Effect of periodontal treatments on blood pressure

Abstract

Background

An association has been hypothesized between periodontitis and hypertension. Periodontal therapy is believed to reduce systemic inflammatory mediators and increase endothelial function, thus having the potential to prevent and treat hypertension.

Objectives

To assess the effect and safety of different periodontal treatment modalities on blood pressure (BP) in people with chronic periodontitis.

Search methods

The Cochrane Hypertension Information Specialist searched for randomized controlled trials (RCTs) up to November 2020 in the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE, Embase, seven other databases, and two clinical trials registries. We contacted the authors of relevant papers regarding further published and unpublished work.

Selection criteria

RCTs and quasi‐RCTs aiming to detect the effect of periodontal treatment on BP were eligible. Participants should have been diagnosed with chronic periodontitis and hypertension (or no hypertension if the study explored the preventive effect of periodontal treatment). Participants in the intervention group should have undergone subgingival scaling and root planing (SRP) and any other type of periodontal treatments, compared with either no periodontal treatment or alternative periodontal treatment in the control group.

Data collection and analysis

We used standard methodological procedures expected by Cochrane for study identification, data extraction, and risk of bias assessment. We used a formal pilot‐tested data extraction form for data extraction, and the Cochrane risk of bias tool for risk of bias assessment. We planned the meta‐analysis, test for heterogeneity, sensitivity analysis, and subgroup analysis. We assessed the certainty of evidence using GRADE. The primary outcome was change in systolic BP (SBP) and diastolic BP (DBP).

Main results

We included eight RCTs. Five had low risk of bias, one had unclear risk of bias, and two had high risk of bias.

Four trials compared periodontal treatment with no treatment. We found no evidence of a difference in the short‐term change of SBP and DBP for people diagnosed with periodontitis and other cardiovascular diseases except hypertension (very low‐certainty evidence). We found no evidence of a difference in long‐term changes in SBP (mean difference [MD] −2.25 mmHg, 95% confidence interval [CI] −9.41 to 4.92; P = 0.54; studies = 2, participants = 108; low‐certainty evidence) and DBP (MD −2.55 mmHg, 95% CI −6.90 to 1.80; P = 0.25; studies = 2, participants = 103; low‐certainty evidence). Concerning people diagnosed with periodontitis, in the short term, two studies of low certainty reported no changes in SBP (MD −0.14 mmHg, 95% CI −4.05 to 3.77; P = 0.94; participants = 294) and DBP (MD −0.15 mmHg, 95% CI −2.47 to 2.17; P = 0.90; participants = 294), and we found no evidence of a difference in SBP and DBP over a long period based on low certainty of evidence.

Three studies compared intensive periodontal treatment with supra‐gingival scaling. We found no evidence of a difference in changes in SBP and DBP for any length of time in people diagnosed with periodontitis (very low‐certainty evidence).

In people diagnosed with periodontitis and hypertension, we found one study reporting a significant reduction in the short term in SBP (MD −11.20 mmHg, 95% CI −15.40 to −7.00; P < 0.001; participants = 101; moderate‐certainty evidence) and DBP (MD −8.40 mmHg, 95% CI −12.19 to −4.61; P < 0.0001; participants = 101; moderate‐certainty evidence).

Authors' conclusions

We found no evidence of a difference of an impact of periodontal treatments on BP in most comparisons assessed in this review, and given the low certainty of evidence and the lack of relevant studies we could not draw conclusions about the effect of periodontal treatment on BP in people with chronic periodontitis. We found only one study suggesting that periodontal treatment may reduce SBP and DBP over a short period in people with hypertension and chronic periodontitis, but the certainty of evidence was moderate.

Plain language summary

Periodontal treatment for blood pressure control

Review question

Can periodontal treatment prevent hypertension or lower the blood pressure of people with hypertension?

Background

Periodontitis is a severe form of gingivitis (gum disease) caused by some specific bacteria that are also found in atherosclerotic plaque (a buildup of fat, cholesterol, calcium, and other substances in the blood vessels), with the latter exerting significant effects on hypertension (high blood pressure). Multiple studies have shown an association between periodontitis and hypertension. It is important to evaluate whether periodontal treatment can prevent or treat hypertension.

Search date

The evidence is current to November 2020.

Study characteristics

We included eight randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) involving 894 participants. The studies looked at the preventive and therapeutic effects of periodontal treatment on changes in blood pressure, with the participants diagnosed with periodontitis of any age and gender with or without hypertension.

Key results

Four studies compared periodontal treatment with no treatment in blood pressure changes in people with periodontitis diagnosed with or without other cardiovascular diseases except hypertension. The results showed no difference in blood pressure between the treated and untreated participants for any length of time.

Three studies compared periodontal treatment with supra‐gingival scaling (by just removing the visible dental calculus with limited treatment effects on periodontitis) in people with chronic periodontitis. The results showed no difference in blood pressure for any length of time.

Only one study on people with hypertension found a reduction in blood pressure between groups in the short term, with no difference in blood pressure changes for the other comparisons.

Quality of the evidence

It was not well documented how the included studies were conducted and described, therefore the quality of evidence was low. Consequently, there was insufficient information to draw firm conclusions.

Summary of findings

Summary of findings 1. Periodontal treatment versus no treatment for different patient composition.

Periodontal treatment versus no treatment for different patient composition
Patient or population: people diagnosed with periodontitis or other cardiovascular diseases except hypertension (or both) Settings: India, Japan, Australia Intervention: periodontal treatment Comparison: no treatment
Outcomes	Mean difference (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)
Short‐term change of SBP (mmHg) – people diagnosed with periodontitis and other cardiovascular diseases except hypertension Follow‐up: 3 months	The mean short‐term change of SBP (mmHg) – people diagnosed with periodontitis and other cardiovascular diseases except hypertension in the intervention groups was 0.59 higher (9.18 lower to 10.36 higher)	55 (1 study)	⊕⊝⊝⊝ Very lowa
Short‐term change of SBP (mmHg) – people diagnosed with periodontitis Follow‐up: 2–3 months	The mean short‐term change of SBP (mmHg) – people diagnosed with periodontitis in the intervention groups was 0.14 lower (4.05 lower to 3.77 higher)	294 (2 studies)	⊕⊕⊝⊝ Lowb
Long‐term change of SBP (mmHg) – people diagnosed with periodontitis and other cardiovascular diseases except hypertension Follow‐up: 6 months	The mean long‐term change of SBP (mmHg) – people diagnosed with periodontitis and other cardiovascular diseases except hypertension in the intervention groups was 2.25 lower (9.41 lower to 4.92 higher)	108 (2 studies)	⊕⊕⊝⊝ Lowc
Long‐term change of SBP (mmHg) – people diagnosed with periodontitis Follow‐up: 12 months	The mean long‐term change of SBP (mmHg) – people diagnosed with periodontitis in the intervention groups was 0.14 higher (4.4 lower to 4.68 higher)	168 (1 study)	⊕⊕⊝⊝ Lowd
Short‐term change of DBP (mmHg) – people diagnosed with periodontitis and other cardiovascular diseases except hypertension Follow‐up: 3 months	The mean short‐term change of DBP (mmHg) – people diagnosed with periodontitis and other cardiovascular diseases except hypertension in the intervention groups was 2.45 lower (7.95 lower to 3.05 higher)	55 (1 study)	⊕⊝⊝⊝ Very lowe
Short‐term change of DBP (mmHg) – people diagnosed with periodontitis Follow‐up: 2–3 months	The mean short‐term change of DBP (mmHg) – people diagnosed with periodontitis in the intervention groups was 0.15 lower (2.47 lower to 2.17 higher)	294 (2 studies)	⊕⊕⊝⊝ Lowb
Long‐term change of DBP (mmHg) – people diagnosed with periodontitis and other cardiovascular diseases except hypertension Follow‐up: 6 months	The mean long‐term change of DBP (mmHg) – people diagnosed with periodontitis and other cardiovascular diseases except hypertension in the intervention groups was 2.55 lower (6.9 lower to 1.8 higher)	103 (2 studies)	⊕⊕⊝⊝ Lowc
Long‐term change of DBP (mmHg) – people diagnosed with periodontitis Follow‐up: 12 months	The mean long‐term change of DBP (mmHg) – people diagnosed with periodontitis in the intervention groups was 0.2 lower (3.02 lower to 2.62 higher)	168 (1 study)	⊕⊕⊝⊝ Lowd
Adverse effects	Only 1 study reported that 1 participant in the treatment group experienced a myocardial infarction during the study period. 1 study reported no adverse effects. The remaining 2 studies did not mention any adverse effects in their reports.	294 (2 study)	⊕⊕⊝⊝ Lowf
CI: confidence interval; DBP: diastolic blood pressure; SBP: systolic blood pressure.
GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: we are very uncertain about the estimate.

^aDowngraded three levels due to serious risk of bias and very serious imprecision: the included study had high risk of bias. The confidence interval of the blood pressure had very low precision.
^bDowngraded two level due to serious inconsistency and serious imprecision: there was moderate heterogeneity between two studies. The confidence interval of the blood pressure has low precision.
^cDowngraded two levels due to serious risk of bias and serious imprecision: one study had high risk of bias, the other had unclear risk of bias. The confidence interval of the blood pressure had low precision.
^dDowngraded two levels due to very serious imprecision: the confidence interval of the blood pressure had low precision and data available from a subgroup of only one study.
^eDowngraded three levels due to serious risk of bias and very serious imprecision: the study had high risk of bias. The confidence interval of the blood pressure had low precision, and data available from a subgroup of only one study and small number of participants.
^fDowngraded two levels due to serious imprecision and serious inconsistency: only two studies reported this outcome, and they did not report data adequately to enable us to evaluate the risk of adverse events.

Summary of findings 2. Periodontal treatment versus supra‐gingival scaling for different patient composition.

Periodontal treatment versus supra‐gingival scaling for different patient composition
Patient or population: people diagnosed with periodontitis or hypertension, or both Settings: Poland, UK, China Intervention: periodontal treatment Comparison: supra‐gingival scaling
Outcomes	Mean difference (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)
Short‐term change of SBP (mmHg) – people diagnosed with periodontitis Follow‐up: 2–3 months	The mean short‐term change of SBP (mmHg) – people diagnosed with periodontitis in the intervention groups was 3.55 lower (10.09 to 2.98 lower)	227 (2 studies)	⊕⊝⊝⊝ Very lowa
Short‐term change of SBP (mmHg) – people diagnosed with periodontitis and hypertension Follow‐up: 2 months	The mean short‐term change of SBP (mmHg) – people diagnosed with periodontitis and hypertension in the intervention groups was 11.2 lower (15.4 to 7 lower)	101 (1 study)	⊕⊕⊕⊝ Moderateb
Long‐term change of SBP (mmHg) – people diagnosed with periodontitis Follow‐up: 6 months	The mean long‐term change of SBP (mmHg)– people diagnosed with periodontitis in the intervention groups was 6.64 lower (16.83 to 3.55 lower)	227 (2 studies)	⊕⊝⊝⊝ Very lowc
Short‐term change of DBP (mmHg) – people diagnosed with periodontitis Follow‐up: 2–3 months	The mean short‐term change of DBP (mmHg) – people diagnosed with periodontitis in the intervention groups was 2.08 lower (4.84 lower to 0.68 higher)	227 (2 studies)	⊕⊕⊝⊝ Lowd
Short‐term change of DBP (mmHg) – people diagnosed with periodontitis and hypertension Follow‐up: 2 months	The mean short‐term change of DBP (mmHg) – people diagnosed with periodontitis and hypertension in the intervention groups was 8.40 lower (12.19 to 4.61 lower)	101 (1 study)	⊕⊕⊕⊝ Moderateb
Long‐term change of DBP (mmHg) – people diagnosed with periodontitis Follow‐up: 6 months	The mean long‐term change of DBP (mmHg) – people diagnosed with periodontitis in the intervention groups was 4.96 lower (13.04 lower to 3.13 higher)	227 (2 studies)	⊕⊝⊝⊝ Very lowa
Adverse effects	3 studies reported no adverse effects.	328 (3 studies)	⊕⊕⊕⊝ Moderatee
CI: confidence interval; DBP: diastolic blood pressure; SBP: systolic blood pressure.
GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: we are very uncertain about the estimate.

^aDowngraded three levels due to very serious inconsistency and serious imprecision: there was considerable heterogeneity between two studies. The confidence interval of the blood pressure had low precision.
^bDowngraded one level due to serious imprecision: data available from a subgroup of only one study.
^cDowngraded three levels due to very serious inconsistency and very serious imprecision: there was considerable heterogeneity between two studies. The confidence interval of the blood pressure had very low precision.
^dDowngraded one level due to serious inconsistency and serious imprecision: there was substantial heterogeneity between two studies. The confidence interval of the blood pressure had low precision.
^eDowngraded two levels due to serious imprecision: small number of participants and studies.

Background

Description of the condition

At present, the diagnostic criteria for hypertension vary in different countries. In European countries, hypertension is defined as office systolic blood pressure (SBP) values of at least 140 mmHg or diastolic blood pressure (DBP) values of at least 90 mmHg (or both) in people not taking antihypertensive agents (Williams 2018). In the US, hypertension is categorized into two levels, stage 1 and 2, based on mean BP. Stage 1 hypertension is defined as an SBP of 130 mmHg to 139 mmHg or DBP of 80 mmHg to 89 mmHg, and stage 2 hypertension is defined as an SBP over 140 mmHg or DBP over 90 mmHg (Whelton 2018). Elevated blood pressure (BP) plays a critical etiologic role in developing adverse cardiovascular events, including stroke, myocardial infarction, and cardiac and renal failure (Whitworth 2003). The estimated global age‐standardized prevalence of hypertension in adults aged 20 years or greater in 2010 was 31.1%, and the estimated number of all‐cause deaths that were associated with SBP greater than or equal 110‐115 mmHg in 2015 was 10.7 million (19.2% of all deaths) (Mills 2020).

Periodontitis is characterized by pathologic loss of periodontal ligament and alveolar bone (Slots 2017). The prevalence of severe periodontitis was 9.8% in 2017, and among the 3.5 billion patients with oral diseases, 796 million suffered from severe periodontitis (GBD 2020). Periodontal disease is a common cause of tooth loss in adults worldwide (Tonetti 2017), and its global burden increased by 57.3% from 1990 to 2010 (Murray 2012).

The association between periodontal diseases and systemic inflammation was demonstrated by elevated plasma levels of inflammatory markers, including high‐sensitivity C‐reactive protein (hs‐CRP), interleukin‐6 (IL‐6), and fibrinogen, in people with periodontal disease (Hada 2015; Nakajima 2010; Vidal 2009; Zhou 2017).

Periodontal infections are commonly believed to impact general health (Bayani 2017). Mounting evidence implicates periodontitis as a potential risk factor for several systemic conditions, including cardiovascular disease (Sanz 2020), premature birth (Iheozor‐Ejiofor 2017), and diabetes mellitus (Simpson 2015).

Moreover, severe periodontitis is associated with increased SBP and left ventricular mass in people with hypertension (Angeli 2003; Martin‐Cabezas 2016; Taguchi 2004). Periodontitis‐related systemic inflammation might help induce hypertension (Jockel‐Schneider 2018; Rivas‐Tumanyan 2013). However, up to 2021, the underlying mechanisms have not been fully understood. There is a widely accepted hypothesis that periodontitis is associated with systemic inflammation, the mediators of which, including C‐reactive protein (CRP), IL‐6, and tumor necrosing factor‐alfa (TNF‐α), might lead to endothelial dysfunction by influencing the endothelial cells, decreasing the local availability of endothelium‐derived relaxing factor (i.e. nitric oxide [NO]), which activates the relaxing activity of vascular vessels (Cockcroft 1994; Muñoz Aguilera 2020). The impaired endothelium‐dependent vasodilation in people with essential hypertension is often regarded as an underlying mechanism for sustained elevated BP (D'Aiuto 2018). In addition, a variety of plausible mechanisms could explain such association. It has been indicated that vascular dysfunction might be effected by oral microbiota‐related bacteremia, caused by a common periodontal pathogen, Porphyromonas gingivalis (Czesnikiewicz‐Guzik 2019a). Besides, there is evidence that primed immune cells in the inflamed periodontium, including T cells, B cells, and monocyte/macrophages, might be more prone to chemotactic recruitment to perivascular adipose tissue. Therefore, perivascular adipose tissue inflammation leads to endothelial dysfunction with loss of NO bioavailability, contributing to hypertension and atherosclerosis (Guzik 2017; Mikolajczyk 2016).

