J Clin Periodontol 2014; 41: 3137 doi: 10.1111/jcpe.

12183

Moderate and severe

periodontitis are independent
risk factors associated with low
cardiorespiratory fitness in
sedentary non-smoking men
aged between 45 and 65 years
Eberhard J, Stiesch M, Kerling A, Bara C, Eulert C, Hilfiker-Kleiner D,
Hilfiker A, Budde E, Bauersachs J, Kuck M, Haverich A, Melk A, Tegtbur U.
Moderate and severe periodontitis are independent risk factors associated with low
cardiorespiratory fitness in sedentary non-smoking men aged between 45 and
65 years. Journal of Clinical Periodontology 2014; 41: 3137. doi: 10.1111/
jcpe.12183.

Abstract
Aim: To investigate the association between periodontal disease severity and
cardiorespiratory fitness (CRF) in a cross-sectional study of sedentary men.
Materials & Methods: Seventy-two healthy men (4565 years) who did not join
any sport activity and had a preferentially sitting working position were recruited.
Periodontal status was recorded and CRF was measured by peak oxygen uptake
(VO2peak) during exercise testing on a cycle ergometer. Physical activity was
assessed by a validated questionnaire and data were transformed to metabolic
equivalent of task scores. Univariate and multivariate regression analyses were
performed to investigate associations.
Results: Differences between VO2peak levels in subjects with no or mild, moderate or
severe periodontitis were statistically significant (p = 0.026). Individuals with low
VO2peak values showed high BMI scores, high concentrations of high-sensitive Creactive protein, low levels of high-density lipoprotein-cholesterol, and used more
glucocorticoids compared to individuals with high VO2peak levels. Multivariate
regression analysis showed that high age (p = 0.090), high BMI scores (p < 0.001),
low levels of physical activity (p = 0.031) and moderate (p = 0.087), respectively,
severe periodontitis (p = 0.033) were significantly associated with low VO2peak levels.
Conclusions: This study demonstrated that moderate and severe periodontitis
were independently associated with low levels of CRF in sedentary men aged
between 45 and 65 years.

rg Eberhard1,#, Meike Stiesch1,#,

Jo
Arno Kerling2, Christoph Bara3,
Christine Eulert4, Denise
Hilfiker-Kleiner4, Andres Hilfiker3,
Eva Budde5, Johann Bauersachs4,
Momme Kuck2, Axel Haverich3,
Anette Melk6,# and Uwe Tegtbur2,#
1

Department of Prosthetic Dentistry and

Biomedical Materials Science, Hannover
Medical School, Hannover, Germany;
2
Institute of Sports Medicine, Hannover
Medical School, Hannover, Germany;
3
Department of Cardiothoracic,
Transplantation and Vascular Surgery,
Hannover Medical School, Hannover,
Germany; 4Department of Cardiology and
Angiology, Hannover Medical School,
Hannover, Germany; 5Institute of Biometry,
Hannover Medical School, Hannover,
Germany; 6Department for Paediatric
Nephrology, Hepatology and Metabolic
Disorders, Hannover Medical School,
Hannover, Germany

These authors contributed equally.

Key words: cardiorespiratory fitness;

periodontitis; physical activity; risk factor;
systemic health
Accepted for publication 14 October 2013

Conflict of interest and source of funding statement

The authors declare no conflicts of interests.
This study was funded in part by the Cluster of Excellence rebirth Hannover and the Cordis Foundation.
2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

31

32

Eberhard et al.

Recently, several publications reviewed

the evidence regarding potential associations between periodontitis and atherosclerotic vascular diseases, diabetes
mellitus or child low-birth weight,
showing that oral health affects that
of the entire body (Chambrone et al.
2011, Lalla & Papapanou 2011,
Lockhart et al. 2012). In addition,
Linden et al. reported in an excellent
review modest associations between
periodontitis and respiratory disease,
chronic kidney disease, obesity, metabolic syndrome and cancer (Linden
et al. 2013). Investigators proposed
periodic transient bacteraemia or
increased levels of circulating cytokines to accelerate pathological processes relevant for the systemic
pathologies associated with periodontitis (Bahrani-Mougeot et al.
2008, Schenkein & Loos 2013).
Cardiorespiratory fitness (CRF)
is a surrogate measure of the functional status of the respiratory, cardiovascular and skeletal muscle
system. There is convincing evidence
that low CRF is associated with
increased cardiovascular morbidity
and mortality in both men and
women, independent of classical risk
factors (for review see Swift et al.,
2013). CRF is usually expressed in
metabolic equivalents or maximal
oxygen uptake (VO2peak), as measured during incremental exercise
testing, using treadmill or cycle
ergometers. In an early attempt to
explore systemic effects of periodontal diseases, Wakai et al. investigated
the relationship between CRF and
periodontal health (Wakai et al.
1999). These authors were not able
to show a clear correlation between
VO2peak and periodontal health
scores. In contrast, Shimazaki et al.
showed that subjects with high Community Periodontal Index scores
exhibited significantly lower levels of
VO2peak than subjects with low index
scores (Shimazaki et al. 2010).
Individual levels of CRF depend
on non-modifiable (age, gender and
genotype) and modifiable (physical
activity, smoking, obesity and medical condition) determinants. However, CRF levels are predominately
determined by physical activity and
exercise training (Lee et al. 2010);
therefore, the scientific values of
both aforementioned studies are
somewhat limited due to the fact
that they did not report the quantity

