Periodontitis As A Risk Factor For Stroke: A Systematic Review And Meta-Analysis

Figures & data

Figure 1 Flow diagram of literature searches and selection, according to the PRISMA statement.

Table 1 Summary Of Characteristics And Results Of The Included Studies

Author, Year, Country; Study Design (Length Of Study In Years)	Participants		Age	Periodontitis Evaluation	Results	Statistical Analysis
	Source Of Sample	n
(Holmlund et al, 2010^Citation37); Sweden, cohort (12 years)	Department of Periodontology at Gavle County Hospital, Gavle, Sweden.	(7674)*	51.7 ± 13.8	Probing depth, periodontal severity index (PDSI) and number of deepened periodontal pockets (NDP).	No significant predictive power to future mortality after adjustment was observed for the periodontitis parameters.	Cox proportional hazard analyses
(Sen et al, 2018^Citation38); United States, cohort (15 years)	ARIC (Atherosclerosis Risk in Communities) study, 4 communities in United States.	(15,792)*	62.3± 5.6	Periodontal profile classes (PPC): interproximal attachment level, probing depth, extent of bleeding on probing, gingival inflammation index, plaque index, presence/absence of full prosthetic crowns for each tooth, and tooth status presence.	584 participants had incident ischemic strokes over a 15-year period. The 7 levels of PPC showed a trend toward an increased stroke risk (χ2 trend P<0.0001); the incidence rate for ischemic stroke/1000-person years was 1.29 for PPC-A (health), 2.82 for PPC-B, 4.80 for PPC-C, 3.81 for PPC-D, 3.50 for PPC-E, 4.78 for PPC-F, and 5.03 for PPC-G (severe periodontal disease).	Cox proportional hazard analyses
(Wu et al, 2000^Citation36); United States, cohort (18 years)	First National Health and Nutrition Examination Survey, United States	(5434) 3634: no disease 1800: periodontitis	25–74 years	CAL	Periodontitis is a significant risk factor for Cerebrovascular accidents and, in particular, nonhemorrhagic stroke ORs (95% CIs): 1.66 (1.15 to 2.39)	Cox proportional hazard model
(Abolfazli et al, 2011^Citation41); Iran, c-c	General surgery ward and staff of Imam Hospital, Tabriz, Iran	(100)*	53.3±13.01	CAL	The more severe periodontitis (CAL≥6 mm) was observed among men in patients with cerebral ischemia (P=0.012).	Chi-squared test and Fisher’s test
(Diouf et al, 2015^Citation44); Senegal, c-c	Fann National University Hospital, Senegal.	(220)*	Not informed	CAL	Periodontitis was significantly associated with stroke (OR= 1.58, 95% CI: 1.1–3.022; p< 0.001)	Logistic regression analysis
(Dörfer et al, 2004^Citation39); Germany, c-c	Residents of the city of Heidelberg or the neighboring county, Germany.	(603)*	18–75 years	CAL	Periodontitis is an independent risk factor for cerebral ischemia and acute exacerbation of inflammatory processes (p<0.001) ORs (95% CIs): 7.38 (1.55–15.03)	Logistic regression analysis
(Ghizoni et al, 2012^Citation42); Brazil, c-c.	Neurosurgery Division of the Intensive Care Unit and Operative Dentistry Clinics of the Bauru School of Dentistry, University of São Paulo	(80)*	30–80 years	Probing depth and CAL	Periodontal disease was specifically defined by the presence of at least one site showing a PPD≥4 mm, which resulted in 19 (95%) diseased patients in the test group and 17 (28.3%) patients in the control group, resulting in an unadjusted odds ratio of 48.06 (95% confidence interval:5.96 to 387.72, p<0.001).	chi-squared test, with a 95% confidence level.
(Leira et al, 2016^Citation45); Spain, c-c.	Stroke Unit of the University Clinical Hospital of Santiago de Compostela, Spain.	(112)*	68 (58–71) years	Probing depth and CAL	A strong association between Chronic periodontitis was reported (odds ratio 4.20; 95% confidence interval 1.81–10.20; p= 0.001).	Logistic regression analysis
(Palm et al, 2014^Citation43); Germany, c-c.	Ludwigshafen, Germany.	(198)*	68.2 ± 9.7 years	Questionnaires, evaluation of A. actinomycetemcomitans	The stroke group presented higher levels of A. Actinomycetemcomitans (p-0.003)	Wilcoxon signed-rank test
(Pradeep et al, 2010^Citation40); India, c-c	Department of Neurology, Victoria Hospital and the National Institute of Mental Health and Neurosciences, Bangalore, India	(200)*	33–68 years	CAL	The clinical attachment loss values of subjects with cerebrovascular accident (3.99 ± 1.21) were significantly higher when compared with those of the control group (3.18 ± 0.94, p<0.05)	Logistic regression analysis

Note: *No information regarding number of participants with periodontitis and without periodontitis.

