Increasingly, 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. Eventually, the arterial wall becomes permeable, allowing toxic LDL molecules to migrate into the inner lining of the artery. The white blood cells combine with LDL cholesterol molecules to form a lipid foam. This lipid foam is the main component of arterial plaque streaks, which appear early in the atherosclerotic process.  

During this 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.

Researchers have also been investigating the link between infection/inflammation and CAD. Based on the connection between inflammation and immune system activation, researchers have hypothesized that chronic, inflammatory conditions, such as rheumatoid arthritis and persistent bacterial infection, may contribute to atherosclerosis.