Leng WD, Zeng XT, Chen YJ, Zhan ZQ, Yang Y. Periodontal disease is associated with increased coronary heart disease risk: A meta-analysis based on 38 case-control studies. World J Meta-Anal 2013; 1(1): 47-56 [DOI: 10.13105/wjma.v1.i1.47]
Corresponding Author of This Article
Wei-Dong Leng, Professor, Department of Stomatology, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan 442000, Hubei Province, China. email@example.com
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Periodontal disease is associated with increased coronary heart disease risk: A meta-analysis based on 38 case-control studies
Wei-Dong Leng, Xian-Tao Zeng, Yong-Ji Chen, Zhong-Qun Zhan, Yong Yang
Wei-Dong Leng, Xian-Tao Zeng, Yong-Ji Chen, Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
Zhong-Qun Zhan, Yong Yang, Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
ORCID number: $[AuthorORCIDs]
Author contributions: Leng WD and Zeng XT contributed equally to this work; Zeng XT, Chen YJ, Zhan ZQ and Yang Y performed the literature search, study selection and data extraction; Leng WD, Zeng XT and Zhan ZQ analyzed the results; Zeng XT and Chen YJ did the statistical analysis; Zeng XT and Zhan ZQ drafted the manuscript; all authors provided input into the development of the manuscript; all authors have approved the final manuscript.
Supported by The Foundation of Education and Science Planning Project of Hubei Province (in part), No.2012A050; and the Intramural Research Program of Hubei University of Medicine, No. 2011CZX01.
Correspondence to: Wei-Dong Leng, Professor, Department of Stomatology, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan 442000, Hubei Province, China. firstname.lastname@example.org
Telephone: +86-719-8801427 Fax: +86-719-8883809
Received: March 5, 2013 Revised: April 4, 2013 Accepted: May 7, 2013 Published online: May 26, 2013
AIM: To investigate whether periodontal disease (PD) is associated with increasing coronary heart disease (CHD) risk by performing a meta-analysis.
METHODS: Two authors independently searched PubMed and China National Knowledge Infrastructure up to January 10th, 2013 for relevant case-control studies that investigated the association between PD and CHD. After quality assessment using Newcastle-Ottawa Scale and data extraction by two independent authors, the overall and subgroup meta-analyses were performed and publication bias were examined using the Comprehensive Meta-Analysis V2 software. Potential publication bias was assessed using visual inspection of the funnel plots, Egger linear regression test, and trims and fill method.
RESULTS: Finally 38 relevant case-control studies were identified, involving 4950 CHD patients and 5490 controls. Eleven studies were rated low quality and 27 were high quality. Based on random-effects, a significant association was identified between PD and CHD (OR 3.79, 95%CI: 2.23-6.43, P < 0.001, I2 = 98.59%), and sensitivity analysis showed that this result was robust. Subgroup analyses according to adjusted/unadjusted ORs, source of control, methodological quality, end point, assessment of PD/CHD, and ethnicity also indicated a significant association. Publication bias was detected, and the estimated OR including the “missing” studies did not substantially differ from our estimate with adjustment for missing studies (OR 4.15, 95%CI: 2.62-6.54, P < 0.001).
CONCLUSION: Based on the meta-analysis, PD is probably associated with CHD risk independently and significantly.
Core tip: Growing evidence indicated that periodontal disease (PD) might be associated with coronary heart disease (CHD), however, results from the studies were inconsistent. This meta-analysis based on 38 case-control studies indicated that PD increased a 3.79-fold risk of CHD (OR = 3.79, 95%CI: 2.23-6.43, P < 0.001, I2 = 98.59%). The results showed that PD is probably an independent and significant risk factor for CHD.
Citation: Leng WD, Zeng XT, Chen YJ, Zhan ZQ, Yang Y. Periodontal disease is associated with increased coronary heart disease risk: A meta-analysis based on 38 case-control studies. World J Meta-Anal 2013; 1(1): 47-56
Coronary heart disease (CHD) is one of the major causes of mortality, account for nearly 30% of deaths worldwide. As almost half of all first onset of CHD events occur in asymptomatic patients, it is important to seek CHD risk factors and accurately identify high-risk individuals and guide the risk reduction interventions, prevention, and lifestyle changes. CHD is a complex disease, epidemiologic studies have suggested that the etiology of CHD involved interactions of genetics, environmental factors, and gene-gene and gene-environment. Environmental factors (including psychological and social factors)[4,5] are the classical risk factors for CHD, however, these markers do not explain the etiology of CHD to the fullest of its extent. Given the importance of fatal health problem related to CHD, efforts are being made to identify other modifiable risk factors that play a role in the etiology of CHD.
