Shimizu Tomohiro, Morishita Tetsuji, Uzui Hiroyasu, Sato Yusuke, Kataoka Tatsuhiro, Miyoshi Machiko, Yamaguchi Junya, Shiomi Yuichiro, Ikeda Hiroyuki, Tama Naoto, Hasegawa Kanae, Ishida Kentaro, Tada Hiroshi
Department of Cardiovascular Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Shimoaizuki, Matsuoka Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.
Department of Internal Medicine, Matsunami General Hospital, Gifu, 501-6062, Japan.
Heart Vessels. 2025 Apr;40(4):312-319. doi: 10.1007/s00380-024-02473-8. Epub 2024 Oct 5.
This study examined the anti-inflammatory and endothelial function-enhancing effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor therapy in the early phase after acute myocardial infarction (AMI) by assessing changes in tumor necrosis factor-α (TNF-α) levels and the L-arginine/asymmetric-dimethylarginine (ADMA) ratio. This retrospective, single-center cohort study included patients who underwent successful timely primary percutaneous coronary intervention (PCI) for first-onset AMI between September 2017 and March 2018. The PCSK9 inhibitor group comprised patients who received 75 mg alirocumab up to 7 days after AMI, while the standard therapy group comprised patients who did not. We evaluated the change in TNF-α levels and the L-arginine/ADMA ratio at the time of hospital admission and prior to discharge. PCSK9 inhibitor therapy in the early phase after AMI suppressed TNF-α levels (standard therapy group, 1.64 ± 2.14 pg/mL vs. PCSK9 inhibitor group, 0.26 ± 0.33 pg/mL; p = 0.033) and increased the L-arginine/ADMA ratio (standard therapy group, - 13.0 ± 39.7 vs. PCSK9 inhibitor group, 23.2 ± 39.7; p = 0.042). Upon multiple regression analysis adjusted for sex, age, and peak creatine kinase levels, PCSK9 inhibitor therapy was associated with TNF-α suppression (p = 0.025; β = - 0.235, 95% confidence interval [CI], - 0.436 to - 0.033). The L-arginine/ADMA ratio was also analyzed using multiple regression, adjusted for sex, age, peak creatine kinase levels, and smoking, showing a significant improvement in the ratio (p = 0.018; β = 41.913, 95% CI, 10.337-73.491). Moreover, a weak negative correlation was suggested between the change in TNF-α levels and the change in L-arginine/ADMA ratio (r = - 0.393, p = 0.058). PCSK9 inhibitor therapy in the early phase after AMI suppresses TNF-α levels and improves the L-arginine/ADMA ratio, potentially indicating anti-inflammatory and endothelial function-enhancing effects.
本研究通过评估肿瘤坏死因子-α（TNF-α）水平和L-精氨酸/不对称二甲基精氨酸（ADMA）比值的变化，探讨了急性心肌梗死（AMI）后早期前蛋白转化酶枯草溶菌素/kexin 9（PCSK9）抑制剂治疗的抗炎和增强内皮功能的作用。这项回顾性、单中心队列研究纳入了2017年9月至2018年3月期间因首次发作的AMI成功接受及时直接经皮冠状动脉介入治疗（PCI）的患者。PCSK9抑制剂组包括AMI后7天内接受75mg阿利西尤单抗治疗的患者，而标准治疗组包括未接受该治疗的患者。我们评估了入院时和出院前TNF-α水平以及L-精氨酸/ADMA比值的变化。AMI后早期的PCSK9抑制剂治疗可降低TNF-α水平（标准治疗组，1.64±2.14pg/mL vs. PCSK9抑制剂组，0.26±0.33pg/mL；p = 0.033）并提高L-精氨酸/ADMA比值（标准治疗组，-13.0±39.7 vs. PCSK9抑制剂组，23.2±39.7；p = 0.042）。在对性别、年龄和肌酸激酶峰值水平进行校正的多元回归分析中，PCSK9抑制剂治疗与TNF-α的降低相关（p = 0.025；β = -0.235，95%置信区间[CI]，-0.436至-0.033）。还使用多元回归分析了L-精氨酸/ADMA比值，对性别、年龄、肌酸激酶峰值水平和吸烟进行了校正，结果显示该比值有显著改善（p = 0.018；β = 41.913，95%CI，10.337 - 73.491）。此外，TNF-α水平的变化与L-精氨酸/ADMA比值的变化之间存在弱负相关（r = -0.393，p = 0.058）。AMI后早期的PCSK9抑制剂治疗可降低TNF-α水平并改善L-精氨酸/ADMA比值，这可能表明其具有抗炎和增强内皮功能的作用。
