Familial Hypercholesterolemia

by Sydney Miller, MBS 2019, Geisinger Commonwealth School of Medicine


Mentor: Gregory Shanower, PhD

High cholesterol is a problem that affects approximately one-third of adults in the United States and is linked to poor diet, lack of physical exercise and smoking. However, for many individuals this can be a genetic issue. A disease known as familial hypercholesterolemia is caused by a genetic mutation that is passed down in families and results in high levels of serum low density lipoprotein (LDL). This high level of LDL cholesterol is responsible for early onset cardiac events in these families, resulting in serious health issues. It is rare that a member of a family with familiar hypercholesterolemia is not affected by this disease.

High cholesterol is a problem because the excess “bad” cholesterol or LDL in the blood can build-up and lead to a blockage of blood vessels. This narrowing of blood vessels is known as atherosclerosis, which reduces the blood flow available to certain parts of the body. As a result, an individual might suffer from a heart attack or another cardiovascular event. For individuals with familial high cholesterol, this can occur very early in life with people experiencing heart attacks in their mid-30s.

There have been many mutations leading to this high cholesterol that runs in families, making it very difficult to treat with the medications that were previously available, including statins. But recently, new medications called PCSK9 inhibitors were developed and approved by the FDA to be given to individuals with familial high cholesterol. These medications are especially effective since they are targeted to the specific mutation that reduces the amount of cholesterol taken up by the body and thus cause the disease to appear.

This new medicine was discovered by analyzing the genomes of families that traditionally have had very low cholesterol levels, much lower than for the average person. It turned out that many of these families with very low cholesterol levels had a mutation in the same gene as those families that had a high cholesterol level. However, instead of a mutation that led to an increase in cholesterol, it resulted in a mutation that reduced cholesterol levels in the blood. Therefore, this new medication was developed to mimic the low cholesterol levels of those families. It was successfully administered to individuals to lower their high cholesterol and reduce the number of potential heart attacks. Thus this medication shows promise to reduce the number of heart attacks and death to individuals with familial hypercholesterolemia in the United States and abroad.

While this new medication was specifically designed to help those with a genetic mutation, it is important to keep in mind that the vast majority of people in the U.S. that have high cholesterol likely have this condition because of poor diet and lack of exercise. So, while statins and this new medication can be used to treat their high cholesterol, it is also important to consider other treatments that effectively manage high cholesterol. These other treatments include increased exercise along with changes in diet. Doctors have found that eating foods high in fiber and omega-3 fatty acids while limiting consumption of red meat have had positive impacts on reducing high cholesterol levels.

Within the U.S. population there are a variety of reasons that individuals have high cholesterol, including poor diet and exercise or a genetic predisposition. However, now there are promising treatments for all of these individuals which help lower their risk of a heart attack through a reduction in cholesterol levels, making America a more heart-healthy nation.