HIF-1α与卵圆孔未闭合并偏头痛患者封堵术后中到大量残余分流的相关性研究

Correlation between HIF-1α and moderate-to-large residual shunt after closure in patients with patent foramen ovale and migraine

摘要

目的: 探讨血浆缺氧诱导因子-1α（hypoxia-inducible factor-1α，HIF-1α）与卵圆孔未闭（patent foramen ovale，PFO）合并偏头痛患者经皮PFO封堵术后中到大量残余分流（moderate-to-large residual shunt，MLRS）的相关性。方法: 前瞻性纳入2023年8月—2024年8月于南通大学附属医院接受PFO封堵治疗的偏头痛患者45例，收集术前、术后6及12个月的临床资料，根据是否发生MLRS分为MLRS组和非MLRS组，比较临床指标及血浆HIF-1α水平。采用多因素Logistic回归筛选术后6及12个月发生MLRS的潜在相关因素，受试者工作特征（receiver operating characteristic，ROC）曲线评估预测效能，并应用广义估算方程（generalized estimating equation，GEE）分析HIF-1α与抗凝血酶Ⅲ（antithrombin Ⅲ，AT-Ⅲ）和中性粒细胞计数比淋巴细胞计数（neutrophil-to-lymphocyte ratio，NLR）的交互效应。结果: 术后6及12个月血浆HIF-1α水平较术前下降（P<0.01）。术后6及12个月MLRS组术前HIF-1α均高于无MLRS组（P<0.05）。多因素Logistic回归显示，术前HIF-1α水平是术后6及12个月MLRS的共同潜在相关因素（P<0.05）。术前AT-Ⅲ水平降低与术后6个月MLRS风险增加相关（P<0.05），而术前NLR水平升高与术后12个月MLRS风险增加相关（P<0.05）。经Bootstrap校正后，术前HIF-1α预测术后6及12个月MLRS的ROC曲线下面积（area under curve，AUC）分别为0.823和0.825；联合AT-Ⅲ及联合NLR的AUC分别为0.953和0.937（P均<0.05）。GEE结果显示HIF-1α与NLR存在显著关联（P<0.05）。结论: PFO封堵术后HIF-1α水平呈持续下降。术前血浆HIF-1α可能是术后MLRS的潜在相关因子，联合AT-Ⅲ或NLR分别对术后6及12个月的MLRS表现出初步的区分效能。

Abstract

Objective: To investigate the association between plasma hypoxia-inducible factor-1α (HIF-1α) and moderate-to-large residual shunt (MLRS) after percutaneous patent foramen ovale (PFO) closure in patients with migraine and PFO. Methods: This prospective study included 45 migraine patients who underwent PFO closure at the Affiliated Hospital of Nantong University from August 2023 to August 2024. Patients were divided into MLRS and non-MLRS groups based on the presence or absence of MLRS. Clinical data and plasma HIF-1α levels were collected and compared before surgery, and 6 and 12 months after surgery. Multivariate logistic regression was used to identify potential factors for MLRS at 6 and 12 months. Receiver operating characteristic (ROC) curves evaluated predictive performance, and generalized estimating equation (GEE) assessed the interaction of HIF-1α with both antithrombin Ⅲ (AT-Ⅲ) and the neutrophil-to-lymphocyte ratio (NLR). Results: Plasma HIF-1α levels at 6 and 12 months postoperatively were significantly lower than preoperative levels (P<0.01). Preoperative HIF-1α levels were significantly higher in the MLRS group than in the non-MLRS group at both follow-up time points (P<0.05). Multivariate logistic regression showed that preoperative HIF-1α was a potential factor associated with MLRS at 6 and 12 months (P<0.05). Decreased preoperative AT-Ⅲ levels were correlated with an increased risk of MLRS at 6 months postoperatively (P<0.05), while elevated preoperative NLR levels were associated with an increased risk of MLRS at 12 months (P<0.05). After Bootstrap correction, ROC analysis demonstrated that the area under curve (AUC) values of preoperative HIF-1α for predicting MLRS at 6 and 12 months were 0.823 and 0.825, respectively. The AUC for HIF-1α combined with AT-Ⅲ was 0.953 (6 months), and with NLR was 0.937 (12 months) (all P<0.05). GEE revealed a significant association between HIF-1α and NLR (P<0.05). Conclusion: Plasma HIF-1α levels show sustained decline after PFO closure. Preoperative plasma HIF-1α is a potential factor associated with postoperative MLRS, and its combination with AT-Ⅲ (at 6 months) and NLR (at 12 months) shows preliminary discriminative performance, respectively.

关键词

卵圆孔未闭 / 偏头痛 / 缺氧诱导因子-1α / 中到大量残余分流

Key words

patent foramen ovale / migraine / hypoxia-inducible factor-1α / moderate-to-large residual shunt

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基金资助

南通市自然科学基金和社会民生科技计划(MSZ2023182)

南通市卫生健康委员会科研课题(QNZ2023003)