European Journal of Cardiovascular Medicine

Cardiovascular disease (CVD) is one of leading causes of death globally due to non-communicable disease. Numerous risk factors are associated with etiopathogenesis of CVD such as hypertension, hyperlipidemia, central obesity, sedentary life style, stress, chronic inflammation etc.¹ It was observed that patients with myocardial infarction were associated with bad oral health.² Periodontitis is inflammatory disease causing the destruction of the tooth supporting structure. It causes elevation of inflammatory mediators in blood such as Metallo matrix proteins (MMPs), C-Reactive Protein (CRP), interleukins (ILs), prostaglandins (PGs), fibrinogen etc. leading to systemic inflammation, endothelial injury and CVD.³

CRP is acute phase protein synthesized by hepatocytes in response to infection or inflammation. CRP primarily eliminates pathogens and damaged cells and complement system activation. It also causes expression of adhesion molecules on the endothelial cells thus contributing to atherogenesis and CVD.^4,5 Hyperlipidemia is a recognized CVD biomarker. LDL cholesterol is particularly implicated in the atherosclerotic plaque formation.⁶ Fibrinogen is a coagulation factor I produced in liver. Its synthesis is upregulated in inflammation by IL-6. It induces atherogenesis by platelet activation, upregulation of adhesion molecule, enhanced macrophage infiltration and thus can act as a biomarker for CVD.⁷

Studies have shown that periodontal treatment (PT) by decreasing metabolic and inflammatory biomarkers lowers the risk of CVD.^8-11 Aim of present review is evaluation of impact of conservative periodontal treatment have on biomarker profile of a cardiovascular disease patient.

Review was conducted according to Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines.¹² The Prospective register of systematic reviews (PROSPERO) identification number of the review is CRD420251122373.

Focused question:

Focused question was formulated according to PICO – patient, intervention, comparison and outcome framework. “In periodontitis patients does conservative periodontal treatment decrease biomarkers of cardiovascular disease compared to those without treatment as measured in terms of CRP, lipid profile – triglyceride (TG), total cholesterol (TC), Low-density lipoprotein cholesterol (LDL), high- density lipoprotein cholesterol (HDL) and fibrinogen blood levels.”

Selection criteria:

Inclusion criteria:

• Studies examining effect of non-surgical periodontal treatment on CVD biomarkers.
• Randomized clinical trials.
• Studies published in English language.
• Studies done on human subjects.

Exclusion criteria:

• Non randomized clinical trials.
• Studies involving surgical periodontal treatment.
• Case reports, case series and review articles.
• Studies published in language other than English.
• Animal studies, in vitro studies.

Outcome variables:

Primary outcome variable in this review was change in CRP and secondary outcome variable was change in lipid profile – TG,TC,LDL,HDL  and fibrinogen level in blood. Reviewers independently extracted the data such as name of author and date of publication, sample size, age, study group, variables and outcome.

Search strategy:

Electronic databases searched for present review were PubMed, Cochrane and google scholar till August 2025.

PubMed:

“conservative periodontal treatment” [TITLE/ABSTRACT] OR “non-surgical periodontal treatment” [TITLE/ABSTRACT] OR “non-surgical periodontal therapy” [TITLE/ABSTRACT] OR “non-surgical periodontal management” [TITLE/ABSTRACT] OR "dental scaling"[MeSH] OR "dental prophylaxis"[MeSH] OR "Root Planing"[Mesh] OR "periodontal debridement"[MeSH Terms] AND   “biomarkers” [MeSH] OR “cardiovascular disease biomarkers” [TITLE/ABSTRACT]

Google scholar:

"non-surgical periodontal treatment" OR "non-surgical periodontal therapy” OR "conservative periodontal therapy"   AND “coronary heart disease" OR "coronary artery disease” OR "cardiovascular disease biomarkers" OR "cardiovascular disease risk markers" AND "biomarkers" OR "risk markers"

Cochrane:

“non-surgical periodontal therapy” [ti,ab,kw] OR “non-surgical periodontal treatment” [ti,ab,kw] OR “conservative periodontal therapy” [ti,ab,kw] AND “cardiovascular disease” [MeSH] OR “cardiovascular disease” [ ti,ab,kw] OR “cardiovascular disease biomarkers” [ti,ab,kw] OR “cardiovascular disease risk markers” [ti,ab,kw]

Trip database:

“non-surgical periodontal treatment” AND “cardiovascular disease biomarkers” OR “cardiovascular disease risk markers”

The references of the selected studies were hand searched for the possible additional researches.

