Prevalence of apical periodontitis and non- retention of root- filled teeth in hypertensive patients: Systematic review and meta-analysis

256 | Int Endod J. 2024;57:256–269.wileyonlinelibrary.com/journal/iej Received: 14 September 2023 | Accepted: 21 November 2023 DOI: 10.1111/iej.14007 REVIEW ARTICLE Prevalence of apical periodontitis and nonretention of rootfilled teeth in hypertensive patients: Systematic review and metaanalysis DanielCabanillas- Balsera1 | VictoriaAreal- Quecuty1 | CristianeCantiga- Silva2 | Carolina de Barros MoraisCardoso2 | Luciano Tavares AngeloCintra2 | JeniferMartín- González1 | Juan J.Segura- Egea1 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2023 The Authors. International Endodontic Journal published by John Wiley & Sons Ltd on behalf of British Endodontic Society. 1Department of Stomatology, Section of Endodontics, School of Dentistry, University of Sevilla, Sevilla, Spain 2Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (Unesp), Araçatuba, São Paulo, Brazil Correspondence Juan J. Segura- Egea and Daniel Cabanillas- Balsera, School of Dentistry, University of Sevilla, C/ Avicena s/n, 41009- Sevilla, Spain. Email: [email protected] and [email protected] Funding information Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES), Grant/Award Number: Finance Code 001 Abstract Background: Several studies have suggested a relationship between AP, as well as the loss of rootfilled teeth (RFT), and hypertension (HTN). Objectives: The aims of this systematic review and metaanalysis were to investigate the prevalence of AP, and nonretention of RFT, in hypertensive patients. Methods: A search was performed in PubMed/MEDLINE, Web of Science, Scopus and EMBASE. The inclusion criteria established were studies published until February 2023, comparing hypertensive subjects with controls, assessing the prevalence of AP and/or providing data on the prevalence of nonretained RFT. Metaanalysis was performed using the RevMan (analyst) tool to determine the pooled prevalence of AP and loss of RFT. Risk of bias was assessed using the Cochrane Risk- of- Bias tool. The quality of evidence was assessed by GRADE. Results: The search strategy identified 454 articles, and only eight met the inclusion criteria. Six studies had analysed the association between AP and HTN and two studies had analysed the association between nonretention of RFT and HTN. Metaanalysis showed and overall OR = 1.71 (95% CI = 0.92–3.16; p = .09) for the prevalence of AP among patients with HTN. The prevalence of nonretention of RFT among patients with HTN has an overall OR = 1.78 (95% CI = 1.60–1.98; p = .000001). The risk of bias in the individual studies was low or moderate, and the quality of the overall evidence has shown a level of certainty very low. Discussion: There is no association between the prevalence of AP and HTN. In addition, hypertensive patients have significantly increased odds of losing RFT. Given the high prevalence of hypertension, it is very common to perform root canal treatments on hypertensive patients. It is imperative to communicate this heightened risk to patients and recommend periodic monitoring of oral health and hypertension, paying special attention to this subset of patients. Registration: PROSPERO CRD42022302385. | 257 CABANILLASBALSERA etal. INTRODUCTION Hypertension (HTN) is a chronic medical condition in which the blood pressure (BP) in the arteries is elevated. The prevalence of high blood pressure is 30–45% in adult subjects with an acute increase with age (Piepoli et al., 2016). It can be primary or essential (90–95% of cases), which refers to high BP for which no medical cause can be found, or secondary (5%–10% of cases), caused by other conditions that affect the kidneys, arteries, heart, or endocrine system (Carretero & Oparil,2000). HTN is diagnosed when the average of 2 or more diastolic BP measurements on at least 2 subsequent visits is ≥90 mm Hg or when the average of multiple systolic BP readings on 2 or more subsequent visits is consistently ≥140 mm Hg (Whitworth,2003). Persistent HTN is one of the risk factors for stroke, heart attacks, heart failure and arterial aneurysm and is a leading cause of chronic kidney failure (Bakris etal.,2023). HTN has been associated with dental problems, difficulties in bone healing after tooth extractions and implant loss as a result of defects in the process of osseointegration (Leite etal.,2005; Manrique etal.,2012). Apical periodontitis (AP), an acute or chronic inflammatory process that involves