High cholesterol (hypercholesterolemia)

What is it?

Cholesterol is a fatty substance that occurs naturally in the body. It performs several vital functions. It is needed to make the walls surrounding the body's cells and is the basic material that is converted to certain hormones. Your body makes all the cholesterol you need. You need only a small amount of fat in your diet to make enough cholesterol to stay healthy.

The fat and cholesterol you eat are absorbed in the intestine and transported to the liver. The liver converts fat into cholesterol, and releases cholesterol into the bloodstream. There are two main types of cholesterol: low-density lipoprotein (LDL) cholesterol (the "bad" cholesterol) and high-density lipoprotein (HDL) cholesterol (the "good" cholesterol).

High levels of LDL cholesterol are linked to atherosclerosis, which is the accumulation of cholesterol-rich fatty deposits in arteries. This can cause arteries to narrow or become blocked, slowing or stopping the flow of blood to vital organs, especially the heart and brain. Atherosclerosis affecting the heart is called coronary artery disease, and it can cause a heart attack. When atherosclerosis blocks arteries that supply blood to the brain, it can cause a stroke.

People with high levels of HDL cholesterol are less likely to develop cardiovascular disease. However, if a person has both a high HDL and high LDL cholesterol level, he or she might still need treatment to lower the LDL level.

According to guidelines established by the government-sponsored National Cholesterol Education Program, the desirable level for LDL cholesterol depends on whether or not a person already has a disease caused by atherosclerosis or diabetes or other risk factors for coronary artery disease. In addition to a high LDL cholesterol level and diabetes, risk factors for coronary artery disease include:

• Being a male older than 45
• Being a female older than 55
• Being a female with premature menopause
• Having a family history of premature coronary artery disease (a father or brother younger than 55 with coronary artery disease or a mother or sister younger than 65 with coronary artery disease)
• Smoking cigarettes
• Having high blood pressure
• Not having enough good cholesterol (high density lipoprotein or HDL)

The ideal cholesterol LDL level is less than 70 milligrams per deciliter. If you have coronary artery disease, peripheral arterial disease or have had a stroke from atherosclerosis, this should be your goal.

However, if you do not have cardiovascular disease and no risk factors for it, an LDL cholesterol level of 100 or even a bit higher may be acceptable.

Your level of HDL cholesterol also matters. People with levels below 40 milligrams per deciliter are more likely to develop atherosclerosis, heart disease and stroke.

Symptoms

Most people with high cholesterol don't have any symptoms until cholesterol-related atherosclerosis causes significant narrowing of the arteries leading to their hearts or brains. The result can be heart-related chest pain (angina) or other symptoms of coronary artery disease, as well as symptoms of decreased blood supply to the brain (transient ischemic attacks or stroke).

About 1 out of every 500 people has an inherited disorder called familial hypercholesterolemia, which can cause extremely high cholesterol levels (above 300 milligrams per deciliter). People with this disorder can develop nodules filled with cholesterol (xanthomas) over various tendons, especially the Achilles tendons of the lower leg. Cholesterol deposits also can occur on the eyelids, where they are called xanthelasmas.

Diagnosis

Your doctor will ask if anyone in your family has had coronary artery disease, high cholesterol or diabetes. The doctor will ask about your diet and if you have ever smoked. He or she will check your blood pressure and look for xanthomas and xanthelasmas. Your doctor can confirm a diagnosis of high cholesterol with a simple blood test.

Expected duration

Your doctor will ask if anyone in your family has had coronary artery disease, high cholesterol or diabetes. The doctor will ask about your diet and if you have ever smoked. He or she will check your blood pressure and look for xanthomas and xanthelasmas. Your doctor can confirm a diagnosis of high cholesterol with a simple blood test.

Prevention

You may help to prevent high cholesterol by staying on a healthy diet and exercising daily. Avoid processed foods, especially those that contain saturated fats. Instead eat more fresh fruits and vegetables, whole-grain breads and cereals, and low-fat dairy products.

Treatment

The initial treatment of high cholesterol should always be lifestyle changes. This means altering your diet and getting more exercise. Some people respond dramatically to dietary changes.

Diet

There is no consensus on the best diet. The most effective diet to lower total and LDL cholesterol is a vegetarian diet. However, this is not an easy diet to follow.

