Atherosclerosis is the hardening and narrowing of the arteries, which occurs when cholesterol, fatty deposits, calcium and other waste products buildup on the inner lining of the artery wall. This buildup is referred to as plaque. Plaque makes it difficult for blood to pass through the artery. This problem is accelerated when conditions like high blood pressure and diabetes and activities like smoking damage the artery's smooth, protective, innermost layer, the endothelium. When fat deposits travel in the blood, they can adhere to damaged artery walls much easier than a smooth, healthy endothelium. In addition, the normally flexible arteries lose some of their elasticity as we age, further complicating this problem.

As plaque builds up and the walls harden, the arteries narrow making it difficult for blood to pass. In some instances a clot forms at the site and blocks the passage of oxygenated blood, a situation that can have deadly consequences if not treated quickly. If the plaque ruptures, the result can also be fatal, because the ruptured plaque can cause blood clots that block the flow of blood in that artery or create clots that travel to other parts of the body. When blood flow to the heart is blocked, a heart attack or myocardial infarction (MI) occurs. If blood is blocked from traveling to the brain, a stroke occurs.

The main cause of heart disease is atherosclerosis.