Periodontal therapy for the management of cardiovascular disease in patients with chronic periodontitis

  • Review
  • Intervention

Authors

  • Chunjie Li,

    1. West China Hospital of Stomatology, Sichuan University, State Key Laboratory of Oral Diseases, Department of Head and Neck Oncology, Chengdu, Sichuan, China
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  • Zongkai Lv,

    1. Nan Chong Central Hospital, Second Clinical Medical College of Chuan Bei Medical College, Department of Stomatology, Nanchong, Sichuan, China
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  • Zongdao Shi,

    1. West China Hospital of Stomatology, Sichuan University, State Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, Chengdu, Sichuan, China
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  • Ye Zhu,

    1. West China Hospital, Sichuan University, Department of Cardiovascular Disease, Chengdu, Sichuan, China
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  • Yafei Wu,

    1. West China Hospital of Stomatology, Sichuan University, State Key Laboratory of Oral Diseases, Department of Periodontology, Chengdu, Sichuan, China
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  • Longjiang Li,

    Corresponding author
    1. West China Hospital of Stomatology, Sichuan University, State Key Laboratory of Oral Diseases, Department of Head and Neck Oncology, Chengdu, Sichuan, China
    • Longjiang Li, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, State Key Laboratory of Oral Diseases, No. 14, Section Three, Ren Min Nan Road, Chengdu, Sichuan, 610041, China. ljli007@163.com.

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  • Zipporah Iheozor-Ejiofor

    1. School of Dentistry, The University of Manchester, Cochrane Oral Health Group, Manchester, UK
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Abstract

Background

There is an association between chronic periodontitis and cardiovascular disease (CVD). However, it is not known whether periodontal therapy could prevent or manage CVD in patients with chronic periodontitis.

Objectives

The objective of this systematic review was to investigate the effects of periodontal therapy in preventing the occurrence of, and management or recurrence of, CVD in patients with chronic periodontitis.

Search methods

The electronic databases that were searched were the Cochrane Oral Health Group's Trials Register (to 7 April 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 3), MEDLINE via OVID (1946 to 7 April 2014), EMBASE via OVID (1980 to 7 April 2014), CINAHL via EBSCO (1937 to 7 April 2014), OpenGrey (to 7 April 2014), the Chinese BioMedical Literature Database (1978 to April 2014), the China National Knowledge Infrastructure (1994 to April 2014) and the VIP database (1989 to April 2014). We searched the US National Institutes of Health Trials Register, the World Health Organization (WHO) Clinical Trials Registry Platform and Sciencepaper Online for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.

Selection criteria

Randomised controlled trials (RCTs) and quasi-RCTs were considered eligible. Studies were selected if they included patients with a diagnosis of chronic periodontitis and previous CVD (secondary prevention studies) or no CVD (primary prevention studies); patients in the intervention group received active periodontal therapy compared to maintenance therapy, no periodontal treatment or another kind of periodontal treatment in the control group.

Data collection and analysis

Two review authors carried out the study identification, data extraction and risk of bias assessment independently and in duplicate. Any discrepancies between the two authors were resolved by discussion or with a third review author. A formal pilot-tested data extraction form was adopted for the data extraction, and the Cochrane Collaboration's tool for risk of bias assessment was used for the critical appraisal of the literature.

Main results

No studies were identified that assessed primary prevention of CVD in people with periodontitis. One study involving 303 participants with ≥ 50% blockage of one coronary artery or a coronary event within three years, but not the three months prior, was included. The study was at high risk of bias due to deviation from the protocol treatment allocation and lack of follow-up data. The trial compared scaling and root planing (SRP) with community care for a follow-up period of six to 25 months. No data on deaths (all-cause or CVD-related) were reported. There was insufficient evidence to determine the effect of SRP and community care in reducing the risk of CVD recurrence in patients with chronic periodontitis (risk ratio (RR) 0.72; 95% confidence interval (CI) 0.23 to 2.22; very low quality evidence). The effects of SRP compared with community care on high-sensitivity C-reactive protein (hs-CRP) (mean difference (MD) 0.62; -1.45 to 2.69), the number of patients with high hs-CRP (RR 0.77; 95% CI 0.32 to 1.85) and adverse events (RR 9.06; 95% CI 0.49 to 166.82) were also not statistically significant. The study did not assess modifiable cardiovascular risk factors, other blood test results, heart function parameters or revascularisation procedures.

Authors' conclusions

We found very low quality evidence that was insufficient to support or refute whether periodontal therapy can prevent the recurrence of CVD in the long term in patients with chronic periodontitis. No evidence on primary prevention was found.

Résumé scientifique

Traitement parodontal pour la gestion des maladies cardiovasculaires chez les patients atteints de parodontite chronique

Contexte

Il existe une association entre la parodontite chronique et les maladies cardiovasculaires. Cependant, on ne sait pas si le traitement du parodonte permet de prévenir ou de traiter les maladies cardiovasculaires chez les patients atteints de parodontite chronique.

Objectifs

L'objectif de cette revue systématique était d'étudier les effets du traitement parodontal dans la prévention et le traitement de maladies cardiaques de novo ou récidivantes chez les patients atteints de parodontite chronique.

Stratégie de recherche documentaire

Les bases de données électroniques dans lesquelles nous avons effectué notre recherche comprenaient le registre d'essais du Groupe Cochrane sur la santé bucco-dentaire (jusqu'au 7 avril 2014), le registre Cochrane des essais contrôlés (CENTRAL) (La Bibliothèque Cochrane 2014, numéro 3), MEDLINE via OVID (de 1946 au 7 avril 2014), EMBASE via OVID (de 1980 au 7 avril 2014), CINAHL via EBSCO (de 1937 au 7 avril 2014), OpenGrey (jusqu'au 7 avril 2014), la Base de données de littérature biomédicale chinoise (de 1978 à avril 2014), l'Infrastructure nationale de connaissances chinoise (de 1994 à avril 2014) et la base de données VIP (de 1989 à avril 2014). Nous avons effectué une recherche dans le Registre des essais des US National Institutes of Health, ainsi que dans le système d'enregistrement international des essais cliniques (ICTRP) de l'Organisation mondiale de la Santé (OMS) et Sciencepaper Online pour trouver des essais en cours. Aucune restriction de langue ou de date de publication n'a été imposée lors de la recherche dans les bases de données électroniques.

Critères de sélection

Les essais randomisés (ECR) et quasi-ECR ont été considérés comme éligibles. Les études ont été sélectionnées si elles incluaient des patients avec un diagnostic de parodontite chronique et des antécédents de maladie cardiovasculaire (études de prévention secondaire) ou sans maladie cardiovasculaire (études de prévention primaire) et si les patients du groupe d'intervention avaient reçu un traitement parodontal actif comparé avec un traitement d'entretien, à l'absence de traitement parodontal ou à un autre type de traitement parodontal dans le groupe témoin.

Recueil et analyse des données

Deux auteurs ont procédé à l'identification des études, à l'extraction des données et à l'évaluation du risque de biais de façon indépendante et en double. Les divergences éventuelles entre les deux auteurs ont été résolues par la discussion ou avec un troisième auteur de la revue. Un formulaire d'extraction de données formel, testé sous son format pilote, a été adopté pour l'extraction des données, et l'outil d'évaluation du risque de biais de la Collaboration Cochrane a été utilisé pour l'évaluation critique de la littérature.

Résultats principaux

Nous n'avons identifié aucune étude évaluant la prévention primaire des maladies cardiovasculaires chez les personnes souffrant de parodontite. Une étude portant sur 303 participants ayant eu une occlusion à ≥ 50 % d'une artère coronaire ou un événement coronarien dans les trois ans, mais pas les trois mois précédents, a été incluse. L'étude était à haut risque de biais en raison de la déviation par rapport au protocole d'affectation du traitement et au manque de données de suivi. L'essai comparait le détartrage et le surfaçage radiculaire avec des soins de proximité sur une période de 6 à 25 mois de suivi. Aucune donnée sur les décès (toutes causes confondues ou causes cardiovasculaires) n'a été rapportée. Il n'y avait pas suffisamment de preuves pour déterminer l'effet du surfaçage radiculaire ou des soins de proximité sur la réduction du risque de récidive de la maladie cardiovasculaire chez les patients atteints de parodontite chronique (risque relatif (RR) 0,72 ; intervalle de confiance (IC) à 95 % de 0,23 à 2,22 ; preuves de très faible qualité). Les effets du surfaçage radiculaire par rapport aux soins de proximité sur le dosage de la protéine C-réactive à haute sensibilité (PCR-hs) (différence moyenne (DM) 0,62 ; IC à 95 % de -1,45 à 2,69), le nombre de patients présentant une élévation de la PCR-hs (RR 0,77 ; IC à 95 % de 0,32 à 1,85) et les événements indésirables (RR 9,06 ; IC à 95 % de 0,49 à 166,82) n'étaient pas non plus statistiquement significatifs. L'étude n'a pas évalué les facteurs modifiables de risque cardiovasculaire, les autres résultats des analyses de sang, les paramètres de la fonction cardiaque ou les procédures de revascularisation.

Conclusions des auteurs

Nous avons trouvé des preuves de très faible qualité, insuffisantes pour confirmer ou infirmer l'idée que le traitement parodontal peut prévenir la réapparition de maladies cardiovasculaires à long terme chez les patients atteints de parodontite chronique. Nous n'avons trouvé aucun élément de preuve concernant la prévention primaire.

Notes de traduction

Traduction réalisée par le Centre Cochrane Français

摘要

對慢性牙周炎病患進行牙周炎治療以助控制心血管疾病

背景

慢性牙周炎與心臟血管疾病之間有關聨。然而,對慢性牙周炎病人進行牙周炎治療,可否防止或控制心血管疾病,則未經證實。

目的

於慢性牙周炎病人進行牙周炎治療,能否預防心血管病初發或復發。

搜尋策略

我們搜尋以下直到2014年4月的12個電子資料庫:考科藍口腔健康註冊試驗, 考科藍對照試驗中心註冊(CENTRAL) (The Cochrane Library, 2014年第3期), MEDLINE via OVID, EMBASE via OVID, CINAHL via EBSCO, OpenGrey, the Chinese BioMedical Literature Database, the China National Knowledge infrastructure, VIP database, the US National Institutes of Health Trials Register, 世界衛生組織(WHO) Clinical Trials Registry Platform, Sciencepaper Online. 搜尋的語文及發表日期不設限制。

選擇標準

我們納入隨機對照試驗 (RCTs) 及準隨機對照試驗 (quasi-RCTs) 中,慢性牙周炎患者曾罹患心血管疾病(次級預防研究),或從未罹患心血管疾病 (初級預防研究); 介入組接受積極牙周炎治療,對照組接受牙周維護、沒有治療、或其他種類治療。

資料收集與分析

2位回顧作者獨立選擇文獻、萃取資料、及評估偏差風險。不同意之處2位作者互相討論,或與第3位作者協商至有共識。資料萃取根據考科藍合作組織風險與誤差評估工具進行嚴格的文獻評讀。

主要結果

沒有文獻記載對於牙周炎患者心血管疾病(CVD)初級預防的評估。只有一篇硏究包含303位在3個月至3年間,曾經有單一冠狀動脈大於50%閉塞,或冠狀動脈事件的病人。它比較6-25個月間,牙結石刮除-牙根整平術 (SRP) 或社區照䕶的效果。由於偏離治療規範分配及缺乏後續資料,此硏究的偏差風險很高,亦沒有報導因仼何原因或心血管疾病引起的死亡。至於牙結石刮除-牙根整平術和社區照顧,可否減低慢性牙周炎患者心血管疾病復發的風險,則沒有足夠證據 (RR 0.72; 95% CI 0.23 -2.22; 證據質量很低)。 關於牙結石刮除-牙根整平術相較於社區照顧,在影響高敏感性C-reactive 蛋白質 (hs-CRP) (MD 0.62; -1.45 -2.69) , 有高hs-CRP (RR 0.77; 95%CI 0.32-1.85) 病人之數量,及不良反應 (RR 9.06; 95% CI 0.49-166.82),於統計學上沒有分別。 這篇文獻亦沒有評價可修正的心血管風險因素,其他驗血結果,心功能特性或血管重建(revascularization)步驟。

作者結論

基於極低的證據質量,我們不能確定或反駁於慢性牙周炎病人實施牙周治療,可否長期防止心血管疾病復發。也未找到關於初級預防的證據。

譯註

翻譯者:Ying Jo Wong, MS, DDS, MAGD
服務單位:New York University College of Dentistry
職稱:Clinical Instructor

本翻譯計畫由臺北醫學大學考科藍臺灣研究中心(Cochrane Taiwan)、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行
聯絡E-mail:cebm@tmu.edu.tw

Plain language summary

Treatment for gum disease (periodontitis) for the management of disease involving the heart and blood vessels in patients with chronic gum disease

Review question

The main question addressed by this review produced by the Cochrane Oral Health Group was whether or not treatment for moderate to severe gum disease (periodontitis) also has an effect on the prevention or management of heart and blood vessel (cardiovascular) disease.