There is evidence from some studies that people with periodontitis exhibit higher mean SBP and DBP than people without periodontitis (i.e. periodontitis increases hypertension risk) (Czesnikiewicz‐Guzik 2019b; Iwashima 2014). As periodontitis is a possible risk factor for hypertension, its prevention and management could potentially impact the treatment or prevention of hypertension. Therefore, a systematic review of the evidence in this area is warranted.

Description of the intervention

The primary goal of periodontal treatment is to control microbial infection of periodontal tissues by removing the inflammatory burden caused by bacterial biofilms, toxins, and calculi to limit periodontal tissue destruction, preserve function, maintain the appearance, and prevent disease (Newman 2002). Periodontal therapy consists of a comprehensive treatment protocol, with a sequence of steps (Greenwell 2001). Patient education, including oral hygiene instructions and counseling on controlling risk factors (e.g. smoking, stress, comorbidities), is considered critical in preventing and treating periodontal diseases. In addition, supra‐gingival and subgingival bacterial plaque and calculi are removed using periodontal scaling and root planing (SRP). Apart from comprehensive periodontal root planing, some other procedures are designed to deal with more advanced forms of the disease, including resective procedures (e.g. gingivectomy, gingivoplasty, and root resection), periodontal regenerative and reconstructive procedures (e.g. soft tissue grafts, guided bone regeneration), and periodontal plastic surgery. In the finishing procedures, postoperative evaluation and reinforcement of personal daily oral hygiene are essential to prevent disease recurrence. Moreover, antiseptics and antibiotics have also been used as adjuncts to mechanical debridement (scaling, subgingival curettage, flap surgery, or gingivectomy) as indicated.

Available evidence suggests that periodontal therapy could help achieve periodontal health and might help manage systemic diseases, such as cardiovascular diseases (Li 2017), diabetes mellitus (Simpson 2015), and premature birth (Iheozor‐Ejiofor 2017).

How the intervention might work

Randomized controlled clinical trials (RCTs) have shown that periodontal treatment could significantly decrease the blood plasma levels of systemic inflammatory markers (hs‐CRP, IL‐6, and fibrinogen) in people with hypertension with periodontitis (Higashi 2008; Lamster 2017; Vidal 2009). Elter and colleagues reported that periodontal therapy significantly improved flow‐mediated dilation, indicating decreased endothelial dysfunction (Elter 2006). Tonetti and colleagues demonstrated that intensive periodontal treatment could lead to acute, short‐term systemic inflammation, impairing endothelial function but improving endothelial function six months after therapy (Tonetti 2007). Another study showed that after two months of intensive periodontal treatment, there was a decrease in SBP in people with hypertension and periodontal diseases (D'Aiuto 2006).

Why it is important to do this review

Both hypertension and periodontal infections are common medical conditions. Long‐term control of BP in people with hypertension is of critical importance in preventing the associated complications. It is worth knowing whether periodontal treatment affects BP and other factors related to both conditions, such as plasma levels of inflammatory markers. If periodontal treatment affects BP control, dentists and dental auxiliary workers can significantly improve BP control among people with hypertension. However, the findings have not been consistent among studies. Therefore, a systematic review of the effect of periodontal treatments on BP is necessary.

Objectives

To assess the effect and safety of different periodontal treatment modalities on blood pressure (BP) in people with chronic periodontitis.

Methods

Criteria for considering studies for this review

Types of studies

We included RCTs and quasi‐RCTs measuring the effect of periodontal treatment on BP. We excluded cross‐over studies.

Types of participants

Men and women of any race, and social and economic status, who met the following criteria:

• had at least five teeth remaining;

• were diagnosed with periodontitis on any of the remaining teeth, which should have had a pocket probing depth (PPD) greater than 4 mm;

• with hypertension (BP greater than 140/90 mmHg) or without hypertension but in trials focusing on the preventive effects of the periodontal treatment with the primary outcomes reported;

• did not accept any periodontal treatment in the past three months;

• studies should not have been specific to participants with a history of any other systemic diseases, except for hypertension‐related illness.

Types of interventions

• Intervention group: received subgingival SRP with or without any other type of periodontal treatment.

• Control group: received no periodontal treatment or supra‐gingival scaling or alternative periodontal treatment.

Periodontal treatment included: supra‐gingival scaling, SRP (which included two types: full‐mouth or quadrant‐wise), systemic or local antibiotic or host modulation treatment, and periodontal surgery.

Types of outcome measures

All outcome variables should have been recorded at least one month after the treatment. We defined less than six months as short term and six months or greater as long term.

Primary outcomes

• Change in SBP and DBP (mmHg).

Secondary outcomes

• Proportion of participants diagnosed with hypertension at trial completion (when focused on the preventive effects of periodontal treatment).

• Proportion of participants who reported adverse events or withdrawing due to adverse events.

• Plasma levels of inflammatory markers of participants with hypertension (such as IL‐6, hs‐CRP).

• Heart rate.

• Endothelial function.

• Periodontal clinical parameters of participants with hypertension: clinical attachment level (CAL), PPD, bleeding on probing (BOP).

Search methods for identification of studies

Electronic searches

The Cochrane Hypertension Information Specialist conducted systematic searches in the following databases for RCTs and quasi‐RCTs without language, publication year or publication status restrictions:

• the Cochrane Hypertension Specialised Register via the Cochrane Register of Studies (CRS‐Web) (searched 7 November 2020) (Appendix 1);

• Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 10) via the Cochrane Register of Studies (CRS‐Web) (searched 7 November 2020) (Appendix 2);

• MEDLINE Ovid (from 1946 onwards), MEDLINE Ovid Epub Ahead of Print, and MEDLINE Ovid In‐Process & Other Non‐Indexed Citations (searched 7 November 2020) (Appendix 3);

• Embase Ovid (searched 7 November 2020) (Appendix 4);

• CINAHL EBSCO (searched 7 November 2020) (Appendix 5);

• LILACS Bireme (searched 7 November 2020) (Appendix 6);

• US National Institutes of Health Ongoing Trials Register (www.clinicaltrials.gov) (searched 7 November 2020) (Appendix 7);

• WHO International Clinical Trials Registry Platform (www.who.int/trialsearch) searched 7 November 2020) (Appendix 8);

• Cochrane Oral Health Specialised Register (searched 7 November 2020) (Appendix 9).

The Information Specialist modeled subject strategies for databases on the search strategy designed for MEDLINE. Where appropriate, they were combined with subject strategy adaptations of the highly sensitive search strategy designed by Cochrane for identifying RCTs (as described in the Cochrane Handbook for Systematic Reviews of Interventions (Chapter 4, Box 3c; Higgins 2021).

We also searched the following Chinese language databases for eligible trials:

• Chinese BioMedical Literature Database (searched 12 November 2020) (Appendix 10);

• VIP (searched 12 November 2020) (Appendix 11);

• China National Knowledge Infrastructure (searched 12 November 2020) (Appendix 12).

Searching other resources

The Cochrane Hypertension Information Specialist searched the Hypertension Specialised Register segment (which includes searches in the MEDLINE and Epistemonikos for systematic reviews) to retrieve existing systematic reviews relevant to this systematic review, so that we could scan their reference lists for additional trials. The Specialised Register also includes searches in CAB Abstracts & Global Health, CINAHL, ProQuest Dissertations & Theses, and Web of Knowledge.

We checked the bibliographies of included studies and any relevant systematic reviews identified for further references to relevant trials.

Where necessary, we contacted the authors of key papers and abstracts to request additional information about their trials.

We searched Sciencepaper Online (in Chinese, up to 12 November 2020) (Appendix 13) for unpublished Chinese studies.

We handsearched the following Chinese journals:

• Chinese Journal of Stomatology (1953 to June 2011);

• Stomatology (1981 to June 2011);

• West China Journal of Stomatology (1983 to June 2011);

• Journal of Practical Stomatology (1985 to June 2011);

• Journal of Clinical Stomatology (1985 to June 2011);

• Journal of Comprehensive Stomatology (1985 to June 2011);

• Journal of Modern Stomatology (1987 to June 2011);

• Chinese Journal of Conservative Dentistry (1991 to June 2011);

• Shanghai Journal of Stomatology (1992 to June 2011);

• Beijing Journal of Stomatology (1993 to June 2011);

• Chinese Journal of Dental Prevention and Treatment (1993 to June 2011);

• Journal of International Stomatology (2001 to June 2011);

• Chinese Journal of Geriatric Dentistry (2002 to June 2011);

• International Journal of Oral Science (2009 to June 2011);

• Chinese Journal of Hypertension (1993 to June 2011).

Data collection and analysis

Selection of studies

Two review authors (YL and HY) independently screened the titles and abstracts of all studies brought up by the search. We excluded studies that did not meet the inclusion criteria. We retrieved the full texts of the remaining studies and two review authors checked them. We classified studies at this stage into categories: included studies, excluded studies, ongoing studies, and studies requiring more information to assess their eligibility. We contacted the authors of the studies in the third category and asked them to provide the required information. If the authors did not reply, we listed them as studies awaiting classification. If any studies were still ongoing, we listed them as ongoing studies. We resolved any disagreement between the two review authors during the evaluation of inclusion criteria by discussion. We presented a flow diagram illustrating the study selection process in a figure.

Data extraction and management

Two review authors (YL and HY) independently extracted data. We resolved disagreements by discussion. We applied a customized data extraction form, which was pilot tested using a sample of the included studies, to all the included studies. We collected the following data during the data extraction process and presented them in the Characteristics of included studies table:

• Source: study ID, citation, and contact details.

• Eligibility: reasons for inclusion or exclusion.

• Study methods: centers and their location, study duration, inclusion and exclusion criteria for the participants, study design, sequence generation, allocation concealment, blinding, and statistical methods.

• Participants: total number, setting, age, sex, diagnostic criteria for both hypertension and periodontitis, inclusion criteria for the trial.

• Interventions: number of intervention groups, intervention details including periodontal therapy, control treatments and other active treatments; time, frequency, dose, and usage if drugs were administered.

• Outcomes: definition of outcome measures and measurement units, time intervals of the measure, sample size calculation, number of participants allocated to each group, number of lost follow‐ups and reasons, and detailed summary data for each group.

• Miscellaneous: funding, key conclusions of each article, correspondence required, and miscellaneous comments.

We performed data extraction for studies awaiting classification and presented the data in the Characteristics of studies awaiting classification table.

We contacted the original investigators of the included studies to request missing information or for further clarification where needed.

Assessment of risk of bias in included studies

Two review authors (YL and HY) independently performed the risk of bias assessment of the included studies. If there was any discrepancy, a third review author (CL) made a final decision. We performed the risk of bias assessment as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We contacted the authors of the included studies by email to request any possible unreported data or unclear information relevant to the risk of bias assessment. The assessment was based on both the published article and any additional information provided by the authors.

The risk of bias assessment consisted of seven domains. For each of the following domains, we presented a description for evaluation, and scored the result as 'low risk', 'unclear risk', or 'high risk'.

• Random sequence generation (selection bias): selection bias (biased allocation to interventions) due to inadequate generation of a randomized sequence.

• Allocation concealment (selection bias): selection bias (biased allocation to interventions) due to inadequate concealment of the allocation.

• Blinding of participants and personnel (performance bias): performance bias due to knowledge of the allocated interventions by participants and personnel during the study.

• Blinding of outcome assessment (detection bias): detection bias due to knowledge of the allocated interventions by outcome assessors.

• Incomplete outcome data (attrition bias): attrition bias due to amount, nature, or handling of incomplete outcome data.

• Selective reporting (reporting bias): reporting bias due to selective outcome reporting.

• Other bias: bias due to problems not covered elsewhere in the table, such as baseline imbalance, confounding bias, contamination, and co‐intervention.

We presented the results of the risk of bias assessment in the Characteristics of included studies table and summarized them in a risk of bias graph.

All the domains except the 'Blinding of participants and personnel' domain were key domains (as it was impossible to achieve blinding of participants and personnel during periodontal treatment, and the outcomes were objective outcomes assessed by the assessor). We assessed the risk of bias of each included study according to the key domains with the criteria listed in Table 3.

1. Summary risk of bias table.

Risk of bias	Interpretation	Within a study	Across studies
Low risk of bias	Plausible bias unlikely to seriously alter the results	Low risk of bias for all key domains	Most information is from studies at low risk of bias
Unclear risk of bias	Plausible bias that raises some doubt about the results	Unclear risk of bias for one or more key domains	Most information is from studies at low or unclear risk of bias
High risk of bias	Plausible bias that seriously weakens confidence in the results	High risk of bias for one or more key domains	The proportion of information from studies at high risk of bias is sufficient to affect the interpretation of results

Measures of treatment effect

For dichotomous data, we calculated risk ratios (RR) with 95% confidence intervals (CIs). We used Peto odds ratio (OR) with 95% CIs if the observed incidence of the events was low.

For continuous data, we used mean difference (MD) and 95% CIs, measuring the change from baseline or the endpoint values if studies measured them using a similar method. We used standardized mean difference (SMD) and 95% CIs if studies used different methods to measure those outcomes.

Unit of analysis issues

We considered two types of non‐standard design RCTs as described below.

Cluster‐randomized trials

We adopted approximate analyses‐effective sample sizes following the Cochrane Handbook for Systematic Reviews of Interventions to avoid the inappropriate analyses in the original studies (Higgins 2021).

Studies with multiple treatment groups

We extracted and presented the data of all groups in the systematic review. However, in the meta‐analysis, which addressed only a single pair‐wise comparison, we considered two approaches for dealing with the data to combine groups to create a single pair‐wise comparison or, if the first approach failed, select the most related pair of interventions.

Dealing with missing data

We contacted the study authors to request any essential missing data. If there was no reply or the answer was still unclear, we considered other methods for imputing data. For example, missing standard deviations (SD) might be calculated from t, P, or Chi² values; a change from the baseline value would be calculated from the baseline value and the final value, and SDs were calculated by methods introduced by Higgins 2021 with a Corr_E = 0.50. If all the methods failed, we described the outcomes qualitatively.

Assessment of heterogeneity

We assessed three types of heterogeneity independently as described below.

Clinical heterogeneity

We used the types of participants, interventions, and outcome measures in each trial to assess clinical heterogeneity. We pooled the data only if the trials had similar types of participants, interventions, and outcome measures.

Methodological heterogeneity

We investigated methodological heterogeneity based on sequence generation, allocation concealment, and blinding.

Statistical heterogeneity

We pooled studies if there was no considerable clinical or methodological heterogeneity. We tested the statistical heterogeneity of the included studies before performing the meta‐analysis. We applied the I² statistics to estimate the impact of the heterogeneity:

• 0% to 40% implied slight heterogeneity;

• 30% to 60% indicated moderate heterogeneity;

• 50% to 90% showed substantial heterogeneity;

• 75% to 100% implied considerable heterogeneity.

We analyzed any apparent heterogeneity (I² > 50%, P < 0.10) to identify its origin and investigated its influence on the conclusion through subgroup analysis and excluding studies that caused significant heterogeneity.

If the methods above could not explain or decrease the statistical heterogeneity, we used the random‐effects model. If there was no or little heterogeneity (I²≤ 50%, P ≥ 0.10), we adopted the fixed‐effect model in the meta‐analysis.

Assessment of reporting biases

We planned to investigate publication bias using a funnel plot only if analyses included more than 10 trials. The asymmetry of the funnel plot might indicate the existence of publication bias.

Data synthesis

We pooled data if there were more than one study with no considerable heterogeneity. We used the Review Manager 5 to perform the meta‐analysis (Review Manager 2020). We used fixed‐effect models in case of no significant heterogeneity between studies (P > 0.1), and we used random‐effects models when heterogeneity measured using the I² statistic was moderate or larger. We used the Mantel‐Haenszel (M‐H) method for dichotomous data, with inverse variance for continuous data. The statistical significance cut‐off point for the hypothesis tested with two‐tailed (z tests) for meta‐analysis was set at α = 0.05.

