Highlights
- •There is a mismatch in clinical and genetic familial hypercholesterolemia diagnosis.
- •Familial hypercholesterolemia is a syndrome including several entities.
- •Monogenic and polygenic familial hypercholesterolemia determines high vascular risk.
- •Familial hypercholesterolemia diagnosis has implications to access new therapies.
- •A new classification including all FH genotypes and phenotypes is warranted.
Abstract
The introduction of singular therapies, such as proprotein convertase subtilisin/kexin
type 9 inhibitors (PCSK9i), to lower high cholesterol levels requires better classification
of patients eligible for intensive lipid lowering therapy. According to the European
Medicines Administration, PCSK9i are recommended in primary prevention only in familial
hypercholesterolemia (FH) patients. Therefore, an FH diagnosis is not simply an academic
issue, because it has many clinical implications. The bases of a diagnosis of FH are
not entirely clear. The availability of genetic testing, including large genome-wide
association analyses and whole genome studies, has shown that some patients with a
clinical diagnosis of definite FH have no mutations in the genes associated with the
disease. This fact does not exclude the very high cardiovascular risk of these patients,
and an early and intensive lipid lowering therapy is recommended in all FH patients.
Because an FH diagnosis is a cornerstone for decisions about therapies, a precise
definition of FH is urgently required. This is an expert consensus document from the
Spanish Atherosclerosis Society. We propose the following classification: familial
hypercholesterolemia syndrome integrated by (1) heterozygous familial hypercholesterolemia:
patients with clinically definite FH and a functional mutation in one allele of the
LDLR, ApoB:100, and PCSK9 genes; (2) homozygous familial hypercholesterolemia: mutations affect both alleles;
(3) polygenic familial hypercholesterolemia: patients with clinically definite FH
but no mutations associated with FH are found (to be distinguished from non-familial,
multifactorial hypercholesterolemia); (4) familial hypercholesterolemia combined with
hypertriglyceridemia: a subgroup of familial combined hyperlipidaemia patients fulfilling
clinically definite FH with associated hypertriglyceridemia.
Keywords
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Article Info
Publication History
Published online: June 19, 2019
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© 2019 Elsevier B.V. All rights reserved.
