Scientific Programme
Abstract
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Abstract
Year 2021
September 2021

SHBC1521

Abstract Title
Examining the effectiveness of Dutch Lipid Clinic Network and Simon Broome Criteria in predicting genetic analysis result of Familial Hypercholesterolemia In Singapore
Authors

W.Y.WAN1, PEK SL1, DISSANAYAKE S1, TANG JI1, HOE J1, SIRAJ F1, ZULKIFLI A1, LIN MX1, CHAN ZL1, KAMARUDDIN SNA1, LIM ETS2

Institutions

Khoo Teck Puat Hospital1, National Heart Centre Singapore2

Background & Hypothesis

Familial Hypercholesterolemia (FH) is a genetic disorder characterized by high blood cholesterol levels from birth. Clinically, FH is diagnosed using Simon Broome (SB) Criteria and Dutch Lipid Clinic Network (DLCN) Criteria. This study aimed to investigate the ability of these diagnostic tools to predict the genetic analysis in FHCARE cohort.

Methods

Patients with LDL-c of >4.4mmol/L and a family history of hyperlipidemia or premature coronary artery diseases were recruited from KTPH, AdMC, KKH, NHCS, SKH, NUH, NTFGH, TTSH, NHGP, CGH and SGH. Blood samples were obtained, molecular genetic analysis was done using Next Generation Sequencing(NGS) in26 lipid-related genes, including LDLR, APOB, PCSK9 and LDLRAP1. Classifications of the criteria were compared to genetic results by Chi2 test(SPSS).

Results

The mean age of the recruited 511 probands is 40.7(±14.6) years old; 356(69.7%) are males.

328(64.2%) probands are positive for LDLR and APOB gene mutations, 1(0.2%) is positive for LDLRAP1.

SB has a sensitivity of 72.13%, specificity of 40.24%, positive predictive value (PPV) of 40.24%and negative predictive value (NPV) of 72.13%(p<0.0001). DLCN (classifying score ≥3 as positive) has a sensitivity of 96.17%, specificity of 10.37%, PPV of 37.45% and NPV of 82.93%(p<0.0001). DLCN classifying score ≥6 as positive, it has the sensitivity of 61.75%, specificity of 57.01%, PPV of 44.49% and NPV of 72.76%(p<0.0001).

Discussion & Conclusion

The high sensitivity of both criteria suggests that they are useful in large-scale screening. With poor to moderate specificity, NGS provides a complementary tool to identify additional cases, which will help in cascade screening.

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