Huang Haomin, Li Lamei, Yang Anni, Chen Tao, Shi Ganwei, Li Feng, Wang Luya, Cai Gaojun
Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Cardiology, Wujin Hospital Affiliated with Jiangsu University, The Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China.
Front Cardiovasc Med. 2024 Oct 24;11:1434392. doi: 10.3389/fcvm.2024.1434392. eCollection 2024.
Coronary artery disease (CAD) remains the primary cause of death worldwide, and familial hypercholesterolemia (FH) is a common disease that leads to CAD. 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.
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).
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 ( > 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 ( < 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 < 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, < 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; 95% CI: 1.16-7.79, < 0.05). In total, 104 FH-related mutations were detected in this study.
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), 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.
冠状动脉疾病（CAD）仍然是全球主要的死亡原因，而家族性高胆固醇血症（FH）是导致CAD的常见疾病。本研究旨在探讨FH患者与低密度脂蛋白胆固醇（LDL-C）水平高的非FH患者之间CAD风险的差异。
连续纳入2016年6月至2020年9月接受冠状动脉造影（CAG）的18岁及以上个体。最终纳入LDL-C水平≥4.0 mmol/L的参与者。对所有参与者进行了下一代测序，使用包括11个基因（LDLR、APOB、PCSK9、LDLRAP1、ABCG5、ABCG8、LIPA、LPA、APOBR、LRPAP1和STAP1）的扩展基因面板。
本研究共纳入223名个体。根据CAG结果，纳入199例CAD患者和24例非CAD患者。无论对3个主要基因还是所有11个基因进行测序，CAD组和非CAD组中FH基因的比例均无显著差异（>0.05）。此外，所有CAD患者被分为三支血管病变（TVD）组和非TVD组。TVD组中3个FH主要基因发生突变的患者比例更高（<0.05）。此外，TVD组的总胆固醇（TC）、LDL-C和修饰LDL-C（MLDL-C）水平高于非TVD组，而估计肾小球滤过率（eGFR）低于非TVD组（均<0.05）。然而，多因素logistic回归分析显示，只有eGFR是TVD的独立危险因素（OR 0.99；95%CI：0.98 - 1.00，<0.05）。为消除eGFR的影响，进行了亚组分析，结果表明，在高eGFR组的CAD患者中，3个主要基因存在FH突变是TVD的独立危险因素（OR 3.00；95%CI：1.16 - 7.79，<0.05）。本研究共检测到104个与FH相关的突变。
FH突变并未增加MLDL-C水平≥4.0 mmol/L个体的CAD发生率。然而，在肾功能几乎正常（≥87.4 ml/min/1.73 m²）的CAD患者（MLDL-C水平≥4.0 mmol/L）中，3个主要基因存在FH突变的患者发生TVD的概率是无FH突变患者的3.00倍。
