DIAgnosis and Management Of familial hypercholesterolemia in a Nationwide Design (DIAMOND-FH): Prevalence in Switzerland, clinical characteristics and the diagnostic value of clinical scores.

Miserez, A R; Martin, F J; Spirk, David (2018). DIAgnosis and Management Of familial hypercholesterolemia in a Nationwide Design (DIAMOND-FH): Prevalence in Switzerland, clinical characteristics and the diagnostic value of clinical scores. Atherosclerosis, 277, pp. 282-288. Elsevier 10.1016/j.atherosclerosis.2018.08.009

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BACKGROUND AND AIMS

In Switzerland, the prevalence of familial hypercholesterolemia (FH) due to pathogenic apolipoprotein B-100 gene (APOB) variants was known, but not the prevalence of FH due to pathogenic low-density lipoprotein-receptor gene (LDLR) variants. Phenotypic differences (LDLR versus APOB) might affect the diagnostic value of the Dutch Lipid Clinic Network (DLCN) score and Simon Broome Diagnostic Criteria (SBDC).

METHODS

A total of 2734 Swiss subjects were investigated, 2221 unselected subjects from three representative population surveys for estimation of the prevalence (LDLR variants), and 513 subjects from the DIAgnosis and Management Of familial hypercholesterolemia in a Nationwide Design (DIAMOND-FH) study for comparisons of phenotypic characteristics (LDLRversusAPOB variants), diagnostic values of clinical scores, and cardiovascular outcome.

RESULTS

In 7 of 2221 individuals, FH (LDLR) was diagnosed (prevalence of FH due to LDLR variants: 1/317, prevalence of FH due to both LDLR and APOB variants: 1/125 to 1/135). In FH (APOB) patients under 35 years of age, mean total cholesterol (TC) was <8.5 mmoL/L but increased above 35. In FH (LDLR), TC was >8.5 mmoL/L in all age groups. This difference was crucial for the diagnosis of FH and resulted in a significantly lower sensitivity of clinical scores in FH (APOB) (DLCN: 13.8%, p < 0.0001; SBDC: 22.5%, p = 0.005). Thus, both scores were not useful for the definite diagnosis of FH due to APOB variants. Regarding the cardiovascular outcome, no differences (LDLR versus APOB) were found above 60 years. In countries with high percentages of FH due to APOB variants, cascade screening and molecular testing appear to be much more cost-effective.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Spirk, David

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0021-9150

Publisher:

Elsevier

Language:

English

Submitter:

Celine Joray

Date Deposited:

30 Jan 2019 12:50

Last Modified:

01 Dec 2020 15:20

Publisher DOI:

10.1016/j.atherosclerosis.2018.08.009

PubMed ID:

30270060

Uncontrolled Keywords:

APOB Apolipoprotein B-100 Clinical scores Diagnostic value Dutch Lipid Clinic Network Familial hypercholesterolemia Familial-defective apolipoprotein B-100 Genotype LDLR Low-density lipoprotein-receptor Pathogenic variants Phenotype Phenotypic characteristics Prevalence Simon Broome Diagnostic Criteria

BORIS DOI:

10.7892/boris.124985

URI:

https://boris.unibe.ch/id/eprint/124985

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