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Dr. Wynn

Dr. Richard L. Wynn is Professor of Pharmacology at the University of Maryland Dental School. He holds a BS degree in pharmacy and a PhD degree in pharmacology. More »He chaired the Department of Pharmacology at the University of Maryland Dental School from 1980 to 1995. He is the lead author of the Drug Information Handbook for Dentistry, co-author of many other dental drug publications, author of over 300 refereed scientific journal articles, consultant to the Academy of General Dentistry, featured columnist, and a featured speaker presenting more than 500 courses in continuing dental education. One of his primary interests continues to be keeping dental professionals informed of all aspects of drug use in dental practice.

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Twice-a-day Toothbrushing Associated With Decreased Levels of C-reactive Protein and Decrease Risk of Heart Disease.

A study out of University College London examined the association between toothbrushing behavior and cardiovascular disease and whether markers of low grade inflammation/coagulation were associated with frequency of toothbrushing. The results suggest that regular twice-a-day toothbrushing is associated with a decreased risk of heart disease and decreased levels of the inflammatory marker C-reactive protein and the coagulation marker fibrinogen. Read full article.

The study, reported in the British Medical Journal, 2010, was designed to investigate whether a single item self-reported measure of frequency of toothbrushing had any association with serum levels of C-reactive protein and fibrinogen and the risk of cardiovascular events. Participants who reported less toothbrushings had a 70% increased risk of cardiovascular disease events compared with participants who brushed their teeth twice-a-day. Also, there were significant associations between frequency of toothbrushing and markers of low grade systemic inflammation. Participants who brushed their teeth less often had increased serum concentrations of both C-reactive protein and fibrinogen.

The reasons for the study were the following. The presence of inflammatory markers in serum has been consistently associated with a higher risk of cardiovascular disease. Periodontal disease is thought to be a contributing factor associated with inflammation, and systemic inflammation could represent an underlying mechanism that links oral health and cardiovascular disease. Oral infections might add to the inflammatory burden, resulting in increased cardiovascular risk based on serum C-reactive protein and fibrinogen concentrations. Thus, C-reactive protein and fibrinogen might be useful predictors for future cardiovascular events. The authors selected the frequency of toothbrushing as a proxy of periodontal disease and tested the relationship between toothbrushing frequency, inflammatory markers, and risk of cardiovascular disease.

Methods

The investigators used data from the Scottish Health Survey, a cross-sectional survey taken every three to five years that draws a nationally representative sample of the general population living in Scottish households. For this dental study, the investigators combined data on adults aged 35 and older from the 1995, 1998, and 2003 surveys.

The following method was used to assess oral health behaviors. Interviewers visited selected households and collected data on demographics and health behaviors, including oral health behaviors. They inquired about activity in the four weeks before the interview and during a typical week. Oral health behavior was assessed in all survey years from self-reported frequency of visits to a dentist (at least once every six months, every one to two years, or rarely/never), and tooth brushing (brushing teeth twice-a-day, once-a-day, less than once-a-day). In addition, frequency of physical activity was assessed across three domains of activity: leisure time sports, walking for any purpose, and domestic physical work.

At separate visits, nurses collected information on medical history and family history of cardiovascular disease, blood pressure, and blood samples taken from consenting individuals.

For follow-up of clinical events

To follow-up the clinical events, the surveys were linked to a database of hospital admissions and deaths in patients. The primary end point was a composite of fatal and nonfatal cardiovascular events. Mortality from cardiovascular disease was documented, and nonfatal events included hospital admissions related to cardiovascular disease: acute myocardial infarction, coronary artery bypass, percutaneous coronary angioplasty, stroke, and heart failure.

Analysis of blood inflammatory markers

To analyze blood inflammatory markers in a subset of 4830 participants, the investigators collected blood samples for the assessment of C-reactive protein and fibrinogen. Both were determined from serum samples using standard analytical techniques with limits of detection around 0.2 mg/l.

Standard statistical models were used to estimate the risk of cardiovascular disease events or death according to oral hygiene. The association between oral hygiene and inflammatory markers and coagulation was examined using standard statistical techniques.

Results

The final sample size was 11,869 individuals with 46% male and mean age 50.0 years. Oral health behavior was generally good: 62% of the individuals reported regular visits to a dentist (at least every 6 months) and 71% reported good oral hygiene (brushing teeth twice-a-day). Those who brushed less often were more likely to be men with a prevalence of risk factors including smoking, physical inactivity, hypertension, and diabetes.

There were 555 cardiovascular events over an average of 8.1 years of follow-up, and 170 of those were fatal. In 74% of the cardiovascular events, the principal diagnosis was coronary artery disease.

In those individuals reporting poor dental hygiene (never/rarely brushed their teeth), there was an increased risk of cardiovascular events and cardiovascular disease deaths.

Participants who reported less toothbrushings had a 70% increased risk of cardiovascular disease events compared with participants who brushed their teeth twice-a-day.

There were significant associations between frequency of toothbrushing and markers of low grade systemic inflammation. Participants who brushed their teeth less often had increased serum concentrations of both C-reactive protein and fibrinogen.

