Editor’s Consensus Report: Periodontitis and Atherosclerotic Cardiovascular Disease

The recent consensus report regarding periodontitis and atherosclerotic cardiovascular disease (CVD) published in The American Journal of Cardiology and in the Journal of Periodontology was enlightening. As a former educator in the oral health professions, I could not help but “put on my teacher’s cap” as I read the text, applying the principles found in many texts regarding the interpretation of published scientific research. One of the first principles is to identify the source of authorship and affiliations. One might wonder why this report was supported by an educational grant from the Colgate-Palmolive Company (New York, New York), especially given the recent media revelation of pharmaceutical industry “guidance” and ghostwriting in professional journals. A logical question to ask is, Were the authors provided with a nominal fee to prepare any part of this report, and if so, did industry-influenced recommendations result? The disclosure listing in this consensus document implies strong financial relationships between industry and many members of the authorship team. I am reminded of a statement at the end of the British Antimicrobial Society’s 2006 recommendations for antibiotic prophylaxis: “All the authors declare that during the preparation of this document they were not in the employment of, nor receiving funding from, any pharmaceutical firm or other organization that may have resulted in a conflict of interest.”

The title of the report clearly distinguishes the level of evidence by noting that it is a consensus report, representing a low level of evidence, just above the lowest level of animal studies. The authors list credentials implying that they are qualified to write on the subject of the report. It is unique to find the editorial teams of various professional publications engaging in this sort of collaboration.

As I read the consensus document, I had some questions. The aim of the document is “to provide health professionals … a better understanding of the link between atherosclerotic CVD and periodontitis, and … [suggest] an approach to reducing the risk for primary and secondary atherosclerotic CVD events in patients with periodontitis.” This is confusing to me, because there is no evidence that atherosclerotic CVD events can be prevented with periodontal therapy. A recent (2009) systematic review of periodontal disease (PD) and coronary artery disease suggested that although PD is an independent risk factor for coronary artery disease, the relation is relatively weak, conferring a 24% to 35% increased risk. In their systematic review, Humphrey et al state that intervention studies showing a clear benefit from periodontal treatment and reductions in inflammation would answer the question of the role of PD in CVD. Intervention studies were included in a 2008 report reviewing PD and CVD and citing 2 meta-analyses that gave odds ratios of 1.1 to 2.2, very weak to moderate associations. An odds ratio of 1 is the neutral value and indicates that there is no difference between the groups being compared. The investigators discussed a recent intervention study and stated, “There is only one recent study that has addressed the outcome of periodontal intervention in subjects with heart disease suggesting that periodontal intervention may not induce more serious adverse events than what might be expected in the community over a 25 month period (Beck et al 2008). Furthermore the study demonstrated that non-surgical routine periodontal therapy did not reduce the risk of serious cardiovascular events.” In the consensus document, the authors note that recent meta-analyses have concluded that “further studies are needed to better define the relation between the two diseases.” They state, “A direct causal relation between periodontitis and atherosclerotic CVD is not established … periodontitis may independently increase the risk for CVD.” My confusion is that the authors’ aim implies that periodontal procedures will reduce the risk for primary and secondary atherosclerotic CVD events in patients with PD. However, the evidence-based science described previously and statements in the consensus report do not appear to support that inference.

As I continued reading, I was distressed by some statements with cited sources that do not support them. For example, “Treatment of PD, especially in patients with elevated glycosylated hemoglobin, improves glycemic control.” Two sources are cited for this statement. Darré et al’s report is a recent meta-analysis of 9 controlled trials examining periodontal therapy and glycemic changes. In this meta-analysis, the investigators state, “Our meta-analysis of nine controlled studies may lead some to conclude that periodontal therapy may improve glycaemic control . … However, this result needs to be viewed with caution for 2 main reasons: first, the lack of robustness revealed by the sensitivity analysis; and, second, deficiencies in the design of some of the included studies, as shown by the quality analysis. By performing an influence analysis, we found that the overall result was not robust. Pooled estimates, calculated by omitting 1 study at a time, became statistically insignificant with the deletion of 1 study.” Darré et al’s conclusion was that “the present meta-analysis represents the best information available to date that addresses this issue, and suggests that periodontal treatment could improve glycaemic control. Nevertheless, these results need to be viewed with caution because of a lack of robustness, and deficiencies in the design of some of the studies included. A randomized controlled trial with sufficient statistical power would help to confirm the results of this meta-analysis.” The investigators’ discussion and conclusions do not seem to support the claim in the consensus document regarding periodontal treatment as a strategy to improve glycemic control, and 7 of the 9 studies reported the lack of a statistically significant improvement in glycemic control.

The second study referenced was an intervention study involving patients with type 2 diabetes mellitus. The investigators reported improved glycosylated hemoglobin levels at a 3-month assessment (but no difference between groups at a 6-month assessment) only in the groups receiving doxycycline as part of the therapy. In fact, 1 group with ultrasonic scaling using 0.12% chlorhexidine in the lavage but that received a placebo (no doxycycline) did not have improved glycemic control. So, the proper phrasing would be “treatment of PD using various therapies plus doxycycline … improves glycemic control for ≤3 months.” In the 6-month assessment of this study, there was no statistically significant difference between baseline glycosylated hemoglobin levels and 6-month levels. In the discussion of Grossi et al’s study, the investigators attributed the improvement in glycosylated hemoglobin levels to a reduction in Porphyromonas gingivalis because of the systemic antibiotic and possibly a doxycycline-mediated inhibition of the glycation process, not the result of receiving periodontal therapy, which included ultrasonic debridement. Other studies in which treatment did not affect glycemic control were not cited in the consensus document. I believe that in general, only studies with positive results were referenced, there was not an adequate inclusion of studies with negative results, the reports cited do not support the statement, and given this, the reader is deceived regarding the strength of the evidence for the claim.

Regarding the section on clinical recommendations, the evidence levels for all but 1 recommendation are low, at C and D. Given this, will periodontists and cardiologists seriously consider following the recommendations in the consensus report? How many individuals would need medical examinations to prevent 1 cardiovascular event? If so, at what cost to patients in terms of laboratory costs, medical visits, and so on? Clearly, patients with established chronic disease (e.g., hypertension, diabetes) will likely be undergoing medical management protocols. What are the cost and benefit to patients with no diagnoses of chronic disease in terms of following these recommendations? The answers to these questions should be investigated.

Finally, I could not help but recall a statement from Michael Glick’s editorial in the Journal of the American Dental Association : “A patient’s socioeconomic status (SES) is a significant risk factor for developing coronary artery disease … yet we do not routinely refer patients with low SES for a cardiovascular work-up. [And] the presence of PD in a specific person has not shown to add any additional discriminatory power to determine if this particular person’s risk of developing cardiovascular disease … is increased.” Glick’s editorial ends with an important statement that profoundly affected me as a member of the oral health care profession: “Editors of professional journals have a responsibility to ensure that the conclusion of a published study is supported by the presented data. Professional organizations and associations have a responsibility to provide their constituencies with legitimate interpretations of scientific findings based on valid interpretation of available data.”

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Dec 23, 2016 | Posted by in CARDIOLOGY | Comments Off on Editor’s Consensus Report: Periodontitis and Atherosclerotic Cardiovascular Disease

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