the periapical portion of a tooth root, is principally caused by a bacterial infection that persists in the pulp space of tooth resulting in destruction of periradicular tissue (Siqueira & Rôças,2008). The infectious aetiology of AP and the fundamental role of microbial factors induction, evolution and endurance have been extensively researched (Siqueira & Rôças, 2014). Radiographically, chronic AP can be observed as a radiolucent area around the root apex (López- López etal.,2015). It is a notable health problem, the worldwide prevalence of subjects with AP is 52%, and 5% at the tooth level incrementing with patients’ age (Jiménez- Pinzón etal.,2004; León- López etal.,2022; Tibúrcio- Machado etal.,2021). The elective treatment for teeth with AP is root canal treatment (RCT). Additionally, the worldwide prevalence of RCT is 8.2%, and the global prevalence of people with at least one RFT is 56% (León- López etal.,2022). RCT outcome has been linked to systemic disease states (Segura- Egea et al., 2023) such as diabetes (Cabanillas- Balsera et al., 2019; Nagendrababu et al., 2020; Segura- Egea et al., 2016) and smoking (Cabanillas- Balsera, Segura- Egea, Bermudo- Fuenmayor, et al., 2020; Cabanillas- Balsera, Segura- Egea, Jiménez- Sánchez, etal.,2020). It is clearly stablished that under certain circumstances the infection can spread to nearby tissue compartments and may cause a severe fatal inflammatory condition. Taking that into consideration, it can be concluded that AP is not entirely a local episode (Carrotte, 2004). Furthermore, in light of the developing consciousness of a possible link between inflammatory disorders of the oral cavity and disease conditions in other locations, it has also been claimed that acute and chronic manifestations of AP may also be involved (Márton,2004). The results of some studies suggest the relationship between periapical inflammation and cardiovascular diseases (Jakovljevic et al., 2020; Jiménez- Sánchez et al., 2020). Moreover, several epidemiological studies have investigated the possible relationship between HTN and AP, with contradictory conclusions (Messing etal.,2019; Segura- Egea etal.,2010). Therefore, it would be interesting to conduct a systematic review to determine whether there is a relationship between AP or RCT and HTN. Knowing whether HTN associates with a greater prevalence of AP or greater RCT failure will allow the dentist to better control hypertensive patients and better monitor their RCT. The main objective of this systematic review and metaanalysis is to provide a comprehensive overview of the prevalence of AP among hypertensive patients, assessing the potential association between these two conditions. As a secondary objective, the possible relationship of hypertension with the loss of RFT is analysed. METHODS Registry protocol This systematic review is reported in accordance with PRISMA and PRISMADTA guidelines (Page etal.,2021) and is registered on PROSPERO (CRD42022302385). Review question A specific review question was structured according to the PICO method (population, intervention, comparison and outcome): In adult subjects (P), does the presence of HTN (I) compared to the absence of HTN (C), affect the prevalence of AP, diagnosed radiographically or the survival of RFT (O)? The null hypothesis tested was that there was no significant difference in the prevalence of AP and in the survival of RFT between hypertensive patients and healthy people without hypertension. KEYWORDS apical periodontitis, endodontic medicine, hypertension, root canal treatment 13652591, 2024, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.14007 by Universidad De Sevilla, Wiley Online Library on [25/06/2024]. 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 258 | HYPERTENSION AND APICAL PERIODONTITIS Eligibility criteria The inclusion criteria established were (a) epidemiological studies published until February 2023; (b) studies comparing hypertensive subjects with healthy control, nonhypertensive subjects; (c) studies assessing the prevalence of AP and /or providing data on the prevalence of nonretained RFT, both in hypertensive subjects and in control nonhypertensive subjects. In vitro studies, animal studies, case series, studies reporting data only from hypertensive subjects, and studies that had no initial agreement among the reviewers were excluded. Search strategy and information sources The selection of the articles was done by three authors individually (J.J.S- E, V.A- Q and C.C- S.). The investigators performed