Silva Ivone, Teixeira Andreia, Oliveira José, Almeida Rui, Vasconcelos Carlos
Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Multidisciplinar Unit of Biomedical Investigation, Porto, Portugal.
Department of Health Information and Decision Sciences, Universidade do Porto, CINTESIS - Centre for Research in Health Technologies and Information Systems, Porto, Portugal.
Clin Hemorheol Microcirc. 2017;66(2):117-130. doi: 10.3233/CH-150044.
To evaluate endothelial dysfunction and microvascular damage in secondary Raynaud Phenomenon (SRP) and Systemic sclerosis (SSc)-associated patients as possible predictors of ischemic fingertip digital ulcers (DU) in a 3-year clinical follow-up.
Flow-mediated dilatation (FMD), nailfold videocapillaroscopy (NVC), endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA) were analysed in a 3-year observational cohort study of 77 SRP patients with systemic sclerosis. The primary outcome was the occurrence of a new DU.
Risk factors for DU at baseline were low FMD% (p < 0.001), NVC pattern (p < 0.001), high microangiopathy evolution score (MES) (p < 0.001), increased ET-1 (p < 0.001) and increased ADMA serum levels (p = 0.001). Median time to the occurrence of a new DU was 4.50 (1.25-16.25) months. The risk factors for the occurrence of at least one new DU episode in follow-up included a history of at least one DU before enrolment (p < 0.001), autoantibody anti-scleroderma-70 (p = 0.012), NVC late pattern (p < 0.001), high MES score (p < 0.001), low FMD% (p < 0.001) and increased ET-1 serum levels (p < 0.001).We used univariate Cox regression analysis to show that FMD >9.41% (HR: 0.37 95% CI: 0.14-0.99) and ET-1 >11.85 pmol/L (HR: 3.81 95% CI: 1.41-10.26) and NVC (HR: 2.29 95% CI: 0.97-5.38) were predictors of DU recurrence. In terms of first DU event in naïve DU patients at baseline, late NVC pattern (HR: 12.66 95% CI: 2.06-77.89) and MES score (HR: 1.693 95% CI: 1.257-2.279) were independent predictors.
This study identified endothelium dysfunction biomarkers (FMD and ET-1) and severe microvascular damage in NVC as strong predictors of new DU in SSc patients.
在一项为期3年的临床随访中，评估继发性雷诺现象（SRP）和系统性硬化症（SSc）相关患者的内皮功能障碍和微血管损伤，作为缺血性指尖溃疡（DU）的可能预测指标。
在一项对77例患有系统性硬化症的SRP患者进行的为期3年的观察性队列研究中，分析了血流介导的血管舒张（FMD）、甲襞微血管造影（NVC）、内皮素-1（ET-1）和不对称二甲基精氨酸（ADMA）。主要结局是新发DU的发生。
基线时DU的危险因素为低FMD%（p<0.001）、NVC模式（p<0.001）、高微血管病变进展评分（MES）（p<0.001）、ET-1升高（p<0.001）和ADMA血清水平升高（p=0.001）。新发DU的中位时间为4.50（1.25-16.25）个月。随访中至少发生一次新DU发作的危险因素包括入组前至少有一次DU病史（p<0.001）、抗硬皮病-70自身抗体（p=0.012）、NVC晚期模式（p<0.001）、高MES评分（p<0.001）、低FMD%（p<0.001）和ET-1血清水平升高（p<0.001）。我们使用单变量Cox回归分析表明，FMD>9.41%（HR：0.37，95%CI：0.14-0.99）、ET-1>11.85 pmol/L（HR：3.81，95%CI：1.41-10.26）和NVC（HR：2.29，95%CI：0.97-5.38）是DU复发的预测指标。就基线时初发DU患者的首次DU事件而言，NVC晚期模式（HR：12.66，95%CI：2.06-77.89）和MES评分（HR：1.693，95%CI：1.257-2.279）是独立预测指标。
本研究确定内皮功能障碍生物标志物（FMD和ET-1）以及NVC中的严重微血管损伤是SSc患者新发DU的强预测指标。
