Atheroma

An atheroma (plural: atheromata) is an abnormal fatty deposit which develops within the walls of arteriesover time. Veinsdo not develop atheromata, unless surgically moved to function as an artery, as in bypasssurgery. In the context of heart or artery matters, atheroma is commonly referred to as "plaque."

Collectively, the process of atheroma development within an individual is called atherogenesisand the overall result of the disease process is termed atherosclerosis.

Stages

In humans, atheroma usually begin in later childhood, about ages 5-9, as fatty streaks. These, and older, larger atheroma lesions have long been observed in autopsy examinations of people who have died for unrelated reasons; they are so common, more so with increasing age, they were long considered normal, even though clearly unhealthy.

More advanced atheroma develop multiple different internal tissuecharacteristics within the same atheroma. By light microscopyvisualization, pathologists have characterized as many as 10 different tissues subtypes within a single atheroma. Generally, these range from collections of macrophage cells, always the initiating cells in the newest sections of atheroma, to more complex structures including living cells, cellular debris of cells which have died and extracelluar deposits of fibrous tissue & calcified crystals, within the oldest, outermost portions of atheroma structures.

Atheroma typically progress silently for decades and remain undetected by most clinical diagnostic approaches, including cardiac stress testingand angiography. Eventually, their presence is revealed by production of disastrous clinical events and permanent disability, such as heart attackor stroke, with the majority of people assuming they were healthy until proven otherwise by events. For some individuals, warning symptoms do occur before the onset of major debility or death, however these are the minority.

Historically physicians, who are trained to treat symptoms and avoid treatment before onset of clear enough symptoms and physical abnormalities, have just considered the processes a normal part of aging, even though unhealthy.

Difficulty of Tracking, Researching and Better Understanding Atheroma

Most people first develop clinical symptoms and debility from atheroma activity within the heart arteries. However, the heart arteries, because (a) they are small (from about 5 mm down to invisible), (b) hidden deep within the chest and (c) never stop moving, have been a difficult target organ to track, especially clinically in individuals who are still asymptomatic. Additionally all mass applied clinical strategies focus on both minimal cost, if not "free", and great safety. Therefore existing diagnostic strategies for detecting atheroma and tracking response to treatment have been extremely limited.

Evolving Concepts and Understanding

In First Worldcountries, with improved public health, infection control and increasing life spans, atheroma processes have become an increasingly important problem and burden for society. Atheroma continue to be the number one underlying basis for disabilityand 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.

In the mid-twentieth century, it was assumed that atheromata simply expanded into the lumenand produced stenosesas they grew, since the disease always developed between the inner endotheliallining and the muscular wall. This belief was based on the angiographyview of the blood column within arteriesand a belief that the smooth musclewall of an artery(the thickest and strongest portion of the artery wall in a healthy artery) would not change in size and structure over time. This belief continued despite contradicting evidence that this was an overly simplistic attempt to explain empiric findings. Most artists' illustrations of atheromata and the atherosclerosisprocess in 2004 still portray this concept, even though quite incorrect. By the late 1980sand early 1990s, careful pathologywork and research using intravascular ultrasound(IVUS) showed clearly that this angiographicassumption was incorrect.

Since the early to mid 1990s, better research has led to a somewhat wider recognition that one of two changes typically occur in the arterywall structure as an atheroma develops and progresses: (a) wall thickening and external enlargement with associated lumenpreservation until late in the process; or (b) wall thickening with both external size and lumenenlargement. These processes both have survival value, as they reduce and hide some of the effects of the atheroma process and prevent symptoms. However they also prevent detection of the disease process by most conventional diagnostic tests, (e.g. cardiac stress testsand angiography), until advanced stages.

According to United States data, 2004, for about 65% of men and 47% of women, the first symptomof cardiovascular disease is heart attackor sudden death (death within one hour of symptom onset.)

Most artery flow disrupting events occur at locations with less than 50% lumennarrowing. From elegantly performed clinical studies published in the late 1990s, and using IVUSto better visualize disease status, the typical heart attack occurs at locations with about 20% stenosis, prior to the heart attack. Cardiac stress testing, traditionally the most commonly performed non-invasive testing method for blood flow limitations generally only detects lumennarrowing of ~75% or greater, although some physicians advocate that nuclear stress methods can sometimes detect as little as 50%.

