Atheroma

An atheroma, or atheromatous plaque, is an abnormal accumulation of material in the inner layer of an arterial wall.
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.

Signs and symptoms

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 they are small, they are hidden deep within the chest and they never stop moving. Additionally, all mass-applied clinical strategies focus on both minimal cost and the overall safety of the procedure. Therefore, existing diagnostic strategies for detecting atheroma and tracking response to treatment have been extremely limited. 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, which reduce/stop blood flow. Yet these events occur suddenly and are not revealed in advance by either stress tests or angiograms.

Mechanism

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 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 of the vessel develops in some areas. Less frequently, the artery enlarges so much that a gross aneurysmal enlargement of the artery results. All three results are often observed, at different locations, within the same individual.

Stenosis and closure

Over time, atheromata usually progress in size and thickness and induce the surrounding muscular central region of the artery to stretch out, which is termed remodeling. Typically, remodeling occurs just enough to compensate for the atheroma's size such that the calibre of the artery opening remains unchanged, until about 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, or a clot forms and organizes over the plaque, then the lumen of the artery becomes narrowed as a result of repeated ruptures, clots and 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.
The endothelium and covering tissue, termed fibrous cap, separate atheroma from the blood in the lumen. If a rupture of the endothelium and fibrous cap occurs, then both a shower of debris from the plaque combined with a platelet and clotting response begins within fractions of a second, eventually resulting in narrowing or sometimes closure of the lumen. Eventually downstream tissue damage occurs due to closure or obstruction of downstream microvessels and/or closure of the lumen at the rupture, both resulting in loss of blood flow to downstream tissues. This is the principal mechanism of myocardial infarction, stroke or other related cardiovascular disease problems.
While clots at the rupture site typically shrink in volume over time, some of the clot may become organized into fibrotic tissue resulting in narrowing of the artery lumen; the narrowings sometimes seen on angiography examinations, if severe enough. Since angiography methods can only reveal larger lumens, typically larger than 200 micrometres, angiography after a cardiovascular event commonly does not reveal what happened.

Artery 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 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. The main stimulus for aneurysm formation is pressure atrophy of the structural support of the muscle layers. The main structural proteins are collagen and elastin. This causes thinning and the wall balloons allowing gross enlargement to occur, as is common in the abdominal region of the aorta.

Histology

The accumulation is always in the tunica intima, between the endothelium lining and the smooth muscle middle layer of the artery wall. While the early stages, based on gross appearance, have traditionally been termed fatty streaks by pathologists, they are not composed of fat cells but of accumulations of white blood cells, especially macrophages, that have taken up oxidized low-density lipoprotein.
After they accumulate large amounts of cytoplasmic membranes they are called foam cells. When foam cells die, their contents are released, which attracts more macrophages and creates an extracellular lipid core near the centre to inner surface of each atherosclerotic plaque.
Conversely, the outer, older portions of the plaque become more calcified, less metabolically active and more physically stiff over time.
Veins do not develop atheromata, because they are not subjected to the same haemodynamic pressure that arteries are, unless surgically moved to function as an artery, as in bypass surgery. In fact, veins grafted to function as arteries in bypass surgeries tend to show faster formation of atheromata, while arteries grafted to function as veins also do not grow atheromata.

Diagnosis

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; while these methods are highly relevant, they totally miss the atheroma within the arterial lumen.
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, are widely used in research and clinical practice today.
Carotid Intima-media thickness Scan 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.
Intravascular ultrasound and intravascular optical coherence tomography are the current most sensitive method detecting and measuring more advanced atheroma within living individuals, but has had limited applications 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. The presence of smaller, spotty plaques may actually be more dangerous for progressing to acute myocardial infarction.
Arterial ultrasound, especially of the carotid arteries, with measurement of the thickness of the artery wall, offers a way to partially track the disease progression. As of 2006, the thickness, commonly referred to as IMT for intimal-medial thickness, is not measured clinically though it has been used by some researchers since the mid-1990s to track changes in arterial walls. Traditionally, clinical carotid ultrasounds have only estimated the degree of blood lumen restriction, stenosis, a result of very advanced disease. 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 within the arterial lumen and never show atheroma; the wall of arteries, including atheroma within the arterial wall remain invisible. 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.

Classification of lesions

Type I: Isolated macrophage foam cells
Type II: Multiple foam cell layers
Type III: Preatheroma, intermediate lesion
Type IV: Atheroma
Type V: Fibroatheroma
Type VI: Fissured, ulcerated, hemorrhagic, thrombotic lesion
Type VII: Calcific lesion
Type VIII: Fibrotic lesion