Periodontal disease (PD) is a group of inflammatory diseases which affect the supporting tissues of the tooth, approximately at least 35% dentate adults aged 30-90 years in United States suffer from PD, and it also affects up to 90% of the worldwide population. Based on the theory of “focal infection” which emerged at the beginning of the 20th century, many studies have observed a possible role of PD as a risk factor for systemic conditions over the past two decades, such as cardiovascular diseases, diabetes, and chronic obstructive pulmonary disease.
Growing evidences indicated that chronic infections and inflammation (such as PD) might play a role in the initiation and progression of CHD. Many epidemiological studies have investigated the link between PD and risk of CHD, and most of them found a positive association, even though some results are varied or even contradictory among studies. There was a published meta-analysis based on 8 cross sectional and 14 case-control studies by Blaizot et al in 2009, which identified that there were higher odds of developing CHD in patients with PD (OR 2.35, 95%CI: 1.87-2.96, P < 0.0001). However, this meta-analysis did not perform subgroup analyses because of the study design, and adjusted or unadjusted factors. As we know, a cross sectional design is subjected to more confounding and biases than a case-control design, and adjusted data could obtain more precise point estimate than unadjusted data. Up to now, there have been 38 case-control studies[13-50] published in English or Chinese.
An improved understanding of this association may have important public health and clinical implications, for prevention and treatment of PD would reduce the CHD events. This meta-analysis aims to (1) evaluate the inconsistent results from published case-control studies on the association between PD and risk of CHD; (2) gain a more precise estimate association; and (3) provide a general interpretation of the results in the context of other evidences and propose suggestions for the prevention and treatment of the diseases.
MATERIALS AND METHODS
We followed the proposed MOOSE (Meta-Analysis of Observational Studies in Epidemiology) guidelines to report the present meta-analysis.
We initially identified published studies that investigated the association between PD and CHD by searching the PubMed and China National Knowledge Infrastructure databases up to January 10th, 2013. The following search terms were used: (1) “PD” or “peridontal disease” or “periodontitis” or “periodontal attachment loss” or “periodontal pocket” or “alveolar bone loss”, and (2) “CHD” or “coronary artery disease” or “myocardial infarction (MI)” or “angina pectoris” or “ischemic heart disease”. The studies were published in either English or Chinese. We also reviewed the reference lists of retrieved articles, previous meta-analysis, and recent reviews.
Any study met all of the following criteria was included: (1) the study was of a case-control design; (2) clear diagnostic criteria for PD and CHD were reported; (3) the association between PD and risk of CHD was investigated, and PD is the exposed factor; and (4) the ORs and the corresponding 95%CIs, or the number of events were reported. Two authors independently evaluated the eligibility of all retrieved studies; disagreements were resolved by discussion or consultation with a third author.
Methodological quality assessment
The methodological quality of included studies was assessed independently by two authors according to the Newcastle-Ottawa Scale (NOS) for case-control study. The NOS for case-control study consists of 3 parameters of quality: selection, comparability, and exposure assessment. It assigns a maximum of 4 points for selection, a maximum of 2 points for comparability, and a maximum of 3 points for exposure. Therefore, 9 points is the highest score, reflecting the highest quality. We defined overall quality rating scores < 6 as low quality, and ≥ 6 as high quality. All discrepancies between authors were addressed by a common reevaluation of the original article.
Two authors independently extracted data of each study using a preliminary standardized data collection form. Data extracted included: first author’s last name, year of publication, country of study; characteristics of study population and age at baseline; number of participants with PD and CHD, and total number of participants, or ORs and relevant 95%CIs; end points of CHD, ascertainment of PD and CHD; and adjustment for covariates. Any disagreement was resolved by consensus. CHD was defined as MI, angina pectoris, and other ischemic heart diseases (IHD).
