Table 2. Characteristics of Included Systematic Reviews, Systematic Umbrella Review of Correlation Between Prevalent Dental Conditions and Chronic Diseases, 1995–2017.
| Study | Years Searched | Study Type(s) | Population | Chronic Systemic Disease | Dental Disease | Interventions | Outcome | Common Risk Factors/Confounders | Quality Assessment Tool Used | Conclusions |
|---|---|---|---|---|---|---|---|---|---|---|
| Abdul-jabbar, Javed et al (2017) (19) | Up to March 2016 | RCTs | 6 Studies, 18–64 patients per study | T2DM | Chronic periodontitis | Laser therapy or antimicrobial photodynamic therapy after SRP | Clinical periodontal outcomes and glycemic outcomes | NA | Jadad | LT alone or aPDT showed significant improvement in the clinical periodontal parameters and glycemic levels in T2DM patients. Future RCTs are warranted to confirm these findings. |
| Abdul-jabbar, Vohra et al (2017) (20) | Up to October 2016 | RCTs | 4 Studies, 53–75 patients per study | DM | Chronic periodontitis | aPDT plus SRP/control SRP only | Clinical periodontal outcomes and glycemic outcomes | NA | Jadad | aPDT improved clinical periodontal and glycemic parameters in DM patients. When compared with SRP alone, none of the studies showed additional benefits of aPDT. |
| Al-Hamoudi (2017) (21) | Up to May 2017 | RCTs | 6 Studies in Brazil and Saudi Arabia. Number of participants, 20–30; 4 studies of patients with T2DM, 3 studies with cigarette smokers | T2DM | Chronic periodontitis | SRP plus aPDT, (control SRP only) | Clinical (PD reduction and CAL gain): microbiological (bacterial count) and immunological (cytokine profile) outcomes | Smoking | Modified Jadad quality scale for reporting randomized controlled trials | SRP plus aPDT improved clinical periodontal and immunological parameters in T2DM and cigarette smokers, no benefits of aPDT compared with SRP alone. |
| Azarpazhooh and Leake (2006) (22) | Up to July 2005 | Case-control and cross-sectional for COPD | Periodontal disease and COPD: 2 cross-sectional studies and 2 case-control studies; 46 to 13,792 participants | COPD | Periodontal disease, tooth loss (dentulous and edentulous patients): dental plaque | Tooth brushing, decontamination/rinsing | Risk of pneumonia/risk of COPD | NA | NA | Fair evidence of an association of pneumonia with oral health, poor evidence supporting a weak association (OR <2.0) between COPD and oral health, good evidence (I, grade A recommendation) that oropharyngeal decontamination with different antimicrobial interventions reduces the progression or occurrence of respiratory diseases. |
| Batista et al (2011) (23) | Up to May 2010 | Longitudinal, cross-sectional, and case-control studies, measuring PD and atherosclerosis clinically | Longitudinal, cross-sectional, and case-control studies, measuring PD and atherosclerosis clinically | Atherosclerosis | Periodontal disease: measures not standardized | NA | Intima-media thickness (atherosclerosis measure) | See Table 3 per study, no confounders assessed in all studies (mostly age and smoking) | NA | Although most studies reviewed found a positive association between PD and atherosclerosis, methodological limitations raise doubts on the validity. All included studies found a significant association. |
| Botero et al (2016) (24) | 1995 to July 2015 | Systematic reviews, with or without meta-analysis | 13 Systematic reviews, ranging from 2 studies with 143 participants to 35 studies with 2,565 participants (mostly included RCTs, some also non-RCTs) | DM type 1 and T2DM | Periodontitis | Nonsurgical periodontal treatment, with/without antibiotics (2 studies, flap surgery) | Glycemic control: HbA1c or fasting glucose levels | NA | AMSTAR | Periodontal treatment could help improve glycemic control in patients with T2DM and periodontitis (10/12 systematic reviews with meta-analysis). Whether reduction in HbA1c values (0.23 to 1.03 percentage points) is significant for T2DM treatment and control is unclear. Impact of PT in patients with type 1 diabetes and adjunctive antimicrobials is inconclusive. Eight Reviews were of high quality, 5 moderate, 1 low. Three reviews had low risk of bias, 6 were unclear, and 5 high. |
