Atherosclerosis

Atherosclerosis is a form of arteriosclerosis where fatty plaques build up inside artery walls. This chronic condition involves inflammation driven by many cell types, and it is fueled by high levels of LDL cholesterol in the blood. The plaques narrow the arteries, and this disease is the leading cause of death and disability in wealthy nations.

The process often starts silently in childhood. Fibrous and gelatinous lesions can appear in children’s coronary arteries, and fatty streaks show up in juveniles. For decades, the arteries enlarge at plaque sites, so blood flow isn’t affected and there are no symptoms. Most plaque ruptures also don’t cause trouble until a clot severely narrows or blocks an artery. Symptoms usually begin around middle age and depend on which artery is affected. In the coronary arteries, narrowing can bring chest pain (angina), shortness of breath, sweating, nausea, dizziness, or palpitations. It can also cause arrhythmias—the heart beating too fast or too slow. Carotid artery narrowing, which supplies the brain, may cause weakness, confusion, trouble speaking, dizziness, blurred vision, numbness in the face or limbs, severe headache, or loss of consciousness—all signs of stroke. Peripheral arteries in the legs, arms, and pelvis can cause pain and numbness when narrowed. Renal artery narrowing reduces kidney blood flow, leading to chronic kidney disease, which is usually symptom-free until late stages. In 2004, U.S. data showed that for about 66% of men and 47% of women, the first sign of atherosclerotic disease was a heart attack or sudden cardiac death (death within an hour of symptoms). Autopsies of U.S. soldiers killed in the Korean War—average age 22.1 years—found that 77.3% had clear evidence of coronary arteriosclerosis.

The exact cause is unknown and likely involves multiple factors. Risk factors include abnormal cholesterol, high inflammatory markers, high blood pressure, diabetes, smoking (active and passive), obesity, genetics, family history, lifestyle, and poor diet. Plaques are made of fat, cholesterol, immune cells, calcium, and other blood components. The narrowing limits oxygen-rich blood flow. Diagnosis relies on a physical exam, electrocardiogram, and exercise stress test, among other methods. Prevention includes a healthy diet, exercise, not smoking, and maintaining a normal weight. Treatment for established disease may involve cholesterol-lowering drugs like statins, blood pressure medication, and anticoagulants to prevent clots. As the disease worsens, more invasive options include percutaneous coronary intervention, coronary artery bypass graft, or carotid endarterectomy. Some people have a strong genetic predisposition.

Atherosclerosis generally starts young and worsens with age. Almost everyone is affected to some degree by age 65. Though first described in 1575, evidence suggests the disease is genetically ingrained in humans, with origins possibly linked to CMAH gene mutations that occurred over two million years ago in hominin ancestors. The inflammatory process involves LDL particles being retained in the vessel wall’s endothelial cells—this retention may be a cause, an effect, or both of the inflammation. The plaque’s presence makes blood vessel muscle cells stretch to compensate for the extra bulk.