We pooled the results from single studies which were found to be both clinically and statistically appropriate. We computed pooled ORs and relevant 95%CIs using Comprehensive Meta-Analysis software, Version 2.2 (Biostat, Englewood, NJ, United States), to generate forest plots, determine whether a statistical association between PD and CHD exists, assess the heterogeneity of the selected studies, and detect whether publication bias present. Heterogeneity was quantified using the I2 statistic, with the low, moderate, and high I2 values of 25%, 50%, and 75%, respectively, where I2 value of 25% or lower indicated no evidence of heterogeneity, we used the fixed-effect model; otherwise, the random-effects model was used.
When heterogeneity existed, we performed subgroup and sensitivity analyses to explore possible explanations for the heterogeneity and examine the influence of various exclusion criteria on the overall risk estimate. We also investigated the influence of single study on the overall risk estimate by sequentially removing each study to test the robustness of the main results.
Potential publication bias was assessed by visual inspection of the funnel plots of overall outcome. The Egger linear regression test was used to examine the association between mean effect estimate and its variance. In addition, to assess the effect of possible publication bias, we calculated the number of unpublished studies which may exist to negate the results, and the pooled OR adjusted for publication bias using the trim and fill method.
Of 682 records searched initially, 38 case-control studies[13-50] were included in this meta-analysis. A detailed flowchart of the selection process is shown in Figure 1.
Figure 1 Flow chart of included case-control studies that tested the association between periodontal disease and risk of coronary heart disease.
PD: Periodontal disease; CHD: Coronary heart disease; CNKI: China National Knowledge Infrastructure.
Characteristics and quality of studies
Table 1 presents the major characteristics and methodological quality of the 38 case-control studies. These studies focused on CHD only. Sample sizes ranged from 34 to 1337, involving 4950 CHD patients and 5490 controls subjects. Twenty-one studies[14,17-20,22,24,25,27,28,30,32,34-36,39,41,44,45,49,50] were adjusted covariates (Table 2), while there was no adjustment of the other 17 studies[13,15,16,21,23,26,29,31,33,37,38,40,42,43,46-48]. The methodological quality of 11 studies[13,15,16,21,23,26,37,38,40,42,47] according to NOS were rated low quality, and 27 were rated high quality[14,17-20,22,24,25,27-36,39,41,43-46,48-50]. All the CHD patients were confirmed and non-CHD patients were excluded by coronary arteriography (CAG), cardiologists, or electrocardiography (ECG).
Table 1 Characteristics and methodological quality of included 38 case-control studies in the meta-analysis.
Age, gender, smoking, alcohol, hypertension, and BMI
DM: Diabetes mellitus; BMI: Body mass index; CRP: C-reactive protein.
PD and risk of CHD
Of all 38 studies, six studies[19,28,29,35,44,49] showed no statistical difference, and all the 38 studies identified significantly increased risk of developing CHD (OR 3.79, 95%CI: 2.23-6.43, P < 0.001). Substantial heterogeneity was observed (I2 = 98.59%, P < 0.001). Figure 2 shows the results from the random-effects model pooling the ORs and 95%CIs.
Figure 2 Forest plot of periodontal disease and risk of coronary heart disease, using pooled random-effects model.
The pooled odds ratio is represented by a diamond of standard height, with the width indicating the 95%CI.
Subgroup and sensitivity analyses
Table 3 shows the results of subgroup analyses by adjustment for covariates, source of control, methodological quality, end point, assessment of PD, assessment of CHD, and ethnicity. All these analyses indicated that PD is a risk factor for CHD. Sensitivity analysis was performed by sequentially removing each study, the significance of pooled ORs was not influenced by the omission of any single study (the values of ORs were between 3.05 and 3, 91, and the relevant 95%CIs between 2.06 and 6.62), suggesting that the results of this meta-analysis were stable (Figure 3).
Table 3 Results of overall and subgroups analyses of pooled odds ratios and 95%CIs.
Figure 3 Forest plot of sensitivity analysis by removing each study in each turn.
The pooled odds ratio is represented by a diamond of standard height, with the width indicating the 95%CI.
Figure 4 shows that the funnel plot was asymmetrical, indicating publication bias existed; this was also confirmed by Egger linear regression test (P < 0.001). As the evidence of bias could be due to inadequate statistical power, we used the non-parametric method of “trim and fill” and estimated 3 possible missing studies based on random-effects model (black spots in Figure 4). The estimated OR including the “missing” studies did not substantially differ from our estimate with adjustment for missing studies (OR 4.15, 95%CI: 2.62-6.54, P < 0.001).
Figure 4 Filled funnel plot with pseudo-95%CIs of the 38 studies.
