Periodontitis and gingival bleeding associate with intracranial aneurysms and risk of aneurysmal subarachnoid hemorrhage

Abstract

Oral bacteria DNA has been found in intracranial aneurysms (IA) and a high prevalence of periodontitis was reported in IA patients. We investigated whether periodontitis associates with IA formation and aneurysmal subarachnoid hemorrhage (aSAH). First, we compared in a case-control setting the prevalence of periodontal disease in IA patients (42 unruptured IA, 34 ruptured IA) and in age-and gender-matched controls (n = 70) from the same geographical area (Health 2000 Survey, BRIF8901). Next, we investigated whether periodontitis at baseline associated with aSAH in a 13-year follow-up study of 5170 Health 2000 Survey participants. Follow-up data was obtained from national hospital discharge and cause of death registries. Univariate analysis, logistic regression, and Cox-regression were used. Periodontitis (≥ 4mm gingival pocket) and severe periodontitis (≥ 6mm gingival pocket) were found in 92% and 49% of IA patients respectively and associated with IAs (OR 5.3, 95%CI 1.1-25.9, p < 0.000 and OR 6.3, 95%CI 1.3-31.4, p < 0.001, respectively). Gingival bleeding had an even stronger association, especially if detected in 4-6 teeth sextants (OR 34.4, 95%CI 4.2-281.3). Severe periodontitis in ≥ 3 teeth or gingival bleeding in 4-6 teeth sextants at baseline increased the risk of aSAH during follow-up (HR 22.5, 95%CI 3.6-139.5, p = 0.001 and HR 8.3, 95%CI 1.5-46.1, p = 0.015, respectively). Association of periodontitis and gingival bleeding with risk of IA development and aSAH was independent of gender, smoking status, hypertension, or alcohol abuse. Periodontitis and gingival bleeding associate with increased risk for IA formation and eventual aSAH. Further epidemiological and mechanistic studies are indicated.

Role of oral pathogens in the pathogenesis of intracranial aneurysm: review of existing evidence and potential mechanisms

“…Recently, our group found the association with periodontitis, formation of intracranial aneurysms (IA), and the risk of aneurysmal subarachnoid hemorrhage (aSAH) [25]. Together with the prior reports that DNA of oral bacteria is found in the wall of many ruptured intracranial aneurysms [64,65], these results raised the intriguing question whether periodontitis and oral bacteria participate to the formation of IAs and to their progression towards rupture.…”

“…Periodontitis has also been associated with atherosclerosis, stroke [38,46,63], and abdominal aortic aneurysms (AAA) [12,45,79]. Very recently, our group showed that periodontitis or gingivitis associate also with aSAH and IA formation [25]. In addition to this, another recent study reported an association between aSAH and being a carriage of specific strains of Streptococcus mutans, a significant contributor to tooth decay [31].…”

“…The fact that the remaining 50% were negative for any bacterial DNA demonstrates that IAs can form without direct bacterial involvement. The combination of having an epidemiological association between periodontal infection and IA formation and rupture [25,66], experimental proof that microbiome exposure modulates IA formation [21,73], and that even presence of oral pathogen remnants is found in many IA walls [64,65] justifies the hypothesis that periodontal pathogens contribute to the risk of IA formation and rupture through indirect or direct modulation of the inflammatory remodeling in the cerebral artery and IA wall.…”

“…Without interventional therapy, periodontitis leads to breakdown of both soft and hard tissue mainly via inflammatory host response [11] causing loss of tooth attachment and eventually loss of alveolar bone in the jaws. Periodontitis not only degenerates tooth surrounding structures but affects the inflammatory system [35,51,52,60,62] and systemic health [12,25,38,45,46,63,79].…”

“…These bacteria simultaneously accelerate complement activity yet evade complementmediated killing is unique and could partially explain inflammation in IA wall, especially since oral bacterial DNA is found in unruptured and ruptured IA walls [18,19,56]. Luminal thrombus is common in IAs [18], as is periodontitis in IA patients [25,66] suggesting that P. gingivalis might accelerate neutrophil-driven thrombus-derived proteolytic and cytotoxic injury in the IA wall similarly to the AAA walls. Indeed, MPO expression has been demonstrated in human IA walls [23,56] and locally higher MPO concentrations have been observed in serum from aneurysm sac than to femoral artery blood [9].…”