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

Abstract

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. 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. 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. 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.