Subgroup analysis and investigation of heterogeneity

We performed subgroup analysis if there was clinical heterogeneity. Because some studies recruited people diagnosed with other cardiovascular diseases, and reported that some of these participants had hypertension, we conducted subgroup analysis considering different patient compositions.

According to participants with hypertension or mixed hypertension and no hypertension, we carried out the following subgroup analyses:

• participants diagnosed with periodontitis and other cardiovascular diseases except hypertension versus participants diagnosed with periodontitis;

• participants diagnosed with periodontitis versus participants diagnosed with periodontitis and hypertension.

Sensitivity analysis

If applicable, we performed sensitivity analysis, such as only including high‐quality studies, different assumptions on missing data, different models of meta‐analysis, exclusion of studies causing significant statistical heterogeneity, and intention‐to‐treat (ITT) analysis. We reported the results of the sensitivity analysis in detail and presented their impact on the robustness of the conclusions in the Discussion section.

Summary of findings and assessment of the certainty of the evidence

We developed summary of findings tables for important outcomes reported in this review using GRADEproGDT software (GRADEpro GDT). We assessed the certainty of the body of evidence concerning the overall risk of bias of the included studies, the directness of the evidence, the inconsistency of the results, the precision of the estimates, the risk of publication bias, the magnitude of the effect, and whether there was evidence of a dose–response relationship. GRADE categorizes the certainty of the body of evidence as high, moderate, low, or very low quality (Atkins 2004; Guyatt 2008; Higgins 2021).

Results

Description of studies

See Characteristics of included studies, Characteristics of excluded studies, Characteristics of studies awaiting classification, and Characteristics of ongoing studies tables.

Results of the search

The search identified 1768 records, including 1520 from the English and Latin databases, 246 from Chinese databases, and two from the handsearch. After removing duplicates, we excluded 775 reports after screening the titles and abstracts. We assessed the full texts of the remaining 40 records. Finally, we included eight studies (15 records), and excluded 17 studies (23 records). One study is awaiting classification because we have not yet obtained adequate information about it, and one study is ongoing (Figure 1).

1.

Flow diagram of study inclusion. RCT: randomized controlled trial.

Included studies

We included eight RCTs in this review. See Characteristics of included studies table.

Setting

One included study was conducted in Poland (Czesnikiewicz‐Guzik 2019b), two in the UK (D'Aiuto 2006; Tonetti 2007), one in India (Hada 2015), one in Japan (Higashi 2009), two in Australia (Kapellas 2014; Taylor 2010), and one in China (Zhou 2017).

Six studies were set in hospitals (Czesnikiewicz‐Guzik 2019b; D'Aiuto 2006; Hada 2015; Kapellas 2014; Taylor 2010; Tonetti 2007), and Higashi 2009 and Zhou 2017 did not report the location. Seven studies were two‐arm parallel‐group RCTs, but D'Aiuto 2006 had three arms.

Participants

There were 894 participants involved in eight RCTs.

Czesnikiewicz‐Guzik 2019b recruited people with hypertension and moderate‐to‐severe periodontitis; D'Aiuto 2006, Kapellas 2014, and Tonetti 2007 recruited people with severe and generalized periodontitis; Hada 2015 and Higashi 2009 recruited people with stable coronary heart diseases and mild‐to‐moderate chronic periodontitis; Taylor 2010 recruited people with chronic periodontitis with some of them reporting hypertension; and Zhou 2017 recruited adults with prehypertension with moderate‐to‐severe periodontitis.

Classification of the interventions

In five studies, there were periodontal treatments in the intervention group, with no periodontal treatment in the control group (D'Aiuto 2006; Hada 2015; Higashi 2009; Kapellas 2014; Taylor 2010). In the remaining three studies, the intervention group underwent intensive periodontal treatment, and the control group received supra‐gingival scaling (Czesnikiewicz‐Guzik 2019b; Tonetti 2007; Zhou 2017). Therefore, we evaluated the following two comparisons.

• Periodontal treatment versus no treatment (five studies: D'Aiuto 2006; Hada 2015; Higashi 2009; Kapellas 2014; Taylor 2010).

• Periodontal treatment versus supra‐gingival scaling (three studies: Czesnikiewicz‐Guzik 2019b; Tonetti 2007; Zhou 2017).

Measures of primary outcome

Change in systolic and diastolic blood pressure (mmHg)

Seven studies fully reported the primary outcome of our review (change in SBP and DBP) (Czesnikiewicz‐Guzik 2019b; D'Aiuto 2006; Hada 2015; Higashi 2009; Kapellas 2014; Tonetti 2007; Zhou 2017). Although Taylor 2010 did not report BP in the manuscript, we obtained supplemental data on BP from their secondary publication (Muñoz Aguilera 2020 under 'Supplementary material online, Appendix 3'). Some data were flawed in D'Aiuto 2006, therefore they were not included in the meta‐analysis.

Measures of secondary outcomes

Participants diagnosed with hypertension

Czesnikiewicz‐Guzik 2019b recruited people with hypertension and moderate‐to‐severe periodontitis. Three studies included participants with mixed hypertension and no hypertension. Hada 2015 diagnosed participants with mild‐to‐moderate chronic periodontitis and stable coronary heart disease. Similarly, Higashi 2009 recruited people with coronary artery disease and mild‐to‐moderate periodontitis, with some having a medical history of hypertension. Taylor 2010 recruited people with chronic periodontitis, with some participants reporting hypertension.

Adverse events

Kapellas 2014 reported one adverse event, and five studies reported no adverse effects (Czesnikiewicz‐Guzik 2019b; D'Aiuto 2006; Taylor 2010; Tonetti 2007; Zhou 2017). The remaining studies did not mention any adverse effects in their reports (Hada 2015; Higashi 2009).

Plasma levels of inflammatory markers

Five studies reported the mean plasma levels of hs‐CRP (Hada 2015; Higashi 2009; Kapellas 2014; Taylor 2010; Zhou 2017), and four studies reported the mean plasma levels of IL‐6 (Czesnikiewicz‐Guzik 2019b; Higashi 2009; Kapellas 2014; Zhou 2017).

Heart rate

Heart rate was only mentioned as an outcome in Higashi 2009.

Endothelial function

Czesnikiewicz‐Guzik 2019b and Tonetti 2007 determined flow‐mediated dilation as an assessment for the vascular endothelial function to assess endothelial‐independent vasodilation. However, we excluded the flow‐mediated dilation results at month two in Tonetti 2007 because the data were considered flawed. Higashi 2009 measured forearm blood flow (FBF) responses to acetylcholine (ACh) and sodium nitroprusside (SNP), both as endothelium‐independent vasodilators, to evaluate of endothelial function. Zhou 2017 measured circulating endothelial microparticles (EMPs) as a biomarker to evaluate endothelial function clinically. Other studies did not report these variables (D'Aiuto 2006; Hada 2015; Kapellas 2014; Taylor 2010).

Periodontal clinical parameters

Four studies reported CAL, PPD, and BOP in participants with hypertension as percentages or continuous data (Hada 2015; Higashi 2009; Taylor 2010; Zhou 2017). Czesnikiewicz‐Guzik 2019b and Kapellas 2014 only reported CAL and PPD. Two studies did not report periodontal clinical parameters above (D'Aiuto 2006; Tonetti 2007).

Flawed data

D'Aiuto 2006 reported six‐month follow‐up results of two treatment groups and the 2005 article reported a three‐month follow‐up of three groups (D'Aiuto 2005). In D'Aiuto 2006, the participants' demographic characteristics were the same as the 2005 article; however, the baseline values of the outcomes were significantly different. Tonetti 2007 also had flawed data on flow‐mediated dilation in the second month. We contacted the author, but he did not remember the data clearly. Therefore, we excluded these data. According to our analysis methods, we adjusted the MD of SBP at month one from 0.72 mmHg to −0.72 mmHg in Tonetti 2007.

Excluded studies

In this review, we excluded 17 studies for the following reasons.

• Eleven studies had no participants with hypertension or BP reports (Amar 2004; Caula 2014; Cortelli 2015; Ide 2003; NCT01201746; Oz 2007; PAVE 2008; Ramírez 2011; Tüter 2007; Tüter 2010; Ushida 2008).

• In three studies, all participants underwent periodontal treatment (Bizzarro 2017; Perio‐Hyperten 2016; Torumtay 2016).

• Two studies were not RCTs (Lin 2013; Mariotti 2013).

• One study was conducted on participants with metabolic syndrome and periodontitis (López 2012).

Risk of bias in included studies

Overall risk of bias

Czesnikiewicz‐Guzik 2019b, Kapellas 2014, Taylor 2010, Tonetti 2007, and Zhou 2017 had low risk of bias overall. Higashi 2009 had unclear risk of bias overall. The remaining two studies had high risk of bias overall (D'Aiuto 2006; Hada 2015). See Characteristics of included studies table, Figure 2, and Figure 3.

2.

Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.

3.

Risk of bias summary: review authors' judgments about each risk of bias item for each included study.

Allocation

Random sequence generation

All studies clearly described a random method of sequence generation, and we assessed they had low risk of bias in this domain. D'Aiuto 2006, Higashi 2009, Kapellas 2014, and Zhou 2017 used the permuted block approach. Czesnikiewicz‐Guzik 2019b, Hada 2015, Taylor 2010, and Tonetti 2007 used computer‐generated numbers.

Allocation concealment

Seven studies clearly described allocation concealment, and we concluded that they had low risk of bias in this domain (Czesnikiewicz‐Guzik 2019b; D'Aiuto 2006; Hada 2015; Kapellas 2014; Taylor 2010; Tonetti 2007; Zhou 2017).

Higashi 2009 did not describe allocation concealment in sufficient detail to determine the risk of bias and we rated this study at unclear risk of bias.

Blinding

Blinding of participants and personnel

In all studies, it was impossible to blind the participants and personnel because the active and control treatments differed significantly. We deemed that these studies were at high risk of performance bias (Czesnikiewicz‐Guzik 2019b; D'Aiuto 2006; Hada 2015; Higashi 2009; Kapellas 2014; Taylor 2010; Tonetti 2007; Zhou 2017).

Blinding of outcome assessment

Five studies described blinding of outcome assessment, which were at low risk of detection bias (Czesnikiewicz‐Guzik 2019b; Kapellas 2014; Taylor 2010; Tonetti 2007; Zhou 2017). In Hada 2015, the examiner noted all the data, and we deemed it at high risk of detection bias. The remaining two studies provided insufficient information, and we rated the risk of detection bias as unclear (D'Aiuto 2006; Higashi 2009).

Incomplete outcome data

In the studies, loss of participants during the study was expected, as the participants dropped out either because they refused to continue to participate or because they withdrew due to adverse events. We rated two studies at high risk of attrition bias, one because the number of participants in intervention group 2 (oral hygiene instruction plus a regimen of SRP under local anesthesia) in the 2006 article was different from that in the previous article (D'Aiuto 2006), and the other one, because it was unclear which group the participant who dropped out of the study and was excluded from the primary analysis belonged to (Higashi 2009).

The remaining six studies either reported all randomized participants, or recorded the number of losses/withdrawals, and we deemed these studies at low risk of attrition bias (Czesnikiewicz‐Guzik 2019b; Hada 2015; Kapellas 2014; Taylor 2010; Tonetti 2007; Zhou 2017).

Selective reporting

Seven studies reported all the detected variables, or trial authors supplied this information, and we deemed these studies at low risk of reporting bias (Czesnikiewicz‐Guzik 2019b; Hada 2015; Higashi 2009; Kapellas 2014; Taylor 2010; Tonetti 2007; Zhou 2017).

D'Aiuto 2006 did not report the outcomes of the control group, so we rated this trial at high risk of reporting bias.

Other potential sources of bias

Hada 2015 reported different baseline DBPs between groups, with significant differences. It is unclear what type of intervention was used for each participant concerning coronary heart disease, therefore, we deemed it at high risk of other potential sources of bias. The remaining seven studies were at low risk of other potential sources of bias (Czesnikiewicz‐Guzik 2019b; D'Aiuto 2006; Higashi 2009; Kapellas 2014; Taylor 2010; Tonetti 2007; Zhou 2017).

Effects of interventions

See: Table 1; Table 2

Comparison 1. Periodontal treatment versus no treatment for different patient composition

The five studies that included this comparison had subgingival SRP as a component of the interventions while the control group received no treatment (D'Aiuto 2006; Hada 2015; Higashi 2009; Kapellas 2014; Taylor 2010). Because some data of D'Aiuto 2006 were flawed, it was not included in the meta‐analysis considering the credibility of the review. D'Aiuto 2006 and Hada 2015 were at high risk of bias. Kapellas 2014 and Taylor 2010 were at low risk of bias, and Higashi 2009 at unclear risk of bias.

1.1 Change of systolic and diastolic blood pressure

The pooled data did not detect any difference in the short‐term changes in SBP between the periodontal treatment and no‐treatment groups (349 participants; Analysis 1.1; Hada 2015; Kapellas 2014; Taylor 2010). Hada 2015 compared periodontal treatment with no treatment in people diagnosed with periodontitis and other cardiovascular diseases except hypertension, and found no difference in SBP changes (MD 0.59 mmHg, 95% CI −9.18 to 10.36; P = 0.91; 55 participants). Kapellas 2014 and Taylor 2010 included people diagnosed with periodontitis and found no difference (MD −0.14 mmHg, 95% CI −4.05 to 3.77; P = 0.94; I² = 44%; 294 participants).

1.1. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 1: Short‐term change of systolic blood pressure (mmHg)

Three studies reported long‐term changes in SBP (276 participants; Analysis 1.2; Hada 2015; Higashi 2009; Kapellas 2014). Hada 2015 and Higashi 2009 reported no significant SBP changes for people diagnosed with periodontitis or other cardiovascular diseases except hypertension (MD −2.25 mmHg, 95% CI −9.41 to 4.92; P = 0.54; I² = 0%; 108 participants).

1.2. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 2: Long‐term change of systolic blood pressure (mmHg)

For the changes in DBP, there was no evidence of a difference for people diagnosed with periodontitis or other cardiovascular diseases except hypertension between the intervention and control groups over a short or long period (401 participants; Analysis 1.3; Analysis 1.4; Hada 2015; Higashi 2009; Kapellas 2014; Taylor 2010).

1.3. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 3: Short‐term change of diastolic blood pressure (mmHg)

1.4. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 4: Long‐term change of diastolic blood pressure (mmHg)

1.2 Adverse events

Kapellas 2014 reported that one participant in the treatment group experienced a myocardial infarction during the study period. Taylor 2010 reported no adverse effects. The remaining studies did not mention any adverse effects in their reports (Hada 2015; Higashi 2009).

1.3 Heart rate

Higashi 2009 reported no differences in heart rate changes between the two groups in people diagnosed with periodontitis and other cardiovascular diseases except hypertension over a long period (MD −0.70 beats per minute, 95% CI −6.06 to 4.66; P = 0.8; 48 participants; Analysis 1.5).

1.5. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 5: Long‐term change of heart rate (beats per minute)

1.4 Plasma levels of inflammatory markers

Hada 2015, Higashi 2009, Kapellas 2014, and Taylor 2010 reported plasma levels of hs‐CRP, while Higashi 2009 and Kapellas 2014 detected changes in IL‐6.

There was no evidence of a difference in short‐term changes of hs‐CRP between periodontal treatment and control in participants diagnosed with periodontitis and other cardiovascular diseases except hypertension (MD 0.65 mg/L, 95% CI −1.23 to 2.53; P = 0.50; 55 participants; Hada 2015), and participants diagnosed with periodontitis (MD −0.18 mg/L, 95% CI −0.42 to 0.05; P = 0.12; I² = 0%; 294 participants; Analysis 1.6; Kapellas 2014; Taylor 2010). Long‐term outcomes also revealed no differences in participants diagnosed with periodontitis and other cardiovascular diseases except hypertension (MD −0.72 mg/L, 95% CI −1.74 to 0.30; P = 0.17; I² = 0%; 103 participants; Hada 2015; Higashi 2009) and participants diagnosed with periodontitis (MD 1.19 mg/L, 95% CI −0.55 to 2.93; P = 0.18; 168 participants; Analysis 1.7; Kapellas 2014).

