The most common cause of ischemic stroke is atherosclerosis, a buildup of fatty deposits inside the arteries that supply blood to the brain. When one of these deposits ruptures or grows large enough to block blood flow, brain tissue downstream loses its oxygen supply within minutes. Atherosclerosis of the large arteries accounts for roughly 25% to 30% of all ischemic strokes, making it the single most identified cause, though a significant share of strokes still have no clear explanation even after thorough testing.
How Atherosclerosis Leads to Stroke
Atherosclerosis is fundamentally a cholesterol-driven process. It starts when the inner lining of an artery becomes damaged, often from years of high blood pressure, smoking, or elevated blood sugar. Cholesterol particles begin collecting in the damaged area, burrowing into the artery wall. White blood cells follow, absorbing the cholesterol and swelling into what researchers call “foam cells.” Over time, smooth muscle cells migrate into this growing mass and lay down a tough, fibrous cap over what is now a fatty plaque.
The danger comes when that fibrous cap weakens. Ongoing inflammation inside the plaque can thin and erode the cap until it cracks open, exposing the fatty core to the bloodstream. The body treats this like a wound and rapidly forms a blood clot on the surface. That clot can do one of two things: grow large enough to block the artery right where it sits, or break free and travel deeper into the brain’s smaller vessels, plugging them further downstream. Either way, the result is the same. Brain cells that depend on that blood supply start dying.
Other Major Causes of Ischemic Stroke
While large artery atherosclerosis is the leading identified cause, ischemic stroke has several other well-recognized origins. Understanding the full picture matters because treatment and prevention differ depending on what triggered the stroke.
Blood clots from the heart (cardioembolic stroke) account for about 15% to 20% of ischemic strokes. The most common scenario involves atrial fibrillation, an irregular heart rhythm that allows blood to pool and clot in the upper chambers of the heart. These clots can then shoot up into the brain’s arteries. Other cardiac sources include recent heart attacks, severely weakened heart muscle, and damaged or artificial heart valves.
Small vessel disease (lacunar stroke) makes up roughly 10% to 25% of cases, depending on the population studied. These strokes happen when the tiny arteries deep inside the brain become thickened and narrowed, usually after years of high blood pressure. The resulting strokes tend to be small, affecting regions that control movement, sensation, or coordination. Chronic, poorly controlled hypertension is the dominant driver of this type.
Strokes of unknown cause are surprisingly common. About 17% of ischemic strokes meet the criteria for what neurologists call “embolic stroke of undetermined source,” meaning a clot clearly traveled to the brain but doctors cannot pinpoint where it formed, even after cardiac monitoring, blood vessel imaging, and blood tests. Some studies put the proportion of unexplained strokes as high as 24%. Many of these are suspected to involve brief, undetected episodes of atrial fibrillation or small cardiac abnormalities that standard testing misses.
How the Cause Changes With Age
Atherosclerosis and atrial fibrillation dominate in older adults, but the picture looks different for younger people. In adults under 35, nontraditional risk factors play an outsized role. Migraine tops the list in this age group, contributing to nearly 35% of strokes in young women and 20% in young men. Other nontraditional causes include arterial tears (dissections), blood clotting disorders, and autoimmune conditions affecting blood vessels.
Traditional risk factors like high blood pressure and high cholesterol become more important as people move through their 30s and 40s. Among adults 35 to 44, traditional factors account for about 40% of strokes in women and 33% in men. By age 45 to 55, high blood pressure alone is responsible for roughly 27% to 28% of strokes regardless of sex. The older someone is at the time of stroke, the more likely the cause traces back to decades of arterial damage from conventional cardiovascular risk factors.
The Risk Factors That Matter Most
High blood pressure is the single greatest modifiable risk factor for ischemic stroke across all subtypes. People with hypertension face nearly three times the stroke risk of those with normal blood pressure. It accelerates atherosclerosis in large arteries, damages small vessels deep in the brain, and contributes to the heart conditions that generate clots. Controlling blood pressure is the most impactful thing a person can do to lower stroke risk.
The World Health Organization identifies ten modifiable factors that account for most of the global stroke burden: high blood pressure, air pollution, smoking, high LDL cholesterol, diets high in sodium, high fasting blood sugar, kidney dysfunction, excess body weight, physical inactivity, and harmful alcohol use. Smoking alone is linked to roughly two out of every five stroke deaths in people under 65. Most of these risk factors work by either promoting atherosclerosis directly or creating conditions (like diabetes or obesity) that accelerate arterial damage over time.
What makes this list important is that every item on it is changeable. Unlike age, sex, or family history, these are factors that respond to lifestyle changes, medication, or both. The majority of ischemic strokes are not random events. They are the end result of arterial damage that builds quietly for years, and the underlying causes are largely preventable.