Li Ben, Shaikh Farah, Zamzam Abdelrahman, Syed Muzammil H, Abdin Rawand, Qadura Mohammad
Department of Surgery, University of Toronto, Toronto, ON M5S 1A1, Canada.
Division of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, 30 Bond Street, Suite 7-076, Toronto, ON M5B 1W8, Canada.
J Clin Med. 2024 Jun 19;13(12):3583. doi: 10.3390/jcm13123583.
Myokines have been demonstrated to be associated with cardiovascular diseases; however, they have not been studied as biomarkers for peripheral artery disease (PAD). We identified interleukin-7 (IL-7) as a prognostic biomarker for PAD from a panel of myokines and developed predictive models for 2-year major adverse limb events (MALEs) using clinical features and plasma IL-7 levels. A prognostic study was conducted with a cohort of 476 patients (312 with PAD and 164 without PAD) that were recruited prospectively. Their plasma concentrations of five circulating myokines were measured at recruitment, and the patients were followed for two years. The outcome of interest was two-year MALEs (composite of major amputation, vascular intervention, or acute limb ischemia). Cox proportional hazards analysis was performed to identify IL-7 as the only myokine that was associated with 2-year MALEs. The data were randomly divided into training (70%) and test sets (30%). A random forest model was trained using clinical characteristics (demographics, comorbidities, and medications) and plasma IL-7 levels with 10-fold cross-validation. The primary model evaluation metric was the F1 score. The prognostic model was used to classify patients into low vs. high risk of developing adverse limb events based on the Youden Index. Freedom from MALEs over 2 years was compared between the risk-stratified groups using Cox proportional hazards analysis. Two-year MALEs occurred in 28 (9%) of patients with PAD. IL-7 was the only myokine that was statistically significantly correlated with two-year MALE (HR 1.56 [95% CI 1.12-1.88], = 0.007). For the prognosis of 2-year MALEs, our model achieved an F1 score of 0.829 using plasma IL-7 levels in combination with clinical features. Patients classified as high-risk by the predictive model were significantly more likely to develop MALEs over a 2-year period (HR 1.66 [95% CI 1.22-1.98], = 0.006). From a panel of myokines, IL-7 was identified as a prognostic biomarker for PAD. Using a combination of clinical characteristics and plasma IL-7 levels, we propose an accurate predictive model for 2-year MALEs in patients with PAD. Our model may support PAD risk stratification, guiding clinical decisions on additional vascular evaluation, specialist referrals, and medical/surgical management, thereby improving outcomes.
肌动蛋白已被证明与心血管疾病有关；然而，它们尚未作为外周动脉疾病（PAD）的生物标志物进行研究。我们从一组肌动蛋白中确定白细胞介素-7（IL-7）为PAD的预后生物标志物，并使用临床特征和血浆IL-7水平建立了2年主要肢体不良事件（MALE）的预测模型。对前瞻性招募的476名患者（312名患有PAD，164名未患有PAD）进行了一项预后研究。在招募时测量了他们血浆中五种循环肌动蛋白的浓度，并对患者进行了两年的随访。感兴趣的结局是两年的MALE（主要截肢、血管介入或急性肢体缺血的综合结果）。进行Cox比例风险分析以确定IL-7是唯一与两年MALE相关的肌动蛋白。数据被随机分为训练集（70%）和测试集（30%）。使用临床特征（人口统计学、合并症和药物治疗）和血浆IL-7水平通过10倍交叉验证训练了一个随机森林模型。主要的模型评估指标是F1分数。使用约登指数将预后模型用于将患者分类为发生肢体不良事件的低风险或高风险。使用Cox比例风险分析比较风险分层组之间两年内无MALE的情况。312名患有PAD的患者中有28名（9%）发生了两年的MALE。IL-7是唯一与两年MALE有统计学显著相关性的肌动蛋白（HR 1.56 [95% CI 1.12 - 1.88]，P = 0.007）。对于两年MALE的预后，我们的模型使用血浆IL-7水平结合临床特征，F1分数达到0.829。预测模型分类为高风险的患者在两年内发生MALE的可能性显著更高（HR 1.66 [95% CI 1.22 - 1.98]，P = 0.006）。从一组肌动蛋白中，IL-7被确定为PAD的预后生物标志物。通过结合临床特征和血浆IL-7水平，我们提出了一个针对PAD患者两年MALE的准确预测模型。我们的模型可能支持PAD风险分层，指导关于额外血管评估、专科转诊以及药物/手术管理的临床决策，从而改善预后。
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