ArticlePDF AvailableLiterature Review

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

Authors:

Abstract and Figures

This systematic review and meta-analysis investigate the association between periodontitis and stroke. This review followed the methods established by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Searches were conducted in five databases and two sources of grey literature. After the selection of the articles, a risk of bias evaluation was performed. Three meta-analyzes were performed: Assessing the overall association between stroke and periodontitis in case-control studies; Ischemic stroke and periodontitis in case-control studies; The association between stroke and periodontitis in cohort studies. Heterogeneity was assessed using the I2 index and the odds ratio was also calculated (p < 0.05). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to evaluate the level of evidence. 2193 potentially relevant studies were identified, with 10 studies included in qualitative and quantitative analysis. All the articles were considered with low risk of bias and a low level of certainty. The results demonstrated a positive association between both disorders and increased risk for stroke among cohort studies (RR 1.88 [1.55, 2.29], p<0.00001, I2=0%) and for ischemic stroke events in case-control studies (RR 2.72 [2.00, 3.71], p<0.00001, I2= 4%). Periodontitis may represent a risk factor for stroke, especially in ischemic events. However, new studies with a robust design are necessary for a reliable conclusion.
Content may be subject to copyright.
REVIEW
Periodontitis As A Risk Factor For Stroke: A
Systematic Review And Meta-Analysis
This article was published in the following Dove Press journal:
Vascular Health and Risk Management
Nathalia Carolina Fernandes
Fagundes
1,2
Anna Paula Costa Ponte
Sousa Carvalho Almeida
1
Kelly Fernanda Barbosa
Vilhena
1
Marcela Baraúna Magno
3
Lucianne Cople Maia
3
Rafael Rodrigues Lima
1
1
Laboratory of Functional and Structural
Biology, Institute of Biological Sciences,
Universidade Federal do Pará, Belém-
Pará, Brazil;
2
School of Dentistry, Faculty
of Medicine and Dentistry, University of
Alberta, Edmonton, Canada;
3
Department of Pediatric Dentistry and
Orthodontics, School of Dentistry,
Universidade Federal do Rio de Janeiro,
Rio de Janeiro, Brazil
Abstract: This systematic review and meta-analysis investigate the association between
periodontitis and stroke. This review followed the methods established by the Preferred
Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Searches
were conducted in ve databases and two sources of grey literature. After the selection of the
articles, a risk of bias evaluation was performed. Three meta-analyzes were performed:
Assessing the overall association between stroke and periodontitis in casecontrol studies;
Ischemic stroke and periodontitis in casecontrol studies; The association between stroke and
periodontitis in cohort studies. Heterogeneity was assessed using the I
2
index and the odds
ratio was also calculated (p < 0.05). The Grading of Recommendations Assessment,
Development and Evaluation (GRADE) was applied to evaluate the level of evidence.
2193 potentially relevant studies were identied, with 10 studies included in qualitative
and quantitative analysis. All the articles were considered with low risk of bias and a low
level of certainty. The results demonstrated a positive association between both disorders and
increased risk for stroke among cohort studies (RR 1.88 [1.55, 2.29], p<0.00001, I
2
=0%) and
for ischemic stroke events in casecontrol studies (RR 2.72 [2.00, 3.71], p<0.00001, I
2
= 4%).
Periodontitis may represent a risk factor for stroke, especially in ischemic events. However,
new studies with a robust design are necessary for a reliable conclusion.
Keywords: central nervous system, cerebrovascular disorders, stroke, periodontitis,
periodontal attachment loss
Introduction
This cerebrovascular damage is characterized by brain vessels occlusion or block-
age (ischemic stroke), as well as blood vessels rupture (hemorrhagic stroke).
1
Based
on the same mechanism of the ischemic stroke with a different period of occur-
rence, the transient ischemic attack is another type of cerebrovascular accident, with
less than 24 hrs of duration.
2
Moreover, other classications or subtypes of these
changes are described in the literature, such as subarachnoid hemorrhage, cerebral
venous thrombosis, and spinal cord stroke.
3
Although these events have different
origins and pathogenesis, they all culminate in vascular changes that present
themselves as one of the main death cause in the world.
2,3
In this context, the
presence of inammatory oral diseases may also act as source of these vascular
changes in a stroke condition.
4
Among oral infections, periodontal diseases are considered as a huge variety of
inammatory conditions that affect the supporting structures of the teeth such as the
gingiva, alveolar bone and periodontal ligament,
58
which could result in tooth loss
and contribute to systemic inammation.
8
Periodontitis, a type of periodontal
Correspondence: Rafael Rodrigues Lima
Laboratory of Structural and Functional
Biology, Institute of Biological Sciences,
Federal University of Pará, Rua Augusto
Corrêa nº 1, Guamá, Belém 66075-900,
PA, Brazil
Email rafalima@ufpa.br
Vascular Health and Risk Management Dovepress
open access to scientic and medical research
Open Access Full Text Article
submit your manuscript | www.dovepress.com Vascular Health and Risk Management 2019:15 519532 519
http://doi.org/10.2147/VHRM.S204097
DovePress © 2019 Fagundes et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.
php and incorporate the Creative Commons Attribution Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the
work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For
permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
disease, is dened as a chronic inammatory disease of
multifactorial origin, being related to plaques (biolm),
8
initiated by gram-negative bacteria that initiate an
immune-inammatory response of the host.
9,10
It is char-
acterized by the progressive destruction of the dental
apparatus, causing the loss of the tissue support period-
ontal, with this leading to loss of clinical insertion (CAL)
and alveolar bone loss, which can be evaluated through
radiographic images, besides the presence of periodontal
pockets and gingival bleeding.
8
Periodontitis is associated with elevated levels of IL-6,
C-Reactive Protein and TNF alpha in blood ow associated
with systemic inammation markers.
11,12
The current evi-
dence also shows that elevated levels of inammatory mar-
kers are related to systemic diseases, such as Rheumatoid
Arthritis,
13
cardiovascular diseases,
14
as well as to severe
neurological decits as dementia,
15
AlzheimersDisease.
16
The association between periodontal disease and
stroke has been previously investigated in systematic
reviews.
1719
However, the interaction among different
types of cerebrovascular accidents has not been synthe-
tized in a review capable to present the relevant clinical
evidence. The aim of this systematic review and meta-
analysis was to investigate the association between stroke
and periodontitis in humans, considering the different
types of cerebrovascular events.
Materials And Methods
Protocol And Registration
This systematic review was registered at PROSPERO
under the code CRD42016033183 and performed accord-
ing to PRISMA (Preferred Reporting Items for Systematic
Review and Meta-Analysis) guidelines.
20
Search Strategy, Eligibility Criteria And
Data Extraction
The PECO strategy was followed in this systematic review.
Observational studies in humans (P) exposed (E) and not
exposed to periodontitis (C), in which the primary outcome
was the risk of cerebrovascular accident, including hemor-
rhagic and ischemic attacks (O) (Supplementary material 1,
Supplementary material 2). As an ischemic attack, the
events of transient ischemic attack and ischemic stroke
were considered in the evaluated studies.
Searches were conducted in the following electronic
databases, without language restriction until september
2018: PubMed, Scopus, Web of Science, The Cochrane
Library, LILACS, OpenGrey and Google Scholar. All
publications presented in the databases contained a com-
bination of controlled pre-dened MeSh and free terms
related to cerebrovascular changes and periodontitis
(Supplementary material 3). The terms previously dened
were adapted to the rules of syntax of each bibliographic
database.
After research in databases, all relevant citations were
saved in a bibliographic reference manager (EndNote, x7
version, Thomson Reuters). Duplicated results were consid-
ered only once. After the importation to reference manager,
the duplicates were removed, followed by exclusion of
opinion articles, technical articles, guides and animal stu-
dies. The selection process was performed in two phases.
The rst phase includes the evaluation of titles and abstracts
according to inclusion and exclusion criteria. In the phase
two, the articles included in the rst phase were evaluated
according to full text by the same criteria. Additional cita-
tions were sought from the analysis of the reference list of
all articles previously selected in phase two. The searches
and selection process were conducted by three examiners
(NCFF, KFBV and APCPSCA) and checked by a third
examiner (RRL), in cases of disagreements.
After the selection, the data extraction was conducted
from the included articles. A table was used to report the
country, year of publication, study design, participant char-
acteristics (source and sample size), age, periodontitis
evaluation, results and statistical analysis.
In case of absence of information that makes data extrac-
tion or risk of bias evaluation impracticable, we attempted to
contact the authors by e-mail. The contact consisted of send-
ing a weekly email, for up to ve consecutive weeks.
Quality Assessment Analysis
The papers that fullled the selection criteria were
included for qualitative evaluation. The quality assessment
of the included studies was made following a check-list
established by Fowkes and Fulton
21
and updated by
Penoni et al
22
(Supplementary material 4).
Risk Of Bias
After quality assessment evaluation, the studies were ana-
lyzed to determine the risk of bias, according to the pos-
sibility of biased results,”“serious confounders,and the
occurrence of chance.
21,22
Three questions were evalu-
ated to determine the value of the study: Are the results
erroneously biased in a certain direction?”“Are there any
serious confounding or other distorting inuences?and
Fagundes et al Dovepress
submit your manuscript | www.dovepress.com
DovePress
Vascular Health and Risk Management 2019:15
520
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
Is it likely that the results occurred by chance?If these 3
summary questions were answered with no,then there
was a high probability that the research presented a low
risk of bias.
Quantitative Synthesis Of The Results
The extracted data were analyzed using RevMan software
(Review Manager v. 5.3, The Cochrane Collaboration;
Copenhagen, Denmark) to assess the relationship between
periodontal disease and stroke.
