Original Researchjpmcp.com/pdf 2/162-171.pdf · Dr. Dinesh Duhan Post Graduate Student, Dept. of...

Changes In Serum Lipid Levels As A Possible Risk For Cardiovascular Disease In Chronic Periodontitis Patients: A Cross Sectional Study.

Khuller N, Duhan D, Raghav YS, Sharma S. Changes In Serum Lipid Levels As A Possible Risk For Cardiovascular Disease In

Chronic Periodontitis Patients: A Cross Sectional Study. J periodontol med clin pract 2014;01:162-171

1 2 2 2Dr. Nitin Khuller , Dr. Dinesh Duhan , Dr. Yashbir Singh Raghav , Dr. Shivli Sharma

Original Research

Journal of Periodontal Journal of Periodontal

Medicine & Clinical PracticeMedicine & Clinical Practice

Journal of Periodontal

Medicine & Clinical PracticeJPMCPJPMCPJPMCPJournal of Periodontal Medicine

& Clinical Practice

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Affiliation:

1.Reader, Deptartment of Periodontology, Swami Devi Dyal Hospital and Dental College, Barwala,

Panchkula, Haryana, India.

2.Post Graduate Student, Department of periodontology, Swami Devi Dyal Hospital and Dental

College, Barwala, Panchkula, Haryana, India.

Corresponding author:-

Dr. Dinesh Duhan

Post Graduate Student, Dept. of Periodontology,

Swami Devi Dyal Hospital and Dental College, Barwala, Panchkula, Haryana, IndiaEmail: [email protected]

Abstract:-

Aim and objective: Periodontitis has a significant

impact on various systemic diseases with high

prevalence, incidence, morbidity, and mortality; e.g.

cardio vascular diseases (CVDs) and diabetes mellitus

(DM). In this study, a diagnostic protocol was designed

to find the possible association for risk of cardiovascular

disease (CVD) in subjects with chronic periodontitis by

assessing the serum cholesterol, triglycerides; high and

low density lipoprotein levels (serum lipid profile).

Materials and method: Total of 40 subjects in the age

group of 30-65 years were selected and divided into the

following two groups equally based on their periodontal

disease status into Test group (group I or group A- 20

subjects with chronic periodontitis), and Control group

(group II or group B- 20 subjects with healthy

periodontium). Their periodontal disease status was

assessed by using the Russell's Periodontal Index

(Russell 1956). Three ml of venous blood samples were

taken for measurement of parameters of lipid

metabolism (serum lipid profile).

Results and conclusion: Highly statistical significance

was achieved for total cholesterol (p=0.002**) and

VLDL (p=0.002**), while statistical significance was

achieved for triglyceride (p=0.018*) when results were

compared among the two groups showing a positive

correlation between cardiovascular disease (CVD) and

chronic periodontitis.

Keywords: Periodontitis, lipoproteins, cardiovascular

disease.

INTRODUCTION

Periodontitis is defined as “an inflammatory disease of

the supporting tissues of the teeth caused by specific

microorganisms, resulting in progressive destruction of

the periodontal ligament and alveolar bone with pocket [1]

formation, recession, or both.” Severe form of the

disease is present in 10% to 15% cases and even in 30% [2]

of the population. It is said that factors that place

individuals at risk for periodontitis may also place them

at risk for cardiovascular disease such as smoking,

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www.jpmcp.comChanges In Serum Lipid Levels As A Possible Risk For Cardiovascular Disease In Chronic Periodontitis Patients

[3]diabetes, behavioural factors, ageing, male gender, etc.

There has been great interest in the systemic effects of

serum pro-inflammatory cytokine levels potentially [4]elevated by periodontitis. These elevated pro-

inflammatory cytokines cause an elevated serum lipid

levels. This alters immune cell function resulting in

increased production of pro-inflammatory cytokines by

polymorphonucleocyctes and decreased production of

growth factors from tissue macrophages reducing tissue

repair capacity and leading to further tissue breakdown,

and a hyper-responsive monocytic state resulting in

further elevations of serum pro-inflammatory cytokines [4,5]and lipids. There is evidence that periodontal

pathogens seed arterial vasculature contributes to a

disruptive paradigm for coronary heart disease [6,7](CHD). Thus, in otherwise healthy individuals,

periodontitis may be potentially associated with the

development of atherosclerosis, a pathologic change of [3]coronary heart disease (CHD).