1.6. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 6: Short‐term change of high‐sensitivity C‐reactive protein (hs‐CRP) (mg/L)

1.7. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 7: Long‐term change of hs‐CRP (mg/L)

Concentrations of IL‐6 remained relatively stable and similar between the groups in the short term (MD ‐0.34 pg/mL, 95% CI −1.06 to 0.38; P = 0.35; 169 participants; Analysis 1.8; Kapellas 2014). Kapellas 2014 reported that periodontal treatment significantly reduced the plasma levels of IL‐6 in the long term, but only in participants diagnosed with periodontitis (MD −1.60 pg/mL, 95% CI −2.31 to −0.89; P < 0.001; 168 participants), with no changes in participants diagnosed with periodontitis and other cardiovascular diseases except hypertension (MD −0.90 pg/mL, 95% CI −2.97 to 1.17; P = 0.40; 48 participants; Analysis 1.9; Higashi 2009).

1.8. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 8: Short‐term change of interleukin (IL)‐6 (pg/mL)

1.9. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 9: Long‐term change of IL‐6 (pg/mL)

1.5 Endothelial function

Higashi 2009 reported endothelial function as change in FBF, but there was no difference (MD 0.10 mL/(min 100 mL tissue), 95% CI −0.67 to 0.87; P = 0.80; 48 participants; Analysis 1.10).

1.10. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 10: Long‐term change of forearm blood flow (FBF) (mL/(min 100 mL tissue))

1.6 Periodontal clinical parameters

Taylor 2010 (125 participants) and Higashi 2009 (48 participants) provided short‐term and long‐term PPD, CAL, and BOP data to illustrate the effect of periodontal treatment on periodontal tissues in participants diagnosed with periodontitis and other cardiovascular diseases except hypertension. There were clinical and significant changes in PPD over a long period (MD −1.94 mm, 95% CI −2.35 to −1.53; P < 0.001; Analysis 1.12), CAL (MD −1.85 mm, 95% CI −2.41 to −1.29; P < 0.001; Analysis 1.14), and BOP (MD −36.80%, 95% CI −46.47 to −27.13; P < 0.001; Analysis 1.16). There were similar results in the short term (Analysis 1.11; Analysis 1.13; Analysis 1.15).

1.12. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 12: Long‐term change of PPD (mm)

1.14. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 14: Long‐term change of CAL (mm)

1.16. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 16: Long‐term change of BOP (%)

1.11. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 11: Short‐term change of pocket probing depth (PPD) (mm)

1.13. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 13: Short‐term change of clinical attachment level (CAL) (mm)

1.15. Analysis.

Comparison 1: Periodontal treatment versus no treatment, Outcome 15: Short‐term change of bleeding on probing (BOP) (%)

Comparison 2. Periodontal treatment versus supra‐gingival scaling for different patient composition

Three studies were included in this comparison (Czesnikiewicz‐Guzik 2019b; Tonetti 2007; Zhou 2017). All the studies were at low risk of bias.

2.1 Change of systolic and diastolic blood pressure

Two studies (227 participants) reported no difference in changes in SBP between the periodontal treatment and supra‐gingival scaling groups (short‐term: MD −3.55 mmHg, 95% CI −10.09 to 2.98; P = 0.29; I² = 91%; Analysis 2.1; long‐term: MD −6.64 mmHg, 95% CI −16.83 to 3.55; P = 0.20; I² = 96%; Analysis 2.2) (Tonetti 2007; Zhou 2017). Tonetti 2007 included participants with no hypertension, while Zhou 2017 included participants with prehypertension. There were no significant changes in DBP (Analysis 2.3; Analysis 2.4).

2.1. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 1: Short‐term change of systolic blood pressure (mmHg)

2.2. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 2: Long‐term change of systolic blood pressure (mmHg)

2.3. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 3: Short‐term change of diastolic blood pressure (mmHg)

2.4. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 4: Long‐term change of diastolic blood pressure (mmHg)

Concerning people diagnosed with periodontitis and hypertension, Czesnikiewicz‐Guzik 2019b reported significant reductions in SBP (MD −11.2 mmHg, 95% CI −15.4 to −7.0; P < 0.001; 101 participants; Analysis 2.1) and DBP (MD −8.40 mmHg, 95% CI −12.19 to −4.61; P < 0.001; 101 participants; Analysis 2.3) in the second month.

2.2 Adverse events

Czesnikiewicz‐Guzik 2019b, Tonetti 2007, and Zhou 2017 reported no adverse effects.

2.3 Plasma levels of inflammatory markers

Tonetti 2007 and Zhou 2017 compared hs‐CRP levels in participants diagnosed with periodontitis between groups and reported no significant differences (short‐term: MD −0.37 mg/L, 95% CI −1.40 to 0.65; P = 0.47; I² = 61%; Analysis 2.5; long‐term: MD −0.16 mg/L, 95% CI −2.15 to 1.83; P = 0.88; I² = 85%; Analysis 2.6).

2.5. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 5: Short‐term change of high‐sensitivity C‐reactive protein (hs‐CRP) (mg/L)

2.6. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 6: Long‐term change of hs‐CRP (mg/L)

Concerning IL‐6, Tonetti 2007 and Zhou 2017 found no differences in participants with no hypertension, the same as participants with hypertension (MD −6.00 pg/mL, 95% CI −12.68 to 0.68; P = 0.08; Analysis 2.7; Analysis 2.8; Czesnikiewicz‐Guzik 2019b).

2.7. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 7: Short‐term change of interleukin (IL)‐6 (pg/mL)

2.8. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 8: Long‐term change of IL‐6 (pg/mL)

2.4 Endothelial function

Zhou 2017 used EMPs to evaluate endothelial function, reporting significant differences between the intervention and control groups in the short term (MD −384.42 μL, 95% CI −625.58 to −143.26; P = 0.002; 107 participants; Analysis 2.9) and the long term (MD −565.52 μL, 95% CI −806.04 to −325.00; P < 0.001; Analysis 2.10).

2.9. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 9: Short‐term change of endothelial microparticles (EMPs) (μL)

2.10. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 10: Long‐term change of EMPs (μL)

Czesnikiewicz‐Guzik 2019b and Tonetti 2007 used flow‐mediated dilation to evaluate endothelial function in participants with hypertension and participants without hypertension. Czesnikiewicz‐Guzik 2019b reported sufficient evidence of a difference in the short term (MD 1.63%, 95% CI 0.43 to 2.83; P = 0.008; Analysis 2.11). At the same time, Tonetti 2007 reported significant evidence that periodontal treatment improved flow‐mediated dilation in the long term (MD 1.48%, 95% CI 0.67 to 2.29; P < 0.001; 120 participants; Analysis 2.12).

2.11. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 11: Short‐term change of flow‐mediated dilation (%)

2.12. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 12: Long‐term change of flow‐mediated dilation (%)

2.5 Periodontal clinical parameters

Zhou 2017 and Czesnikiewicz‐Guzik 2019b reported PPD, CAL, and BOP. There was a difference in PPD in the short term (MD −11.47 mm, 95% CI −18.54 to −4.40; P = 0.001; Analysis 2.13) and the long term (MD −18.90 mm, 95% CI −26.34 to −11.46; P < 0.001; Analysis 2.14), the same as participants with hypertension in the short term (MD −0.55 mm, 95% CI −0.70 to −0.40; P < 0.001; Analysis 2.13). Zhou 2017 also detected a decrease in CAL in the short term (MD −10.50 mm, 95% CI −17.17 to −3.83; P = 0.002; Analysis 2.15) and the long term (MD −9.38 mm, 95% CI −15.85 to −2.91; P = 0.004; Analysis 2.16), the same as participants with hypertension in the short term (MD −0.49 mm, 95% CI −0.67 to −0.32; P < 0.001; Analysis 2.15). Zhou 2017 reported sufficient evidence that periodontal treatment reduced BOP in the short term (MD −0.42%, 95% CI −0.47 to −0.37; P < 0.001; Analysis 2.17) and the long term (MD −0.40%, 95% CI −0.45 to −0.35; P < 0.001; Analysis 2.18).

2.13. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 13: Short‐term change of pocket probing depth (PPD) (mm)

2.14. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 14: Long‐term change of PPD (mm)

2.15. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 15: Short‐term change of clinical attachment level (CAL) (mm)

2.16. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 16: Long‐term change of CAL (mm)

2.17. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 17: Short‐term change of bleeding on probing (BOP) (%)

2.18. Analysis.

Comparison 2: Periodontal treatment versus supra‐gingival scaling, Outcome 18: Long‐term change of BOP (%)

Discussion

Summary of main results

We included eight RCTs in this review, seven of which reported changes in SBP and DBP. Although Taylor 2010 made no mention of BP in the manuscript, we obtained further information about BP in Muñoz Aguilera 2020 (under 'Supplementary material online, Appendix 3'). Since D'Aiuto 2006 had flawed data, the remaining seven studies were considered suitable for inclusion in the meta‐analysis (Czesnikiewicz‐Guzik 2019b; Hada 2015; Higashi 2009; Kapellas 2014; Taylor 2010; Tonetti 2007; Zhou 2017). These seven studies evaluated the effect of periodontal interventions on BP and were subcategorized into two comparisons.

Periodontal treatment versus no treatment for different patient composition

We analyzed four studies with different compositions (Hada 2015; Higashi 2009; Kapellas 2014; Taylor 2010; 401 participants). Hada 2015 and Higashi 2009 included people diagnosed with periodontitis and other cardiovascular diseases except hypertension; however, there were no significant changes in BP with various patient conditions. Meanwhile, there is insufficient evidence that periodontal treatment could decrease SBP or DBP in the short or long term (Table 1). We found no difference in heart rate, hs‐CRP, or endothelial function after periodontal treatment. However, Kapellas 2014 (168 participants with no hypertension) reported sufficient evidence that periodontal treatment reduced the plasma levels of IL‐6 in the long term. Higashi 2009 and Taylor 2010 (173 participants) noted significant changes in PPD, CAL, and BOP in any length of time.

Periodontal treatment versus supra‐gingival scaling for different patient composition

According to Tonetti 2007 and Zhou 2017 (227 participants), intensive periodontal treatment in participants with no hypertension did not decrease SBP or DBP. However, concerning hypertension, moderate‐certainty evidence proved a reduction in SBP or DBP between the two groups in the second month (101 participants; Table 2; Czesnikiewicz‐Guzik 2019b). In addition, there were no adverse effects reported, and no differences in hs‐CRP and IL‐6 in different patient conditions. Moreover, all the studies indicated the short‐term and long‐term improvements in endothelial function in participants with or without hypertension. Zhou 2017 and Czesnikiewicz‐Guzik 2019b found differences in PPD, CAL, and BOP between intensive periodontal treatment and supra‐gingival scaling.

Overall completeness and applicability of evidence

In this review, we included studies that compared periodontal treatment with either no treatment or supra‐gingival scaling. We noted no differences in SBP and DBP changes between the intervention and control groups in the short or long term. If we focus on participants with hypertension, periodontal treatment could significantly decrease SBP and DBP; however, we consider it imprudent to draw a conclusion based on one single‐center study.

The intervention group underwent intensive periodontal treatment, and the control group received no treatment or supra‐gingival scaling. It is impossible to blind the participants and personnel during periodontal treatment, and we deemed studies at high risk of performance bias. Therefore, all the other domains, except performance bias, were considered key domains.

Some other variables might have influenced the outcomes in the included studies. The diagnosis of moderate‐to‐severe periodontitis in the included studies was at least partly subjective and might have been based on variable diagnostic criteria. We also believe that the participants were diagnosed with some other diseases because of the different aims in different studies. The difference in interventions in people with coronary heart disease (Hada 2015) and coronary artery disease (Higashi 2009) might have influenced the outcomes; however, there were no differences in crucial parameters between the intervention and control groups.

Another source of variability might be the loss of participants in the follow‐up. The studies reported loss of participants due to refusal to continue or because of adverse events. The number of participants in the intervention group 2 (oral hygiene instruction + a regimen of SRP under local anesthesia) in D'Aiuto 2006 was different from that in the previous article, and there was insufficient information about the participants who dropped out of the study (Higashi 2009), leading to incomplete outcome data.

Concerning secondary outcomes, Czesnikiewicz‐Guzik 2019b included participants with hypertension, Hada 2015 and Higashi 2009 included participants with periodontitis and other cardiovascular diseases except hypertension, and the others only included participants diagnosed with periodontitis. This review reported one adverse event in the meta‐analysis. For participants without hypertension, periodontal treatment could decrease IL‐6 after an extended period, but there was no evidence of a reduction in hs‐CRP (Kapellas 2014), and only Higashi 2009 reported heart rate, with no difference. Additionally, this review revealed statistically significant evidence on the improvement in endothelial function. Furthermore, clinical and statistically significant changes could be noted in periodontal clinical parameters between the intervention and control groups.

Quality of the evidence

We included eight RCTs with 894 participants in this review. All studies were prospective RCTs. Five studies were at low risk of bias in all domains except performance bias (Czesnikiewicz‐Guzik 2019b; Kapellas 2014; Taylor 2010; Tonetti 2007; Zhou 2017). In fact, we did not believe that the impact of bias weakened our confidence in the meta‐analysis. Higashi 2009 had an unclear risk of bias, the remaining two studies in the meta‐analysis had a high risk of bias for at least one domain except for performance bias.

We included seven studies suitable for combination in the meta‐analysis. D'Aiuto 2006 did not report the outcomes of the control group, therefore, we did not include it in the meta‐analysis. Tonetti 2007 had flawed data of flow‐mediated dilation at two months, which were excluded. We also changed the MD of SBP from 0.72 to −0.72 at one month, considering the credibility of all the data.

In some results of our review, the high risk of bias, the imprecise CI of the BP, and the considerable heterogeneity between studies provided support for our decision to consider the certainty of the evidence (see Table 1 and Table 2). By comparing periodontal treatment versus no treatment, we considered the certainty of the evidence for short‐term and long‐term changes in SBP and DBP in participants diagnosed with periodontitis and other cardiovascular diseases except hypertension to be very low or low. In contrast, there was low‐certainty evidence for a change in SBP and DBP in participants diagnosed with periodontitis. Meanwhile, by comparing intensive periodontal treatment versus supra‐gingival scaling, we deemed the certainty of evidence for short‐term and long‐term changes in SBP and long‐term changes in DBP in participants diagnosed with periodontitis to be very low, and for short‐term changes in DBP to be low. Instead, the evidence for short‐term changes in SBP and DBP in participants with hypertension deemed to be moderate quality, providing support for our conclusion.

Potential biases in the review process

We limited bias during preparation of this systematic review. Two review authors searched broadly for published and unpublished studies and the reference lists of the included studies with no language restrictions. We contacted some authors to request missing information and received some replies. We contacted the author of Tonetti 2007, but he did not remember the data clearly. Consequently, we changed the MD of SBP at one month from 0.72 to −0.72 according to the reported 95% CI. Additionally, we made several changes to this review since the publication of the protocol (see Differences between protocol and review). A new part named "Presentation of main results" and methods of calculating SD changes from the baseline were added to the methods part. Concerning subgroup analysis, a new subgroup replaced the former because the former became the clue for different comparisons. We acknowledge that such post hoc changes might have introduced the risk of bias in this review. The supplement details were added to the included criteria for this review, including "studies should not have been specific to participants with a history of any other systemic diseases, except for hypertension‐related illness" and "All outcome variables should have been recorded at least one month after the treatment. We defined less than six months as short term and six months or greater as long term".