Background

Gum disease (periodontitis) is a common chronic or persisting condition that can get worse over time. It involves inflammation of the gums, which surround and support the teeth, causing swollen and painful gums and in severe cases loss of the bone (alveolar) that supports the teeth.

Clinical investigations have shown that there might be a link or association between chronic, ongoing gum disease (periodontitis) and heart and blood vessel disease (cardiovascular disease). Some investigators believe that the treatment for gum disease, which gets rid of bacteria and infection and controls inflammation, might prevent the occurrence or recurrence of heart disease.

Study characteristics

The evidence on which this review is based was from a search of the clinical data on 7 April 2014. The included randomised controlled study involved 303 participants.

Key results

At present there is only one suitable study looking at this issue. The study had problems with its design. Based on this evidence it was not possible to determine whether or not treatment for gum (periodontal) disease has any effect on the occurrence or recurrence of heart disease in people with chronic gum disease.

Quality of the evidence

The quality of the evidence was very low as there was only one study with problems in its design and how the study was conducted.

Résumé simplifié

Traitement de la parodontite pour la gestion des maladies du cœur et des vaisseaux sanguins chez les patients atteints de parodontite chronique

Question de la revue

La principale question posée par cette revue produite par le groupe Cochrane sur la santé bucco-dentaire était de savoir si le traitement d'une maladie modérée à grave des gencives (parodontite) avait également un effet sur la prévention ou le traitement des maladies du cœur et des vaisseaux sanguins (cardiovasculaires).

Contexte

La parodontite est une maladie courante des gencives, chronique ou persistante, qui peut s'aggraver avec le temps. Elle consiste en une inflammation des gencives qui entourent et soutiennent les dents : celles-ci deviennent enflées et douloureuses et, dans les cas graves, il se produit une perte de l'os alvéolaire qui soutient les dents.

Des investigations cliniques ont montré qu'il pourrait y avoir un lien ou une association entre la parodontite chronique et les maladies du cœur et des vaisseaux sanguins (maladies cardiovasculaires). Certains chercheurs pensent que le traitement de la maladie des gencives, en éliminant les bactéries et l'infection et en jugulant l'inflammation, pourrait prévenir l'apparition ou la réapparition de maladies du cœur.

Caractéristiques des études

Les preuves sur lesquelles se fonde cette revue sont issues d'une recherche des données cliniques effectuée le 7 avril 2014. L'étude contrôlée randomisée incluse porte sur 303 participants.

Principaux résultats

À l'heure actuelle, il existe une seule une étude adéquate qui examine cette question. Cette étude pose des problèmes de conception. Sur la base de ces éléments, il n'a pas été possible de déterminer si le traitement de la parodontite avait un quelconque effet sur l'apparition ou la réapparition de maladies cardiaques chez les personnes souffrant de parodontite chronique.

Qualité des preuves

La qualité des preuves était très mauvaise car nous avons trouvé une seule étude, défectueuse dans sa conception et dans la manière dont elle a été conduite.

Notes de traduction

Traduction réalisée par le Centre Cochrane Français

Laički sažetak

Terapija parodontitisa u liječenju bolesti žila i krvožilnog sustava u pacijenata s kroničnim parodontitisom

Istraživačko pitanje

Glavno pitanje ovog sustavnog pregleda, koji je izrađen u okviru Cochrane skupine za oralno zdravlje (engl. Cochrane Oral Health Group), jest utječe li liječenje umjerenog do jakog parodontitisa na sprečavanje ili tijek krvožilnh bolesti.

Dosadašnje spoznaje

Parodontitis je često kronično ili trajno stanje koje se može tijekom vremena pogoršavati. Uključuje upalu zubnog mesa (gingive), koje okružuje i podupire zube, uzrokujući natečene i bolne desni i u nekim slučajevima gubitak alveolarne kosti koja je potpora zubima.

Klinička ispitivanja su pokazala da postoji povezanost između kroničnog, a postojećeg parodontitisa i bolesti srca i krvnih žila (kardiovaskularne bolesti). Neki istraživači vjeruju da se liječenjem bolesti desni, kojim se smanjuje broj bakterija, a time i infekcija i upala, može smanjiti pojava ili povratak krvožilnih bolesti.

Značajke istraživanja

Dokaz na kojem se temelji ovaj sustavni pregled proistječe iz pretraživanja kliničkih studija objavljenih do 7. travnja 2014. Pronađen je jedan kontrolirani randomizirani pokus koji uključuje 303 ispitanika.

Ključni rezultati

Danas postoji samo jedno kliničko istraživanje u vezi s postavljenim kliničkim pitanjem. Istraživanje je bilo problematično ustrojeno. Prema tim dokazima nije moguće odrediti utječe li liječenje parodontne bolesti na pojavu ili ponovnu pojavu krvožilnih bolesti u bolesnika s kroničnom bolesti desni.

Kvaliteta dokaza

Kvaliteta ovog istraživanja je vrlo niska, jer se radi samo o jednom istraživanju koje ima problematičan ustroj i način provedbe.

Bilješke prijevoda

Cochrane Hrvatska
Prevela: Nikolina Carić
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr

淺顯易懂的口語結論

於慢性牙周炎患者實施牙齦疾病(牙周炎)治療以助控制心臓血管疾病

回顧問題

本篇文獻回顧的主題在於探討治療中度到高度嚴重牙周炎能否防止或控制心臓血管疾病 (CVD)。

背景

牙齦疾病(牙周炎)是常見的慢性病,會愈趨嚴重。症狀包括牙齦發炎、腫脹、疼痛,甚或令支撐牙齒的骨骼萎縮。

臨床硏究指出,慢性牙周炎和心血管病之間,可能有關連。有硏究者認為,治療牙周炎可消除細菌及感染、控制發炎,或可防止心臟病初發或復發。

研究特性

我們搜尋了直至2014年4月7日的數據庫,找到一篇包含303位病人的隨機對照試驗。

主要成果

目前只有一篇文獻符合,但是它的設計很有問題,提供的證據亦不足夠證實,於慢性牙齦疾病患者治療牙周炎,能否防止心臟病初發或復發。

證據質量

由於只有一篇文獻,而它的硏究方法及設計執行充滿問題,證據質量十分低。

譯註

翻譯者:Ying Jo Wong, MS, DDS, MAGD
服務單位:New York University College of Dentistry
職稱:Clinical Instructor

本翻譯計畫由臺北醫學大學考科藍臺灣研究中心(Cochrane Taiwan)、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行
聯絡E-mail:cebm@tmu.edu.tw

Ringkasan bahasa mudah

Rawatan untuk penyakit gusi (periodontitis) bagi pengendalian penyakit yang melibatkan jantung dan salur darah dalam kalangan pesakit yang mengalami penyakit gusi kronik.

Soalan ulasan

Soalan utama ulasan yang dihasilkan oleh Kumpulan Kesihatan Oral Cochrane ini adalah sama ada rawatan penyakit gusi sederhana atau teruk (periodontitis) memberi kesan terhadap pencegahan atau pengendalian penyakit jantung dan salur darah (kardiovaskular).

Latarbelakang

Penyakit gusi (periodontitis) adalah keadaan lazim yang kronik atau berpanjangan yang boleh menjadi lebih teruk. Ia melibatkan keradangan gusi yang mengelilingi dan menyokong gigi, menyebabkan gusi bengkak dan sakit dan di dalam keadaan yang lebih teruk menyebabkan kehilangan tulang (alveolar) yang menyokong gigi.

Penyelidikan klinikal menunjukkan kemungkinan kaitan penyakit gusi kronik (periodontitis) dengan penyakit jantung dan salur darah (kardiovaskular) Sesetengah penyelidik percaya rawatan untuk penyakit gusi yang menghapuskan bakteria dan jangkitan dan mengawal keradangan, mungkin boleh mencegah kejadian atau penyakit jantung berulang.

Ciri kajian

Ulasan ini berdasarkan bukti carian data klinikal sehingga 7 April 2014. Ia termasuk kajian rawak terkawal melibatkan 303 peserta.

Keputusan utama

Sehingga kini hanya ada satu kajian yang sesuai yang meneliti isu ini. Kajian ini bermasalah dari sudut rekabentuk. Bukti yang ada tidak dapat menentukan sama ada rawatan penyakit gusi (peridontium) mempunyai kesan terhadap kejadian atau ulangan penyakit jantung dalam kalangan orang yang ada penyakit gusi kronik.

Kualiti bukti

Kualiti bukti adalah rendah kerana hanya ada satu kajian dan bermasalah pada rekabentuk dan perlaksanaannya.

Catatan terjemahan

Diterjemah oleh Noorliza Mastura Ismail, Kolej Perubatan Melaka-Manipal. Disunting oleh Teguh Haryo Sasongko, Universiti Sains Malaysia. Untuk sebarang pertanyaan berkaitan terjemahan ini sila hubungi noorliza.mastura@manipal.edu.my

Summary of findings(Explanation)

Summary of findings for the main comparison. Secondary prevention: periodontal treatment versus community care for the management of cardiovascular disease in patients with chronic periodontitis
  1. 1 Lack of blinding. Poor compliance with study protocol
    2 Wide confidence interval

Secondary prevention: periodontal treatment versus community care for the management of cardiovascular disease in patients with chronic periodontitis
Patient or population: patients with cardiovascular disease and chronic periodontitis
Settings: the USA
Intervention: secondary prevention, periodontal treatment versus community care
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
Control Secondary prevention: periodontal treatment versus community care
All-cause and CVD-related death  Outcomes not reported 
All cardiovascular events
Follow-up: 25 months
Study population (control group incidence) RR 0.72
(0.23 to 2.22)
303
(1 study)
⊕⊝⊝⊝
very low 1,2
 
46 per 1000 33 per 1000
(11 to 102)
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in the table. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; CVD: cardiovascular disease; RR: risk ratio
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: 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 quality: We are very uncertain about the estimate.

Background

Description of the condition

Cardiovascular disease (CVD) covers a wide array of disorders (including diseases of the cardiac muscle and the vascular system supplying the heart, brain and other vital organs) such as coronary heart disease (with narrowing or blockage of the coronary arteries, which can cause angina and myocardial infarction) and stroke (with narrowing, blockage or haemorrhage of the cerebrovascular system), which are the world's largest killers causing the death of 17.1 million individuals per year (Nabel 2003; Jamison 2006). There are a variety of risk factors involved in the pathogenesis of CVD, such as smoking or passive smoking (Law 1997; He 1999; Kallio 2010), hypertension, excess sodium intake (Strazzullo 2009) and hyperlipidaemia (Austin 1999). Numerous successful modalities of treatment that are based on these aetiological or risk factors have been developed (Brunner 2007; Law 2009; Manktelow 2009). However, in modern society people are increasingly exposed to such factors and the aforementioned therapies are still not enough, thus the incidence of CVD increases year on year (WHO 2007).