| Dai et al (2015) (25) | Up to November 2013 | Observational studies (clinical trials were excluded) | 23 Observational studies: 6 tooth loss, 4 caries, 3 oral hygiene, 4 periodontal health, with 20−706 patients per study | Stroke | Tooth loss, periodontitis, caries experience | NA | Oral health outcomes and oral health–related behaviors | Oral health behaviors | MORE | Poorer oral health status among patients with a stroke diagnosis compared with healthy controls, greater tooth loss, higher dental caries experience, and poorer periodontal status. |
| D’Aiuto et al (2017) (26) | 2005–2015 | Systematic reviews/meta-analyses | 30 Systematic reviews: 5–78 studies included per review. Number of participants unclear. Various types of studies included in systematic reviews. | DM | Periodontal disease, tooth loss, caries | NA | Bidirectional relationship, oral health–diabetes | NA | AMSTAR | Strong evidence of T2DM being a risk factor for periodontal diseases, weak evidence in relation to type 1 diabetes. Weak evidence in relation to dental caries experience in children. Limited evidence of periodontitis being a risk factor for diabetes, but evidence of periodontal treatment leading to modest short-term improvement in glycemic control (not sustained beyond 3 months). |
| D’Aiuto et al (2013) (27) | Up to July 2012 | RCT for meta-analysis | 14 Studies: 32–160 participants per study | CVD | Periodontal disease | SRP or surgical treatment, tooth extraction, antibiotics | CVD risk factors | Biomarkers subject to methodological and environmental confounders | NA | Main consistent finding after periodontal therapy was a reduction of serum levels of CRP (stable measure of systemic inflammation) and an improvement of measures of endothelial function (which represents a surrogate marker of CVD). |
| Dietrich et al (2017) (28) | 2005–2015 | Systematic reviews and/or meta-analyses | 22 Systematic reviews. 3–89 studies per systematic review of various types. Number of participants not reported | CVD | Oral health: periodontitis, caries, tooth loss | Oral health promotion, periodontal treatment | NA | NA | AMSTAR and PRISMA | High quality evidence of association between CVD and oral health. Mainly association between chronic periodontitis and atherosclerotic heart disease and is independent of confounding factors. No causal relationship has been established. Firm association between oral health (periodontitis, caries and tooth loss) and atherosclerotic cardiovascular disease, that is, coronary heart disease, stroke, and peripheral vascular disease. Little or no evidence to support any links between oral health and other forms of cardiovascular disease that are non-atherosclerotic such as HT, arrhythmias, and heart failure. Periodontal therapy is associated with reductions in surrogate markers of atherosclerotic CVD. |
| Faggion et al (2016) (29) | Up to March 2015 | Systematic reviews with meta-analysis | 11 Meta-analyses, original studies based on 12–514 patients | DM type 1 and T2DM | Periodontal disease | Periodontal treatment | HbA1c levels | NA | AMSTAR and OQAQ | SRs showing an average decrease of 0.46% (median, 0.40%) of HbA1c levels. These values, nevertheless, are not significant when meta-analyses of longer follow-ups (up to 6 mos) are evaluated. Furthermore, most primary studies included in those SRs had several methodological limitations. |
| Hasuike et al (2017) (30) | Up to July 2015 | Systematic reviews with meta-analysis | 9 Studies, 60–1,135 participants | DM type 1 and T2DM | Periodontal disease | Periodontal treatment with or without adjunctive use of local drug delivery and systemic antibiotics. | Changes in HbA1c | NA | AMSTAR | Significant effect of periodontal treatment on improvement of HbA1c levels in diabetes patients, although effect size is extremely small. In addition to this small effect size, the supporting evidence cannot be regarded as high quality. |