Three meta-analyses (MAs) were performed:
1. To evaluate the association between periodontitis and
stroke in casecontrol studies, odds ratio (OR) and
its 95% CI of the association between these two
diseases (periodontitis and stroke) from included
studies were extracted. Adjusted odds ratio was
also used whenever possible; otherwise, crude odds
ratio estimates were considered to measures effect as
a log OR and the standard error of the log OR using
generic inverse-variance weighting method.
Combined results were presented as a pooled OR.
2. To evaluate the association between periodontitis and
ischemic stroke in casecontrol studies, odds ratio (OR)
and its 95% CI of the association between these two
diseases (periodontitis and ischemic stroke) from
included studies were extracted. Adjusted odds ratio
was also used whenever possible; otherwise, crude
odds ratio estimates were considered to measures effect
as a log OR and the standard error of the log OR using
generic inverse-variance weighting method. Combined
results were presented as a pooled OR.
3. To evaluate the association between periodontitis
and stroke in cohort studies, risk ratio (RR) and its
95% CI of the association between these two dis-
eases (periodontitis and stroke) from included stu-
dies were extracted. Adjusted RR was also used
whenever possible; otherwise, crude RR estimates
were considered to measures effect as a log RR and
the standard error of the log RR using generic
inverse-variance weighting method. Combined
results were presented as a pooled RR.
When necessary, the effect estimates were converted to
OR or RR with the help of RevMan software tools.
If some of the necessary information was absent from
any of the included studies, the authors were contacted
(one contact by week, up to ve weeks) to provide the
missing data. After contacts, studies that remaining with-
out sufcient data were excluded from the meta-analysis.
Besides that, only studies that did not present methodolo-
gical bias were included. Random effect model was
applied when the studies were not functionally equivalent
in which the objective was to generalize the results from
the meta-analysis.
23
Heterogeneity was tested using the I
2
index and, if the
heterogeneity was substantial or considerable (>50%), a
sensitivity analyses were performed to verify the inuence
of each study on the pooled results.
24
Level Of Evidence
The assessment of quality of the evidence was determined
for the outcomes meta-analysis using the Grading of
Recommendations Assessment, Development and
Evaluation (GRADE) approach.
25
Observational studies
start as low evidence, and the quality of, or certainty in,
the body of evidence decreases to very low quality if
serious or very serious issues related to risk of bias,
inconsistency, indirectness, imprecision and publication
bias are present and increase if confounding factors and
if the magnitude of effect is large or very large were
detected. In this way, the quality of the evidence can
range from very low, low, moderate and high.
Results
Study Selection
A total of 2193 articles was identied from the searches of
databases, and 958 were excluded because they are dupli-
cated. All 1235 titles and abstracts retrieved were analyzed
according to the criteria of inclusion and exclusion, with
an exclusion of 1214 studies. The remaining studies
(n= 21) were evaluated by full-text. 11 studies were
excluded in the full-text evaluation due to the absence of
control group
18,2635
see supplementary material 5.
A total of ten studies was included and submitted to
quality assessment (Figure 1).
Characteristics Of Included Studies
All the 10 articles included in this review were observa-
tional, 3 presented a prospective cohort design,
3638
while
7 were case-controlled studies.
3945
Only one study did not
report a signicant association between periodontitis and
cerebrovascular changes.
37
Among the studies, ischemic
damages were the most evaluated, including ischemic
Dovepress Fagundes et al
Vascular Health and Risk Management 2019:15 submit your manuscript | www.dovepress.com
DovePress 521
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
Figure 1 Flow diagram of literature searches and selection, according to the PRISMA statement.
Fagundes et al Dovepress
submit your manuscript | www.dovepress.com
DovePress
Vascular Health and Risk Management 2019:15
522
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
stroke,
3840,43
transient ischemic attack,
39
acute cerebral
ischemia
41
and lacunar infarct.
45
Four studies investigated
both hemorrhagic and non-hemorrhagic strokes.
36,37,42,44
The Clinical Attachment Loss was the most used method
of assessment for periodontitis identication
36,3942,44,45
(Table 1).
Risk Of Bias
After the quality and risk of bias assessments, it could be
observed that all studies had methodological soundness
with low susceptibility to bias (Table 2).
However, some methodological limitations were
identied among the included studies. Among the
casecontrol studies included, problems were identied
regarding the sampling method
4042,45
and sample size
calculation.
39,40,42,45,46
Moreover, four studies did not
provide information regarding the blinding of the out-
come evaluation by the accessors among the included
studies.
36,38,40,44
Quantitative Analysis
Considering the studies included in this systematic review,
Abolfazili et al
41
have two control groups and the result
from both control groups were added and considered in
these meta-analyses.
Dorfer et al
44
and Holmlund et al
37
presented OR and
RR values from mild, moderate and severe periodontitis,
respectively, while Sen et al
38
presented RR values from
mild and severe periodontitis. In these cases, a pooled OR
and RR were calculated and employed in the rst and
second meta-analysis. Pooled RR was also calculated to
Wu et al
36
to obtain a pooled result including all stroke
types (RR for cerebrovascular diseases not specied, RR
for hemorrhagic stroke and RR for non-hemorrhagic
stroke).
The results were presented separately for the three MA:
1. Stroke in casecontrol studies. In the rst MA,
seven studies were included.
36,3945
The overall
heterogeneity was considerable (I
2
=77%). During
sensitivity analysis, the heterogeneity ranges from
70% to 80% and, as no signicant heterogeneity
reduction was observed, none study was removed.
The pooled results present data on the direction of
association between periodontitis and stroke.
Individuals with periodontitis had two times higher
chance to suffer stroke (OR 2.31 [1.39, 3.84],
p=0.001, I
2
= 77%) (Figure 2).
2. Ischemic stroke in casecontrol studies. In this second
MA ve studies were included.
36,3941,43,45
The over-
all heterogeneity was considerable (I
2
=72%). During
sensitivity analysis, the heterogeneity ranges from 4%
to 78% and, in attempt to reduce heterogeneity, Palm
et al study was removed from this analysis. The
pooled results present data on the direction of associa-
tion between periodontitis and ischemic stroke.
Individuals with periodontitis had two times higher
chance to suffer ischemic stroke (OR 2.72 [2.00,
3.71], p<0.00001, I
2
= 4%) (Figure 3).
3. stroke in cohort studies. In this third MA, three
studies were included
3638
and presented null het-
erogeneity (I
2
=0%). The pooled results present data
on showed, again, association between periodontitis
and stroke. Individuals with periodontitis had
higher risk to suffer stroke (RR 1.88 [1.55, 2.28],
p<0.00001) (Figure 4).
Assessment Of The Level Of Evidence
(GRADE)
Ten studies were used in the meta-analysis and were eval-
uated for the level of evidence.for the association between
periodontitis and stroke in casecontrol studies, seven stu-
dies were included,
36,39,40,4245
although the large effect
(OR> 2), this evidence was classied as low due to serious
problems in inconsistencyrelated to considerable overall
heterogeneity. In the present study, it was found that the
association between periodontitis and ischemic stroke in
casecontrol studies
3941,43,45
the large effect (OR> 2), this
evidence was classied as low due to serious problems in
imprecisionrelated to initial and nal IC variation greater
than 25%. In the evaluation of the Association between
periodontitis and stroke in cohort studies, three studies
were included.
36,37
This evidence presented no serious pro-
blem and was qualied as low. Tabl e 3 shows all the results
found in the GRADE evaluation.
Discussion
This systematic review has gathered scientic evidence
based on the literature showing association between peri-
odontitis and the various types of stroke. The results of the
meta-analysis showed that individuals with periodontitis
had a greater chance, about twice as much of suffering
from some type of stroke, as to have ischemic stroke.
Mixed results were observed between qualitative and
Dovepress Fagundes et al
Vascular Health and Risk Management 2019:15 submit your manuscript | www.dovepress.com
DovePress 523
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
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
37
); 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 signicant predictive power to future
mortality after adjustment was observed for
the periodontitis parameters.
Cox
proportional
hazard
analyses
(Sen et al, 2018
38
);
United States, cohort
(15 years)
ARIC (Atherosclerosis Risk in
Communities) study, 4
communities in United States.
(15,792)* 62.3± 5.6 Periodontal prole classes (PPC):
interproximal attachment level, probing
depth, extent of bleeding on probing, gingival
inammation 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
36
);
United States, cohort
(18 years)
First National Health and
Nutrition Examination Survey,
United States
(5434) 3634:
no disease
1800:
periodontitis
2574
years
CAL Periodontitis is a signicant 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
41
);
Iran, c-c
General surgery ward and staff
of Imam Hospital, Tabriz, Iran
(100)* 53.3±13.01 CAL The more severe periodontitis (CAL6 mm)
was observed among men in patients with
cerebral ischemia (P=0.012).
Chi-squared
test and
Fishers test
(Diouf et al, 2015
44
);
Senegal, c-c
Fann National University
Hospital, Senegal.
(220)* Not
informed
CAL Periodontitis was signicantly associated with
stroke (OR= 1.58, 95% CI: 1.13.022; p<
0.001)
Logistic
regression
analysis
(Dörfer et al, 2004
39
);
Germany, c-c
Residents of the city of
Heidelberg or the neighboring
county, Germany.
(603)* 1875
years
CAL Periodontitis is an independent risk factor for
cerebral ischemia and acute exacerbation of
inammatory processes (p<0.001) ORs (95%
CIs): 7.38 (1.5515.03)
Logistic
regression
analysis
(Continued)
Fagundes et al Dovepress
submit your manuscript | www.dovepress.com
DovePress
Vascular Health and Risk Management 2019:15
524
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
Table 1 (Continued).
Author, Year,
Country; Study
Design (Length Of
Study In Years)
Participants Age Periodontitis Evaluation Results Statistical
Analysis
Source Of Sample n
(Ghizoni et al,
2012
42
); 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)* 3080
years
Probing depth and CAL Periodontal disease was specically dened
by the presence of at least one site showing a
PPD4 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% condence interval:5.96 to 387.72,
p<0.001).
chi-squared
test, with a
95%
condence
level.
