Atherosclerosis is a condition where fatty deposits, called plaques, build up inside the walls of your arteries, gradually narrowing them and restricting blood flow. It develops over decades, often without any symptoms, and is the underlying cause of most heart attacks and strokes. Cardiovascular diseases driven by atherosclerosis account for roughly 20.5 million deaths worldwide each year, a number projected to reach 35.6 million by 2050.
How Plaques Form Inside Your Arteries
Atherosclerosis begins with damage to the inner lining of an artery. This lining, called the endothelium, is a single-cell-thick barrier that normally keeps blood flowing smoothly and prevents harmful substances from seeping into the artery wall. When that barrier is injured or stressed, it stops functioning properly. The artery wall becomes prone to constriction, allows fatty molecules to infiltrate, and starts attracting immune cells and blood-clotting particles.
Once the lining is compromised, LDL cholesterol (the “bad” cholesterol) slips beneath it and lodges in the artery wall. The body treats this as an injury. Chemical signals draw immune cells called monocytes from the bloodstream, pulling them through the damaged lining. Once inside the artery wall, these monocytes transform into macrophages, which are essentially cleanup cells. They engulf the trapped cholesterol, swelling up into what scientists call foam cells. Clusters of foam cells form a visible fatty streak, the earliest stage of a plaque.
Over time, smooth muscle cells migrate into the area and produce a tough, fibrous cap over the fatty core. Calcium deposits accumulate. What started as a thin streak of fat-filled immune cells becomes a hardened, complex structure that bulges inward and narrows the artery. This entire process is driven by inflammation at every stage, from the initial lining damage through plaque growth to the dangerous final event: a plaque breaking open.
Stable Plaques vs. Dangerous Ones
Not all plaques are equally threatening. A stable plaque has a thick fibrous cap, relatively few inflammatory cells, and a small fatty core. It may narrow an artery enough to cause symptoms during physical activity, but it’s unlikely to rupture suddenly.
A vulnerable plaque is different. It has a large pool of lipids, a thin cap that’s been weakened by inflammatory enzymes breaking down its collagen, and it’s packed with macrophages. Inflammatory signals also increase the production of a powerful clotting trigger within the plaque. When the thin cap tears, blood is exposed to this material, and a clot forms rapidly. That clot can block the artery entirely in seconds, cutting off blood flow to the heart, brain, or limb it supplies.
There’s a second, less well-known mechanism. Some plaques cause problems not because the cap ruptures, but because the surface lining erodes away. These eroded plaques look quite different: they contain more smooth muscle cells and structural tissue but fewer inflammatory cells and less fat. Neutrophils, another type of immune cell, play a key role by casting out web-like structures that promote clotting on the exposed surface. Both rupture and erosion can trigger heart attacks, but they involve distinct biology.
Where It Happens and What You Feel
Atherosclerosis can develop in any large or medium-sized artery, but the symptoms you experience depend entirely on which arteries are affected. Many people have significant plaque buildup with no symptoms at all until a major event occurs.
Heart (Coronary Arteries)
Plaque in the arteries feeding the heart muscle causes coronary heart disease. Symptoms include chest pain or pressure (angina), shortness of breath, dizziness, cold sweats, extreme fatigue, and nausea. Chest pain typically worsens with exertion and eases with rest. A complete blockage causes a heart attack. Ischemic heart disease is projected to remain the leading cause of cardiovascular death globally through at least 2050, responsible for an estimated 20 million deaths that year alone.
Neck (Carotid Arteries)
Plaque in the carotid arteries, which supply blood to the brain, often produces no warning signs. A doctor may hear a whooshing sound called a bruit through a stethoscope. Many people discover they have carotid artery disease only after a mini-stroke (transient ischemic attack) or a full stroke, which can cause sudden numbness, confusion, trouble speaking, or vision loss.
Legs (Peripheral Arteries)
Peripheral artery disease causes pain, aching, heaviness, or cramping in the legs during walking or climbing stairs that eases when you stop and rest. This pattern is called intermittent claudication. The discomfort is most common in the calf but can appear in the buttocks, thighs, or feet. Some people with peripheral artery disease have no leg symptoms at all, or they experience them differently, like numbness or weakness.
What Drives the Process
Several factors accelerate or trigger the endothelial damage that starts atherosclerosis. High LDL cholesterol is the most direct driver: more LDL in the blood means more cholesterol available to infiltrate artery walls. High blood pressure physically stresses the artery lining, especially at branch points where blood flow is turbulent. Smoking damages the endothelium through chemical toxicity and promotes inflammation and clotting. Diabetes accelerates plaque formation through multiple pathways, including elevated blood sugar damaging vessel walls.
A cluster of risk factors known as metabolic syndrome dramatically raises cardiovascular risk. You meet the criteria if you have three or more of the following five conditions: a waist circumference of 40 inches or more for men (35 inches for women), triglycerides at or above 150 mg/dL, low HDL cholesterol, blood pressure at or above 130/85, or fasting blood sugar at or above 100 mg/dL. Each factor on its own contributes to atherosclerosis, but in combination their effects compound.
How Atherosclerosis Is Detected
Because atherosclerosis is silent for years or decades, screening plays a critical role. One of the most useful tools is a coronary artery calcium (CAC) scan, a quick CT scan that measures calcium deposits in heart arteries. The score directly reflects how much plaque has accumulated.
A CAC score of zero means no detectable calcified plaque, which is associated with very low short-term cardiovascular risk. Scores between 1 and 99 indicate mild plaque. Scores between 100 and 300 signal moderate buildup that warrants closer attention and often changes treatment decisions. Scores above 300 are associated with 10-year event rates as high as 13% to 26%. Scores above 1,000 carry even higher risk of heart disease, stroke, and death from all causes compared to scores in the 400 to 999 range.
Other common assessments include cholesterol blood tests, blood pressure measurement, ankle-brachial index (comparing blood pressure in the ankle to the arm to check for peripheral artery disease), and ultrasound of the carotid arteries. Stress tests can reveal whether coronary narrowing is limiting blood flow during exercise.
How It’s Managed
Treatment focuses on slowing plaque progression, stabilizing existing plaques so they’re less likely to rupture, and reducing the chance of a heart attack or stroke. The foundation is lifestyle change: quitting smoking is one of the most impactful steps, as it reduces the risk of developing atherosclerosis, slows progression of existing disease, and lowers the risk of limb complications and death. Regular physical activity, a diet low in saturated fat and processed foods, and maintaining a healthy weight all improve the metabolic environment driving plaque growth.
For people with established atherosclerotic disease, current guidelines recommend high-intensity cholesterol-lowering medication aiming for at least a 50% reduction in LDL cholesterol, with a target below 70 mg/dL. For the highest-risk patients, the target drops to below 55 mg/dL, though only about 21% of those patients actually achieve that level. Blood pressure management targets below 130/80. Most patients are also placed on a blood-thinning medication to reduce the risk of clot formation on existing plaques. For those with diabetes, blood sugar management becomes an essential part of the treatment plan.
When narrowing is severe enough to significantly limit blood flow or threaten a limb or organ, procedures to physically open the artery may be necessary. These range from balloon angioplasty with stent placement to surgical bypass, depending on the location and extent of disease. But even after these procedures, the underlying atherosclerosis remains, making ongoing medical management and lifestyle changes essential to prevent new events.