Hypercholesterolemia: Causes and Management

Two in five Americans have harmful levels of cholesterol in their blood. Hypercholesterolemia, or high cholesterol, remains one of the significant risk factors for heart disease and stroke, two leading causes of death in the United States. Knowing how to prevent and manage the condition is vital, as there are almost no symptoms.

What is hypercholesterolemia?

Hypercholesterolemia, also known as dyslipidemia, is a condition marked by high amounts of cholesterol in the blood. It is defined as a concentration of total blood cholesterol over 200 mg/dL and affects about 40% of adults in the United States.

What is cholesterol? Cholesterol is a type of dietary fat that the body uses to repair old and build new cells. It travels through the bloodstream and is usually attached to proteins. The mix of cholesterol and protein is called a "lipoprotein." Two of the more important lipoproteins related to hypercholesterolemia are:

• High-density lipoprotein (HDL), commonly known as "good" cholesterol, carries cholesterol to the liver, where it gets utilized or broken down.
• Low-density lipoprotein (LDL), or "bad" cholesterol, carries cholesterol throughout your body. If there is too much of it, cholesterol starts to build up in the arteries’ walls, forming plaques that narrow them.

What are the causes of hypercholesterolemia?

The most prominent causes of high blood cholesterol include the following::

• Poor diet. Consuming large amounts of saturated and trans fats.
• Obesity. A body mass index (BMI) of 30 or greater.
• Lack of exercise. Physical activity has been found to increase HDL and lower LDL levels.
• Smoking. Cigarette smoking may reduce HDL and increase levels of LDL.
• Drinking. Excessive use of alcohol may lead to an increase in the total cholesterol level.
• Stress. Being under a lot of stress triggers the release of hormones that increase the production of cholesterol.
• Genetics. Some people have a genetic makeup that makes it challenging to reduce LDL. This is called “familial hypercholesterolemia”.

How is hypercholesterolemia treated?

The backbone of hypercholesterolemia treatment is lifestyle and dietary modifications. In some cases, your doctor may also prescribe medications.

• Lifestyle changes. Exercise for at least 20 minutes a few times per week and increase your overall activity levels, like walking or biking to work. Start the journey of losing extra pounds by exercising, modifying your diet, and keeping track of your caloric intake. Quit smoking and drink alcohol in moderation.
• Dietary changes. Reduce or eat less saturated and trans fats and refined carbohydrates. This includes highly processed foods such as refined vegetable oils, baked goods, and deep-fried foods. Choose healthier fat sources, such as lean meats, nuts, and oils high in omega-3, such as olive oil. Consume whole foods, including fruits and vegetables, that contain plenty of soluble fiber. Eat fish high in omega-3 fatty acids and limit your salt intake.
• Medications. Related to hypercholesterolemia, several medications are available for the treatment of dyslipidemia:
  • Statins block the production of cholesterol in the liver.
  • Cholesterol absorption inhibitors such as ezetimibe limit the amount of fat absorbed from food and are often used with statins.
  • PCSK9 inhibitors help the liver remove LDL from your blood by blocking a protein called PCSK9.
  • Fibrates reduce the levels of triglycerides (a type of fat in your blood) and increase the concentration of HDL.
  • Nicotinic acid (niacin) decreases the concentration of LDL and triglycerides and increases HDL levels.
  • Inclisiran lowers the circulating levels of LDL by targeting PCSK9. This is one of the most recently approved drugs for treating hypercholesterolemia.

Emerging therapies

As discussed, across the globe, hypercholesterolemia is a major risk factor for heart disease, also referred to as cardiovascular disease. It can be managed through vigorous lifestyle and dietary changes. Some people may also need to work with their healthcare provider to find out which drugs will work for them. While some  FDA-approved drugs are already available, several drugs are under development for treating high blood cholesterol. These include:

• ARO-APOC3. This therapy has been found to reduce plasma triglyceride and apolipoprotein C3 levels. Effectively, apolipoprotein C3 helps encourage fat levels in your blood. Reducing its presence is one of the most common techniques to help reduce hypercholesterolemia.
• Volanesorsen. This experimental drug holds promise to reduce the levels of LDL. It has been approved for use in the European Union but not in the United States.
• Pemafibrate. The experimental selective peroxisome proliferator-activated receptor alpha modulator might be able to reduce plasma triglyceride levels.
• Vaccines against PCSK9. This immune therapy might trigger the production of host anti-PCSK9 antibodies.

As these therapies are fairly recent, there are many ongoing clinical trials to evaluate their safety and effectiveness. If you are interested in exploring these emerging therapies, be sure to find ways to participate by talking to your healthcare provider or search for a clinical trial at ClinicalTrials.gov.