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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2024, Vol. 17 ›› Issue (04) : 585 -589. doi: 10.3877/cma.j.issn.1674-6902.2024.04.015

论著

特发性肺动脉高压血清PCSK9表达及预后意义
罗霞1, 王宝梅1, 李淑景1, 杨英1,†()   
  1. 1. 266000　青岛，青岛大学附属青岛市海慈医院（青岛市中医医院）呼吸内科
  • 收稿日期:2024-01-13 出版日期:2024-08-25
  • 通信作者: 杨英
  • 基金资助:
    山东省中医药科技项目(2020Q078)

Expression of serum PCSK9 in idiopathic pulmonary hypertension and its prognostic significance

Xia Luo1, Baomei Wang1, Shujing Li1, Ying Yang1,†()   

  1. 1. Department of Respiratory Medicine, Qingdao Haici Hospital, Qingdao University, Qingdao 266000, China
  • Received:2024-01-13 Published:2024-08-25
  • Corresponding author: Ying Yang
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罗霞, 王宝梅, 李淑景, 杨英. 特发性肺动脉高压血清PCSK9表达及预后意义[J]. 中华肺部疾病杂志(电子版), 2024, 17(04): 585-589.

Xia Luo, Baomei Wang, Shujing Li, Ying Yang. Expression of serum PCSK9 in idiopathic pulmonary hypertension and its prognostic significance[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2024, 17(04): 585-589.

目的

分析血清前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/Kexin 9, PCSK9)与特发性肺动脉高压(idiopathic pulmonary hypertension, IPAH)的临床特征、血液动力学和预后相关性。

方法

选择2019年12月至2022年11月我院收治的42例IPAH患者为对象。采用酶联免疫吸附测定法检测血清PCSK9水平。记录随访1年无临床恶化生存率。

结果

IPAH者血清PCSK9水平135.63(77.93，216.69)ng/ml。受试者工作特征曲线(receiver operating characteristic, ROC)分析显示，血清PCSK9水平诊断IPAH曲线下面积为0.763(95%CI：0.655～0.871，P<0.05)，最佳截断值血清PCSK9为107.48 ng/ml，特异性为88.2%。IPAH血清PCSK9水平与肺动脉收缩压(r＝0.488)、舒张压(r＝0.634)、平均肺动脉压(mean pulmonary artery pressure, mPAP)(r＝0.653)、平均肺血管楔压(r＝0.315)、肺血管阻力(r＝0.576)、世界卫生组织功能分级(r＝0.519)呈正相关(P<0.05)，与6 min步行距离(r＝－0.361，P<0.05)呈负相关。随访1年，IPAH患者死亡11例(26.19%)，存活31例(73.81%)。Kaplan-Meier分析显示，PCSK9>107.48 ng/ml的IPAH临床无恶化生存5例(11.90%)低于PCSK9≤107.48 ng/ml IPAH者26例(61.90%)(P<0.05)。多因素COX分析显示，BNP(HR: 1.476，95%CI: 1.082～2.013)和PCSK9(HR：1.007，95%CI: 1.001～1.014)是临床恶化的预测因子。受限三次样本时，PCSK9与临床恶化HR线性相关。

结论

PCSK9与肺动脉高压状态、血液动力学和预后相关。

关键词: 特发性肺动脉高压, 前蛋白转化酶枯草溶菌素9, 疾病严重程度, 血液动力学
Objective

To analyze the relationship between serum proprotein convertase subtilisin/Kexin 9 (PCSK9) and clinical features hemodynamics, and prognosis of idiopathic pulmonary hypertension(IPAH).

Methods

All of 42 patients with IPAH in our hospital from December 2019 to November 2022 were selected as subjects. Serum PCSK9 level was detected by enzyme-linked immunosorbent assay. The 1-year survival rate without clinical deterioration was recorded.

