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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
www.jpmcp.com
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: drdineshduhan1987@gmail.com
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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www.jpmcp.comChanges In Serum Lipid Levels As A Possible Risk For Cardiovascular Disease In Chronic Periodontitis Patients
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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Journal of Periodontal Journal of Periodontal
Medicine & Clinical PracticeMedicine & Clinical Practice
Journal of Periodontal
Medicine & Clinical PracticeJPMCPJPMCPJPMCPJournal of Periodontal Medicine
& Clinical Practice
www.jpmcp.comChanges In Serum Lipid Levels As A Possible Risk For Cardiovascular Disease In Chronic Periodontitis Patients
Vol- I, Issue - 2, May - Aug 2014
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Journal of Periodontal Journal of Periodontal
Medicine & Clinical PracticeMedicine & Clinical Practice
Journal of Periodontal
Medicine & Clinical PracticeJPMCPJPMCPJPMCPJournal of Periodontal Medicine
& Clinical Practice
www.jpmcp.com
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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Vol- I, Issue - 2, May - Aug 2014Changes In Serum Lipid Levels As A Possible Risk For Cardiovascular Disease In Chronic Periodontitis Patients
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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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Vol- I, Issue - 2, May - Aug 2014Changes In Serum Lipid Levels As A Possible Risk For Cardiovascular Disease In Chronic Periodontitis Patients
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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
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