had already suffered a heart attack, the overall mortality rate reduction for those taking the statin, vs. placebo, was 30%. For the subgroup of people in the trial who had Diabetes Mellitus, the mortality rate reduction between statin and placebo was 54%. 4S was a 5.4 year trial which 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.  The [http://jama.ama-assn.org/cgi/reprint/jama;295/13/1556.pdf?ijkey=Md42dlk7z9TzyL8&keytype=finite |ASTEROID] trial, mentioned above and in reference 3, has been the first to show actual disease volume regression (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 has no placebo group.
 
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. Additionally, 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.
 
Patients at risk for atherosclerosis-related diseases are increasingly being treated [[prophylaxis|prophylactically]] with low-dose [[aspirin]] and a [[statin]]. The high incidence of cardiovascular disease led Wald and Law<ref name="Polypill">Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. ''[[British Medical Journal|BMJ]]'' 2003;326:1419. PMID.</ref> to propose a ''[[Polypill]]'', a once-daily pill containing these two types of drugs in addition to an [[ACE inhibitor]], [[diuretic]] and [[beta blocker]] and [[folic acid]]. They maintain that high uptake by the general population by such a ''Polypill'' would reduce cardiovascular mortality by 80%. It must be emphasized however that this is purely theoretical, as the Polypill has never been tested in a clinical trial.
 
== Recent research ==
Methods to increase [[high density lipoprotein]] (HDL) particle concentrations, which in some animal studies largely reverses and remove atheromas, are being developed and researched.  [[Niacin]] has HDL raising effects (by 10 - 30%) and showed clinical trial benefit in the Coronary Drug Project, however, the drug [[torcetrapib]] most effectively raising HDL (by 60%) also raised deaths by 60% and all studies regarding this drug were halted in December 2006.[http://www.nlm.nih.gov/medlineplus/news/fullstory_42459.html]
 
An indication of the role of HDL on atherosclerosis has been with the rare Apo-A1 Milano human genetic variant of this HDL protein. Ongoing work starting in the 1990s may lead to human clinical trials probably by about 2008, on using either synthesized Apo-A1 Milano HDL directly or by gene-transfer methods to pass the ability to synthesize the Apo-A1 Milano HDL protein.
 
The ASTEROID trial used a high-dose of a powerful statin, [[rosuvastatin]], and found plaque (intima + media volume) reduction; see the ''Effect of Very High-Intensity Statin Therapy'' reference below. No attempt has yet been made to compare this drug with placebo regarding clinical benefit.
 
Since about 2002, progress in understanding and developing techniques for modulating immune system function so as to significantly suppress the action of macrophages to drive atherosclerotic plaque progression are being developed with considerable success in reducing plaque development in both mice and rabbits. Plans for human trials, hoped for by about 2008, are in progress. Generally these techniques are termed immunomodulation of atherosclerosis.
 
Genetic expression and control mechanism research, including (a) the PPAR [[peroxisome proliferator activated receptors]] known to be important in blood sugar and variants of lipoprotein production and function and (b) of the multiple variants of the proteins which form the lipoprotein transport particles, is progressing.
 
Some controversial research has suggested a link between atherosclerosis and the presence of several different [[nanobacterium|nanobacteria]] in the arteries, e.g. [[Chlamydophila pneumoniae]], though trials of current antibiotic treatments known to be usually effective in suppressing growth or killing these bacteria have not been successful in improving outcomes.
 
