Matta Anthony, Rabès Jean Pierre, Taraszkiewicz Dorota, Carrié Didier, Roncalli Jérôme, Ferrières Jean
Department of Cardiology, Civilians Hospital of Colmar, Colmar, France.
Department of Cardiology, Notre Dame des Secours University Hospital Center, Byblos, Lebanon.
Front Cardiovasc Med. 2023 Jul 19;10:1182554. doi: 10.3389/fcvm.2023.1182554. eCollection 2023.
Heterozygous familial hypercholesterolemia (HFH) is an autosomal dominant genetic disorder leading to a lifetime exposure to high low-density lipoprotein cholesterol (LDL-c) level and an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). We evaluate the effect of a causative genetic variant to predict ASCVD in HFH patients undergoing treatment.
A retrospective cohort was conducted on 289 patients with possible, probable, and definite diagnosis of HFH according to Dutch Lipid Clinic Network Score and in whom DNA analyses were performed and mean LDL-c level was above 155 mg/dl. The study population was divided into groups based on the presence or not of a causative variant (pathogenic or likely pathogenic). We observed each of the study's participants for the occurrence of ASCVD.
A causative variant was detected in 42.2% of study participants, and ASCVD has occurred in 21.5% of HFH patients. The incidence of ASCVD (27% vs. 17.4%, = 0.048) and the mean of LDL-c under an optimal medical treatment (226 ± 59 mg/dl vs. 203 ± 37 mg/dl, = 0.001) were higher in HFH-causative variant carriers than others. After adjusting on confounders, ASCVD was positively associated with LDL-c level [OR = 2.347; 95% (1.305-4.221), = 0.004] and tends toward a negative association with HDL-c level [OR = 0.140; 95% (0.017-1.166), = 0.059]. There is no more association between the detection of a causative variant and the occurrence of ASCVD [OR = 1.708; 95% (0.899-3.242), = 0.102]. Kaplan Meier and log rank test showed no significant differences in event-free survival analysis between study groups ( = 0.523).
In this study population under medical care, it seems that the presence of a causative variant did not represent an independent predictor of adverse cardiovascular outcomes in HFH patients, and LDL-c level played an undisputable causal role.
杂合子家族性高胆固醇血症（HFH）是一种常染色体显性遗传病，会导致患者终生处于高低密度脂蛋白胆固醇（LDL-c）水平，并增加过早发生动脉粥样硬化性心血管疾病（ASCVD）的风险。我们评估了一种致病性基因变异对接受治疗的HFH患者发生ASCVD的预测作用。
根据荷兰脂质诊所网络评分，对289例可能、很可能和确诊为HFH的患者进行回顾性队列研究，这些患者均进行了DNA分析，且平均LDL-c水平高于155mg/dl。根据是否存在致病性变异（致病或可能致病）将研究人群分组。我们观察了每位研究参与者ASCVD的发生情况。
42.2%的研究参与者检测到致病性变异，21.5%的HFH患者发生了ASCVD。HFH致病性变异携带者的ASCVD发病率（27%对17.4%，P = 0.048）和最佳药物治疗下的LDL-c平均值（226±59mg/dl对203±37mg/dl，P = 0.001）高于其他患者。在对混杂因素进行调整后，ASCVD与LDL-c水平呈正相关[比值比（OR）= 2.347；95%置信区间（1.305 - 4.221），P = 0.004]，与高密度脂蛋白胆固醇（HDL-c）水平呈负相关趋势[OR = 0.140；95%置信区间（0.017 - 1.166），P = 0.059]。致病性变异的检测与ASCVD的发生之间不再存在关联[OR = 1.708；95%置信区间（0.899 - 3.242），P = 0.102]。Kaplan Meier法和对数秩检验显示研究组间无事件生存分析的显著差异（P = 0.523）。
在本接受医疗护理的研究人群中，致病性变异的存在似乎并非HFH患者不良心血管结局的独立预测因素，而LDL-c水平发挥了无可争议的因果作用。
