SHBC1521

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

Khoo Teck Puat Hospital¹, National Heart Centre Singapore²

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.

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).

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).

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.