Familial Combined Hyperlipidemia: Myth or Reality?

Abstract

Purpose of Review: Familial combined hyperlipidemia (FCHL) was first described by Goldstein and co-workers in 1973 as a multiple-type hyperlipidemia in pedigrees with premature myocardial infarction. However, it can be questioned what actually defines FCHL. Recent Findings: Although initially regarded as an autosomal dominant disorder, quantitative trait linkage analyses have revealed multiple genes that are associated with the FCHL phenotype. With the advent of genome-wide association studies and next generation sequencing it has been confirmed that FCHL is a polygenic disorder and the associated gene variants, mostly with a triglyceride-raising effect, are not unique to FCHL. Furthermore, epidemiological studies have demonstrated that the multiple-type hyperlipidemia is also not specifically confined to FCHL. Summary: This review provides a historical overview of the metabolic and genetic abnormalities that characterize FCHL. Integration of these findings with recent population-based, genetic studies results in a new pathophysiological concept of FCHL. This model provides practical guidance on how to approach an individual patient with an ‘FCHL phenotype’.