Associations of plasma MMP-9 and MPO with functional outcome in moderate to severe acute ischemic stroke

Abstract

Abstract Inflammation plays a pivotal role in acute ischemic stroke (AIS), with neutrophil granulocytes acting as major contributors to the post-stroke immune response. Upon degranulation, neutrophils release matrix metalloproteinase-9 (MMP-9) and myeloperoxidase (MPO), both of which may influence functional outcomes following AIS. The aim of this study was to investigate the association between systemic levels of MMP-9 and MPO, functional outcome, and neutrophil counts in patients with moderate to severe AIS, with a focus on their pathophysiological relevance rather than standalone prognostic performance. This prospective single-center cohort study included patients with moderate to severe AIS in the anterior circulation (NIHSS score ≥ 6 points and /or indication for mechanical recanalization). Venous blood was sampled in order to assess plasma concentrations of MMP-9 via zymography as well as MPO plasma levels via ELISA. Furthermore, differential blood count was determined simultaneously to venous biomarker sampling. Poor outcome was defined as mRS score ≥ 3. Uni- and multivariable regression analyses were performed. Between 07/2020 and 09/2022 a total of 279 patients with blood samples taken up to 48 h after symptom onset with a median NIHSS score of 13 and a median age of 79 were included. Of these patients, 81.0% underwent mechanical recanalization and 42.7% received systemic thrombolytic therapy. Systemic MMP-9 and MPO plasma levels were significantly higher in patients with poor functional outcome compared to patients with good functional outcome at 3-months (MMP-9: 359.1 vs. 303.5 ng/ml, p  = 0.0006; MPO: 27.0 vs. 19.2 ng/ml, p  = 0.0010). Both biomarkers were associated with a poor outcome in unadjusted analyses [MMP-9: unadjusted OR = 15.63 (95% CI: 3.54-80.69), p  = 0.0005; MPO: unadjusted OR = 4.02 (95% CI: 1.84-9.21), p  = 0.0007]. In addition, MMP-9 and MPO concentrations correlated with neutrophil counts (MMP-9: r  = 0.39, p  < 0.0001; MPO: r  = 0.31, p  < 0.0001). In conclusion, systemic MMP-9 and MPO plasma concentrations are associated with functional outcome in patients with moderate to severe AIS and reflect neutrophil-driven inflammatory processes. Their value appears to lie in complementing established clinical predictors rather than serving as independent prognostic markers.