Atherosclerosis, the gradual buildup of fatty deposits inside artery walls, is the leading cause of cardiovascular disease. It underlies the majority of heart attacks, strokes, and peripheral artery disease cases worldwide. What drives atherosclerosis is not a single factor but a combination of conditions, with high blood pressure (hypertension) and high cholesterol sitting at the top of the list.
How Atherosclerosis Develops
Atherosclerosis begins with damage to the inner lining of your arteries. This lining, called the endothelium, normally keeps blood flowing smoothly and prevents harmful substances from seeping into the artery wall. When it’s disrupted by high blood pressure, high blood sugar, smoking, or chronic inflammation, it loses the ability to maintain that balance. The artery wall becomes vulnerable to vasoconstriction, lipid infiltration, and oxidative stress.
Once the lining is compromised, LDL cholesterol particles slip through into the artery wall. There, stripped of the antioxidants that protect them in the bloodstream, they become oxidized. Oxidized LDL is intensely inflammatory. It triggers the immune system to send white blood cells (monocytes) into the artery wall, where they gorge on the oxidized cholesterol and transform into swollen “foam cells.” These foam cells cluster together to form what’s known as a fatty streak, the earliest visible sign of atherosclerosis.
Over years and decades, these fatty streaks grow. Smooth muscle cells migrate into the area, fibrous tissue accumulates, and calcium deposits harden the mass into a full plaque. The artery narrows, restricting blood flow. If a plaque ruptures, it can trigger a blood clot that blocks the artery entirely, causing a heart attack or stroke in minutes.
Hypertension: The Top Metabolic Risk Factor
High blood pressure contributes more to cardiovascular disease than any other single modifiable risk factor. In a large population-based study published in eClinicalMedicine, hypertension accounted for roughly 14% of the population-attributable fraction of cardiovascular events, meaning that if hypertension were eliminated, about 14% of all cardiovascular disease cases could theoretically be prevented. That figure was the highest of any individual factor studied, across all age groups.
The damage is mechanical. Elevated pressure forces blood against artery walls with excessive force, gradually injuring the endothelial lining and accelerating every step of the atherosclerotic process. It also causes the heart muscle to thicken over time as it works harder to pump against the resistance, eventually weakening the heart itself.
Current guidelines define normal blood pressure as below 120/80 mmHg. The American Heart Association recommends keeping sodium intake below 1,500 mg per day, because sodium directly raises blood pressure. Cutting sodium by about 2,300 mg per day lowers systolic blood pressure by roughly 5 to 7 points in people with hypertension, enough to meaningfully reduce cardiovascular risk.
High Cholesterol and LDL Targets
Elevated LDL cholesterol is the fuel for atherosclerosis. The more LDL circulating in your blood, the more likely it is to infiltrate artery walls and kick off plaque formation. Clinical guidelines set different LDL targets depending on your overall risk profile. If you have no other risk factors, keeping LDL below 130 mg/dL is the general goal. For people with two or more risk factors, the target drops to below 100 mg/dL. Those with established heart disease, diabetes, or chronic kidney disease should aim for below 70 mg/dL, and people with progressive cardiovascular disease may need levels below 55 mg/dL.
These targets exist because lowering LDL doesn’t just slow atherosclerosis. It can stabilize existing plaques, making them less likely to rupture and cause a sudden heart attack or stroke.
Smoking and Cardiovascular Risk
Smoking is the leading behavioral risk factor for cardiovascular disease across all age groups. It increases the risk of coronary heart disease by two to four times and the risk of stroke by the same margin, according to the CDC. Cigarette smoke damages the endothelial lining directly, promotes oxidation of LDL cholesterol, raises blood pressure, and makes blood more prone to clotting. It essentially accelerates every phase of atherosclerosis simultaneously.
The good news is that quitting reverses much of the damage over time. Within a few years of stopping, your cardiovascular risk begins dropping substantially, and over a decade it approaches that of someone who never smoked.
Abdominal Obesity and Diabetes
Abdominal obesity, the fat stored around your midsection rather than your hips or thighs, is the second most impactful metabolic risk factor, responsible for nearly 10% of the population-attributable fraction of cardiovascular events. This type of fat is metabolically active, releasing inflammatory signals and hormones that raise blood pressure, increase blood sugar, and worsen cholesterol profiles.
Diabetes compounds the problem. Chronically elevated blood sugar damages blood vessels directly and accelerates the buildup of cholesterol-laden plaque. Coronary artery disease is the most common cardiovascular complication of diabetes, and the combination of high blood sugar with other metabolic risk factors creates a particularly aggressive form of atherosclerosis.
Physical Inactivity and Diet
A sedentary lifestyle contributes to nearly every upstream risk factor for cardiovascular disease: it promotes weight gain, raises blood pressure, worsens cholesterol ratios, and increases insulin resistance. The Surgeon General recommends at least 2 hours and 30 minutes of moderate-intensity exercise per week, such as brisk walking or cycling. That threshold is enough to produce measurable improvements in blood pressure, cholesterol, and blood sugar control.
Diet quality matters independently of weight. High sodium intake raises blood pressure. Diets rich in saturated fat and ultra-processed foods elevate LDL cholesterol. Conversely, diets emphasizing vegetables, fruits, whole grains, and unsaturated fats from sources like fish and nuts consistently lower cardiovascular risk in large studies. The specific mechanisms overlap: better food choices reduce inflammation, improve the cholesterol particles circulating in your blood, and help maintain a healthy endothelial lining.
Air Pollution: A Less Obvious Contributor
Environmental factors play a larger role than most people realize. Fine particulate matter (tiny particles from vehicle exhaust, industrial emissions, and wildfires) enters the lungs and triggers systemic inflammation that damages blood vessels throughout the body. Air pollution contributed to an estimated 2.46 million cardiovascular deaths globally in 2021, according to an analysis of Global Burden of Disease data. For people living in heavily polluted areas, this is a risk factor that’s largely outside individual control but increasingly recognized as a driver of more severe heart disease.
How Risk Factors Interact
Cardiovascular risk isn’t simply additive. Having both high blood pressure and high cholesterol doesn’t just double your risk; the two conditions amplify each other. High pressure damages the artery lining, making it easier for LDL to infiltrate. High LDL ensures there’s plenty of cholesterol available to form plaques once the lining is compromised. Layer on smoking, diabetes, or obesity, and the process accelerates further. This is why prevention guidelines focus on managing multiple risk factors at once rather than treating any single one in isolation.
The practical takeaway: atherosclerosis is both the mechanism and the leading cause of cardiovascular disease, but it’s driven by a cluster of conditions you can largely influence. Controlling blood pressure, keeping LDL cholesterol in a healthy range, not smoking, staying physically active, and maintaining a reasonable weight collectively address the root of the problem rather than any one branch of it.