| Kelly et al (2013) (31) | Up to May 2012 | Systematic reviews | 13 Systematic reviews, 9 with meta-analyses. Not reported how many studies were included in each systematic review | Chronic heart disease | Periodontal disease | NA | Quality appraisal | NA | AMSTAR and Glenny et al (51) | Apart from analyzing the methodological and structural quality of the selected systematic reviews and meta-analyses, we did not attempt to perform any outcome analyses. There was substantial heterogeneity in the types of articles included in the 13 reviews, with varying study designs including cohort, cross-sectional, case-control, and RCTs. |
| Kothari et al (2017) (32) | Through January 2016 | Observational studies, case-control studies, and 1 mixed-methods study | 27 Studies; no information on number of participants per study | Acquired brain injury, including cerebrovascular diseases | Tooth loss, periodontal status, caries | Professional oral health care or oral hygiene instruction (in some studies) | NA | NA | NA | Currently low level of interest in topic. All included studies reported poor oral health in patients with brain injury. Studies also showed significant improvements in oral health if appropriate measures were implemented at rehabilitation settings. Stroke patients seemed to present with higher incidence of missing teeth and tooth mobility. |
| Lafon et al (2014) (33) | Up to April 2012 | Cohort studies | 9 Studies: 5 in North America, started during 1970–1980. Participants ranged from 1,137–51,529. Length of follow-up from 12–57 years | Stroke | Periodontal disease | NA | Periodontitis and tooth loss | NA | Evaluation grid | Results suggested a link between stroke and periodontal diseases. The association was significant for periodontitis and tooth loss. The risk of ischemic or hemorrhagic stroke was higher in people with periodontitis (estimated adjusted risk, 1.63 [1.25–2.00]). Tooth loss was also a significant risk factor for stroke (estimated adjusted risk, 1.39 [1.13–1.65]). In this review, gingivitis did not significantly influence the occurrence of stroke. |
| Lam et al (2011) (34) | NA | 3 RCTs, 3 pre–post interventions, 1 split-mouth, 1 quasi-experimental | 8 Studies, ranging from 6–303 patients | CVD | Oral health: periodontal health | Oral health instruction, extractions, periodontal treatment | Periodontal health and changes in systemic blood marker levels | NA | NA | Periodontal interventions were found to be capable of modifying numerous surrogate markers of cardiovascular outcomes including CRP, Ox-LDL, WBC, fibrinogen, IL-6, and endothelial dysfunction. It must be accepted, however, that neither a cause-and-effect relationship, nor the exact mechanism whereby periodontal disease may affect cardiovascular disease risk has been established. Whether the reduction of systemic inflammatory markers can truly decrease the risk of secondary cardiovascular events remains to be shown by studies of longer duration. Interventions aimed at improving periodontal parameters such as plaque and gingival bleeding were successful in patients with HT, CHD, and previous heart transplantation. Periodontal interventions were less successful at effecting changes in CsA-induced gingival overgrowth in heart transplantation patients. None of the effective articles included assessments on the effect of oral promotion interventions on oral microflora. |
| Leira et al (2017) (35) | Up to March 2015 | 3 cohort (retrospective and prospective), 5 case-control studies | 8 Studies, 95–9,962 patients. Europe, North America, and Asia. Data collected between 1968 and 2012 | Ischemic stroke (assessed as acute ischemic lesion on brain imaging and/or neurological deficit, TOAST and ICD) | Periodontitis (assessed with CAL, PPD, and radiographic bone loss) | NA | Risk of ischemic stroke | Most commonly adjusted vascular risk factors were: age, sex, DM, HT, smoking status, hypercholesterolemia, and BMI | GRADE | Suggested a positive association between ischemic stroke and prevalence of periodontitis. The risk of cerebral ischemia was higher in subjects with periodontitis (RR, 2.88 [95% CI, 1.53–5.41]). |
