Abstract
BackgroundPatients with monogenic familial hypercholesterolemia (FH) have high risk for coronary artery disease (CAD). A recent FH Expert Panel suggested that FH was underdiagnosed and undertreated which needs early diagnosis. Moreover, the proportion of DNA-confirmed FH patients hospitalized with very early-onset (≤ 35 years) CAD remains uncertain.MethodsOne hundred and five patients with age ≤ 35 years and LDL-C ≥ 3.4 mmol/L were tested for 9 genes (LDLR, APOB, PCSK9, APOE, STAP1, LIPA, LDLRAP1, ABCG5/8). Dutch Lipid Clinic Network (DLCN) and Simon Broome (SB) criteria for FH were also performed.ResultsThe prevalence of genetically confirmed FH was 38.1% (n = 40) in 105 patients. DLCN categorized 26.7% patients to probable and definite FH while SB identified 17.1% of patients with possible to definite FH. Twenty-five (62.5%) and seventeen (42.5%) patients with pathogenic mutations were undiagnosed according to SB and DLCN criteria. FH variant carriers, especially homozygotes, had significantly higher plasma LDL-C levels. The best LDL-C threshold for genetically confirmed FH was 4.56 mmol/L in the present study.ConclusionsFH is really a common cause for very young CAD patients (≤ 35 years) with a 38.1% of causative mutations in China and best LDL-C threshold for predicting mutations was 4.56 mmol/L. The underdiagnostic rate of clinical criteria was around 42.5–62.5%, suggesting that the expanded genetic testing could indeed promote the diagnosis of FH.
Highlights
Patients with monogenic familial hypercholesterolemia (FH) have high risk for coronary artery disease (CAD)
Familial hypercholesterolemia (FH), a monogenic autosomal dominant disorder of low-density lipoprotein cholesterol (LDL-C) metabolism, is a worldwide health burden demonstrated by a recent FH Expert Panel [1]
FH has been classified into heterozygous and homozygous forms depending on the presence of affected alleles in genes encoding the LDL receptor (LDLR), apolipoprotein B (ApoB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) [1, 2]
Summary
Patients with monogenic familial hypercholesterolemia (FH) have high risk for coronary artery disease (CAD). Familial hypercholesterolemia (FH), a monogenic autosomal dominant disorder of low-density lipoprotein cholesterol (LDL-C) metabolism, is a worldwide health burden demonstrated by a recent FH Expert Panel [1]. Patients with FH have lifelong elevated levels of low-density lipoprotein (LDL) particles, as well as increased LDL-C arterial deposits, leading to coronary artery disease (CAD), namely myocardial infarction (MI) and angina pectoris [2, 3]. The diagnosis of FH is commonly performed according to genetic testing and clinical phenotypes. The recent published Expert Panel suggested that genetic testing is the “gold standard” for FH diagnosis and expand panels could be performed to improve the diagnostic rate [1]
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