independent electronic searches of PubMed/ MEDLINE, Web of Science, Scopus and EMBASE. The search was conducted without filters, language or publication year restrictions and was updated until February 2023. Further manual searches were conducted of the references of the included articles. Articles identified in the searches were screened for eligibility by the three authors by inspection of the title and abstract, or full text if further clarification was necessary. Disagreements on eligibility were resolved by discussion and consensus. Full texts were obtained for all studies meeting the eligibility and inclusion criteria. No filters and limits were considered. In addition, hand searches were performed by considering some periodicals, a references list of some articles, and the grey literature using the databases ProQuest and OpenGrey. After articles were selected, the disagreements among the authors were resolved by consensus (Figure1). The terms used for this search were as follows: (Apical periodontitis[Mesh] OR Root filled teeth[Mesh] OR root canal treatment[Mesh] OR Periapical lesion[Mesh] OR Periapical inflammation [Mesh] OR Periapical radiolucency[Mesh] OR Endodontic[All fields]) AND (Cardiovascular disease[Mesh] OR Atherosclerosis[Mesh] OR Hypertension[Mesh] OR Valvular heart disease[Mesh] OR Angina pectoris [Mesh] OR Heart failure [Mesh] OR Acute myocardial infarction[Mesh]). Risk of bias assessment To assess the risk of bias in the selected articles, the Cochrane Scientific Committee recommendation was followed (Higgins etal.,2023). Thus, the ROBINS- I tool (Risk Of Bias In Nonrandomized Studies – of Interventions) FIGURE 1 Flowchart of the studies included in the systematic review and metaanalysis. 13652591, 2024, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.14007 by Universidad De Sevilla, Wiley Online Library on [25/06/2024]. 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 | 259 CABANILLASBALSERA etal. (Sterne et al., 2016) was used. In this tool, the aspects of risk of bias are evaluated individually without assigning scores and are divided into seven domains: random sequence generation, allocation concealment, blinding of outcome assessors, blinding of participants and personnel, incomplete outcome data and selective outcome reporting, comprising the assessment of selection, performance, attrition, reporting and detection bias. Each domain is classified as having a low risk, unclear risk or high risk of bias (Wells etal.,2011). Articles were assessed independently by four reviewers (J.J.S- E., D.C- B., V.A- Q. and C.C- S), and cases of disagreements in the risk of bias were discussed until a consensus was achieved. Data extraction and analysis One of the authors (V.A- Q) was responsible for data extraction, while three reviewers (C.C- S, D.C- B and J.J.S- E) verified the tabulated data to ensure the absence of typo errors and carried out the analysis of the articles; the articles in disagreement were discussed. To analyse and synthesize the data, the following details were extracted from the studies: author and year of publication, study design, sample size, objective and results. Pooled estimates from the studies were analysed using a randomeffects model metaanalysis. The variables analysed were the prevalence of AP and nonretention of RFT among patients with HTN and nonhypertension control subjects. Forest plots were produced to graphically represent the odds ratio of AP and retention of RFT in both patients with and without HTN. The level of significance was applied to p = .05. To determine the heterogeneity among trials, the Tau2 and the Higgins I2 test were employed, considering that substantial heterogeneity is considered if I2 test is higher than 50% (Higgins & Thompson,2002). The 5.4 RevMan software tool was employed in the statistical analysis (Review Manager (RevMan) [Computer program]. Version 5.4). Grading of recommendations assessment, development and evaluation The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach (Guyatt etal.,2011) was used for the assessment of the overall quality of the evidence. This procedure defines an initial level of certainty according to the design of the included studies and, subsequently, analyses different domains such as the risk of bias, inconsistency, indirectness, imprecision, publication bias, dose–response gradient, confounding factors or the magnitude of the effect to conclude at a final level of certainty. RESULTS The baseline search recovered 454 titles and abstracts found through