While numerous cross-sectional and prospective

epidemiologic studies have demonstrated an association

between CHD and periodontal disease, several recent

studies have failed to identify an association between the

two. A key question is whether periodontitis is a causal

factor in the aetiology of CHD or its presence is just a co-

incident. Much epidemiological research is devoted to

the estimation of causal effects using non-experimental

data. Unfortunately, the results of epidemiological

studies, typically yielding a measure of association are

insufficient to conclude whether such associations are [2,3]causal. The correct interpretation of statistical

associations between periodontal disease and CHD

depend on a variety of issues, including but not limited [11]to confounding bias, other sources of bias and chance.

Periodontitis-related atherogenic alterations have also [7]been associated with lipoprotein metabolism.

Hyperlipidaemia is a state with an abnormal lipid

profile, which is characterized by elevated blood

concentrations of triglycerides, elevated levels of total

cholesterol and low-density lipoprotein (LDL) and

decreased levels of high-density lipoprotein-cholesterol [8](HDL). It has been suggested that hyperlipidaemia

[9]could be associated with periodontitis. There are

common risk factors for periodontal disease and

cardiovascular disease. Serum lipids may be the most

important among these factors. Reduced high-density

lipoprotein cholesterol levels are well recognized risk

factors for cardiovascular disease and ischaemic [7,8,9]stroke.

An intra-oral source of infection like periodontitis can

create an inflammatory immune response, thereby

placing an apparently healthy individual at an increased

risk for cardiovascular disease. Periodontal disease can

be treated and thereby, the risk of developing [12,13,15]cardiovascular disease can be reduced.

According to Sridhar R, Byakod G, Pudakalkatti P, [3]Patil R (2009) , periodontal disease did not cause an

increase in total CHL, LDL or triglyceride levels or a

decrease in the HDL levels in an otherwise systemically

healthy individual or in a CHD patient. Periodontitis in a

CHD patient did not seem to exacerbate the destruction

of periodontal tissue. Higher triglyceride levels did not

have any correlation with the severity of attachment loss

in a periodontitis subject.

According to Katz J, Chaushu G, Sharabi Y (2001),

hypercholesterolaemia and cardiovascular diseases are [9]related to periodontal disease.

According to Sandi RM, Pol KG, Basavaraj P, [2]Khuller N (2014) , Subjects with chronic periodontitis

showed increased serum cholesterol and LDL levels.

This may suggest that these subjects are potentially at a

risk of getting cardiovascular disease.

Hence,to find as to whether an association between

serum lipid profile (and an indirect association with


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cardiovascular disease) in patients with chronic

periodontitis exists an attempt to investigate this

hypothesis was made. The study was carried out on 30-

65 year old subjects who attended Swami Devi Dayal

Hospital & Dental college.

Aim and Objective

To find the possible association for r isk of

cardiovascular disease (CVD) in subjects with chronic

periodontitis by assessing the serum cholesterol,

triglycerides, high and low density lipoprotein levels

(serum lipid profile).

MATERIALS AND METHOD

Study Design and Study Population

This cross-sectional study was conducted from

December, 2013 to February, 2014 on subjects aged 30-

65 years (who were not matched for age/sex), seeking

dental and medical consultation at OPD of department

of Periodontology and Oral Implantology, and The

Medical OPD of Swami Devi Dyal Hospital, Barwala,

Panchkula.

Ethical Considerations

The study protocol was reviewed by the Ethical

Committee of Swami Devi Dyal Hospital and Dental

College, Barwala, Panchkula and it was granted ethical

clearance. Written informed consents were obtained

from the participants who fulfilled the eligibility criteria

and were willing to participate in the study.

Training and Calibration

Prior to the commencement of the study, the examiner

was standardized and calibrated with a consultant in the

Department of Periodontology and Oral Implantology,

to ensure uniform interpretations, understanding and

application of the data obtained to ensure consistent

examination.

Methodology

A total of 40 subjects in the age group of 30-65 years

were selected from the OPD of Department of

Periodontology and Oral Implantology which were then

divided into the following two groups based on their

periodontal disease status.

1. Test group (group I or group A- 20 subjects with

chronic periodontitis), and

2. Control group (group II or group B- 20 subjects with

healthy periodontium).

Inclusion criteria

1. Patients diagnosed as having CHD based on coronary

angiogram showing evidence of atherosclerosis.

2. Age group between 30 and 65 years.

3. Patients should have at least 18 natural teeth present.

4. Periodontitis group patients should exhibit clinical

attachment loss of >1 mm and ⁄ or probing depth of >4

mm in around 30% of the existing natural teeth.

