An atheroma (plural: atheromata) is an unhealthy tissue growth which develops within the walls of arteries over time. Veins do not develop atheromata, unless surgically moved to function as an artery, as in bypass surgery.
Collectively, the process of atheroma development within an individual is called atherogenesis and the overall result of the disease process is termed atherosclerosis.
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 tissue characteristics within the same atheroma. By light microscopy visualization, 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, outer portions of atheroma structures.
Atheroma typically progress silently for decades and remain undetected by most clinical diagnostic approaches, including cardiac stress testing and angiography. Eventually, their presence is revealed by production of disastrous clinical events and permanent disability, such as heart attack or stroke, with the majority of people assuming they are healthy until proven otherwise. 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 world countries, with improved public health, infection control and increasing life spans, atheroma processes have become an increasingly important problem and burden for society.
They continue to be the number one 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.
In the mid-twentieth century, it was assumed that atheromata simply expanded into the lumen and produced stenoses as they grew, since the disease always developed between the inner endothelial lining and the muscular wall.
This belief was based on the angiography view of the blood column within arteries and a belief that the smooth muscle wall of an artery (the thickest and strongest portion of the artery wall in a healthy artery) would not change overtime.
This belief continued despite contradicting evidence that this was an overly simplistic attempt to explain empirical findings.
Most artists' illustrations of atheromata and the atherosclerosis process in 2004 still portray this concept incorrectly.
By the late 1980s and early 1990s, careful pathology work and research using intravascular ultrasound (IVUS) showed clearly that this angiographic assumption was incorrect.
Since the early to mid 1990s, better research has led to a wide recognition that one of two overall changes typically occurs in the artery wall structure as an atheroma develops and progresses:
(a) wall thickening and external enlargement with associated lumen preservation until late in the process; or
(b) wall thickening and both external size and lumen enlargement.
These processes probably have survival value, as they reduce and hide some of the effects of the atheroma process in terms of both symptoms and detection by most conventional diagnostic tests (e.g., cardiac stress tests) until advanced stages.
According to United States data, 2004, for about 65% of men and 47% of women, the fist symptom of cardiovascular disease is heart attack or sudden death (death within one hour of symptom onset.)
Most artery flow disrupting events occur at locations with less than 50% lumen narrowing. Cardiac stress testing, traditionally the most commonly performed non-invasive testing method for blood flow limitations generally only detects lumen narrowing of ~75% or greater, although some physicians advocate that nuclear stress methods can detect as little as 50%.
Actual Artery/Atheroma Behavior:
1. External Artery Enlargement; Eventual Possible Stenosis and/or Closure
Over time, atheroma usually progress in size and thickness and induce the surrounding muscular wall of the artery to stretch out, termed remodeling, typically just enough to compensate for their size such that the opening of the artery remains unchanged until typically over 40-50% of the artery wall cross sectional area consists of atheromatous tissue.
If the muscular wall enlargement eventually fails to keep up with the enlargement of the atheroma volume, then the lumen of 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 endothelium and 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. Platelet and clot accumulation over the rupture may produce narrowing/closure of the lumen and tissue damage may occur due to either closure of the lumen and loss of blood flow beyond the ruptured atheroma and/or by occlusion of smaller downstream vessels by debris. See vulnerable plaque.
This is the principle mechanism of heart attack, stroke or other related cardiovascular disease problems. As research has shown, this process is not a result of stenosis. Prior to the rupture, there may have been no lumen narrowing, 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, stenoses of about 75% are required to produce detectable abnormalities during cardiac stress tests.
2. External Artery Enlargement and Lumen Enlargement
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 can also rupture and shower of 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, 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. Angiography and later stress testing was begun to either visualize or indirectly detect stenosis. 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 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 streaks in 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 IVUS technology. Angiography does not visualize atheroma; it only makes the blood flow within blood vessels visible. 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 computerized tomography (CT; lead by the EBT form given its greater speed) and magnetic resonance imaging (MRI). The most promising since the early 1990s has 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 are known.