Rayyan database searching, including 116 from PubMed/ MEDLINE, 98 from Web of Science, 118 from Scopus and 122 from EMBASE. After the removal of duplicates, 159 articles remained, of which 125 were excluded after reading abstract and 34 were selected for full text. After reading the articles in full, 12 were excluded for the following reasons: four did not address AP or RFT as a specific topic (Almoznino et al., 2020; Janket etal.,2014; Nivethitha etal.,2020; Ojehanon & Akhionbare,2007), three did not have the hypertension as a specific topic (Costa etal.,2014, Donders etal.,2020, Paju etal.,2021), one did not deal any of the specific topics (Bajaj etal.,2012), two were animal studies (Cosme- Silva etal.,2019; Martins etal.,2016) and two were review studies (Sasaki etal.,2016, Verhulst etal.,2019). Twentytwo studies were selected for the qualitative synthesis, but 14 were excluded for not providing the necessary data for metaanalysis (Ahirwar etal.,2021; Almoznino etal.,2021; Assiri etal.,2020; Caplan etal.,2009; Frisk etal., 2003; Gomes et al., 2016; Liljestrand et al., 2016; Meurman et al., 2017; Poornima et al., 2021; Rashmi et al., 2017; Ravikumar et al., 2020; Ruiz et al., 2017; Segura- Egea et al., 2011; Vidal et al., 2016) (Figure1; Table1). Characteristics of the included studies Finally, eight studies were selected and included for systematic review and metaanalysis (Table2). Six studies analysed the association between HTN and AP (An et al., 2016; Katz & Rotstein, 2021; Khalighinejad etal.,2017; Messing etal.,2019; Segura- Egea etal.,2010; Yip et al., 2021), and two studies analysed the association between HTN and nonretention of RFT (Mindiola etal.,2006; Wang etal.,2011). Study design, study sample, diagnosis, main results and evidence level of these studies are summarized in Table2. Metaanalysis of the prevalence of apical periodontitis An evidence table was elaborated with data from the included articles (Table3). The estimated variance between studies was examined using the Tau2 test and was found to be significant (τ2 = 0.53; χ2 = 1468.17; df = 5; p < .01). The evidence for heterogeneity (I2 = 100%) was very high; therefore, the weights of each study were calculated using the random effects model, considering that there 13652591, 2024, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.14007 by Universidad De Sevilla, Wiley Online Library on [25/06/2024]. 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 260 | HYPERTENSION AND APICAL PERIODONTITIS was variation between the included studies and allowing the study results to vary in a normal distribution. The overall OR was calculated using the inverse variance method with random effects, resulting in an OR = 1.73 (95% CI = 0.94–3.21; p = .08). The ORs of each study and the pooled OR of the metaanalysis are shown in a forest plot (Figure2). This result indicates that there is a difference, but not statistically significant, between the prevalence of patients presenting at least one tooth with apical periodontitis and hypertensive or control subjects. Metaanalysis of the prevalence of nonretention of rootfilled teeth The data from both articles were collected in a table (Table4). The estimated variance among the two studies was examined by Tau2 test, resulting nonsignificant (τ2 = 0.00; χ2 = 0.76; df = 1; p = .38). Although I2 = 0%, demonstrating that the studies were very homogeneous, the weights for each study were calculated using the random effects model, allowing study results to vary in a normal distribution. Moreover, statistical homogeneity does not exclude clinical heterogeneity. The overall OR was calculated using the inverse variance method with random effects, resulting in an OR = 1.78 (95% CI = 1.60–1.98; p < .00001). The ORs of both studies and the pooled OR of the metaanalysis are shown in a forest plot (Figure3). This result indicates that there is a significant difference in the prevalence of extracted RFT between patients with HTN and healthy control subjects. Publication bias Publication bias could not be assessed quantitatively as there were fewer than the required minimum of 10 studies (Higgins etal.,2023). Risk of bias According to the ROBINS- I tool, of the six studies included for the prevalence of AP, five were classified as low risk of bias, with none or only one domain at high risk of bias, while the other was classified as moderate risk of bias, with two domains at high risk of bias (Messing etal.,2019) (Figure4). On the other hand, for the prevalence of nonretention of RFT, one