The immunomodulation approaches mentioned above, because they deal with innate responses of the host to promote atherosclerosis, have far greater prospects for success. <ref>Stevens, Karen M.J. Douglas, Athanasios N. Saratzis and George D. Kitas Inflammation and atherosclerosis in rheumatoid arthritis Robert J. Expert Rev. Mol. Med. Vol. 7, Issue 7</ref> <ref>Mol, A 2002 _The Body Multiple: Ontology in medical practice_ London: Duke University Press</ref>
 
==Pathological Findings==
 
[http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
 
<gallery>
Image:Atherosclerosis 1.jpg|Atherosclerosis: Gross, close-up of fatty streak and intimal thickening
Image:Atherosclerosis 2.jpg|Atherosclerosis: Gross, very good example of fibrous plaques with ulceration and thrombosis
Image:Atherosclerosis 3.jpg|Atherosclerosis: Gross, proximal left anterior descending artery showing faint fatty streaks and penetrating arteries
Image:Atherosclerosis 4.jpg|Atherosclerosis: Gross, close-up view of aorta. A plaque with ulceration and thrombosis
</gallery>
 
 
<gallery>
Image:Atherosclerosis 5.jpg|Atherosclerosis: Gross, good example of plaques in aorta
Image:Atherosclerosis 6.jpg|Atherosclerosis: Coronary artery: Gross, close-up view of excellent plaque lesion causing more than 90% occlusion
Image:Atherosclerosis 7.jpg|Atherosclerosis: Gross, good example of advanced calcific atherosclerosis in aorta.
Image:Atherosclerosis 8.jpg|Atherosclerosis: Gross, very good example of calcified and ulcerated atheromatous plaques in aorta
</gallery>
 
 
<gallery>
Image:Atherosclerosis with dissecting aneurysm 1.jpg|Atherosclerosis: Dissecting Aortic Aneurysm: Gross, shows dilated aorta with extensive atherosclerosis dissection is seen. A small abdominal aorta, atherosclerotic aneurysm is present. A good picture for association of dilation with dissection
Image:Atherosclerosis 10.jpg|Atherosclerosis: Gross, close-up, an excellent view but appearance much like that of syphilitic aortitis
Image:Atherosclerosis 11.jpg|Atherosclerosis: Gross, an excellent example of ulcerated lesions with many mural thrombi
Image:Atherosclerosis 12.jpg|Atherosclerosis: Gross, very good example of plaque lesion and small mural thrombi
</gallery>
 
 
<gallery>
Image:Atherosclerosis coronary artery 111.jpg|Atherosclerosis: Coronary artery: Gross, an excellent example of plaque, 80% occlusion, uncomplicated lesion.
Image:Atherosclerosis coronary artery in situ 1.jpg|Atherosclerosis: Coronary artery: Atherosclerosis and thrombotic occlusion: Gross, (an excellent example) in situ on heart
Image:Atherosclerosis 15.jpg|Atherosclerosis: Coarctation: Gross, adult lesion with dramatic demonstration of accelerated atherosclerosis
Image:Atherosclerosis 16.jpg|Atherosclerosis: Coronary artery: Gross, cross section well shown hemorrhage into plaque and thrombosis
</gallery>
 
 
<gallery>
Image:Atherosclerosis 17.jpg|Atherosclerosis: Aorta: Gross, good example of fibrous plaques
Image:Atherosclerosis 18.jpg|Atherosclerosis: Aorta: Gross, an excellent example of fibrous plaques and mural thrombi
Image:Atherosclerosis 19.jpg|Atherosclerosis: Aorta: Gross, thrombi at the origin of celiac axis and superior mesenteric arteries
Image:Atherosclerosis 20.jpg|Atherosclerosis: Aorta: Gross, thrombotic occlusion extending from just below renal arteries into iliac artery
</gallery>
 
 
<gallery>
Image:Atherosclerosis 21.jpg|Atherosclerosis: Abdominal Aneurysm Ruptured: Gross, a good example, opened kidneys in marked place. Atherosclerosis in lower thoracic aorta
Image:Atherosclerosis 22.jpg|Atherosclerosis: Adult type coarctation with atherosclerosis in aortic arch
Image:Atherosclerosis 23.jpg|Atherosclerosis: Abdominal Aneurysm Graft Repair: Gross natural color, close-up, an excellent example of Dacron graft that has been in place for years with pseudointima and atherosclerosis
Image:Atherosclerosis 24.jpg|Atherosclerosis: Renal Transplant: Gross, natural color, a close-up view of severe atherosclerosis in abdominal segment of aorta and fatty streaks in descending thoracic much advanced lesions for a 22 years old male with chronic glomerulonephritis
</gallery>
 