(Leira et al, 2016
45
);
Spain, c-c.
Stroke Unit of the University
Clinical Hospital of Santiago de
Compostela, Spain.
(112)* 68 (5871)
years
Probing depth and CAL A strong association between Chronic
periodontitis was reported (odds ratio 4.20;
95% condence interval 1.8110.20; p=
0.001).
Logistic
regression
analysis
(Palm et al, 2014
43
);
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
40
); India, c-c
Department of Neurology,
Victoria Hospital and the
National Institute of Mental
Health and Neurosciences,
Bangalore, India
(200)* 3368
years
CAL The clinical attachment loss values of subjects
with cerebrovascular accident (3.99 ± 1.21)
were signicantly 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, casecontrol study; CAL, clinical attachment loss.
Dovepress Fagundes et al
Vascular Health and Risk Management 2019:15 submit your manuscript | www.dovepress.com
DovePress 525
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
Table 2 Risk Of Bias Assessment According To Fowkes And Fulton
Guideline Checklist (Holmlund
et al,
2010
37
)
(Sen
et al,
2018
38
)
(Wu
et al,
2000
36
)
(Abolfazli
et al,
2011
41
)
(Diouf
et al,
2015
44
)
(Dörfer
et al,
2004
39
)
(Ghizoni
et al,
2012
42
)
(Leira
et al,
2016
45
)
(Palm
et al,
2014
43
)
(Pradeep
et al,
2010
40
)
Study design
appropriate to
objectives?
Prevalence Cross-sectional
Prognosis Cohort 0 0 0
Treatment Controled trial
Cause Cohort, case-control, cross-
sectional
0000000
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?
Denition 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
inuences?
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
(Continued)
Fagundes et al Dovepress
submit your manuscript | www.dovepress.com
DovePress
Vascular Health and Risk Management 2019:15
526
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
quantitative analysis of the included studies. While most
of the selected articles described an association between
stroke and periodontitis in qualitative evaluation, this asso-
ciation was only detected among cohort studies and for
ischemic stroke events in casecontrol studies. Even
though a positive association was detected between both
conditions in casecontrol studies, these results are ques-
tionable due to the high heterogeneity among the included
studies.
Systematic reviews can summarize clinical questions
by condensing much information on a critical evaluation
of published studies, following a solid-stated method of
development.
24,47
When it is possible to perform them
from randomized clinical trials, this type of study repre-
sents the best level of evidence available, even though this
could be mutable according to the evaluated question.
47
In
a Systematic review, the performing of a meta-analysis can
provide a quantitative evaluation of the problem investi-
gated, comparing data of each study in a statistical analysis
weighted in heterogeneity of studies evaluation.
24
Besides the results, the quality of the identied articles
in this review pointed absence of signicant bias after the
quality assessment evaluation (Table 2). Problems were
observed in the methodological quality of some studies,
mainly in the study sample, quality of measurements and
blinding. In ve articles, the sample size was marked as a
Table 2 (Continued).
Guideline Checklist (Holmlund
et al,
2010
37
)
(Sen
et al,
2018
38
)
(Wu
et al,
2000
36
)
(Abolfazli
et al,
2011
41
)
(Diouf
et al,
2015
44
)
(Dörfer
et al,
2004
39
)
(Ghizoni
et al,
2012
42
)
(Leira
et al,
2016
45
)
(Palm
et al,
2014
43
)
(Pradeep
et al,
2010
40
)
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
inuences?
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 casecontrol studies.
Figure 3 Forest plot to Ischemic stroke in casecontrol studies.
Figure 4 Forest plot to CVA in cohort studies.
Dovepress Fagundes et al
Vascular Health and Risk Management 2019:15 submit your manuscript | www.dovepress.com
DovePress 527
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
Table 3 Evidence Prole: 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 casecontrol 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 casecontrol 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:
a
Considerable heterogeneity (I
2
=70%).
b
Initial and nal IC variation greater than 25%. Overall certainty of evidence: very low, low, moderate and high.
Abbreviations: CI, condence interval; OR, odds ratio; RR, risk ratio.
Fagundes et al Dovepress
submit your manuscript | www.dovepress.com
DovePress
Vascular Health and Risk Management 2019:15
528
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
problem due to the absence of a sample size calculation or
lack of representativeness.
3942,45
The sampling method
was pointed as problem in four studies.
4042,45
The blind-
ing of the outcome was not performed in four of the
included studies.
36,38,40,44
The quality control was regis-
tered as a major problem in one study
43
due to the absence
of clinical assessment.
Even without compromising the major quality of the
studies, these registered pitfalls must be avoided because
they can induce to confounding effects on a trial.
48
Due to
its chronic and infectious origin, periodontitis may be asso-
ciated as a source of mediators of inammation into the
blood circulation, which may contribute to exacerbate sev-
eral diseases. This local inammatory process may induce a
systemic inammatory state through mechanisms that
include dissemination of pro-inammatory cytokine and/or
bacteria from the oral to extra-oral sites.
49
In the present
study, periodontitis was described as an independent risk
factor of stroke. Ischemic or hemorrhagic events were both
described in the selected studies, even though the ischemic
events were more reported/investigated
3841,43,45
than both
conditions.
36,37,42,44
The presence of a wide spectrum inammatory condi-
tion can increase the risk of a stroke episode in acute and
chronic phases, in which inammatory markers such as
C-Reactive protein, IL-6 and lipoprotein-associated phos-
pholipase A2 were pointed as indicators of increase of
stroke risk.
31,50
Some of these factors, such as the IL-6
and the C-Reactive protein
12,51
are also identied as bio-
markers of periodontitis and are found on blood ow,
suggesting a possible triggering of aggravation of stroke
process.
Moreover, the presence of external inammatory fac-
tors can also aggravate subsequent events that happen after
the stroke.
50
At this moment, an ischemic penumbral tis-
sue surrounding the infarcted core is formed. A damaged
tissue without electrical communication characterizes the
penumbra area, but with sufcient cellular energy to its
nutrition.
52
However, due to this damage, this area is
susceptible to secondary cell death, which occurs hours
and days after the establishment of the primary center of
the lesion.
53
A systemic inammation process was also
associated with changes in microglia. It was suggested that
this process could result on changes of phenotype in this
tissue, resulting on the increase of neuroinammation and
neurodegeneration.
54
The occurrence of cell death on the penumbra area can
be enhanced by several factors, such as oxidative stress,
reperfusion of tissue and microglial activity,
31
which
results on increased damage to stroke area, due to second-
ary neuronal death. The activation of these events can be
triggered by a systemic inammation,
52,55
indicating that
the periodontitis may represent a potential risk to aggra-
vate the stroke condition.
In the present study, the selected articles (Table 3)
focused on present an association between periodontitis
and the incidence of stroke. Seven of the ten articles
were casecontrol studies,
3945
only elucidating a static
relationship between the evaluated conditions. Among
the longitudinal studies, two presented periodontitis as a
risk factor for stroke.
36,38
In view of quantifying the systematic review, three
meta-analyses were performed. The results show a positive
association between stroke and the presence of periodonti-
tis, with a risk of 2.31 (95% CI= 1.393.84; I
2
= 77%;
p=0.0003) of suffering from a stroke in the periodontitis
group of patients in casecontrol studies. However, these
results must be questionable due to the high heterogeneity
detected. The presence of an I
2
indexhigherthan70%may
indicate a lack of homogeneity among studies, invalidating
the results presented. The study design (case-control) may
be associated with the phenomena, including their retro-
spective design and the presence of bias related to the
denition and selection of the sample inherent to this type
of study (egger).
When these studies were subgrouped, and only the
casecontrol studies which reported ischemic events were
considered, a higher risk to present stroke among period-
ontitis patients (2.72 (95% CI= 23.71; I
2
= 4%;
p<0.00001) was detected. Even though these results must
be cautiously evaluated due to the type of study and a low
evidence was attributed to them, these results may suggest
an association between ischemic attacks and periodontal
problems.
A previous meta-analysis evaluated the association
among ischemic stroke and periodontitis
19
and a similar
RR (RR= 2.88) was presented by these authors, suggesting
the association among two conditions. However, different
inclusion criteria for periodontitis and cerebrovascular dis-
ease were adopted in the cited study. In our study, for the
rst time, we evaluated the prevalence of different types of
cerebrovascular damages at the same time, comparing a
healthy group and a periodontitis group.
Among the cohort studies, a greater risk of suffer cere-
brovascular diseases (1.88 (95% CI= 1.552.28; I
2
=0%;
p<0.00001) was detected in periodontitis patients. Two of
Dovepress Fagundes et al
Vascular Health and Risk Management 2019:15 submit your manuscript | www.dovepress.com
DovePress 529
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
the three evaluated studies included only stroke cases asso-
ciated with mortality,
36,37
suggesting the need of further
investigation of this association in prospective studies.
In our review, we tried to investigate the association of
periodontitis and different types of cerebrovascular acci-
dent. Among the included studies, case-control and cohort
studies were included and only 4 studies
36,37,42,44
evaluated
both conditions. Only one study evaluated the prevalence of
periodontitis and hemorrhagic or non-hemorrhagic stroke
and their association.
36
So, we cannot state which condition
is the most associated due to the limitations of the studies.
The suggested association between stroke and period-
ontitis highlights the systemic involvements of the diseases.
Periodontitis has been associated with many conditions
such as cardiovascular diseases, diabetes and obesity, rheu-
matoid arthritis,
56
which shows the importance to correlate
the identied risk factors and reinforce the needing of a
multidisciplinary work on these conditions.
Due to the different classications used for periodonti-
tis regarding their severity among studies and the absence
of enough numerical data, an assessment of the association
between stroke risk and periodontitis was not performed.