Recently considerable attention has been paid to the aetiological role of acute or chronic infections on CVD, and infections which accelerate vascular inflammation and promote thrombosis of vascular vessels (Herzberg 2005; Viles-Gonzalez 2006) are believed to be a secondary pathogenic pathway (Smeeth 2004; Hansson 2006; Moutsopoulos 2006). Among the infections, periodontitis might be the most common. It is an infectious disease resulting in inflammation within the supporting tissues of teeth resulting in progressive attachment and alveolar bone loss (Armitage 1999). In the last century, periodontitis was reported to affect 6% to 20% of the population (Oliver 1991; AAP 1999); and the estimate of disease in the United States (US) population exceeds 47%. In those over 65 years, 64% have either moderate or severe periodontitis based on a recently published article (Eke 2012). There are two reasons why periodontitis and CVD are believed to be related. Firstly, the levels of systemic inflammation increase when moderate or severe periodontitis is present, and when treating periodontitis there is a clear reduction in the clinical signs with a decrease in the levels of systemic inflammatory mediators (Tonetti 2007; Paraskevas 2008). Secondly, the periodontal bacteria may invade the damaged periodontal tissue, enter the bloodstream and further invade the cardiovascular system. Several periodontal pathogens, such as P. gingivalis, B. forsythus, P. intermedia and A. actinomycetemcomitans (Haraszthy 2000; Padilla 2006) have been detected in carotid atheromas by polymerase chain reaction. Experimental studies have shown that the presence of these periodontal pathogens and oral bacteria in the atheromas could induce platelet activation and aggregation through collagen-like platelet aggregation-associated protein expression. The activated and aggregated platelets could then play an important role in atheromatous formation and thrombosis, and finally lead to cardiovascular events (Herzberg 1983; Herzberg 1996). Besides this, periodontal bacteria may play a role in the formation of coronary atherosclerotic plaques, which is indirectly proven by the presence of bacterial DNA from the oral pathogenic micro-organisms in coronary atherosclerotic plaques and the special characteristics of the aortic aneurysms in cardiovascular disease patients harbouringP. gingivalis (Mahendra 2010; Nakano 2011). They can induce cell-specific innate immune inflammatory pathways causing and maintaining a chronic state of inflammation at sites distant from the periodontitis (Hayashi 2010). Also, an indirect association between the two diseases was identified by investigators as they share similar risk factors such as smoking, diabetes mellitus, obesity and hypertension (Friedewald 2009). The association between periodontitis and CVD was proved by some clinical trials and further confirmed by meta-analysis (Janket 2003; Scannapieco 2003; Khader 2004). Based on this evidence, some investigators have concluded that there could be a mild to moderate association between periodontitis and CVD (Genco 2002; Hujoel 2002).

As a relationship between periodontitis and CVD is evident, it is rational to explore whether CVD can be managed or its occurrence or recurrence prevented by treating periodontitis.

Description of the intervention

It is believed that bacterial infection is the main aetiological factor for periodontitis. Other factors such as occlusal trauma, calculus and smoking would be considered as risk factors accelerating the progression of periodontitis (Meng 2009). Fortunately, there are several effective ways to control these factors and further control periodontitis. Full mouth disinfection, supragingival and subgingival scaling and root planing (SRP) could remove the periodontal bacteria or calculus and create a relatively healthy environment to reduce bacterial regrowth (Eberhard 2008; Worthington 2013;). Occlusal adjustment has also been reported as an effective method by eliminating the harmful occlusal trauma which induces abnormal stress on the periodontal tissue (Weston 2008). Periodontal surgery, including guided tissue regeneration (GTR), replaces the lost or necrotic bone and periodontal tissue (Needleman 2006; Esposito 2009). All of these therapies play a role in reducing the biofilm or number of bacteria and controlling the accelerating factors. Such maintenance and preventive interventions should be adopted for periodontitis sufferers as a life-long commitment to control periodontal inflammation and disease recurrence.

Periodontal medicine has recently been created and is now recognised. It aims to treat the systemic diseases which are suspected to be associated with periodontal disease through applying periodontal therapies. Up to now, one Cochrane systematic review has shown that periodontal treatment could help to control diabetes mellitus (Simpson 2010). Two ongoing Cochrane systematic reviews are focusing on periodontal therapies in the prevention of preterm birth (Crowther 2005) and the care of people with rheumatoid arthritis (Vergnes 2012). It is recognised that such treatments may have a beneficial effect not only on the periodontal disease but also on some major systemic diseases.

How the intervention might work

Periodontal treatment could clean up the infectious sources and control the acceleration of periodontitis. Some studies have already confirmed that high blood pressure could be lowered and serum inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP) could be significantly reduced after such treatment (D'Aiuto 2005; Blum 2007). Tüter and co-workers indicated that periodontal treatment with a subantimicrobial dose of doxycycline could increase serum levels of apolipoprotein-A and high-density lipoprotein, reduce total cholesterol levels and further decrease the risk of cardiovascular events (D'Aiuto 2005; Tüter 2007). However, as we have mentioned previously, periodontitis and CVD may have similar risk factors (smoking, obesity, hypertension and diabetes mellitus) some of which are modifiable and some non-modifiable. The mechanism of periodontal treatment in the management of CVD, which could be based on controlling periodontitis directly or changing the modifiable risk factors, or both, is still unknown.

Why it is important to do this review

Some studies have investigated the effects of periodontal treatment for the management of CVD, but the reliability of the methods and validity of their results should be further evaluated. This review aimed to evaluate the scientific quality of the studies, by the participants, specific interventions, comparisons and outcomes, and provide some evidence on the effect of periodontal therapy in CVD management for clinicians and consumers.

Objectives

The objective of this systematic review was to investigate the effects of periodontal therapy in preventing the occurrence of, and management or recurrence of, cardiovascular disease (CVD) in patients with chronic periodontitis.

Methods

Criteria for considering studies for this review

Types of studies

Only randomised controlled trials (RCTs) and quasi-RCTs with follow-up times ≥ one year that aimed to test the effects of different periodontal therapies for patients with cardiovascular disease (CVD) were eligible. The studies could be primary prevention studies or secondary prevention studies. In the former, the focus would be on using periodontal treatment to prevent the occurrence of CVD in patients who do not have CVD. Participants in the secondary prevention studies would presently have, or have previously been diagnosed with, CVD. Studies that did not focus on the primary or secondary prevention of CVD were excluded.

Types of participants

Patients meeting the following criteria, regardless of age, gender, race, social and economical status, were considered for inclusion.

  1. Diagnosis of at least moderate chronic periodontitis with pocketing greater than or equal to 4 mm.

  2. Absence of any known genetic or congenital heart defects and aggressive periodontitis.

  3. An existing or previous diagnosis of CVD (including angina, myocardial infarction, stroke); for primary prevention studies investigating the preventive effect of periodontal treatment on CVD participants should not have CVD.

  4. Absence of other sources of inflammation such as pulpal infections and active caries.

  5. No periodontal treatment within six months (participants should have active disease and not be in a periodontal maintenance programme).

Patients with severe systemic diseases other than CVD, who were pregnant or lactating, or were unable to return for follow-up were not considered.

Types of interventions

  • Active therapy: scaling and root planing (SRP), which included subgingival SRP or SRP in combination with systemic antibiotic or host modulation with or without other active remedies.

  • Maintenance therapy (supragingival scaling, antimicrobial rinses) or no periodontal treatment with or without the same basic remedies as those in the intervention group.

Types of outcome measures

The outcomes were divided into two categories: primary outcomes (which would be the main outcomes considered when forming conclusions) and secondary outcomes (which would assist in forming conclusions from the primary outcomes). Any outcomes detected within less than one year of completion of the treatment were considered as short-term outcomes and were not reported while those detected at one year or more were reported as long-term outcomes.

Primary outcomes
  1. All-cause and CVD-related death.

  2. All cardiovascular events (angina, myocardial infarction, stroke).

Secondary outcomes
  1. Modifiable cardiovascular risk factors: blood pressure; lipids including cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C).

  2. Blood test results, including serum levels of high-sensitivity C-reactive protein (hs-CRP), apolipoprotein-A (APO-A), apolipoprotein-B (APO-B).

  3. Heart function parameters (such as ejection fraction).

  4. Revascularisation procedures.

  5. Adverse events due to periodontal therapy (tooth sensitivity, mouth discomfort).

Search methods for identification of studies

For the identification of studies included in or considered for this review, we developed detailed search strategies for each database searched. These were based on the search strategy developed for MEDLINE (OVID) but revised appropriately for each database. The search strategy used a combination of controlled vocabulary and free text terms and was linked with the Cochrane Highly Sensitive Search Strategy (CHSSS) for identifying RCTs in MEDLINE: sensitivity maximising version (2008 revision) as referenced in Chapter 6.4.11.1 and detailed in box 6.4.c of the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0 (updated March 2011) (Higgins 2011). Details of the MEDLINE search are provided in Appendix 1. The searches of EMBASE and CINAHL were linked to the Cochrane Oral Health Group filters for identifying RCTs.

Electronic searches

We searched the following databases:

  • The Cochrane Oral Health Group's Trials Register (to 7 April 2014) (Appendix 2);

  • The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 3) (Appendix 3);

  • MEDLINE via OVID (1946 to 7 April 2014) (Appendix 1);

  • EMBASE via OVID (1980 to 7 April 2014) (Appendix 4);

  • CINAHL via EBSCO (1937 to 7 April 2014) (Appendix 5);

  • OpenGrey (to 10 April 2014) (Appendix 6);

  • Chinese BioMedical Literature Database (CBM) (1978 to April 2014);

  • China National Knowledge Infrastructure (CNKI) (1994 to April 2014);

  • VIP (1989 to April 2014).

The search attempted to identify all relevant studies irrespective of language. Non-English papers were translated.

Searching other resources

We searched the following databases for ongoing trials:

The reference lists of all eligible trials were checked for additional studies. The first authors of all included studies were contacted by email for any ongoing or unpublished studies examining the efficacy and safety of periodontal therapy for the management of CVD.

Handsearching

All the Chinese professional journals and some important English journals in relation to the dental and cardiovascular fields were handsearched from the first issue to May 2011 (see Additional Table 1 and Additional Table 2 for details).

Table 1. Journals on stomatology for handsearching
Journal name By ZD Shi et al By CJ Li et alBy CJ Li and ZK Lv
Chinese Journal of Stomatology1953 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Stomatology1981 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
West China Journal of Stomatology1983 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Journal of Practical Stomatology1985 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Journal of Clinical Stomatology1985 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Journal of Comprehensive Stomatology1985 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Journal of Modern Stomatology1987 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Chinese Journal of Conservative Dentistry1991 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Journal of Maxillofacial Surgery1991 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Shanghai Journal of Stomatology1992 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Chinese Journal of Dental Material and Devices1992 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Beijing Journal of Stomatology1993 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Chinese Journal of Dental Prevention and Treatment1993 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Chinese Journal of Orthodontics1994 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Chinese Journal of Implantology1996 to Dec 2000Jan 2001 to Dec 2009Jan 2010 to May 2011
Journal of International Stomatology Jan 2001 to Dec 20091974 to Dec 2000, Jan 2010 to May 2011
Chinese Journal of Prosthodontics Jan 2001 to Dec 20091999 to Dec 2000, Jan 2010 to May 2011
China Journal of Oral and Maxillofacial Surgery 2003 to Dec 2009Jan 2010 to May 2011
Chinese Journal of Geriatric Dentistry 2002 to Dec 2009Jan 2010 to May 2011
International Journal of Oral Science  2009 to May 2011
International Journal of Periodontics & Restorative Dentistry  1981 to May 2011
Journal of Clinical Periodontology  1974 to May 2011
Journal of Periodontal Research  1966 to May 2011
Journal of Periodontology  1949 to May 2011
Periodontology 2000  1993 to May 2011
Table 2. Journals on cardiovascular disease for handsearching
Journal nameBy CJ Li and ZK Lv
Journal of Cardiovascular and Pulmonary Diseases1982 to May 2011
Chinese Journal of Cardiology1973 to May 2011
International Journal of Cerebrovascular Diseases1993 to May 2011
Prevention and Treatment of Cardio-Cerebral-Vascular Disease2001 to May 2011
Chinese Journal of Cerebrovascular Diseases2004 to May 2011
Chinese Journal of Geriatric Heart Brain and Vessel Diseases1999 to May 2011
Chinese Journal of Integrative Medicine on Cardio-/Cerebrovascular Disease2003 to May 2011
Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease 1993 to May 2011
Circulation1950 to May 2011
European Heart Journal1980 to May 2011
Cardiovascular Research1967 to May 2011
Circulation Research1953 to May 2011
Cardiology1937 to May 2011
Arteriosclerosis, Thrombosis, and Vascular Biology1981 to May 2011
American Journal of Cardiology1958 to May 2011

Data collection and analysis

Selection of studies

Two review authors (Chunjie Li and Zongkai Lv) carried out the study selection in duplicate according to the selection criteria. Titles and abstracts of the search results were initially screened to look for possible eligible studies. Full texts of these studies were retrieved and assessed by both review authors to further assess eligibility. Any disagreements on study inclusion were discussed to reach consensus and, when necessary, a third review author arbitrated. A PRISMA flow diagram of the whole process was used as recommended (Liberati 2009).