 
===Saphenous Vein Graft===
 
<gallery>
Image:Atherosclerosis 29.jpg|Saphenous vein coronary bypass graft: Atherosclerosis: Micro, an excellent demonstration of myofibroblastic type cells in thickened intima
Image:Atherosclerosis 30.jpg|Saphenous vein coronary bypass graft: Atherosclerosis: Micro, trichrome low mag, advanced plaque with hemorrhage into atheroma and complete lumen occlusion with fresh thrombus
Image:Atherosclerosis 31.jpg|Saphenous vein coronary bypass graft: Atherosclerosis: Micro, low mag, early atheromata consisting of subendothelial foam cells, whole graft and fibrous intimal thickening, (102 months after CABG)
Image:Atherosclerosis 32.jpg|Saphenous vein coronary bypass graft: Atherosclerosis: Micro, high mag, subendothelial foam cells
</gallery>
 
 
<gallery>
Image:Atherosclerosis 32a.jpg|Saphenous vein coronary bypass graft: Atherosclerosis: Micro, trichrome, low mag, large athero plaque and recanalized thrombus in lumen
Image:Atherosclerosis 32b.jpg|Saphenous vein coronary bypass graft: Atherosclerosis: Micro, H&E, low mag, large and ruptured atheromatous plaque with focal hemorrhage and calcification
Image:Atherosclerosis 32c.jpg|Saphenous vein coronary bypass graft: Atherosclerosis: Micro, trichrome, low mag, very complicated hemorrhagic and necrotic plaque with lumen occlusion. A recanalized thrombus and a large aneurysm at side filled with old blood and atheroma crystals
Image:Atherosclerosis 32d.jpg|Saphenous vein coronary bypass graft: Atherosclerosis: Micro, ald. fusch., complicated occlusive lesion with organized and recanalized thrombus and old hemorrhage into atheroma
</gallery>
 
===Coronary Arteries===


[http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
==Case Studies==
 
[[Atherosclerosis case study one|Case #1]]
<gallery>
Image:Atherosclerosis 33.jpg|Coronary artery: Atherosclerosis: Micro, H&E, low mag, injected artery, good demonstration of organized and recanalized thrombus
Image:Atherosclerosis 34.jpg|Coronary artery: Atherosclerosis: Micro, H&E, low mag, injected artery, very good example of marked lumen stenosis due to typical fibrous plaque with some calcifications
Image:Atherosclerosis 35.jpg|Coronary artery: Atherosclerosis: Micro, H&E, injected artery, marked large plaque with thin fibrous cap has eroded to adventitia, the start of an aneurysm
Image:Atherosclerosis 36.jpg|Coronary artery: Atherosclerosis: Micro, H&E, low mag, an excellent example of plaque with calcification and marked narrowing of lumen. 90% lumen is occluded by thrombus
</gallery>
 
 
<gallery>
Image:Atherosclerosis 37.jpg|Coronary artery: Atherosclerosis: Micro, low mag, an excellent example of atheromatous plaque causing marked lumen obstruction. An uncomplicated plaque
Image:Atherosclerosis 38.jpg|Coronary artery: Atherosclerosis: Micro, H&E, low mag, an excellent example of athero plaque. the lumen is completely occluded
Image:Atherosclerosis 39.jpg|Coronary artery: Atherosclerosis: Micro, H&E, low mag, a plaque with hemorrhage and organizing mural thrombus in lumen
Image:Atherosclerosis 40.jpg|Coronary artery: Atherosclerosis: Micro, H&E, low mag, a good example of plaque with old hemorrhage and marked lumen compensation 
</gallery>
 