Even though there is no reliable evidence that the
treatment of periodontitis can reduce the chances of suffer-
ing from a stroke, due to the difculties to collect and
design a reliable study,
57
the control of infectious diseases
may represent a decrease in other risk factors also related
to stroke.
50
Moreover, the control of oral health in post-
stroke patients has shown benets related to oropharyngeal
dysphagia and oral intake level.
58
Therefore, oral care must be carried out in a preventive
manner, avoiding the appearance of periodontal changes
that may be the target of an increased predisposition to
other diseases, such as stroke. The periodontal treatment
can result in lower levels of oral bacteria and markers of
inammation, which may inuence systemic disorders.
59
In addition, in post-stroke patients, periodontal disease
control may represent a way of trying to control the
aggravation of the condition,
60
especially in a hospital
environment, where the control of oral health conditions
is critical
61
and may result in lower expenses in Public
health at future times.
Despite the presented results, the studies included on
this meta-analysis and systematic review present some
limitations, including some methodological design pro-
blems, such as the lack of blinding and randomization; as
well as the absence of the use of the same method to
evaluate periodontitis. This compromise the establishment
of a solid conclusion about the investigated problem. Most
of the studies presented problems on sample
18,33,3943,62
and blinding process.
18,3032,36,40,42,44
Conclusion
This systematic review and meta-analysis suggest an
increased risk of stroke in patients with periodontitis,
especially in ischemic events. In addition, there is a strong
association between both diseases. However, these results
should be evaluated with caution due to the need for well-
planned prospective studies for a more reliable conclusion,
especially regarding the degree of severity of periodontitis
and stroke, as well as to investigate the relationship of
periodontitis in post-survival cases stroke.
Acknowledgments
The KFBV that analyzed all the studies and extracted the
information from the eligible studies, analyzed the data
and prepared the numbers and the table. The MBM and
LCM that assisted in the quantitative analysis and evalua-
tion of GRADE. AO RRL that was present at all stages of
this review. This work was supported by Pró-Reitoria de
Pesquisa da UFPA (PROPESP, UFPA, Brazil), Brazilian
National Council for Scientic and Technological
Development (CNPq). This study was nanced in party
by Coordenação de Aperfeiçoamento de Pessoal de Nível
Superior - Brasil (CAPES) Finance Cod 001.
Disclosure
The authors report no conicts of interest in this work.
References
1. Lima RR, Santana LN, Fernandes RM, et al. Neurodegeneration and
glial response after acute striatal stroke: histological basis for neuro-
protective studies. Oxid Med Cell Longev.2016;2016:3173564. doi:10.
1155/2016/3173564
2. Colaianni V, Mazzei R, Cavallaro S. Copy number variations and
stroke. Neurol Sci.2016;37(12):18951904. doi:10.1007/s10072-016-
2658-y
3. Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Hennerici
MG. Classication of stroke subtypes. Cerebrovasc Dis.2009;27
(5):493501. doi:10.1159/000210432
4. Dziedzic T. Systemic inammation as a therapeutic target in acute
ischemic stroke. Expert Rev Neurother.2015;15(5):523531. doi:10.
1586/14737175.2015.1035712
5. Dye BA. Global periodontal disease epidemiology. Periodontol 2000.
2012;58(1):1025. doi:10.1111/j.1600-0757.2011.00413.x
6. Eke PI, Dye BA, Wei L, et al. Update on prevalence of periodontitis in
adults in the United States: NHANES 2009 to 2012. J Periodontol.
2015;86(5):611622. doi:10.1902/jop.2015.140520
7. Oppermann RV, Haas AN, Rosing CK, Susin C. Epidemiology of
periodontal diseases in adults from Latin America. Periodontol 2000.
2015;67(1):1333. doi:10.1111/prd.12061
Fagundes et al Dovepress
submit your manuscript | www.dovepress.com
DovePress
Vascular Health and Risk Management 2019:15
530
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
8. Papapanou PN, Sanz M, Buduneli N, et al. Periodontitis: consensus
report of workgroup 2 of the 2017 world workshop on the classication
of periodontal and peri-implant diseases and conditions. J Periodontol.
2018;89 Suppl 1:S173S182. doi:10.1002/JPER.17-0721
9. Kamer AR, Craig RG, Dasanayake AP, Brys M, Glodzik-Sobanska L,
de Leon MJ. Inammation and Alzheimers disease: possible role of
periodontal diseases. Alzheimers Dement.2008;4(4):242250.
doi:10.1016/j.jalz.2007.08.004
10. Teixeira FB, Saito MT, Matheus FC, et al. Periodontitis and alzhei-
mers disease: a possible comorbidity between oral chronic inam-
matory condition and neuroinammation. Front Aging Neurosci.
2017;9(OCT). doi:10.3389/fnagi.2017.00077.
11. Passoja A, Puijola I, Knuuttila M, et al. Serum levels of interleukin-10 and
tumour necrosis factor-alpha in chronic periodontitis. J Clin Periodontol.
2010;37(10):881887. doi:10.1111/j.1600-051X.2010.01602.x
12. Gani DK, Mallineni SK, Ambalavanan, Ramakrishnan,
Deepalakshmi EP. Estimation of the levels of C-reactive protein,
interleukin-6, total leukocyte count, and differential count in periph-
eral blood smear of patients with chronic periodontitis in a South
Indian population. West Indian Med J.2012;61(8):826831.
13. Kaur S, Bright R, Proudman SM, Bartold PM. Does periodontal
treatment inuence clinical and biochemical measures for rheumatoid
arthritis? A systematic review and meta-analysis. Semin Arthritis
Rheum.2014;44(2):113122. doi:10.1016/j.semarthrit.2014.04.009
14. Zeng XT, Leng WD, Lam YY, et al. Periodontal disease and carotid
atherosclerosis: a meta-analysis of 17,330 participants. Int J Cardiol.
2016;203:10441051. doi:10.1016/j.ijcard.2015.11.092
15. Lee YT, Lee HC, Hu CJ, et al. Periodontitis as a modiable risk
factor for dementia: a nationwide population-based cohort study. J
Am Geriatr Soc.2017;65(2):301305. doi:10.1111/jgs.14449
16. Ide M, Harris M, Stevens A, et al. Periodontitis and cognitive decline
in Alzheimers disease. PLoS One.2016;11(3):e0151081. doi:10.13
71/journal.pone.0151081
17. Janket SJ, Baird AE, Chuang SK, Jones JA. Meta-analysis of period-
ontal disease and risk of coronary heart disease and stroke. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod.2003;95(5):559569.
doi:10.1067/moe.2003.107
18. Lafon A, Tala S, Ahossi V, Perrin D, Giroud M, Béjot Y. Association
between periodontal disease and non-fatal ischemic stroke: a case-
control study. Acta Odontol Scand.2014;72(8):687693. doi:10.31
09/00016357.2014.898089
19. Leira Y, Seoane J, Blanco M, et al. Association between periodontitis
and ischemic stroke: a systematic review and meta-analysis. Eur J
Epidemiol.2017;32(1):4353. doi:10.1007/s10654-016-0170-6
20. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting
items for systematic reviews and meta-analyses: the PRISMA state-
ment. PLoS Med.2009;6(7):e1000097. doi:10.1371/journal.pmed.10
00097
21. Fowkes FG, Fulton PM. Critical appraisal of published research:
introductory guidelines. BMJ.1991;302(6785):11361140. doi:10.11
36/bmj.302.6785.1136
22. Penoni DC, Fidalgo TK, Torres SR, et al. Bone density and clinical
periodontal attachment in postmenopausal women: a systematic
review and meta-analysis. J Dent Res.2017;96(3):261269.
doi:10.1177/0022034516682017
23. Borenstein M, Hedges L, Higgins JPT, Rothstein H. An Introduction
to Meta-Analysis. Vol. 19; 2009.
24. Higgins J, Green S. Cochrane handbook for systematic reviews of
interventions. Versão 5.1.0. A Colaboração cochrane; 2011. Available
from: http://handbook-5-1.cochrane.org. Accessed October 8, 2019.
25. Balshem H, Helfand M, Schunemann HJ, et al. GRADE guidelines:
3. Rating the quality of evidence. J Clin Epidemiol.2011;64(4):401
406. doi:10.1016/j.jclinepi.2010.07.015
26. Elter JR, Offenbacher S, Toole JF, Beck JD. Relationship of period-
ontal disease and edentulism to stroke/TIA. J Dent Res.2003;82
(12):9981001. doi:10.1177/154405910308201212
27. Joshipura KJ, Hung HC, Rimm EB, Willett WC, Ascherio A.
Periodontal disease, tooth loss, and incidence of ischemic stroke.
Stroke.2003;34(1):4752. doi:10.1161/01.str.0000052974.79428.0c
28. Grau AJ, Becher H, Ziegler CM, et al. Periodontal disease as a risk
factor for ischemic stroke. Stroke.2004;35(2):496501. doi:10.1161/
01.STR.0000110789.20526.9D
29. Lee HJ, Garcia RI, Janket SJ, et al. The association between cumu-
lative periodontal disease and stroke history in older adults. J
Periodontol.2006;77(10):17441754. doi:10.1902/jop.2006.050339
30. Sim SJ, Kim HD, Moon JY, et al. Periodontitis and the risk for non-
fatal stroke in Korean adults. J Periodontol.2008;79(9):16521658.
doi:10.1902/jop.2008.080015
31. Jimenez M, Krall EA, Garcia RI, Vokonas PS, Dietrich T.
Periodontitis and incidence of cerebrovascular disease in men. Ann
Neurol.2009;66(4):505512. doi:10.1002/ana.21742
32. Kim HD, Sim SJ, Moon JY, Hong YC, Han DH. Association between
periodontitis and hemorrhagic stroke among Koreans: a case-control
study. J Periodontol.2010;81(5):658665. doi:10.1902/jop.2010.09
0614
33. Hashemipour MA, Afshar AJ, Borna R, Seddighi B, Motamedi A.
Gingivitis and periodontitis as a risk factor for stroke: a case-control
study in the Iranian population. Dent Res J (Isfahan).2013;10
(5):613619.