Data extraction and management

Two review authors (Chunjie Li and Zongkai Lv) carried out the data extraction in duplicate. Disagreements were resolved by discussion and an arbitrator was involved when the disagreement remained unresolved. A customised data extraction form designed in Microsoft Access 2007 was developed according to the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0 (Higgins 2011) and was pilot-tested using a sample of the studies focusing on this topic and was then applied to all the included studies. The following data were collected.

  • Source: study identification (ID), reviewer ID, citation and contact details.

  • Eligibility: reasons for inclusion and exclusion.

  • Methods of the study: centres and their location, study duration, study design, sequence generation, allocation concealment, blinding and statistical methods.

  • Participants: total number, setting, age and sex, diagnostic criteria for both cardiovascular disease and periodontitis, inclusion and exclusion criteria of the participants.

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

  • Outcomes: definition of outcome measures and units of the measurements, time points of measurement, sample size calculation, number of participants allocated to each group, numbers lost to follow-up and the reasons, detailed summary data for each group.

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

For studies which had multiple groups the data for all the groups, if they were relevant to this review, were to be extracted and displayed in the 'Characteristics of included studies' section of the systematic review.

If there was any missing information, the original investigators of the included studies were contacted for clarification.

Assessment of risk of bias in included studies

Risk of bias assessment was carried out following the approach described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0 (Higgins 2011) and the Cochrane systematic review by Shi 2013. Authors of the included studies were contacted by email to obtain or clarify any unreported or unclear information on the risk of bias of the studies. Two review authors (Chunjie Li and Zongkai Lv) independently measured the risk of bias according to the published article and the trial authors' responses. Any discrepancies were discussed and a third review author arbitrated when necessary.

Risk of bias assessment of the included studies

The risk of bias for each of the individual included studies was judged for seven domains (as identified in the Cochrane Collaboration's tool for risk of bias assessment). For each of the following domains a judgment of either 'low risk', 'high risk' or 'unclear risk' of bias was assigned.

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

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

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

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

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

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

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

Summary risk of bias assessment at the study level

For some kinds of periodontal therapy it is nearly impossible to achieve participant blinding, so all the domains except the third were considered as key domains. Study limitations were allotted to one of the following three categories:

  • low risk of bias, there was a low risk of bias for all key domains or any plausible bias was unlikely to seriously alter the study results;

  • unclear risk of bias, there was an unclear risk of bias for one or more key domains or any plausible bias raised some doubt about the study results;

  • high risk of bias, there was a high risk of bias for one or more key domains or any plausible bias might seriously weaken confidence in the results.

Measures of treatment effect

Selection of statistical methods was dependent on whether the data were dichotomous, continuous or presented as time-to-event. Both primary outcomes were treated as dichotomous data or time-to-event data.

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

For continuous data, mean differences (MD) and 95% CIs were calculated for change from baseline or the final values if they were measured by similar indices. If the data were measured using different indices, standardised mean differences (SMD) and 95% CIs were to be adopted for the outcome measurements.

Unit of analysis issues

Cluster-randomised trials and studies with more than two intervention groups were to be analysed differently from RCTs. For cluster-randomised trials, to avoid any inappropriate analyses in the original studies, approximate analyses-effective sample sizes were to be adopted following the guidance of the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0 (Higgins 2011). For studies with more than two intervention groups, as each meta-analysis addressed only a single pair-wise comparison two approaches were to be considered. The first was to combine groups to create a single pair-wise comparison and if this first approach failed the most relevant pair of interventions was to be selected.

Dealing with missing data

For trials with missing data, the review authors contacted the trial authors for supplementation of the data and clarification. If there was no reply, certain statistical methods were to be adopted.

If the standard deviation (SD) of the continuous data was not reported, it was to be calculated through one of the following ways: (i) from the standard error (SE), 95% CIs, P values or t-values, ranges or interquartile ranges reported in the article; or (ii) if the SD of change from baseline values was missing it was to be calculated using the correlation coefficient.

Intention-to-treat (ITT) analysis was conducted whenever possible.

If the methods mentioned above could not be used, only the available data were to be analysed and interpreted with caution.

Assessment of heterogeneity

The Chi2 test for heterogeneity was to be implemented to examine if heterogeneity existed among the included studies. The I2 statistic was to be applied to estimate the impact of the heterogeneity:

  • 0% to 40% indicating slight heterogeneity;

  • 30% to 60% indicating moderate heterogeneity;

  • 50% to 90% indicating substantial heterogeneity;

  • 75% to 100% indicating considerable heterogeneity.

Assessment of reporting biases

To avoid reporting biases, a comprehensive search that included grey literature and ongoing studies was carried out (see Search methods for identification of studies). Publication bias and other reporting biases were to be addressed with the help of the funnel plot only if there were more than 10 trials providing results in one outcome. The asymmetry of the funnel plot would reveal a potential publication bias and be further tested by the methods introduced by Egger 1997 (continuous outcomes) and Rücker 2008 (dichotomous outcomes).

Data synthesis

Data would be pooled if there was more than one study with similar comparisons that reported the same variable. Fixed-effect or random-effects models were to be adopted depending on the number of studies included in the meta-analysis: a random-effects model would be used if there were four studies or more, otherwise a fixed-effect model would be adopted.

The method of the meta-analysis for computing different kinds of data varied. The RevMan (RevMan 2012) default fixed-effect model Mantel-Haenszel (M-H) method was used for dichotomous data; MD or SMD for continuous data, unless the data were only in the appropriate form for generic inverse variance (GIV) for continuous data; and for time-to-event data (O minus E and variance) the Peto or inverse variance (IV) method.

Subgroup analysis and investigation of heterogeneity

Subgroup analysis was to be conducted according to the different modes of periodontal treatment and different categories of CVD. If there was clinical heterogeneity, subgroup analysis was also to be implemented however this was not possible because of the low number of studies.

Sensitivity analysis

To test the stability of the conclusions, sensitivity analysis was to be carried out based on different assumptions such as excluding studies with evident biases, using different methods to deal with missing data, different models of meta-analysis, exclusion of studies causing significant statistical heterogeneity, ITT analysis. The results were to be reported in detail and their impact on the stability of the conclusions evaluated in the discussion section.

Presentation of main results

To provide key information on the effects and safety of periodontal therapy for CVD management in a quick and accessible format, a 'Summary of findings' table was presented. The summary of findings table shows the quality of a body of evidence on the primary outcomes (all-cause and CVD-related death, all cardiovascular events). Quality assessment of the body of evidence involved the consideration of risk of bias at the outcome level, directness of the evidence, heterogeneity, precision of effect estimates and risk of publication bias (see Assessment of reporting biases). The GRADE system for evaluating the quality of the evidence in systematic reviews (Atkins 2004; Guyatt 2008; Higgins 2011) was adopted by using the GRADEprofiler software, which was designed as an assessment of the quality of a body of evidence for each individual outcome. The quality was classified into four categories: high, moderate, low, and very low. The strength of the recommendations derived from the evidence was to be considered as either strong or weak (Guyatt 2008).

Results

Description of studies

For details of the studies examined and the reasons for inclusion or exclusion please see the Characteristics of included studies, Characteristics of ongoing studies, Characteristics of studies awaiting classification and Characteristics of excluded studies tables.

Results of the search

A total of 933 records were identified, including 657 records identified from English databases, 271 from Chinese databases (two were duplicate records) and 7 from handsearching. Among the records, 884 were excluded. Full texts of the other 49 studies were retrieved and 38 published studies (41 articles) were excluded, three were ongoing studies, one study (three articles) was considered as awaiting classification because all the included participants were female and had osteopenia of the lumber spine or femoral neck so that its eligibility was not clear. Some data needed confirmation from the authors and their eligibility needs further discussion. One study (four articles) was finally included.

The process of study identification is summarised in a flow diagram and presented in Figure 1.

Figure 1.

Study flow diagram.

Included studies

From the searches, only one randomised controlled trial (RCT) was identified (303 participants).

1. Primary prevention

No study addressing primary prevention was identified.

2. Secondary prevention

The only included study was a secondary prevention study (PAVE 2008). It is a multicentre, parallel group, single-blind RCT with 303 participants randomised into the periodontal treatment group or the community care group.

Participants

Participants had to have ≥ 50% blockage of one coronary artery or have had a coronary event within three years but ≥ three months previously. The periodontal inclusion criteria were: the presence of at least six natural teeth, including third molars, with at least three teeth with probing pocket depth (PPD) ≥ 4 mm, at least two teeth with interproximal clinical attachment loss (CAL) ≥ 2 mm, and ≥ 10% of sites having bleeding on probing (BOP).

Intervention

The intervention group (n = 151) received oral hygiene instruction and one regimen of full mouth scaling and root planing (SRP) with local anaesthesia (30% of the treatment being completed > two months after randomisation). Only 92.7% of the participants received the treatment; and one participant received SRP outside the study.

Control

Participants in the control group (community care group) (n = 152) received oral hygiene instruction and were given a copy of their oral radiographs, a letter stating the tentative oral findings, and were recommended to seek the opinion of a dentist (9% of the participants in the control group got SRP outside the study within six months and 11% of them got SRP within the entire follow-up period).

Outcome

The participants were observed for 6 months to 25 months. The following outcomes were reported: serious cardiovascular adverse events (all cardiovascular events), serum hs-CRP, number of participants that had high hs-CRP, and adverse events measured as the development of an undesirable medical or dental condition or the deterioration of a pre-existing medical or dental condition following or during exposure to a pharmaceutical product or medical or dental procedure, whether or not considered causally related to the intervention. Only data on adverse events due to periodontal therapy were analysed in this review.

Excluded studies

Thirty-eight studies (41 articles) were excluded based on the inclusion and exclusion criteria. The reasons for exclusion are listed in the Characteristics of excluded studies table.

Risk of bias in included studies

The only included study was at high risk of bias. See the Characteristics of included studies table and Figure 2.

Figure 2.

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

Allocation

Random sequence generation: a computer generated randomised table was used and was considered adequate.

Allocation concealment: central allocation was adopted, which was graded as adequate.

Blinding

Blinding of participants and personnel: due to the nature of the intervention (periodontal treatment), it was impossible to achieve the blinding of participants and personnel.

Blinding of outcome assessment: blinding of outcome assessment was reported.