of physical activity of the subjects

under investigation. In addition,
periodontal disease assignment was
drawn in both studies by the Community Periodontal Index, which
was originally not designed to assess
the prevalence of periodontal disease
in a population (Page & Eke 2007).
Based on these limitations, it was
obvious to investigate the association
between periodontitis and CRF
including data of routine physical
activity and using a valid case definition of periodontitis. The investigation of a correlation between
periodontitis and CRF was of special concern, because in contrast to
the repeatedly described associations
with the cardiovascular system, CRF
addresses several organ systems. The
present cross-sectional study was
conducted in a cohort of physically
inactive men aged between 45 and
65 years, with the simultaneous
assessment of CRF, physical activity
and their periodontal conditions. It
was our hypothesis that periodontal
disease severity is negatively associated with CRF.
Methods
Study subjects

We recruited between 15th May and

30th July 2011 by advertisement for
otherwise healthy men aged between
45 and 65 years within our own
institution
(Hannover
Medical
School), who had not joined any
exercise programme or sports activities, did not have any physical
activity at leisure, and had a preferentially sitting working position
during the last 3 years. To make an
enquiry about physical and work
place activity a questionnaire was
sent to all male employees at Hannover Medical School. Employees
who self-reported no physical activity and had a preferentially sitting
working position during the last
3 years were invited for the interview. A comprehensive medical history
including
anti-hypertensive
medications, glucocorticoids and
lipid-lowering agents was recorded
by interview. Subjects with known
cardiac diseases, diabetes mellitus,
cancer and current or former (last
cigarette >3 years) cigarette smokers
were excluded. Subjects were also
excluded if they had less than

eight teeth, received antibiotics within

3 months prior to the study or periodontal treatment within 6 months
prior to the study. The subjects were
subsequently included and provided
informed consent in accordance with
the policies of the institutional
Review Board of Hannover Medical
School (no. 5909). The study was
registered at the WHO trials registry
(DRKS00003097).
Periodontal examination

An experienced periodontist (JE)

assessed each subject for the presence and severity of periodontal
disease. For all measurements, a
pressure
calibrated
periodontal
probe was used (Florida Probe System, Florida Probe). This evaluation
included the measurement of the
probing depth (PD) and clinical
attachment level (CAL) at six sides
per tooth. The presence of no or
mild, moderate or severe periodontal
conditions were classified by the clinical case definitions of periodontitis
introduced by the Centres for
Disease Control and Prevention and
the American Academy of Periodontology (CDC-AAP) (Page & Eke
2007, Eke et al. 2012). Subjects were
classified as moderate periodontitis
by 2 interproximal sides with CAL
4 mm, or by 2 interproximal sides
with PD 5 mm (not at the same
tooth). Severe periodontitis was
characterized by 2 interproximal
sides with CAL 6 mm and 1 interproximal side with PD 5 mm (not
at the same tooth). No or mild periodontitis was specified if neither
moderate nor severe periodontitis
was diagnosed.
Analysis of oxygen consumption (VO2peak)

Cardiorespiratory fitness was measured directly from respiratory gas

exchange during a standardized
cardiopulmonary stepwise exercise
testing on a cycle ergometer (Ergoline, Bitz, Germany). Maximum oxygen consumption was defined as the
maximum mean value over a period
of 30 s during the test. For this
study, the term VO2peak instead of
VO2max was used because it was
uncertain how close to their maximum the subjects would cycle. All
tests have been stopped with the
onset of dyspnoea and/or peripheral

2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Periodontitis is associated with CRF

muscle fatigue. The resulting VO2peak
value in ml O2 per kg body weight
per minute allowed a direct comparison of individuals regardless of body
weight.
Assessment of activity

