Abstract WP452: Matrix Metalloproteinase Expression as Sex-specific Biomarker of Secondary Injury and Functional Outcomes After Spontaneous Hypertensive Intracerebral Hemorrhage

Abstract

Introduction: Intracerebral hemorrhage (ICH) affects approximately 2 million individuals per year. Incidence of ICH is roughly equal in men and women, but few studies have examined the influence of sex on long-term outcomes after ICH and secondary injury. Previous studies have shown that women in the post-partum period and post-menopausal women are especially susceptible to poor functional outcomes after ICH. Matrix metalloproteinases (MMPs) promote vessel rupture during ICH and may lead to poorer outcomes in female patients due to blood-brain barrier breakdown. We hypothesized that MMP isoform levels would be predictive of injury severity, secondary injury and long-term functional outcomes after ICH in males and females. Methods and Results: Patients from our prospectively collected ICH database were included. We included patients with deep hypertensive ICH, and excluded secondary ICH. Baseline clinical, radiographic and laboratory data were collected. Neurologic deterioration was defined as increase in NIHSS score and/or reduction in GCS score. Functional outcomes were assessed by modified Rankin Scale (mRS) and EuroQol at 90 DPI. Discharge disposition was recorded. With a total of 55 patients (n = 39 male, 16 female) we demonstrated a significantly higher risk of IVH (p = 0.012) and neurologic deterioration (p = 0.005) in females compared to males. We found that MMP levels in serum reliably predict injury severity in males, and secondary injury in females. Using multiplex ELISA we demonstrated that serum MMP-2 levels are negatively correlated with IVH severity (p = 0.028) in females. Additionally, serum levels of MMP-3 (p= 0.011) in males and MMP-10 (p= 0.044) in females predicted long-term functional outcomes in a sex-specific manner. Conclusion: Our work demonstrates the importance of studying sex-specific factors in ICH outcomes. We have found that there is a potential use of serum MMP expression as a sex-specific diagnostic tool for physicians treating patients after ICH. To our knowledge, this is the first sex-specific study to examine serum MMP levels and their correlation with clinicoradiologic measures after ICH. Further research to confirm these findings is necessary.