What is Hypercholesterolemia?
Cholesterol is a waxy substance that travels throughout the body in blood. It is important because it helps create the outer coating of our cells. It also aids the body in making vitamin D and certain hormones.1
The body makes the cholesterol it needs, but you also get it in your diet. However, excessively high levels of cholesterol in your blood (hypercholesterolemia) can be dangerous. Over time, cholesterol and fat can build up in the inner walls of the arteries that supply blood to your heart. This causes narrowing of these arteries, a major cause of heart (or cardiovascular) disease.1
Cardiovascular disease (CVD) remains the leading cause of death and a major cause of disability. There are many causes and factors associated with CVD that are strongly influenced by lifestyle, particularly an unhealthy diet, tobacco use, and sedentary habits; in addition to having high blood pressure and diabetes.2
Familial Hypercholesterolemia (FH)
Familial Hypercholesterolemia or “FH” is a disease passed down from generation to generation. About 1 in 500 people in the world have FH. If one parent has FH, there is a 50% chance that their son or daughter will also have it.3 This is called heterozygous FH. When both parents have FH, their children inherit the defective gene from both parents. This is called homozygous FH. Homozygous FH is much rarer, but is more severe and more difficult to treat.
Heterozygous FH: One parent passed the gene to you
Homozygous FH: Both parents passed the gene to you
In FH there is a malfunction in the gene that codes for the LDL-receptor. This receptor sits on the surface of cells. It can be thought of as an arm that reaches out and grabs cholesterol in the blood. If defective, the LDL-receptor cannot remove cholesterol from the blood. This results in high or very high blood cholesterol levels, and higher risk for cardiovascular events such as heart attacks.3
Diagnosing FH at a young age is very important. Treatment is much more effective when started early before cholesterol has begun to collect very much on blood vessel walls.3
Cholesterol in our Body and Food
Buildup of LDL-C, or “bad cholesterol” over time leads to the narrowing of arteries—a condition called atherosclerosis. This increases the risk of CVD.2 Excess amounts of dietary fats get absorbed by the body and raise the level of LDL-C in the blood. Saturated and trans fats in the diet raise blood levels of LDL-C, thereby increasing the risk of heart disease. Foods high in animal fat (full-fat milk, cheese, meat); foods prepared with butter, shortening, or partially hydrogenated oils; and sweets (cookies and cakes) are often the main culprits.1
As LDL-C in the blood goes up, the risk of atherosclerosis increases.4 Other types of cholesterol include high-density lipoprotein-cholesterol (HDL-C, or “good cholesterol”) and triglycerides. HDL-C is not particularly associated with atherosclerotic risk, but is thought to help eliminate bad cholesterol from the body.5 While triglycerides do not directly cause atherosclerosis, they are a marker of a higher risk due to their association with other lipoproteins.6
Lifestyle and Medication:
Primary Treatments for High Cholesterol
- Diet changes
While exercise and dietary changes are important initial changes for lowering cholesterol, medication is often needed, particularly in patients with FH. Statins and other drugs have been clearly shown to decrease LDL-C in the blood by reducing the liver’s production of cholesterol. Other data have shown the beneficial effects of statins and non-statin agents, such as ezetimibe or PCSK9 inhibitors in further reducing cholesterol.7–9 Another recently-approved drug – evinacumab – is approved specifically for the homozygous form of FH. Only about 1,300 people in the US have homozygous FH, but it is characterized by extremely high LDL-C. Patients with this type of FH are at risk for premature CVD and cardiac events as early as their teenage years.10
- American College of Cardiology (ACC) CardioSmart. High cholesterol. Last Edited September 8, 2021. www.cardiosmart.org/Heart-Conditions/High-Cholesterol
- Agabiti Rosei E, Salvetti M. Management of hypercholesterolemia, appropriateness of therapeutic approaches and new drugs in patients with high cardiovascular risk. High Blood Press Cardiovasc Prev. 2016;23:217-230.
- Ose L. National Lipid Association (NLA). Familial Hypercholesterolemia. An Educational Booklet for Patients with Familial Hypercholesterolemia. http://nlaresourcecenter.lipidjournal.com/Content/PDFs/FA-Patient-Book-English.pdf
- Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38:2459-2472.
- Goldstein JL, Ho YK, Basu SK, Brown MS. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci USA. 1979;76:333-337.
- Talayero BG, Sacks FM. The role of triglycerides in atherosclerosis. Curr Cardiol Rep. 2011;13:544-552.
- Zheng C, Khoo C, Furtado J, Sacks FM. Apolipoprotein C-III and the metabolic basis for hypertriglyceridemia and the dense low-density lipoprotein phenotype. Circulation. 2010;121:1722-1734.
- Dadu RT, Ballantyne CM. Lipid lowering with PCSK9 inhibitors. Nat Rev Cardiol. 2014;11:563-575.
- Farnier M. PCSK9: From discovery to therapeutic applications. Arch Cardiovasc Dis. 2014;107:58-66.
- Stiles S. FDA Approves Orphan Drug Evinacumab-dgnb for Homozygous FH. Medscape Medical News. February 11, 2021. https://www.medscape.com/viewarticle/945719