High Serum Level of Matrix Metalloproteinase-7 Is Associated with Increased Risk of Spontaneous Subarachnoid Hemorrhage

Abstract

Background and Purpose-Increased degradation of the extracellular matrix in the arterial wall by matrix metalloproteinases (MMPs) may be an important mechanism in the pathogenesis of intracranial aneurysms and subarachnoid hemorrhage (SAH). MMP-2 and MMP-9 have been suggested to be involved in matrix degradation preceding SAH. We studied serum levels of MMP-1,-2,-3,-7,-9,-10, and-12 and the risk of incident SAH. Methods-A nested case-control study within the population-based cohort, Malmö Diet and Cancer study, was performed including incident cases of spontaneous SAH (n=79) and controls matched by age, sex, and follow-up time (n=232). MMPs were measured in serum from the baseline examination in 1991 to 1996. MMPs were compared between cases and controls, using conditional logistic regression adjusting for risk factors. Results-Baseline levels of MMP-7, MMP-10, and MMP-12 were significantly higher in incident SAH cases compared with controls. Odds ratios (95% confidence interval) for SAH per 1 SD increase of MMP-7, MMP-10, and MMP-12 were 1.78 (1.31-2.41), 1.45 (1.11-1.91), and 1.53 (1.17-2.01), respectively. After adjustment for SAH risk factors, MMP-7 was still significantly associated with SAH (odds ratio: 1.64; 95% confidence interval: 1.19-2.27; P=0.0026), whereas associations for MMP-10 and MMP-12 were attenuated and nonsignificant. We did not find any association between high serum levels of MMP-2 or MMP-9 and SAH risk. Conclusions-High serum level of MMP-7 was associated with increased risk of incident spontaneous SAH, independently of the main risk factors for SAH. High serum levels of MMP-2 and MMP-9 did not predict SAH risk.