Evaluation of the association between chronic periodontitis and acute coronary syndrome: A case control study.

BACKGROUND: The periodontal tissues mount an immune inflammatory response to bacteria and their products and the systemic challenge with these agents also induce a major vascular response. Although many studies have found a correlation between chronic periodontitis and cardiovascular diseases, the role of infection in acute coronary syndrome is disputed. The aim of this study is to investigate whether there is an association between chronic periodontitis and acute coronary syndrome.
MATERIALS AND METHODS: A total of 30 patients, ages ranging from 30 -80. 15 patients from A. B. Shetty Memorial Institute of Dental Sciences and 15 patients admitted to Coronary Care Unit of Justice K. S. Hegde Charitable Hospital Deralakatte Mangalore were included in the study. Variables age more than 40 and gender were also analyzed.
RESULTS: Of the 30 patients analyzed in this study, periodontitis was recognized in 11 patients of the acute coronary syndrome group and 10 patients in the healthy group. Fisher's exact test yielded a p value of 0.4539 with an odds ratio of 0.727(95% confidence interval 0.151 to 3.493).
CONCLUSION: No significant association was found between periodontal disease and acute coronary syndrome. Periodontitis may contribute to cardiovascular disease and stroke in susceptible subjects. Properly powered longitudinal case control and intervention trials are needed to identify how periodontitis and periodontal interventions may have an impact on cardiovascular diseases.

INTRODUCTION

Cardiovascular disease comprises a variety of heart and vascular conditions including ischemia, atherosclerosis, peripheral artery disease, infective endocarditis, and acute myocardial infarction.[1] Evidence suggests that an association between inflammatory markers such as interleukins, C-reactive proteins,[2] protease activated receptors, and matrix metalloproteinase-9[3] for atherogenesis and acute ischemic events. It has been hypothesized that coronary artery disease (CAD) may be triggered by systemic mechanisms, in addition to local inflammatory factors, and chronic periodontal infection is one of the possibilities to be considered.[4567] Taking this into account studies suggest an association between periodontal disease and CAD.

The sub gingival micro biota in patients with periodontitis provides a significant and persistent gram-negative bacterial challenge to the host. These organisms and their products such as lipopolysaccharide have a ready access to the periodontal tissues and to the circulation via the sulcular epithelium which is frequently ulcerated.[8] Several studies assessing the presence of bacteria associated with periodontitis in specimens collected from the aorta or other blood vessels have identified bacteria associated with periodontitis in samples from aorta and heart valves.[1]

Risk-factors for atherosclerosis and thereby for CAD have been identified in epidemiological studies linking their presence with the incidence of clinically overt disease.[9] Foremost among modifiable risk-factors associated with increased incidence of coronary disease are hyperlipidemia, systemic arterial hypertension, smoking, and diabetes mellitus.[10] Age, gender, and family history are among the major non-modifiable risk-factors associated with ischemic heart disease.[111213]

The aim of this study was to see if there is an association between chronic periodontitis and acute coronary syndrome (ACS).

MATERIALS AND METHODS

The present clinical study was carried out in the Department of Periodontology and Implantology, A B Shetty Memorial Institute of Dental Sciences and K. S. Hegde Superspecialty Hospital, Mangalore after obtaining approval from the ethical committee. This was a case control study and all patients were enrolled after signing an informed consent.

The cases were 15 patients admitted with ACS to the Coronary Care Unit of K. S. Hegde Hospital, who met the ACS diagnostic criteria.

ACS comprised of patients with either ST segment elevation which was defined as acute myocardial infarction characterized by: Chest pain, radiating or not to the upper extremities, lower jaw, upper back or epigastrium lasting 30 min or more: Presence of ST segment elevation of 1 mm in two or more peripheral contiguous leads or 2 mm in two or more contiguous precordial leads on electrocardiogram: And elevation in serum markers of myocardial injury and necrosis (Creatine phospho kinase/creatinin kinase-MB, cardiac troponin) 3 times their reference value.[14]

Non-ST segment elevation ACS on, Electrocardiogram was defined as a clinical condition similar to that mentioned above but with chest pain lasting less than 30 min, with or without elevation of serum enzyme markers of myocardial injury and necrosis.[14]

Inclusion criteria

The control group comprised of patients with no history of CAD and systemically healthy aged between 30 and 80 years reporting to the Department of Periodontology were selected randomly

The cases were patients with ACS aged between 30 and 80 years

Those who had not taken any vitamins or mineral supplements for the past 3 months

Presence of minimum 15 natural teeth

Patients with any of the following conditions were excluded from the study

Patients who were completely edentulous. Neoplasias, liver cirrhosis, chronic inflammatory diseases like arthritis. Those who have undergone any periodontal treatment in the last 3 months. Pregnant and lactating women.

Screening examination

The severity of chronic periodontitis was determined by clinical attachment loss (CAL) more than 4 mm in more than 30% of sites. CAL was assessed using a Williams's graduated periodontal probe in both arches, examining all the teeth on six surfaces [Figure 1]. The severity of gingivitis was determined by gingival index as given by Loe and Silness, in 1963. Scores 1-3 were recorded with four scoring points on each teeth.

Figure 1

Measurement of clinical attachment level in a healthy patient with chronic Periodontitis

All measurements and readings were done before the collection of blood sample.