 
 
<gallery>
Image:Atherosclerosis 41.jpg|Coronary artery: Atherosclerosis: Micro, H&E, med mag, plaque rupture with thrombosis
Image:Atherosclerosis 42.jpg|Coronary artery: Atherosclerosis: Micro, H&E, low mag, injected artery, a good example of atheromatous plaque that appears to owe much of its mass to an organized mural thrombus
Image:Atherosclerosis 43.jpg|Coronary artery: Atherosclerosis: Micro, H&E, low mag, typical uncomplicated fibrous plaque
Image:Atherosclerosis 44.jpg|Coronary artery: Atherosclerosis: Micro, H&E, low mag, a good example of athero plaque with marked lumen narrowing. A small mural thrombus in lumen
</gallery>
 
 
 
<gallery>
Image:Atherosclerosis 44a.jpg|Coronary artery: Atherosclerosis: Micro, low mag, hemorrhage into plaque and thrombosis
Image:Atherosclerosis 44b.jpg|Coronary artery: Atherosclerosis: Recanalized Thrombus: Micro, low mag, H&E, lesion is nearly completely organized, small adventitial dissection probably related to bypass surgery about 24 hours before death (a good example)
Image:Atherosclerosis 44c.jpg|Coronary artery: Atherosclerosis: Plaque Hemorrhage and Thrombosis: Micro, low mag, H&E, quite good photo, large plaque with hemorrhage, organizing thrombus in lumen
Image:Atherosclerosis 44d.jpg|Coronary artery: Atherosclerosis, Severe: Micro, low mag, H&E, more than 90% stenosis, also shown a side branch
</gallery>
 
===Aorta===
 
[http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
 
<gallery>
Image:Atherosclerosis Aorta 1.jpg|Kidney: Atheromatous Embolus: Gross, natural color, external view of kidney with typical scarring pattern of repeated infarction and aorta with severe atherosclerosis (quite good example)
Image:Atherosclerosis Aorta 2.jpg|Aorta, Atherosclerosis: Gross, natural color, opened thoracic segment showing sessile plaques covering intima with several mural thrombi
Image:Atherosclerosis Aorta 3.jpg|Aorta, Atherosclerosis: Gross natural color view of descending thoracic and abdominal segments with expected distribution of atherosclerotic lesions in subject over 60 years old. Not much in thoracic segment and extensive plaques in abdominal segment, some with ulceration
Image:Atherosclerosis aorta, renal and iliac 1.jpg|Thrombus: Gross natural color aorta with kidneys showing thrombotic occlusion due to atherosclerosis beginning just below renal arteries and extending into common iliac (very good example)
</gallery>
 
===Carotid Artery===
 
[http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
 
<gallery>
Image:Atherosclerosis carotid artery 2.jpg|Carotid artery: Atherosclerosis: Gross, internal carotid plaque with thrombosis
Image:Atherosclerosis carotid artery 3.jpg|Carotid artery: Atherosclerosis: Gross, plaque with hemorrhage in carotid bulb
Image:Atherosclerosis carotid artery 4.jpg|Carotid artery bifurcation, atherosclerosis
Image:Atherosclerosis carotid artery 5.jpg|Carotid artery, atherosclerosis and thrombosis
Image:Atherosclerosis carotid artery 6.jpg|Carotid artery: Atherosclerosis: Gross, good example of carotid bulb plaque with thrombus
</gallery>
 
===Lung===
 
[http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
 
<gallery>
Image:Atherosclerosis lung 1.jpg|Lung: Pulmonary fibrosis and atherosclerosis of pulmonary artery
Image:Atherosclerosis lung 2.jpg|Lung: Pulmonary fibrosis and atherosclerosis of pulmonary artery
Image:Atherosclerosis lung 3.jpg|Lung: Pulmonary fibrosis and atherosclerosis of pulmonary artery
Image:Atherosclerosis lung 4.jpg|Lung: Atherosclerosis: Gross, natural color, arteries show atherosclerotic plaque lesions
</gallery>
 
