Periodontitis in ischemic stroke: impact of Porphyromonas gingivalis on thrombus composition and ischemic stroke outcomes

Abstract

Background: Periodontitis is associated with an increased risk of ischemic stroke, but the mechanisms underlying this association remain unclear.

Objectives: Our objective was to determine whether Porphyromonas gingivalis (Pg), a periodontal bacterium, could be detected within thrombus aspirates, modify thrombus composition, and endovascular therapy responses.

Methods: The presence of Pg gingipain in 175 consecutive thrombi from patients with large vessel occlusion stroke enrolled in the multicenter research cohort compoCLOT was investigated by immunostaining. Thrombus blood cell composition according to gingipain status was analyzed in a subset of 63 patients.

Results: Pg gingipain immunostaining was positive in 33.7% of thrombi (95% CI, 26.7%-40.8%). The percentage of near to complete reperfusion (modified Thrombolysis in Cerebral Infarction Score 2c/3) at the end of the procedure was lower in the Pg^pos group than the Pg^neg group (39.0% vs 57.8% respectively; adjusted odds ratio, 0.38; 95% CI, 0.19-0.77). At 3 months, 35.7% of patients in the Pg^pos group had a favorable neurological outcome vs 49.5% in the Pg^neg group (odds ratio, 0.65; 95% CI, 0.30-1.40). Quantitative analysis of a subset of 63 thrombi showed that neutrophil elastase content was significantly (P < .05) higher in Pg^pos thrombi than in Pg^neg thrombi.

Conclusion: Our results indicate that intrathrombus Pg gingipain is associated with increased neutrophil content and resistance to endovascular therapy.

Keywords: Porphyromonas gingivalis; endovascular therapy; ischemic stroke; neutrophils; periodontitis; thrombus.

Figure 1

Impact of Porphyromonas gingivalis (Pg) status on recanalization and stroke outcome. (A) Distribution of recanalization grade in percentage. The bar indicates the separation between excellent (modified Thrombolysis in Cerebral Infarction Score 3 and 2c) and poor (modified Thrombolysis in Cerebral Infarction Score ≤ 2b) recanalization grades. (B) Distribution of 90-day modified Rankin Scale (mRS) in percentage. The bar indicates the separation between favorable (mRS 0 to 2) and poor (mRS ≥ 3) outcomes.

Figure 2

Detection of Porphyromonas gingivalis (Pg) within ischemic stroke thrombi. Thrombus samples obtained after mechanical thrombectomy were used for immunohistochemistry. In a representative image of Pg^neg and Pg^pos thrombi, Pg (green) was detected with a mouse anti-gingipain, and neutrophils (red) were detected using a human anti-myeloperoxidase (MPO). Nuclei (blue) were stained with DAPI. DAPI, 4',-6 ddiamino-2-phenylindole.