Abstract
BackgroundPrevious studies have observed that high level of lipoprotein (a) [Lp(a)] was common in the phenotypic familial hypercholesterolemia (FH) and may explain part of the clinical diagnosis of FH.HypothesisWe aim to develop a modified model including Lp(a) and compare its diagnostic performance with Dutch Lipid Clinic Network (DLCN) criteria.MethodsData of 10 449 individuals were utilized for the model establishment (7806 for derivation and 2643 for validation) from January 2011 to March 2018. The novel score model was modified on the basis of DLCN. Furthermore, 718 patients were screened for LDLR, APOB, and PCSK9 gene mutations.ResultsThe novel modified model consisted of untreated low‐density lipoprotein cholesterol (LDL‐C) level, Lp(a), personal premature coronary heart disease (CHD), tendon xanthomas and family history of CHD and/or hypercholesterolemia. It has shown high discrimination (area under curve [AUC] 0.991, 95% confidence interval [CI[ 0.988‐0.994, P < .001) for distinguishing clinical FH from non‐FH diagnosed using DLCN. Furthermore, a concordance analysis was performed to compare the modified model with DLCN and it showed a good agreement with DLCN (κ = 0.765). External validation of the novel model also showed good accordance (κ = 0.700). Further genetic analysis showed that the agreements between the new model and mutation improved a little compared to that between DLCN and mutation.ConclusionsThe novel modified model, including Lp(a), could provide new insights into FH diagnosis in Chinese population with more concerns on the patients with high level of Lp(a).
Highlights
Di Sun and Ye-Xuan Cao contributed .Familial hypercholesterolemia (FH) has been recognized as an inherited disease with extremely elevated level of low-density wileyonlinelibrary.com/journal/clcClinical Cardiology. 2019;42:988–994
The results showed that the new model had a little better agreement with the mutation than Dutch Lipid Clinic Network (DLCN), but both of them showed poor agreement with mutations (κ = 0.355 vs κ = 0.340). of note, the new model had a moderate agreement with mutations in the validation cohort (κ = 0.470)
The new modified model has shown high discrimination for distinguishing clinical familial hypercholesterolemia (FH) from non-FH diagnosed using DLCN, which was higher than sole low-density lipoprotein cholesterol (LDL-C) level and LDL-C plus Lp(a) level
Summary
Di Sun and Ye-Xuan Cao contributed . Familial hypercholesterolemia (FH) has been recognized as an inherited disease with extremely elevated level of low-density. Lipoprotein cholesterol (LDL-C) and premature coronary heart disease (CHD).[1]. The discordance between different clinical diagnostic criteria and heterogeneity of phenotype and genotype often confused the physicians,[10] especially for those without their own diagnostic guidelines including China. Ruel et al have proposed a simplified Canadian definition for FH, which had a comparable performance with the existing criteria SBR and DLCN.[18]. Studies addressing this issue for Chinese population have been lacked. We aim to develop a modified model including Lp(a) to facilitate the diagnosis of FH in the clinical practice, which could be adapted to Chinese population well
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