What is Hypercholesterolemia?
Cholesterol is a waxy, fat-like substance that travels throughout the body in blood. It is important because it helps create the outer coating of our cells and aids the body in making vitamin D and certain hormones.1
The body makes the cholesterol it needs; however, you also get it in your diet. A high level 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, causing a 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
Control of lipid (fat in blood) levels is one of the most effective strategies for CVD prevention. It is well understood that the buildup of cholesterol-rich low-density lipoprotein-cholesterol (LDL-C, or “bad cholesterol”) over time leads to the narrowing of arteries—a condition called atherosclerosis—that 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 that are high in animal fat (full-fat milk, cheese, meat) and/or are prepared with butter, shortening, or partially hydrogenated oils (cookies and cakes) are often the main culprits.1
Research has confirmed that LDL-C and other apoB-containing lipoproteins, such as very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and lipoprotein (a), are involved in atherosclerosis.3 As the level of LDL-C in the blood goes up, the risk of atherosclerosis increases.4
Higher levels of another source of cholesterol—high-density lipoprotein-cholesterol (HDL-C, or “good cholesterol”)—are not associated with atherosclerotic risk. HDL-C is thought to remove cholesterol from peripheral vessels and carry it to the liver to be eliminated 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 To avoid atherosclerosis, triglyceride-rich lipoproteins must be cleared from the bloodstream and broken down by the liver.6,7
Lowering LDL-C reduces atherosclerosis—the cause of several types of cardiovascular events—and helps maintain the structural integrity of the blood vessel.
Statins and other drugs have been 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 (inhibits intestinal cholesterol absorption) or PCSK9 inhibitors (help increase LDL-C clearance from the blood), in further reducing cholesterol levels.8–10
- American College of Cardiology (ACC) CardioSmart. High cholesterol. www.cardiosmart.org/Heart-Conditions/High-Cholesterol. Accessed November 20, 2019.
- 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.
- Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473:317-325.
- 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.
- Ooi EM, Barrett PH, Chan DC, Watts GF. Apolipoprotein C-III: understanding an emerging cardiovascular risk factor. Clin Sci (Lond). 2008;114:611-624.
- 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.