Familial Hypercholesterolemia

Cholesterol is a waxy, fat-like substance that can be found in your blood. The liver either makes cholesterol or re-uses cholesterol obtained from other sources: dietary cholesterol and saturated fat, cholesterol carried in the blood, or by reabsorbing bile from the gastrointestinal tract.

Cholesterol is crucial to the healthy functioning of the body, which needs it to build healthy cells and make vitamin D and other hormones. But too much cholesterol can lead to serious problems, including heart disease and stroke.

High blood cholesterol is one of the major risk factors for heart disease, heart attack and stroke.

Cholesterol is carried through your blood attached to proteins. This combination of proteins and cholesterol is called a lipoprotein. There are different types of cholesterol, based on what the lipoprotein carries, including low-density lipoprotein (LDL) and high-density lipoprotein (HDL), among others.

LDL-cholesterol is sometimes called “bad” cholesterol because it can build up inside our arteries, causing them to harden and narrow (a process called atherosclerosis) and limiting blood flow. This can ultimately lead to a heart attack or stroke.

HDL-cholesterol is often referred to as “good” cholesterol, because it carries unnecessary cholesterol away from our arteries and back to our liver, where it’s broken down and eliminated from the body. A healthy level of HDL cholesterol can protect against heart attack and stroke.

Individuals with FH are unable to properly regulate and remove the excess of “bad” cholesterol from the blood stream. Over time, cholesterol accumulates, builds up in the walls of the arteries, and leads to premature cardiovascular disease.

FH is inherited. Typically, parents with one pathogenic mutation have a 50% chance of passing down the condition to each child. Therefore, it is essential to screen first- and second-degree relatives (i.e. parents, siblings children, aunts/uncles, nieces/nephews, and grandparents) of an individual diagnosed with FH, to detect other family members who may have inherited the disorder.

Individuals who inherited one mutation develop heterozygous familial hypercholesterolemia (HeFH), the most common form of FH. In contrast, individuals who inherited two abnormal mutations develop homozygous familial hypercholesterolemia (HoFH), a particularly rare and life-threatening form of FH, characterized by extreme levels of blood cholesterol.

FH is severely underdiagnosed. Today, only 10% of individuals born with FH have been diagnosed worldwide. This is a direct consequence of low levels of awareness and education among the public and the medical community. In addition, many people with FH do not develop any visible symptoms and therefore do not seek care.

Early diagnosis and lifelong treatment of FH reduces the risk of premature cardiovascular disease and heart attacks.

FH can be diagnosed with a simple blood test and a set of diagnostic criteria. Some untreated patients can also develop a characteristic skin condition called xanthoma, which is caused by a build-up of fat under the surface of the skin. In some settings, the diagnosis of FH can also be confirmed by a genetic test.

Untreated men and women with heterozygous FH will generally experience a cardiovascular event by the age of 30 to 50 and 40 to 60, respectively. In contrast, individuals with homozygous FH will experience a cardiovascular event in childhood or adolescence and die before the age of 30, if left untreated.

Untreated men and women with heterozygous FH will generally experience a cardiovascular event by the age of 30 to 50 and 40 to 60, respectively. In contrast, individuals with homozygous FH will experience a cardiovascular event in childhood or adolescence and die before the age of 30, if left untreated.

Individuals with FH can live longer and healthier lives if treatment begins early in life. In the case of FH, lifestyle and diet interventions are not enough. Patients will always require cholesterol-lowering therapies. FH drug treatment focuses on reducing the extremely high levels of LDL-cholesterol. This lowers the risk of heart attack and death. Many people with FH will need to take more than one medication to control their LDL-cholesterol levels. Standard cholesterol-lowering medications act by blocking the liver’s ability to produce cholesterol, by blocking cholesterol absorption from the gut, or by increasing cholesterol uptake from the blood.

In recent years, a number of new drugs (with different mechanisms of action) have been discovered and commercialised. Most novel medications and medical interventions are generally expensive and/or resource intensive. Therefore, accessibility, availability, and affordability of high-quality drugs and care should be ensured for all patients.

In 1998, the World Health Organization (WHO) officially recognized familial hypercholesterolemia as a global public health issue and published a set of 11 recommendations to address its burden. In the past two decades, tremendous scientific progress has been achieved in the fields of genetics, lipidology, cardiology, and drug development. In spite of these breakthroughs, implementation of the WHO recommendations has been largely insufficient in many countries and regions.

In January 2020, representatives from the global FH community published a Global Call to Action and highlighted a new set of recommendations, in 9 areas of priority, to reduce the clinical and public health burden of familial hypercholesterolemia:

1. Raise awareness of FH
2. Advocate for FH
3. Screen, test, and diagnose for individuals with FH
4. Manage and treat FH patients
5. Guarantee care for severe and homozygous FH patients
6. Develop family-based care plans for people living with FH
7. Establish FH registries
8. Conduct research and implement FH programmes
9. Understand the value and costs of FH interventions

JView/AMA Cardiology: Reducing the Clinical and Public Health Burden of FH: A Global Call to Action

Global Call to Action on FH: Summary Document