What is FH (Familial Hypercholesterolemia)

FH stands for Familial Hypercholesterolemia. It is an inherited disease characterized by a reduced ability of the liver to clear cholesterol from the blood. On the other hand, the liver continues to produce cholesterol. As a consequence, patients with FH have very high levels of LDL-cholesterol that cannot be normalized by following a cholesterol-poor diet or by a healthy lifestyle. Without treatment, patients with FH have a high risk of developing problems like heart attacks and strokes (collectively called cardiovascular disease). Importantly, the large majority of patients do not have any symptoms before they develop cardiovascular disease.

The cause of FH is a mutation in the gene encoding for a protein called the LDL-receptor. Normally the LDL-receptor is expressed in the liver and removes LDL-cholesterol from the blood. The LDL-receptor is not working normally in FH patients.

We have two copies of all genes in our body. There are several types of FH. If one copy of the LDL-receptor is affected, then a person has heterozygous FH. If two copies are affected, then a person has homozygous FH. In recent years, it has been shown that heterozygous FH is far more common than previously thought. Approximately 1 in 250 people worldwide has heterozygous FH. Homozygous FH is far less common (about 1 in 160,000 to one million people).

When left untreated, individuals with FH have a 20-fold increased lifetime risk of heart disease compared with the general population. Heart disease also occurs at a younger age in people with FH: untreated men have a 50% risk of heart disease before the age of 50, and untreated women have a 30% risk of heart disease by the age of 60. These numbers are even more disturbing when considering that the percentage of affected individuals that have been diagnosed in the United States is probably <5%, while the consequences in terms of cardiovascular disease in FH patients can be largely prevented if cholesterol-lowering therapy is started early enough.