Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Open Heart. 2018 Sep 18;5(2):e000765. doi: 10.1136/openhrt-2017-000765. eCollection 2018.
It is unclear if activation of inflammatory pathways regulates proprotein convertase subtilisin-kexin type 9 (PCSK9) levels.
We evaluated (1) the temporal course of serum PCSK9 during hospitalisation following acute coronary syndrome and associations with markers of inflammation (leucocyte counts, interleukin (IL)-6, C-reactive protein) and lipid levels and (2) the effect of inhibition of IL-6 signalling with the IL-6 receptor antibody tocilizumab on PCSK9 levels in a randomised, double-blind, placebo-controlled trial release in patients with non-ST-elevation myocardial infarction.
Serum PCSK9 increased during the acute phase and this response was modestly associated with neutrophil counts (r=0.24, p=0.009) and presence of hypercholesterolaemia (r=0.019, p=0.045), but was not modified by tocilizumab. However, a modifying effect of tocilizumab on PCSK9 levels was observed in patients with hypercholesterolaemia (p=0.024, repeated measures analysis of variance) and this effect was strongly correlated with the decrease in neutrophils (r=0.66, p=0.004).
Our study suggests that patients with a more atherogenic profile may benefit from anti-IL-6 therapy with regard to PCSK9.
NCT01491074.
目前尚不清楚炎症通路的激活是否调节前蛋白转化酶枯草溶菌素/κexin 9（PCSK9）水平。
我们评估了（1）急性冠状动脉综合征后住院期间血清 PCSK9 的时间过程及其与炎症标志物（白细胞计数、白细胞介素（IL）-6、C 反应蛋白）和血脂水平的关系，以及（2）用 IL-6 受体抗体托珠单抗抑制 IL-6 信号对非 ST 段抬高型心肌梗死患者随机、双盲、安慰剂对照试验释放中 PCSK9 水平的影响。
血清 PCSK9 在急性期增加，这种反应与中性粒细胞计数（r=0.24，p=0.009）和高胆固醇血症的存在（r=0.019，p=0.045）适度相关，但托珠单抗并未改变。然而，托珠单抗对高胆固醇血症患者的 PCSK9 水平有修饰作用（p=0.024，重复测量方差分析），这种作用与中性粒细胞的减少呈强烈相关（r=0.66，p=0.004）。
我们的研究表明，具有更多动脉粥样硬化特征的患者可能会从抗 IL-6 治疗中受益于 PCSK9。
NCT01491074。