Subjects were selected according to a

low status of physical activity with
respect to sport and leisure activities
or work conditions; however, for all
analyses physical activity was
assessed by a validated questionnaire
that evaluates activities during normal daily routine and leisure time
(Frey et al. 1999). This questionnaire
included an extensive array of questions related to daily activities,
leisure-time activities and sedentary
activities at home. Frequency (times
per day, week or month) and duration per session (min or hours per
day) were reported for each activity.
Frequency and duration of participation in activities within each intensity
category were summarized to create
estimates for daily physical activity.
Physical activity data were transformed to represent metabolic equivalent of task scores (MET = 3.5 ml/
min./kg body weight representing
resting energy expenditure). Weekly
average time spent on activities was
calculated by adding the METweighted hours for each leisure time
activity and daily activities, divided
by 60 and multiplied by 7 days.
Assessment of blood pressure

Blood pressure was recorded before

any intervention or measurement by
an experienced cardiologist (CE)
using sphygmomanometric measurements on a rested participant prior to
treadmill testing. Measurements were
taken with a blood pressure cuff
adapted to the broadness of the participants upper arm (boso manuell;
Bosch & Sohn, Jungingen, Germany).
Participants actively treated with
antihypertensive drugs or exhibiting a
systolic and/or diastolic blood pressure equal or greater than 140/
90 mmHg were designated as being
hypertensive.

ments of lipid levels, glucose concentration, etc., were done by standard

laboratory testing (Modular analytic eco analyser; Roche Diagnostic
GmbH,
Mannheim,
Germany).
Serum concentrations of high-sensitive C-reactive protein (hsCRP) were
determined by immunonephelometry (Cardiophase hsCRP; Siemens
AG, Erlangen, Germany).
Statistical analysis

For all statistical analyses the statistical software package SPSS 19.0
(IBM Corp., Armonk, NY, USA)
was used. Descriptive statistics
included calculation of mean values
and standard deviations for quantitative variables. Qualitative variables
were expressed as frequency and
percentage.
Differences between individual
VO2peak-groups (25%-percentiles) for
single variables were tested using
ANOVA for continuous variables and
the Chi-Square or Fischer exact test,
respectively, for categorical variables. A p-value (0.05) was considered significant.
The influences of each variable
were investigated with univariate
regression models, considering the
mean VO2peak as the outcome variable. All variables with a p-value
p < 0.2 were considered significant
and investigated in a multivariate
regression
model.
Correlations
between variables were tested using
Pearson correlation coefficient and
highly dependent variables were
excluded from analysis. A multivariate analysis (backward stepwise linear regression with p = 0.10 to enter
and p = 0.05 to leave) was performed. Possible predictor variables
were age, weight, BMI, physical
activity, heart rate, diastolic blood
pressure, anti-hypertensive medication, glucocorticoids and periodontal
disease severity (no/mild, moderate
or severe periodontitis according to

33

the CDC-AAP classification). The

estimates for each variable were
derived from SPSS output, as well as
standard deviation and corresponding 95% confidence interval.
Results

Eighty-three subjects were screened

and a total of 72 healthy eligible men
(mean age: 52.7  5.4 years) were
included. Eleven subjects did not
comply with the inclusion criteria.
Thirty subjects were classified as no/
mild periodontitis, 30 were classified
as moderate periodontitis and 12
participants were classified with
severe
periodontitis.
Descriptive
statistics for clinical case definitions
and VO2peak levels are summarized in
Table 1. The differences between
VO2peak levels in subjects with no or
mild periodontitis, moderate or severe
periodontitis were statistically significant (p = 0.026). Individuals with
VO2peak values in the lower quartile
showed higher weight (p < 0.001) and
BMI (p < 0.001) scores, low levels of
high-density lipoprotein (HDL)cholesterol (p = 0.036), high serum
concentrations of hsCRP (p = 0.045)
and used more glucocorticoids
(p = 0.027) compared to individuals
with VO2peak levels in the upper 25%
quartile of the study population
(Table 2). No differences were
observed between different VO2peak
quartiles for age, physical activity,
heart rate, systolic or diastolic blood
pressure, serum glucose, total cholesterol, triglycerides and low-density
lipoprotein-cholesterol. In addition,
no significant differences were found
between VO2peak-quartiles with respect
to anti-hypertensive medication and
lipid-lowering agents.
Univariate regression analysis
showed that age, BMI and no or
mild periodontitis (CDC-AAP) were
significantly associated with VO2peak.
Variables retained in the multivariate
model after the stepwise selection

Table 1. Cardiorespiratory fitness significantly decreased with periodontal disease severity

(p = 0.026)
VO2peak (ml/min./kg)

Laboratory assessments

CDC-AAP

Blood samples were obtained after

an overnight fasting period at
8:00 a.m. from all subjects. Measure-

CI, confidence interval.

