Haomin Huang ¹ Lamei Li ² Anni Yang ² TAO CHEN ² Ganwei Shi ² Feng Li ² Luya Wang ³ Gaojun Cai ^2*

• ¹ Department of Cardiology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
• ² Changzhou Wujin People's Hospital, Changning, Jiangsu Province, China
• ³ Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

Background: Coronary artery disease (CAD) remains the primary cause of death worldwide, and familial hypercholesterolemia (FH) is a common disease that leads to CAD.Objective: This study aimed to explore the difference in CAD risk between FH and non-FH patients with high low-density lipoprotein cholesterol (LDL-C) levels. Methods: Individuals (≥18 years) who underwent coronary angiography (CAG) from June 2016 to September 2020 were consecutively enrolled. Participants with LDL-C levels ≥4.0 mmol/L were ultimately included in this study. For all participants, next-generation sequencing was performed with expanded gene panels including 11 genes (LDLR, APOB, PCSK9, LDLRAP1, ABCG5, ABCG8, LIPA, LPA, APOBR, LRPAP1, and STAP1). Results: A total of 223 individuals were included in this study.According to the CAG findings, 199 CAD patients and 24 non-CAD patients were included. The proportions of FH genes, regardless of whether 3 major genes or all 11 genes were sequenced, were not significantly different between the CAD and non-CAD groups (P>0.05). In addition, all CAD patients were divided into a triple vessel disease (TVD) group and a non-TVD group. The TVD group had a greater proportion of patients with mutations in 3 FH major genes (P<0.05). In addition, TC, LDL-C and modified LDL-C (MLDL-C) levels were higher and the estimated glomerular filtration rate (eGFR) was lower in the TVD group than in the non-TVD group (all P<0.05). However, multivariate logistic regression analyses revealed that only the eGFR was an independent risk factor for TVD (OR 0.99; 95% CI: 0.98-1.00, P<0.05). To eliminate the impact of the eGFR, subgroup analysis was conducted, and the results indicated that among CAD patients in the high-eGFR group, having FH mutations in 3 major genes was an independent risk factor for TVD (OR 3.00; P<0.05). Conclusions: FH mutation did not increase the rate of CAD in individuals with an MLDL-C level ≥4.0 mmol/L. However, among CAD patients (MLDL-C level ≥4.0 mmol/L) with almost normal renal function (≥87.4 ml/min/1.73 m 2 ), the probability of enduring TVD in those with FH mutations in 3 major genes was 3.00 times greater than that in those without FH mutations.