Periodontal treatment improves endothelialdysfunction in patients with severe periodontitisGerald Seinost, MD,a Gernot Wimmer, MD,b Martina Skerget, MD,a Erik Thaller, DDS,b Marianne Brodmann, MD,aRobert Gasser, MD,c Rudolf O. Bratschko, MD,b and Ernst Pilger, MDa Graz, Austria
Background Because epidemiological studies provide evidence that periodontal infections are associated with anincreased risk of progression of cardiovascular and cerebrovascular disease, we postulated that endothelial dysfunction, acritical element in the pathogenesis of atherosclerosis, would be present in patients with periodontal disease.
Methods We tested endothelial function in 30 patients with severe periodontitis and 31 control subjects using flow-mediated dilation (FMD) of the brachial artery. The groups were matched for age, sex, and cardiovascular risk factors. Threemonths after periodontal treatment, including both mechanical and pharmacological therapy, endothelial function wasreassessed by brachial artery FMD. Markers of systemic inflammation were measured at baseline and at follow up.
Results Flow-mediated dilation was significantly lower in patients with periodontitis than in control subjects(6.1% F 4.4% vs 8.5% F 3.4%, P = .002). Successful periodontal treatment resulted in a significant improvement in FMD(9.8% F 5.7%; P = .003 compared to baseline) accompanied by a significant decrease in C-reactive protein concentrations(1.1 F 0.9 vs 0.8 F 0.8 at baseline, P = .026). Endothelium-independent nitro-induced vasodilation did not differ betweenthe study groups at baseline or after periodontal therapy.
Conclusion These results indicate that treatment of severe periodontitis reverses endothelial dysfunction. Whetherimproved endothelial function will translate into a beneficial effect on atherogenesis and cardiovascular events needs furtherinvestigation. (Am Heart J 2005;149:1050 - 4.)
Periodontal disease is a common chronic infection
endothelial function would be impaired in patients with
caused by gram-negative bacteria such as Porphyromo-
severe periodontitis. We further hypothesized that
nas gingivalis, Actinobacillus actinomycetemcomi-
periodontal treatment would improve endothelial dys-
function, thereby supporting the concept that thera-
subgingival severe periodontitis, gingival
peutic strategies aimed at reducing cardiovascular risk
infection and inflammation destroy the attachment
factors translate into improved endothelial health.
apparatus, leading to alveolar bone and tooth loss.
Epidemiological research provides strong evidence
that severe periodontitis is a risk factor for cardiovas-
cular disease. A number of studies have demonstrated
Patients aged 25 to 50 years with severe periodontitis were
eligible to participate in the study. Patients were excluded if
they had a history of cardiovascular disease, diabetes mellitus,
identified relationships between periodontal disease
hypertension, or hypercholesterolemia, if they were suffering
and cardiovascular disease by no means indicate a
from any systemic illnesses or if they had been treated for
periodontitis within 6 months of the study. None of them werecurrently taking cardiovascular or antiinflammatory medica-tion, and none of them had been taking antibiotic medication
From the aDivision of Angiology, Department of Medicine, University Hospital, Graz,
or antioxidant agents within 3 months of the study. In
Austria, bDepartment of Prosthetics and Periodontology, School of Dentistry, Graz,Austria, and cDivision of Cardiology, Department of Medicine, University Hospital,
addition, healthy volunteers matched for age and sex served as
Submitted July 8, 2004; accepted September 23, 2004.
Reprint requests: Gerald Seinost, MD, Division of Angiology, Department of Medicine,
University Hospital, Graz, Auenbruggerplatz 15, A-8036 Graz, Austria.
systolic blood pressure z140 mm Hg and/or diastolic blood
n 2005, Elsevier Inc. All rights reserved.
pressure V90 mm Hg, according to the American
Association/American College of Cardiology All
Table I. Participants’ baseline characteristics
Table II. Brachial artery parameters and markers for systemicinflammation in control subjects and in patients before and after
Values are mean (SD) unless otherwise indicated.
subjects provided written informed consent as approved by
yP b .01 versus before treatment. zP b .05 versus controls.