Agreements and disagreements with other studies or reviews

We found two reviews focusing on the effect of periodontal treatments on BP (Lanau 2020; Oshiro dos Santos 2017). Because of the heterogeneity of the identified studies, Lanau 2020 did not perform a meta‐analysis and reported, by describing the study characteristics, that five of the included studies showed a statistically significant reduction in SBP values, which was unreliable. Oshiro dos Santos 2017 included two studies that recruited people with chronic periodontitis (Hada 2015; Kapellas 2014). Similar to our results, it did not show a statistically significant decrease in SBP and DBP after treatment. In addition, concerning the secondary outcomes, one systematic review focused on the efficacy of periodontal treatment to manage cardiovascular risk factors, claiming that periodontal treatment does not significantly affect hs‐CRP (Deng 2013). Our review confirmed this finding. One systematic review investigated the atherosclerotic profile after periodontal treatment and found that the plasma levels of inflammatory markers (hs‐CRP and IL‐6) significantly reduced after periodontal treatment, and the effect of periodontal treatment on endothelial function was positive (Teeuw 2014). The discrepancy in IL‐6 levels between these two reviews can be explained because some studies included in the Teeuw 2014 meta‐analysis were excluded from our review because of their flawed data and unbalanced baseline. With a more strict assessment of the risk of bias in the included studies, we believe our findings are reliable. Further trials are necessary to establish an association between plasma levels of inflammatory and periodontal treatment.

Authors' conclusions

Implications for practice.

Although the overall benefits of periodontal treatment are well known (preserve the periodontium, improve periodontal health, comfort, esthetics, and function), we could not draw conclusions on the effect of periodontal treatment on blood pressure in people with chronic periodontitis due to a lack of relevant studies and the low certainty of evidence in the few existing studies.

Implications for research.

Studies are needed to explore the effect of periodontal treatment on blood pressure, especially in people with hypertension, overcoming the significant limitations of incomplete outcome data reporting and selective data reporting. Studies should follow the CONSORT statement during reporting to increase the value of research (CONSORT 2012).

For the periodontal treatment application, we suggest using intensive periodontal treatment aiming to control periodontal inflammation, with no limitations on the frequency of supra‐gingival scaling and root planing.

A comparison of intensive periodontal treatment with supra‐gingival scaling can better control for variables and eliminate confounding factors. Studies exploring the effect of different periodontal treatments for periodontitis could routinely record the blood pressure at baseline and different time points, which could quickly provide sufficient data on the effect of periodontal treatment on blood pressure.

History

Protocol first published: Issue 11, 2011

Notes

None.

Appendices

Appendix 1. Cochrane Hypertension Specialised Register via Cochrane Register of Studies (CRS‐Web) search strategy

Search date: 7 November 2020
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

#1 Periodontal Diseases EXPLODE ALL AND INSEGMENT
#2 periodont* AND INSEGMENT
#3 (gingivitis or gingiva*) AND INSEGMENT
#4 paradont* AND INSEGMENT
#5 #1 OR #2 OR #3 OR #4 AND INSEGMENT
#6 (CCT OR RCT):DE AND INSEGMENT
#7 Review:MISC2 AND INSEGMENT
#8 #6 OR #7 AND INSEGMENT
#9 #5 AND #8 AND INSEGMENT

Appendix 2. Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Register of Studies (CRS‐Web) search strategy

Search date: 7 November 2020
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

#1 MESH DESCRIPTOR Periodontal Diseases EXPLODE ALL AND CENTRAL:TARGET
#2 periodont* AND CENTRAL:TARGET
#3 (gingivitis or gingiva*) AND CENTRAL:TARGET
#4 paradont* AND CENTRAL:TARGET
#5 #1 OR #2 OR #3 OR #4 AND CENTRAL:TARGET
#6 MESH DESCRIPTOR Periodontics EXPLODE ALL AND CENTRAL:TARGET
#7 MESH DESCRIPTOR Preventive Dentistry EXPLODE ALL AND CENTRAL:TARGET
#8 MESH DESCRIPTOR Dental Care EXPLODE ALL AND CENTRAL:TARGET
#9 MESH DESCRIPTOR Dental Prophylaxis EXPLODE ALL AND CENTRAL:TARGET
#10 (dental OR dentistry) NEAR2 (prevent* OR prophyla*) AND CENTRAL:TARGET
#11 (scale* OR scaling) NEAR4 polish* AND CENTRAL:TARGET
#12 root NEAR4 plan* AND CENTRAL:TARGET
#13 (dental OR teeth OR tooth) NEAR6 (scale* OR scaling) AND CENTRAL:TARGET
#14 (gingivectomy OR gingivoplasty OR subgingival curretage OR guided tissue regeneration) AND CENTRAL:TARGET
#15 MESH DESCRIPTOR Surgical Flaps AND CENTRAL:TARGET
#16 surgical flap* AND CENTRAL:TARGET
#17 (#15 OR #16) AND periodont* AND CENTRAL:TARGET
#18 periodont* NEAR3 (therap* OR treat* OR surger*) AND CENTRAL:TARGET
#19 MESH DESCRIPTOR Oral Hygiene EXPLODE ALL AND CENTRAL:TARGET
#20 MESH DESCRIPTOR Oral Health AND CENTRAL:TARGET
#21 (mouthrinse* OR mouth rinse* OR mouthwash* OR mouth wash* OR toothbrush* OR tooth brush* OR floss*) AND CENTRAL:TARGET
#22 (mouth hygien* OR oral hygien* OR oral health*) AND CENTRAL:TARGET
#23 MESH DESCRIPTOR Dentifrices EXPLODE ALL AND CENTRAL:TARGET
#24 (dentifrice* OR toothpaste* OR tooth‐paste* OR tooth paste*) AND CENTRAL:TARGET
#25 MESH DESCRIPTOR Chlorhexidine AND CENTRAL:TARGET
#26 (chlorhexidine OR chlorohex* OR corsodyl OR eludril) AND CENTRAL:TARGET
#27 MESH DESCRIPTOR Anti‐Bacterial Agents EXPLODE ALL AND CENTRAL:TARGET
#28 (antibiotic* OR anti‐biotic* OR antibacterial* OR anti‐bacterial* OR antiinfective* OR anti‐infective*) AND CENTRAL:TARGET
#29 MESH DESCRIPTOR Tetracyclines EXPLODE ALL AND CENTRAL:TARGET
#30 (tetracycline* OR doxycycline* OR minocycline* OR roxithromycin* OR moxifloxacin* OR ciprofloxacin* OR metronidazole*) AND CENTRAL:TARGET
#31 (Periostat OR Atridox OR Elyzol OR PerioChip OR Arestin OR Actisite) AND CENTRAL:TARGET
#32 #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #14 OR #13
#33 #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31
#34 #32 OR #33
#35 MESH DESCRIPTOR Hypertension AND CENTRAL:TARGET
#36 (antihypertens* OR hypertens* OR prehypertens*) AND CENTRAL:TARGET
#37 MESH DESCRIPTOR Blood Pressure EXPLODE ALL AND CENTRAL:TARGET
#38 (arterial pressure OR blood pressure OR bloodpressure) AND CENTRAL:TARGET
#39 (bp OR dbp OR sbp) AND CENTRAL:TARGET
#40 #35 OR #36 OR #37 OR #38 OR #39
#41 #5 AND #34 AND #40

Appendix 3. Ovid MEDLINE search strategy

Database: Ovid MEDLINE(R) 1946 to present with Daily Update
Search date: 7 November 2020
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

1 exp periodontal diseases/
2 periodont$.mp.
3 (gingivitis or gingiva$).mp.
4 paradont$.mp.
5 or/1‐4
6 exp periodontics/
7 exp preventive dentistry/
8 exp dental care/ )
9 exp dental prophylaxis/
10 ((dental or dentistry) adj2 (prevent$ or prophyla$)).mp.
11 ((scale$ or scaling) adj4 polish$).mp.
12 (root$ adj4 plan$).mp.
13 ((dental or teeth or tooth) adj6 (scale$ or scaling)).mp.
14 (gingivectomy or gingivoplasty or subgingival curretage or guided tissue regeneration).mp.
15 surgical flaps/
16 surgical flap$.mp.
17 (15 or 16) and periodont$.mp.
18 (periodont$ adj3 (therap$ or treat$ or surger$)).mp.
19 oral hygiene/
20 oral health/
21 (mouthrinse$ or mouth rinse$ or mouthwash$ or mouth wash$ or toothbrush$ or tooth brush$ or floss$).mp.
22 (mouth hygien$ or oral hygien$ or oral health$).mp.
23 exp dentifrices/
24 (dentifrice$ or toothpaste$ or tooth paste$).mp.
25 chlorhexidine/
26 (chlorhexidine or eludril or chlorohex$ or corsodyl).mp.
27 exp anti‐bacterial agents/
28 (antibiotic$ or anti‐biotic$ or antibacterial$ or anti‐bacterial$ or antiinfective$ or anti‐infective$).mp.
29 exp tetracyclines/
30 (tetracycline$ or doxycycline$ or minocycline$ or roxithromycin$ or moxifloxacin$ or ciprofloxacin$ or metronidazole$).mp.
31 (Periostat or Atridox or Elyzol or PerioChip or Arestin or Actisite).mp.
32 or/6‐14
33 or/17‐31
34 32 or 33
35 hypertension/
36 (antihypertens$ or hypertens$ or prehypertens$).tw,kf.
37 exp blood pressure/
38 (arterial pressure or blood pressure or bloodpressure).mp.
39 (bp or dbp or sbp).tw,kf.
40 or/35‐39
41 randomized controlled trial.pt.
42 controlled clinical trial.pt.
43 randomized.ab.
44 placebo.ab.
45 dt.fs.
46 randomly.ab.
47 trial.ab.
48 groups.ab.
49 or/41‐48
50 animals/ not (humans/ and animals/)
51 49 not 50
52 5 and 34 and 40 and 51
53 remove duplicates from 52

Appendix 4. Embase search strategy

Database: Embase <1974 to 6 November 2020>
Search date: 7 November 2020
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

1 exp periodontal disease/
2 periodont$.mp.
3 (gingivitis or gingiva$).mp.
4 paradont$.mp.
5 or/1‐4
6 exp periodontics/
7 exp preventive dentistry/
8 exp dental care/
9 exp dental prophylaxis/
10 ((dental or dentistry or oral) adj2 (prevent$ or prophyla$)).mp.
11 ((scale$ or scaling) adj4 polish$).mp.
12 (root$ adj4 plan$).mp.
13 ((dental or teeth or tooth) adj6 (scale$ or scaling)).mp.
14 (gingivectomy or gingivoplasty or subgingival curretage or guided tissue regeneration).mp.
15 (surgical flap$ and periodont$).mp.
16 (periodont$ adj3 (therap$ or treat$ or surger$)).mp.
17 mouth hygiene/
18 (mouth hygien$ or oral hygien$ or oral health$).mp.
19 (mouthrinse$ or mouth rinse$ or mouthwash$ or mouth wash$ or toothbrush$ or tooth brush$ or floss$).mp.
20 toothpaste/
21 (dentifrice$ or toothpaste$ or tooth paste$).mp.
22 chlorhexidine/
23 (chlorhexidine or eludril or chlorohex$ or corsodyl).mp.
24 exp antiinfective agent/
25 (antibiotic$ or anti‐biotic$ or antibacterial$ or anti‐bacterial$ or antiinfective$ or anti‐infective$).mp.
26 exp tetracycline derivative/
27 (tetracycline$ or doxycycline$ or minocycline$ or roxithromycin$ or moxifloxacin$ or ciprofloxacin$ or metronidazole$).mp.
28 (Periostat or Atridox or Elyzol or PerioChip or Arestin or Actisite).mp.
29 or/6‐28
30 exp hypertension/
31 (antihypertens$ or hypertens$ or prehypertens$).tw,kw.
32 exp blood pressure/
33 (arterial pressure or blood pressure or bloodpressure).mp.
34 (bp or dbp or sbp).tw,kw.
35 or/30‐34
36 randomized controlled trial/
37 crossover procedure/
38 double‐blind procedure/
39 (randomi?ed or randomly).tw.
40 (crossover$ or cross‐over$).tw.
41 placebo.ab.
42 (doubl$ adj blind$).tw.
43 assign$.ab.
44 allocat$.ab.
45 or/36‐44
46 (exp animal/ or animal.hw. or nonhuman/) not (exp human/ or human cell/ or (human or humans).ti.)
47 45 not 46
48 5 and 29 and 35 and 47
49 remove duplicates from 48

Appendix 5. CINAHL EBSCO search strategy

Database: EBSCO CINAHL <1980 to 2020>
Search date: 7 November 2020
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

S54 S5 AND S33 AND S39 AND S53
S53 S40 OR S41 OR S42 OR S43 OR S44 OR S45 OR S46 OR S47 OR S48 OR S49 OR S50 OR S51 OR S52
S52 TI clinic* N1 trial* OR AB clinic* N1 trial*
S51 TI placebo* OR AB placebo*
S50 MH placebos
S49 TI random* OR AB random*
S48 TI trial OR AB trial
S47 AB groups
S46 (singl* blind* OR doubl* blind* OR trebl* blind* OR tripl* blind*)
S45 PT Randomized Controlled Trial
S44 PT Clinical Trial
S43 (MH "Clinical Trials+")
S42 MH Single‐blind Studies OR MH Double‐blind Studies OR MH Triple‐blind Studies OR MH Crossover design OR MH Factorial Design
S41 (MH "Random Assignment")
S40 (MH "Randomized Controlled Trials")
S39 S34 OR S35 OR S36 OR S37 OR S38
S38 TX (bp OR dbp OR sbp)
S37 TX (arterial pressure OR blood pressure OR bloodpressure)
S36 (MH "Blood Pressure+")
S35 TX (antihypertens* OR hypertens* OR prehypertens*)
S34 (MH "Hypertension+") 57,971
S33 S31 OR S32 70,223
S32 S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 51,699
S31 S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 30,645
S30 (Periostat OR Atridox OR Elyzol OR PerioChip OR Arestin OR Actisite
S29 (tetracycline* OR doxycycline* OR minocycline* OR roxithromycin* OR moxifloxacin* OR ciprofloxacin* OR metronidazole*)
S28 (MH "Tetracyclines+")
S27 (antibiotic* OR anti‐biotic* OR antibacterial* OR anti‐bacterial* OR antiinfective* OR anti‐infective*)
S26 (chlorhexidine OR eludril OR chlorohex* OR corsodyl)
S25 (MH "Chlorhexidine")
S24 (dentifrice* OR toothpaste* OR tooth‐paste* OR "tooth paste*")
S23 (MH "Dentifrices")
S22 (mouth hygiene* OR oral hygiene* OR oral health*)
S21 (mouthrinse* OR mouth‐rinse* OR "mouth rinse*" OR mouthwash* OR mouth‐wash* OR "mouth wash*" OR toothbrush* OR "tooth brush*" OR tooth‐brush* OR floss*)
S20 (MH "Oral Health") 7,
S19 (MH "Oral Hygiene+")
S18 periodont* N3 (therap* OR treat* OR surger*)
S17 (S15 OR S16) AND TX periodont*
S16 TX surgical flap*
S15 (MH "Surgical Flaps+")
S14 (gingivectomy OR gingivoplasty OR subgingival curettage* OR guided tissue regeneration)
S13 (dental OR teeth OR tooth) N6 (scale* OR scaling)
S12 root* N4 plan*
S11 (scale* or scaling) N4 polish*
S10 (dental OR dentistry) N2 (prevent* OR prophyla*)
S9 (MH "Dental Prophylaxis+")
S8 (MH "Dental Care+")
S7 (MH "Preventive Dentistry+")
S6 (MH "Periodontics+")
S5 S1 OR S2 OR S3 OR S4
S4 paradont*
S3 (gingivitis OR gingiva*)
S2 periodont*
S1 (MH "Periodontal Diseases+")

Appendix 6. LILACS search strategy

Database: LILACS Bireme <1982 to 2020>
Search date: 7 November 2020
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

(tw:(((gingiv* OR paradont* OR periodon* OR root plan* OR scaling) AND (acaso* OR aleatori* OR azar* OR blind* OR cega* OR cego* OR ciega* OR ciego* OR clinic$ ensaio$ OR clinic$ estud$ OR clinic$ trial$ OR control$ ensaio$ OR control$ stud$ OR control$ trial$ OR mask* OR placebo* OR random*) AND (antihipertens* OR antihypertens* OR blood pressure OR hipertens* OR hypertens* OR prehypertens*)) )) AND (instance:"regional") AND ( db:("LILACS") AND mj:("Hypertension" OR "Cardiovascular Diseases" OR "Blood Pressure") AND type_of_study:("clinical_trials") AND limit:("humans"))

