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European Society of Cardiology, BJC Arrhythmia Watch

Clinical Articles, Lead Article

CHD patients with no teeth have nearly double risk of death

Coronary heart disease (CHD) patients with no teeth have nearly double the risk of death as those with all of their teeth, according to research published in the European Journal of Preventive Cardiology.1 The study in more than 15,000 patients from 39 countries found that levels of tooth loss were linearly associated with increasing death rates.

“The positive effects of brushing and flossing are well established.”

“The relationship between dental health, particularly periodontal (gum) disease, and cardiovascular disease has received increasing attention over the past 20 years,” said lead author Dr Ola Vedin, cardiologist at Uppsala University Hospital and Uppsala Clinical Research Center in Uppsala, Sweden. “However it has been insufficiently investigated among patients with established coronary heart disease who are at especially high risk of adverse events and death and therefore in need of intensive prevention measures.”

This was the first study to prospectively assess the relationship between tooth loss and outcomes in CHD patients. The results are from a substudy of the STABILITY trial 2 which evaluated the effects of the Lp-PLA2 inhibitor darapladib versus placebo, in patients with CHD.

The present analysis included 15,456 patients from 39 countries on five continents from the STABILITY trial.2 At the beginning of the study patients completed a questionnaire about lifestyle factors (smoking, physical activity, etc), psychosocial factors and number of teeth in five categories (26–32 [considered all teeth remaining], 20–25, 15-19, 1–14 and none).

Patients were followed for an average of 3.7 years. Associations between tooth loss and outcomes were calculated after adjusting for cardiovascular risk factors and socioeconomic status. The primary outcome was major cardiovascular events (a composite of cardiovascular death, myocardial infarction and stroke).

Patients with a high level of tooth loss were older, smokers, female, less active and more likely to have diabetes, higher blood pressure, higher body mass index and lower education. During follow up there were 1 543 major cardiovascular events, 705 cardiovascular deaths, 1 120 deaths from any cause and 301 strokes.

After adjusting for cardiovascular risk factors and socioeconomic status, every increase in category of tooth loss was associated with a 6% increased risk of major cardiovascular events, 17% increased risk of cardiovascular death, 16% increased risk of all-cause death and 14% increased risk of stroke.

Compared to those with all of their teeth, after adjusting for risk factors and socioeconomic status, the group with no teeth had a 27% increased risk of major cardiovascular events, 85% increased risk of cardiovascular death, 81% increased risk of all-cause death and 67% increased risk of stroke.

“The risk increase was linear, with the highest risk in those with no remaining teeth,” said Dr Vedin. “For example the risks of cardiovascular death and all-cause death were almost double to those with all teeth remaining. Heart disease and gum disease share many risk factors such as smoking and diabetes but we adjusted for these in our analysis and found a seemingly independent relationship between the two conditions.”

“Many patients in the study had lost teeth so we are not talking about a few individuals here,” continued Dr Vedin. “Around 16% of patients had no teeth and roughly 40% were missing half of their teeth.”

During the study period 746 patients had a myocardial infarction. There was a numerically increased risk of myocardial infarction for every increase in tooth loss but this was not significant after adjustment for risk factors and socioeconomic status. Dr Vedin said: “We found no association between number of teeth and risk of myocardial infarction. This was puzzling since we had robust associations with other cardiovascular outcomes, including stroke.”

Periodontitis is one of the most common causes of tooth loss. Poor dental hygiene is one of the strongest risk factors for gum disease.

“This was an observational study so we cannot conclude that gum disease directly causes adverse events in heart patients,” said Dr Vedin. “But tooth loss could be an easy and inexpensive way to identify patients at higher risk who need more intense prevention efforts. While we can’t yet advise patients to look after their teeth to lower their cardiovascular risk, the positive effects of brushing and flossing are well established. The potential for additional positive effects on cardiovascular health would be a bonus.”

Dr Vedin, spoke to BJC Arrhythmia Watch outlining further aspects of the study:

What is the most acceptable working hypothesis on why tooth loss is associated with poor outcomes in CHD patients e.g. chronic low grade infection?

The most commonly proposed hypothesis is the host-mediated inflammatory response to the periodontal infection which is the basis for periodontal disease (PD), generating systemic inflammation and thereby possibly promoting various aspects of atherosclerosis. It is however important to note that this hypothesis regards the possible connection between PD and CV disease. While tooth loss is commonly caused by PD, it may also have other causes and the demonstrated associations in our recent publication could also be due to unmeasured or residual confounding. Moreover, if the inflammatory hypothesis is indeed true, it is a complex one as elegantly illustrated by Professor George Hajishengallis.3

Do the possible risks associated with tooth loss and PD also apply to patients who do not have existent CHD?

Most of the evidence thus far regarding tooth loss/PD and outcomes in fact comes from non-CHD populations and ours was the first (to the best of my knowledge) to assess the tooth loss/outcomes relationship in a CHD population. Keeping in mind that negative studies are not as likely to be published as those demonstrating significant associations, most of the studies out there regarding PD/tooth loss and CHD in primary preventive populations have demonstrated a significant, albeit moderate, association between various measures of PD and increased risk of CV disease and events. This was also the case in at least three meta-analyses, all based on findings from non-CHD populations. However, it is important to note there is significant heterogeneity and varying quality between these observational studies.

What is the main clinical message from the results of the study e.g., should cardiologists take a dental history?

Whether the association between tooth loss and outcomes in our study is causal cannot be elucidated from our results. The absent association with myocardial infarction can certainly be interpreted as a negative finding in this respect, although a positive association with CV death and stroke remained after multivariable adjustment. Nevertheless, and irrespective of causality, our results show that patients with tooth loss are at higher risk of adverse outcome than those with less or no tooth loss even after traditional CV risk factors and SES was taken into consideration and I think that this is valuable prognostic information in itself. Tooth loss is also an easily obtainable measure of dental health but its definite utility as a risk prediction tool needs to be further assessed and there is no evidence available that supports periodontal treatment as a means to lower CV risk.

Are there further sub studies planned in this area?

Yes. We are currently exploring the relationship between tooth loss and a wide range of prognostic biomarkers in the same population. We are hoping this could tell us more about possible pathophysiological connections, not only ”traditional” inflammatory ones. It could also help us to further assess the prognostic utility of the tooth loss measure in this population.

References

1. Vedin O, Hagström E, Budaj A, et al. on behalf of the STABILITY Investigators. Tooth loss is independently associated with poor outcomes in stable coronary heart disease. Euro J Prev Cardiol 2015; http://dx.doi.org/10.1177/2047487315621978

2. The STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) study evaluated the efficacy of darapladib, an oral inhibitor of lipoprotein-associated phospholipase A2, compared to placebo. Patients were eligible to participate if they had coronary heart disease, defined as prior myocardial infarction, prior coronary revascularisation, or multivessel coronary heart disease without revascularisation.

3. Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nature Reviews Immunology. 2015;15:30–44. http://dx.doi.org/10.1038/nri3785

Published on: January 14, 2016

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