School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University.
Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center.
J Atheroscler Thromb. 2024 May 1;31(5):572-586. doi: 10.5551/jat.64326. Epub 2023 Dec 12.
Critical limb ischemia (CLI) is an emerging public health threat and lacks a reliable score for predicting the outcomes. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD-GENE) risk score helps identify patients with coronary artery disease who have cytochrome P450 2C19 (CYP2C19) polymorphism-related drug resistance and are at risk for cardiovascular adverse events. However, its application to CLI remains unknown. In this study, we aim to validate a modified ACD-GENE-CLI score to improve the prediction of major adverse limb events (MALEs) in patients with CLI receiving clopidogrel.
Patients with CLI receiving clopidogrel post-endovascular intervention were enrolled prospectively in two medical centers. Amputation and revascularization as MALEs were regarded as the outcomes.
A total of 473 patients were recruited, with a mean follow-up duration of 25 months. Except for obesity, old age, diabetes, chronic kidney disease (CKD), and CYP2C19 polymorphisms were significantly associated with MALEs. Using bootstrap regression analysis, we established a modified risk score (ACD-GENE-CLI) that included old age (≥ 65 years), diabetes, CKD, and CYP2C19 polymorphisms. At a cutoff value of 8, the ACD-GENE-CLI score was superior to the CYP2C19 deficiency only, and the conventional ABCD-GENE score in predicting MALEs (area under the curve: 0.69 vs. 0.59 vs. 0.67, p=0.01). The diagnostic ability of the ACD-GENE-CLI score was consistent in the external validation. Also, Kaplan-Meier curves showed that in CYP2C19 deficiency, the ABCD-GENE and ACD-GENE-CLI scores could all differentiate patients with CLI who are free from MALEs.
The modified ACD-GENE-CLI score could differentiate patients with CLI receiving clopidogrel who are at risk of MALEs. Further studies are required to generalize the utility of the score.
严重肢体缺血(CLI)是一种新出现的公共卫生威胁,目前缺乏可靠的评分系统来预测其结局。年龄、体重指数、慢性肾脏病、糖尿病和基因分型(ABCD-GENE)风险评分有助于识别存在细胞色素 P450 2C19(CYP2C19)多态性相关药物抵抗且存在心血管不良事件风险的冠心病患者。然而,其在 CLI 中的应用尚不清楚。本研究旨在验证改良的 ABCD-GENE-CLI 评分,以改善接受氯吡格雷治疗的 CLI 患者主要不良肢体事件(MALEs)的预测。
前瞻性纳入两所医学中心接受血管内介入治疗后接受氯吡格雷治疗的 CLI 患者。截肢和血运重建作为 MALEs 的结局。
共纳入 473 例患者,平均随访 25 个月。除肥胖外,高龄、糖尿病、慢性肾脏病(CKD)和 CYP2C19 多态性与 MALEs 显著相关。采用 Bootstrap 回归分析建立改良风险评分(ACD-GENE-CLI),包括高龄(≥65 岁)、糖尿病、CKD 和 CYP2C19 多态性。在截断值为 8 时,ACD-GENE-CLI 评分在预测 MALEs 方面优于仅 CYP2C19 缺乏和传统的 ABCD-GENE 评分(曲线下面积:0.69 比 0.59 比 0.67,p=0.01)。在外部验证中,ACD-GENE-CLI 评分的诊断能力保持一致。Kaplan-Meier 曲线显示,在 CYP2C19 缺乏时,ABCD-GENE 和 ACD-GENE-CLI 评分均能区分无 MALEs 的 CLI 患者。
改良的 ACD-GENE-CLI 评分可区分接受氯吡格雷治疗的 CLI 患者 MALEs 风险。需要进一步研究来推广该评分的应用。