Exclusion criteria

1. Non-ambulatory cardiovascular disease patients.

2. Patients with any other systemic diseases.

3. Patients on any drugs for hyperlipidaemia prior to the

study.

4. Patients on any antibiotics 4 weeks prior to the study.

5. Patients who have undergone dental treatment 6

months prior to the study.

6. Patients having habits like smoking, tobacco

chewing, etc.

Data were collected by using an interviewer-

administered questionnaire, which consisted of two

parts. The first part was used to collect information on

socio-demographic data and the second part contained

oral examination. Oral examination was carried out

immediately following the interview using a mouth

mirror, and William's graduated periodontal probe.


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Parameters

The parameters that were measured were as follows:

1. Russels Periodontal Index (Russell 1956)

2. Clinical attachment loss

The parameters were used to diagnose the case as

Periodontitis (Test) or Healthy (Control).

Laboratory estimation of serum lipid profile

Informed consent was obtained from all subjects.

Estimation of serum lipid was carried out using (Coral

Clinical Systems, Goa, India). Estimation of serum

cholesterol, high density lipoprotein (HDL) cholesterol

was carried out by Cholesterol oxidase⁄ Phenol-amino-

4-antipyrine peroxidase (PAP) method and Poly-

Ethylene-Glycerol (PEG) precipitation method,

respectively, using a Erba Mannheim Clinical Systems

biochemistry auto analyser (Fig. 6). Calculation of low

density lipoprotein (LDL) cholesterol in mg dl)1 was

carried out using Freldewald's formula. Estimation of

triglyceride was carried out by Glycerol-3-phosphate-

oxidase ⁄PAP method and cut-off levels of serum lipid

levels in Indian population were taken according to the

Indian Council of Medical Research (ICMR) 1995 and

Indian consensus 1997. Venous blood (3 ml) was

collected from each subject after an overnight fasting

period of 8–12 h for estimation of serum lipid profile

from the central veins through the skin in the cubital

fossa from the selected subjects. The blood samples

were then centrifuged at 3,000 rpm (revolutions per

minute) for 5 minutes. Serum was separated.

Results and interpretation (Graph I-III; Table 1)

The mean age for test group was 52.95 years while it

was 55 years for control group.

The Russell's Periodontal index exhibited a poorer

periodontal condition in group- I subjects (test group)

when even compared with Group II subjects (control

group).

Levels of total cholesterol, triglyceride, HDL, LDL and

VLDL in blood serum were measured in both groups

and the results were achieved by use of “Unpaired-T

Test, Chi Square Test and Fisher's Exact Test”.

Mean total cholesterol of test and control groups

(237.0000±42.01128 mg/dl and 199.6500±29.81924

mg/dl, respectively) showed highly significant

difference (T=3.242, p=0.002**).

Triglyceride level of test and control groups (169.7000±

35.33464 mg/dl in test and 146.8000± 21.26673in

control showed significant difference (T=2.483,

p=0.018*).

Comparing mean HDL between the two groups

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(50.0500±10.67449 in the test and 44.9500±5.06250

mg/dl in the control group) showed no significant

difference (T=1.931, p=0.061). Regarding mean LDL

levels (147.8000±46.85656 mg/dl in the test and

126.5500±27.51167 in the control group), the difference

was not statistically significant (T=1.749, p=0.088).

M e a n V L D L o f t e s t a n d c o n t r o l g r o u p s

(37.1500±10.50451 mg/dl and 28.6500±4.19618 mg/dl,

respectively) showed highly significant difference

(T=3.242, p=0.002**). Highly statistical significance

was achieved for Total cholesterol and VLDL, while

statistical significance was achieved for Triglyceride

when results were compared among the two groups

showing a positive correlation. No more than 60%

subjects (test subjects) showed any deviation from

normal range irrespective of significant results.





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Discussion

A relationship between periodontitis, a common

chronic oral disease in adults, and cardiovascular [12]diseases has been identified in several studies.

This case-control study was designed and

performed in order to explore the relationship

between presence of periodontal disease and level

of serum lipids. We compared serum lipid levels

between two groups, one with and one without

periodontal disease. According to the results, levels

of total cholesterol and VLDL were found to be

highly significant while triglyceride was found to

be of significant value showing correlation with

periodontal disease. This is in accordance with

reports indicating altered lipid profile could be a

r i sk fac tor for var ious d isease such as

atherosclerosis and cardiac ischemic disease.

Coronary heart disease remains one of the leading

causes of death and morbidity despite the

remarkable progress in our understanding of the

pathogenesis and treatment of the disease.