| Leng et al (2015) (36) | Up to May 2015 | Prospective cohort studies | 15 Studies enrolling 230–406 participants | Coronary heart disease | Periodontal disease | NA | CHD-related morbidity (fatal and nonfatal) or mortality, evaluated using relative risk or hazard ratio | Sex, BMI, smoking, age, family history of heart disease, education, blood pressure (most common confounders) | NA | Patients with periodontal disease were at a significantly increased risk of developing CHD (RR, 1.19; 95% CI, 1.13–1.26; P < .001). Subgroup analyses according to the effect measure, adjustment for confounding factors, median follow-up time, country of study origin, assessment method of periodontal disease, and sex all indicated significant associations between periodontal disease and CHD. |
| Li et al (2014) (37) | Up to April 2014 | RCT and quasi-RCT | 1 RCT, 303 participants | CVD | Chronic periodontitis | SRP and community care | Cardiovascular events | NA | Cochrane’s RoB assessment tool, GRADE | The study recorded 12 cardiovascular events, but results were not significant. Also, serum high sensitivity CRP: who had high CRP, and adverse events all reported nonsignificant results. Because only 1 was study eligible for inclusion, which was also judged to be at high risk of bias, the results should be interpreted with caution. |
| Lira et al (2017) (38) | Up to September 2016 | Clinical trials | 12 Studies qualitative analysis; 8 meta-analyses, 30–70 patients per study | DM | Periodontal disease | Adjunctive use of systemic antibiotics in nonsurgical periodontal treatment, compared with nonsurgical periodontal treatment alone. | Changes in HbA1c | NA | Cochrane’s RoB assessment tool | Shows no additional benefit of associating systemic antibiotics to nonsurgical periodontal treatment versus SRP alone in improving HbA1c levels 3–4 months after treatment. |
| Martin-Cabezas et al (2016) (39) | 2000 to June 2016 | Longitudinal studies or case-control studies and cross-sectional studies | 25 Studies in review; 18 in meta-analysis: 20 cross-sectional, 3 case-control, and 2 longitudinal studies, across Asia, Europe, United States, and Africa. Ranging from 8,124–1,025,340 participants. | HT | Periodontal disease | NA | HT | Age, sex, smoking, BMI, binge drinking | NOS | Results from the present meta-analysis support the association between HT and periodontal diseases with a range of ORs from 1.15 to 1.67. Highest OR was calculated when severe form of periodontitis with secure diagnosis criteria was considered (OR, 1.64). |
| Mauri-Obradors et al (2017) (40) | 1998 to January 2016 | Primary studies | 19 Studies: 4× longitudinal studies; 15× cross-sectional studies. A total of 3,712 patients, of whom 2,084 had diabetes. | DM type 1 and T2DM | Caries, periodontal disease, BMS, oral mucosa alterations | NA | Oral manifestations | NA | Recommendations made by OCEBM | DM leads to multiple complications, which increase when glycemic control of the patient is inadequate. The main oral complication attributed to diabetes is periodontal disease: considered the sixth complication of DM. Higher prevalence of periapical lesions in patients with poorly controlled diabetes. Information presented in the literature about the relationship between the DM and tooth decay is inconsistent. |
| Orlandi et al (2014) (41) | Through January 2014 | Cross-sectional studies, case-control studies, population surveys, cohort studies, pilot studies, controlled trials, RCTs | 35 Studies for systematic review, 22 studies for meta-analysis; 2,021 cases, 3,431 control | c-IMT; FMD | Periodontitis | Periodontal intervention | Increase in c-IMT. Effects of periodontal treatment on FMD. | CVD (age, sex, systolic blood pressure, HDL-C, smoking, diabetes, HT treatment, and total cholesterol). Athero-sclerosis | Newcastle-Ottawa Quality Assessment Scale | Diagnosis of PD was associated with a mean increase in c-IMT of 0.08 mm (95% CI, 0.07–0.09 mm) and a mean difference in FMD of 5.1% compared with controls (95% CI, 2.08%–8.11%). A meta-analysis of the effects of periodontal treatment on FMD showed a mean improvement of 6.64% between test and control (95% CI, 2.83%–10.44%). Periodontal disease is associated with greater subclinical atherosclerosis as assessed by increased c-IMT and an independent predictor of cardiovascular events in high-risk populations. There is evidence of an impaired FMD, which is restored by periodontal treatment in individuals having periodontal disease. |