2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

No/mild
Moderate
Severe

Mean  SD

95% CI

30.5  5.3
27.9  4.9
25.8  6.6

28.6; 32.5
26.1; 29.7
21.6; 30.0

34

Eberhard et al.

Table 2. Descriptive statistics (mean  SD) for participating subjects and

ANOVA

analysis for quartiles of VO2peak (ml/min./kg)

All participants
(n = 72)
First Quartile
Age, year
Weight, kg
BMI
VO2peak, ml/min.
VO2peak, ml/min./kg
Physical activity, MET
Heart rate, bpm
Systolic blood pressure, mmHg
Diastolic blood pressure, mmHg
Maximum power, Watt
Maximum systolic blood
pressure, mmHg
Maximum diastolic blood
pressure, mmHg
Serum glucose, mmol/l
Total cholesterol, mg/dl
Triglycerides, mg/dl
LDL cholesterol, mmol/l
HDL cholesterol, mmol/l
hsCRP, mg/l
Anti-hypertensive medication (C07)*, n
Lipid-lowering agents (C10A)*, n
Glucocorticoids (H02)*, n

52.7
87.6
27.2
2495.8
28.9
29.2
74.6
122.2
83.3
227.9
207.3













5.4
12.1
3.5
430.7
5.8
18.8
12.3
14.1
9.7
33.4
24.1

88.2  12.9
5.3
215.9
135.8
146.5
50.8
1.7
20
4
3








0.4
33.5
93.5
28.0
10.6
2.9

VO2peak

53.8
95.7
29.8
2094.5
22.0
21.7
77.2
123.6
86.9
207.3
216.1













4.5
13.5
4.2
367.4
2.7
14.3
13.8
14.0
8.4
24.9
26.5

90.2  13.5
5.4
213.0
166.5
143.9
45.5
2.7
8
0
3








0.4
26.2
85.7
18.6
9.4
3.9

Second Quartile
54.4
91.1
27.7
2418.6
26.6
27.3
72.0
123.17
84.4
218.4
205.6













6.2
12.8
3.4
336.2
0.9
15.0
9.7
16.4
11.6
27.7
21.3

90.2  12.7
5.4
218.8
166.2
147.1
48.8
1.0
6
1
0








0.5
38.1
145.9
30.8
9.0
0.7

Third Quartile
51.1
84.5
26.7
2550.6
30.2
29.6
77.3
122.0
82.3
227.8
206.8













5.2
7.6
2.6
257.0
1.4
21.3
10.4
13.6
10.9
35.0
26.4

86.9  16.9
5.3
219.7
121.2
151.1
52.9
2.6
4
2
0








0.5
38.6
51.7
33.5
13.0
4.0

Fourth Quartile
51.0
79.6
24.8
2897.0
36.5
38.1
71.3
118.72
79.4
256.9
202.8













5.2
7.3
1.3
308.9
2.7
22.1
13.2
12.5
7.1
25.9
21.3

0.115
<0.001
<0.001
<0.001
<0.001
0.070
0.266
0.729
0.129
<0.001
0.380

85.8  7.3

0.658








0.874
0.750
0.062
0.752
0.036
0.045
0.211
0.519
0.027

5.3
208.8
96.2
141.2
54.7
0.6
2
1
0

0.4
32.1
46.9
28.7
8.3
0.84

*ATC code in parenthesis.

LDL, low-density lipoprotein; HDL, high-density lipoprotein; hsCRP, high-sensitive C-reactive protein.

procedures were age, BMI, physical

activity, and moderate or severe
periodontitis (Table 3). High age
(p = 0.090),
high
BMI
scores
(p < 0.001), low levels of physical
activity (p = 0.031), and moderate
(p = 0.087), respectively, severe periodontitis (p = 0.033) were significantly associated with low VO2peak
levels.
Discussion

The results of this study showed an

association between periodontal
disease severity and the functional
status of the respiratory, cardiovascular and skeletal muscle system in
sedentary non-smoking men aged
between 45 and 65 years; stepwise
regression analysis showed that moderate and severe periodontitis are risk
factors for reduced CRF. This association was independent of other
known risk factors for CRF and indicated a yet not documented adverse
systemic health effect of periodontal
diseases affecting a combined parameter of systemic health integrating
several organ systems of the body.
Cardiorespiratory fitness was
found to be associated with age,
gender, physical activity, smoking