Log of odds ratio (OR) represents the natural logarithm of the OR of individual studies; Standard error by Log OR represents the standard error in the natural logarithm of the OR of individual studies. A circle in the figure represents a study, while a black spot represents an unpublished study which may exist to negate the results of the meta-analysis.
In 1989, Mattila et al reported that dental health was significantly associated with acute MI, and this association remained valid after adjustment for age, social class, smoking, serum lipid concentrations, and the presence of diabetes. Since then, many observational studies have emerged to investigate the relationship between oral health and CHD, and PD was of special concern. However, the result remains controversial. In the present study, we performed a meta-analysis about the association between PD and CHD risk based on 38 case-control studies, and identified that subjects with PD had higher odds and higher risk of developing CHD than subjects without PD. Subgroup analyses based on adjustment for covariates, source of control, methodological quality, end point, assessment of PD, assessment of CHD, and ethnicity yielded significant and consistent results.
Compared with the previous meta-analysis by Blaizot et al in 2009, whose result based on pooled 8 cross-sectional and 14 case-control studies identified 2.35 times higher risk of developing CHD in patients with PD (OR 2.35, 95%CI: 1.87-2.96, P < 0.001), our meta-analysis identified the higher risk (OR 3.79, 95%CI: 2.23-6.43, P < 0.001) based on 38 case-control studies. Obviously, our meta-analysis separated case-control studies from cross-sectional studies, therefore, the result was subjected to fewer confounding and biases of study design.
Second, except for geographic area, end point, and assessment of PD, we added subgroup analysis according to adjustment for covariates, source of control, methodological quality, and assessment of CHD. We found that the populations of America (OR 4.75, 95%CI: 1.50-15.02) had higher risk than Europeans (OR 3.81, 95%CI: 2.46-5.91), and Europeans had higher risk than Asians (OR 3.46, 95%CI: 1.73-6.94). This was different from previous meta-analysis, whose result showed American populations seem to present weaker association between PD and CHD than European ones. If it is due to the individual and social economic factors, why the oral health awareness and healthcare level of European and American populations are higher than Asians, but the trend of risk is just opposite. Whether other factors, such as racial predisposition of CHD or dietary difference (e.g., Asians like drinking green tea) caused this result still needs to be identified by further researches.
Third, when stratified by adjustment for covariates, the risk of adjusted data was lower (OR 2.72, 95%CI: 2.13-3.46, P < 0.001) than unadjusted ones (OR 4.62, 95%CI: 2.10-10.18, P < 0.001), and the relevant 95%CI was also narrower. This showed that adjusted data could obtain more precise point estimate than unadjusted data, and also confirmed that PD was an independent risk factor of CHD. When stratified by assessment of CHD, we observed that a definite diagnosis by cardiologists showed higher risk (OR 5.09, 95%CI: 1.71-15.14) than by CAG (OR 2.85, 95%CI: 2.23-3.64) or ECG (OR 2.06, 95%CI: 2.06-6.12). This may be because that objective diagnostic approach is more accurate than subjective one, therefore, similar researches in future combining objective and subjective diagnostic approaches would be more beneficial to confirm CHD. The high methodological quality studies obtained narrower CI (OR 4.16, 95%CI: 2.71-6.40) than low quality ones (OR 3.38, 95%CI: 1.75-6.52), and this was in accordance with PB (OR 3.08, 95%CI: 2.23-4.26) compared with HB (OR 4.04, 95%CI: 2.00-8.12). It could be concluded that high methodological quality and PB study can more effectively control confounding bias.
Some limitations also should be indicated. The major limitation of this meta-analysis was the clinical heterogeneity among the studies with regard to both outcome and exposure definitions. Although we performed subgroup analyses according to the possible sources of heterogeneity, clinical heterogeneity also could not be removed completely. However, the result of sensitivity analysis supported that overall result was not influenced by any included single study. Second, 17 studies did not adjust covariates, and the pooled results also showed that the risk reduction sequence was unadjusted, followed by total (combined with adjusted and unadjusted), and adjusted. This means that the overall result may exaggerate the risk. Third, this study only included articles published in Chinese and English, and articles in the other languages (representing the populations of other races) were under-represented. The funnel plot, Egger linear regression test, and “trim and fill” method also indicated publication bias. Finally, according to the the American Association of Periodontology in 1999, PD should be confirmed by the measure of clinical attachment loss (CAL). However, other periodontal outcomes such as periodontal pocket depth, alveolar bone loss, community periodontal index, periodontal index, or by dentist according to questionnaire were conducted in 28 included studies. This variety of criteria leads to careful interpretation of the meta-analysis results.
