Division of Angiology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; Swiss Cardiovascular Center, Division of Clinical and Interventional Angiology Inselspital, University Hospital and University of Bern, Switzerland.
Clinical Trial Unit Bern, Department of Clinical Research, and Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland.
Clin Chim Acta. 2015 Jul 20;447:16-22. doi: 10.1016/j.cca.2015.05.003. Epub 2015 May 13.
Biomarkers are a promising tool for the management of patients with atherosclerosis, but their variation is largely unknown. We assessed within-subject and between-subject biological variation of biomarkers in peripheral artery disease (PAD) patients and healthy controls, and defined which biomarkers have a favorable variation profile for future studies.
Prospective, parallel-group cohort study, including 62 patients with stable PAD (79% men, 65±7years) and 18 healthy control subjects (44% men, 57±7years). Blood samples were taken at baseline, and after 3-, 6-, and 12-months. We calculated within-subject (CVI) and between-subject (CVG) coefficients of variation and intra-class correlation coefficient (ICC).
Mean levels of D-dimer, hs-CRP, IL-6, IL-8, MMP-9, MMP-3, S100A8/A9, PAI-1, sICAM-1, and sP-selectin levels were higher in PAD patients than in healthy controls (P≤.05 for all). CVI and CVG of the different biomarkers varied considerably in both groups. An ICC≥0.5 (indicating moderate-to-good reliability) was found for hs-CRP, D-Dimer, E-selectin, IL-10, MCP-1, MMP-3, oxLDL, sICAM-1 and sP-selectin in both groups, for sVCAM in healthy controls and for MMP-9, PAI-1 and sCD40L in PAD patients.
Single biomarker measurements are of limited utility due to large within-subject variation, both in PAD patients and healthy subjects. D-dimer, hs-CRP, MMP-9, MMP-3, PAI-1, sP-selectin and sICAM-1 are biomarkers with both higher mean levels in PAD patients and a favorable variation profile making them most suitable for future studies.
生物标志物是一种有前途的动脉粥样硬化患者管理工具，但它们的变异性在很大程度上尚不清楚。我们评估了外周动脉疾病（PAD）患者和健康对照者体内生物标志物的个体内和个体间生物学变异性，并确定了哪些生物标志物具有未来研究的有利变异性特征。
这是一项前瞻性、平行群组队列研究，纳入 62 例稳定型 PAD 患者（79%为男性，65±7 岁）和 18 例健康对照者（44%为男性，57±7 岁）。在基线、3 个月、6 个月和 12 个月时采集血样。我们计算了个体内（CVI）和个体间（CVG）变异系数和组内相关系数（ICC）。
与健康对照组相比，PAD 患者的 D-二聚体、hs-CRP、IL-6、IL-8、MMP-9、MMP-3、S100A8/A9、PAI-1、sICAM-1 和 sP-选择素水平均较高（所有 P≤.05）。两组不同生物标志物的 CVI 和 CVG 差异很大。在两组中，hs-CRP、D-二聚体、E-选择素、IL-10、MCP-1、MMP-3、oxLDL、sICAM-1 和 sP-选择素的 ICC≥0.5（表明具有中度至良好的可靠性），在健康对照组中 sVCAM 的 ICC≥0.5，在 PAD 患者中 MMP-9、PAI-1 和 sCD40L 的 ICC≥0.5。
由于个体内变异性较大，无论是在 PAD 患者还是健康受试者中，单次生物标志物测量的实用性均有限。D-二聚体、hs-CRP、MMP-9、MMP-3、PAI-1、sP-选择素和 sICAM-1 是生物标志物，它们在 PAD 患者中的平均水平较高，且变异性特征良好，因此最适合未来的研究。