Also, using this model, the investigators found that other independent predictors of cardiovascular events were smoking, hypertension, and diabetes. The 70% extra risk of heart disease in nonbrushers could be compared to the 135% extra risk of heart disease in those who smoked.

Interpretation of the results

According to the authors, this was the first study to show an association between a single item self-reported measure of toothbrushing and the incidence of cardiovascular disease in a large population sample without overt cardiovascular disease.

These results confirm and strengthen the suggested association between oral hygiene and the risk of cardiovascular disease, in that inflammatory markers were significantly associated with poor oral health behavior. However, the study does not prove that brushing your teeth leads to lower heart disease.

This study adds to previous works on serum markers of inflammation in both cardiovascular and periodontal research. Increased pro-inflammatory cytokines are present in both cardiovascular disease and periodontal disease. This study suggests a possible role of poor oral hygiene in the risk of cardiovascular disease via systemic inflammation.

The reference to the full report is de Oliveira C, Watt R, and Hamer M, "Toothbrushing, Inflammation, and Risk of Cardiovascular Disease: Results from Scottish Health Survey," Brit Med J, 2010, 340:c2451. This study confirms two previous reports by Bahekar AA, Singh S, Saha S, et al, "The Prevalence and Incidence of Coronary Heart Disease is Significantly Increased in Periodontitis: A Meta-analysis,"Am Heart J, 2007, 154(5):830-7, and Mustapha IZ, Debrey S, Oladubu M, et al, "Markers of Systemic Bacterial Exposure in Periodontal Disease and Cardiovascular Disease Risk: A Systematic Review and Meta-anaylsis," J Periodontol, 2007, 78(12):2289-302.

The Bahekar study showed that both the prevalence and incidence of coronary heart disease are significantly increased in periodontal disease. The Mustapha study showed that periodontal disease with elevated markers of systemic bacterial exposure was strongly associated with coronary heart disease.

The Bahekar study analyzed previous published reports involving coronary heart disease and periodontal disease. The analysis revealed 5 prospective cohort studies, 5 case-control studies, and 5 cross-sectional studies that addressed the relationship between coronary heart disease and periodontal disease. The three study categories were analyzed separately.

The analysis of the 5 prospective cohort studies involving 86,092 patients indicated that individuals with periodontal disease had a 1.14 times higher risk of developing coronary heart disease than controls. A cohort study involves an analysis of risk factors and follows a group of people who do not have the disease and uses correlations to determine the absolute risk of acquiring the disease. In analyzing five other studies defined as case-control studies involving 1,423 patients, they demonstrated an even greater risk of developing coronary heart disease in individuals with periodontal disease. A case-control study collects specifically-designed data on all participants, including data fields designed to allow the hypothesis of interest to be tested. Also, the prevalence of coronary heart disease in cross sectional studies involving 17,724 patients was significantly greater among individuals with periodontal disease than those without. The prevalence of coronary heart disease was 1.59 times higher than in patients with periodontal disease. Cross-sectional studies differ from case control studies in that they involve data collected at a defined time and are used to answer questions about the causes of disease or the results of medical intervention.

The report by Bahekar concluded that both the prevalence and incidence of coronary heart disease are significantly increased in periodontal disease and that periodontal disease may be a risk factor for coronary heart disease.

The Mustapha study reviewed and analyzed the association between periodontal disease with elevated systemic bacterial exposure and cardiovascular disease. The authors of the study searched online databases for all literature examining periodontal disease and cardiovascular disease. From 10 selected publications, they extracted 5 cohort studies and 7 cross-sectional studies. Analysis of the studies showed coronary heart disease, stroke, and carotid-intima thickening as a measure of early atherosclerosis. Systemic bacterial exposure was measured by periodontal bacterial burden, periodontitis-specific serology, or C-reactive protein.

The results showed that periodontal disease with elevated markers of systemic bacterial exposure was strongly associated with coronary heart disease (1.75 times) compared to subjects without periodontal disease. This group was associated with a significant increase in carotid-intima thickening but not with any specific cardiovascular disease event or stroke.

The authors concluded that periodontal disease with elevated bacterial exposure is associated with coronary heart disease events and early atherogenesis (carotid-intima thickening), suggesting that the level of systemic bacterial exposure from periodontitis is a biologically important factor with regard to atherosclerotic risk.

The reader is reminded of two previous studies, described in our October 2009 e-Newsletter, on the relationship between C-reactive protein and periodontal disease. The report by Yoshii S, Tsuboi S, Morita I, et al ("Temporal Association of Elevated C-reactive Protein and Periodontal Disease in Men," J Periodontol, 2009, 80(5):734-9) found that periodontal disease increased the risk for high serum levels of C-reactive protein in men after one year of follow-up after baseline measurements. No significant correlation was seen between baseline C-reactive protein and periodontal disease one year later for the men without periodontal disease. The report by Marcaccini AM, Meschiari CA, Sorgi CA, et al ("Circulating Interleukin-6 and High-sensitivity C-reactive Protein Decrease After Periodontal Therapy in Otherwise Healthy Subjects," J Periodontol, 2009, 80(4):594-602) showed that periodontal disease was associated with increased levels of interleukin-6 and C-reactive protein, which decreased three months after nonsurgical periodontal therapy.


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