Appendix 7. ClinicalTrials.gov search strategy

Search date: 7 November 2020
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

Study Type: Interventional
Other Terms: randomized
Intervention/Treatment: gingiv* OR paradont* OR periodont* OR root plan* OR scaling
Outcome Measures: blood pressure

Appendix 8. World Health Organization International Clinical Trials Registry Platform (ICTRP) search strategy

Search date: 7 November 2020
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

antihypertens* AND gingiv*
antihypertens* AND paradont*
antihypertens* AND periodont*
antihypertens* AND root plan*
antihypertens* AND scaling
blood pressure AND gingiv*
blood pressure AND paradont*
blood pressure AND periodont*
blood pressure AND root plan*
blood pressure AND scaling
hypertens* AND gingiv*
hypertens* AND paradont*
hypertens* AND periodont*
hypertens* AND root plan*
hypertens* AND scaling
prehypertens* AND gingiv*
prehypertens* AND paradont*
prehypertens* AND periodont*
prehypertens* AND root plan*
prehypertens* AND scaling

Appendix 9. Cochrane Oral Health Specialised Register search strategy

Search date: 7 November 2020
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

#1 (antihypertens* OR arterial pressure OR blood pressure OR bp OR dbp OR hypertens* OR prehypertens* OR sbp) AND ORAL:INREGISTER
#2 (gingiva* OR gingivitis OR paradont* OR periodont*) AND ORAL:INREGISTER
#3 #1 AND #2

Appendix 10. Chinese BioMedical Literature Database search strategy

Search date: 12 November 2020
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

#1. 主题词:高血压/全部树/全部副主题词

#2. 主题词:牙周疾病/全部树/全部副主题词

#3. #1 and #2

Appendix 11. VIP search strategy

Search date: 12 November 2020
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

m=牙周*m=血压

Appendix 12. China National Knowledge Infrastructure search strategy

Search date: 12 November 2020
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

题名='牙周' AND （摘要='血压'）

Appendix 13. Sciencepaper Online search strategy

Search date: 12 November 2020
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

题名=牙周 AND 摘要=血压

Data and analyses

Comparison 1. Periodontal treatment versus no treatment.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Short‐term change of systolic blood pressure (mmHg)	3	349	Mean Difference (IV, Fixed, 95% CI)	‐0.04 [‐3.67, 3.59]
1.1.1 Participants diagnosed with periodontitis and other cardiovascular diseases except hypertension	1	55	Mean Difference (IV, Fixed, 95% CI)	0.59 [‐9.18, 10.36]
1.1.2 Participants diagnosed with periodontitis	2	294	Mean Difference (IV, Fixed, 95% CI)	‐0.14 [‐4.05, 3.77]
1.2 Long‐term change of systolic blood pressure (mmHg)	3	276	Mean Difference (IV, Fixed, 95% CI)	‐0.54 [‐4.38, 3.29]
1.2.1 Participants diagnosed with periodontitis and other cardiovascular diseases except hypertension	2	108	Mean Difference (IV, Fixed, 95% CI)	‐2.25 [‐9.41, 4.92]
1.2.2 Participants diagnosed with periodontitis	1	168	Mean Difference (IV, Fixed, 95% CI)	0.14 [‐4.40, 4.68]
1.3 Short‐term change of diastolic blood pressure (mmHg)	3	349	Mean Difference (IV, Fixed, 95% CI)	‐0.50 [‐2.64, 1.64]
1.3.1 Participants diagnosed with periodontitis and other cardiovascular diseases except hypertension	1	55	Mean Difference (IV, Fixed, 95% CI)	‐2.45 [‐7.95, 3.05]
1.3.2 Participants diagnosed with periodontitis	2	294	Mean Difference (IV, Fixed, 95% CI)	‐0.15 [‐2.47, 2.17]
1.4 Long‐term change of diastolic blood pressure (mmHg)	3	271	Mean Difference (IV, Fixed, 95% CI)	‐0.90 [‐3.27, 1.47]
1.4.1 Participants diagnosed with periodontitis and other cardiovascular diseases except hypertension	2	103	Mean Difference (IV, Fixed, 95% CI)	‐2.55 [‐6.90, 1.80]
1.4.2 Participants diagnosed with periodontitis	1	168	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐3.02, 2.62]
1.5 Long‐term change of heart rate (beats per minute)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.5.1 Participants diagnosed with periodontitis and other cardiovascular diseases except hypertension	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.6 Short‐term change of high‐sensitivity C‐reactive protein (hs‐CRP) (mg/L)	3	349	Mean Difference (IV, Fixed, 95% CI)	‐0.17 [‐0.40, 0.06]
1.6.1 Participants diagnosed with periodontitis and other cardiovascular diseases except hypertension	1	55	Mean Difference (IV, Fixed, 95% CI)	0.65 [‐1.23, 2.53]
1.6.2 Participants diagnosed with periodontitis	2	294	Mean Difference (IV, Fixed, 95% CI)	‐0.18 [‐0.42, 0.05]
1.7 Long‐term change of hs‐CRP (mg/L)	3	271	Mean Difference (IV, Fixed, 95% CI)	‐0.23 [‐1.11, 0.65]
1.7.1 Participants diagnosed with periodontitis and other cardiovascular diseases except hypertension	2	103	Mean Difference (IV, Fixed, 95% CI)	‐0.72 [‐1.74, 0.30]
1.7.2 Participants diagnosed with periodontitis	1	168	Mean Difference (IV, Fixed, 95% CI)	1.19 [‐0.55, 2.93]
1.8 Short‐term change of interleukin (IL)‐6 (pg/mL)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.8.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.9 Long‐term change of IL‐6 (pg/mL)	2	216	Mean Difference (IV, Fixed, 95% CI)	‐1.53 [‐2.20, ‐0.86]
1.9.1 Participants diagnosed with periodontitis and other cardiovascular diseases except hypertension	1	48	Mean Difference (IV, Fixed, 95% CI)	‐0.90 [‐2.97, 1.17]
1.9.2 Participants diagnosed with periodontitis	1	168	Mean Difference (IV, Fixed, 95% CI)	‐1.60 [‐2.31, ‐0.89]
1.10 Long‐term change of forearm blood flow (FBF) (mL/(min 100 mL tissue))	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.10.1 Participants diagnosed with periodontitis and other cardiovascular diseases except hypertension	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.11 Short‐term change of pocket probing depth (PPD) (mm)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.11.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.12 Long‐term change of PPD (mm)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.12.1 Participants diagnosed with periodontitis and other cardiovascular diseases except hypertension	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.13 Short‐term change of clinical attachment level (CAL) (mm)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.13.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.14 Long‐term change of CAL (mm)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.14.1 Participants diagnosed with periodontitis and other cardiovascular diseases except hypertension	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.15 Short‐term change of bleeding on probing (BOP) (%)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.15.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.16 Long‐term change of BOP (%)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.16.1 Participants diagnosed with periodontitis and other cardiovascular diseases except hypertension	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 2. Periodontal treatment versus supra‐gingival scaling.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Short‐term change of systolic blood pressure (mmHg)	3		Mean Difference (IV, Random, 95% CI)	‐5.92 [‐11.45, ‐0.39]
2.1.1 Participants diagnosed with periodontitis	2		Mean Difference (IV, Random, 95% CI)	‐3.55 [‐10.09, 2.98]
2.1.2 Participants diagnosed with periodontitis and hypertension	1		Mean Difference (IV, Random, 95% CI)	‐11.20 [‐15.40, ‐7.00]
2.2 Long‐term change of systolic blood pressure (mmHg)	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.2.1 Participants diagnosed with periodontitis	2		Mean Difference (IV, Random, 95% CI)	‐6.64 [‐16.83, 3.55]
2.3 Short‐term change of diastolic blood pressure (mmHg)	3		Mean Difference (IV, Random, 95% CI)	‐4.04 [‐8.07, ‐0.01]
2.3.1 Participants diagnosed with periodontitis	2		Mean Difference (IV, Random, 95% CI)	‐2.08 [‐4.84, 0.68]
2.3.2 Participants diagnosed with periodontitis and hypertension	1		Mean Difference (IV, Random, 95% CI)	‐8.40 [‐12.19, ‐4.61]
2.4 Long‐term change of diastolic blood pressure (mmHg)	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.4.1 Participants diagnosed with periodontitis	2		Mean Difference (IV, Random, 95% CI)	‐4.96 [‐13.04, 3.13]
2.5 Short‐term change of high‐sensitivity C‐reactive protein (hs‐CRP) (mg/L)	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.5.1 Participants diagnosed with periodontitis	2		Mean Difference (IV, Random, 95% CI)	‐0.37 [‐1.40, 0.65]
2.6 Long‐term change of hs‐CRP (mg/L)	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.6.1 Participants diagnosed with periodontitis	2		Mean Difference (IV, Random, 95% CI)	‐0.16 [‐2.15, 1.83]
2.7 Short‐term change of interleukin (IL)‐6 (pg/mL)	3		Mean Difference (IV, Random, 95% CI)	‐0.20 [‐1.13, 0.73]
2.7.1 Participants diagnosed with periodontitis	2		Mean Difference (IV, Random, 95% CI)	‐0.08 [‐0.78, 0.61]
2.7.2 Participants diagnosed with periodontitis and hypertension	1		Mean Difference (IV, Random, 95% CI)	‐6.00 [‐12.68, 0.68]
2.8 Long‐term change of IL‐6 (pg/mL)	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.8.1 Participants diagnosed with periodontitis	2		Mean Difference (IV, Random, 95% CI)	‐0.20 [‐1.33, 0.93]
2.9 Short‐term change of endothelial microparticles (EMPs) (μL)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.9.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.10 Long‐term change of EMPs (μL)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.10.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.11 Short‐term change of flow‐mediated dilation (%)	2		Mean Difference (IV, Random, 95% CI)	0.67 [‐1.18, 2.51]
2.11.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Random, 95% CI)	‐0.25 [‐1.30, 0.80]
2.11.2 Participants diagnosed with periodontitis and hypertension	1		Mean Difference (IV, Random, 95% CI)	1.63 [0.43, 2.83]
2.12 Long‐term change of flow‐mediated dilation (%)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.12.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.13 Short‐term change of pocket probing depth (PPD) (mm)	2		Mean Difference (IV, Random, 95% CI)	‐5.42 [‐16.05, 5.22]
2.13.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Random, 95% CI)	‐11.47 [‐18.54, ‐4.40]
2.13.2 Participants diagnosed with periodontitis and hypertension	1		Mean Difference (IV, Random, 95% CI)	‐0.55 [‐0.70, ‐0.40]
2.14 Long‐term change of PPD (mm)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.14.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.15 Short‐term change of clinical attachment level (CAL) (mm)	2		Mean Difference (IV, Random, 95% CI)	‐4.92 [‐14.66, 4.82]
2.15.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Random, 95% CI)	‐10.50 [‐17.17, ‐3.83]
2.15.2 Participants diagnosed with periodontitis and hypertension	1		Mean Difference (IV, Random, 95% CI)	‐0.50 [‐0.67, ‐0.32]
2.16 Long‐term change of CAL (mm)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.16.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.17 Short‐term change of bleeding on probing (BOP) (%)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.17.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.18 Long‐term change of BOP (%)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.18.1 Participants diagnosed with periodontitis	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Czesnikiewicz‐Guzik 2019b.

Study characteristics
Methods	Type of study: single‐center parallel RCT Stratification: unclear Sample size calculation: not reported Funding: the European Research Council (ERC and InflammaTENSION; ERC‐CoG‐726318; to T.J.G.) and National Science Centre of Poland grant (2997/B/P01/2009/36) and British Heart Foundation (RE/13/5/30177) Country: Poland Time frame of the study: 10 December 2009 to 5 January 2015
Participants	Centers: 1. University Dental Clinic in Krakow, Poland Inclusion criteria: diagnosed with hypertension in accordance with ESC/ESH diagnostic criteria; receiving stable treatment using ≥ 1 antihypertensive agent, since ≥ 6 months, and had an office BP > 140/90 mmHg at the time of visit (mean of ≥ 3 resting measurements); with moderate (≥ 2 interproximal sites with AL ≥ 4 mm, not on same tooth, or ≥ 2 interproximal sites with PD ≥ 5 mm, not on same tooth) to severe periodontitis (≥ 2 interproximal sites with AL ≥ 6 mm, not on same tooth and ≥ 1 interproximal site with PD ≥ 5 mm), using the Centre for Disease Control–American Association of Periodontology case definitions Exclusion criteria: acute and major chronic inflammatory/immune disorders including autoimmune conditions, infections (including tuberculosis, HIV, hepatitis B, and hepatitis C), pulmonary, liver diseases and malignancies (within the last 5 years) as assessed by the examining clinician; had received treatment with medications known to affect periodontal status (phenytoin and cyclosporine); using any form of systemic or local immunosuppression (including steroids) within the previous 6months; any cause of secondary hypertension Participants type: people with hypertension and moderate‐to‐severe periodontitis Number of participants: total: 101; intervention group: 50; control group: 51 Gender of participants (men/women): total: 57/44; intervention group: 26/24; control group: 31/20 Age of participants (years): total: range: 50–58, mean 54.5; intervention group: range 50–56, mean 53; control group: range 54–58, mean 56 Lost to follow‐up: total: 10; intervention group: 5; control group: 5
Interventions	Intervention group: 1 session of whole mouth supra‐gingival and subgingival scaling of the teeth under local anesthesia with the topical application of 0.2% chlorhexidine gel (PerioKin; UK) + dental hygiene instructions Control group: a single session of supra‐gingival scaling of the teeth + dental hygiene instructions Duration of follow‐up: 2 months
Outcomes	Ambulatory 24‐hour mean SBP (assessed at baseline and 2 months) Ambulatory 24‐hour mean DBP (assessed at baseline and 2 months) Proportion of participants who reported adverse events (2 months) IL‐6 (assessed at baseline and 2 months) Endothelial function: flow‐mediated dilation (assessed at baseline and 2 months) PPD (assessed at baseline and 2 months) CAL (assessed at baseline and 2 months)
Notes	AL: attachment level; BOP: bleeding on probing; BP: blood pressure; CAL: clinical attachment level; DBP: diastolic blood pressure; ESC: European Society of Cardiology; ESH: European Society of Hypertension; hs‐CRP: high‐sensitivity C‐reactive protein; IL‐6: interleukin‐6; PD: probing depth; PPD: pocket probing depth; RCT: randomized controlled trial; SBP: systolic blood pressure; SD: standard deviation; SRP: scaling and root planing.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "All patients who fulfilled criteria and provided informed consent were randomized, after run‐in period, 1:1 using a computer‐generated table to receive either IPT [intensive periodontal treatment] or CPT [control periodontal treatment]". Comment: randomization was adequate.
Allocation concealment (selection bias)	Low risk	Quote: "Treatment allocation was concealed in an opaque envelope". Comment: allocation concealment was adequate.
Blinding of participants and personnel (performance bias) all outcomes	High risk	Quote: "Treatment allocation was concealed in an opaque envelope that was opened on the day of treatment by the treating physician". Comment: intervention group received supra‐gingival and subgingival scaling, and control group received supra‐gingival scaling. It was impossible to achieve blinding of participants and personnel.
Blinding of outcome assessment (detection bias) all outcomes	Low risk	Quote: "All other investigators, including cardiovascular physicians, blood pressure nurses, laboratory staff as well as staff involved in data collection and analysis remained masked to the treatment allocation". Comment: low risk.
Incomplete outcome data (attrition bias) all outcomes	Low risk	Quote: "All the analyses were performed based on the intention‐to‐treat principle, per‐protocol analyses for the outcomes reported are included". Comment: low risk.
Selective reporting (reporting bias)	Low risk	Quote: "Additional details are provided in Supplementary material online". Comment: all the variables detected were reported.
Other bias	Low risk	Quote: "Both study groups did not significantly differ in any of the medical or dental characteristics at baseline". Comment: baseline was comparable.

D'Aiuto 2006.