Table 3. Uni- and multivariate regression analysis with VO2peak (ml/min./kg) as the dependent variable. The regression coefficient corresponds to a one-unit change of the dependent
variable.
Regression coefficient
Univariate regression
Age, year
BMI
Physical activity, MET
Heart rate, bpm
Systolic blood pressure, mmHg
Diastolic blood pressure, mmHg
Serum glucose, mmol/l
Total cholesterol, mg/dl
Triglycerides, mg/dl
LDL cholesterol, mmol/l
HDL cholesterol, mmol/l
hsCRP, mg/l
Clinical case definition, CDC-AAP
No or mild periodontitis
Moderate periodontitis
Severe periodontitis
Multivariate regression
Age, year
BMI
Physical activity, MET
Clinical case definition, CDC-AAP
Moderate periodontitis
Severe periodontitis

95% CI
0.018
0.121
0.114
0.085
0.215
0.149
3.673
0.122
0.077
0.407
0.574
0.485

p-value

0.257
0.588
0.049
0.033
0.084
0.029
0.751
0.153
0.028
0.131
0.241
0.052

0.495;
1.056;
0.016;
0.152;
0.046;
0.207;
2.170;
0.428;
0.022;
0.146;
0.092;
0.381;

0.036
0.015
0.135
0.574
0.201
0.742
0.608
0.270
0.266
0.347
0.153
0.809

4.110
1.811
2.753

0.215; 8.004
1.925; 5.547
6.404; 0.897

0.173
0.702
0.062

0.374; 0.027
0.981; 0.323
0.006; 0.119

0.090
<0.001
0.031

2.008
3.431

4.313; 0.297
6.568; 0.294

0.087
0.033

0.039
0.335
0.136

CI, confidence interval; LDL, low-density lipoprotein; HDL, high-density lipoprotein;

hsCRP, high-sensitive C-reactive protein.

and obesity (Lee et al. 2010). The

associations between CRF and age
as well as body weight, respectively,

BMI has been confirmed in the present study. Ageing is a confounding

factor for both the prevalence of

2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Periodontitis is associated with CRF

periodontal disease and CRF; however, the statistical analyses revealed
periodontal disease severity as an
independent risk factor. The negative
association between BMI and CRF
observed in the present study has
also been demonstrated in US obese
individuals who had approximately
1015% lower CRF values than
non-obese individuals (Wang et al.
2010). The risk for obesity is reduced
by physical activity (Coakley et al.
1998) and longitudinal studies supported a weak association between
overweight or obesity and periodontal infections (Saxlin et al. 2010). In
this regard, metabolic disorders like
diabetes, hypercholesterolemia and
low HDL-cholesterol levels have also
been associated with impaired skeletal muscle functions including CRF
or cardiovascular disease (Carnethon
et al. 2005). In this study, ANOVA
analysis found differences between
quartiles of CRF regarding triglycerides (p = 0.062) and HDL-cholesterol, however, both parameters were
highly correlated to BMI scores and
were therefore eliminated from uniand multivariate regression analyses.
Basically CRF is determined by
the extent of physical activity
(Church et al. 2007), this association
was also confirmed in the present
regression analyses. Subjects in the
lowest quartile of VO2peak presented
low levels of physical activity compared to subjects in the highest
VO2peak quartile. Physical activity is
regarded as the main confounding
factor for the observed association
between CRF and periodontal disease severity in the present study,
because both variables showed a few
interdependent associations. For
example, several studies showed an
independent association between low
levels of physical activity and an
increased frequency of periodontitis
(Merchant et al. 2003, Al-Zahrani
et al. 2005, Bawadi et al. 2011). Of
importance is that improved oral
hygiene, which someone might suggest be associated with increased
physical activity, did not necessarily
account for lower frequencies of
periodontal disease (Bawadi et al.
2011). The link between physical
activity and periodontitis is an antiinflammatory effect of regular exercise and this anti-inflammatory effect
might also result in a suppressive
effect on periodontal disease (Peter-