Incomplete outcome data

There were 21 (6.9%) participants lost to follow-up by the six-month clinic visit. In one year only 37 of the 303 participants received follow-up. The number of participants lost to follow-up by study group was not specifically reported, therefore it was not clear whether there was a difference between the groups in that regard. Follow-up data at other time points were not reported.

Selective reporting

All the variables were reported as stated in the protocol so the study was considered to be at low risk of reporting bias.

Other potential sources of bias

About 92.7% of the participants in the treatment group received the treatment. One participant in the intervention group received SRP outside the study while 11% of the participants in the control group had received SRP by the end of the follow-up period. Contamination and co-intervention resulted in a high risk of other biases.

Effects of interventions

See: Summary of findings for the main comparison Secondary prevention: periodontal treatment versus community care for the management of cardiovascular disease in patients with chronic periodontitis

1. Primary prevention

There was no relevant study on primary prevention.

2. Secondary prevention

2.1 Periodontal treatment versus community care

Participants in the periodontal treatment group, who received scaling and root planing (SRP) and advice, were compared with those in the community care group, who only received advice.

2.1.1 All-cause death

Not reported.

2.1.2 All CVD-related death

Not reported.

2.1.3 All cardiovascular events

Of the 15 serious adverse events (SAE) reported, 12 were cardiovascular events. In the article the authors did not clearly report the number of non-cardiovascular events in each group, but they stated via e-mail correspondence that all the three non-cardiovascular SAEs were in the community care group. Five participants in the periodontal treatment group reported cardiovascular events during the 25 months of the study compared to seven participants in the community care group. There was no significant difference in cardiovascular events when patients who received periodontal treatment were compared to those who received community care (risk ratio (RR) 0.72; 95% confidence interval (CI) 0.23 to 2.22) (Analysis 1.1).

2.1.4 Blood test results

Serum high-sensitivity C-reactive protein (hs-CRP) was tested at one year but the results showed that SRP had no significant effect on serum hs-CRP compared to community care (mean difference (MD) 0.62; 95% CI -1.45 to 2.69) (Analysis 1.2).

The number of participants who had high CRP was also analysed. High CRP, defined as CRP > 3 mg/l, was reported at one year follow-up but the results were not statistically significant (RR 0.77; 95% CI 0.32 to 1.85) (Analysis 1.3).

2.1.5 Adverse events due to periodontal therapy

During the 25 months, four adverse events (high blood pressure, a tooth abscess, elevated blood pressure, and a bicycle accident) occurred in the treatment group (RR 9.06; 95% CI 0.49 to 166.82). The effect was not statistically significant (Analysis 1.4).

Discussion

Summary of main results

The aim of the review was to evaluate the effect of periodontal treatment in the primary and secondary prevention of cardiovascular disease (CVD) in patients with chronic periodontitis. Through a comprehensive search we identified 933 records of which only one randomised controlled trial (RCT) (303 participants) qualified for inclusion. The RCT focused on the effect of periodontal treatment for the secondary prevention of CVD in patients with chronic periodontitis. No primary prevention studies were identified, but some were excluded because of a short follow-up period.

For secondary prevention, periodontal treatment was compared with community care. All-cause and CVD-related deaths were not reported in the trial. The study recorded 12 cardiovascular events but the results were not statistically significant. Also, serum high-sensitivity C-reactive protein (hs-CRP), the number of participants who had high CRP, and adverse events all reported non-significant results. Since there was only one study eligible for inclusion, which was also judged to be at high risk of bias, the results should be interpreted with caution.

Overall completeness and applicability of evidence

The review had aimed to include both primary and secondary prevention studies assessing periodontal treatment in CVD patients with chronic periodontitis. However, the only qualifying study was a secondary prevention study. The evidence from this review can be applied to adults in most age groups, except those over the age of 75 years. The following outcomes are not covered in this review: modifiable cardiovascular risk factors, heart function parameters and revascularisation procedures. Although the investigators reported on adverse events and serious adverse events, there is no indication that death (all-cause or CVD-related) was an outcome objective of the trial. Therefore, this review does not provide any understanding about the effect of the intervention on deaths.

Quality of the evidence

The evidence is very low quality due to serious limitations of the one identified study and the imprecision of the results (Summary of findings for the main comparison). The only included study was assessed as being at high risk of bias (Figure 2). This was because of the lack of blinding of patients and personnel and the failure of some patients to comply with their assigned therapy, thus confounding the results and reducing the observed treatment effect. Very serious imprecision in the result was due to the inclusion of only one study with an inadequate sample size. The authors indicated (via correspondence) that the outcome results covered a follow-up period of 0 to 25 months. Therefore, the results may have included both short- and long-term outcome results since the authors made no distinction in that regard.

Potential biases in the review process

The protocol for this review underwent some minor changes (Differences between protocol and review). Some of the changes include a change in the definition of chronic periodontitis to include patients with a pocket depth of 4 mm or more. The follow-up period was also changed to ≥ one year and heart function parameters were included in the protocol as a secondary outcome. These changes may be justified but could still be a source of bias in the review process.

Agreements and disagreements with other studies or reviews

Other reviews focusing on the preventive or treatment effects of periodontal therapy and oral health promotion for the management of cardiovascular diseases have been published (Ioannidou 2006; Lam 2010) and they show inconsistent results with respect to the effect of periodontal therapy on systemic markers. Whilst the results of our review may be in agreement with the Ioannidou 2006 review, which found no significant difference in serum hs-CRP levels in patients with severe periodontal disease that underwent non-surgical periodontal treatment. The two reviews are largely incomparable with this present review because of the inadequate follow-up period.

Authors' conclusions

Implications for practice

We found very low quality evidence that was insufficient to determine the effect of periodontal treatment on cardiovascular disease (CVD) in patients with chronic periodontitis. Therefore, we are unable to make conclusions regarding the effect of periodontal treatment on cardiovascular events, serum high-sensitivity C-reactive protein (hs-CRP), the number of patients with high CRP and adverse events. This review did not find any trials examining the primary preventive effect of periodontal treatment on CVD in patients with chronic periodontitis.

Implications for research

Due to the insufficient number of trials, there is a need for more randomised controlled trials (RCTs) examining the secondary preventive effects of periodontal therapeutics. There is also a need for research on the primary preventive effects of periodontal treatment. Periodontal treatment can be a single- or multi-regimen of scaling and root planing (SRP). Since the included study only offered a single regimen, new studies could focus on the effect of multi-regimen SRP in controlling periodontitis. Multiple kinds of host modulation drugs could also be chosen.

There is need for more studies reporting on all-cause or cardiovascular-related deaths and cardiovascular events observed after long-term follow-up of one year or more. Most of the studies identified with our search strategy were excluded on the basis of inadequate follow-up period. The included study provided outcome data for a period covering 0 to 25 months, without indicating the time points when the outcome results were observed. Therefore, it is important for new studies to have a long-term follow-up period whilst specifying the time when the outcome results were observed.

For future research, it is important to stratify study participants according to the severity of the periodontitis together with the number of remaining teeth. Again, certain confounding factors should be carefully considered and controlled for, such as acute inflammation, smoking and diabetes mellitus. Limitations of the included study were due to non-compliance with the protocol, incomplete follow-up and lack of blinding of participants and personnel. In future studies, lack of compliance with the study protocol and incomplete follow-up of the participants can be reduced, as suggested by PAVE 2008, if patients are followed up by a cardiologist. Although blinding of the participants and personnel is difficult to achieve in most periodontal RCTs, blinded outcome assessment is still achievable. Offering supra-gingival scaling to the control group might be useful for blinding participants.

Acknowledgements

  • The review authors would like to thank the Trials Search Co-ordinator of the Cochrane Oral Health Group (COHG), Anne Littlewood, and Jane Ronson for designing the search strategies.

  • We would also like to thank Professor Helen Worthington (Contact Editor for this review), Luisa Fernandez Mauleffinch (Managing Editor of the COHG) and Philip Riley (Methodologist), for their assistance in processing the systematic review.

  • We would like to thank Professor Hongde Hu for helping with the title registration.

  • We would also like to thank Professor Jing Li from the Chinese Cochrane Center, Prof Philip J Wiffen, Dr Marialena Trivella and Dr Sally Hopewell from the UK Cochrane Centre, and Mrs Susan Furness from COHG for their assistance and guidance in the conducting of the systematic review; and Dr Yan Wang and Xiangyu Ma from West China College of Stomatology for their help with the revision of the systematic review.

  • We thank Dr Feng Li, Dr Qiushi Wang, Dr Chenyang Xiang, Dr Zhaoyang Ban and Dr Wenhang Dong for their help with handsearching.

  • We thank Professor Aubrey Sheiham for the Aubrey Sheiham Public Health & Primary Care Scholarship (2011) for supporting the systematic review.

  • We also thank Dr Beck and Dr Couper (PAVE 2008) and Dr Ide (Ide 2003) who provided valuable information about the included study.

Data and analyses

Download statistical data

Comparison 1. Secondary prevention: periodontal treatment versus community care
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 All cardiovascular events (25 months)1303Risk Ratio (M-H, Fixed, 95% CI)0.72 [0.23, 2.22]
2 Serum hs-CRP (1 year)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
3 Number of participants who had high hs-CRP (1 year)1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
4 Adverse events related to the treatment (25 months)1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
Analysis 1.1.

Comparison 1 Secondary prevention: periodontal treatment versus community care, Outcome 1 All cardiovascular events (25 months).

Analysis 1.2.

Comparison 1 Secondary prevention: periodontal treatment versus community care, Outcome 2 Serum hs-CRP (1 year).

Analysis 1.3.

Comparison 1 Secondary prevention: periodontal treatment versus community care, Outcome 3 Number of participants who had high hs-CRP (1 year).

Analysis 1.4.

Comparison 1 Secondary prevention: periodontal treatment versus community care, Outcome 4 Adverse events related to the treatment (25 months).

Appendices

Appendix 1. MEDLINE via OVID search strategy

1. exp Cardiovascular diseases/
2. ((myocardial or heart$) adj5 infarc$).mp.
3. (heart adj6 (disease$ or attack$)).mp.
4. (coronary adj6 (disease$ or syndrome$)).mp.
5. (angina or "transient ischaemic attack$").mp.
6. exp Atherosclerosis/
7. (atherosclerosis or arteriosclerosis).mp.
8. "peripheral arterial disease".mp.
9. exp Cerebrovascular Disorders/
10. (stroke$ or (ischemia adj3 brain$) or (infarc$ adj3 brain$) or "intercranial haemorrhage$" or "intercranial hemorrhage$").mp.
11. exp Thrombosis/
12. (thrombosis or occulsion$ or thromboses or aneurysm$ or embolism$).mp.
13. DVT.ti,ab.
14. ("atheromatous plaque" or atheromata$).mp.
15. or/1-14
16. exp Periodontal Diseases/
17. periodont$.mp.
18. (gingivitis or gingiva$).mp.
19. paradont$.mp.
20. or/16-19
21. exp Preventive Dentistry/
22. Dental Care for Chronically Ill/
23. exp Periodontics/
24. (scal$ adj4 polish$).mp.
25. (root$ adj4 plan$).mp.
26. ((tooth adj6 scal$) or (teeth adj6 scal$) or (dental adj6 scal$)).mp.
27. (oral and dental and prophylaxis).mp.
28. (gingivectomy or gingivoplasty or "subgingival curretage" or "guided tissue regeneration").mp.
29. Surgical flaps/
30. "surgical flap$".mp.
31. ((29 or 30) and periodont$).mp.
32. (periodont$ adj3 (therap$ or treat$ or surger$)).mp.
33. Oral Health/
34. exp Oral Hygiene/
35. (mouthrinse$ or mouth-rinse$ or "mouth rinse$" or mouthwash$ or mouth-wash$ or "mouth wash$" or toothbrush$ or "tooth brush$" or tooth-brush$ or floss$).mp.
36. exp Dentifrices/
37. (dentifrice$ or toothpaste$ or tooth-paste$ or "tooth paste$").mp. [mp=title, original title, abstract, name of substance word, subject heading word, unique identifier]
38. Chlorhexidine/
39. (chlorhexidine or eludril or chlorohex$ or corsodyl).mp.
40. exp Anti-bacterial agents/
41. (antibiotic$ or anti-biotic$ or antibacterial$ or anti-bacterial$).mp.
42. exp Tetracyclines/
43. (tetracycline$ or doxycycline$ or minocycline$ or roxithromycin$ or moxifloxacin$ or ciprofloxacin$ or metronidazole$).mp.
44. (Periostat or Atridox or Elyzol or PerioChip or Arestin or Actisite).mp.
45. 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44
46. 15 and 20 and 45

The above subject search was linked to the Cochrane Highly Sensitive Search Strategy (CHSSS) for identifying randomised trials in MEDLINE: sensitivity maximising version (2008 revision) as referenced in Chapter 6.4.11.1 and detailed in box 6.4.c of theCochrane Handbook for Systematic Reviews of Interventions, version 5.1.0 [updated March 2011] (Higgins 2011).