In conclusion, this meta-analysis indicated that PD was associated with CHD risk independently and significantly, and we can conclude that an effective oral hygiene regimen would effectively prevent the progression of CHD, an effective PD intervention treatment can control CHD, and correct and effective brushing of teeth, use of dental floss, and regular periodontal scaling would be the simplest and most cost-effective actions. However, whether this is a causal association or PD is only a marker of CHD needs to be confirmed by well-designed studies with larger sample sizes and by taking the certain genetic or environmental confounding factors into account; and whether periodontal interventions are effective also needs to be validated by high quality studies with strict design, large sample size and the standardized implementation, and multi-center randomized controlled trials.
Growing evidence indicated that periodontal disease (PD) might be associated with coronary heart disease (CHD), however, results from these studies were inconsistent. Thus, whether PD is a risk factor of CHD remains to be clarified.
CHD is one of the major causes of mortality, account for nearly 30% of deaths worldwide; PD is one of the major two oral diseases and affect up to 90% of the worldwide population. Therefore, it is very important to identify the association between PD and CHD, in order to provide evidence for prevention and treatment of the diseases.
Innovations and breakthroughs
This is a comprehensive meta-analysis, in which the authors performed subgroup analyses to identify the similarities and differences between the adjustment for covariates, source of control, methodological quality, end point, assessment of PD, assessment of CHD, and ethnicity. All these analyses indicated that PD is a risk factor for CHD.
According to this meta-analysis, an effective oral hygiene regimen would effectively prevent the progression of CHD, an effective PD intervention treatment can control CHD, and correct and effective brushing of teeth, use of dental floss, and regular periodontal scaling would be the simplest and most cost-effective actions. In addition, whether this is a causal association or PD is only a marker of CHD, and whether periodontal interventions are effective remain to be confirmed.
The authors have made a good meta-analysis, complete and deep enough.
P- Reviewers Del Fabbro M, Vieira AR S- Editor Song XX L- Editor Ma JY E- Editor Zheng XM
Negi S, Anand A. Atherosclerotic coronary heart disease-epidemiology, classification and management.Cardiovasc Hematol Disord Drug Targets. 2010;10:257-261.
Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B. Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee.Circulation. 2007;115:e69-171.
Mi X, Eskridge KM, George V, Wang D. Structural equation modeling of gene-environment interactions in coronary heart disease.Ann Hum Genet. 2011;75:255-265.
Albus C. Psychological and social factors in coronary heart disease.Ann Med. 2010;42:487-494.
Dent TH. Predicting the risk of coronary heart disease I. The use of conventional risk markers.Atherosclerosis. 2010;213:345-351.
Albandar JM, Brunelle JA, Kingman A. Destructive periodontal disease in adults 30 years of age and older in the United States, 1988-1994.J Periodontol. 1999;70:13-29.
Cullinan MP, Ford PJ, Seymour GJ. Periodontal disease and systemic health: current status.Aust Dent J. 2009;54 Suppl 1:S62-S69.
Blaizot A, Vergnes JN, Nuwwareh S, Amar J, Sixou M. Periodontal diseases and cardiovascular events: meta-analysis of observational studies.Int Dent J. 2009;59:197-209.
Preshaw PM, Alba AL, Herrera D, Jepsen S, Konstantinidis A, Makrilakis K, Taylor R. Periodontitis and diabetes: a two-way relationship.Diabetologia. 2012;55:21-31.
Zeng XT, Tu ML, Liu DY, Zheng D, Zhang J, Leng W. Periodontal disease and risk of chronic obstructive pulmonary disease: a meta-analysis of observational studies.PLoS One. 2012;7:e46508.
Lowe GD. The relationship between infection, inflammation, and cardiovascular disease: an overview.Ann Periodontol. 2001;6:1-8.
Li YG, Li WL. [Assessing the relationship between periodotal infection and coronary heart disease in elderly people].Linchuang Kouqiang Yixue Zazhi. 2001;17:15-16.
López R, Oyarzún M, Naranjo C, Cumsille F, Ortiz M, Baelum V. Coronary heart disease and periodontitis -- a case control study in Chilean adults.J Clin Periodontol. 2002;29:468-473.