All clinical parameters were assessed by trained periodontists
and a calibration exercise was performed to obtain acceptable
the patient’s request. Chlorhexidine gluconate (0.1%) mouth
intraexaminer reproducibility. The evaluation included the
washes were continued for 14 days. Systemic antimicrobial
assessment of bleeding on probing as an indication of an
therapy was administered for 7 days and consisted of a
existing periodontal inflammation and the measurement of
combination of amoxicillin acid and metroni-
probing depth and gingival recession on 6 sites on each tooth
dazole as adjunctive patients were reevaluated
(with the exception of the third molars) using a pressure-
12 weeks after periodontal treatment. In the intervening
calibrated digital recording device. Probing depth is defined as
period, their compliance was checked twice and a professional
the distance from the gingival margin to the base of the
cleaning was performed. Residual pockets of more than 5 mm
probeable crevice. Gingival recession was measured as the
that bled after probing were rescaled. Treatment of periodon-
distance from the cementoenamel junction to the gingival
titis was considered successful when there was no bleeding on
margin. These 2 values were summed for clinical attachment
probing and no pocket depth N5 mm at follow-up.
levels, a valid measure of historical periodontalpresence of was
Brachial artery reactivity was assessed within 1 week of the
involvement of at least 6 teeth with pocket depth N5 mm and
initial treatment and 3 months after end of treatment.
loss of attachment of z3 mm in 3 aspects of each involved
Endothelium-dependent flow-mediated dilation (FMD) and
tooth. In control subjects, periodontal disease was excluded if
endothelium-independent nitroglycerin-associated dilation of
they had no tooth pocket depth z2 mm and no attachment loss
z3 mm. Subjects with intermediate-severity periodontitis were
a previously described brief, patients were
excluded from the study. Periodontal parameters were
studied in a quiet, temperature controlled room in the morning
recorded at baseline and 3 months after end of treatment.
after an overnight fast. Two-dimensional images from the rightbrachial artery were obtained above the antecubital crease at
baseline and after 1 minute of hyperemia created by 5 minutes’
All underwent conservative nonsurgical periodontal
forearm cuff occlusion with an Acuson Sequoia 512 ultrasound
consisted of extensive explanation of the
system equipped with a 13.0-MHz linear array transducer
disease and oral hygiene instruction with several supragingival
(Acuson, Mountain View, Calif). After at least 10 minutes of
cleaning sessions. After a satisfactory hygiene index had been
rest, to allow restoration of baseline conditions, we assessed
achieved, all clinical parameters were recorded and a careful
endothelium-independent brachial artery dilation by recording
subgingival instrumentation was performed. The scaling and
2-dimensional images before and 4 minutes after administra-
root planing were carried out according to the individual needs
tion of sublingual nitroglycerin. Nitroglycerin was not admin-
of the patients, using a variety of hand instruments and, where
istered to individuals with clinically significant bradycardia or
appropriate, a piezoelectric ultrasonic scaler. The entire
hypotension or to individuals with a history of migraine
procedure was completed in 2 sessions. Usually, one jaw was
headaches. Digitized end-diastolic images were analyzed off-
treated per session, starting with the advanced sites. Local
line by a single investigator who was blinded to the individuals’
anesthesia was used only occasionally for isolated sites, upon
clinical status and image sequence. The lumen-intima bound-
Relative flow-mediated (%FMD) and nitroglycerin-associated
Markers of systemic inflammation of patients with severe period-
(%NAD) dilation of the brachial artery of patients with severe
ontitis before and after periodontal treatment and of control subjects.
periodontitis before and after periodontal treatment and of control
hs-CRP, high sensitive C-reactive protein.
