Content uploaded by Natnicha Leelaviwat
Author content
All content in this area was uploaded by Natnicha Leelaviwat on Sep 17, 2023
Content may be subject to copyright.
Journal of Arrhythmia. 2023;00:1–5.
|
1www.journalofarrhythmia.org
1 | INTRODUCTION
Periodontal disease (PD) is a chronic inflammatory disease caused
by the accumulation of dental plaque that triggers an immune re-
sponse.1 Studies have found that individuals with PD are at a higher
risk of developing cardiovascular diseases (CVD). Recent evidence
suggested the possibility of an association between PD and atrial
fibrillation (AF).2 AF and atrial flutter (AFL) have a significant impact
on morbidity and mortality and can lead to various complications
such as stroke, systemic thromboembolism, dementia, heart failure,
and myocardial infarction. These complications not only affect the
quality of life but also increase healthcare costs.3 In this systematic
review and meta- analysis, we aim to evaluate the relationship be-
tween PD and AF/AFL.
2 | METHODS
A literature search was performed in the MEDLINE, EMBASE, and
SCOPUS, using the search terms “periodontal” and “atrial fibrilla-
tion,” “periodontitis” and “atrial fibrillation,” and “periodontal” and
“atrial flut ter”. Studies were included if they were human studies,
Received: 12 June 2023
|
Revised: 4 August 2023
|
Accepted: 20 Au gust 2023
DOI: 10.1002/joa3.12921
RAPID COMMUNICATION
Periodontal disease and risk of atrial fibrillation or atrial flutter:
A systematic review and meta- analysis
Natnicha Leelaviwat MD1 | Jakrin Kewcharoen MD2 | Kiddee Poomprakobsri MD3 |
Angkawipa Trongtorsak MD4 | Gaspar Del Rio- Pertuz MD5 | Mahmoud Abdelnabi MD1 |
Juthipong Benjanuwattra MD1 | Leenhapong Navaravong MD6,7
This is an op en access ar ticle under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in
any medium, provided t he original work is properly cited, the use is non-commercial an d no modific ations or adaptations a re made.
© 2023 The Authors. Journal of Arrhythmia published by John Wiley & Sons Austr alia, Ltd on be half of Japanese Heart R hythm Soc iety.
1Depar tment of Internal Medici ne, Texas
Tech University Health Sciences Center,
Lubbock, Texas, USA
2Division of Cardiology, Loma Linda
University Healt h, Loma Linda, California,
USA
3Advanced Education Program in Im plant
Dentis try, Loma Linda University School
of Dentis try, Loma Lin da, Califo rnia, USA
4Department of Cardiovascular Medicine,
Virginia Commonwealth University,
Richmond, Virginia, USA
5Cardiovascular Division, University of
Minnesota, Minneapolis, Minnesota, USA
6Division of Cardiovascular Medicine,
University of Utah H ealth, Salt Lake City,
Utah, USA
7Intermountain Heart Institute— Utah
Valley, Provo, Ut ah, USA
Correspondence
Leenhapong Navaravong, Intermountain
Heart Institute— Utah Valley, 395 W
Cougar B lvd, Suite 50 3 Provo, UT 846 04,
USA.
Email: leenhapong.navaravong@imail.org
Abstract
Background: We conducted a study to evaluate the risk of atrial fibrillation (AF) and
atrial flutter (AFL) in periodontal disease (PD) patients.
Methods: Cohort studies that evaluate the risk of AF or AFL in PD patients were
included. The risk was expressed in the pooled odd ratio (OR) with 95% confidence
interval (CI).
Results: A total of four cohort studies were included. We found that patients with
PD have a significantly higher risk of AF/AFL compared to those without PD with the
pooled OR of 1.33 (95% CI 1.29– 1.38; p = 0.357, I2 = 3.0%).
Conclusions: PD increases the risk of AF and AFL.
