Morales-Portano Julieta Danira, Trujillo-Cortés Rafael, Roa-Martínez Bricia Margarita, Pérez-Cabeza de Vaca Rebeca, García Silvia, Mondragón-Terán Paul, Suárez-Cuenca Juan A
Cardiology Department, National Medical Center "20 de Noviembre," ISSSTE, Mexico City, Mexico.
Coordination of Research, National Medical Center "20 de Noviembre," ISSSTE, Mexico City, Mexico.
Front Cardiovasc Med. 2024 Jul 18;11:1417044. doi: 10.3389/fcvm.2024.1417044. eCollection 2024.
Some clinical dyslipidemia cases do not respond to statins, known as statin-resistant familial hypercholesterolemia (SR-FH), in which patients are under a high cardiovascular risk despite statin therapy. Therefore, novel therapeutic alternatives are required. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce cholesterol levels and cardiovascular disease risk, particularly in patients with SR-FH, where PCSK9i may differentially affect pro- and anti-inflammatory mediators depending on the clinical setting.
To evaluate the effect of PCSK9i treatment on pro- and anti-inflammatory cytokines in patients with SR-FH.
Before-after comparison, quasi-experimental, single-center study in patients with SR-FH. Blood samples were processed to obtain complete blood counts of glycated hemoglobin and serum lipid levels. Flow cytometry was performed to characterize baseline circulating M1- and M2-macrophages and monocytes. Multiplexing of plasma samples was used to compare plasma fraktaline, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha. The endpoints were lower serum lipid levels and pro-inflammatory mediator modification.
Twenty patients with SR-FH, aged 58 years and most of them males, were included, with a mean body-mass index of 26.4 and showing ischemic heart disease and similar values of baseline M1- and M2-macrophages and monocytes. Six-month iPSCK-9 therapy considerably reduced LDLc, increased anti-inflammatory cytokine (IL-4), and modified pro-inflammatory cytokine (TNF-alpha and MCP-1) levels. No notable effects were observed for the other markers.
PCSK9i therapy exerted subclinical anti-inflammatory and anti-atherogenic effects, indicating potential benefits for clinical outcomes.
一些临床血脂异常病例对他汀类药物无反应，即他汀抵抗性家族性高胆固醇血症（SR-FH），尽管接受了他汀类药物治疗，这些患者仍面临较高的心血管疾病风险。因此，需要新的治疗选择。前蛋白转化酶枯草溶菌素/kexin 9型抑制剂（PCSK9i）可降低胆固醇水平并降低心血管疾病风险，尤其是在SR-FH患者中，在不同临床环境下，PCSK9i可能对促炎和抗炎介质产生不同影响。
评估PCSK9i治疗对SR-FH患者促炎和抗炎细胞因子的影响。
对SR-FH患者进行前后比较的准实验单中心研究。处理血样以获取糖化血红蛋白全血细胞计数和血脂水平。进行流式细胞术以表征基线循环M1和M2巨噬细胞及单核细胞。采用血浆样本多重分析比较血浆fraktaline、白细胞介素（ILs）、单核细胞趋化蛋白-1（MCP-1）和肿瘤坏死因子（TNF）-α。终点为降低的血脂水平和促炎介质的改变。
纳入20例SR-FH患者，年龄58岁，多数为男性，平均体重指数为26.4，患有缺血性心脏病，基线M1和M2巨噬细胞及单核细胞水平相似。6个月的iPSCK-9治疗显著降低了低密度脂蛋白胆固醇（LDLc），增加了抗炎细胞因子（IL-4），并改变了促炎细胞因子（TNF-α和MCP-1）水平。其他标志物未观察到明显影响。
PCSK9i治疗具有亚临床抗炎和抗动脉粥样硬化作用，表明对临床结局可能有益。