aries were identified manually with electronic calipers and the
The clinical characteristics of 30 otherwise healthy
diameter of a vessel segment was determined as an average
patients with severe periodontitis and 31 healthy
derived from multiple diameter measurements.
controls are summarized in . As shown, the
Intima and media thickness (IMT) of the brachial artery was
measured at the far wall with electronic calipers above the
The structural and functional brachial artery parame-
antecubital fossa at the peak of the vessel arch. Measurementswere obtained at 2 sites per image in 2 different images per
ters as well as markers of systemic inflammation are
patient. The mean of 4 measurements was defined as brachial
summarized in Baseline diameter of the brachial
artery was comparable between the patient and thecontrol groups and did not change after treatment of
periodontitis. Flow-mediated dilation expressed as
Concentrations of total cholesterol, triglycerides, high-
change in diameter and as percent change was signifi-
density lipoprotein, and hemoglobin A1c were measured using
cantly lower in patients with periodontitis before treat-
automated analyzers (Modular Analytics, Roche/Hitachi, Basel,
ment than in healthy controls. Three months after
Switzerland; Adams A1c HA-8160, Menarini Diagnostics,
treatment, FMD significantly improved and returned to
Firenze, Italy). Low-density lipoprotein cholesterol (LDL-C)
values comparable to those of healthy controls ).
concentrations were calculated with Friedewald formula.
On regression analysis using age, sex, smoking status,
High-sensitivity C-reactive protein was measured with a
body mass index, and high-density lipoprotein choles-
nephelometric method (Dade-Behring Inc, Deerfield Ill).
terol (HDL-C) as covariates, brachial artery FMD was still
significantly impaired in patients with periodontitis( P
Group differences in age, blood pressure, lipid profile,
b .0001). Nitroglycerin-associated dilation did not
erythrocyte sedimentation rate (ESR), high-sensitive C-reactive
differ significantly between controls and patients with
protein, brachial artery diameter, flow-mediated and nitro-
periodontitis before and after treatment (
glycerin-mediated dilation of the brachial artery, and brachial
To investigate structural vessel wall alterations, we
artery wall thickness were analyzed using unpaired t test.
measured brachial artery IMT. As shown, there was no
Analysis of normality was performed with the Kolmogorov-
significant difference in brachial artery IMT between
Smirnov test. Nonnormally distributed data were logarithmi-
cally transformed before comparative analysis. Categorical
Patients with periodontitis had significantly higher
parameters were analyzed by v2 test or Fisher exact test when
baseline levels of ESRs and concentrations of C-reactive
required. Univariate analysis of variance with FMD as a
protein (than did controls. After periodontal
dependent variable and periodontal disease as a fixed factor
treatment, C-reactive protein concentrations significant-
was used to control for confounders identified by univariate
ly decreased and there was a trend toward a reduction in
analysis. The paired t test was used to assess changes inbrachial artery diameters and biochemical markers. A P value
ESRs (However, differences in white bloodcells did not reach statistical significance in controls and
b.05 was considered statistically significant. All analyses werecompleted with SPSS for Windows version 10.1 (SSCP Inc,
in patients at baseline and follow-up. There was a trend
Chicago, Ill). Data are presented as mean F SD.
toward an inverse correlation between FMD and ESR
(r = À0.28, P = .05) and between FMD and C-reactive
patients. In the Atherosclerotic Risk in Communities
protein concentration (r = À0.24, P = .1) that did not
study, the multivariable logistic regression model of
cross-sectional data on 6017 persons aged 52 to 75 years
There was no statistically significant change in total
indicates that severe periodontitis (OR 1.31, CI
cholesterol ( P = .28), LDL-C ( P = .37), HDL-C ( P = .71),
triglycerides ( P = .06), and systolic ( P = .68) and
endothelial dysfunction is an early event in
diastolic ( P = .2) blood pressure at follow-up.
atherogenesis before anatomic evidence of atheroscle-rosis appears.
