Circulating Levels of Interleukin-17 and Cardiovascular Outcomes in Patients With Acute Myocardial Infarction
What is the association between serum levels of interleukin (IL)-17 on cardiovascular (CV) outcomes following acute myocardial infarction (AMI)?
Data were analyzed from 981 patients enrolled in a prospective, multicenter French registry of AMI.
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 CV risk factors, C-reactive protein, and treatments including statins (hazard ratio [HR], 1.40; p = 0.03). IL-17 inhibited mononuclear cell adhesion to endothelium and reduced endothelial vascular cell adhesion molecule (VCAM)-1 expression. Patients with low IL-17 levels and high soluble VCAM-1 (sVCAM-1) levels were at particularly increased risk of death and MI (adjusted HR, 2.22 compared with the high IL-17/low sVCAM-1 group; p = 0.002).
The authors concluded that low serum levels of IL-17 are associated with a higher risk of major CV events in patients with AMI.
IL-17 is produced by a subset of T cells and shown to regulate complex inflammatory responses in a variety of diseases. The complexity is underscored by preclinical data demonstrating both protective and deleterious effects of IL-17 in models of vascular disease. Human clinical data are needed as trials testing IL-17 antagonists are underway for a variety of disease states, some of which are associated with elevated cardiac risk. Although the association of low levels of IL-17 and worse outcomes does not prove causation, these results raise a cautionary flag that CV outcomes should be closely monitored in trials using IL-17 inhibitors.
Keywords: Myocardial Infarction, Vascular Cell Adhesion Molecule-1, Interleukin-17, Interleukin-12, T-Lymphocytes, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Risk Factors, Psychomotor Performance, Interleukin-1, Registries, Endothelium, C-Reactive Protein, Biological Markers, Troponin I, Cardiovascular Diseases
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