sen & Pedersen 2005). Another systemic effect of physical activity is the
reduction of high blood pressure,
which is also associated to low CRF
(Sawada et al. 1993). In addition,
high blood pressure was found to be
associated with periodontal disease
(Howell et al. 2001, DAiuto et al.
2006, Franek et al. 2009, Rivas-Tumanyan et al. 2012). These contrary
effects may at least in part explain
that no association was observed
between blood pressure, respectively,
physical activity and CRF in this
study. In addition, the high frequency of anti-hypertensive drug use
in subjects belonging to the lower
25% quartile of VO2peak levels did
not allow any reliable calculation of
an association between these variables. However, based on the association between high blood pressure
and low CRF, VO2peak values in
subjects in the lowest quartile may
even be worse without using antihypertensive medications.
C-reactive protein concentration
is, a strong predictor for myocardial
infarction and stroke risk (Ridker
et al. 1997). In this study, CRP concentrations were significant higher in
subjects with low CRF compared to
subjects with high CRF, the former
also suffering more frequently from
moderate or severe periodontitis.
This observation is in accordance
with studies showing that periodontal disease was associated with acute
phase response and changes in serum
C-reactive protein levels (Whelton
et al. 2002, DAiuto et al. 2004).
Again, physical activity may be a
confounding factor for the observed
associations, because C-reactive protein concentrations in individuals
were also determined by the level of
physical activity (Andersson et al.
2008).
The findings of this study fit well
with prior clinical studies linking
periodontal and systemic diseases
(Lockhart et al. 2012, Linden et al.
2013). Although the outcome measure CRF is a compound parameter
including several organ systems of
the body, CRF is associated with
increased cardiovascular morbidity
and mortality in both men and
women (Swift et al. 2013). In a
recent meta-analysis Kodama et al.
(2009) calculated that a one-MET
increase in CRF was associated with
a 13% reduction in cardiovascular

2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

35

mortality. The difference between subjects with no or mild periodontitis and

subjects with severe periodontitis was
approximately one MET (based on a
regression coefficient of 3.431 ml/
min./kg), representing a significant
reduced cardiovascular mortality in
subjects with no or mild periodontitis
compared to subjects with severe periodontitis. The magnitude of the effect
and the clinical significance of the presented data is illustrated by a recent
publication that reported an immediate 14% reduction in cardiovascular
mortality rate following the national
workplace smoking ban in 2004 in the
Republic of Ireland (Stallings-Smith
et al. 2013).
Limitations of the study are
related to sample size and selection
criteria. A power calculation was not
done in advance because of the
explorative character to this study.
Especially the exclusion of women
from the study restricted generalization of the results. The reasons to
include only men were existing sex
differences in cardiovascular aging
and adaptive responses to physical
activity, as well as hormonal differences in pre- and postmenopausal
women (Parker et al. 2010). Another
limitation of the study is that information of the socio-economic status
or education levels were not
recorded. However, the socio-economic status with respect to years of
education, employment status and
income was quite similar within the
population, because the occupational
situation of all included subjects did
show
only
minor
differences.
Strength of the study is that subjects
with diabetes or current smokers
were excluded to reduce confounding
from these established risk factors
for periodontal disease (Hujoel et al.
2002, Mealey & Oates 2006). In
addition, this study accurately determined and characterized physical
activity levels of the selected subjects
by self-assessment and by an extensive questionnaire (Frey et al. 1999)
confirming the sedentary lifestyle of
the subjects.
Summary

In summary, the presented study

demonstrated that moderate and
severe periodontitis were associated
with reduced levels of CRF in sedentary men. It appeared that this study

36

Eberhard et al.

