Li Ben, Zamzam Abdelrahman, Syed Muzammil H, Jahanpour Niousha, Jain Shubha, Abdin Rawand, Qadura Mohammad
Division of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada.
Department of Medicine, McMaster University, Hamilton, ON, Canada.
Front Cardiovasc Med. 2022 Jun 20;9:875244. doi: 10.3389/fcvm.2022.875244. eCollection 2022.
Despite its significant association with limb loss and death, peripheral artery disease (PAD) remains underdiagnosed and undertreated. The current accepted gold-standard for PAD screening, the ankle brachial index (ABI), is limited by operator dependence, erroneous interpretation, and unreliability in patients with diabetes. Fatty acid binding protein 3 (FABP3) is an intracellular protein that becomes released into circulation and excreted into urine following skeletal muscle injury. We examined the prognostic ability of urinary FABP3 (uFABP3) in predicting adverse PAD-related events.
In this prospective case-control study, urine samples were collected from patients with PAD ( = 142) and without PAD ( = 72). The cohort was followed for 2 years. uFABP3 was normalized to urinary creatinine (uCr) (uFABP3/uCr). The primary outcome was major adverse limb event (MALE; composite of vascular intervention [open or endovascular] or major limb amputation). The secondary outcome was worsening PAD status (drop in ABI≥0.15). Cox regression analyses with multivariable adjustment for baseline demographic and clinical variables were performed to assess the prognostic value of uFABP3/uCr with regards to predicting MALE and worsening PAD status.
Patients with PAD had significantly higher median [IQR] uFABP3/uCr levels (3.46 [2.45-6.90] vs. 2.61 [1.98-4.62], = 0.001). MALE and worsening PAD status were observed in 21 (10%) and 28 (14%) patients, respectively. uFABP3/uCr predicted MALE and worsening PAD status with adjusted hazard ratios (HR) of 1.28 (1.16-1.41, = 0.001) and 1.16 (1.02-1.27, = 0.021), respectively. Patients with high uFABP3/uCr had a lower 2-year freedom from MALE (86 vs. 96%, = 0.047) and worsening PAD status (78 vs. 99%, = 0.001). There was good discriminatory ability for uFABP3/uCr in predicting the primary outcome of MALE, with an area under the receiver operating characteristics curve (AUROC) of 0.78.
Measuring uFABP3/uCr levels in patients with PAD can help identify those at high risk of adverse PAD-related events. This study highlights the prognostic value of uFABP3 in risk-stratifying individuals for further diagnostic vascular evaluation or aggressive medical management.
尽管外周动脉疾病（PAD）与肢体缺失和死亡显著相关，但仍存在诊断不足和治疗不足的情况。目前公认的PAD筛查金标准——踝臂指数（ABI），受操作者依赖性、解读错误以及糖尿病患者中不可靠性的限制。脂肪酸结合蛋白3（FABP3）是一种细胞内蛋白，在骨骼肌损伤后会释放到循环中并排泄到尿液中。我们研究了尿FABP3（uFABP3）预测PAD相关不良事件的预后能力。
在这项前瞻性病例对照研究中，从患有PAD的患者（n = 142）和未患PAD的患者（n = 72）中收集尿液样本。对该队列进行了2年的随访。uFABP3以尿肌酐（uCr）进行标准化（uFABP3/uCr）。主要结局是主要不良肢体事件（MALE；血管介入[开放或血管内]或大肢体截肢的综合情况）。次要结局是PAD状态恶化（ABI下降≥0.15）。进行了Cox回归分析，并对基线人口统计学和临床变量进行多变量调整，以评估uFABP3/uCr对预测MALE和PAD状态恶化的预后价值。
PAD患者的uFABP3/uCr水平中位数[四分位间距]显著更高（3.46[2.45 - 6.90]对2.61[1.98 - 4.62]，P = 0.001）。分别在21例（10%）和28例（14%）患者中观察到MALE和PAD状态恶化。uFABP3/uCr预测MALE和PAD状态恶化的调整后风险比（HR）分别为1.28（1.16 - 1.41，P = 0.001）和1.16（1.02 - 1.27，P = 0.021）。uFABP3/uCr高的患者无MALE的2年自由度较低（86%对96%，P = 0.047），且无PAD状态恶化的2年自由度也较低（78%对99%，P = 0.001）。uFABP3/uCr在预测MALE的主要结局方面具有良好的鉴别能力，受试者工作特征曲线下面积（AUROC）为0.78。
测量PAD患者的uFABP3/uCr水平有助于识别那些有PAD相关不良事件高风险的患者。本研究强调了uFABP3在对个体进行风险分层以进行进一步诊断性血管评估或积极药物治疗方面的预后价值。
