From the Laboratory for Clinical Thrombosis and Hemostasis, Department of Biochemistry, Maastricht University, the Netherlands (B.K., H.t.C., H.S., A.t.C.-H.).
Department of Vascular Surgery (L.W., B.M.), Maastricht University Medical Center, the Netherlands.
Arterioscler Thromb Vasc Biol. 2020 Sep;40(9):2018-2032. doi: 10.1161/ATVBAHA.120.314774. Epub 2020 Jul 9.
Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events. Numerous plasma biomarkers have been investigated in lower extremity PAD, but none are used for clinical risk assessment. We aimed to provide a comprehensive overview of biomarker testing in PAD as a first step to improve risk stratification. Approach and Results: A systematic literature review in MEDLINE/PubMed, Cochrane, and Embase was performed, identifying all studies investigating plasma biomarkers in association with cardiovascular events and mortality in lower extremity PAD. Forty-seven studies comprising 21 473 PAD patients met our criteria and were included. Effect estimates were provided by the studies based on a minimum follow-up of 1 year. Meta-analyses were performed by pooling studies per biomarker for each end point. Patients with increased high-sensitivity CRP (C-reactive protein) levels had a relative risk of 1.86 (1.48-2.33) for major adverse cardiovascular events and a relative risk of 3.49 (2.35-5.19) for mortality. Increased fibrinogen and d-dimer levels were associated with an increased relative risk of mortality of 2.08 (1.46-2.97) and 2.22 (1.24-3.98), respectively. Additionally, patients with increased NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cTnT (cardiac troponin T) levels were at an even higher risk of mortality with relative risks of 4.50 (2.98-6.81) and 3.33 (2.70-4.10), respectively.
This systematic review identifies promising biomarkers representing different pathophysiological processes implicated in lower extremity PAD, including high-sensitivity CRP, neutrophil-lymphocyte ratio, fibrinogen, d-dimer, NT-proBNP, and high-sensitivity cTnT. Clinical implementation should be preceded by a management study to test the utility of a combination of these markers for individual risk stratification. Ultimately, this may contribute to tailored treatment and increased effectiveness of current treatment strategies in PAD.
下肢外周动脉疾病（PAD）患者发生主要不良心血管事件的风险增加。已经在下肢 PAD 中研究了许多血浆生物标志物，但没有一种用于临床风险评估。我们旨在提供对 PAD 中生物标志物检测的全面概述，作为改善风险分层的第一步。
在 MEDLINE/PubMed、Cochrane 和 Embase 中进行了系统的文献检索，以确定所有研究调查了与下肢 PAD 中的心血管事件和死亡率相关的血浆生物标志物。符合我们标准的 47 项研究共纳入了 21473 例 PAD 患者。研究根据至少 1 年的随访提供了效应估计值。根据每个终点的每个生物标志物对研究进行了荟萃分析。高敏 C 反应蛋白（CRP）水平升高的患者发生主要不良心血管事件的相对风险为 1.86（1.48-2.33），死亡率的相对风险为 3.49（2.35-5.19）。纤维蛋白原和 D-二聚体水平升高与死亡率的相对风险增加分别为 2.08（1.46-2.97）和 2.22（1.24-3.98）相关。此外，N 端脑钠肽前体（NT-proBNP）和高敏肌钙蛋白 T（hs-cTnT）水平升高的患者死亡率风险更高，相对风险分别为 4.50（2.98-6.81）和 3.33（2.70-4.10）。
本系统评价确定了有前景的生物标志物，代表了涉及下肢 PAD 的不同病理生理过程，包括高敏 CRP、中性粒细胞-淋巴细胞比值、纤维蛋白原、D-二聚体、NT-proBNP 和 hs-cTnT。在进行临床应用之前，应进行管理研究，以测试这些标志物组合用于个体风险分层的效用。最终，这可能有助于为 PAD 患者制定个体化治疗方案，并提高现有治疗策略的效果。
