ReviewScreening and treatment of familial hypercholesterolemia - Lessons from the past and opportunities for the future (based on the Anitschkow Lecture 2014)

- Familial hypercholesterolemia is a prevalent hereditary disorder that greatly increases the risk for premature CHD events.
- Nationwide genetic cascade screening saves lifes and is cost-effective.
- Large screening programmes improve both public and personal health and provide unique opportunities to advance science.
- A substantial residual CHD risk remains in FH patients, despite treatment with statins and ezetimibe.
- New treatment strategies like inhibition of apoB, MTP, PCSK9 and CETP are currently in development and are very promising.

In this review, we discuss the screening and treatment of familial hypercholesterolemia (FH), an autosomal dominant inherited disease, characterized by severely increased levels of low-density lipoprotein cholesterol (LDL-C) and increased risk for premature coronary heart disease (CHD).Genetic family based cascade screening for FH was shown to be cost-effective and a screening program with such an approach was carried out in the Netherlands from 1994 to 2014. Over 64,000 persons have participated in this program of whom 40.3% were found to carry an FH causing mutation. We will discuss the results of this screening program, as well as the scientific opportunities it has provided.Currently, statins and ezetimibe are the only registered LDL-C lowering treatment options for FH patients. Many of them do not attain the treatment goals that are recommended by treatment guidelines. In this review, we will also provide a comprehensive overview of promising new modalities that could lower LDL-C in FH patients.