1. randomized controlled trial.pt.
2. controlled clinical trial.pt.
3. randomized.ab.
4. placebo.ab.
5. drug therapy.fs.
6. randomly.ab.
7. trial.ab.
8. groups.ab.
9. or/1-8
10. exp animals/ not humans.sh.
11. 9 not 10

Appendix 2. The Cochrane Oral Health Group's Trials Register search strategy

From July 2013, searches of the Cochrane Oral Health Group's Trials Register were undertaken using the Cochrane Register of Studies and the search strategy below:

#1 ((cardiovascular or myocardial or heart* or coronar* or "artery disease*" or angina or "transient ischaemic attack*" or atherosclerosis or arteriosclerosis or "peripheral arterial disease*" or cerebrovascular or stroke* or ischemia or "intercranial hemorrhage" or "intercranial haemorrhage" or thrombosis or thromboses or aneurysm* or embolism* or DVT):ti,ab) AND (INREGISTER)
#2 ((periodont* or gingivitis or gingiva* or paradont*):ti,ab) AND (INREGISTER)
#3 (#1 and #2) AND (INREGISTER)

Previous searches were undertaken using the Procite software and the search strategy below:

((cardiovascular or myocardial or heart* or coronar* or "artery disease*" or angina or "transient ischaemic attack*" or atherosclerosis or arteriosclerosis or "peripheral arterial disease*" or cerebrovascular or stroke* or ischemia or "intercranial hemorrhage" or "intercranial haemorrhage" or thrombosis or thromboses or aneurysm* or embolism* or DVT) AND (periodont* or gingivitis or gingiva* or paradont*))

Appendix 3. The Cochrane Central Register of Controlled Trials (CENTRAL) search strategy

#1. Exp CARDIOVASCULAR DISEASES
#2. (myocardial or heart*) NEAR infarc*
#3. heart NEAR (disease* or attack*)
#4. (coronary NEAR (artery disease* or syndrome*))
#5. (angina pectoris OR "transient ischaemic attack*")
#6. exp ATHEROSCLEROSIS
#7. (atherosclerosis OR arteriosclerosis)
#8. "peripheral arterial disease"
#9. exp CEREBROVASCULAR DISORDERS
#10. (stroke* or (ischemia NEAR brain*) OR (infarc* NEAR brain*) OR "intercranial haemorrhage*" or "intercranial hemorrhage*")
#11. exp THROMBOSIS
#12. (thrombosis or occlusion* or thromboses or aneurysm* or embolism*)
#13. (DVT):ti,ab
#14. ("atheromatous plaque" or atheromata*)
#15. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14
#16. exp PERIODONTAL DISEASES
#17. periodont*
#18. (gingivitis or gingival*)
#19. paradont*
#20. #16 OR #17 OR #18 OR #19
#21. exp PREVENTIVE DENTISTRY
#22. Dental Care for Chronically Ill
#23. exp PERIODONTICS
#24. (scal* NEAR polish*)
#25. (root* NEAR plan*)
#26. (tooth NEAR scal*) OR (teeth NEAR scal*) OR (dental NEAR scal*)
#27. (oral AND dental AND prophylaxis)
#28. (gingivectomy OR gingivoplasty OR "subgingival curretage" OR subgingival curettage" OR "guided tissue regeneration")
#29. Surgical flaps
#30. "surgical flap*"
#31. ((#29 OR #30) AND periodont*)
#32. (periodont* NEAR (therap* OR treat* OR surger*))
#33. Oral Health
#34. exp ORAL HYGIENE
#35. (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*)
#36. exp DENTIFRICES
#37. (dentifrice* OR toothpaste* OR tooth-paste* OR "tooth paste*")
#38. Chlorhexidine
#39. (chlorhexidine OR eludril OR chlorohex* or corsodyl)
#40. exp ANTI-BACTERIAL AGENTS
#41. (antibiotic* or anti-biotic* or antibacterial* or anti-bacterial*)
#42. exp TETRACYCLINES
#43. (tetracycline* OR doxycycline* OR minocycline* OR roxithromycin* OR moxifloxacin* OR ciprofloxacin* OR metronidazole*)
#44. (Periostat OR Atridox OR Elyzol OR PerioChip OR Arestin OR Actisite)
#45. #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR 41 OR #42 OR #43 OR #44
#46. #15 AND #20 AND #45

Appendix 4. EMBASE via OVID search strategy

1. exp Cardiovascular diseases/
2. ((myocardial or heart$) adj5 infarc$).mp.
3. (heart adj6 (disease$ or attack$)).mp.
4. (coronary adj6 (artery disease$ or heart muscle ischemia)).mp.
5. (angina pectoris or "transient ischaemic attack$").mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
6. exp Atherosclerosis/
7. (atherosclerosis or arteriosclerosis).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
8. "peripheral arterial disease".mp.
9. exp Cerebrovascular Disorders/
10. (stroke$ or (ischemia adj3 brain$) or (infarc$ adj3 brain$) or "inter cranial haemorrhage$" or "inter cranial hemorrhage$").mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
11. exp Thrombosis/
12. (thrombosis or occlusion$ or "occlusive cerebrovascular disease" or aneurysm$ or embolism$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
13. DVT.ti,ab.
14. ("atherosclerotic plaque" or atheroma$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
15. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14
16. exp Periodontal Diseases/
17. periodont$.mp.
18. (gingivitis or gingiva$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
19. paradont$.mp.
20. 16 or 17 or 18 or 19
21. exp Preventive Dentistry/
22. Dental Care for Chronically Ill/
23. exp Periodontics/
24. (scal$ adj4 polish$).mp.
25. (root$ adj4 plan$).mp.
26. ((tooth adj6 scal$) or (teeth adj6 scal$) or (dental adj6 scal$)).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
27. (oral and dental and prophylaxis).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
28. (gingivectomy or gingivoplasty or "subgingival curretage" or "subgingival curettage" or "guided tissue regeneration").mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
29. Surgical flaps/
30. "surgical flap$".mp.
31. (29 or 30) and periodont$.mp.
32. (periodont$ adj3 (therap$ or treat$ or surger$)).mp.
33. Oral Health/
34. exp Oral Hygiene/
35. (mouthrinse$ or mouth-rinse$ or "mouth rinse$" or mouthwash$ or mouth-wash$ or "mouth wash$" or toothbrush$ or "tooth brush$" or tooth-brush$ or floss$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
36. exp Dentifrices/
37. (dentifrice$ or toothpaste$ or tooth-paste$ or "tooth paste$").mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
38. Chlorhexidine/
39. (chlorhexidine or eludril or chlorohex$ or corsodyl).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
40. exp Anti-bacterial agents/
41. (antibiotic$ or anti-biotic$ or antibacterial$ or anti-bacterial$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
42. exp Tetracyclines/
43. (tetracycline$ or doxycycline$ or minocycline$ or roxithromycin$ or moxifloxacin$ or ciprofloxacin$ or metronidazole$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
44. (Periostat or Atridox or Elyzol or PerioChip or Arestin or Actisite).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer]
45. 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44
46. 15 and 20 and 45

The above subject search was linked to the Cochrane Oral Health Group filter for identifying RCTs in EMBASE via OVID:

1. random$.ti,ab.
2. factorial$.ti,ab.
3. (crossover$ or cross over$ or cross-over$).ti,ab.
4. placebo$.ti,ab.
5. (doubl$ adj blind$).ti,ab.
6. (singl$ adj blind$).ti,ab.
7. assign$.ti,ab.
8. allocat$.ti,ab.
9. volunteer$.ti,ab.
10. CROSSOVER PROCEDURE.sh.
11. DOUBLE-BLIND PROCEDURE.sh.
12. RANDOMIZED CONTROLLED TRIAL.sh.
13. SINGLE BLIND PROCEDURE.sh.
14. or/1-13
15. ANIMAL/ or NONHUMAN/ or ANIMAL EXPERIMENT/
16. HUMAN/
17. 16 and 15
18. 15 not 17
19. 14 not 18

Appendix 5. CINAHL via EBSCO search strategy

S1 MH Cardiovascular diseases
S2 (myocardial or (heart* N5 infarc*))
S3 (heart N6 disease* or attack*)
S4 (coronary N6 disease* or syndrome*)
S5 (angina or "transient ischaemic attack*")
S6 MH Atherosclerosis
S7 (atherosclerosis or arteriosclerosis)
S8 "peripheral arterial disease"
S9 MH Cerebrovascular Disorders
S10 (stroke* or (ischemia N3 brain*) or (infarc* N3 brain*) or intracranial haemorrhage* or intracranial hemorrhage*)
S11 MH Thrombosis
S12 (thrombosis or occlusion* or thromboses or aneurysm* or embolism*)
S13 TI DVT or AB DVT
S14 ("atheromatous plaque" or ¡°atherosclerotic plaque¡± or atheromata*)
S15 S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11 or S12 or S13 or S14
S16 MH Periodontal Diseases
S17 periodont*
S18 (gingivitis or gingival*)
S19 paradont*
S20 S16 or S17 S18 or S19
S21 MH Preventive Dentistry
S22 Dental Care for Chronically Ill
S23 MH Periodontics
S24 (scal* N4 polish*)
S25 (root* N4 plan*)
S26 (tooth N6 scal*) or (teeth N6 scal*) or (dental N6 scal*)
S27 oral and dental and prophylaxis
S28 (gingivectomy or gingivoplasty or subgingival curettage* or guided tissue regeneration)
S29 Surgical flaps
S30 "surgical flap*"
S31 ((S29 or S30) and periodont*)
S32 (periodont* N3 therap* or treat* or surger*)
S33 Oral Health
S34 MH Oral Hygiene
S35 (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*)
S36 MH Dentifrices
S37 (dentifrice* or toothpaste* or tooth-paste* or "tooth paste*")
S38 Chlorhexidine
S39 (chlorhexidine or eludril or chlorohex* or corsodyl)
S40 Anti bacterial agents
S41 (antibiotic* or anti-biotic* or antibacterial* or anti-bacterial*)
S42 Tetracyclines
S43 (tetracycline* or doxycycline* or minocycline* or roxithromycin* or moxifloxacin* or ciprofloxacin* or metronidazole*)
S44 (Periostat or Atridox or Elyzol or PerioChip or Arestin or Actisite)
S45 S21 or S22 or S23 or S24 or S25 or S26 or S27 or S28 or S31 or S32 or S33 or S34 or S35 or S36 or S37 or S38 or S39 or S40 or S41 or S42 or S43 or S44
S46 S15 and S20 and S45

The above subject search was linked to the Cochrane Oral Health Group filter for CINAHL via EBSCO:

S1 MH Random Assignment or MH Single-blind Studies or MH Double-blind Studies or MH Triple-blind Studies or MH Crossover design or MH Factorial Design  
S2 TI ("multicentre study" or "multicenter study" or "multi-centre study" or "multi-center study") or AB ("multicentre study" or "multicenter study" or "multi-centre study" or "multi-center study") or SU ("multicentre study" or "multicenter study" or "multi-centre study" or "multi-center study") 
S3 TI random* or AB random*  
S4 AB "latin square" or TI "latin square" 
S5 TI (crossover or cross-over) or AB (crossover or cross-over) or SU (crossover or cross-over)  
S6 MH Placebos  
S7 AB (singl* or doubl* or trebl* or tripl*) or TI (singl* or doubl* or trebl* or tripl*)
S8 TI blind* or AB mask* or AB blind* or TI mask*  
S9 S7 and S8
S10 TI Placebo* or AB Placebo* or SU Placebo*  
S11 MH Clinical Trials 
S12 TI (Clinical AND Trial) or AB (Clinical AND Trial) or SU (Clinical AND Trial) 
S13 S1 or S2 or S3 or S4 or S5 or S6 or S9 or S10 or S11 or S12  

Appendix 6. OpenGrey search strategy

(periodont* or paradont*) AND cardiovascular
(periodont* or paradont*) AND heart*
(periodont* or paradont*) AND stroke*
(periodont* or paradont*) AND coronar*

Appendix 7. US National Institutes of Health Trials Register (ClinicalTrials.gov) search strategy

cardiovascular AND periodontitis
heart AND periodontitis
stroke AND periodontitis
coronary AND periodontitis

Appendix 8. WHO International Clinical Trials Registry Platform search strategy

cardiovascular AND periodont*
stroke AND periodont*
"heart disease" AND periodont*
coronar* AND periodont*

Contributions of authors

  • Chunjie Li and Zongkai Lv proposed this clinical question, registered the title with the Cochrane Oral Health Group and were first authors of this review.

