Effect of advanced periodontal self-care in patients with early-stage periodontal diseases on endothelial function: An open-label, randomized controlled trial

Abstract

Although a significant association between periodontal disease and atherosclerotic cardiovascular disease has been reported, their cause-to-effect relationship remains controversial. This randomized controlled clinical trial aimed to investigate the effect of advanced self-care on atherosclerotic cardiovascular disease-related vascular function markers flow-mediated brachial artery dilatation (FMD) and serum asymmetric dimethylarginine (ADMA) level in patients with early-stage periodontal disease. The study was designed as a parallel group, 3-month follow-up, open-label, randomized controlled trial. The control group received standard care for periodontal diseases, whereas the test group additionally applied disinfectant using a custom-fabricated prescription tray for advanced self-care twice a day. Overall, 110 patients provided data for FMD and serum ADMA level. No significant improvements in FMD were observed in the control (mean increase, −0.1%; 95% confidence interval [CI], −1.0–0.8; P = 0.805) or test (mean increase, −0.3%; 95% CI, −1.1–0.4; P = 0.398) group. No significant changes in serum ADMA levels were observed (mean reduction, 0.01 μmol/L; 95% CI, −0.00–0.02; P = 0.366 and mean reduction, 0.00 μmol/L; 95% CI, −0.01–0.01; P = 0.349, respectively). No significant between-group differences were found in FMD (mean difference, −0.2%; 95% CI, −1.4–0.9; p = 0.708) or serum ADMA levels (mean difference, 0.01 nmol/L; 95% CI, −0.00–0.03; p = 0.122). Significant improvements in the average probing pocket depth were observed in the control and test groups. The bleeding on probing score in the test group was significantly reduced, while that in the control group was reduced, although not significantly. Periodontal care for a 3-month duration did not provide better endothelial function although improvements of periodontal status in patients with early-stage periodontal diseases. This trial is registered in UMIN Clinical Trials Registry (www.umin.ac.jp/ctr/; ID: UMIN000023395).

The Impact of Periodontal Inflammation on Endothelial Function Assessed by Circulating Levels of Asymmetric Dimethylarginine: A Single-Blinded Randomized Clinical Trial

“…These findings are consistent with data reported by Seinost et al [ 37 ], who showed that flow-mediated dilation was significantly lower in patients with periodontitis when compared with healthy control (6.1% ± 4.4% vs. 8.5% ± 3.4%, p = 0.002), and that periodontal treatment caused a significant improvement in FMD (9.8% ± 5.7%; p = 0.003 in comparison to baseline values) and a simultaneously significant decrease in C-reactive protein concentrations ( p = 0.026). To date, limited studies have examined ADMA concentrations in relation to periodontitis and endothelial function [ 29 ]. Recently, ADMA was proposed to be useful for CV risk stratification and for predicting endothelial function.…”

“…Tsioufis et al [ 38 ] conducted a trial involving untreated hypertensive subjects with concomitant periodontal disease and demonstrated the reduction of asymmetric dimethylarginine (ADMA) concentration after periodontal treatment. Okada et al [ 29 ] recently investigated the impact of periodontal treatment on ADMA levels and FMD values. In contrast with our observations, the authors reported no significant between-group differences in FMD (mean difference, −0.2%; 95% CI, −1.4–0.9; p = 0.708) and serum ADMA levels (mean difference, 0.01 nmol/L; 95% CI, −0.00–0.03; p = 0.122).…”

“…Prior to starting the trial, a power analysis for sample size calculation was employed. Based on a previous study [ 29 ], the sample size was determined by using a number of groups equal to two, an effect size of 0.30 for ADMA, a two-sided α error of 0.05, and 80% power. Assuming a 20% dropout rate, it was estimated that ≈ 70 patients per group would be needed.…”

“…The biological plausibility of the association between periodontitis and endothelial dysfunction is exemplified by two potential pathways: (1) the dissemination of periodontal pathogens through blood and their invasion within endothelial cells, promoting platelet aggregation, foam-cell formation, and the development of atheroma; (2) the amplification of systemic inflammation, which directly exacerbates a pre-existent inflammatory setting [ 24 , 25 , 26 ]. Several studies have demonstrated that periodontal treatment is an effective resource for improving endothelial dysfunction [ 27 , 28 , 29 ]. However, the results of prospective studies investigating its potential beneficial effects on asymmetric dimethylarginine (ADMA) are lacking.…”

The Effect of Periodontal Treatment on the Reactive Hyperemia Index. A 1-Year Follow-Up Pilot Study

“…The degree of improvement was associated with improvement in measures of periodontal disease ( 17 ). More recent studies did not find clinical evidence for a positive effect on endothelial function after periodontal therapy, and therefore a possible cause-to-effect relationship remains controversial ( 18 , 19 ).…”