highlight strong confounding effects

between physical activity, periodontal disease and systemic health that
should take into consideration in
future research design.
References
Al-Zahrani, M. S., Borawski, E. A. & Bissada, N.
F (2005) Increased physical activity reduces
prevalence of periodontitis. Journal of Dentistry
33, 703710.
Andersson, J., Boman, K., Jansson, J. H., Nilsson, T. K. & Lindahl, B. (2008) Effect of intensive lifestyle intervention on C-reactive protein
in subjects with impaired glucose tolerance and
obesity. Results from a randomized controlled
trial with 5-year follow-up. Biomarkers 13,
671679.
Bahrani-Mougeot, F. K., Paster, B. J., Coleman,
S., Ashar, J., Barbuto, S. & Lockhart, P. B.
(2008) Diverse and novel oral bacterial species
in blood following dental procedures. Journal
of Clinical Microbiology 46, 21292132.
Bawadi, H. A., Khader, Y. S., Haroun, T. F.,
Al-Omari, M. & Tayyem, R. F. (2011) The
association between periodontal disease, physical activity and healthy diet among adults in
Jordan. Journal of Periodontal Research 46, 74
81.
Carnethon, M. R., Gulati, M. & Greenland, P.
(2005) Prevalence and cardiovascular disease
correlates of low cardiorespiratory fitness
in adolescents and adults. JAMA 294, 2981
2988.
Chambrone, L., Guglielmetti, M. R., Pannuti, C.
M. & Chambrone, L. A. (2011) Evidence grade
associating periodontitis to preterm birth and/
or low birth weight: I. A systematic review of
prospective cohort studies. Journal of Clinical
Periodontology 38, 795808.
Church, T. S., Earnest, C. P., Skinner, J. S. &
Blair, S. N. (2007) Effects of different doses of
physical activity on cardiorespiratory fitness
among sedentary, overweight or obese postmenopausal women with elevated blood pressure: a randomized controlled trial. JAMA 297,
20812091.
Coakley, E. H., Rimm, E. B., Colditz, G., Kawachi, I. & Willett, W. (1998) Predictors of
weight change in men: results from the Health
Professionals Follow-up Study. International
Journal of Obesity and Related Metabolic Disorders 22, 8996.
DAiuto, F., Parkar, M., Andreou, G., Suvan, J.,
Brett, P. M., Ready, D. & Tonetti, M. S.
(2004) Periodontitis and systemic inflammation:
control of the local infection is associated with
a reduction in serum inflammatory markers.
Journal of Dental Research 83, 156160.
DAiuto, F., Parkar, M., Nibali, L., Suvan, J.,
Lessem, J. & Tonetti, M. S. (2006) Periodontal
infections cause changes in traditional and
novel cardiovascular risk factors: results from a
randomized controlled clinical trial. American
Heart Journal 151, 977984.
Eke, P. I., Page, R. C., Wei, L., Thornton-Evans,
G. & Genco, R. J. (2012) Update of the case
definitions for population-based surveillance of
periodontitis. Journal of Periodontology 83,
14491454.

Franek, E., Klamczynska, E., Ganowicz, E.,

Blach, A., Budlewski, T. & Gorska, R. (2009)
Association of chronic periodontitis with left
ventricular mass and central blood pressure in
treated patients with essential hypertension.
American Journal of Hypertension 22, 203207.
Frey, I., Berg, A., Grathwohl, D. & Keul, J.
(1999) Freiburg Questionnaire of physical
activitydevelopment, evaluation and application. Sozial- und Praventivmedizin 44, 5564.
Howell, T. H., Ridker, P. M., Ajani, U. A.,
Hennekens, C. H. & Christen, W. G. (2001)
Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians.
Journal of the American College of Cardiology
37, 445450.
Hujoel, P. P., Drangsholt, M., Spiekerman, C. &
DeRouen, T. A. (2002) Periodontitis-systemic
disease associations in the presence of
smokingcausal or coincidental? Periodontol
30, 5160.
Kodama, S., Saito, K., Tanaka, S., Maki, M.,
Yachi, Y., Asumi, M., Sugawara, A., Totsuka,
K., Shimano, H., Ohashi, Y., Yamada, N. &
Sone, H. (2009) Cardiorespiratory fitness as a
quantitative predictor of all-cause mortality
and cardiovascular events in healthy men and
women: a meta-analysis. JAMA 301, 2024
2035.
Lalla, E. & Papapanou, P. N. (2011) Diabetes
mellitus and periodontitis: a tale of two common interrelated diseases. Nature Reviews
Endocrinology 7, 738748.
Lee, D. C., Artero, E. G., Sui, X. & Blair, S. N.
(2010) Mortality trends in the general population: the importance of cardiorespiratory fitness. Journal of Psychopharmacology 24, 2735.
Linden, G. J., Lyons, A. & Scannapieco, F. A.
(2013) Periodontal systemic associations: review
of the evidence. Journal of Periodontology 84,
S8S19.
Lockhart, P. B., Bolger, A. F., Papapanou, P. N.,
Osinbowale, O., Trevisan, M., Levison, M. E.,
Taubert, K. A., Newburger, J. W., Gornik, H.
L., Gewitz, M. H., Wilson, W. R., Smith, S. C.
Jr & Baddour, L. M. (2012) Periodontal disease
and atherosclerotic vascular disease: does the
evidence support an independent association?:
a scientific statement from the american heart
association. Circulation 125, 25202544.
Mealey, B. L. & Oates, T. W. (2006) Diabetes
mellitus and periodontal diseases. Journal of
Periodontology 77, 12891303.
Merchant, A. T., Pitiphat, W., Rimm, E. B. &
Joshipura, K. (2003) Increased physical activity
decreases periodontitis risk in men. European
Journal of Epidemiology 18, 891898.
Page, R. C. & Eke, P. I. (2007) Case definitions
for use in population-based surveillance of periodontitis. Journal of Periodontology 78, 1387
1399.
Parker, B. A., Kalasky, M. J. & Proctor, D. N.
(2010) Evidence for sex differences in cardiovascular aging and adaptive responses to physical activity. European Journal of Applied
Physiology 110, 235246.
Petersen, A. M. & Pedersen, B. K. (2005) The
anti-inflammatory effect of exercise. Journal of
Applied Physiology 98, 11541162.
Ridker, P. M., Cushman, M., Stampfer, M. J.,
Tracy, R. P. & Hennekens, C. H. (1997)
Inflammation, aspirin, and the risk of cardio-