34. Holmlund A, Lampa E, Lind L. Oral health and cardiovascular
disease risk in a cohort of periodontitis patients. Atherosclerosis.
2017;262:101106. doi:10.1016/j.atherosclerosis.2017.05.009
35. Beck JD, Moss KL, Morelli T, Offenbacher S. Periodontal prole
class is associated with prevalent diabetes, coronary heart disease,
stroke, and systemic markers of C-reactive protein and interleukin-6.
J Periodontol.2018;89(2):157165. doi:10.1002/JPER.17-0426
36. Wu TJ, Trevisan M, Genco RJ, Dorn JP, Falkner KL, Sempos CT.
Periodontal disease and risk of cerebrovascular disease - The rst
national health and nutrition examination survey and its follow-up
study. Arch Intern Med.2000;160(18):27492755. doi:10.1001/
archinte.160.18.2749
37. Holmlund A, Holm G, Lind L. Number of teeth as a predictor of
cardiovascular mortality in a cohort of 7,674 subjects followed for 12
years. J Periodontol.2010;81(6):870876. doi:10.1902/jop.2010.090
680
38. Sen S, Giamberardino LD, Moss K, et al. periodontal disease, regular
dental care use, and incident ischemic stroke. Stroke.2018;49
(2):355362. doi:10.1161/STROKEAHA.117.018990
39. Dörfer CE, Becher H, Ziegler CM, et al. The association of gingivitis
and periodontitis with ischemic stroke. J Clin Periodontol.2004;31
(5):396401. doi:10.1111/j.1600-051x.2004.00579.x
40. Pradeep AR, Hadge P, Raju PA, Shetty SR, Shareef K, Guruprasad
CN. Periodontitis as a risk factor for cerebrovascular accident: a case-
control study in the Indian population. J Periodontal Res.2010;45
(2):223228. doi:10.1111/j.1600-0765.2009.01220.x
41. Abolfazli N, Ghoreishizadeh A, Ayramlu H, Ghavimi M,
Ghoreishizadeh M, Salehsaber F. Periodontal disease and risk of
cerebral ischemic stroke. J Neurol Sci.2011;28(3):307316.
42. Ghizoni JS, Taveira L, Garlet GP, et al. Increased levels of
Porphyromonas gingivalis are associated with ischemic and hemor-
rhagic cerebrovascular disease in humans: an in vivo study. J Appl
Oral Sci.2012;20(1):104112. doi:10.1590/s1678-77572012000100
019
43. Palm F, Lahdentausta L, Sorsa T, et al. Biomarkers of periodontitis
and inammation in ischemic stroke: a case-control study. Innate
Immun.2014;20(5):511518. doi:10.1177/1753425913501214
44. Diouf M, Basse A, Ndiaye M, Cisse D, Lo CM, Faye D. Stroke and
periodontal disease in Senegal: case-control study. Public Health.
2015;129(12):16691673. doi:10.1016/j.puhe.2015.02.033
45. Leira Y, Lopez-Dequidt I, Arias S, et al. Chronic periodontitis is
associated with lacunar infarct: a case-control study. Eur J Neurol.
2016;23(10):15721579. doi:10.1111/ene.13080
Dovepress Fagundes et al
Vascular Health and Risk Management 2019:15 submit your manuscript | www.dovepress.com
DovePress 531
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
46. Abd El-AleemSA, Morales-Aza BM, Donaldson LF.Sensory neuropep-
tide mRNa up-regulation is bilateral in periodontitis in the rat: a possible
neurogenic component to symmetrical periodontal disease. Eur J
Neurosci.2004;19(3):650658. d oi:10.1111/j. 1460-95 68.2004 .03179.x
47. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for
reporting systematic reviews and meta-analyses of studies that eval-
uate healthcare interventions: explanation and elaboration. BMJ.
2009;339:b2700. doi:10.1136/bmj.b2651
48. Fleming PS, Lynch CD, Pandis N. Randomized controlled trials in
dentistry: common pitfalls and how to avoid them. J Dent.2014;42
(8):908914. doi:10.1016/j.jdent.2014.06.004
49. Hajishengallis G. Periodontitis: from microbial immune subversion to
systemic inammation. Nat Rev Immunol.2015;15(1):3044. doi:10.
1038/nri3785
50. Esenwa CC, Elkind MS. Inammatory risk factors, biomarkers and
associated therapy in ischaemic stroke. Nat Rev Neurol.2016;12
(10):594604. doi:10.1038/nrneurol.2016.125
51. Pejcic A, Kesic LJ, Milasin J. C-reactive protein as a systemic marker
of inammation in periodontitis. Eur J Clin Microbiol Infect Dis.
2011;30(3):407414. doi:10.1007/s10096-010-1101-1
52. Vidale S, Consoli A, Arnaboldi M, Consoli D. postischemic inam-
mation in acute stroke. J Clin Neurol.2017;13(1):19. doi:10.3988/
jcn.2017.13.1.1
53. Hoffmann A, Zhu G, Wintermark M. Advanced neuroimaging in stroke
patients: prediction of tissue fate and hemorrhagic transformation. Expert
Rev Cardiovasc Ther.2012;10(4):515524. doi:10.1586/erc.12.30
54. Perry VH, Teeling J. Microglia and macrophages of the central
nervous system: the contribution of microglia priming and systemic
inammation to chronic neurodegeneration. Semin Immunopathol.
2013;35(5):601612. doi:10.1007/s00281-013-0382-8
55. Alhadidi Q, Shah ZA. Colin mediates LPS-induced microglial cell
activation and associated neurotoxicity through activation of NF-
kappaB and JAK-STAT pathway. Mol Neurobiol.2018;55(2):1676
1691. doi:10.1007/s12035-017-0432-7
56. Winning L, Linden GJ. Periodontitis and systemic disease: associa-
tion or causality? Current Oral Health Rep.2017;4(1):17. doi:10.
1007/s40496-017-0121-7
57. Li C, Lv Z, Shi Z, et al. Periodontal therapy for the management of
cardiovascular disease in patients with chronic periodontitis.
Cochrane Database Syst Rev.2017;2017:11.
58. Mituuti CT, Bianco VC, Bentim CG, de Andrade EC, Rubo JH,
Berretin-Felix G. Inuence of oral health condition on swallowing
and oral intake level for patients affected by chronic stroke. Clin
Interv Aging.2015;10:2935. doi:10.2147/CIA.S62314
59. Darby IB, Mooney J, Kinane DF. Changes in subgingival microora
and humoral immune response following periodontal therapy. J Clin
Periodontol.2001;28(8):796805. doi:10.1034/j.1600-051x.2001.280
812.x
60. Ajwani S, Jayanti S, Burkolter N, et al. Integrated oral health care for
stroke patients - a scoping review. J Clin Nurs.2017;26(78):891
901. doi:10.1111/jocn.13520
61. Terezakis E, Needleman I, Kumar N, Moles D, Agudo E. The impact
of hospitalization on oral health: a systematic review. J Clin
Periodontol.2011;38(7):628636. doi:10.1111/j.1600-051X.2011.01
727.x
62. Grau AJ, Buggle F, Ziegler C, et al. Association between acute
cerebrovascular ischemia and chronic and recurrent infection.
Stroke.1997;28(9):17241729. doi:10.1161/01.str.28.9.1724
Vascular Health and Risk Management Dovepress
Publish your work in this journal
Vascular Health and Risk Management is an international, peer-
reviewed journal of therapeutics and risk management, focusing on
concise rapid reporting of clinical studies on the processes involved in
the maintenance of vascular health; the monitoring, prevention and
treatment of vascular disease and its sequelae; and the involvement
of metabolic disorders, particularly diabetes. This journal is indexed
on PubMed Central and MedLine. The manuscript management
system is completely online and includes a very quick and fair peer-
review system, which is all easy to use. Visit http://www.dovepress.
com/testimonials.php to read real quotes from published authors.
Submit your manuscript here: https://www.dovepress.com/vascular-health-and-risk-management-journal
Fagundes et al Dovepress
submit your manuscript | www.dovepress.com
DovePress
Vascular Health and Risk Management 2019:15
532
Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 179.61.154.206 on 07-Nov-2019
For personal use only.
Powered by TCPDF (www.tcpdf.org) 1 / 1
... Therefore, stroke survivors often have a higher burden of dental caries, periodontitis, and tooth loss, combined with a lower frequency of dental attendance [14]. Moreover, periodontitis has been reported to be a potential risk factor for stroke, whereby a risk ratio of 1.88 and 2.27 was found, depending on study design [15]. Those issues make the oral situation of patients after stroke a field of high scientific and clinical interest [14]. ...
... Oral diseases, including tooth loss and periodontal diseases, can negatively affect OHRQoL [38,39]. It is known that patients after stroke show worse oral conditions, and periodontal diseases could even be related to stroke onset [14,15]. Although evidence is limited, a systematic review concluded stroke to be associated with tooth loss [40]. ...
... Therefore, oral conditions and their potential impact on quality of life require consideration during rehabilitation and care after stroke. With regard to the association between worse oral conditions, periodontitis, tooth loss, and stroke [14,15,40], oral health should be fostered in this patient group, starting immediately in the rehabilitation of patients. Therefore, medical staff and caregivers should be sensitized for oral health issues and support oral hygiene and dental (prevention oriented) consultations. ...
