From the, First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA.
J Intern Med. 2021 Feb;289(2):179-192. doi: 10.1111/joim.13150. Epub 2020 Jul 30.
Pro-protein convertase subtilisin/kexin 9 (PCSK9) is a proenzyme primarily known to regulate low-density lipoprotein receptor re-uptake on hepatocytes. Whether PCSK9 can concurrently trigger inflammation or not remains unclear. Here, we investigated the potential association between circulating levels of PCSK9 and mortality in patients with severe sepsis or septic shock.
Plasma PCSK9 levels at days 1, 2 and 7 were measured in 958 patients with severe sepsis or septic shock previously enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. Correlations between levels of PCSK9 and pentraxin 3 (PTX3), a biomarker of disease severity, were evaluated with ranked Spearman's coefficients. Cox proportional hazards models were used to assess the association of PCSK9 levels at day 1 with 28- and 90-day mortality.
Median plasma PCSK9 levels were 278 [182-452] ng mL on day 1. PCSK9 correlated positively with PTX3 at the three time-points, and patients with septic shock within the first quartile of PCSK9 showed higher levels of PTX3. Similar mortality rates were observed in patients with severe sepsis across PCSK9 quartiles. Patients with septic shock with lower PCSK9 levels on day 1 (within the first quartile) showed the highest 28- and 90-day mortality rate as compared to other quartiles.
In our sub-analysis of the ALBIOS trial, we found that patients with septic shock presenting with lower plasma PCSK9 levels experienced higher mortality rate. Further studies are warranted to better evaluate the pathophysiological role of PCSK9 in sepsis.
前蛋白转化酶枯草溶菌素/胰凝乳蛋白酶 9（PCSK9）是一种主要调节肝细胞内低密度脂蛋白受体再摄取的酶原。PCSK9 是否可以同时引发炎症尚不清楚。在这里，我们研究了循环 PCSK9 水平与严重脓毒症或感染性休克患者死亡率之间的潜在关联。
在先前参加 Albumin Italian Outcome Sepsis（ALBIOS）试验的 958 名严重脓毒症或感染性休克患者中，测量了第 1、2 和 7 天的血浆 PCSK9 水平。使用等级 Spearman 系数评估 PCSK9 水平与疾病严重程度标志物 pentraxin 3（PTX3）之间的相关性。Cox 比例风险模型用于评估第 1 天 PCSK9 水平与 28 天和 90 天死亡率之间的关联。
第 1 天的中位血浆 PCSK9 水平为 278[182-452]ng/ml。PCSK9 与 PTX3 在三个时间点均呈正相关，PCSK9 四分位 1 内的感染性休克患者 PTX3 水平更高。严重脓毒症患者在 PCSK9 四分位 1 内观察到相似的死亡率。第 1 天（四分位 1 内）PCSK9 水平较低的感染性休克患者与其他四分位相比，28 天和 90 天死亡率最高。
在 ALBIOS 试验的亚分析中，我们发现血浆 PCSK9 水平较低的感染性休克患者死亡率更高。需要进一步研究以更好地评估 PCSK9 在脓毒症中的病理生理作用。
