Scicali Roberto, Di Pino Antonino, Ferrara Viviana, Rabuazzo Agata Maria, Purrello Francesco, Piro Salvatore
Department of Clinical and Experimental Medicine, University of Catania, Internal Medicine, Garibaldi Hospital, Via Palermo 636, 95122, Catania, Italy.
Acta Diabetol. 2021 Jul;58(7):949-957. doi: 10.1007/s00592-021-01703-z. Epub 2021 Mar 21.
Subjects with familial hypercholesterolemia (FH) are characterized by an increased amount of low-density lipoprotein cholesterol (LDL-C) that promotes a continuous inflammatory stimulus. Our aim was to evaluate the effect of PCSK9-i on inflammatory biomarkers, neutrophil-to-lymphocyte ratio, monocyte-to-high-density lipoprotein ratio (MHR), and on early atherosclerosis damage analyzed by pulse wave velocity (PWV) in a cohort of FH subjects.
In this prospective observational study, we evaluated 56 FH subjects on high-intensity statins plus ezetimibe and with an off-target LDL-C. All subjects were placed on PCSK9-i therapy and obtained biochemical analysis as well as PWV evaluation at baseline and after six months of PCSK9-i therapy.
After six months of add-on PCSK9-i therapy, only 42.9% of FH subjects attained LDL-C targets. As expected, a significant reduction of LDL-C (- 49.61%, p < 0.001) was observed after PCSK9-i therapy. Neutrophil count (NC) and MHR were reduced by PCSK9-i (-13.82% and -10.47%, respectively, p value for both < 0.05) and PWV significantly decreased after PCSK9-i therapy (- 20.4%, p < 0.05). Finally, simple regression analyses showed that ∆ PWV was significantly associated with ∆ LDL-C (p < 0.01), ∆ NC and ∆ MHR (p value for both < 0.05).
In conclusion, PCSK9-i therapy significantly improved lipid and inflammatory profiles and PWV values in FH subjects; our results support the positive effect of PCSK9-i in clinical practice.
家族性高胆固醇血症（FH）患者的特点是低密度脂蛋白胆固醇（LDL-C）水平升高，这会引发持续的炎症刺激。我们的目的是评估前蛋白转化酶枯草溶菌素9抑制剂（PCSK9-i）对一组FH患者炎症生物标志物、中性粒细胞与淋巴细胞比值、单核细胞与高密度脂蛋白比值（MHR）以及通过脉搏波速度（PWV）分析的早期动脉粥样硬化损伤的影响。
在这项前瞻性观察研究中，我们评估了56名接受高强度他汀类药物加依泽替米贝治疗且LDL-C未达标的FH患者。所有受试者均接受PCSK9-i治疗，并在基线时以及PCSK9-i治疗6个月后进行生化分析和PWV评估。
在添加PCSK9-i治疗6个月后，只有42.9%的FH患者达到了LDL-C目标。正如预期的那样，PCSK9-i治疗后LDL-C显著降低（-49.61%，p<0.001）。PCSK9-i使中性粒细胞计数（NC）和MHR降低（分别降低-13.82%和-10.47%，两者p值均<0.05），并且PCSK9-i治疗后PWV显著降低（-20.4%，p<0.05）。最后，简单回归分析表明，∆PWV与∆LDL-C（p<0.01）、∆NC和∆MHR显著相关（两者p值均<0.05）。
总之，PCSK9-i治疗显著改善了FH患者的血脂和炎症指标以及PWV值；我们的数据支持PCSK9-i在临床实践中的积极作用。
