Vulnerable plaque

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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.[1] 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. increased blood pressure, especially pulse pressure (systolic blood pressure vs. diastolic blood pressure difference), correlates with increased rates of major cardiovascular events associated with exercise, especially exercise beyond levels the individual does routinely. This video [1], examining autopsy specimens from an actual heart attack resulting in sudden death, shows the sequence. These videos, [2] and [3], illustrate the sequence of events and why, though the underlying process develops over decades, the symptoms are usually of sudden onset.

Generally an atheroma becomes vulnerable if it grows more rapidly and has a thin cover separating it from the bloodstream inside the arterial lumen. Tearing of the cover is called plaque rupture.

Repeated atheroma rupture and healing is one of the mechanisms, perhaps the dominant one, that creates artery stenosis.

Causes[edit]

Researchers have found that accumulation of white blood cells, especially macrophages, termed inflammation, in the walls of the arteries leads to the development of "soft" or vulnerable plaque, which when released aggressively promotes blood clotting.

Researchers now think that vulnerable plaque, (see atherosclerosis) is formed in the following way:[2]

  • Lipoprotein LDL particles, which carry fats (including the fat cholesterol made by every human cell) within the water/plasma portion of the blood stream, are absorbed into the artery wall, past the endothelium lining, some of the LDL-lipoprotein particles become oxidized and this attracts macrophages that eat the particles. This process typically starts in childhood. To be specific:
  • oxidized lipoprotein particles in the artery wall are an irritant which causes the release of proteins (called cytokines) which attract monocyte white blood cells (white blood cells are the inflammatory cells within the body).
  • The cytokines induce the endothelial cells lining the artery wall to display adhesion molecules that attract immune-system white blood cells (to be specific, monocytes).
  • The monocytes squeeze into the artery wall. Once inside, they transform into eating cells called macrophages and ingest the oxidized lipoprotein particles.
  • The macrophages sometimes become so overloaded with oxidized lipoprotein particles, the cholesterol contained therein and membrane-laden that they are called foam cells. Some of these cells die in place, releasing their fat and cholesterol-laden membranes into the intercellular space. This attracts more macrophages.
  • In some regions of increased macrophage activity, macrophage-induced-enzymes erode away the fibrous membrane beneath the endothelium so that the cover separating the plaque from blood flow in the lumen becomes thin and fragile.
  • Mechanical stretching and contraction of the artery, with each heart beat, i.e. the pulse, results in rupture of the thin covering membrane, spewing clot-promoting plaque contents into the blood stream.
  • The clotting system reacts and forms clots both on the particles shed into the blood stream and locally over the rupture. The clot, if large enough, can block all blood flow. Since all the blood, within seconds, passes through 5-micrometre capillaries, any particles much larger than 5 micrometres block blood flow. (most of the occlusions are too small to see by angiography).
  • Most ruptures and clotting events are too small to produce symptoms, though they still produce heart muscle damage, a slow progressive process resulting in ischemic heart disease, the most common basis for congestive heart failure.
  • The clot organizes and contracts over time, leaving behind narrowing(s) called stenoses. These narrowing(s) are responsible for the symptoms of the disease and are identified, after the fact, by the changes seen on stress tests and angiography, and treated with bypass surgery and/or angioplasty, with or without stents.

When this inflammation is combined with other stresses, such as high blood pressure (increased mechanical stretching and contraction of the arteries with each heart beat), it can cause the thin covering over the plaque to split, spilling the contents of the vulnerable plaque into the bloodstream. The sticky cytokines on the artery wall capture blood cells (mainly platelets) that accumulate at the site of injury. When these cells clump together, they form a thrombus, sometimes large enough to block the artery.

The most frequent cause of a cardiac event following rupture of a vulnerable plaque is blood clotting on top of the site of the ruptured plaque that blocks the lumen of the artery, thereby stopping blood flow to the tissues the artery supplies.