Article
Full-text available
Objectives: Aim of this systematic review was to assess oral health-related quality of life (OHRQoL) of patients after stroke. Methods: The systematic literature search was performed on December 2021 based on PubMed, Medline, Web of Science, and Scopus, with the search terms: “oral health-related quality of life” AND stroke OR apoplexy OR ischemic stroke OR apoplectic insult. Articles exclusively examining patients after stroke and reporting a well-documented and valid OHRQoL measurement were included. Results: Out of 68 findings, 8 studies were included. The number of patients ranged between 31 and 549 individuals, mean age between 55.7 and 73.9 years, and 49–72% of individuals were male. Two studies included a healthy control group. Oral health parameters were rarely reported across studies. Five studies reported on the Oral Health Impact Profile (OHIP) 14 for OHRQoL, showing means between 2.87 and 33.0 in sum score. Three studies applied Geriatric Oral Assessment Index (GOHAI), with sum scores between 45.6 and 55.0. Only one study found worse OHRQoL in stroke patients compared to healthy controls. Two studies reported on an association between OHRQoL and general quality of life. Three studies found OHRQoL to be associated with different oral health parameters. Only one study found OHRQoL to be associated with stroke-related parameters. Conclusions: Patients after stroke show a reduced OHRQoL. Medical staff and caregivers should support oral hygiene and dental visits, to foster patients’ oral health and OHRQoL. Keywords: oral health; oral health-related quality of life; stroke; oral hygiene; quality of life
... 9 Chronic inflammation is characterized by an increase in the inflammatory cytokines' level, which causes a weakening of the immune system function, thus increasing the risk of atherosclerosis and insulin resistance, which are the main triggers for developing CVd. 10 in literature, the association between Pd and diabetes is well-documented in an umbrella review by Seitz et al., 11 whereas the association between Pd and CVd is currently less investigated. Since diabetes is also an important CVd 17, 21, 22 microbiological, 17, 23, 24 immunological, 17,18,[25][26][27] pathophysiological, [28][29][30][31][32][33][34][35][36][37][38][39] risk of onset 22 and treatment 19,40,41 ) and different manifestations of cardiovascular diseases (coronary heart disease, 9,18,25,42,43 ...
... [61][62][63] Several studies have investigated the possible association between Pd and multiple causes of stroke. in a recent metaanalysis Fagundes et al. explored the association between stroke and periodontitis, concluding that there is a strong association between both diseases and that periodontitis may represent a risk factor especially for ischemic strokes. 29 Cheng et al., performed a dose-response metaanalysis showing a statistically significant correlation between tooth loss and both cardiovascular and stroke risk, suggesting that tooth loss was independently associated with lethal coronary heart disease and stroke risk increase. 28 lafon et al., aimed to determine the relationship between Pd and stroke incidence by a meta-analysis including cohort studies that evaluated the incidence of stroke (fatal or non-fatal, ischaemic or haemorrhagic) and baseline periodontal status. ...
Article
Introduction: Periodontal disease (PD) and cardiovascular diseases (CVD) are among the most common pathologies in the world and their relationship has long been studied. Both conditions lead to a chronic inflammatory process with degenerative characteristics and their bi-univocal correlation is now well established. The aim of this umbrella review on cardiovascular and periodontal disease was to evaluate the real degree of association between these two pathological conditions. Evidence acquition: We conducted a comprehensive literature search on PubMed/Medline and in the Cochrane Library for systematic reviews focused on clinical evidence regarding the relationship between PD and CVD. The internal validity of systematic reviews and meta-analyses was formally analyzed using the Overview Quality Assessment Questionnaire (OQAQ) tool. The umbrella review was planned in accordance with current international recommendations and was described as specified by the PRISMA guidelines. Evidence synthesis: Thirty-one systematic reviews, including 8 meta-analyses for a total of 507 clinical studies and over 3,549,966 patients were included. PD resulted to be associated with a higher risk of developing CVD (acute coronary syndrome, acute myocardial infarction) and cerebrovascular diseases (ischemic stroke); however, if the treatment of periodontitis reduces the risk of CVD events related is yet to be investigated. Conclusions: To date, the relationship between CVD and PD provides heterogeneous data. There is an association between PD and CVD but a causal relationship cannot be established. Further research with properly designed long-term follow-up studies are needed in order to examine various physiopathological aspects of their association.
... A risk ratio of 2.88 (95% confidence interval CI 1. 53-5.41) of IS in periodontitis patients has been reported [10]. More recent information suggests that, globally, periodontitis patients have about twice greater chance of experiencing some type of stroke, as to having IS [16,17]. Therefore, it can be inferred that the reported association between IS and periodontitis [10][11][12][13]15,18] emphasizes the systemic implications of periodontitis [17]. ...
... More recent information suggests that, globally, periodontitis patients have about twice greater chance of experiencing some type of stroke, as to having IS [16,17]. Therefore, it can be inferred that the reported association between IS and periodontitis [10][11][12][13]15,18] emphasizes the systemic implications of periodontitis [17]. ...
Article
Full-text available
The identification of the associative relationships between ischemic stroke (IS) and risk factors such as advanced age and periodontitis is essential to design real screening protocols and to address them using primary and secondary preventive policies. This study primarily aimed to evaluate the diagnostic performance of the 2018 European Federation of Periodontology/American Academy of Periodontology (EFP/AAP) case definition in detecting periodontitis against the 2012 Centers for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP) case definition in a group of IS patients. Secondarily, we report the periodontal status of IS patients and the associative relationship with respect to some risk factors. Patients with their first IS were assessed based on demographic data, medical, oral risk factors and periodontal parameters. The two case definitions were applied to identify the periodontitis burden. The agreement between the two case definition systems, as well as the misclassification ratio, were calculated. A total of 141 patients were included. According to the 2012 CDC/AAP and the 2018 EFP/AAP case definitions, a frequency of periodontitis of 98.5% and 97.8% based on two modalities of inclusion of cases in the severity groups, sensitivity values of 98.54% or 100%, and specificity values of 25% or 14.7% were calculated. Thus, the new case definition system has a higher capacity to detect periodontitis, especially the well-established forms.
... Diabetes, obesity, and aging are associated with the pathogenic factors of periodontitis [2][3][4]. Periodontitis may be a potential risk factor for other human diseases like Alzheimer's disease and stroke, which affect human systemic health [5,6]. The periodontal ligament (PDL), made up of collagen fiber bundles and cells, has many functions, including tooth support, tooth nutrition, alveolar bone remodeling, and damage tissue repair [7]. ...
Article
Full-text available
Background: Long noncoding RNAs (lncRNAs) are dysregulated in periodontitis development and involved in osteogenesis. The current study was aimed at investigating the function of lncRNA ANRIL in periodontal ligament cells (PDLCs) and potential molecular mechanisms. Methods: Firstly, the level of ANRIL was tested by qPCR. Then, PDLCs were treated with a mineralizing solution to induce osteogenic differentiation. ALP activity was measured, and protein levels of BMP2, Osterix, and OCN were measured by Western blot. A target of ANRIL was verified using dual-luciferase reporter assay. miR-7 level was measured by qPCR, and the signals of the NF-κB pathway were tested by Western blot. Results: ANRIL expression was downregulated in PDL tissues. Next, ALP activity and protein levels of BMP2, Osterix, and OCN were increased to show that PDLCs were differentiated. ANRIL level was increased in differential PDLCs, in which knockdown inhibited osteogenic differentiation. Then, miR-7 was found as a target of ANRIL. The miR-7 level was upregulated in PDL tissues and reduced in differential PDLCs. Inhibition of miR-7 suppressed ALP activity and BMP2, Osterix, and OCN expression. Moreover, inhibition of miR-7 reversed the effects on the osteogenic differentiation induced by knockdown of ANRIL. Besides, the levels of p-P65 and p-IκBα were elevated by ANRIL downregulation and were rescued by suppressing miR-7. Conclusions: Knockdown of ANRIL inhibited osteogenic differentiation via sponging miR-7 through the NF-κB pathway, suggesting that ANRIL might be a therapeutic target for periodontitis.