| Sanchez et al (2017) (42) | NA | 3 MA/SR of RCT, 1 MA/SR of RCT and single cohort studies, 1 SR of oral health promotion interventions, 1x SR of RCT/quasi-RCT, 1 MA/SR, 1 MA/SR of intervention trials, 1 MA of pilot trials, 1 MA/SR of intervention and nonintervention trials, SR of intervention trials; 2 SR, 1 LR, 1x pre–post mixed design, 1 pilot of an oral health program, 1 oral health guidelines for prenatal care, 1x best practice recommendations; 1 RCT, 1 pre–post test design, 1 pilot of an education program, 1 pre–post mixed design, 1 pilot of an oral health education model, 2 cross-sectional studies, 3 pilots of a screening tool, 1 best practice recommendations | 34 Studies included from Australia, Europe, United States, France, Italy, United Kingdom, Turkey, Sweden, England | CVD | Periodontal disease | Periodontal treatment | CVD | NA | AMSTAR | Strong association between periodontal disease and CVD. Although a causal link has not been confirmed between periodontal disease and CVD, the general consensus is that cardiovascular patients need to be made aware of this association and its potential implications. |
| Schmitt et al (2015) (43) | Up to September 2014 | RCTs: case-control studies, cross-sectional studies, prospective cohort pilot study | Studies included in qualitative synthesis = 10; studies included in quantitative synthesis =7; sample size in total 2,257 (range, 26–814) | Arterial stiffness | Periodontitis | Periodontal treatment | Primary outcome had to be the measure of arterial stiffness by means of pulse wave velocity assessment. | Age, sex, smoking, or diabetes | GRADE system | The present systematic review and meta-analysis support an association between severe periodontitis and increased pulse wave velocity. The measurement of arterial stiffness provides a cardiovascular marker of the cumulative impact of both known and unknown risk factors, which may include periodontitis. |
| Teeuw et al (2014) (44) | Up to June 2013 | RCTs, CCTs | Studies included n = 20; cases in total n = 865 (11–212 patients per study)/control in total n = 657 (11–105 patients per study). Cases and control in total n = 1522. | Atherosclerosis | Periodontitis | Treatment of periodontitis | Clinical CVD parameters (ie, clinical event, such as angina pectoris, MI, stroke, death) and/or markers related to atherosclerosis and CVD risk, including markers of systemic inflammation and thrombosis, lipid and glucose metabolism, and vascular function. | Overweight and smoking | GRADE | PT reduces the risk for CVD by improving plasma levels of inflammatory (CRP, IL-6, TNF-a), thrombotic (fibrinogen), and metabolic (triglycerides, TC, HDL-C, HbA1c) markers and endothelial function. This improvement is sustained well more than 6 months after therapy, and it is greater in those individuals having both periodontitis and co-morbidities like CVD and/or DM. Our findings emphasize the effectiveness and need for periodontal diagnosis and periodontal therapy in atherosclerotic and diabetic individuals to improve their systemic health. |
| Tonsekar et al (2017) (45) | Up to April 2016 | 4x retrospective cohort, 3x prospective cohort, 1x case-control study nested in a longitudinal study | Studies included n = 8; 4,075 participants; number of participants 144 to 911; countries: United States, South Korea, France, Sweden. | Dementia | Periodontal disease, tooth loss | NA | Outcome measured was assessed by verified cognitive tests such as Mini-Mental State Examination: Delayed Word Recall and Digit Symbol Substitution Test. | Apolipoprotein E (ApoE) allele, considered a major genetic risk factor for Alzheimer disease and a possible confounding factor in the association between periodontitis and dementia. | Newcastle-Ottawa Scale | Association between subsequent dementia, periodontal disease and tooth loss was inconclusive. |
| Ungprasert et al (2017) (46) | Up to July 2016 | Case-control or cohort study | Studies included n = 5; number of subjects (cases/comparators) 1) 115,365/115,365; 2) 1,358/70,020; 3) 100/100; 4) 50/121; 5) 60/45. The 5 studies included 312,584 subjects. Countries: Taiwan, United States, Greece, Norway, Italy. | Psoriasis | Periodontitis | NA | Periodontitis and risk of psoriasis | Confounders: smoking, obesity, and DM | Newcastle–Ottawa quality assessment scale | Patients with periodontitis have a significantly increased risk of psoriasis. |
