Atherosclerosis (also known as arteriosclerotic vascular disease or ASVD) is a condition in which an artery wall thickens as the result of a build-up of fatty materials such as cholesterol. It is a syndrome affecting arterial blood vessels, a chronic inflammatory response in the walls of arteries, in large part due to the accumulation of macrophage white blood cells and promoted by low-density lipoproteins (plasma proteins that carry cholesterol and triglycerides) without adequate removal of fats and cholesterol from the macrophages by functional high density lipoproteins (HDL), (see apoA-1 Milano). It is commonly referred to as a hardening or furring of the arteries. It is caused by the formation of multiple plaques within the arteries.
The atheromatous plaque is divided into three distinct components:
1. The atheroma which is the nodular accumulation of a soft, flaky, yellowish material at the center of large plaques, composed of macrophages nearest the lumen of the artery
2. Underlying areas of cholesterol crystals
3. Calcification at the outer base of older/more advanced lesions.
Causes
Atherosclerosis develops from low-density lipoprotein molecules (LDL) becoming oxidized (ldl-ox) by free radicals, particularly reactive oxygen species (ROS). When oxidized LDL comes in contact with an artery wall, a series of reactions occur to repair the damage to the artery wall caused by oxidized LDL. The LDL molecule is globular shaped with a hollow core to carry cholesterol throughout the body. Cholesterol can move in the bloodstream only by being transported by lipoproteins.
The body's immune system responds to the damage to the artery wall caused by oxidized LDL by sending specialized white blood cells (macrophages and T-lymphocytes) to absorb the oxidized-LDL forming specialized foam cells. These white blood cells are not able to process the oxidized-LDL, and ultimately grow then rupture, depositing a greater amount of oxidized cholesterol into the artery wall. This triggers more white blood cells, continuing the cycle.
Eventually, the artery becomes inflamed. The cholesterol plaque causes the muscle cells to enlarge and form a hard cover over the affected area. This hard cover is what causes a narrowing of the artery, reduces the blood flow and increases blood pressure. Some researchers believe that atherosclerosis may be caused by an infection of the vascular smooth muscle cells; chickens, for example, develop atherosclerosis when infected with the Marek's disease herpesvirus. Herpesvirus infection of arterial smooth muscle cells has been shown to cause cholesteryl ester (CE) accumulation. Cholesteryl ester accumulation is associated with atherosclerosis.
Also, cytomegalovirus (CMV) infection is associated with cardiovascular diseases.
Diagnosis
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 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 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.
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.
Prevention
Combinations of statins, niacin, intestinal cholesterol absorption-inhibiting supplements (ezetimibe and others, and to a much lesser extent fibrates) have been the most successful in changing common but sub-optimal lipoprotein patterns and group outcomes. In the many secondary prevention and several primary prevention trials, several classes of lipoprotein-expression-altering (less correctly termed "cholesterol-lowering") agents have consistently reduced not only heart attack, stroke and hospitalization but also all-cause mortality rates. The first of the large secondary prevention comparative statin/placebo treatment trials was the Scandinavian Simvastatin Survival Study (4S) with over fifteen more studies extending through to the more recent ASTEROID trial published in 2006. The first primary prevention comparative treatment trial was AFCAPS/TexCAPS with multiple later comparative statin/placebo treatment trials including EXCEL, ASCOT and SPARCL. While the statin trials have all been clearly favorable for improved human outcomes, only ASTEROID showed evidence of atherosclerotic regression (slight). Both human and animal trials that showed evidence of disease regression used more aggressive combination agent treatment strategies, which nearly always included niacin.
Diet and dietary supplements
Niacin (vitamin B3), in pharmacologic doses, (generally 1,000 to 3,000 mg/day), sold in many OTC and prescription formulations, tends to improve (a) HDL levels, size and function, (b) shift LDL particle distribution to larger particle size and (c) lower lipoprotein(a), an atherosclerosis promoting genetic variant of LDL. Additionally, individual responses to daily niacin, while mostly evident after a month at effective doses, tends to continue to slowly improve further over time. (However, careful patient understanding of how to achieve this without nuisance symptoms is needed, though not often achieved.) Research work on increasing HDL particle concentration and function, beyond the usual niacin effect/response, even more important, is slowly advancing.http://www.elsevier.com/wps/find/journaldescription.authors/522790/description#description
http://www.healthscout.com/ency/68/38/main.html
Courtesy: Various Sources Over Internet.
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