KEYWORDS
atrial fibrillation, atrial flutter, cardiovascular disease, periodontal disease
2
|
LEEL AVIWAT et al.
cohort or case– control studies, and required to report the associa-
tion between AF or AFL and PD or report the incidence of AF or
AFL comparing patients who had PD and patients who did not have
PD. AF or AFL was identified from the diagnosis codes or death
certificates using the International Classification of Diseases, Ninth
Revisions, Clinical Modification (ICD- 9- CM) codes or by a standard
12- lead ECG. PD was defined differently among the four s tudies that
were included. It was defined by ICD- 9- CM code together with re-
ceiving antibiotic therapy or periodontal treatment in one study. An-
other study defined PD by diagnosis code and subgingival curettage
treatment code. Another study defined PD if meeting the World
Health Organization Community Periodontal Index greater than or
equal to code 3 of periodontitis diagnosis. The last study defined PD
according to the Periodontal Profile Class.
The risk of AF or AFL in PD was expressed in the pooled odd
ratio (OR) with 95% confidence interval (CI). All statistical analyses
in this meta- analysis were performed using STATA 14.2 software.
3 | RESULTS
Our search strategy yielded 344 results. A total of 4 cohort stud-
ies met the inclusion criteria.2 , 4 – 6 However, one study6 was further
excluded because of a small sample size resulting in a larger confi-
dence interval. A final of 3 studies2,4,5 including 1 358 568 patient s
(680 549 with PD and 677 974 without PD) were included in the
study. Figure 1 outlines our search methodology and selection pro-
cess; the baseline characteristics of the included studies are summa-
rized in Table 1. We found that the patients who had PD had a 33%
increased risk of having AF or AFL compared to patients who did
not have PD (pooled OR 1.33, 95% CI 1.29– 1.38; p = .357, I2 = 3.0%)
(Figure 2).
4 | DISCUSSION
To our knowledge, this is the first systematic review and meta-
analysis to assess the risk of AF and AFL associated with PD. We
found that PD is associated with an increased 1.3- fold risk of AF
and AFL.
Several mechanisms have been proposed to explain the potential
link between PD and CVD with systemic inflammation being one of
the most important.7 Multiple studies demonstrated that patients
who have higher levels of c- reactive protein (CRP) have a greater risk
of acute myocardial infarction and cardiovascular events.8 Inflam-
mation is a key pathophysiologic factor of AF. Chronic inflammation
in the atrial leads to fibrosis and dilatation, which can disrupt the
normal electrical activity of the heart and increase risk of AF. This
process is referred to as atrial remodeling.9 The high incidence of AF
in a state of the inflammator y process such as postcardiac surgery
FIGURE 1 Prisma flow diagram
demonstrates search methodology and
selection process. For more information,
visit www.prism a- state ment.org.
Records idenfied
throughMEDLINE
databasesearching
(n=66)
ScreeningIncluded Eligibility Idenficaon
Addionalrecords
idenfiedthrough EMBASE
database searching
(n=172)
Records duplicate removed
(n =192)
Records screened
(n=152) Titlesand Abstractsreviewed
excluded:
n=103
Full-text arcles assessed
foreligibility
n=49
Full-text articles were excluded due to:
Does not evaluate our topic: 15
Does not compare patients with
periodontal disease and patients without
periodontal disease: 14
Does not evaluate atrial fibrillation as an
outcome: 4
Studies included in
qualitavesynthesis
n=16
Studies included in qualitave
synthesis(meta-analysis)
(n=4)
Addionalrecords idenfied
throughSCOPUSdatabase
searching
(n=106)
Small samplesize
excluded:
n=1
Studiesfinally includedin
qualitavesynthesis
(meta-analysis)
n=3
18832148, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/joa3.12921, Wiley Online Library on [16/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
|
3
LEELAVIWAT et al.
TABLE 1 Characteristics of studies in the meta- analysis that investigate the association between periodontal disease and atrial fibrillation/atrial flut ter.
