Department of Clinical Pharmacology, URC-EST, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital St Antoine Paris, University of Pierre et Marie Curie, 27 Rue Chaligny, 75012 Paris, France.
Eur Heart J. 2013 Feb;34(8):570-7. doi: 10.1093/eurheartj/ehs263. Epub 2012 Sep 6.
Interleukin (IL)-17 pathway is being clinically targeted in immune-mediated diseases, most of which are associated with a significant cardiovascular risk. We investigated the relationship between serum levels of IL-17 and the risk of cardiovascular events in patients with acute myocardial infarction.
We used data from 981 patients enrolled in the prospective, multicentre French registry of Acute ST elevation, or non-ST-elevation Myocardial Infarction (Fast-MI, NCT00673036). Serum levels of IL-17 were associated with the risk of all-cause death and recurrent MI at 2 years, with levels of IL-17 below the median indicative of a worse outcome. The impact of IL-17 remained significant after adjustment for known cardiovascular risk factors, C-reactive protein, and treatments including statins: hazard ratio (HR) = 1.40 (1.03-1.91); P = 0.03. IL-17 inhibited mononuclear cell adhesion to endothelium and reduced endothelial vascular cell adhesion molecule (VCAM-1) expression. Patients with low (below the median) IL-17 levels and high (above the median) soluble VCAM-1 (sVCAM-1) levels were at particularly increased risk of death and MI: adjusted HR = 2.22 (1.32-3.75) compared with the high IL-17/low sVCAM-1 group (P = 0.002).
Low serum levels of IL-17 are associated with a higher risk of major cardiovascular events in Caucasian patients with acute MI. Our results raise possible concern about the use of inhibitors of the IL-17 pathway in clinical settings associated with a high cardiovascular risk.
NCT00673036.
白细胞介素（IL）-17 途径正在免疫介导的疾病中进行临床靶向治疗，其中大多数疾病与显著的心血管风险相关。我们研究了急性心肌梗死患者血清中 IL-17 水平与心血管事件风险之间的关系。
我们使用了前瞻性、多中心法国急性 ST 段抬高或非 ST 段抬高心肌梗死登记处（Fast-MI，NCT00673036）中 981 例患者的数据。IL-17 的血清水平与 2 年内全因死亡和复发性 MI 的风险相关，中位数以下的 IL-17 水平提示预后较差。在调整已知心血管危险因素、C 反应蛋白和包括他汀类药物在内的治疗后，IL-17 的影响仍然显著：风险比（HR）=1.40（1.03-1.91）；P=0.03。IL-17 抑制单核细胞黏附在内皮细胞上，并降低内皮血管细胞黏附分子（VCAM-1）的表达。IL-17 水平低（低于中位数）和可溶性 VCAM-1（sVCAM-1）水平高（高于中位数）的患者死亡和 MI 的风险特别增加：与高 IL-17/低 sVCAM-1 组相比，调整后的 HR=2.22（1.32-3.75）；P=0.002）。
在白人急性心肌梗死患者中，血清中 IL-17 水平较低与主要心血管事件风险增加相关。我们的研究结果表明，在与心血管风险较高相关的临床环境中，使用 IL-17 途径抑制剂可能存在潜在的风险。
NCT00673036。