Blood reports and blood pressure recording were also taken.

Statistical analysis

It was performed with Fishers exact test. P ≤ 0.05 was considered significant.

RESULTS

Thirty subjects were analyzed in this study, 15 patients were evaluated in the ACS group of whom chronic periodontitis was diagnosed in 11 patients. In the control group, 15 patients were evaluated of whom ten members had chronic periodontitis.

The results translated into an odds ratio (OR) of 0.727 (95% confidence interval (CI) =0.151-3.493) as shown in Table 1.

Table 1

Chronic periodontitis in patients with acute coronary syndrome compared with control group

P value calculated by Fisher's exact test was 0.4539, which was statistically insignificant.

The cluster bar graph for the two groups with the percentage of patients with and without periodontitis is shown in Figure 2.

Figure 2

Cluster bar graph - Comparing chronic periodontitis between the two groups

Nine patients out of 15 in the ACS group were aged more than 40 years and eight in the control group were more than 40 years which translated into a total of 17 patients and an OR of 1.889. 95% CI (1.207-2.957) as shown in Table 2.

Table 2

Chronic periodontitis in cases and controls more than 40 years of age

17 (85%) patients age more than 40 years had periodontitis and 3 (15%) patients age more than 40 years did not have periodontitis.

The mean age for the ACS group was 57 years with a standard deviation (SD) of 12.7. The mean age for the control group was 42 years with a SD of 8.75 as shown in Table 3 and Figure 3.

Table 3

Mean age of cases and controls

Figure 3

Mean age of the patients in the two groups

In both the group, 15 men were diagnosed with chronic periodontitis compared to only six females with chronic periodontitis. The Fisher's exact test showed a P value of 0.331 which was statistically insignificant as shown in Table 4.

Table 4

Fisher's test showing P value of males and females with and without chronic periodontitis

All these were comparative results with no statistical significance.

DISCUSSION

Cardiovascular diseases rank among the leading causes of death and thereby have an important clinical and epidemiological role.[1516] Results from studies relating periodontal disease to cardiovascular disease have been mixed. A study carried out by Emingil et al. suggests that the presence of periodontal disease may induce a systemic inflammatory response,[7] resulting in elevated serum levels of inflammatory makers, such as tumor necrosis factor, interleukin and C-reactive protein that contribute to plaque instability and atherosclerotic events.[23]

Meta-analysis of prospective and retrospective follow-up studies have shown that periodontal disease may only slightly increase the risk of cardiovascular disease.[171819] In contrast, some studies have found a significant relationship between periodontal status (based on clinical measures of probing pocket depth/CAL) and acute myocardial infarction.

Most studies provide an OR of periodontitis (defined by clinical measures of probing pocket depth and clinical attachment levels) as a risk for cardiovascular disease at levels less than a ratio of 3:1. Studies resulting in higher OR have commonly used alveolar bone loss as a definition of periodontitis rather than CAL level.[2021] Disparities in prevalence rates of periodontitis in study populations with different age groups, ethnicity, and geographic location makes it difficult to assess the likelihood of an association between periodontitis and cardiovascular diseases.

Age is an important factor associated with both periodontitis and cardiovascular diseases. Available studies suggest that periodontitis prevalence in older subjects is high.[22] In the study done by Persson et al. approximately 50% of subjects older than 60 years of age had periodontitis. In addition, approximately 55% had either a diagnosis of atherosclerosis, or a history of stroke, or ACS.[23] In this study, mean age of the patients with ACS was greater than that of the control group. It is known that the age factor also accounts for increased cardiovascular risk, and this finding may have reduced both the significance and magnitude of the results.[17]

Another subset analysis with gender in this study did not show any association of ACS with chronic periodontitis in either males or females. There is evidence to suggest that the extent of atheroma assessed by intravascular ultrasound in women is less severe and prevalent than in men and independent of other traditional cardiovascular risk-factors.[24] Whereas in another study, investigators failed to identify gender differences in the association between periodontitis and cardiovascular diseases.[25]

Hujoel et al. published a prospective cohort study involving patients with periodontal and medical evaluation who were followed for 10 years. The endpoints evaluated were coronary death, ACS, or need for myocardial revascularization. After adjusting for risk-factors, no association was found either between gingivitis or CAD or between periodontitis and CAD.[26]

The limitations of this study however, were that, the sample size taken was also too small to come to any definitive conclusion and it was not possible to accesses the amount of bone loss by radiographic evaluation due to the non-ambulatory condition of the patients with ACS.

CONCLUSION

The aim of our study was to emphasize the hypothesis that oral infectious processes may be implicated in inflammatory and thrombotic phenomena, leading to the development of acute coronary events. Such processes may induce cytokine release in the presence of lipopolysaccharide. It is believed that these substances act systemically from the periodontal vascular complex, or are released from coronary endothelial cells, promoting platelet aggregation and thrombus formation.[67]

In this study, however, no independent association was found between chronic periodontitis and ACS. More multicenter properly powered longitudinal case-control trials are needed to specifically assess the prevalence and distribution of periodontitis in relation to cardiovascular disease. Interventional trials are needed to identify how periodontitis and periodontal interventions may have an impact on cardiovascular disease.