The mechanism by which periodontal disease dis-
rupts vascular homeostasis remains unclear. However,
The results from this study showed that severe
in our study, markers of systemic inflammation were
periodontitis generates an inflammatory reaction asso-
significantly elevated in patients with periodontitis and
ciated with endothelial dysfunction in the conduit
decreased after treatment. This finding is consistent
brachial artery. These findings are with a
with the observation that a variety of therapeutic
recently published study by Amar were able
strategies to improve endothelial dysfunction are
to demonstrate that patients with advanced, but not
associated in parallel with a decrease of C-reactive
with mild, periodontal disease exhibited endothelial
protein levels.A possible pathway of systemic
dysfunction and elevated C-reactive protein. A number
inflammation in oral infection is the release of exo-
of studies have demonstrated associations between the
toxins or such as lipopolysaccharides into
direct invasion of the vessel wall by oral pathogens
ingly, in a recent study, Prasad et able to
triggering, in part, an inflammatory response that
demonstrate that the serologic response to multiple
translates into endothelial dysfunction. Indeed, topical
intracellular pathogens (cytomegalovirus, herpes sim-
oral inoculation with the major periodontal pathogen
plex virus 1, hepatitis A virus, and bacteria such as
P gingivalis has recently been demonstrated to
Chlamydia pneumoniae and Helicobacter pylori) was
an independent risk factor for the endothelial dysfunc-
tion and the presence and severity of coronary artery
have demonstrated that periodontal pathogens exist in
disease. The results from their study support the
atherosclerotic lesions actively invade human and
concept that cardiovascular risk is related to the
aggregate number of potentially atherogenic pathogens
A potential limitation to our study is that the
association between severe periodontitis and endothelial
Endothelial dysfunction significantly improved after
dysfunction may reflect residual confounding by known
successful periodontal treatment and returned to values
or yet unknown cardiovascular risk factors despite our
comparable to those of the healthy control group. Thus,
attempt to match the groups and check for confounding
our results indicate that there is a causal relationship
with regression analysis. Whether the effect on endo-
between periodontal disease and endothelial dysfunc-
thelial function and C-reactive protein actually was due
tion. The influence of infectious agents, especially C
to mechanical or pharmacological periodontal treatment
pneumoniae, as contributors to atherogenic
remains unclear. It is, however, unlikely that an
unspecific antiinflammatory effect of antibiotic therapy
randomized, prospective, controlled trial, Parchure et
was responsible for improved endothelial function and
were able to show that azithromycin treatment for 5
inflammatory markers 12 weeks after the end of
weeks produced significant improvement in FMD in
patients with coronary artery disease and serologic
Regardless of the mechanisms, we have shown that
evidence of C pneumoniae infection. Another
severe periodontitis is associated with significant
gation has failed to demonstrate an association
endothelial dysfunction that is reversible after success-
treatment of C pneumoniae and endothelial
ful periodontal treatment. There is increasing evidence
a disparity that may be caused by the short-term
from numerous clinical trials that improvement of
antibiotic treatment regimens used in that study. How-
ever, there is a lack of direct proof that therapeutic
cardiovascular is therefore reasonable to
improvement in endothelial function due to reduction of
conduct further research to determine whether
pathogen burden translates into lower cardiovascular
improved endothelial health after successful periodon-
tal treatment in high-risk patients prevents atheroscle-
We demonstrated functional brachial artery impair-
rotic complications. In the meanwhile, patients should
ment in patients with periodontal disease in the absence
be made aware of the possible relationship between
of structural vessel wall alterations in relatively young
periodontal disease and cardiovascular events.
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Carbon Sequestration as Greenhouse Gas Mitigation Policy K.S Kavi Kumar Associate Professor , MSE Forest ecosystem has potential to capture and retain large volumes of carbon over long periods as trees absorb carbon through photosynthesis process. A young forest, when growing rapidly, can sequester relatively large volumes of additional carbon roughly proportional to the forest.s grow
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