There are many theories about the root cause of atherosclerosis. Studies have shown a genetic component to the disease, and a family history of coronary artery disease is a strong predictor for atherosclerosis.

Other strongly associated risk factors include:

• High blood pressure (hypertension)
• Smoking
• Diabetes
• Advanced age
• Obesity
• Lack of exercise
• Poor diet

A number of emerging risk factors, especially inflammatory markers, have also attracted considerable attention in recent years. Inflammation has been singled out as an underlying factor that both causes and accelerates atherosclerosis. Atherosclerosis itself is an inflammatory process, characterized by activation of the body's inflammatory cascade at the level of the endothelium. This inflammatory cascade is part of a normal immune response. It is thought that atherosclerosis is characterized by a local immune response caused by damage to the arterial wall. As a result, white blood cells gather at the site of the injury and release inflammatory chemicals (such as interleukin-6 [IL-6]) that further damage the arterial wall and attract more white blood cells.

During the atherosclerotic process, the body releases a number of inflammatory markers that can be measured in the blood. These include C-reactive protein, IL-6, lipoprotein-associated phospholipase A2 and others. Currently, only C-reactive protein is regularly used as a marker of heart disease risk, while researchers are examining the role of other inflammatory markers. So far, the data on C-reactive protein has been somewhat mixed. Some studies have found that C-reactive protein is a useful independent measure of heart attack risk, while others have found conflicting results. The source of this conflict might lie in the fact that C-reactive protein is not specific: levels are raised in response to inflammation and injury anywhere in the body. Nevertheless, some physicians recommend monitoring C-reactive protein to measure inflammation in the body.

In the future, lipoprotein-associated phospholipase A2 might emerge as another important tool to measure risk of heart attack. Studies have found that elevated levels of this enzyme are a strong risk factor for heart attack, even in the presence of other normal LDL cholesterol levels.

Another marker of interest is homocysteine. There is considerable debate over the role of homocysteine in heart disease. Homocysteine is an amino acid that is produced as a byproduct of other chemical reactions in the body. High levels of homocysteine may be related to the development of atherosclerosis because it is thought that the amino acid may damage the endothelium and increase the risk of blood clots. Numerous studies have also shown that people with elevated homocysteine are at greater risk for heart attack, stroke and other cardiovascular problems.

However, researchers have been unable to determine if elevated homocysteine levels are caused by heart disease, or if they cause heart disease. Also, two large, well-designed studies have recently shown that moderately lowering homocysteine among people with diabetes and existing heart disease had no effect on lowering risk for cardiovascular events.

At this point, the American Heart Association has not identified elevated homocysteine as a major risk factor for heart disease and does not recommend widespread use of folic acid and vitamin B supplements to lower homocysteine. However, because of the association between homocysteine and heart disease, people are advised to obtain these important nutrients through a healthy diet that includes fruits, vegetables, whole grain and fortified grain products. Additionally, people who have a family history or personal history of heart disease but lack other well-defined risk factors, such as smoking or obesity, should consider monitoring their homocysteine levels.