Huang HM, Wang QT, Yan YP. [A clinical questionnaire about the relationship between the periodontal disease and coronary heart disease].Yati Yasui Yazhoubingxue Zazhi. 2003;13:218-221.
Liu CL. [Clinical observation of the relationship between chronic periodontitis and incidence of coronary heart disease].Xiandai Kouqiang Yixue Zazhi. 2003;17:374-375.
Rutger Persson G, Ohlsson O, Pettersson T, Renvert S. Chronic periodontitis, a significant relationship with acute myocardial infarction.Eur Heart J. 2003;24:2108-2115.
Geerts SO, Legrand V, Charpentier J, Albert A, Rompen EH. Further evidence of the association between periodontal conditions and coronary artery disease.J Periodontol. 2004;75:1274-1280.
Montebugnoli L, Servidio D, Miaton RA, Prati C, Tricoci P, Melloni C. Poor oral health is associated with coronary heart disease and elevated systemic inflammatory and haemostatic factors.J Clin Periodontol. 2004;31:25-29.
Renvert S, Ohlsson O, Persson S, Lang NP, Persson GR. Analysis of periodontal risk profiles in adults with or without a history of myocardial infarction.J Clin Periodontol. 2004;31:19-24.
Tang LY, Huang W. [Study on the relationship between peridontal disease and coronary heart disease].Huaxia Yixue. 2004;17:959-960.
Buhlin K, Gustafsson A, Ahnve S, Janszky I, Tabrizi F, Klinge B. Oral health in women with coronary heart disease.J Periodontol. 2005;76:544-550.
Liu P, Wang SJ, Zhang Y, Zhang CH, Zheng PH. [The incidence of peridontal disease is higher among coronary heart disease population].Zhongguo Dongmai Yinghua Zazhi. 2005;13:36.
Wang J, Liu CL, Zhang SC, Zheng G. [The influence of chronic periodontitis on coronary heart disease].Zhongguo Manxingbing Yufang Yu Kongzhi. 2005;13:27-28.
Andriankaja OM, Genco RJ, Dorn J, Dmochowski J, Hovey K, Falkner KL, Scannapieco F, Trevisan M. The use of different measurements and definitions of periodontal disease in the study of the association between periodontal disease and risk of myocardial infarction.J Periodontol. 2006;77:1067-1073.
Barilli AL, Passos AD, Marin-Neto JA, Franco LJ. Periodontal disease in patients with ischemic coronary atherosclerosis at a University Hospital.Arq Bras Cardiol. 2006;87:695-700.
Briggs JE, McKeown PP, Crawford VL, Woodside JV, Stout RW, Evans A, Linden GJ. Angiographically confirmed coronary heart disease and periodontal disease in middle-aged males.J Periodontol. 2006;77:95-102.
Geismar K, Stoltze K, Sigurd B, Gyntelberg F, Holmstrup P. Periodontal disease and coronary heart disease.J Periodontol. 2006;77:1547-1554.
Li GZ, Xu L, Quan ZL, Kou Z, Cai LN, Su LZ, Li XY, Zhong YF. [Study of the relationship between periodotal disease and coronary heart disease in elderly people].Nanfang Yike Daxue Xuebao. 2006;26:1652-1654.
Spahr A, Klein E, Khuseyinova N, Boeckh C, Muche R, Kunze M, Rothenbacher D, Pezeshki G, Hoffmeister A, Koenig W. Periodontal infections and coronary heart disease: role of periodontal bacteria and importance of total pathogen burden in the Coronary Event and Periodontal Disease (CORODONT) study.Arch Intern Med. 2006;166:554-559.
Zhang DJ, Liu J, Zhao XZ. [Research of the relationship between the periodontal and coronary heart disease].Yati Yasui Yazhoubingxue Zazhi. 2006;16:38-40.
Zhang YM, Zhong LJ, He BX, Nie J, Wang X, Li WC. [Study on the correlation between coronary heart disease and chronic periodontitis].Zhonghua Liuxingbingxue Zazhi. 2006;27:256-259.
Latronico M, Segantini A, Cavallini F, Mascolo A, Garbarino F, Bondanza S, Debbia EA, Blasi G. Periodontal disease and coronary heart disease: an epidemiological and microbiological study.New Microbiol. 2007;30:221-228.