study was classified as moderate risk of bias, with two domains at high risk of bias (Mindiola etal.,2006), while the other was classified as low risk of bias, with one of the domains at high risk of bias (Wang etal.,2011) (Figure5). GRADE evaluation Assessment of the overall quality of evidence for each variable analysed was carried out using the GRADE tool, showing in both cases a very low quality of evidence (Figure6). DISCUSSION The aim of this study was to analyse the association between HTN and two endodontic variables, the prevalence of AP and the prevalence of nonretained RFT. For this, a systematic review and metaanalysis were performed, TABLE 1 Studies excluded in the systematic review: excluded reason, authors and year. Excluded reason Author (year) AP, RFT or HTN are not specific topics Ojehanon & Akhionbare,(2007) Bajaj etal.(2012) Costa etal.(2014) Janket etal.(2014) Almoznino etal.(2020) Donders etal.(2020) Nivethitha etal.(2020) Paju etal.(2021) Animal study Martins etal.(2016) Cosme- Silva etal.(2019) Review study Sasaki etal.(2016) Verhulst etal.(2019) Missing data Frisk etal.(2003) Segura- Egea etal.(2011) Gomes etal.(2016) Liljestrand etal.(2016) Vidal etal.(2016) Meurman etal.(2017) Rashmi etal.(2017) Ruiz etal.(2017) Caplan etal.(2009) Assiri etal.(2020) Ravikumar etal.(2020) Ahirwar etal.(2021) Almoznino etal.(2021) Poornima etal.(2021) 13652591, 2024, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.14007 by Universidad De Sevilla, Wiley Online Library on [25/06/2024]. 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 | 261 CABANILLASBALSERA etal. TABLE 2 Studies on the prevalence of apical periodontitis (AP) and nonretention of root filled teeth (RFT) in hypertensive patients included in the metaanalysis. Author (year) Study design Subjects Variable Diagnosis Main results Evidence level Mindiola etal.(2006)Crosssectional Control – 3753 Hypertensive – 424 Retention of RFT An electronic survey of the dental database from 1991 to 2000 Association p < .05 OR: 2.10 CI (1.42–3.11) 4 Segura- Egea etal.(2010)Crosssectional Control – 51 Hypertensive – 40 AP Periapical No association p = .15 OR: 1.94 CI (0.78–4.81) 4 Wang etal. (2011)Crosssectional Control – 40 024 Hypertensive – 9310 Retention of RFT An electronic survey of the dental database from 1995 to 2003 Association p < .05 OR: 1.75 CI (1.57–1.96) 4 An etal.(2016)Crosssectional Control – 252 Hypertensive – 112 AP Periapical No association p = .26 OR: 1.29 CI (0.83–2.02) 4 Khalighinejad etal.(2017)Crosssectional Control – 50 Preeclampsia – 50 AP Panoramic Association p = .002 OR: 2.49 CI (1.1–5.62) 4 Messing etal.(2019)Crosssectional Control – 33 967 Hypertensive – 13 349 AP Endodontic pathology/RFT An electronic survey of the dental database from 1996 to 2016 Association p < .0004 OR: 0.87 CI (0.83–0.91) 4 Katz and Rotstein(2021)Crosssectional Control – 1 414 898 Hypertensive – 265 078 AP Periapical abscess An electronic survey of the dental database from 2011 to 2020 Association p < .0001 OR: 3.12 CI (2.98–3.26) 4 Yip etal.(2021)Crosssectional Control – 11 289 Hypertensive – 4209 AP An electronic survey of the dental database from 2015 to 2018 Association p < .0001 OR: 1.76 CI (1.64–1.89) 4 Note: Study design, subjects and sample size, diagnosis, main results and evidence level. 13652591, 2024, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.14007 by Universidad De Sevilla, Wiley Online Library on [25/06/2024]. 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 262 | HYPERTENSION AND APICAL PERIODONTITIS including the available evidence. The results show that there is no association between the prevalence of AP and HTN. In addition, hypertensive patients have significantly increased odds of losing RFT. However, the quality of the overall evidence has shown a level of certainty very low. After searching the literature, eight studies were included in the final analysis, six analysing the prevalence of AP (An etal.,2016; Katz & Rotstein,2021; Khalighinejad etal.,2017; Messing etal.,2019; Segura- Egea etal.,2010; Yip et al., 2021) and two evaluating the prevalence of TABLE 3 Studies about hypertensive patients and the prevalence of AP. Authors Year N° patients Nonhypertensive control subjects Hypertensive patients Odds ratio (95% CI) pAP/Total AP (%) AP/Total AP (%) Segura- Egea etal. 2010 91 31/51 60.8 30/40 75.0 1.94 (0.78–4.81) p = .15 An etal. 2016 364 121/252 48.0 61/112 54.5 1.29 (0.83–2.02) p = .26 Khalighinejad etal. 2017 100 16/50 32.0 27/50 54.0 2.49 (1.11–5.63) p = .03 