First author/
year Country Study design
Patients (n)
Study population/inclusion criteria Exclusion criteria
Periodontal disease
diagnosis
Atrial fibrillation/atrial
flutter diagnosis
Periodontal
disease
Nonperiodontal
disease
Chen/2016 Taiwan A retrospective
cohort
393 745 393 745 Participants from The Taiwanese National
Health Insurance Research Database
(NHIRD) included patients with PD and
non- PD that were individually matched
with a 1:1 ratio based on gender and
individual age
Previous diagnoses of
AF or AFL
A diagnosis code
(ICD9- CM Codes
523.3– 5)
A diagnosis code
(ICD9- CM Codes
4 2 7 . 3 1– 2 )
Hsu/2022 Taiwan A retrospective
cohort
282 560 282 560 Participants from The Taiwanese National
Health Insurance Research Database
(NHIRD) included patients with
periodontitis and nonperiodontitis that
were individually matched with a 1:1 ratio
based on age, urbanization level, income,
and index day
Prior stroke A diagnosis code 523.X
with subgingival
curettage treatment
code (91006– 91 0 08)
N/A
Sen/2021 United
States
A prospective
cohort
4289 1669 Par ticipant s from the Atherosclerosis Risk in
Communities (ARIC) Study
Prior AF, participants
with medical
contraindications
to a dental exam,
those with dental
implant s only, not
African American
or white (because
of limited sample
size of other races)
The periodontal
profile class (PPC);
periodontal health
(PPC- A), mild PD
(PPC- B and C),
moderate PD (PPC- D
and E), and severe PD
(PPCF and G)
A standard 12- lead ECG,
hospitalization, and
death certificates
using ICD- 9- CM
codes 427.31 or
42 7.3 2
18832148, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/joa3.12921, Wiley Online Library on [16/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
4
|
LEEL AVIWAT et al.
also suggested the link between inflammation and AF.10 Studies have
reported an association between inflammator y markers, such as CRP
and interleukin- 6 (IL- 6), and AF.9 Furthermore, Im et al. found that AF
patients with periodontitis had a higher risk of major cardiac events
compared to those without periodontitis. The study also found that
patients with periodontitis had a higher prevalence of other arrhyth-
mias, including atrial premature beat, atrial tachycardia, and ventric-
ular tachycardia.6 Not only we found an elevation of inflammator y
markers in AF, but an elevation of CRP and IL- 6 is also seen in PD
as well,2 and there is a reduction of inflammatory markers including
CRP, IL- 6, and tumor necrosis factor- alpha after dental treatment.11
This may be a reasonable presumption based on the evidence avail-
able that decreasing systemic inflammation through dental treat-
ment could potentially lower the risk of developing AF and improve
prognosis in patients who have established AF diagnosis.
Not only inflammation, but platelet and coagulation cascade ac-
tivations also play a role in the development of AF and lead to con-
sequent AF thrombotic complications.9 The study in 76 AF patients
suggests that periodontitis is not only positively correlated with LAA
fibrosis but also with the presence of atrial thrombi, further high-
lighting the potential link between poor dental health and cardio-
vascular event.12
The current 2019 AHA/ACC/HRS guideline for the management
of patients with AF emphasizes addressing the risk factors as one
of the treatment approaches for AF.13 Weight reduction resulted in
a reduction in AF burden with the explanation that obesity is as-
sociated with a systemic proinflammatory state and diastolic dys-
function.14 Thus, reducing systemic inflammatory conditions by
promoting oral hygiene care could be another easy way to reduce
the risk of developing AF.
5 | CONCLUSIONS
Our study suggested that PD is associated with an increased risk
of AF/AFL. Thus, better oral health might be an easily modifiable
risk factor to reduce the risk of developing AF/AFL. However, more
research is needed to clarify the relationship to identify the most ef-
fective strategy for preventing and managing both conditions.
CONFLICT OF INTEREST STATEMENT
All the authors declare no conflict of interest.
ETHICS APPROVAL STATEMENT, PATIENT CONSENT
STATEMENT, AND CLINICAL TRIAL REGISTR ATION
Not applicable.
ORCID
Natnicha Leelaviwat https://orcid.org/0000-0001-7994-639X
Jakrin Kewcharoen https://orcid.org/0000-0003-0959-5576
Leenhapong Navaravong https://orcid.
org/0000-0001-7087-1707
TWITTER
Natnicha Leelaviwat NLeelaviwat
REFERENCES
1. Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases.
Nat Rev Dis Primers. 2017;3:17038.
