Explore The Value Of Modified Dutch Lipid Clinic Network Criteria In Diagnosing Familial Hypercholesterolemia

Objective The aim of this study was to estimate the prevalence of familial hypercholesterolemia(FH)in individuals undergoing coronary angiography(CAG)in Hospital using the Modified Dutch Lipid Clinic Network(MDLCN)criteria and try to explore the likely predictors of carrying FH-mutation in clinical FH patients according to the results of genetic testing.Methods Individuals(≥18 years)who underwent CAG from June 2016 to September 2020 were consecutively enrolled in the study.Then we explored the FH prevalence in all individuals according to MDLCN criteria(including definite FH and probable FH),and those with a score ≥6 were clinically diagnosed with FH.According to sex,the results of CAG and the age when they suffered from coronary artery disease(CAD)at the first time,FH proportions were explored in different subgroups.Genetic testing covering all the coding exons of the low-density lipoprotein receptor(LDLR),low-density lipoprotein receptor adaptor protein(LDLRAP),apolipoprotein B(APOB)and proprotein convertase subtilisin/kexin type 9(PCSK9)genes was conducted to estimate the FH proportion in all clinical FH patients identified by MDLCN criteria.And the mutation ratio in these four genes were calculated in the light of the genetic testing results.Those clinical FH patients were divided into two groups according to the testing result,and compared the genenal characteristics of patients in these two groups.Finally,multivariate Binary logistic regression analysis was used to explore the likely related factors of carrying FH mutation in clinical FH patients.Results A total of 3,267 individuals with age of 66(58,72)years were involved after the inclusion and exclusion criteria were applied including 2,117 males and 1,150 females.According to the MDLCN criteria,2.88%(94/3,267)FH individuals were clinically identified.In subgroup analysis,3.9%(45/1150)FH individuals were clinically identified in females,which was higher than 2.3%(49/2,117)in males(P<0.05);3.63%(90/2,476)FH individuals in CAD group was higher than 0.51%(4/791)in Non-coronary artery disease(Non-CAD)group(P<0.001);9.4%(57/604)FH individuals in Premature coronary artery disease(PCAD)group was higher than1.8%(33/1,872)in Non-Premature coronary artery disease(Non-PCAD)group(P<0.001).73 clinical FH individuals identified by MDLCN criteria gave blood samples to undergo genetic testing and of whom 26(35.6%)were genetically verified as having FH.There were totally 25 FH mutations found in this study,including 16(64%)in LDLR gene,8(32%)in APOB gene and 1(4%)in PCSK9 gene,and no mutation was found in LDLRAP gene.In FH-mutation positive group,Total cholesterol(TC),Low-density lipoprotein cholesterol(LDL-C)and Modified low-density lipoprotein cholesterol(MLDL-C)levels and the proportion of three vessel disease(TVD)were higher than FH-mutation negative group,but the proportion of Primary hypertension(PH)was lower [TC:(6.9 ± 1.4)mmol/L vs(6.0 ±1.5)mmol/L,P<0.05;LDL-C:(5.1 ± 1.2)mmol/L vs(4.2 ± 1.1)mmol/L,P<0.05;MLDL-C: 6.2(5.9,6.8)mmol/L vs 5.7(4.5,6.5)mmol/L,P<0.05;TVD: 14(53.8%)vs 15(31.9%),P<0.05;PH: 14(53.8%)vs 39(83.0%),P<0.05].In multivariate logistic regression analysis,PH status,TC and triglyceride(TG)levels were independently related to FH-positive mutations in clinical FH cases identified by the MDLCN criteria with a score ≥6.Conclusions The prevalence of FH in individuals with CAG estimated by MDLCN criteria was 2.88%,among them,35.6%(26/73)clinical FH individuals were found with FH mutations according to the results of genetic testing.In addition,those individuals with clinical FH identified by the MDLCN criteria who without primary hypertension or had high total cholesterol or low triglyceride levels were more likely to have FH mutations.