Since the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI. This single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α. Unadjusted Kaplan–Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28–5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12–5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively). The study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI. Trial registration: This study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians’ Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan—Clinical Trials Registry, UMIN-CTR 000035587).

中文翻译：

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血浆无活性基质细胞衍生因子 1α 水平升高预示糖尿病患者经皮冠状动脉介入治疗后长期预后不佳

由于糖尿病（DM）并发症是冠状动脉疾病（CAD）患者不良心血管结局的风险，因此需要对接受经皮冠状动脉介入治疗（PCI）后的糖尿病患者进行适当的风险评估。然而，没有有用的生物标志物来预测该人群的结果。尽管基质细胞衍生因子 1α (SDF-1α)（一种循环趋化因子）被证明具有心脏保护作用，但 SDF-1α 对患有 CAD 的糖尿病患者的预后影响尚未完全阐明。此外，SDF-1α亚型在结果预测中的作用仍不清楚。因此，本研究旨在评估三种形式的 SDF-1α（包括总、活性和非活性形式的 SDF-1α）对 DM 患者和 PCI 后的预后影响。这项单中心回顾性分析涉及 2008 年至 2018 年间首次接受 PCI 的连续糖尿病患者 (n = 849)。主要和次要结局指标分别是全因死亡以及心血管死亡、非致命性心肌梗死和缺血性卒中的复合死亡（3P-MACE）。为了测定 SDF-1α 的血浆水平，我们不仅测量了 SDF-1α 的总量，还通过 ELISA 测量了 SDF-1α 的活性类型。通过从总 SDF-1α 中减去活性异构体来计算 SDF-1α 的非活性异构体。未经调整的 Kaplan-Meier 分析显示，非活性 SDF-1α 水平升高的患者全因死亡和 3P-MACE 的风险增加。然而，总 SDF-1α 和活性 SDF-1α 的血浆水平与结果指标的累积发生率无关。多变量 Cox 风险分析反复表明，1 个较高的对数转换非活性 SDF-1α 与全因死亡风险增加显着相关（风险比 (HR)：2.64，95% 置信区间 (CI)：1.28–5.34，p = 0.008）和 3P-MACE（HR：2.51，95% CI：1.12–5.46，p = 0.02）。此外，非活动 SDF-1α 的预测性能高于总 SDF-1α（非活动 SDF-1α 和总 SDF-1α 全因死亡的 C 统计量：0.631 vs 0.554，3P-MACE：0.623 vs 0.524） ）。研究结果表明，血浆非活性 SDF-1α 水平升高可能是糖尿病患者 PCI 后长期预后不良的有用指标。试验注册：本研究描述了对在日本东京顺天堂大学医院（顺天堂临床试验医师联盟，J-PACT）接受 PCI 的患者的前瞻性注册数据库的回顾性分析，该数据库已公开注册（大学医学信息网络）日本—临床试验注册中心，UMIN-CTR 000035587）。