White matter hyperintensity volume correlates with matrix metalloproteinase-2 in acute ischemic stroke

Background: White matter hyperintensity (WMH), a common radiographic finding associated with stroke risk and outcome, has been linked to matrix metalloprotei- nase (MMP) activity and increased levels of oxidative stress in nonstroke popula- tions. We sought to determine whether WMH severity is associated with plasma levels of MMPs and oxidative stress (F2-isoprostane) in subjects with acute ischemic stroke (AIS). Methods: We measured plasma biomarker levels at baseline and 48 hours in consecutive AIS subjects. White matter hyperintensity volume (WMHv) was quantified on admission magnetic resonance imaging using a vali- dated semiautomated protocol, and Spearman correlation coefficients were derived for all measured biomarkers. Results: We enrolled 405 AIS subjects (mean age 70 6 15 years; 58% male; median WMHv 3.4 cm 3 , interquartile range 1.4-9.5). WMHv and age were strongly correlated (r 5 .57, P , .0001). WMHv and MMP-2 levels were correlated at baseline (r 5 .23, P , .0001) and at 48 hours poststroke (r 5 .19, P 5 .002). In multivariate analysis, 48-hour MMP-2 levels were indepen- dently associated with WMHv (b 5 .12, P 5 .04). MMP-9 and F2-isioprostane levels did not correlate with WMHv. Conclusions: In AIS patients, MMP-2 levels are asso- ciated with the pre-existing burden of WMH. If validated, these findings may further elucidate the role of MMP-2 in pathophysiology of chronic cerebrovascular injury, such as WMH, and in brain susceptibility to acute ischemia.