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

Author:

Yoshioka Shotaro1,Miyamoto Takeshi1,Satomi Junichiro1,Tada Yoshiteru1,Yagi Kenji1,Shimada Kenji1,Naruishi Koji2,Shikata Eiji1,Yamaguchi Izumi1,Yamaguchi Tadashi1,Korai Masaaki1,Okayama Yoshihiro3,Harada Masafumi4,Kitazato Keiko T1,Kanematsu Yasuhisa1,Nagahiro Shinji1,Takagi Yasushi1

Affiliation:

1. Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan

2. Department of Periodontology and Endodontology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan

3. Clinical Trial Center, Tokushima University and Tokushima University Hospital, Tokushima, Japan

4. Department of Radiology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan

Abstract

ABSTRACT 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.

Funder

Grants-in-Aid for Scientific Research

Grant-in-Aid for Research Activity start-up

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

General Medicine

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