Disequilibrium of Plasma Protease/Anti-Protease Due to Severe Periodontal Disease Contributes to Human Subarachnoid Hemorrhage

BACKGROUND: The pathophysiology of subarachnoid hemorrhages (SAHs) due to ruptured intracranial aneurysms (IAs) remains unclear.Although a relationship between SAHs and periodontal disease (PD) has been suggested, the mechanism requires clarification.
OBJECTIVE: To evaluate the relationship between PD and SAHs and to identify periodontal pathogens associated with SAHs.
METHODS: This prospective study included consecutive patients with ruptured (n = 11) and unruptured (n = 14) IAs and healthy controls (n = 8). The plasma and plaque subgingival bacterial deoxyribonucleic acid (DNA) levels in PD were evaluated by a dentist using the Community Periodontal Index of Treatment Needs (CPITN). Plasma levels of matrix metalloproteinase (MMP-9), tissue inhibitors of matrix metalloproteinase (TIMP2), and procollagen I were analyzed.
RESULTS: Patients with ruptured IAs, had significantly higher CPITN scores than the controls, suggesting that ruptured IAs were associated with severe PD. Although no rupture-specific bacteria were identified, the positive rate of plaque subgingival bacterial DNA was significantly higher in patients with severe PD than in those without severe PD. Multivariate logistic regression analysis indicated that bleeding on probing (BOP)was associated with ruptured IAs (odds ratio, 1.10; 95% confidence interval 1.04–1.20; P = .0001). BOP was positively associated with plasma MMP-9 levels and a disequilibrium in the MMP-9/TIMP2 ratio. BOP was negatively correlated with plasma procollagen I levels (P < .05, for each). This suggested that local inflammation with severe PD might have systemic effects and lead to ruptured IAs.
CONCLUSION: Disequilibrium of plasma protease/anti-protease associated with a high BOP rate in severe PD may be attributable to IA rupture.

内容要旨・審査要旨・論文本文の公開
本論文は，著者Shotaro Yoshiokaの学位論文として提出され，学位審査・授与の対象となっている。

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