  • Drafting and revising of the protocol: Chunjie Li, Zongkai Lv, Zongdao Shi, Ye Zhu, Yafei Wu and Longjiang Li.

  • Searching of Chinese databases: Zongkai Lv.

  • Study identification: Chunjie Li and Zongkai Lv.

  • Data extraction and risk of bias assessment: Chunjie Li and Zongkai Lv.

  • Data management and data analysis: Chunjie Li.

  • Data interpreting: Yafei Wu and Ye Zhu.

  • Drafting the systematic review: Chunjie Li.

  • Revising of the systematic review: Zongkai Lv, Zongdao Shi, Ye Zhu, Yafei Wu, Longjiang Li and Zipporah Iheozor-Ejiofor.

Declarations of interest

  • Chunjie Li was supported by the 2011 Aubrey Sheiham Public Health & Primary Care Scholarship and finished the systematic review at the UK Cochrane Centre. We declare that the scholarship had no impact on the review content.

  • Zongkai Lv, Zongdao Shi, Ye Zhu, Yafei Wu, Longjiang Li, Zipporah Iheozor-Ejiofor: no interests to declare.

Sources of support

Internal sources

  • West China College of Stomatology, Sichuan University, China.

  • Chinese Cochrane Center, China.

  • National University Student Innovation Test Plan, China.

    Grant Number: 101061001

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

  • School of Dentistry, The University of Manchester, UK.

External sources

  • Cochrane Oral Health Group Global Alliance, UK.

    All reviews in the Cochrane Oral Health Group are supported by Global Alliance member organisations (British Association of Oral Surgeons, UK; British Orthodontic Society, UK; British Society of Paediatric Dentistry, UK; British Society of Periodontology, UK; Canadian Dental Hygienists Association, Canada; Mayo Clinic, USA; National Center for Dental Hygiene Research & Practice, USA; New York University College of Dentistry, USA; and Royal College of Surgeons of Edinburgh, UK) providing funding for the editorial process (http://ohg.cochrane.org/).

  • UK Cochrane Centre, UK.

  • National Institute for Health Research (NIHR), UK.

    CRG funding acknowledgement:
    The NIHR is the largest single funder of the Cochrane Oral Health Group.

    Disclaimer:
    The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health.

Differences between protocol and review

  • In the inclusion criteria, the depth of the periodontal pockets was changed from 5 mm to 4 mm. This decision was based on clinical expert advice to shift focus from the severity to any clinical diagnosis of periodontitis.

  • The following exclusion criteria: 'patients with severe systemic diseases other than cardiovascular disease, who are pregnant, lactating or unable to return for follow-up' and 'studies not focusing on primary or secondary prevention' were added to the review as they were erroneously omitted from the protocol.

  • 'Follow-up time of one year or longer' was added to the types of studies as suggested by the Cochrane Oral Health Group.

  • Heart function parameters (such as ejection fraction, etc.) were added as a secondary outcome considering the aims of this review.

  • The Cochrane Heart Group's Trials Register was not searched as all trials in the register were also available in CENTRAL.

  • The US National Institutes of Health Trials Register was added to the search in accordance with the new standards for the conduct of Cochrane systematic reviews (Methodological standards for the conduct of new Cochrane intervention reviews (MECIR) version 2.3).

  • The description of the seven domains used for risk of bias assessment changed (as the Cochrane Handbook for Systematic Reviews of Interventions evolved from version 5.0 to 5.1), but the essence stayed exactly the same.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

PAVE 2008

  1. a

    AE = adverse events; BOP = bleeding on probing; CAL = clinical attachment level; CVD = cardiovascular disease; hs-CRP = high-sensitivity C-reactive protein; PPD = probing pocket depth; RCT = randomised controlled trial; SAE = serious adverse event; SD = standard deviation; SRP = scaling and root planing

Methods
  • Type of study: parallel RCT

  • Stratification: randomisation was stratified by clinic and smoking status (whether subjects were smokers in the past 5 years)

  • Sample size calculation: not reported

  • Funding: NIDCR grant

  • Country: USA

  • Timeframe of the study: January 2003 to June 2005

(other methods detail: please see the risk of bias table)

Participants
  • Centres: 5, the University at Buffalo, the University of North Carolina at Chapel Hill, Boston University, Kaiser Permanente Center for Health Research/Oregon Health and Sciences University, and the University of Maryland, Baltimore, Maryland

  • Inclusion criteria: to be eligible for the study, participants had to satisfy cardiac and periodontal inclusion criteria. For the cardiovascular criteria, participants had to be ≤ 75 years of age with ≥ 50% blockage of one coronary artery or have had a coronary event within 3 years but ≥ 3 months previously, including myocardial infarction, coronary artery bypass graft surgery, or coronary transluminal angioplasty with or without a stent. The periodontal inclusion criteria were the presence of at least 6 natural teeth, including third molars, with at least 3 teeth with PPD ≥ 4 mm, at least 2 teeth with interproximal CAL ≥ 2 mm, and ≥ 10% of sites having BOP. The criteria were applied after accounting for tooth extractions that were deemed clinically necessary

  • Exclusion criteria: not reported

  • Participants type: moderate to severe periodontitis and CVD

  • Number of participants: total 303; intervention group 151; control group 152

  • Gender of participants: total, male 216, female 87; intervention group 104/47; control group 112/40

  • Age of participants: total mean = 59.6±8.8 (SD); intervention group 59.5±9.1; control group 59.8±8.7

  • Lost to follow-up: by the time of the 6-month visit, 14 participants had withdrawn consent and 7 had been lost to follow-up. They were all considered as drop-outs. Among follow-up participants, only 228 had clinical follow-up. By the time of 1 year, only 37 had clinical follow-up

Interventions
  • Both groups had hopeless teeth extracted before randomisation

  • Intervention group: oral hygiene instruction + full mouth SRP under local anaesthesia (30% of the treatment being completed > 2 months after randomisation; 92.7% of the participants received the treatment; 85% of them received supra-gingival scaling)

  • Control group (community care group): oral hygiene instruction and given a copy of their oral radiographs and a letter stating the tentative oral findings and recommended to seek the opinion of a dentist (9% of the participants in the control group got SRP outside the study within 6 months and 11% of them got SRP within the whole follow-up process)

  • Besides the study treatment, some participants sought dental care via other ways (such as their own dental providers); 1% of the participants in the intervention group got SRP outside the study and 9% (6 months) and 11% (whole study follow-up) of the participants in the control group got SRP

  • Duration of follow-up: 6 to 25 months

Outcomes
  • Cardiovascular SAE (all cardiovascular events, measured during the whole study (means 25 months follow-up)) (the time frame was declared in the e-mail from the trial authors)

  • Serum hs-CRP (measured by latex-enhanced nephelometry at baseline, 6 months and 1 year)

  • Number of participants with high hs-CRP (serum hs-CRP > 3 mg/l measured at baseline, 6 months and 1 year)

  • AE (the development of an undesirable medical/dental condition or the deterioration of a pre-existing medical/dental condition following or during exposure to a pharmaceutical product or medical/dental procedure, whether or not considered causally related to the intervention, measured during the whole study)

  • SAE (an experience that is known with certainty or suspected with good reason to constitute a threat to life or to cause severe or permanent damage, measured during the whole study)

NotesThe author provided extra information about the study
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk
  • Quote: "Randomization was stratified by clinic and smoking status (whether subjects were smokers in the past 5 years). A permuted block randomization scheme was used with a random mixture of block sizes within each stratum." In authors' letter "the randomization was by computer using a random number generator in SAS"

  • Comment: random number generation was adequate, low risk of bias

Allocation concealment (selection bias)Low risk
  • Quote: "Clinical centre staff obtained treatment assignments through a Web-based system designed and maintained by the coordinating centre. When a participant was deemed eligible, a staff member used the Web interface to enter the eligibility information, and the system returned the treatment assignment"

  • Comment: the allocation concealment was adequately achieved, low risk of bias

Blinding of participants and personnel (performance bias)
All outcomes
High risk
  • Comment: it was not possible to achieve participant and personnel blinding in this study, high risk of bias

Blinding of outcome assessment (detection bias)
All outcomes
Low risk
  • Quote: in authors' letter "the outcome assessment was blinded"

  • Comment: the previous protocol stated that the study was a single-blind study, low risk of bias

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk
  • Comment: in 6 months, 16/152 (10.5%) in the control group, 5/151 (3.3%) in the intervention group were lost to follow-up, and only 228/303 got clinical follow-up. In 1 year, only 37/303 got clinical follow-up. The follow-up status at other time points was unclear. It is not clear whether there was a significant difference between the study groups in losses to follow-up, unclear risk of bias

Selective reporting (reporting bias)Low risk
  • Comment: all the outcomes were reported, low risk of bias

Other biasHigh risk
  • Comment: only 92.7% of the participants in the intervention group received the treatment, 1% of the participants in intervention group got SRP outside the study and 9% (6 months) and 11% (whole study follow-up) of the participants in control group got SRP. Therefore this study had contamination and co-intervention, high risk of bias

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
  1. a

    CCT = controlled clinical trial; CVD = cardiovascular disease; RCT = randomised controlled trial

Amar 2004Follow-up shorter than 1 year
Bokhari 2012Follow-up shorter than 1 year
Brown 2004No participants had periodontitis
Cullinan 2005Participants in the intervention group did not get any active periodontal treatment
D'Aiuto 2005Follow-up shorter than 1 year
Dietrich 2005A review article, not an RCT
Domínguez 2010No cardiovascular patients involved, no CVD closely-related outcomes reported
Ebersole 1997Not comparing periodontal treatment
El-Sharkawy 2010No cardiovascular patients involved, no CVD closely-related outcomes reported
Elter 2006Not an RCT
Emingil 2011No cardiovascular patients involved, no CVD closely-related outcomes reported
Fajardo 2010Participants got the same periodontal treatment in both groups
Golub 2002No cardiovascular patients involved, no CVD closely-related outcomes reported
Gottehrer 2006Not an RCT
Gottehrer 2007Not an RCT
Gottehrer 2007aNot an RCT
Gunupati 2011Not an RCT
Ide 2003Follow-up shorter than 1 year
Ide 2004Not an RCT
Kamil 2011Follow-up shorter than 1 year
Lösche 2007A review article, not an RCT
Michalowicz 2009All the participants were pregnant
Offenbacher 2006All the participants were pregnant
Ortiz 2009All the participants had rheumatoid arthritis
Oz 2007Follow-up shorter than 1 year
Paju 2006Participants in the intervention group did not get any active periodontal treatment
Quintero 2010Participants included had obesity or diabetes or hypertension
Ramírez 2011Follow-up shorter than 1 year
Sun 2010All the participants had type 2 diabetes
Taylor 2010Follow-up shorter than 1 year
Tonetti 2007Follow-up shorter than 1 year
Tüter 2007Follow-up shorter than 1 year
Tüter 2010Follow-up shorter than 1 year
Ushida 2008Follow-up shorter than 1 year
Vidal 2009All the participants had refractory arterial hypertension
Wozakowska-Kapłon 2009A review article, not an RCT
Yuan 2010Not an RCT, it is a CCT
Zhao 2010Half of the included participants had aggressive periodontitis