Notwithstanding their importance, the classic

coronary risk factors do not explain all clinical and

epidemiological features of CHD. Several studies

have suggested that development of CHD is [5,6]influenced by infections. An association between

poor oral status and coronary heart disease exists

and improvement in periodontal status may [14]influence the systemic and haemostatic situation.

Periodontal disease could result in repeated

systemic exposure to bacteria, endotoxin,

lipopolysaccharide and other bacterial products.

The lipopolysaccharides of dental plaque diffuse

into the systemic circulation and they elicit a

systemic lipopolysaccharide specific antibody

response. This may lead to lipid metabolism

disturbance and a hypercoagulable state through

elevation of circulating cytokines. Monocyte

derived cytokines such as TNF-α, IL-1, 6 and 8

have powerful effects on hepatic protein synthesis

(e.g. in upregulating fibrinogen synthesis), tissue

catabolism and lipid metabolism. Both TNF-α and

IL-1 inhibit the production of lipoprotein lipase, [4,5]thus causing lipid metabolism disturbance. This

results in increase in the levels of serum cholesterol,

triglyceride and VLDL. The scope of infections

associated with CHD also includes dental

infections, especially periodontitis. In the present

study data were collected using a detailed

proforma.

It was observed that there was an increase in the

serum cholesterol, triglycerides and VLDL values

in subjects with chronic periodontitis. This could

reflect an increased risk for cardiovascular disease

in these subjects. This finding could be of benefit in

early recognition/prevention of CVD and it could

thereby minimize the risk for cardiovascular

disease in these individuals through prevention

and/or control of the periodontal disease.

Serum lipid profile for the Indian population has

been assessed by councils like the ICMR, programs

like the National Cholesterol Education Program

(1998) and by authors like and Goswami Reddy and [11] [16]Tendon and Bandyopadhyay. The values of

serum lipid levels obtained in our study for the

healthy group (B) corroborate well with the normal

values obtained by the aforementioned authors. The

l ipid profile values obtained in chronic

periodontitis group (A) too were within the normal

limits though relatively higher (Total Cholesterol,

triglyceride and VLDL) than the healthy group (B).

In the present study, no significant increase in LDL





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and HDL was observed in chronic periodontitis. [4]

Lui J, Wu Y, Ding Y, Meng S, Ge S, Deng H (2010)

reported that chronic periodontitis was associated

with decreased HDL concentrations, which

suggested that there light exist some relationship

between periodontal inflammation and CHD.

Similar results were reported by Pussinen PJ, [7]

Mattila K (2004) . These findings may be

attributed to the influences on lipid metabolism,

exerted by the release of lipopolysaccharide and

proinflammatory cytokines, caused by periodontal

inflammation. Gufran K et al (2011) also confirmed

that there was no significant relationship between

periodontal disease, regardless of its intensity, and [3]

blood lipid levels in systematic healthy subjects.

HDL cholesterol has anti-inflammatory and anti-

atherogenic properties and decreased HDL

cholesterol levels have also been considered to be a

risk factor for CHD. For patients with periodontitis,

decreased HDL cholesterol concentrations suggest

that a periodontal inflammation might be associated [2,3]

with CHD Palle AR (2013) also reported that

there was a significant relationship between obesity

and periodontitis in population of patients with [2]

cardiovascular disease.

Nevertheless, the exact mechanism of this

association was not clarified in this study and it

needs to be further explored. Since this study was of

a cross sectional nature, which was conducted on a

modest sample size of 40 subjects, studies with

larger sample sizes and standard protocols need to

be carried out in future, to endorse the results

observed in our study. While the etiology of

hyperlipidaemia is multifactorial, it has been

suggested that some true experimental design

research should be done, to exactly confirm the

effect of chronic periodontitis.

Conclusion

The elevated levels of total cholesterol,

triglycerides and VLDL which were observed in

chronic periodontitis subjects in comparison to

healthy subjects suggest an increased risk for

cardiovascular disease in chronic periodontitis

subjects. As this study was of a modest sample size

of 40 subjects and limited to the geographical area

of Barwala, Panchkula the results of this study

cannot be applied to wide-spread population as

various etiological factors may vary. So for proper

application of results to apply a large sample sized

subjects spread over large geographical area is

needed.

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Competing interest / Conflict of interest The author(s) have no competing interests for financial support, publication of this research, patents and royalties through this collaborative research. All authors were equally involved in discussed research work. There is no financial conflict with the subject matter discussed in the manuscript. Source of support: NIL

Copyright © 2014 JPMCP. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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