Study characteristics
Methods	Type of study: parallel RCT Stratification: based on smoking status (current vs non‐current smoker) Sample size calculation: not reported Funding: unrestricted educational grant from Orapharma and by the Periodontal Research Fund of the Eastman Dental Institute Country: UK Time frame of the study: January 2003 to July 2003
Participants	Centers: 1. Department of Periodontology of the Eastman Dental Hospital, University College London Inclusion criteria: ≥ 50% of their dentition with periodontal PPD > 4 mm and with documented radiographic alveolar bone loss Exclusion criteria: known systemic diseases, history or presence (or both) of other infections, systemic antibiotic treatment in the preceding 3 months, treatment with any medication known to affect the serum level of inflammatory markers, lipids, or BP, pregnancy or lactating women, allergy to tetracyclines, as assessed by medical history and physical examination Participants type: people with severe and generalized periodontitis Number of participants: total: 65; intervention group 1: 20; intervention group 2: 21; control group: 24 Gender of participants (men/women): total: 38/27; intervention group 1: 11/9; intervention group 2: 11/10; control group: 16/8. Age of participants (years): total: mean 48; intervention group 1: mean 49 (SD 7); intervention group 2: mean 48 (SD 7); control group: mean 48 (SD 6) Lost to follow‐up: 0
Interventions	Intervention group 1: oral hygiene instruction + regimen of SRP under local anesthesia + local delivery of minocycline (80 [SD 25] mg/participants) Intervention group 2: oral hygiene instruction + a regimen of SRP under local anesthesia Control group: no treatment Duration of follow‐up: 6 months
Outcomes	SBP (assessed at baseline, 1 month, 2 months, and 6 months) DBP (assessed at baseline, 1 month, 2 months, and 6 months) Proportion of participants who reported adverse events (6 months)
Notes	Some data were flawed, so this trial was not included in the statistical analysis regarding the credibility of the data. 2 articles identified. The article published in 2006 reported 6‐month follow‐up results of the 2 treatment groups (all the numbers under 'Participants' above were based on 2 groups) and the 2005 article reported 2‐month follow‐up of 3 groups. The demographic character of the included participants were the same as the 2005 article but the baseline values of the outcomes differed considerably (judgment from the review authors: the investigators might have tested the blood samples at baseline again when testing the 6‐month blood samples, so there might be some differences between the 2 articles). Author replied but provided no useful data.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomized (random permuted block approach) to receive either an IPT [intensive periodontal treatment] or control SPT [standard periodontal treatment]". Comment: the exact methods of sequence generation was described. Low risk.
Allocation concealment (selection bias)	Low risk	Quote: "Allocation to treatment was concealed in an opaque envelope opened by the therapist after completion of the common component of the treatment". Comment: allocation concealment was adequate. Low risk.
Blinding of participants and personnel (performance bias) all outcomes	High risk	Comment: intervention group received SRP under local anesthesia and control group no treatment; it was impossible to achieve blinding of participants and personnel. High risk.
Blinding of outcome assessment (detection bias) all outcomes	Unclear risk	Comment: unclear risk.
Incomplete outcome data (attrition bias) all outcomes	Unclear risk	Comment: in the previous article, there were 21 participants in Intervention group 2 and in 2006 article, there were only 20. We considered that 1 participant in the control group might have been lost to follow‐up after 2 months. Unclear risk.
Selective reporting (reporting bias)	High risk	Comment: the outcomes of control group were not reported. High risk.
Other bias	Low risk	Comment: baseline was comparable. Low risk of bias.

Hada 2015.

Study characteristics
Methods	Type of study: parallel RCT Stratification: unclear Sample size calculation: not reported Funding: unclear Country: India Time frame of the study: May 2013 to October 2014
Participants	Centers: 1. Department of Cardiology of Maharana Yashwantrao Hospital, Mahatma Gandhi Memorial Medical College, Indore, Madhya Pradesh (MP), India Inclusion criteria: > 35 years of age, clinically diagnosed stable coronary heart diseases cases, including stable angina, non‐ST elevation myocardial infarction, ST elevation myocardial infarction, no other systemic disease, never‐smoker, ≥ 14 teeth, with advanced chronic gingivitis and mild‐to‐moderate chronic periodontitis, not undergone any periodontal therapy in the last 12 months Exclusion criteria: not fulfilling criteria of the defined stable coronary heart diseases cases, past or present (or both) smoker, pregnant or lactating women, with any other systemic disease such as diabetes, taking systemic antibiotic therapy in the last 3 months, < 14 teeth, with advanced chronic periodontitis, received any periodontal therapy within last 12 months Participants type: people with stable coronary heart diseases and mild‐to‐moderate chronic periodontitis Number of participants: total: 55; intervention group: 30; control group: 25 Gender of participants (men/women): total: 39/16; intervention group: 18/12; control group: 21/4. Age of participants (years): total: mean 60.33; intervention group: mean 60.43 (SD 10.31); control group: mean 60.21 (SD 9.23) Lost to follow‐up: 3 in the control group
Interventions	Intervention group: SRP + oral hygiene instructions Control group: no periodontal therapy + oral hygiene instructions Duration of follow‐up: 6 months
Outcomes	SBP (assessed at baseline, 1 month, 3 months, and 6 months) DBP (assessed at baseline, 1 month, 3 months, and 6 months) hs‐CRP (assessed at baseline, 1 month, 3 months, and 6 months) PPD (assessed at baseline, 1month, 3 months, and 6 months) CAL (assessed at baseline, 1 month, 3 months, and 6 months) BOP (assessed at baseline, 1 month, 3 months, and 6 months)
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "list of random numbers was generated by using computer in 1:1 ratio". Comment: randomization was adequate.
Allocation concealment (selection bias)	Low risk	Quote: "Allocation concealment was done by sealed opaque envelopes that were sequentially numbered. Only the statistician was blinded for the present study". Comment: allocation concealment was adequate.
Blinding of participants and personnel (performance bias) all outcomes	High risk	Quote: "All patients were given oral hygiene instructions and emphasis was given on proper maintenance of oral hygiene". Comment: intervention group received SRP and control group did not. It was impossible to achieve blinding of participants and personnel.
Blinding of outcome assessment (detection bias) all outcomes	High risk	Quote: "All the biochemical and clinical cardiovascular parameters were noted by the examiner and recorded in the patient's case file for further reference. Data from 55 patients completing the study, were analyzed by the statistician, who was blinded regarding study group identification". Comment: high risk.
Incomplete outcome data (attrition bias) all outcomes	Low risk	Comment: all analyses were based on the intention‐to‐treat principle.
Selective reporting (reporting bias)	Low risk	Comment: all variables detected were reported. Data on CAL, PPD, and BOP were presented in figures.
Other bias	High risk	Quote: "Patient populations were taken only from a single center and drop‐out of the patient resulting in the decrease in the final study population. Impact of medical drug management of coronary heart disease has not been taken into consideration in the final outcome of the study". Comment: unclear what type of intervention for coronary heart disease used for each participant. Baseline DBP differed between groups. High risk.

Higashi 2009.

Study characteristics
Methods	Type of study: parallel RCT Stratification: stratified by site Sample size calculation: no Funding: the Ministry of Education, Science and Culture of Japan Country: Japan Time frame of the study: unclear
Participants	Centers: not reported Inclusion criteria: presence of ≥ 2 teeth with PD ≥ 4 mm and AL ≥ 3 mm; with stenosis ≥ 70% in ≥ 1 proximal epicardial coronary artery; with objective evidence of myocardial infarction or ≥ 1 coronary stenosis ≥ 80%; classic angina without provocative testing Exclusion criteria: people with refractory heart failure and cardiogenic shock with ejection fraction < 30%; had undergone revascularization, percutaneous coronary intervention, or coronary artery bypass grafting within the previous 6 months; with myocardial infarction within the previous 6 months; past and current smokers Participants type: people with coronary artery disease and mild‐to‐moderate periodontitis Number of participants: total: 48; intervention group: 24; control group: 24 Gender of participants (men/women): total: 37/11; intervention group: 19/5; control group: 18/6 Age of participants (years): total: mean 63.5; intervention group: mean 64 (SD 14); control group: mean 63 (SD 13) Lost to follow‐up: 1
Interventions	Intervention group: oral hygiene instructions + subgingival scaling and root planning under local anesthesia + antibiotics used for 4–7 days after intensive therapy + mouth washing and teeth and subgingival brushing every day for 24 weeks Control group: no periodontitis treatment Duration of follow‐up: 24 weeks
Outcomes	SBP (assessed at baseline and 24 weeks) DBP (assessed at baseline and 24 weeks) hs‐CRP (assessed at baseline and 24 weeks) IL‐6 (assessed at baseline and 24 weeks) Heart rate (assessed at baseline and 24 weeks) Endothelial function: forearm blood flow (assessed at baseline and 24 weeks) PPD (assessed at baseline and 24 weeks) CAL (assessed at baseline and 24 weeks) BOP (assessed at baseline and 24 weeks)
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The 48 patients with periodontitis were assigned in a 1:1 ratio using a computer‐generated permuted block randomization". Comment: randomization was adequate.
Allocation concealment (selection bias)	Unclear risk	Comment: allocation concealment was not reported.
Blinding of participants and personnel (performance bias) all outcomes	High risk	Quote: "Dentists who were unaware of any of the study protocols performed a routine oral examination for diagnosis of periodontitis and confirmed the presence of the disease". Comment: intervention group received subgingival SRP and control group did not. It was impossible to achieve blinding of participants and personnel.
Blinding of outcome assessment (detection bias) all outcomes	Unclear risk	Comment: blinding of outcome assessment was not reported.
Incomplete outcome data (attrition bias) all outcomes	Unclear risk	Quote: "Data for one patient who dropped put of the study were excluded from the primary analysis". Comment: it was unclear which group the participant belonged to.
Selective reporting (reporting bias)	Low risk	Comment: all the variables detected were reported.
Other bias	Low risk	Comment: baselines were comparable.

Kapellas 2014.

Study characteristics
Methods	Type of study: parallel RCT Stratification: recruitment site Sample size calculation: yes Funding: the National Health and Medical Research Council (NHMRC) project grant and fellowship, NHMRC Career Development Award, Viertel Senior Medical Research Fellowship, University of Adelaide Divisional scholarship Country: Australia Time frame of the study: begun in June 2010
Participants	Centers: 6. Danila Dilba Health Services (Darwin and Palmerston), Bagot Community Health Centre (Darwin), Royal Darwin Hospital, Darwin Dental Centre (Northern Territory Oral Health Services, Department of Health), Northern Territory Correctional Services (Darwin), and Wurli Wurlinjang (Katherine), Australia Inclusion criteria: aboriginal Australian people aged ≥ 18 years with no history of cardiovascular disease; ≥ 5 natural teeth; ≥ 2 interproximal sites with CAL ≥ 4 mm or ≥ 2 interproximal sites with PD ≥ 5 mm Exclusion criteria: receiving periodontal treatment in the preceding 6 months; history of any cardiovascular condition; rheumatic fever or any other cardiac or medical conditions requiring preventive antibiotic prophylaxis; pregnant women; people with clinically visible endodontic or orofacial infections Participants type: people with moderate periodontitis Number of participants: total: 273; intervention group: 138; control group: 135 Gender of participants (men/women): total: 158/115; intervention group: 77/61; control group: 81/54 Age of participants (years): total: mean 40.25; intervention group: mean 40.2 (SD 10.9); control group: mean 40.3 (SD 9.6) Lost to follow‐up: total: 209; intervention group: 100; control group: 109
Interventions	Intervention group: oral hygiene instructions + supra‐gingival and subgingival SRP Control group: oral hygiene instructions Duration of follow‐up: 12 months
Outcomes	SBP (assessed at baseline, 3 months, and 12 months) DBP (assessed at baseline, 3 months, and 12 months) Proportion of participants who reported adverse events (12 months) hs‐CRP (assessed at baseline, 3 months, and 12 months) IL‐6 (assessed at baseline, 3 months, and 12 months) PPD (assessed at baseline and 12 months) CAL (assessed as percentage of sites with CAL ≥ 3 mm at baseline, 3 months, and 12 months)
Notes	Author contacted and key information on BP at month 3 and month 12 provided.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Participants were randomized on a 1:1 basis to either intervention or control group using permuted block randomization with variable block sizes". Comment: randomization was adequate.
Allocation concealment (selection bias)	Low risk	Quote: "Randomization was allocated by the study clinicians unaware of block sizes following baseline measures". Comment: allocation concealment was adequate.
Blinding of participants and personnel (performance bias) all outcomes	High risk	Quote: "Because of the mode of intervention, clinicians and study participants could not be blinded from allocation grouping". Comment: intervention group received an untimed single‐visit full‐mouth non‐surgical removal of sub‐ and supra‐gingival calculus and plaque biofilm following and control group did not. It was impossible to achieve blinding of participants and personnel.
Blinding of outcome assessment (detection bias) all outcomes	Low risk	Quote: "We made concerted efforts to minimize detection bias in this study by not informing examining clinicians of the original study participant group allocation". Comment: low risk.
Incomplete outcome data (attrition bias) all outcomes	Low risk	Quote: "Loss to follow‐up was ≈35% at both 3 and 12 months, and as such the potential for attrition bias cannot be completely eliminated. There were no significant differences, however, in baseline PWV [pulse wave velocity], IMT [intima‐media thickness], or periodontal parameters when compared between those lost to follow‐up and those completing the follow‐up visits". Comment: low risk.
Selective reporting (reporting bias)	Low risk	Comment: all variables detected were reported.
Other bias	Low risk	Comment: no other bias was detected.

Taylor 2010.

Study characteristics
Methods	Type of study: RCT Stratification: gender Sample size calculation: yes Funding: the Ramaciotti Foundation Country: Australia Time frame of the study: May 2003 to July 2007
Participants	Centers: 1. Sydney Dental Hospital Inclusion criteria: ≥ 6 sites with ≥ 5 mm probing PD and ≥ 2 mm AL at teeth other than the third molars Exclusion criteria: people who reported any other systemic inflammation, infection, or condition requiring antibiotic cover for dental treatment Participants type: people with chronic periodontitis Number of participants: total: 136; intervention group: 68; control group: 68 Gender of participants (men/women): total: 61/64; intervention group: 29/32; control group: 32/32 Age of participants (years): total: mean 53.9; intervention group: mean 52.1 (SD 13.3); control group: mean 55.7 (SD 12.2) Lost to follow‐up: total: 11; intervention group: 7; control group: 4
Interventions	Intervention group: oral hygiene instruction + SRP + necessary extractions of teeth with loss of supporting bone and attachment to the apex, or that could not be restored Control group: no periodontal treatment + additional dental extractions to alleviate pain or discomfort Duration of follow‐up: 3 months
Outcomes	SBP (assessed at baseline and 3 months) DBP (assessed at baseline and 3 months) Proportion of participants who reported adverse events (3 months) hs‐CRP (assessed at baseline and 3 months) BOP (assessed at baseline and 3 months) PPD (assessed at baseline and 3 months) CAL (assessed at baseline and 3 months)
Notes	Further information about BP was provided by Muñoz Aguilera 2020, in an evidence table for interventional studies (under 'Supplementary material online, Appendix 3').
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Subjects were randomized to the intervention or control groups by use of a computer‐generated table with permutations in blocks of four". Comment: randomization was adequate.
Allocation concealment (selection bias)	Low risk	Quote: "Subjects were randomized to the intervention or control groups by use of a computer‐generated table with permutations in blocks of four and with stratification by gender by one of the authors independent of the clinical part of the study (MW). The table was held by a person independent of the study". Comment: allocation concealment was adequate.
Blinding of participants and personnel (performance bias) all outcomes	High risk	Quote: "The table was held by a person independent of the study who would then inform the therapist of the randomization result for the subject". Comment: high risk.
Blinding of outcome assessment (detection bias) all outcomes	Low risk	Quote: "Analysis of the blood samples was performed blinded". Comment: low risk.
Incomplete outcome data (attrition bias) all outcomes	Low risk	Quote: "In the statistical analyses, we elected to include only those patients who attended the appointments at all three scheduled time‐points and not to replace the values missing caused by non‐attendance (complete‐case analysis strategy)". Comment: statistical analyses were adequate including intention‐to‐treat analysis and per‐protocol analysis.
Selective reporting (reporting bias)	Low risk	Comment: all the variables detected were reported.
Other bias	Low risk	Quote: "This indicates that it is unlikely that a bias with regard to hyperlipidemia, hypertension or percentage of sites with bleeding on probing influenced the outcome of the statistical tests". Comment: baseline was comparable.