| Xu et al (2017) (47) | Up to July 2016 | 6x cross-sectional, 12x case control, 4x cohort studies | Studies included n = 22; 129,630 participants; countries: United States, Sweden, Japan, India, Spain, Iran, China, Germany, Greece. | MI | Periodontal disease | NA | Periodontal disease (including pocket probing depth, attachment loss, bleeding on probing, plaque index, gingival index, X-ray, and microbiological results) and the risk of myocardial infarction | Risk factors including age, smoking, and diabetes are common in both PD and MI | Newcastle-Ottawa Scale | Significant association between periodontal disease and MI. Subgroup analyses also confirmed the elevated risk for MI in periodontal disease subjects. |
| Zeng, Leng et al (2016) (48) | Up to February 20, 2015 | 10x cross-sectional, 5x case control | Studies included n = 15; 17,330 participants; countries: United States, Sweden, Germany, Austria, Italy, Spain, Japan, Portugal, Poland, South Korea, China. | Carotid atherosclerosis | Periodontal disease | NA | Risk of carotid atherosclerosis as diagnosed by c-IMT (by ultrasound) or carotid plaque thickness (by panoramic radiographs) | Common risk factor: smoking; confounder: DM | NA | Periodontal disease was associated with carotid atherosclerosis, although available evidence is insufficient to confirm the causal relationship of periodontal disease and carotid atherosclerosis. |
| Zeng et al (2012) (49) | Up to January 10, 2012 | Observational studies (cross-sectional, case-control, or cohort design) | Studies included n = 14; subjects (case/control): between 28/30 and 810/12,982. Countries: United States, Poland, Norway, Iran, China, India. | COPD | Periodontal disease | NA | Relationship between PD and COPD | NA | NA | Periodontal disease significantly increases the risk of COPD, with the increase being likely independent of conventional COPD risk factors. Dental plaque that contains bacteria may be responsible for COPD, therefore, good attention to teeth brushing and general oral hygiene care may reduce the risk of COPD. |
| Zeng, Xia et al (2016) (50) | Up to June 10, 2015 | Cohort and nested case-control studies | Studies included n = 5; subjects: (lung cancer/sample): 1)191/11,328; 2)236/48,375; 3) 225/30,666; 4) 243/153,566; 5) 754/77,485. Countries: United States, Sweden, China. | Lung Cancer | Periodontal disease | NA | Risk of lung cancer in patients with periodontal disease | Smoking | NA | Periodontal disease is associated with a significant and increased risk of lung cancer. |
Abbreviations: AMSTAR, Assessing the Methodological Quality of Systematic Reviews; aPDT, antimicrobial PhotoDynamic Therapy; BMI, body mass index; BMS, burning mouth syndrome; CAL, clinical attachment level (14); CAL, clinical attachment loss (29); CCT, controlled clinical trial; CHD, coronary heart disease; CI, confidence interval; c-IMT, carotid intima-media thickness; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; CsA, cyclosporin A; CVD, cardiovascular disease; DM, diabetes mellitus; FMD, flow-mediated dilation; GRADE Grading of Recommendations, Assessment, Development and Evaluations; HbA1c, glycated hemoglobin; HDL-C, high-density lipoprotein cholesterol; HT, hypertension; ICD, International Classification of Diseases; IL, interleukin; LT, laser therapy; MA, meta-analysis; MI, myocardial infarction; MORE, Methodological Evaluation of Observational Research; NA, not applicable; NOS, Newcastle-Ottowa Scale; OCEBM, Centre for Evidence-Based Medicine, Oxford; OQAQ, Overview Quality Assessment Questionnaire; PD, probing depth; PPD, probing pocket depth; PT, periodontal therapy; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; OR, odds ratio; Ox-LDL, oxidized low-density lipoprotein; RCT, randomized controlled trial; SR, systematic review; SRP, scaling and root planing; T2DM, type 2 diabetes mellitus; TC, total cholesterol; TOAST, Trial of Org 10172 in Acute Stroke Treatment; WBC, white blood cell.