Abbreviations: c-c, case–control study; CAL, clinical attachment loss.

Table 2 Risk Of Bias Assessment According To Fowkes And Fulton

Guideline	Checklist	(Holmlund et al, 2010^Citation37)	(Sen et al, 2018^Citation38)	(Wu et al, 2000^Citation36)	(Abolfazli et al, 2011^Citation41)	(Diouf et al, 2015^Citation44)	(Dörfer et al, 2004^Citation39)	(Ghizoni et al, 2012^Citation42)	(Leira et al, 2016^Citation45)	(Palm et al, 2014^Citation43)	(Pradeep et al, 2010^Citation40)
Study design appropriate to objectives?	Prevalence Cross-sectional
	Prognosis Cohort	0	0	0
	Treatment Controled trial
	Cause Cohort, case-control, cross-sectional				0	0	0	0	0	0	0
Study sample representative?	Source of sample	0	0	0	0	0	0	0	0	0	0
	Sampling method	0	0	0	+	0	0	+	+	0	+
	Sample size	0	0	0	+	0	+	+	+	0	+
	Entry criteria/exclusion	0	0	0	0	0	0	0	0	0	0
	Non-respondents	0	0	0	0	0	0	0	0	0	0
Control group acceptable?	Definition of controls	0	0	0	0	0	0	0	0	+	0
	Source of controls	0	0	0	0	0	0	0	0	0	0
	Matching/randomization	NA	NA	NA	0	0	0	0	0	0	0
	Comparable characteristics	0	0	0	0	0	0	0	0	0	0
Quality of measurements and outcomes?	Validity	0	0	0	0	0	0	0	0	+	0
	Reproducibility	0	0	0	0	0	0	0	0	0	0
	Blindness	0	++	++	0	++	0	0	0	0	++
	Quality control	0	0	0	0	0	0	0	0	++	0
Completeness	Compliance	0	0	0	0	0	0	0	0	0	0
	Drop outs	NA	NA	NA	0	0	0	0	0	0	0
	Deaths	0	0	0	NA	NA	NA	NA	NA	NA	NA
	Missing data	NA	NA	NA	0	0	0	0	0	0	0
Distorting influences?	Extraneous treatments	0	0	0	0	0	0	0	0	0	0
	Contamination	0	0	0	0	0	0	0	0	0	0
	Changes over time	0	0	0	0	0	0	0	0	0	0
	Confounding factors	0	0	0	0	0	0	0	0	0	0
	Distortion reduced by analysis	0	0	0	0	0	0	0	0	0	0
Summary questions	Bias: Are the results erroneously biased in certain direction?	No	No	No	No	No	No	No	No	No	No
	Confounding: Are there any serious confusing or other distorting influences?	No	No	No	No	No	No	No	No	No	No
	Chance: Is it likely that the results occurred by chance?	No	No	No	No	No	No	No	No	No	No

Figure 2 Forest plot to CVA in case–control studies.

Figure 3 Forest plot to Ischemic stroke in case–control studies.

Figure 4 Forest plot to CVA in cohort studies.

Table 3 Evidence Profile: Association Between Periodontitis And Stroke

Certainty Assessment							Summary Of Findings
№ Studies	Risk Of Bias	Inconsistency	Indirectness	Imprecision	Other Considerations	Overall certainty of evidence	Relative effect (95% CI)	Anticipated Absolute Effects
								Risk With Control	Risk Difference With Periodontitis
Association between periodontitis and stroke in case–control studies
7 case-control studies	Not serious	Serious^a	Not serious	Not serious	Strong association	⨁⨁◯◯ LOW	OR 2.31 (1.39 to 3.84)	Low
								0 per 1.000	0 fewer per 1.000 (0 fewer to 0 fewer)
Association between periodontitis and ischemic stroke in case–control studies
4 case-control studies	Not serious	Not serious	Not serious	Serious^b	Strong association	⨁⨁◯◯ LOW	OR 2.72 (2.00 to 3.71)	Low
								0 per 1.000	0 fewer per 1.000 (0 fewer to 0 fewer)
Association between periodontitis and stroke in cohort studies
3 cohort studies	Not serious	Not serious	Not serious	Not serious	None	⨁⨁◯◯ LOW	RR 1.88 (1.55 to 2.28)	0 per 1.000	0 fewer per 1.000 (0 fewer to 0 fewer)

Notes: ^aConsiderable heterogeneity (I²=70%). ^bInitial and final IC variation greater than 25%. Overall certainty of evidence: very low, low, moderate and high.

Abbreviations: CI, confidence interval; OR, odds ratio; RR, risk ratio.

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