Tonetti 2007.

Study characteristics
Methods	Type of study: parallel RCT Stratification: unclear Sample size calculation: yes Funding: grants from the University College London Hospital Research and Development Directorate, the British Heart Foundation, the European Research Group on Periodontology, the Periodontology Research Fund of the Eastman Dental Institute, Johnson & Johnson (an unrestricted grant), the Coronary Artery Disease Research Association, the British Heart Foundation, the European Social Fund and Il Circolo, and the Italian Society of Periodontology Country: UK Time frame of the study: September 2003 to March 2005
Participants	Centers: 1. Eastman Dental Hospital, University College London Inclusion criteria: severe generalized periodontitis (PPD > 6 mm and marginal alveolar bone loss of > 30%) with ≥ 50% of their teeth affected Exclusion criteria: presence of systemic disease (e.g. diabetes mellitus or cardiovascular, kidney, liver, or lung disease); history or the presence of any other acute or chronic infections, as assessed on clinical examination and routine laboratory testing, and systemic antibiotic treatment within the previous 3 months or any other, regular medication Participants type: people with severe generalized periodontitis Number of participants: total: 120; intervention group: 61; control group: 59 Gender of participants (men/women): total: 60/60; intervention group: 30/31; control group: 30/29 Age of participants (years): total: mean 47.7; intervention group: mean 47.8 (SD 6.3); control group: mean 47.7 (SD 7.9) Lost to follow‐up: total 6; intervention group: 3; control group: 3
Interventions	Intervention group: oral hygiene instruction + supra‐gingival scaling + subgingival SRP + local delivery of microspheres of minocycline + necessary teeth extraction Control group: oral hygiene instruction + supra‐gingival scaling Duration of follow‐up: 6 months
Outcomes	SBP (assessed at baseline, 1 month, 2 months, and 6 months) DBP (assessed at baseline, 1 month, 2 months, and 6 months) Proportion of participants who reported adverse events (6 months) Endothelial function: flow‐mediated dilation (assessed by ultrasound imaging, assessed at baseline, 1 month, 2 months, and 6 months) hs‐CRP (assessed at baseline, 1 month, 2 months, and 6 months) IL‐6 (assessed at baseline, 1 month, 2 months, and 6 months)
Notes	Some error existed in the data provided from the article. We contacted the authors, who stated that they did not remember the data clearly. After analysis, we changed the MD of SBP at 1 month from 0.72 to −0.72 and excluded the results of flow‐mediated dilation at 2 months for those data with errors.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomly assigned with the use of a computer‐generated table to receive intensive periodontal treatment (the intensive‐treatment group) or community‐based periodontal care (the control‐treatment group)". Comment: randomization was adequate. Low risk.
Allocation concealment (selection bias)	Low risk	Quote: "Treatment assignments were concealed in opaque envelopes and revealed to the therapist only on the day the treatment was administered". Comment: allocation concealment was adequate. Low risk
Blinding of participants and personnel (performance bias) all outcomes	High risk	Comment: intervention group received SRP under local anesthesia and control group only received supra‐gingival scaling; it was impossible to achieve blinding of participants and personnel. High risk.
Blinding of outcome assessment (detection bias) all outcomes	Low risk	Quote: "Serum and plasma samples were obtained from the patients and were immediately processed and stored at −70°C until analysis by laboratory staff who were unaware of the treatment assignments and vascular findings". Comment: low risk.
Incomplete outcome data (attrition bias) all outcomes	Low risk	Quote: "All analyses were based on the intention‐to‐treat principle and were performed by investigators who were unaware of the treatment assignments". Comment: low risk.
Selective reporting (reporting bias)	Low risk	Comment: all the variables detected were reported. Low risk.
Other bias	Low risk	Quote: "Supported by grants from … Johnson & Johnson (an unrestricted grant) …" Comment: baselines were comparable. Although there was some funding from companies, we believe the influence to the risk of bias was extremely small. Low risk.

Zhou 2017.

Study characteristics
Methods	Type of study: parallel RCT Stratification: unclear Sample size calculation: yes Funding: 973 Program from Ministry of Science and Technology, the National Nature Science Foundation of China, Guangdong Province Science and Technology Plan Foundation and the Internal Program of the First Affiliated Hospital of Guangdong Pharmaceutical University Country: China Time frame of the study: 7 December 2012 to 31 May 2014
Participants	Centers: not reported Inclusion criteria: aged ≥ 18 years; with prehypertension (SBP 120–139 mm Hg or DBP 80–89 mm Hg, or both); with moderate periodontitis (either 2 sites between adjacent teeth with ≥ 4 mm AL or ≥ 2 such sites with ≥ 5 mm PD) to severe periodontitis (≥ 2 sites between adjacent teeth with ≥ 6 mm AL and ≥ 1 ≥ 5 mm PD); having ≥ 16 natural teeth excluding third molars; be capable of providing informed consent and be never smoked Exclusion criteria: history of antibiotic use in the previous 3 months; pregnant or lactating women; systemic diseases such as diabetes, HIV/AIDS, liver disease, chronic renal failure, tuberculosis, and autoimmune diseases; medical history of cardiovascular disease: acute myocardial infarction, stable angina, unstable angina, heart failure, atrial fibrillation, atrioventricular blockade, peripheral vascular disease, cerebrovascular accident, hypertension; received periodontal treatment within last 6 months; required antibiotic prophylaxis before exam or treatment; with mental retardation and dementia Participants type: people with prehypertension with moderate‐to‐severe periodontitis Number of participants: total: 107; intervention group: 53; control group: 54 Gender of participants (men/women): total: 56/51; intervention group: 28/25; control group: 28/26 Age of participants (years): total: mean 39.68; intervention group: mean 38.38 (SD 9.31); control group: mean 41 (SD 8.64) Lost to follow‐up: total: 12; intervention group: 7; control group: 5
Interventions	Intervention group: oral hygiene instructions + supra‐gingival scaling + subgingival SRP + necessary extraction of teeth + minocycline hydrochloride ointment locally delivered into the periodontal pockets once per week for 4 continued weeks Control group: oral hygiene instructions + supra‐gingival scaling Duration of follow‐up: 6 months
Outcomes	SBP (assessed at baseline, 1 month, 3 months, and 6 months) DBP (assessed at baseline, 1 month, 3 months, and 6 months) Proportion of participants who reported adverse events (6 months) hs‐CRP (assessed at baseline, 1 month, 3 months, and 6 months) IL‐6 (assessed at baseline, 1 month, 3 months, and 6 months) Endothelial function: endothelial microparticles (assessed at baseline, 1 month, 3 months, and 6 months) PPD (assessed as percentage of sites with PPD ≥ 4 mm at baseline, 3 months, and 6 months) CAL (assessed as percentage of sites with CAL ≥ 3 mm at baseline, 3 months, and 6 months) BOP (assessed at baseline, 3 months, and 6 months)
Notes	Author not contacted.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A computer‐generated permuted block randomization sequence was used to assigned participants (1:1)". Comment: randomization was adequate.
Allocation concealment (selection bias)	Low risk	Quote: "The random allocation sequence was implemented with sequentially numbered study opaque envelopes, and the assignments were revealed to the dentists only on the day the treatment was administered". Comment: allocation concealment was adequate.
Blinding of participants and personnel (performance bias) all outcomes	High risk	Quote: "Participants and calibrated dentists knew the allocation groups". Comment: intervention group got SRP and control group did not. It was impossible to achieve blinding of participants and personnel.
Blinding of outcome assessment (detection bias) all outcomes	Low risk	Quote: "All calibrated investigators and outcomes assessors were blinded to the treatment assignments throughout the study". Comment: low risk.
Incomplete outcome data (attrition bias) all outcomes	Low risk	Quote: "Incomplete data were imputed, whereby the last observation was carried forward to allow for analysis on completed participant data". Comment: low risk.
Selective reporting (reporting bias)	Low risk	Comment: all the variables detected were reported.
Other bias	Low risk	Comment: baseline was comparable.

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Amar 2004	Participants with no hypertension. Blood pressure not reported.
Bizzarro 2017	All participants received periodontal treatment.
Caula 2014	Participants with no hypertension. Blood pressure not reported.
Cortelli 2015	Participants with no hypertension. All participants received periodontal treatment. Blood pressure not reported.
Ide 2003	Participants with no hypertension. Blood pressure not reported.
Lin 2013	Not randomized controlled trials or quasi‐randomized controlled trials.
López 2012	Clinical trial conducted in people with metabolic syndrome and periodontitis.
Mariotti 2013	Not randomized controlled trials or quasi‐randomized controlled trials.
NCT01201746	Trial specified to participants with cardiovascular disease. Blood pressure not reported.
Oz 2007	Participants with no hypertension. Blood pressure not reported.
PAVE 2008	Trial specified to people with cardiovascular disease. Blood pressure not reported.
Perio‐Hyperten 2016	All participants received scaling and root planing.
Ramírez 2011	Participants with no hypertension. Blood pressure not reported.
Torumtay 2016	All participants received supra‐gingival scaling. Blood pressure not reported.
Tüter 2007	Not all the participants had hypertension. Blood pressure not reported.
Tüter 2010	Participants with no hypertension. Blood pressure not reported.
Ushida 2008	Participants with no hypertension. Blood pressure not reported.

Characteristics of studies awaiting classification [ordered by study ID]

Vidal 2009.

Methods	Type of study: parallel RCT Stratification: unclear Sample size calculation: yes Funding: the Rio de Janeiro State Research Foundation, Rio de Janeiro, Brazil Country: Brazil Time frame of the study: June 2007 to December 2007
Participants	Centers: 1. Hypertension Department, National Institute of Cardiology, Brazil Inclusion criteria: ≥ 12 teeth, ≥ 4 sites with PD ≥ 4 mm and 5 sites with CAL ≥ 6 mm, and compliance with treatment for hypertension; with severe primary non‐responsive (refractory) arterial hypertension (blood pressure levels remain > 140/90 mm Hg while a participant is engaged in a treatment program and uses ≥ 3 classes of antihypertensive drugs, including a diuretic) Exclusion criteria: pregnancy, previous periodontal therapy, systemic conditions that contraindicated periodontal therapy or that might affect the progression or treatment of periodontitis (e.g. diabetes mellitus or history of infective endocarditis), and the use of medications (e.g. antibiotics or anti‐inflammatory drugs) Participants type: people with moderate generalized periodontitis and refractory arterial hypertension. Number of participants: total: 22; intervention group: 11; control group: 11 Gender of participants (men/women): total: 11/11; intervention group: 5/6; control group: 6/5 Age of participants (years): total: range: 39–62, mean 49.3; intervention group: range 43–56, mean 48.9 (SD 3.9); control group: range 39–62, mean 49.7 (SD 6.0) Lost to follow‐up: 0.
Interventions	Intervention group: oral hygiene instruction + subgingival scaling and root planing + supra‐gingival scaling Control group: no treatment Duration of follow‐up: 6 months
Outcomes	hs‐CRP (assessed at baseline and 3 months) IL‐6 (assessed at baseline and 3 months) PPD (assessed as percentage of sites with PPD ≥ 4 mm at baseline and 3 months) CAL (assessed as percentage of sites with CAL ≥ 4 mm at baseline and 3 months) BOP (assessed at baseline and 3 months)
Notes	Author provided blood pressure at baseline, did not report that at 3 months. Author contacted but not replied.

BOP: bleeding on probing; CAL: clinical attachment level; hs‐CRP: high‐sensitivity C‐reactive protein; IL‐6: interleukin‐6; PD: probing depth; PPD: pocket probing depth; RCT: randomized controlled trial.

Characteristics of ongoing studies [ordered by study ID]

PERIOTENSION 2020.

Study name	Periodontal management in hypertensive patients
Methods	Type of study: parallel double‐blind RCT Stratification: unclear Sample size calculation: unclear Funding: unclear Country: Italy Estimated completion date: December 2024
Participants	Centers: 1. University of L'Aquila Inclusion criteria: treated hypertension; have ≥ 20 natural teeth; presence of any form of periodontal diseases according to guidelines; absence of other significant oral infections Exclusion criteria: secondary hypertension (known plasma renin screening, abdominal ultrasound with doppler and other investigations); pregnant or lactating women; primary pulmonary hypertension; professional oral hygiene within past 6 months; influenza, rhinitis, sinusitis, etc. within past 4 weeks; use of antibiotics within past 4 weeks; hospitalization for any reason within the past 3 months; allergic disorders; history of chronic infectious disease, chronic hepatitis B or C infection; chronic obstructive pulmonary disease, tuberculosis; other known chronic inflammatory or autoimmune condition such as lupus or rheumatoid arthritis, ulcerative colitis, or Crohn's disease; use of systemic or local steroids or immunosuppressive agents within 6 months of the inclusion; history of alcohol abuse or unwillingness to limit alcohol consumption to < 4 drinks per week Participants type: people with periodontal diseases and hypertension Estimated enrollment: total: 100
Interventions	Intervention group: full‐mouth professional oral hygiene consisting in scaling and root planing, 4 quadrants in 1 session Control group: electric toothbrushes twice a day Duration of follow‐up: 1 week
Outcomes	Systolic blood pressure (assessed at baseline and 1 week) Diastolic blood pressure (assessed at baseline and 1 week) BOP (assessed at baseline and 1 week) PPD (assessed at baseline and 1 week) CAL (assessed at baseline and 1 week)
Starting date	June 2024
Contact information	Davide Pietropaoli, telephone: +39 0862 434974; email: davide.pietropaoli@univaq.it Rita Del Pinto, email: rita.delpinto@univaq.it
Notes	NCT04328389

BOP: bleeding on probing; CAL: clinical attachment level; PPD: pocket probing depth; RCT: randomized controlled trial.

Differences between protocol and review

We updated the review to comply with current Cochrane guidelines (Higgins 2021).

Xiaoping Chen was a co‐author of the protocol but is not a co‐author of this review.

Dealing with missing data: we added methods of calculating changes from the baseline standard deviation "and SD were calculated by methods introduced by Higgins 2011 with a Corr_E = 0.50".

Subgroup analysis and investigation of heterogeneity: we replaced "the different types of periodontal treatment" with "different patient composition", with the former becoming the clue for different comparisons.

Types of participants: we replaced "studies should not be specific to participants with a history of any other systemic diseases" with "studies should not have been specific to participants with a history of any other systemic diseases, except for hypertension‐related illness".

Types of outcome measures: we added "We defined less than six months as short term and six months or greater as long term" to "All outcome variables should have been recorded at least one month after the treatment".

Contributions of authors

YL, HY, and WL were first co‐authors of this review.

YL and HY carried out the study selection, data extraction and risk of bias assessment procedures.

WL, ZL, YJ, YZ, and CL carried out statistical analysis and outcome explanation.

WL, ZL, YZ, and CL wrote the draft and revised the review.

ZL and CL provided clinical input for this review.

YL, HY, WL, ZL, YJ, YZ, and CL revised and approved the final version of the review.

Sources of support

Internal sources

• West China School of Stomatology, Sichuan University, China

  This review was supported by the West China College of Stomatology, Sichuan University academically and in staff resources; statistical analysis was supported by the Chinese Cochrane Center.

External sources

• UK Cochrane Centre, UK

  The UK Cochrane Centre supported this project. The production of this review received the supports of many editors from the Cochrane Hypertension Group.

• 2011 Aubrey Sheiham Public Health & Primary Care Scholarship, UK

  The Aubrey Sheiham Public Health and Primary Care Scholarship is a three‐month scholarship offered annually by Cochrane to health workers, consumers, and researchers living in low‐ to middle‐income countries. Thẹ aim of the Scholarship is to enable the development of skills in preparing systematic reviews of healthcare interventions within Cochrane. The Scholarship is awarded annually for work on a topic related to public health or primary health care.

Declarations of interest

LY: nothing to declare.

YH: nothing to declare.

LW: nothing to declare.

LZL: nothing to declare.

JY: nothing to declare.

LC: nothing to declare.

ZY: nothing to declare.

Huilin Ye, Yuxue Luo and Wei Liu are co‐first authors of this review

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