Also known as “hardening of the arteries,” atherosclerosis is a disease in which the arteries are hardened and narrowed as a result of plaque, which has built up along the inside of the artery walls. The disease is a chief contributor to cardiovascular disease, the leading cause of death among men and women in the United States. According to the American Heart Association 2007 Heart and Stroke Statistical Update, atherosclerosis accounts for nearly 75 percent of all deaths from cardiovascular disease.

Millions of Americans have been diagnosed with atherosclerosis, and millions more have the disease but do not know it. Men, African-Americans and all individuals over the age of 65 are especially prone to developing advanced atherosclerosis. In addition, the following factors increase the risk of atherosclerosis, particularly in people with more than one risk factor:

In recent years, scientists have made great strides forward in understanding the atherosclerotic process. The disease tends to be gradual, often taking decades before the affected person is in danger of cardiovascular or cerebrovascular problems. In the early stages of the disease, the inner lining of the artery (endothelium) is damaged. This causes white blood cells to gather at the site of the injury. This in turn provokes an inflammatory immune response that causes further damage to the artery wall. Over time, the endothelium is compromised and large, toxic LDL cholesterol molecules can penetrate into the artery wall. The white blood cells and cholesterol combine to form a lipid foam. In the early stages of atherosclerosis, these fatty streaks are present on the arterial wall as plaque deposits. Fatty streaks have been detected in the arteries of teenagers who were genetically predisposed to develop atherosclerosis.

Over time, the plaque may calcify, or form a hardened "shell." This reduces the supple artery's ability to contract and expand and narrows the artery, thus reducing the amount of blood that can flow through it. A narrowed artery is said to suffer from stenosis, while a completely blocked artery is described as occluded. If the plaque deposit ruptures, a blood clot can form at the site of the rupture, or pieces of the plaque can travel through the arteries until they eventually cause a blockage.

If the affected artery is one of the coronary arteries (located on the surface of the heart), then a lack of oxygen-rich blood to the heart (cardiac ischemia) could cause coronary artery disease (CAD) and, consequently, increase an individual’s risk of the following:

• Angina. A certain type of chest pain, pressure or vague discomfort that indicates an increased risk of a heart attack.
  
  
• Heart attack. An event that results in permanent heart damage and can result in death. It is also known as a myocardial infarction, because part of the heart muscle (myocardium) may die (infarction) from lack of oxygen.
  
  
• Cardiac arrest. A life-threatening situation in which the heart abruptly stops. The person must be treated with a defibrillator within minutes in order to survive.
  
  
• Sudden cardiac death. Death due to cardiac arrest.

Atherosclerosis is also dangerous in arteries other than the coronary arteries. For instance, blocked carotid arteries in the neck or cerebral arteries in the brain can lead to a stroke. Additionally, inadequate blood flow to the lower extremities can cause peripheral arterial disease – a condition that can lead to poor circulation, leg pain with walking (claudication), non-healing leg ulcers and gangrene.

Biology of atherosclerosis

A normal artery has many layers. The adventitia is the outermost wall, made up of a fibrous material as well as smooth muscle cells. The media is the central layer of the artery, consisting of multiple layers of smooth muscle cells. The intima is an innermost layer of the artery and is made up of connective tissue, with endothelial cells acting as a lining inside the arteries.

Injury to the endothelial cells is the first step toward atherosclerosis. Researchers have uncovered evidence that atherosclerosis begins with a local injury to the endothelial cells. This injury attracts white blood cells, which provoke a natural inflammatory immune response. Inflammation is central to the healing process. However, in this case, the inflammation occurs in an inappropriate area and tends to further damage the endothelial layer.

In time, the endothelial layer becomes compromised, allowing large, unstable LDL cholesterol molecules to penetrate the endothelium and reach the inner layers of the artery. There, the LDL molecules are exposed to free radicals that are produced as a byproduct of the immune response. This results in the oxidation of the LDL. Oxidized LDL releases a number of toxins into the arterial wall that exacerbates the injury, thus recruiting more white blood cells, which further damage the artery and allow more LDL to penetrate the arterial wall.

Gradually, these substances, including LDL molecules, toxins and white blood cells, form a lipid foam. This lipid foam is the building block of arterial plaque deposits. The foam expands on the arterial wall, slowly growing. Throughout the early stages of this process, the person will likely experience no symptoms.

Once exposed to the circulating blood, the lipid streaks attract minerals such as calcium, which form a hard shell over the plaque deposit. This process is similar to the calcification of plumping pipes, with calcium deposits growing on the inside of arterial walls. In recent years, researchers have made great strides forward in classifying and understanding the nature of the calcified plaque deposits. Deposits covered with a hard, smooth layer of minerals are more stable than those with a soft interior and a brittle and bumpy calcium deposit. A plaque deposit can grown undetected for many years. In fact, some stable plaque deposits can almost totally occlude their artery with no effect. In response to the reduced capacity in that artery, blood is shunted through nearby arteries via collaterals to supply oxygen to the jeopardized heart muscle.

However, plaque deposits that occur in major coronary arteries (e.g., the left main descending coronary artery) or the carotid arteries can pose a significant health hazard. For unknown reasons, a plaque deposit can rupture. When the deposit ruptures, pieces of calcified plaque shower downstream in the artery, where they may become lodged in smaller arteries, thus rapidly blocking blood flow. Alternatively, circulating blood platelets can detect the site of the rupture and initiate a clotting cascade. In a normal skin injury, this cascade forms a scab, or blood clot. However, when this occurs inside an artery, the result can be the relatively rapid loss of blood flow to organs and tissues beyond the blockage. The result may be a heart attack or stroke.