vascular disease in apparently healthy men.

New England Journal of Medicine 336, 973979.
Rivas-Tumanyan, S., Spiegelman, D., Curhan, G.
C., Forman, J. P. & Joshipura, K. J. (2012)
Periodontal disease and incidence of hypertension in the health professionals follow-up
study. American Journal of Hypertension 25,
770776.
Sawada, S., Tanaka, H., Funakoshi, M., Shindo,
M., Kono, S. & Ishiko, T. (1993) Five year
prospective study on blood pressure and maximal oxygen uptake. Clinical and Experimental
Pharmacology and Physiology 20, 483487.
Saxlin, T., Ylostalo, P., Suominen-Taipale, L.,
Aromaa, A. & Knuuttila, M. (2010) Overweight and obesity weakly predict the development of periodontal infection. Journal of
Clinical Periodontology 37, 10591067.
Schenkein, H. A. & Loos, B. G. (2013) Inflammatory mechanisms linking periodontal diseases
to cardiovascular diseases. Journal of Periodontology 84, S51S69.
Shimazaki, Y., Egami, Y., Matsubara, T., Koike,
G., Akifusa, S., Jingu, S. & Yamashita, Y.
(2010) Relationship between obesity and physical fitness and periodontitis. Journal of Periodontology 81, 11241131.
Stallings-Smith, S., Zeka, A., Goodman, P.,
Kabir, Z. & Clancy, L. (2013) Reductions in
cardiovascular, cerebrovascular, and respiratory mortality following the national irish
smoking ban: interrupted time-series analysis.
PLoS ONE 8, e62063.
Swift, D. L., Lavie, C. J., Johannsen, N. M.,
Arena, R., Earnest, C. P., OKeefe, J. H.,
Milani, R. V., Blair, S. N. & Church, T. S.
(2013) Physical activity, cardiorespiratory
fitness, and exercise training in primary and
secondary coronary prevention. Circulation
Journal 77, 281292.
Wakai, K., Kawamura, T., Umemura, O., Hara,
Y., Machida, J., Anno, T., Ichihara, Y., Mizuno, Y., Tamakoshi, A., Lin, Y., Nakayama,
T. & Ohno, Y. (1999) Associations of medical
status and physical fitness with periodontal disease. Journal of Clinical Periodontology 26,
664672.
Wang, C. Y., Haskell, W. L., Farrell, S. W.,
Lamonte, M. J., Blair, S. N., Curtin, L. R.,
Hughes, J. P. & Burt, V. L. (2010) Cardiorespiratory fitness levels among US adults 20
49 years of age: findings from the 19992004
National Health and Nutrition Examination
Survey. American Journal of Epidemiology 171,
426435.
Whelton, S. P., Chin, A., Xin, X. & He, J. (2002)
Effect of aerobic exercise on blood pressure: a
meta-analysis of randomized, controlled trials.
Annals of Internal Medicine 136, 493503.

Address:
Jorg Eberhard
Periimplant and Oral Infections
Department of Prosthetic Dentistry and
Biomedical Materials Science
Hannover Medical School
Carl-Neuberg-Str. 1
30625 Hannover
Germany
E-mail: eberhard.joerg@mh-hannover.de

2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Periodontitis is associated with CRF

Clinical Relevance

Scientific rationale for the study: To

investigate the association between
periodontitis and a surrogate measure of the functional status of the
respiratory, cardiovascular and
skeletal muscle system.

Principle findings: In this study periodontal disease severity was associated with low cardiorespiratory
fitness in sedentary men aged
between 45 and 65 years.
Practical implications: Future research
aimed to investigate the association

2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

37

between periodontal and cardiovascular diseases should include data of

physical activity and capacity.