Upon rupture, atheroma tissue debris may spill into the blood stream; this debris is often too large (over 5 micrometers) to pass on through the capillaries downstream. In this, the usual situation, the debris obstruct smaller downstream branches of the artery resulting in temporary to permanent end artery/capillary closure with loss of blood supply to, and death of, the previously supplied tissues. A severe case of this can be seen during angioplasty in the slow clearance of injected contrast down the artery lumen. This situation is often termed non-reflow.

In addition, atheroma rupture may allow bleeding from the lumen into the inner tissue of the atheroma, making the atheroma size suddenly increase and protrude into the lumen of the artery, producing lumen narrowing or even total obstruction.

Detection[edit]

While a single ruptured plaque can be identified during autopsy as the cause of a coronary event, there is currently no way to identify a culprit lesion before it ruptures.[3]

Because artery walls typically enlarge in response to enlarging plaques, these plaques do not usually produce much stenosis of the artery lumen. Therefore, they are not detected by cardiac stress tests or angiography, the tests most commonly performed clinically with the goal of predicting susceptibility to future heart attack. In contrast to conventional angiography, cardiac CT angiography does enable visualization of the vessel wall as well as plaque composition. Some of the CT derived plaque characteristics can help predict for acute coronary syndrome.[4] In addition, because these lesions do not produce significant stenoses, they are typically not considered "critical" and/or interventionable by interventional cardiologists, even though research indicates that they are the more important lesions for producing heart attacks.

The tests most commonly performed clinically with the goal of testing susceptibility to future heart attack include several medical research efforts, starting in the early to mid-1990s, using intravascular ultrasound (IVUS), thermography, near-infrared spectroscopy, careful clinical follow-up, and other methods, to predict these lesions and the individuals most prone to future heart attacks. These efforts remain largely research with no useful clinical methods to date (2006).

Another approach to detecting and understanding plaque behavior, used in research and by a few clinicians, is to use ultrasound to non-invasively measure wall thickness (usually abbreviated IMT) in portions of larger arteries closest to the skin, such as the carotid or femoral arteries. While stability vs. vulnerability cannot be readily distinguished in this way, quantitative baseline measurements of the thickest portions of the arterial wall (locations with the most plaque accumulation). Documenting the IMT, location of each measurement and plaque size, a basis for tracking and partially verifying the effects of medical treatments on the progression, stability, or potential regression of plaque, within a given individual over time, may be achieved.

Prevention[edit]

Patients can lower their risk for vulnerable plaque rupture in the same ways that they can cut their heart attack risk: Optimize lipoprotein patterns, keep blood glucose levels low normal (see HbA1c), stay slender, eat a proper diet, quit smoking, and maintain a regular exercise program. Researchers also think that obesity and diabetes may be tied to high levels of C-reactive protein.[2]

Current research[edit]

Newer clinical trial results (2007), e.g. the COURAGE trial,[5] have demonstrated that aggressively treating some of the physiologic behavioral factors that promote atheromas with "optimal medical therapy" (not opening narrowing(s), aka stenoses, per se) produced the most effective results in terms of improving human survival and quality of life for those identified as having already developed advanced cardiovascular disease with many vulnerable plaques.

References[edit]

  1. ^ Moreno, P. R. (2010). "Vulnerable Plaque: Definition, Diagnosis, and Treatment". Cardiology Clinics 28 (1): 1–30. doi:10.1016/j.ccl.2009.09.008. PMID 19962047.  edit
  2. ^ a b Texas Heart Institute, Heart Information Center
  3. ^ Heart Disease and Stroke Statistics – 2006 update, American Heart Association.
  4. ^ Versteylen, MO, et al. Additive value of semi-automated quantification of coronary artery disease using cardiac CT-angiography to predict for future acute coronary syndrome. J Am Coll Cardiol. 2013;():. doi:10.1016/j.jacc.2013.02.065
  5. ^ Boden WE, O'Rourke RA, Teo KK, et al. (April 2007). "Optimal medical therapy with or without PCI for stable coronary disease". N. Engl. J. Med. 356 (15): 1503–16. doi:10.1056/NEJMoa070829. PMID 17387127.