Rogozik Joanna, Grabowski Marcin, Główczyńska Renata
First Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
Front Cardiovasc Med. 2024 Sep 17;11:1417432. doi: 10.3389/fcvm.2024.1417432. eCollection 2024.
Familial hypercholesterolemia (FH) is a serious genetic condition that results in abnormally high levels of low-density lipoprotein cholesterol (LDL-C) in the bloodstream, significantly increasing the risk of early onset of cardiovascular disease. The heterozygous form of FH (HeFH) is widespread, affecting around 1 in 500 people worldwide.
In this clinical report, we present the case of a patient who suffers from HeFH due to a mutation in the LDL receptor (LDLR) gene. A woman exhibited intolerance to statin therapy and did not attain adequate reduction in low-density lipoprotein cholesterol (LDL-C) levels on ezetimibe monotherapy. Genetic testing confirmed the presence of a pathogenic variant for FH with the deletion of exons 7-14. The administration of alirocumab (a dose of 150 mg sc) as the primary therapy did not exhibit the desired therapeutic outcome. Consequently, the patient was given inclisiran therapy (a dose of 284 mg sc), which significantly reduced LDL cholesterol levels after 3 months of treatment and during the 1-year follow-up.
Inclisiran therapy has shown promising results for individuals with HeFH who experience statin intolerance. This therapy works by using a small interfering RNA (siRNA) to target the mRNA of proprotein convertase subtilisin/kexin type 9 (PCSK9), which leads to a significant reduction of LDL-C levels. This approach can be an alternative for patients without significant reductions in LDL-C levels with PCSK9 inhibitor therapy. For HeFH patients with limited treatment options due to statin intolerance and genetic mutations, inclisiran can represent a promising therapeutic option.
家族性高胆固醇血症（FH）是一种严重的遗传性疾病，可导致血液中低密度脂蛋白胆固醇（LDL-C）水平异常升高，显著增加心血管疾病早发风险。FH的杂合形式（HeFH）很常见，全球约每500人中就有1人受影响。
在本临床报告中，我们介绍了一名因低密度脂蛋白受体（LDLR）基因突变而患有HeFH的患者。一名女性对他汀类药物治疗不耐受，且依折麦布单药治疗未能使低密度脂蛋白胆固醇（LDL-C）水平充分降低。基因检测证实存在FH的致病性变异，外显子7 - 14缺失。以阿利西尤单抗（皮下注射剂量150mg）作为主要治疗未显示出预期的治疗效果。因此，给予该患者英克西兰治疗（皮下注射剂量284mg），治疗3个月后及1年随访期间，低密度脂蛋白胆固醇水平显著降低。
对于他汀类药物不耐受的HeFH患者，英克西兰治疗已显示出有前景的结果。该疗法通过使用小干扰RNA（siRNA）靶向前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）的mRNA起作用，从而导致LDL-C水平显著降低。对于接受PCSK9抑制剂治疗后LDL-C水平未显著降低的患者，这种方法可以作为一种替代方案。对于因他汀类药物不耐受和基因突变而治疗选择有限的HeFH患者，英克西兰可能是一种有前景的治疗选择。