===Pulmonary Artery===
 
[http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
 
<gallery>
Image:Atherosclerosis 57.jpg|Pulmonary artery atherosclerosis in patient with pulmonary hypertension
Image:Atherosclerosis 58.jpg|Pulmonary Artery Atherosclerosis: Gross, essentially natural color, artery stained by hemolysis, small plaque lesions 
Image:Atherosclerosis pulmonary artery 1.jpg|Atherosclerosis: Gross, natural color, close-up fatty plaques in large pulmonary artery
Image:Atherosclerosis 60.jpg|Atherosclerosis: Micro, low mag, van Gieson, thickened intima with fatty streak type lesion and preservation of fetal medial structure, a large pulmonary artery, 4yo male with primary pulmonary hypertension
</gallery>
 
===Brain===
 
[http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
 
<gallery>
Image:Atherosclerosis brain 1.jpg|Brain: Atherosclerosis: Gross, a good example of atherosclerosis in vessels at base of brain. 
Image:Atherosclerosis brain 2.jpg|Brain: Basilar Artery Atherosclerosis: Gross, fixed tissue, an external view of base of brain (typical lesion) 
Image:Atherosclerosis brain 3.jpg|Brain: Old Cystic Encephalomalacia: Gross, fixed tissue, frontal lobe lesion with frontal artery atherosclerosis
Image:Atherosclerosis brain 4.jpg|Brain: Watershed Infarct and Carotid Atherosclerosis
</gallery>
 
===Liver===
 
[http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
 
<gallery>
Image:Atherosclerosis 65.jpg|
Image:Atherosclerosis 66.jpg|
Image:Atherosclerosis 67.jpg|
Image:Atherosclerosis 68.jpg|
</gallery>
 
===Kidney===
 
[http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
 
<gallery>
Image:Atherosclerosis renal 1.jpg|Atherosclerosis: Kidney: Atheromatous Embolus: Gross, natural color, kidney with typical scarring pattern of repeated embolism and aorta with severe atherosclerosis (a quite good example)
Image:Atherosclerosis renal 2.jpg|Atherosclerosis: Kidney: Atrophy secondary to renal artery atherosclerosis: Gross, natural color, both kidneys one very atrophic the large left kidney weighed 220 grams and the small left one 90 gram
</gallery>
 
===Spleen===
 
[http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
 
<gallery>
Image:Atherosclerosis spleen 1.jpg|
Image:Atherosclerosis spleen 2.jpg|
Image:Atherosclerosis spleen 3.jpg|
Image:Atherosclerosis spleen 4.jpg|
</gallery>
 
==References==
{{reflist|2}}


==See also==
==Related Chapters==
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*[[Monckeberg's arteriosclerosis]]
*[[Monckeberg's arteriosclerosis]]
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Revision as of 15:04, 28 May 2020

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Atherosclerosis Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-In-Chief: Maheep Singh Sangha, M.B.B.S.Niloofarsadaat Eshaghhosseiny, MD[2]

Synonyms and keywords: Plaque buildup - arteries; hardening of the arteries

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Atherosclerosis from other Diseases

Epidemiology and Demographics

Risk Factors

Atherosclerosis screening

Overview

There is insufficient evidence to recommend routine screening for [disease/malignancy].

OR

According to the [guideline name], screening for [disease name] is not recommended.

OR

According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].

Screening

There is insufficient evidence to recommend routine screening for [disease/malignancy].

OR

According to the [guideline name], screening for [disease name] is not recommended.

OR

According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with:

  • [Condition 1]
  • [Condition 2]
  • [Condition 3]

References

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Natural History, Complications and Prognosis

Diagnosis

History and Symptoms | Physical Examination | Laboratory Findings | Other Diagnostic Studies

Treatment

Medical Therapy | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

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