Nonnenmacher C, Stelzel M, Susin C, Sattler AM, Schaefer JR, Maisch B, Mutters R, Flores-de-Jacoby L. Periodontal microbiota in patients with coronary artery disease measured by real-time polymerase chain reaction: a case-control study.J Periodontol. 2007;78:1724-1730.
Rech RL, Nurkin N, da Cruz I, Sostizzo F, Baião C, Perrone JA, Wainstein R, Pretto D, Manenti ER, Bodanese LC. Association between periodontal disease and acute coronary syndrome.Arq Bras Cardiol. 2007;88:185-190.
Ge S, Wu YF, Liu TJ, Meng S, Zhao L. [Study of the correlation between moderately and severely chronic periodontitis and coronary heart disease].Huaxi Kouqiang Yixue Zazhi. 2008;26:262-266.
Meng PS, Wei ZM, Bai XF, Li ZQ. [Research of the Relationship between the Periodontal Disease and Coronary Heart Disease].Zhongguo Yiyao Daokan. 2008;10:486-487.
Wu ZZ, Yao XL. [Study the association between Periodontal Disease and coronary atherosclerotic heart disease].Xiandai Yixue. 2008;36:185-187.
Zamirian M, Raoofi S, Khosropanah H, Javanmardi R. Relationship Between Periodontal Disease and Acute Myocardial Infarction.ICRJ. 2008;1:216-221.
Zhu L, Yan LY. [Investgation of peridontal status of community population with diabetes mellitus or myocardial infarction].Zhongxiyi Jiehe Xinnaoxueguanbing Zazhi. 2008;6:1118-1120.
Dong LW, Xing CY, Wang XH, Huang W. [Research of the relationship between the periodontal disease and coronary heart disease].Guangdong Yabing Fangzhi. 2009;17:357-361.
Ma HW, Li F. [Study of relationship between periodontal disease and coronary heart disease].Shangdong Yiyao. 2009;49:76-78.
Oikarinen K, Zubaid M, Thalib L, Soikkonen K, Rashed W, Lie T. Infectious dental diseases in patients with coronary artery disease: an orthopantomographic case-control study.J Can Dent Assoc. 2009;75:35.
Sun SY, Jin AM, Fan WH, Zhang JC. [Evalution of peridontal status in patients with coronary heart disease].Nanfang Yike Daxue Xuebao. 2009;29:144-147.
Willershausen B, Kasaj A, Willershausen I, Zahorka D, Briseño B, Blettner M, Genth-Zotz S, Münzel T. Association between chronic dental infection and acute myocardial infarction.J Endod. 2009;35:626-630.
Bokhari SA, Khan AA, Khalil M, Abubakar MM, Mustahsen-U-Rehaman M. Oral health status of CHD and non-CHD adults of Lahore, Pakistan.J Indian Soc Periodontol. 2011;15:51-54.
Chen JX. [Investigation and analysis of relationship between periodontitis and coronary heart disease].Zhongguo Shequ Yishi. 2011;13:163.
Sikka M, Sequeira PS, Acharya S, Bhat M, Rao A, Nagaraj A. Poor oral health in patients with coronary heart disease: a case-control study of Indian adults.N Z Med J. 2011;124:53-62.
Ashraf J, Hussain Bokhari SA, Manzoor S, Khan AA. Poor oral health and coronary artery disease: a case-control study.J Periodontol. 2012;83:1382-1387.
Zhang LP, Li XQ, Zhou GX, Fan HM. [Periodontal disease was an independent risk factor of coronary heart disease by multi-factors Logistic regression analysis].Zhongguo Zonghe Linchuang. 2012;28:284-286.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.JAMA. 2000;283:2008-2012.
Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.JCO. 2010;28:e121.
Borenstein M, Hedges L, Higgins J, Rothstein H. Comprehensive Meta-analysis. 2nd ed. Englewood, NJ: BioStat 2005; .
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis.Stat Med. 2002;21:1539-1558.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test.BMJ. 1997;315:629-634.
Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis.Biometrics. 2000;56:455-463.
Mattila KJ, Nieminen MS, Valtonen VV, Rasi VP, Kesäniemi YA, Syrjälä SL, Jungell PS, Isoluoma M, Hietaniemi K, Jokinen MJ. Association between dental health and acute myocardial infarction.BMJ. 1989;298:779-781.