Many people prefer a "Mediterranean style" diet. There is no strict definition for what should be included in this type of diet. In general, this means

• Getting the majority of daily food calories from plant sources, especially fruits and vegetables, grains, beans, nuts, and seeds
• Using olive oil as the principal fat, replacing other fats and oils
• Having some low fat cheese and/or yogurt daily
• Eating fish at least a couple times per week
• Limiting processed foods
• Drinking alcohol in moderation unless medically not indicated. No more than two drinks per day for men and one per day for women.

To maintain a desirable weight, you should take in only as many calories as you burn each day. If you need to lose weight, you need to take in fewer calories than you burn.

People who aren't sure how to follow such a diet may find it useful to work with a health care professional such as a dietitian, nutritionist, doctor or nurse.

In addition to dietary changes, you should get at least 30 minutes of moderate-intensity exercise, such as brisk walking, daily.

Medications

Whether you need medication to lower your cholesterol level depends on how you respond to diet and your personal risk of heart attack and stroke. Doctors primarily prescribe medications to lower LDL cholesterol, and most often a statin drug is  the first choice to lower LDL cholesterol.

Statins are also called HMG-CoA reductase inhibitors. They include lovastatin (Mevacor), simvastatin (Zocor), pravastatin (Pravachol), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). Statins block an enzyme called HMG-CoA reductase, which is necessary for the production of cholesterol.

Statins do much more than lower your LDL cholesterol number. They lower your risk of developing hardening of the arteries (atherosclerosis) and reduce the chance that you will have a heart attack or stroke.

When a person taking a statin does not reach goal, doctors sometimes add ezetimibe. Ezetimibe inhibits absorption of cholesterol from the intestine. By itself the brand name drug is called Zetia. When combined with simvastatin, it’s known as Vytorin.

Newer LDL cholesterol lowering therapies include:

Bempedoic acid. Like statins, bempedoic acid comes as a pill and works by interfering in the same cholesterol pathway. Taken alone, bempedoic acid lowers LDL by about 25%. Bempedoic acid is also available in combination with ezetimibe, sold under the trade name Nexlizet.

PCSK9 inhibitors. They are more potent than statins and combined with a statin dramatically lower blood LDL cholesterol levels. The PCSK9 inhibitors target the protein known as PCSK9, which is made in the liver and regulates LDL. The original ones use antibodies to grab on to and block PCSK9 after it’s been made.PCSK9 inhibitors are much more expensive than most statins. Also they are not available as pills. They must be injected.

Inclisiran. Like the current PCSK9 inhibitors, inclisiran slashes LDL levels by about 50%. Both types of drugs target the protein known as PCSK9, which is made in the liver and regulates LDL. However, inclisiran has a different mechanism of action. It interferes with PCSK9’s genetic blueprint, preventing the protein from being made in the first place. Another difference: the first two PCSK9 inhibitors must be injected once or twice a month, while inclisiran requires just two injections per year.

PCSK9 inhibitors and inclisiran are most useful for people with familial hypercholesterolemia. These people have extremely high cholesterol levels. People with coronary artery disease who either don’t reach goal with a high dose statin drug or cannot tolerate statins because of side effects may also be candidates for one of these newer therapies.

In addition to dietary changes or medication, people with high cholesterol should try to control their other risk factors for coronary artery disease. This means keeping blood pressure at normal levels, not smoking, controlling your blood sugar, maintaining or losing weight and following a regular exercise schedule.

When to call a professional

Because it is possible to have high cholesterol for many years without symptoms, it is important to have your blood cholesterol level checked periodically. Current guidelines recommend that adults older than 20 undergo a full lipid profile once every five years. This test measures LDL and HDL cholesterol and triglyceride levels. If the numbers are outside the desirable range, your doctor may suggest that you change your diet and monitor your cholesterol more frequently.

Prognosis

The effectiveness of following a healthy diet and using medications to lower cholesterol varies from person to person. On average, diet and exercise can lower LDL cholesterol by about 10%. Medications can lower LDL cholesterol by another 20% to more than 50%

Additional info

National Heart, Lung, and Blood Institute (NHLBI)
https://www.nhlbi.nih.gov/