2. Sen S, Redd K, Trivedi T, Moss K, Alonso A , Soliman EZ,
et al. Periodontal disease, atrial fibrillation and stroke. Am Heart J.
2021;235:36– 43.
3. Staerk L, Sherer JA, Ko D, Benjamin EJ, Helm RH. Atrial fibrillation:
epidemiology, pathophysiology, and clinical outcomes. Circ Res.
2017;12 0(9):1501– 17.
4. Chen DY, Lin CH, Chen YM, Chen HH. Risk of atrial fibrillation or
flutter associated with periodontitis: a nationwide, population-
based, cohort study. PloS One. 2016;11(10):e0165601.
5. Hsu PW, Shen YW, Syam S, Liang WM, Wu TN, Hsu JT, et al. Patient s
with periodontitis are at a higher risk of stroke: a Taiwanese cohort
study. J Chin Med Assoc. 2022;85(10):1006– 10.
6. Im SI, Heo J, Kim BJ, Cho KI, Kim HS, Heo JH, et al. Impact of peri-
odontitis as representative of chronic inflammation on long- term
clinical outcomes in patients with atrial fibrillation. Open Heart.
2018;5(1):e000708.
FIGURE 2 Forest plot of the
included studies that evaluate the risk of
developing atrial fibrillation/atrial flutter
between patients with and without
periodontal disease.
18832148, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/joa3.12921, Wiley Online Library on [16/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
|
5
LEELAVIWAT et al.
7. Demmer RT, Desvarieux M. Periodontal infections and car-
diovascular disease: the heart of the matter. J Am Dent Assoc.
2006;137(Suppl):14S– 20S. quiz 38S.
8. Fischer RG, Lira Junior R, Retamal- Valdes B, Figueiredo LC ,
Malheiros Z, Stewart B , et al. Periodontal disease and its impact on
general health in Latin America. Section V: treatment of periodon-
titis. Braz Oral Res. 2020;34(supp1 1):e026.
9. Carrizales- Sepúlveda EF, Ordaz- Farías A, Vera- Pineda R , Flores-
Ramírez R. Periodontal disease, systemic inflammation and the risk
of cardiovascular disease. Heart Lung Circ. 2018;27(11):1327– 34.
10. Bruins P, Velthuis H, Yazdanbakhsh AP, Jansen PGM, van Hardevelt
FWJ, de Beaumont EMFH, et al. Activation of the complement sys-
tem during and after cardiopulmonary bypass surgery: postsurgery
activation involves C- reac tive protein and is associated with post-
operative arrhythmia. Circulation. 1997;96(10):3542– 8.
11. Sun WL, Chen LL, Zhang SZ, Ren YZ, Qin GM. Changes of adi-
ponectin and inflammatory cytokines after periodontal interven-
tion in type 2 diabetes patients with periodontitis. Arch Oral Biol.
2010;55(12):970– 4.
12. Goette A . Is periodontitis a modifiable risk f actor for atrial fibrilla-
tion subs trate? JACC Clin Elec trophysiol. 2023;9(1):54– 6.
13. January CT et al. 2019 AHA/ACC/HRS focused update of the 2014
AHA/ACC/HRS guideline for the management of patients with atrial
fibrillation: a report of the American College of Cardiology/American
Heart Association task force on clinical practice guidelines and the
Heart Rhythm Society. Heart Rhythm. 2019;16(8):e66– e93.
14. Abed HS, Wittert GA, Leong DP, Shirazi MG, Bahrami B,
Middeldorp ME, et al. Effect of weight reduction and cardiomet-
abolic risk factor management on symptom burden and severit y in
patient s with atrial fibrillation: a randomized clinical trial. JAMA .
2013;310(19):2050– 60.
How to cite this article: Leelaviwat N, Kewcharoen J,
Poomprakobsri K, Trongtorsak A, Del Rio- Pertuz G,
Abdelnabi M, et al. Periodontal disease and risk of atrial
fibrillation or atrial flutter: A systematic review and meta-
analysis. J Arrhythmia. 2023;00:1–5. ht t p s :// d oi .
org /10.100 2/joa3.12921
18832148, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/joa3.12921, Wiley Online Library on [16/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