Messing etal. 2019 47 316 7965/33 967 23.4 2805/13349 21.0 0.87 (0.83–0.91) p < 0.001 Katz and Rotstein 2021 1 679 976 5519/1414898 0.4 3196/265078 1.2 3.12 (2.98–3.26) p = .00 Yip etal. 2021 15 498 5216/11289 46.2 2533/4209 60.2 1.76 (1.64–1.89) p = .00 Overall 1 743 345 18 868/1460507 1.29 8652/282838 3.06 1.73 (0.42–3.21) p = .08 Note: Results were extracted and compiled, and descriptive statistics and odds ratios were calculated. FIGURE 2 Forest plot for the prevalence of apical periodontitis. TABLE 4 Studies about hypertensive patients and the prevalence of nonretained RFT. Authors Year N° RFT Nonhypertensive control subjects Hypertensive patients Odds ratio (95% CI) p RFT*Ext/ Total RFT RFT*Ext (%) RFT*Ext/ Total RFT RFT*Ext (%) Mindiola etal. 2006 91 145/3753 3.9 33/424 7.8 2.10 (1.42–3.11) p = .0001 Wang etal. 2011 476 1138/40024 2.8 454/9310 4.9 1.75 (1.57–1.96) p < .0001 Overall 1 743 457 1283/43777 2.93 487/9734 5.0 1.78 (1.60–1.98) p = .00001 Note: Results were extracted and compiled, and descriptive statistics and odds ratios were calculated. Abbreviations: RFT, rootfilled teeth; RFT*Ext, extracted RFT. FIGURE 3 Forest plot for the prevalence of nonretention of rootfilled teeth. 13652591, 2024, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.14007 by Universidad De Sevilla, Wiley Online Library on [25/06/2024]. 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 | 263 CABANILLASBALSERA etal. nonretention of RFT teeth (Mindiola etal.,2006; Wang etal.,2011). The design of all studies was crosssectional. Assessment of the risk of bias of the studies for the prevalence of AP shows that although five of the six included studies present a low risk of bias, at least three studies present serious imprecision. This, together with a very serious inconsistency due to the high heterogeneity, degrades the quality of the global evidence using GRADE methodology to a very low certainly. Very low level of certainty was also obtained for the prevalence of nonretention of rootfilled teeth. Despite the included studies showing consistency for this association, the inclusion of only two studies that met the inclusion criteria along with an individual bias presenting one and two highrisk domains downgraded overall certainty. The first study designed to explore a possible association between endodontic disease variables and coronary heart disease did not find a significant association between periapical disease and HTN (Frisk etal.,2003). The study by Segura- Egea etal.(2010), also found no significant differences in the prevalence of AP in hypertensive patients compared with healthy patients, but the authors say that some factors were not recorded, such as the prevalence of diabetes and smoking habits, which may have confounded the results. The analysis of the extracted data from the study of An etal.(2016) concluded that the prevalence of AP in hypertensive patients was similar to that in control subjects. However, the study showed a statistically significant association between CVD and the number of RFTs. The third study included in the metaanalysis was conducted by Khalighinejad etal.(2017) provided evidence that pregnant women with undiagnosed/untreated AP are almost two times more likely to develop preeclampsia than pregnant women with no AP. The preeclampsia is characterized by HTN and proteinuria after the 20th week of gestation (Backes etal.,2011). One of the most common adverse outcomes of pregnancy and is among the leading causes of maternal mortality (Mammaro etal.,2009). Despite the association found between AP and preeclampsia, the authors emphasize that the data were collected before pregnancy and consider it important to reevaluate the endodontic status at the end of pregnancy (Khalighinejad etal.,2017), since oral hygiene can be poor during this period (Onigbinde etal.,2014). Several studies have observed the independent association between AP and inflammatory markers linked to cardiovascular diseases (Gomes et al., 2013; Warner etal.,2004). Systemic elevation of proinflammatory cytokines such as interleukin (IL) 1 beta and tumour necrosis factor alpha has been shown to be a result of AP (Gomes etal.,2013) and initiate structural and functional changes in endothelial cells leading to systemic signs associated with preeclampsia (Roberts etal.,1989). HTN results from the interaction between genetic and environmental factors (Kato etal.,2015) Is a known FIGURE 4 Summary of risk of bias assessments for the prevalence of apical periodontitis. FIGURE 5 Summary of risk of bias assessments for the prevalence of nonretention of rootfilled teeth. 