Article
Full-text available
Abstract Background Stroke patients have poor oral hygiene, experience oral dysfunction due to disease factors, and have impaired oral health-related quality of life (OHRQoL). This study aimed to determine the oral health knowledge, attitudes, and practices of stroke inpatients, assess the OHRQoL of these patients, and identify their correlates. Methods In this cross-sectional study, 281 stroke inpatients aged between 22 and 88 years (57.94 ± 10.94) were conveniently selected from three hospitals in Guangzhou, China. OHRQoL was measured among these stroke patients using a Chinese version of the Oral Health Impact Profile-14 (OHIP-14). SPSS 26.0 was used for statistical analysis. Mean scores, standard deviations, and frequency distributions were obtained. The Mann–Whitney U test, Kruskal‒Wallis H test, Spearman's correlation, and multiple linear regression were used in the analysis. Results The mean score of the patients' OHRQoL was 8.37 ± 6.67, with the highest score in the pain or discomfort of the mouth dimension (3.11 ± 2.13) and pain being the most common negative effect (13.5%). In multiple linear regression analysis, significant differences were found between patients only in age (P = 0.008), toothache (P
Thesis
Les maladies cardiovasculaires (MCV) constituent la première cause de mortalité mondiale. Par ailleurs, de nombreux travaux de par le monde révèlent l’existence d’une relation de causalité entre les maladies parodontales (MP) et les MCV.Ainsi, pour être efficaces, les actions de santé publique visant à lutter contre l’expansion des MCV devraient non seulement viser la réduction des facteurs de risque cardiovasculaires (FDRCV) modifiables ; mais aussi intégrer l’amélioration de la santé buccale dans le cadre global de lutte contre les MCV. La mise en place des dites actions requiert au préalable l’identification du niveau d’exposition des populations grâce à des données épidémiologiques suffisantes et précises sur la distribution de ces FDRCV. Au Cameroun, des données existent sur la distribution des FDRCV au sein de la population générale, mais aucune information n’existe sur le niveau d’exposition des militaires camerounais aux MCV. Pourtant, des travaux à travers le monde ont montré que la population militaire qui semblait à l’abri de ces pathologies se trouve aujourd’hui autant exposée que la population civile, parfois même plus.L’objectif général de ce travail de thèse était donc de d’évaluer le niveau d’exposition des militaires camerounais aux MCV et le lien qui existe entre leur risque cardiovasculaire et leur statut parodontal. Pour atteindre cet objectif général, 3 objectifs spécifiques ont été définis.Le premier objectif spécifique était de déterminer le niveau d’exposition des militaires camerounais aux FDRCV. Sur un échantillon de 566 adultes dont 295 étaient militaires, il a été observé que les FDRCV comportementaux étaient plus prévalents chez les militaires que chez les civils, le tabagisme et la consommation excessive d’alcool notamment, 13,9% versus 4,4% (p < 0,001) et 61,7% versus 14,8% (p < 0,001) respectivement.Le second objectif spécifique était de décrire le statut parodontal de la population militaire camerounaise. Sur 857 personnels militaires examinés, il a été observé que 68,6% souffraient de gingivite et 13,7% de parodontite.Le troisième objectif spécifique était de déterminer le lien qui existe entre les paramètres parodontaux des militaires camerounais et leurs profils de risque cardiovasculaire. Au sein d’un échantillon de 205 militaires, il a été observé que le tabagisme était associé à la parodontite, OR : 4, 44 [1,73-11,43]. Et qu’une hygiène buccale inadéquate était associée à un profil de risque cardiovasculaire élevé, mauvaise/bonne, OR : 3,96 [1,07-14,57] et moyenne/bonne, OR : 3,44 [1,11-10,66].En conclusion, les militaires camerounais sont particulièrement exposés à des facteurs de risque cardiovasculaires et parodontaux comportementaux. Ils devraient par conséquent modifier leur hygiène de vie, notamment en réduisant la consommation de tabac et d’alcool et en améliorant la qualité de leur hygiène buccale. Par ailleurs, les programmes nationaux de lutte contre les maladies non transmissibles (MNT) devraient intégrer la promotion de la santé bucco-dentaire, de même qu’il serait souhaitable que des programmes spécifiques destinés aux forces de défense soient mis en œuvre.
Article
Full-text available
Congenital hypogonadotropic hypogonadism is characterized by delayed or absent puberty and infertility due to abnormally low levels of gonadotropic hormones and sex steroids. The most common reason for its development is Kallmann syndrome - a rare congenital disorder resulting from impaired migration of GnRH-secreting neurons from the olfactory epithelium to the hypothalamus. It is associated with hyposmia and anosmia. In 1942 Klinefelter described 9 men with gynecomastia, sparse facial and body hair, small testes and inability to produce sperm. In 1959 the additional X chromosome was discovered - genotype 47, XXY, characteristic of the complete and most common form of Klinefelter syndrome. The classic phenotype includes low serum testosterone, high LH and FSH levels. We present a rare clinical case of an 18-year-old boy with disomy X- 47, XXY, hormonal constellation for hypogonadotropic hypogonadism, atypical for Klinefelter syndrome, and olfactory defect - Kallmann syndrome. Key words: Hypogonadotropic hypogonadism, Kallmann syndrome, Klinefelter syndrome
Article
Aim: Tinnitus, ringing in the ears, is speculated to be driven by inflammation. This study examined whether periodontitis is a risk factor for tinnitus using Taiwan's National Health Insurance Research Database. Materials and methods: Among the 79,456 patients who visited for dental concerns, 11,055 patients who were diagnosed with periodontitis and underwent periodontal treatment were enrolled between 2000 and 2015 as Group 1. After matching for sex, age, and index year, 11,055 patients with periodontitis who received no treatment were enrolled as Group 2. Similarly, 11,055 participants without periodontitis were included as controls. Results: At the end of follow-up, 412 and 404 participants in the two periodontitis groups and 321 participants in the control group had tinnitus. Cumulative risk for tinnitus in Group 1 or 2 was significantly greater than in the control group. More periodontitis patients than controls developed tinnitus (adjusted hazard ratios were 1.71 (95% CI: 1.49-1.97, p<0.001) and 1.64 (95% CI: 1.37-1.86, p<0.001) in Groups 1 and 2, respectively). The risks were not significantly different between Groups 1 and 2. Similar findings were obtained after excluding data for the first 1 or 5 years. Conclusion: The study findings indicate that periodontitis is associated with tinnitus.
Chapter
Periodontitis is a chronic inflammatory disease of the tooth-supporting connective tissue and alveolar bone that is initiated by a bacterial biofilm in periodontal pockets. It affects about half of adults in the Western world, and is associated with a range of systemic comorbidities, e.g., cardiovascular disease (CVD), diabetes and rheumatoid arthritis, and these diseases share overlapping systemic and target tissue inflammatory mechanisms. Indeed, mounting evidence has indicated that their association is causal and built on the presence of systemic low-grade inflammation (LGI). Prior research linking periodontitis to CVD has mainly been derived from experimental studies, observational data, and small interventional trials with surrogate markers of CVD, e.g., endothelial dysfunction. However, recent data from randomised studies have demonstrated that intensive treatment of periodontitis can reduce blood pressure in patients with hypertension in conjunction with reduction of systemic inflammatory markers. Furthermore, targeted anti-inflammatory therapy has been shown to reduce recurrent events in patients with established CVD and LGI. Along this line, the concept of residual inflammatory risk has emerged as an independent new risk factor for atherothrombotic CVD. The present review summarizes translational evidence indicating that periodontitis is a risk factor for CVD dependent on LGI, and we conclude that treatment of periodontitis is likely to contribute importantly to reduction of residual inflammatory risk.
Article
Full-text available
Background: Chronic periodontitis is highly prevalent among older adults. The study aimed to compare periodontal disease among Australian older adults in two generations. We hypothesized that the prevalence and severity of periodontitis would decrease from the previous generation to the recent generation. Methods: Data were obtained from the South Australian Dental Longitudinal Study (SADLS) in 1991-92 (SADLSI) and 2013-14 (SADLS II); population-based longitudinal surveys of Australian older adults aged 60+ years. American Academy Periodontology (AAP), the U.S. Centres for Disease Control and Prevention (AAP/CDC), and the 2018 European Federation of Periodontology (EFP/AAP) classification case definitions were used to define and calculate prevalence of chronic periodontitis. Multivariable log-Poisson regression models were used to identify risk indicators for severe periodontitis after adjusting for other covariates. Results: There were total of 801 and 355 participants had a periodontal exam in SADLS I and II, respectively. The prevalence of severe periodontitis was higher in the recent generation (88% and 56%) than the previous generation (75% and 46.7%) under the CDC/AAP and EFP/AAP case definitions, respectively. The mean number of missing teeth was lower in the recent generation (6) than the previous generation (13). The prevalence ratio of severe periodontitis was around 2 times higher in the younger age group, males, those not born in Australia and current smokers across both generations. Conclusion: Our findings indicated that the recent generation of older adults has higher prevalence and severity of chronic periodontitis than the previous generation. Our findings indicated that ageing, being male, born in overseas, low household income, no dental insurance, and being a current smoker are significant risk factors associated with severe periodontitis among older Australians. This article is protected by copyright. All rights reserved.
Article
Full-text available
A new periodontitis classification scheme has been adopted, in which forms of the disease previously recognized as “chronic” or “aggressive” are now grouped under a single category (“periodontitis”) and are further characterized based on a multi‐dimensional staging and grading system. Staging is largely dependent upon the severity of disease at presentation as well as on the complexity of disease management, while grading provides supplemental information about biological features of the disease including a history‐based analysis of the rate of periodontitis progression; assessment of the risk for further progression; analysis of possible poor outcomes of treatment; and assessment of the risk that the disease or its treatment may negatively affect the general health of the patient. Necrotizing periodontal diseases, whose characteristic clinical phenotype includes typical features (papilla necrosis, bleeding, and pain) and are associated with host immune response impairments, remain a distinct periodontitis category. Endodontic‐periodontal lesions, defined by a pathological communication between the pulpal and periodontal tissues at a given tooth, occur in either an acute or a chronic form, and are classified according to signs and symptoms that have direct impact on their prognosis and treatment. Periodontal abscesses are defined as acute lesions characterized by localized accumulation of pus within the gingival wall of the periodontal pocket/sulcus, rapid tissue destruction and are associated with risk for systemic dissemination.
Article
Full-text available
Periodontitis is an oral chronic infection/inflammatory condition, identified as a source of mediators of inflammation into the blood circulation, which may contribute to exacerbate several diseases. There is increasing evidence that inflammation plays a key role in the pathophysiology of Alzheimer’s disease (AD). Although inflammation is present in both diseases, the exact mechanisms and crosslinks between periodontitis and AD are poorly understood. Therefore, this article aims to review possible comorbidity between periodontitis and AD. Here, the authors discuss the inflammatory aspects of periodontitis, how this oral condition produces a systemic inflammation and, finally, the contribution of this systemic inflammation for worsening neuroinflammation in the progression of AD.