Characteristics of studies awaiting assessment [ordered by study ID]

Payne 2011

  1. a

    hs-CRP = high-sensitivity C-reactive protein; LDL = low-density lipoprotein; RCT = randomised controlled trial; VLDL = very-low-density lipoprotein

Methods
  • Type of study: placebo-controlled, double-blinded parallel RCT

  • Stratification: the randomisation was stratified by study centre (University of Nebraska Medical Center College of Dentistry (UNMC COD) or Stony Brook) and current smoking status (current smoker or not current smoker)

  • Sample size calculation: reported

  • Funding: NIDCR grant

  • Country: USA

  • Timeframe of the study: June 2012 to October 2005

Participants
  • Centres: 2, UNMC COD and the School of Dental Medicine at Stony Brook University (Stony Brook)

  • Inclusion criteria: 45-70 years of age at telephone screening; postmenopausal for at least 6 months and not receiving hormone replacement therapy (HRT); osteopenia of the lumber spine or femoral neck (T-score of -1.0 to -2.5 inclusive); history of generalized moderate to advanced periodontitis and undergoing periodontal maintenance; and having at least 9 posterior teeth and at least 2 sites with probing depths ≥ 5 mm together with bleeding on probing, ≥ 5 mm clinical attachment level loss, and radiographic evidence of alveolar bone height loss, were undergoing periodontal maintenance therapy. Subjects had no history of myocardial infarction, angina, or stroke. Subjects also had to be willing to sign UNMC and Stony Brook Institutional Review Board-approved consent forms and had to be in good general health without co-morbidities that may interfere with adherence to the study protocol, planned follow-up or endpoint measurement

  • Exclusion criteria: allergy or hypersensitivity to tetracyclines; diseases or regular drug therapy that would affect the inflammatory or immune response (e.g., chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs)) or bone remodeling (e.g., prescription estrogens, bisphosphonates, calcitonin, and steroids); requirement for antibiotic premedication; diabetes; active periodontal therapy within the past year; normal bone mineral density (BMD) at both the lumbar spine and femoral neck (T-score above -1.0) or osteoporosis of the lumbar spine or femoral neck (T-score less than -2.5)

  • Participants: postmenopausal patients with chronic periodontitis and osteopenia of the lumber spine or femoral neck

  • Number of participants: total 113; intervention group 51; control group 62

  • Gender of participants: total male 0, female 113; intervention group 51/0; control group: 62/0

  • Age of participants: total mean = 58.31; intervention group: 58.62±5.96 (SD); control group 58.06±5.73

  • Lost to follow-up: the protocol was amended in April 2004, at which point 13 subjects had withdrawn consent (placebo n = 2, SDD n = 10) or had withdrawn (SDD n = 1) due to a serious adverse event, to allow measurement of inflammatory biomarkers in stored (-80°C) serum. 2 additional SDD subjects withdrew following the protocol amendment and refused to complete an exit exam that included the addendum study consent request. 53 subjects were randomised at Stony Brook; 46 Stony Brook subjects completed the trial and signed an addendum consent form to conduct additional serum analyses (ApoA-I and ApoA-II assessment) and serum was not collected from 1 subject at the 1 year visit

Interventions
  • Intervention group: 20 mg doxycycline twice daily for 2 years (low-dose or subantimicrobial dose doxycycline; SDD)

  • Control group: a placebo look-alike twice daily for 2 years

  • All subjects received calcium and vitamin D supplements twice daily (a total of 1200 mg of calcium and 400 IU of vitamin D daily). Subjects were instructed not to take the study drug and calcium/vitamin D at the same time, being certain the supplements were taken at least 1 hour after taking the study drug. All subjects received periodontal maintenance every 3-4 months throughout the study, delivered by the subjects' own dental care providers and not by the study clinicians

  • Duration of follow-up: 24 months

Outcomes
  • Serum hs-CRP (measured by ELISA-based assay, at baseline, 1 year and 2 years)

  • Total cholesterol, HDL-C and triglycerides (measured by ELISA-based assay, measured at baseline, 1 year and 2 years)

  • LDL, VLDL (measured by calculation, at baseline, 1 year and 2 years)

  • Serum ApoA-I and ApoA-II (measured by ELISA-based assay, at baseline, 1 year and 2 years) (Only the data from Stony Brook subjects were included because insufficient amounts of serum remained from the Nebraska subjects after completion of the biomarker analyses)

NotesAll the included participants were female and had osteopenia of the lumber spine or femoral neck. The eligibility is not clear. Some data need confirmation from the authors and the eligibility needs further discussion

Characteristics of ongoing studies [ordered by study ID]

Azhar 2010

Trial name or title
  • Scientific title: influence of periodontal treatment on systemic inflammatory mediators: hsC-reactive protein, fibrinogen and white blood cells in CHD patients

  • Public title: influence of periodontal treatment on systemic inflammatory mediators perio-CHD

Methods
  • Study type: parallel RCT

  • Randomisation: not clearly stated

  • Allocation concealment: not clearly stated

  • Blinding: single-blinded (investigator)

Participants
  • Inclusion criteria: A) General/medical: 1) any race/ethnic group; 2) aged > 30 years; 3) male or female; 4) coronary heart disease (CHD) case confirmed by CHD angiography; 5) CHD diagnosed > 3 months prior to entry into study; 6) no acute or chronic systemic conditions (see exclusion criteria below); 7) no medications/medication history that can interfere with the study (see exclusion criteria below); 8) non-smoker (= never smoked) or former smoker (= does not smoke now and has not smoked at all for a minimum of the last 12 consecutive months); 9) able and willing to comply with study procedures; 10) able and willing to be available for the duration of the study; 11) able and willing to provide signed informed consent. B) Oral/periodontal: 1) dentate with at least 14 natural teeth, excluding third molars, which can be evaluated periodontally; 2) baseline whole mouth BOP > 20% of sites; 3) periodontitis case: periodontitis case defined as subject having ≥ 4 teeth with ≥ 1 site with PPD ≥ 4 mm and CAL ≥ 3 mm at same site; 4) no mechanical periodontal therapy in the last 6 months; 5) no acute oral diseases (mucosal lesions), oral infections, need for immediate dental/periodontal care (e.g., NUG)

  • Exclusion criteria: A) General/medical: 1) former smoker who does not smoke but who has smoked = 1 cigarette (or equivalent, in form of water pipe, pipe, cigar) in the last 12 months; 2) females pregnant or lactating; 3) systemic chronic conditions known to be associated with periodontitis or with changes in systemic inflammation: diabetes, rheumatoid arthritis, rheumatic fever, SLE, malignancy, respiratory diseases, renal diseases, other (e.g. autoimmune diseases, fungal infections, immunological deficiencies, etc.); 4) systemic acute conditions known to affect systemic markers of inflammation: acute bacterial infection, acute viral infection (common cold, influenza, sinusitis), orthopaedic trauma, surgery; 5) medications known to affect systemic inflammatory biomarker: statins, systemic steroids, non-steroidal anti-inflammatory drugs, immunosuppressants; 6) medications potentially affecting systemic inflammatory markers, if therapy started less than 3 months prior to study such as hormone replacement therapy, contraceptives; 7) systemic antibiotic therapy in the last 3 months. B) Oral/periodontal: 1) BOP = 20% of sites; 2) topical/local antibiotic or anti-inflammatory therapy in last 6 months; 3) acute oral infections; 4) oral wounds, including recent (< 2 months) extractions

  • Total number of participants: 317

Interventions
  • Intervention group: SRP and oral hygiene instructions

  • Control group: no treatment

  • Follow-up: unclear

OutcomesChanges in hs-CRP (the time of recording is unclear)
Starting dateJuly 2008
Contact information
  • Person: Mohammad Azhar

  • Address: Punjab Institute of Cardiology

  • Country: Pakistan

NotesRecruitment has finished

Haas 2013

Trial name or title
  • Scientific title: periodontal therapy in coronary artery patients (PerioCardio)

  • Public title: periodontal therapy in coronary artery patients (PerioCardio)

Methods
  • Study type: parallel RCT

  • Randomisation: mentioned but the detail was not clear

  • Allocation concealment: not clearly stated

  • Blinding: single-blinded (outcomes assessor)

Participants
  • Inclusion criteria: 35-70 years coronary artery disease more than 10 teeth chronic periodontitis defined as 2 non-adjacent teeth with probing depth > 5 mm and periodontal attachment loss > 4 mm

  • Exclusion criteria: use of antibiotics in the last 6 months, periodontal therapy in the last 12 months

  • Total number of participants: 100

Interventions
  • Intervention group: SRP under local anaesthesia + oral hygiene instruction and motivation

  • Control group: 1 session of supra-gingival calculus removal

  • Follow-up: 1 year

OutcomesChanges of hs-CRP, HDL-C, LDL-C and total cholesterol levels (3, 6 months and 1 year after the treatment)
Starting dateJanuary 2012
Contact information
  • Person: Haas

  • Address: Federal University of Rio Grande do Sul

  • Country: Brazil

Notes 

Skilton 2011

  1. a

    BOP = bleeding on probing; CAL = clinical attachment level; hs-CRP = high-sensitivity C-reactive protein; HDL = high-density lipoprotein; LDL = low-density lipoprotein; PPD = probing pocket depth; RCT = randomised controlled trial; SLE = systemic lupus erythematosus; SRP = scaling and root planing

Trial name or title
  • Scientific title: associations between periodontal disease and cardiovascular surrogate endpoints following periodontal treatment in an adult indigenous population with moderate/severe periodontal disease

  • Public title: associations between periodontal disease and cardiovascular surrogate endpoints in an adult indigenous population

Methods
  • Study type: parallel RCT

  • Randomisation: after screening for periodontal disease, those with moderate or severe periodontal disease will be randomised on a 1:1 basis to either the treatment or control group. A computer generated permuted block randomisation sequence will be used, stratified by recruitment site (Darwin/Palmerston, Katherine)

  • Allocation concealment: not clearly stated

  • Blinding: the measurement of cardiovascular endpoints and the statistical analysis will be blinded

Participants
  • Inclusion criteria: indigenous persons aged > 25 years that have lived in their current location for more than 2 years, and who plan to live at their current location for the next 2 years, with moderate/severe periodontal disease

  • Exclusion criteria: those with rheumatic heart disease history or other cardiac conditions requiring antibiotic prophylaxis for prevention of subacute bacterial endocarditis, or with obvious endodontic lesions or other sources of oral infection

  • Total number of participants: 266

Interventions
  • Intervention group: SRP

  • Control group: no treatment

  • Follow-up: 1 year

Outcomeshs-CRP, HDL-C, LDL-C, APO-A1, APO-B and total cholesterol (3 months and 1 year after the treatment)
Starting dateJune 2010
Contact information
  • Person: Lisa M Jamieson

  • Address: Australian Research Centre for Population Oral Health, School of Dentistry, University of Adelaide, Adelaide, Australia

  • Country: Australia

NotesRegistered (but retrospectively registered)

Ancillary