13652591, 2024, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.14007 by Universidad De Sevilla, Wiley Online Library on [25/06/2024]. 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 264 | HYPERTENSION AND APICAL PERIODONTITIS major risk factor for CVD, as well as cerebrovascular and renal disease (Warren etal.,2017) and the biggest single contributor to disease and mortality worldwide (Kato etal.,2015). Studies have identified polymorphisms in a variety of diseaserelevant genes as significantly associated with HTN (Warren etal.,2017). The study conducted by Messing et al. (2019) carried out a genetic association analysis of AP with known hypertensionassociated polymorphisms gene and a trend toward association was found between AP and a polymorphism in the KCNK3 gene. Mutations in this gene can cause idiopathic pulmonary arterial hypertension, a rare disorder characterized by high blood pressure in the pulmonary arteries that can lead to elevated pulmonary arterial pressure, right ventricular failure, and death (Bohnen etal.,2017). Furthermore, studies of chronic periodontitis genes in humans and mouse models have suggested the involvement of other genes whose roles in other systemic diseases are more established (de Vries etal.,2017). This find can explain the results of Messing etal.(2019) which highlight as limitations of the study the crosssectional design and the use of selfreported information in the dental electronic records, the scarce availability of dental history information on the medical records, and an independent cohort of limited sample size for the genetic association study. Tiburcio- Machado et al. (2021) compiled data from different communities and reported that 52% of individuals had endodontic disease, without, however, identifying which factors may modify the prevalence of AP worldwide. A subgroup analysis revealed the factors that can influence the prevalence of AP: socioeconomic status of the country; location of recruitment; the systemic conditions; the risk of bias of the primary studies; the image method used and the method used to assess the AP. Previous studies have found an association between systemic diseases, such as diabetes (Segura- Egea etal.,2019) and cardiovascular diseases (Messing et al., 2019), and some biological mechanisms have been proposed to explain this relationship (Segura- Egea et al., 2015). Also in the case of HTN, some biological mechanisms can be proposed by which it can influence the periapical status. Martins etal.(2016) found that a hypertensive condition leads to higher osteoclastic differentiation, which could influence the endodontic treatment outcome in such a systemic condition. Vidal et al. (2016) reported that the presence of chronic apical periodontitis was associated with higher plasma levels of C reactive protein, interleukin 6, and fibrinogen in a population of severely hypertensive patients. In good accordance with these findings, the results of the crosssectional study by Katz and Rotstein(2021) indicate that the prevalence of periapical abscesses is significantly higher in hypertensive patients. Increased calcium secretion has also been observed in hypertensive patients (Tsuda etal.,2001). Another study concluded that primary HTN can significantly reduce the body's bone mineral density (Ye etal.2017). According to the authors, periapical abscesses are associated with inflammatory processes elicited mainly by microorganisms, it is plausible that existing pathoses can be aggravated by a systemic condition such as hypertension that may also contribute to a delay in bony healing (Katz & Rotstein,2021). Although, they suggest that the results should be viewed with caution, since they only evaluated the presence of periapical lesions, not considering whether the lesions present were in the healing process. The quality of endodontic treatment and coronal restorations were also not evaluated, and these may be a confounding factor in the results (Katz & Rotstein,2021). In the crosssectional study by Yip et al. (2021), the authors found a higher prevalence of AP associated with TDM2 as well as with an HbA1c higher than 8.0. The data extracted from this study showed a significant association between HTN and AP. FIGURE 6 Grade assessment. 13652591, 2024, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.14007 by Universidad De Sevilla, Wiley Online Library on [25/06/2024]. 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