Actual Artery/Atheroma Behavior:

1. External ArteryEnlargement; Eventual Possible Stenosisand/or Closure

Over time, atheroma usually progress in size and thickness and induce the surrounding muscular wall of the arteryto stretch out, termed remodeling, typically just enough to compensate for their size such that the openingof the arteryremains unchanged until typically over 40-50% of the artery wall cross sectional area consists of atheromatous tissue (see: Glasgov, below).

If the muscular wall enlargement eventually fails to keep up with the enlargement of the atheroma volume, then the lumenof the artery begins to narrow, commonly as a result of repeated ruptures of the covering tissues separating the atheroma from the blood stream. This becomes a more common event after decades of living, increasingly more common after people are over 40 years old.

If a rupture occurs, a rupture of the endotheliumand covering tissue, termed fibrous cap, which separates an atheroma from the blood in the lumen, then a platelet and clotting response over the rupture rapidly develops. Additionally, the rupture may result in a shower of debris. Plateletand clotaccumulation over the rupture may produce narrowing/closure of the lumenand tissue damage may occur due to either closure of the lumenand loss of blood flow beyond the ruptured atheroma and/or by occlusion of smaller downstream vessels by debris. See vulnerable plaque.

This is the principal mechanism of heart attack, strokeor other related cardiovascular diseaseproblems. As research has shown, this process is not a result of stenosis. Prior to the rupture, there may have been no lumennarrowing, even aneurysmal enlargement, at the atheroma. On average, by clinical research using IVUS, there is a minor stenosis, about 20%, present over those unstable atheroma which rupture and result in major disability or death. Comparatively, stenosesof about 75% are required to produce detectable abnormalities during cardiac stress tests.

2. External ArteryEnlargement and LumenEnlargement

If the muscular wall enlargement is overdone over time, then a gross enlargementof the artery results, usually over decades of living. This is a less common outcome. Atheroma within aneurysmal enlargement can also rupture and shower of debris of atheroma and clot downstream. If the arterial enlargementcontinues 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, major symptoms and debility; often rapid death.

Evolution of Strategies and Changing Focus

The sudden nature of the complications of pre-existing atheroma, vulnerable plaque, have led, since the 1950s, to the development of intensive care units and complex medical and surgical interventions. Angiographyand later stress testingwas begun to either visualize or indirectly detect stenosis. Next came bypasssurgery, to plumb transplanted veins, sometimes arteries, around the stenosesand more recently angioplasty, now including stents, most recently drug coated stents, to stretch the stenosesmore open.

Yet despite these medical advances, with success in reducing the symptoms of anginaand 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 surgeryand angioplastyprocedures have had only a minimal effect, some would argue no effect, on improving overall survival. Additionally, these treatments are often done only after an individual is symptomatic, often already partially disabled, as a result of the disease.

The older methods for understanding atheroma, dating to before WWII, relied on autopsy data. Autopsy data has long shown initiation of fatty streaksin later childhood with slow asymptomatic progession over decades.

Since the later 1980s, the best way to see atheroma and better understand atheroma behaviour in living individuals has been IVUStechnology. Angiographydoes not visualize atheroma; it only makes the blood flowwithin blood vesselsvisible. Alterative 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; lead by the EBTform given its greater speed) and magnetic resonance imaging(MRI). The most promising since the early 1990shas been EBT, typically detecting and recognizing advanced calcification within the base of atheroma about 10 years before most individuals start having clinically recognized symptoms and debility. However, though these methods are used in research, they are not widely available to most patients, still have mild to 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. However, this effort has been slow, partly because the asymptomatic nature of atheromata make them especially difficult to study. Additionally, understanding what drives atheroma development is complex with multiple factors involved, only some of which, such as lipoprotein patterns and blood sugar levels, are known and well researched. Evolving areas of understanding include immune system triggers of macrophage responses.

References

• Steven Glasgov: Compensatory Enlargement of Human Atherosclerotic Coronary Arteries, N Engl J Med, 316:131-1375, 1987

See also

• Atherogenesis
• Atherosclerosis
• Artery
• Heart
• Coronary circulation
• Coronary catheterization
• Angiogram
• IVUS
• EBT
• Lipoprotein
• LDL, HDL, IDLand VLDLda:Åreforkalkning

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It uses material from the http://en.wikipedia.org/wiki/Atheroma Wikipedia article Atheroma.