Atherosclerosis

Atherosclerosis is a disease of arterial blood vessels. Veins are not involved unless surgically moved to function as an artery. Atherosclerosis is commonly referred to as a "hardening of blood vessels", but this is not precise. Vascular lesions known as atheromatous plaques or atheromata are formed in the vessel wall, which may reduce or restrict blood flow in the inside of the artery. When the inner covering of an unstable atheroma breaks, it may lead to excessive internal bleeding into the plaque, very often leading to severe health conditions and even death. ‘Athero’ is porridge in Latin, as the plaque changes have a foamy appearance under high power light microscopy. ‘Sclerosis’ denotes hardening.

Atherosclerosis typically begins in later childhood, is usually found in most major arteries, and yet is asymptomatic and not detected by most diagnostic methods during life. It becomes serious when interfering with the circulation of blood to the heart or the brain, and is considered the most important underlying cause of strokes, heart attacks, various heart diseases including congestive heart failure. For about 59% of men and women, the first symptom of atherosclerosis is heart attack.

Most artery flow disrupting events occur at locations with less than 50% lumen narrowing. Cardiac stress testing, the most commonly performed non-invasive testing method for blood flow limitations generally only detects lumen narrowing of about 75% or greater, although some physicians advocate that nuclear stress methods can detect as little as 50%.

Atherogenesis

Atherogenesis refers to the state of having many lesions present in many arteries. It is characterized by remodeling of arteries involving an accumulation of these atheromatous plaques, which contain an excess of fatty cellular membranes within the arterial wall. The plaques are always located between the epithelial lining and muscular portion of the artery wall, typically without producing any narrowing of the artery opening.

The resident cells within the artery wall seem to signal an intrusion and an inflammation response. Monocytes, one of the 5 main types of white blood cells circulating in the blood, enter the artery wall. Within tissues, monocytes change characteristics and are called macrophages. The macrophages ingest oxidized cholesterol, slowly turning into large "foam cells" – so described because of their appearance to accommodate their high lipid content. Foam cells eventually die, and further propagate the inflammatory process.

Small calcium deposits form within vascular smooth muscle cells of the surrounding muscular layer, specifically in the muscle cells adjacent to the atheromas. In time, as cells die, this leads to extracellular calcium deposits between the muscular wall and outer portion of the atheromatous plaques.

Cholesterol is delivered into the wall by minute LDL particles (low density lipoprotein). To attract and stimulate macrophages, the cholesterol must be released from the LDL particles and oxidized, a key step in the ongoing inflammatory process. Additionally, the macrophages must be unable to remove excess cholesterol fast enough, into functioning HDL particles (high density lipoprotein) to avoid becoming foam cells and dying.

A protective fibrous cap normally forms between the fatty deposits and the artery lining (the intima). These capped fatty deposits (atheromas) produce enzymes, which cause the artery to enlarge. The artery becomes expanded and egg shaped, still with a circular opening. If the enlargement is beyond proportion to the atheroma thickness, then an aneurysm is created. This process usually starts in childhood and continues, thereby making the diagnosis very difficult.

However, atheromas within the vessel wall are soft and fragile with little elasticity. Arteries constantly expand and contract with each heartbeat. In addition, the calcification deposits between the outer portion of the atheroma and the muscular wall, lead to a loss of elasticity, stiffening, of the artery as a whole. Although the disease process tends to be slowly progressive over decades, in later stages, it also becomes unstable with repetitive sudden problems, most without obvious symptoms at the time of occurrence. These problems result from instability of the newer, soft atheromas.

If the fibrous cap separating a soft atheroma from the bloodstream within the artery ruptures, atheroma tissue fragments are exposed and released. Atheroma tissue fragments are very clot promoting; they attract blood platelet accumulation and activate the blood clotting system proteins. This leads to a temporary patch covering and partial narrowing (stenosis) within the artery lumen. However, sometimes the combination of atheroma material release, platelet accumulation and accumulation of blood clotting proteins may suddenly create a near complete obstruction. The obstruction, either at the site of rupture, or as a result of debris sent downstream, prevents adequate blood flow to cells downstream. Cells starved for adequate blood supply are injured and may die.