Article
Full-text available
Microglial cells are activated in response to different types of injuries or stress in the CNS. Such activation is necessary to get rid of the injurious agents and restore tissue homeostasis. However, excessive activation of microglial cells is harmful and contributes to secondary injury. Pertinently, microglial cell activity was targeted in many preclinical and clinical studies but such strategy failed in clinical trials. The main reason behind the failed attempts is the complexity of the injury mechanisms which needs either a combination therapy or targeting a process that is involved in multiple pathways. Cofilin is a cytoskeleton-associated protein involved in actin dynamics. In our previous study, we demonstrated the role of cofilin in mediating neuronal apoptosis during OGD conditions. Previous studies on microglia have shown the involvement of cofilin in ROS formation and phagocytosis. However, additional studies are needed to delineate the role of cofilin in microglial cell activation. Therefore, in the current study, we investigated the role of cofilin in LPS-induced microglial cell activation using cofilin siRNA knockdown paradigms. The viability of differentiated PC12 cells was used as a measure of the neurotoxic potential of conditioned medium derived from cofilin siRNA-transfected and LPS-activated microglial cells. Cofilin knockdown significantly inhibited LPS-induced microglial cell activation through NF-κB and JAK-STAT pathways. The release of proinflammatory mediators (NO, TNF-α, iNOS, and COX2) as well as microglial proliferation and migration rates were significantly reduced by cofilin knockdown. Furthermore, differentiated PC12 cells were protected from the neurotoxicity induced by conditioned medium derived from cofilin-transfected and LPS-activated microglial cells. In conclusion, we demonstrated that cofilin is involved in the cascade of microglial cell activation and further validates our previous study on cofilin's role in mediating neuronal apoptosis. Together, our results suggest that cofilin could present a common target in neurons and microglial cells and might prove to be a promising therapy for different brain injury mechanisms including stroke.
Article
Full-text available
Purpose of Review The aim was to assess recent evidence that diabetes, metabolic syndrome (MetS) and obesity impact the progression of periodontitis. Recent Findings Electronic searches using Embase, Medline, and Web of Science were carried out for epidemiological studies on humans, published between 2014 and 2016. A small number of prospective studies and systematic reviews were identified that in general provide further support for the hypothesis that diabetes, metabolic syndrome and obesity can adversely affect the periodontal condition. Summary Confounding remains the most challenging issue in the interpretation of the associations found between diabetes, MetS, obesity and periodontal disease. Recent research applying a Mendelian randomisation approach concluded that the association between obesity and periodontitis is confounded and questioned a role for obesity in causation. Further studies are warranted to assess the issue of causality.
Article
Full-text available
Cerebral ischemia is caused by arterial occlusion due to a thrombus or an embolus. Such occlusion induces multiple and concomitant pathophysiological processes that involve bioenergetic failure, acidosis, loss of cell homeostasis, excitotoxicity, and disruption of the blood-brain barrier. All of these mechanisms contribute to neuronal death, mainly via apoptosis or necrosis. The immune system is involved in this process in the early phases after brain injury, which contributes to potential enlargement of the infarct size and involves the penumbra area. Whereas inflammation and the immune system both exert deleterious effects, they also contribute to brain protection by stimulating a preconditioning status and to the concomitant repair of the injured parenchyma. This review describes the main phases of the inflammatory process occurring after arterial cerebral occlusion, with an emphasis on the role of single mediators.
Article
Background: This paper focuses on the Periodontal Profile Class (PPC) System that may be more informative and representative of periodontitis phenotypes than current case definitions of periodontitis. This study illustrates the unique aspects of the PPC compared with other periodontal indices for studying associations between periodontal disease and prevalent systemic conditions. Methods: We computed odds ratios and 95% confidence intervals to compare associations between periodontal disease and prevalent systemic conditions using our new PPC and two traditional indices. We used the Bayesian Information Criterion (BIC) to determine the fit of the model and the magnitude of the contribution attributable to periodontal disease beyond traditional risk factors. The Atherosclerosis Risk in Communities (ARIC) Study (1996-1998) results were compared with results from the combined National Health and Nutrition Examination Survey 2009-2014 datasets. Results: In the ARIC Study, high gingival inflammation, tooth loss, severe tooth loss, and severe disease PPC components were significantly associated with diabetes, coronary heart disease (CHD), high-sensitivity C-reactive protein, and interleukin (IL)-6, while only severe disease was associated with stroke. Severe disease was associated with CHD using the Centers for Disease Control/American Academy of Periodontology index, and the European Periodontal index was associated with CHD and IL-6. Conclusions: The addition of the PPC to traditional variables associated with prevalent diabetes, stroke, CHD, and systemic measures of inflammation resulted in very strong improvement of the overall models, while the traditional indices were less likely to be associated and, if present, the associations were weaker. The PPC system provides specific insight into the individuals and periodontal characteristics of the phenotype that are associated with systemic conditions that may be useful in designing treatment interventions.
Article
Background and purpose: Periodontal disease is independently associated with cardiovascular disease. Identification of periodontal disease as a risk factor for incident ischemic stroke raises the possibility that regular dental care utilization may reduce the stroke risk. Methods: In the ARIC (Atherosclerosis Risk in Communities) study, pattern of dental visits were classified as regular or episodic dental care users. In the ancillary dental ARIC study, selected subjects from ARIC underwent fullmouth periodontal measurements collected at 6 sites per tooth and classified into 7 periodontal profile classes (PPCs). Results: In the ARIC study 10 362 stroke-free participants, 584 participants had incident ischemic strokes over a 15-year period. In the dental ARIC study, 6736 dentate subjects were assessed for periodontal disease status using PPC with a total of 299 incident ischemic strokes over the 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). Periodontal disease was significantly associated with cardioembolic (hazard ratio, 2.6; 95% confidence interval, 1.2-5.6) and thrombotic (hazard ratio, 2.2; 95% confidence interval, 1.3-3.8) stroke subtypes. Regular dental care utilization was associated with lower adjusted stroke risk (hazard ratio, 0.77; 95% confidence interval, 0.63-0.94). Conclusions: We confirm an independent association between periodontal disease and incident stroke risk, particularly cardioembolic and thrombotic stroke subtype. Further, we report that regular dental care utilization may lower this risk for stroke.
Article
Background: There is an association between chronic periodontitis and cardiovascular disease (CVD). However, it is not known whether periodontal therapy could prevent or manage CVD in patients with chronic periodontitis. Objectives: The objective of this systematic review was to investigate the effects of periodontal therapy in preventing the occurrence of, and management or recurrence of, CVD in patients with chronic periodontitis. Search methods: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 31 August 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2017, Issue 7), MEDLINE Ovid (1946 to 31 August 2017), Embase Ovid (1980 to 31 August 2017) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL EBSCO) (1937 to 31 August 2017) . The US National Institutes of Health Trials Registry (ClinicalTrials.gov), the World Health Organization International Clinical Trials Registry Platform and Open Grey were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.We also searched the Chinese BioMedical Literature Database (1978 to 27 August 2017), the China National Knowledge Infrastructure (1994 to 27 August 2017), the VIP database (1989 to 27 August 2017) and Sciencepaper Online (2003 to 27 August 2017). Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs were considered eligible. Studies were selected if they included patients with a diagnosis of chronic periodontitis and previous CVD (secondary prevention studies) or no CVD (primary prevention studies); patients in the intervention group received active periodontal therapy compared to maintenance therapy, no periodontal treatment or another kind of periodontal treatment in the control group. Data collection and analysis: Two review authors carried out the study identification, data extraction and risk of bias assessment independently and in duplicate. Any discrepancies between the two authors were resolved by discussion or with a third review author. A formal pilot-tested data extraction form was adopted for the data extraction, and the Cochrane tool for risk of bias assessment was used for the critical appraisal of the literature. Main results: No studies were identified that assessed primary prevention of CVD in people with periodontitis. One study involving 303 participants with ≥ 50% blockage of one coronary artery or a coronary event within three years, but not the three months prior, was included. The study was at high risk of bias due to deviation from the protocol treatment allocation and lack of follow-up data. The trial compared scaling and root planing (SRP) with community care for a follow-up period of six to 25 months. No data on deaths (all-cause or CVD-related) were reported. There was insufficient evidence to determine the effect of SRP and community care in reducing the risk of CVD recurrence in patients with chronic periodontitis (risk ratio (RR) 0.72; 95% confidence interval (CI) 0.23 to 2.22; very low quality evidence). The effects of SRP compared with community care on high-sensitivity C-reactive protein (hs-CRP) (mean difference (MD) 0.62; -1.45 to 2.69), the number of patients with high hs-CRP (RR 0.77; 95% CI 0.32 to 1.85) and adverse events (RR 9.06; 95% CI 0.49 to 166.82) were also not statistically significant. The study did not assess modifiable cardiovascular risk factors, other blood test results, heart function parameters or revascularisation procedures. Authors' conclusions: We found very low quality evidence that was insufficient to support or refute whether periodontal therapy can prevent the recurrence of CVD in the long term in patients with chronic periodontitis. No evidence on primary prevention was found.
Article
Background and aims: The aim of this study was to determine whether oral health is uniformly associated with three different cardiovascular diseases (CVDs), including myocardial infarction (MI), stroke, and heart failure (HF), which has not been studied previously. Methods: A full mouth investigation was performed in 8999 individuals referred to a specialized periodontology clinic between 1979 and 2012. The number of deepened pockets (NDP), number of teeth (NT), and bleeding on probing (BOP) were investigated. Incident CVD diagnosis was obtained from the Swedish cause of death and the hospital discharge registers. Results: During a median follow-up time of 15.8 years (153,103 person years at risk), 1338 incident cases of fatal/non-fatal CVD occurred (672 fatal/non-fatal MI, 545 stroke and 302 HF). When NT, BOP and NDP were all included in the same model with age, sex, smoking, calendar time, and education level, NT and NDP, but not BOP, were significantly related to future CVD (combined end-point, p = 0.0003 for NT and p = 0.007 for NDP). In similar analyses of 3 separate CVD outcomes, NT was significantly related to MI, with an incidence rate ratio (IRR) for a given interquartile range change of 0.90 (95% CI 0.82-0.99) and to HF, with an IRR of 0.87 (95% CI 0.77-0.99). However, NT was not significantly related to stroke. BOP and NDP were not significantly related to any of the three separate CVD outcomes. Conclusion: Oral health, mainly represented by NT, was related to incident MI and HF, but not to incident stroke. Therefore, oral health does not seem to relate to all major CV disorders in a similar fashion.