Results

The level of PCSK9 in patients with IPAH was 135.63 (77.93, 216.69) ng/ml. Receiver operating characteristic (ROC) analysis showed that the area under the IPAH curve of serum PCSK9 level diagnosis was 0.763 (95%CI: 0.655 ~ 0.871)(P<0.05), the optimal cut-off value of serum PCSK9 was 107.48ng/ml, and the specificity was 88.2%. Serum PCSK9 level in IPAH was positively correlated with systolic blood pressure (r=0.488), diastolic blood pressure (r=0.634) and mean pulmonary artery pressure (mean pulmonary artery pressure(mPAP) (r=0.653), mean pulmonary vascular wedge pressure (r=0.315), pulmonary vascular resistance (r=0.576), World Health Organization functional classification (r=0.519) (P<0.05), and were negatively correlated with 6min walking distance (r=-0.361, P<0.05). After 1 year of follow-up, 11 IPAH patients died (26.19%) and 31 survived (73.81%). Kaplan-Meier analysis showed that 5 cases (11.90%) of IPAH patients with PCSK9>107.48 ng/ml were clinically progression-free compared with 26 cases (61.90%) of IPAH patients with PCSK9≤107.48 ng/ml (P<0.05). Multivariate COX analysis showed that BNP (HR: 1.476, 95%CI: 1.082-2.013) and PCSK9 (HR: 1.007, 95%CI: 1.001-1.014) were predictors of clinical deterioration. PCSK9 was linearly correlated with clinical deterioration HR (P<0.05) when three samples were restricted.

Conclusion

PCSK9 is associated with the functional status, hemodynamics and prognosis of pulmonary hypertension.

Key words: Idiopathic pulmonary hypertension, Proproteinase subtilysin 9, Severity of the disease, Hemodynamics
表1 mPAP相关多因素分析
变　量 非标准化系数 标准化系数 t值 P值 95%CI
β SE
年龄 0.035 0.097 0.050 0.358 0.723 －0.163～0.232
性别 0.975 2.445 0.052 0.399 0.693 －4.019～5.968
体质量指数 1.348 2.248 0.072 0.600 0.553 －3.242～5.939
高血压史 1.253 2.690 0.058 0.466 0.645 －4.241～6.747
血脂异常史 －1.158 2.758 －0.065 －0.420 0.677 －6.790～4.473
糖尿病史 0.074 0.316 0.034 0.235 0.816 －0.572～0.720
Hb 0.157 0.580 0.033 0.271 0.788 －1.028～1.342
eGFR 0.013 0.088 0.027 0.149 0.882 －0.166～0.192
Cre －0.246 1.025 －0.037 －0.240 0.812 －2.339～1.847
BNP 0.012 0.006 0.271 1.997 0.042 0.001～0.025
PCSK9 0.057 0.012 0.629 4.632 0.000 0.032～0.083
表2 临床恶化比例风险单因素COX分析
影响因素 β SE Wald P值 HR 95%CI
年龄 0.004 0.025 0.021 0.886 1.004 0.956～1.054
性别 －1.164 0.607 3.676 0.050 0.312 0.095～1.026
体质量指数 －0.048 0.081 0.350 0.554 0.953 0.814～1.117
高血压史 0.370 0.627 0.349 0.555 1.448 0.424～4.948
血脂异常史 3.378 3.154 1.147 0.284 29.305 0.061～141.320
糖尿病史 －0.167 0.627 0.071 0.789 0.846 0.248～2.889
WHO-FC 0.677 0.537 1.589 0.208 1.968 0.687～5.639
6MWD －0.004 0.002 3.456 0.043 0.996 0.991～1.001
Hb －0.112 0.164 0.469 0.493 0.894 0.648～1.233
eGFR －0.023 0.015 2.328 0.127 0.977 0.948～1.007
Cre 0.009 0.216 0.002 0.966 1.009 0.661～1.540
BNP 0.334 0.122 7.440 0.006 1.396 1.098～1.774
PCSK9 0.007 0.003 7.347 0.007 1.007 1.002～1.012
PASP －0.002 0.018 0.018 0.895 0.998 0.962～1.034
PADP 0.045 0.047 0.902 0.342 1.046 0.954～1.146
mPAP 0.055 0.025 4.901 0.027 1.056 1.006～1.109
mPAWP 0.055 0.242 0.052 0.820 1.057 0.658～1.697
CI －0.012 0.106 0.014 0.906 0.988 0.803～1.215
CO 0.168 0.385 0.191 0.662 1.183 0.556～2.517
PVR 0.001 0.001 0.090 0.764 1.001 0.997～1.002
表3 临床恶化比例风险的多因素COX分析
变　量 β SE Wald P值 HR 95%CI
性别 －1.045 0.707 2.188 0.139 0.352 0.088～1.405
6MWD －0.002 0.002 1.021 0.312 0.998 0.994～1.002
BNP 0.389 0.158 6.054 0.014 1.476 1.082～2.013
PCSK9 0.007 0.003 4.736 0.030 1.007 1.001～1.014
mPAP 0.004 0.041 0.010 0.920 1.004 0.926～1.089
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