Screening and study selection:

Reviewers (AK and DK) evaluated title and abstract of the selected studies based on inclusion and exclusion. After screening full text was scrutinised for eligibility criteria. Studies which met inclusion criteria was selected for the systematic review with meta-analysis. Any dispute between the reviewers (AK and DK) was be resolved by discussion. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) flowchart (Figure 1).

Risk of bias:

Quality assessment of studies was done with Cochrane Collaboration’s tool for assessment of risk of bias in randomised trials¹³ and following domains were judged- 1) Random Sequence generation, 2) Allocation concealment, 3) Performance bias: blinding of participants and personnels, 4) Detection bias: blinding of outcome assessment, 5) Attrition bias: incomplete outcome data, 6) Reporting bias: selective outcome reporting, and 7) other sources of bias.

Statistical analysis:

RevMan was used for statistical analysis. In accordance with heterogenicity random or fixed effect model was selected. Forest plot was used for the presentation of summary effect as standardised mean difference (SMD) of studies at 95% confidence interval (CI) for CRP, Lipid Profile – TG,TC,LDL,HDL and fibrinogen levels.

Electronic databases search provided 1479 studies from which 33 were removed as duplicates. Title and abstract were screened and 16 articles were selected for full text assessment. Based on inclusion criteria 5 articles were selected for systematic review with meta-analysis (Figure 1). The detailed characteristics of the selected studies are presented in the Table 1.

Figure 1: Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) flowchart for study selection.

Risk of bias:

Methodological quality of selected studies was assessed by Cochrane risk of bias tool.¹³ Two studies^17,18 showed low overall risk of bias while rest had moderate risk.^14,15,16 (Figure 2) All studies reported low random sequence generation bias except one¹⁵. For allocation concealment three studies^16,17,18 reported low risk and two moderate risk^14,15. In performance bias two studies^17,18 reported low risk while rest reported moderate risk. All the studies reported low detection bias risk. For attrition bias, reporting bias and other bias all studies reported low risk. (Figure 3)

Figure 2. Risk of bias graph.

Figure 3. Risk of bias summary.

Outcome variable:

C-reactive protein (CRP):

Random effect was utilized due to high heterogenicity (Figure 4). Test group (with periodontal treatment) showed a statistically significant reduction in the CRP level compared to control group (without periodontal treatment) at 1-3 months follow up (SMD=-0.68, 95% CI: -1.24 to -0.12, p=0.0003). At 6 months follow-up test group showed statistically insignificant reduction in CRP level compared control group (SMD=-1.17, 95% CI: -2.86 to -0.51,p=0.0001). Overall SMD for CRP level demonstrated statistically significant reduction in test group compared to control group (SMD=-0.82, 95% CI: -1.37 to -0.26, p<0.00001).

Figure 4. Forest plot demonstrating change in C-reactive protein (CRP) level at 1-3 months and 6 months between test (with periodontal treatment) and control group (without periodontal treatment).

Lipid Profile:

Triglyceride (TG):

Control group demonstrated a statistically non-significant reduction in TG level compared to the test group at 3 months (SMD=0.12, 95% CI:-0.12 to 0.36,p=0.44), at 6 months (SMD=0.18,95% CI:-0.34 to 0.70) and also as overall SMD for change in TG level (SMD=0.13,95% CI:-0.09 to0.35, p=0.64) (Figure 5).

Figure 5. Forest plot demonstrating change in Triglyceride (TG) level at 3 months and 6 months between Test group (with periodontal treatment) and Control group (without periodontal treatment).

Total cholesterol (TC):

A statistically non-significant reduction of TC was observed in control group compared to test group at 3 months (SMD=0.11, 95% CI:-0.13 to 0.35,p=0.41) and at 6 months (SMD=0.19, 95% CI:-0.33 to 0.71). Overall  SMD for TC showed a statistically non-significant reduction in control group compared to test group (SMD=0.12, 95% CI:-0.10 to 0.34,p=0.61) (Figure 6).

Figure 6. Forest plot of change in Total cholesterol (TC) level at 3 months and 6 months between Test group (with periodontal treatment) and Control group (without periodontal treatment).

