Abnormal cholesterol levels are considered a major risk factor for heart attack because cholesterol is intimately related to hardening of the arteries, or atherosclerosis. Using data from the Framingham heart study, physicians are able to use risk factors such as high cholesterol to determine a person's 10-year risk of experiencing a heart attack. This risk level helps guide treatment. Risk factors include:

• Age (45 years or older for men; 55 years or older for women, or premature menopause)
• High blood pressure
• Diabetes
• Smoking
• A diet high in saturated fats
• Obesity
• Lack of exercise
• A family history of cardiovascular disease

It is recommended that people at high risk for heart attack aim for a lower LDL cholesterol level than healthy people or people at moderate risk.

Although cholesterol levels are at least partially determined by genetic factors, they are also sensitive to diet and lifestyle. Cholesterol levels can rise to abnormally high levels when someone eats a diet high in saturated fats or trans fats – especially when that person is obese and/or rarely exercises (even moderate exercise has a heart-healthy effect). In particular, trans fats are especially dangerous. Trans fats not only increase levels of “bad” LDL cholesterol, but also decrease “good” HDL levels. This is especially worrisome because trans fats (which prolong the shelf life of processed foods) are common ingredients in potato chips and other snack foods, many types of margarine and shortening, and deep fried and fast foods. As of January 1, 2006, all processed foods in the United States were required to list trans fatty acid levels on their nutritional labels. 

High cholesterol levels can also be caused by a number of different genetic conditions. The most widespread inherited cholesterol disorder is familial hypercholesterolemia (FH). The cholesterol levels of people with this disorder may reach as high as 550 milligrams per deciliter – almost four times the level considered desirable for the average person. With cholesterol this high, people with FH are at a high risk for an early heart attack, regardless of the presence of other risk factors. If FH is suspected, children as young as 2 years of age may be appropriate for a cholesterol screening.

Another genetic condition associated with high cholesterol levels is familial dysbetalipoproteinemia (or familial combined hyperlipoproteinemia) in which cholesterol and triglyceride levels are elevated.

Role of cholesterol in heart disease

Cholesterol is intimately related to the development of atherosclerosis, which is a leading cause of heart attack and death in the United States. During the atherosclerotic process, cholesterol is carried into the inner lining of arteries on LDL molecules. Inside the artery, the cholesterol oxidizes, causing an injury to the artery wall and inflammation. Inside the artery, the cholesterol combines with white blood cells and other materials to create a lipid foam. This lipid foam provides the building material for plaque deposits on the inner wall of arteries, including the coronary arteries in the heart and the carotid arteries in the brain.

As plaque deposits grow, they may attract calcium and other minerals that form a hard, brittle shell over the deposit. If the deposit grows large enough, it may obstruct the flow of the blood through the artery, especially during times of stress or increased demand for oxygen such as exercise. In the heart, this can cause a type of chest pain known as angina. In the brain, this can cause a kind of “mini stroke” known as a transient ischemic attack. Both are very serious warning signs that a plaque rupture may be imminent. If the plaque deposit ruptures, a blood clot may rapidly form, causing a heart attack or stroke.

Although the National Center for Health Statistics reported that Americans’ average total cholesterol levels dropped considerably between 1978 and 1990, the American Heart Association reported that 104.7 million American adults still have borderline-high cholesterol levels (200 to 239 milligrams per deciliter). Of these, about 37 million have high cholesterol levels (240 milligrams per deciliter). Taken together, these statistics mean that the average American’s cholesterol level puts him or her at greater risk of heart disease or stroke.