Areas of severe narrowing, detectable by angiography, and to a lesser extent "stress testing" have long been the focus of human diagnostic techniques for heart disease and cardiovascular diseases. However, these methods focus only on detecting severe narrowing, not the underlying atherosclerosis disease. Plaque rupture can lead to artery lumen occlusion within seconds to minutes, and potential permanent debility and sometimes sudden death.

75% lumen stenosis used to be considered by cardiologists as the hallmark of clinically significant disease because it is only at this severity of narrowing of the larger heart arteries that recurring episodes of angina and detectable abnormalities by stress testing methods are seen. However, clinical trials have shown that only about 14% of clinically debilitating events occur at locations with this, or greater severity of narrowing. The majority of events occur due to atheroma plaque rupture at areas without narrowing sufficient enough to produce any angina or stress test abnormalities. Though any artery in the body can be involved, usually only severe narrowing or obstruction of some arteries, those that supply more critically important organs, are recognized. Obstruction of arteries supplying the heart muscle result in a heart attack while obstruction of arteries supplying the brain result in a stroke.

Risk factors

These anatomic, physiological & behavioral risk factors for atherosclerosis are known:

·           Documented atheroma in any artery (unfortunately not detected by most medical tests)

·           Having diabetes or just upper normal blood glucose and insulin levels

·           Dyslipidemia (cholesterol and triglyceride level disturbances):

·           Having a high or elevated blood concentration of low-density lipoprotein (LDL, "bad cholesterol") particles

·           Having a low concentration of functioning high-density lipoprotein (HDL, "good cholesterol") particles.

·           Higher fibrinogen blood concentrations

·           Homocysteine in the upper half of the normal range, and especially elevated levels

·           Aging

·           Tobacco smoking, even just once a day

·           Having close relatives who had heart disease or a stroke at a relatively young age

·           Having high blood pressure

·           Having trouble managing stress, especially anger

·           Being obese (especially central obesity, i.e. fat at waist level more than fat below the skin)

·           Several internal chemical markers indicating ongoing inflammation may also relate to relative risk

Treatment

Most humans develop arteriosclerosis. Usually only "high-risk" patients are advised to change dietary choices, exercise, lose weight, take cholesterol-lowering mediation and lower blood sugar levels. Most of the proven, more effective cholesterol medications are only available by prescription. There is ongoing debate about what dietary changes are wisest and how to adjust these for different people.

If arteriosclerosis leads to symptoms, the symptoms can be treated. Medicines are usually the first 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.

Lipoprotein imbalances, diabetes, high blood pressure, stopping smoking, taking anticoagulants (anti-clotting agents) which target platelets, taking Omega 3 oils from salt-water fish meats, exercising and losing weight are the usual focus of treatments which have proved to be helpful in clinical trials.

Dramatic lowering of lipoprotein levels, including to very abnormally low levels for adults (and especially the smaller lipoprotein particles), and elevating the large particle (HDL) can slow, stop, or even partially reverse the buildup of plaque, as demonstrated in clinical trials. This can be achieved with large daily doses of niacin (B3). Combinations of statins, niacin, cholesterol absorption inhibiting supplements (ezetimibe). Evidence has increased that people with diabetes, though without clinically detectable atherosclerotic disease, have more severe debility from atherosclerotic events over time than even non-diabetics who have already suffered atherosclerotic events. Thus diabetes has been upgraded to be viewed as an advanced atherosclerotic disease equivalent.

Aerobic exercise, weight loss, and dietary changes can also help in major ways, but are often more problematic for many to achieve and continue long term.

Medical treatments often focus predominantly on the symptoms. Over time, the treatments which focus on decreasing the underlying atherosclerosis processes, as opposed to treating the symptoms resulting from the atherosclerosis, have been shown by clinical trials to be more effective.

Other physical treatments, helpful in the short term, include minimally invasive angioplasty procedures to physically expand narrowed arteries and major invasive surgery, such as bypass surgery, to create a blood supply connection which goes around the more severely narrowed areas.

In summary, the key to more effective approaches has been better understanding of the insidious nature of the disease and to combine multiple different treatment strategies, not rely on just one or a few approaches. Additionally, for those approaches, such as lipoprotein transport behaviors, which have been shown to produce the most success, being more treatment aggressive has generally produced better results, both before and especially after people are symptomatic. However treating asymptomatic people remains controversial.