High density lipoprotein (HDL):

A statistically non-significant reduction in HDL level was observed in the control group compared to test group at 3 months follow-up (SMD=0.09, 95% CI:-0.15 to 0.33, p=0.91). At 6 months follow-up statistically non-significant reduction was observed in the test group compared to control group (SMD=-0.03, 95% CI:-0.55 to 0.49). Overall SMD for HDL showed a statistically non-significant reduction in control group (SMD=0.07,95% CI:-0.15 to 0.29,p=0.95) (Figure 7).

Figure 7. Forest plot of change in High density lipoprotein (HDL) at 3 months and 6 months between Test group (with periodontal treatment) and Control group (without periodontal treatment).

Low density lipoprotein (LDL):

At 3 months follow-up control group showed a statically non-significant reduction in LDL level (SMD=0.05,95% CI:-0.20 to 0.29,p=0.90) while at 6 months statistically insignificant reduction was observed in the test group (SMD=-0.21, 95% CI:-0.73 to 0.31). The overall SMD depicted no difference between test and control group (Figure 8).

Figure 8. Forest plot of change in Low density lipoprotein (LDL) at 3 months and 6 months between Test group (with periodontal treatment) and Control group (without periodontal treatment).

Fibrinogen:

Random effect model was utilized due to high heterogeneity (Figure 9). Test group showed statistically non-significant reduction in the fibrinogen level at 3 months compared to the control group (SMD=-0.98, 95% CI:-2.79 to 0.83, p<0.00001). At 6 months follow-up control group demonstrated a statistically non-significant reduction in the fibrinogen level (SMD=1.26, 95% CI:-1.29 to 3.81, p<0.00001). Overall SMD for fibrinogen level showed a statistically non-significant reduction in the test group compared to the control group (SMD=-0.09,95% CI:-1.76 to 1.57, p<0.00001).

Figure 9. Forest plot of change in Fibrinogen at 3 months and 6 months between Test group (with periodontal treatment) and Control group (without periodontal treatment).

Table 1. General characteristics of the selected studies.

CRP- C-reactive protein; TG- Triglyceride; TC- Total Cholesterol; HDL- High density lipoprotein; LDL- Low density lipoprotein; B-Baseline; 1-1 Month; 2-2 Months; 3- 3 Months; 6- 6 Months.

Cardiovascular disease forms one of the major health challenges. It is now believed that atherosclerosis is inflammatory condition.¹⁹ Thus the risk of CVD disease is increased with elevated levels of inflammatory makers²⁰ (CRP and fibrinogen) and metabolic markers. Periodontitis have been shown to cause a low-grade systemic inflammation leading to elevated level of CRP and other inflammatory markers which increases the risk of CVD. ²¹ Present systematic review with meta-analysis studied impact of conservative periodontal treatment on biomarkers of the cardiovascular disease.

CRP levels showed statistically significant reduction in test group compared to control group. Similar results were reported in the previous researches. Teeuw et al.,²² Roca-Millan et al.,²³ Meng et al.,²⁴ D’Aiuto et al.,²⁵ and Su et al.,²⁶ also demonstrated statistically significant reduction of CRP level in periodontal treatment group compared to group which received no periodontal treatment. As subgingival bacterial load has been found to be significantly associated with CRP levels²⁷  therefore treatment of periodontitis by decreasing the bacterial count subsequently decreases CRP levels.¹⁷

In present review, lipid profile (TG,TC,HDL,LDL) did not show any significant difference between test and control group. Similar findings were reported by other researchers.^23,24,25 Teeuw et al., however reported a significant reduction in the lipid profile levels in treatment group compared control group.²² Test group demonstrated a small statistically insignificant reduction in the fibrinogen level compared to control group. Similar findings were reported by D’Aiuto et al.²⁵

Strengths of current review are conducting comprehensive screening and selection process according to the Preferred Reporting Items for Systematic Review and Meta-analysis, inclusion of only randomized clinical trials, assessment of risk of bias of selected studies and main characteristics of the selected studies are presented in the review. Limitations of this review are high heterogeneity, language limitation and short duration of selected study.

Present systematic review and meta-analysis demonstrated that conservative periodontal treatment in cardiovascular disease patient significantly reduced C-reactive protein levels while no beneficial effect was observed in Fibrinogen level and lipid profile. Studies with larger sample size and duration are required to further provide evidence in support of the beneficial effect of conservative periodontal treatment in the management of cardiovascular disease patients.

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