Abstract P237: Matrix Metalloproteinases (MMPs) And Risk Of Incident Hemorrhagic And Ischemic Stroke: The Atherosclerosis Risk In Communities Study (ARIC)

Abstract

Introduction: Matrix metalloproteinases (MMPs), belong to a family of zinc-dependent endopeptidases, have been found to induce stroke through its role in extracellular matrix destruction. MMPs also affect the stroke prognosis by disrupting blood brain barrier during stroke. Genetic association studies suggest that MMPs are involved in the pathogenesis of both ischemic and hemorrhagic stroke. Hypothesis: High MMP-2, MMP-9 and ratio of MMP-9/TIMP-1 are associated with higher risk of ischemic and hemorrhagic stroke. Method: After exclusion of missing data and prevalent stroke, 11,393 ARIC participants were followed from midlife (visit 3; 1993-1995) and 4,924 participants followed from late life (visit 5; 2011-2013) to 2019. Plasma levels of MMPs were measured by SOMAscan version 4 assay. Stroke cases were reviewed and adjudicated by neurologists. We used Cox models to examine the relationship between MMPs and stroke risk. Result: Mean age of participants were 60±5.7 at visit 3 and 76±5.2 at visit 5. At visit 3 55% were female and 21% Black. A total of 1,013 ischemic and 127 hemorrhagic strokes occurred over 22.34 years of follow-up for the visit 3 analysis and 319 ischemic and 30 hemorrhagic strokes over 7.24 years for the visit 5 analysis. A significant and positive association was detected for MMP-2 at visit 3 baseline for hemorrhagic stroke (HR (95% CI): 2.28 (1.14-4.57)) and at visit 5 baseline with ischemic stroke (1.65 (1.08-2.53)), after covariate adjustment. No associations were observed with MMP-9 and TIMP-1. Conclusion: Results of MMP-2 indicate a possible relationship with MMPs and stroke subtypes, but were not consistent. Though no significance were found for MMP-9 and TIMP-1, their direction of associations with stroke was consistent with the hypothesis.