Schult, Schlitt Use of Interdental

Use of floss/interdentalbrushes is associated withlower risk for newcardiovascular eventsamong patients withcoronary heart disease

Reichert S, Schlitt A, Beschow V, Lutze A, Lischewski S, Seifert T, Dudakliewa T,

Gawe R, Werdan K, Hofmann B, Schaller H-G, Schulz S. Use of floss/interdental

brushes is associated with lower risk for new cardiovascular events among patients

with coronary heart disease. J Periodont Res 2014; doi: 10.1111/jre.12191 . 2014John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Background and Objective: Periodontitis has been found to be associated with

coronary heart disease (CHD) and stroke. However, only little is known about

whether periodontitis and associated confounders are associated with new car-

diovascular events among patients with CHD.

Material and Methods: A total of 942 inpatients with CHD were examined

regarding periodontitis, oral care habits, bacteria in the subgingival biofilm and

the expression of interleukin-(IL)-6 c. (coding DNA)174 genotypes (rs 1800793)

to determine whether these confounders are associated with new cardiovascular

events within a 1-year follow-up period. Adjusted hazard ratios (HR) with

respect of age, gender, smoking, body mass index, use of aids for interdental

hygiene, plaque index, occurrence of severe periodontitis and further internal

diseases such as diabetes, hypertension, dyslipoproteinemia, number of missing

teeth, serological parameters and IL-6 genotypes were generated with Cox

regression.

Results: In all, 941 cardiovascular patients completed the 1-year follow up and

7.3% of the patients achieved the primary endpoint (myocardial infarction:

2.1%, stroke/transient ischemic attack: 1.8%, cardiovascular deaths: 3.4%).

Patients who reported practicing interdental cleaning were younger, less likely to

be male or to have severe periodontitis, had a reduced tobacco exposure, had

fewer missing teeth, less indices for plaque and bleeding on probing and a

significant decreased adjusted risk for new cardiovascular events (HR = 0.2, CI0.060.6, p = 0.01) than those patients with CHD who did not report practicinginterdental cleaning. We did not obtain significant increased HR for patients

with severe periodontitis (HR = 1.2, CI 0.72.1, p = 0.53), carriers of the IL-6genotypes GC or CC (HR = 1.4, CI 0.82.5, p = 0.24) and did not find a signifi-cant association between the number of detected various oral species and the

incidence of the combined endpoint (HR = 0.9, CI 0.81.01, p = 0.07).

S. Reichert1, A. Schlitt2,

V. Beschow1, A. Lutze1,3,

S. Lischewski1, T. Seifert1,3,

T. Dudakliewa3, R. Gawe3,

K. Werdan3, B. Hofmann4,

H.-G. Schaller1, S. Schulz11Department of Operative Dentistry and

Periodontology, Martin Luther University Halle-

Wittenberg, Halle, Germany, 2Department of

Cardiology, Paracelsus-Harz-Clinic Bad

Suderode, Quedlinburg, Germany, 3Department

of Internal Medicine III, Heart Centre of the

University Clinics Halle (Saale), Martin Luther

University Halle-Wittenberg, Halle, Germany

and 4Department of Cardiothoracic Surgery,

Heart Centre of the University Clinics Halle

(Saale), Martin Luther University Halle-

Wittenberg, Halle, Germany

Dr Stefan Reichert, PD, Department of

Operative Dentistry and Periodontology, Martin

Luther University Halle-Wittenberg, Groe

Steinstrasse 19, 06108 Halle (Saale), Germany

Tel: +49 345 557 3772

Fax: +49 345 557 3773

e-mail: [email protected]

Key words: coronary heart disease; gene

polymorphism; interleukin-6; periodontitis;

prognostic marker

Accepted for publication March 26, 2014

J Periodont Res 2014All rights reserved

2014 John Wiley & Sons A/S.Published by John Wiley & Sons Ltd

JOURNAL OF PERIODONTAL RESEARCH

doi:10.1111/jre.12191

Conclusions: These findings suggest that flossing and brushing of interdental

spaces might reduce the risk for new cardiovascular events among patients with

CHD. The hypothesis that interdental cleaning per se reduces the risk of new

cardiovascular events should be examined in an interventional study.

In the last years numerous studies

were carried out to investigate

whether periodontitis is a putative

risk factor for atherosclerosis (1,2)

and subsequent diseases such as coro-

nary heart disease (CHD) (3) and

stroke(4). Indeed, meta-analyses have

shown that periodontal disease is an

independent risk factor for CHD

(57) and cerebrovascular disease (8).Furthermore, the occurrence of peri-

odontopathogens in the subgingival

plaque was found to be associated

with the occurrence of CHD (9).

Interleukin (IL)-6 is a proinflamma-

tory cytokine, which stimulates hepa-

tic production of acute phase proteins

such as C-reactive protein (CRP),

modulates adhesion of monocytes on

endothelial cells and promotes coagu-

lation of platelets (10). Therefore,

IL-6 might be involved in the patho-

genesis of both periodontitis (1113)and CHD (1416). It has beenreported that IL-6 c.174G/C poly-morphisms influenced IL-6 serum lev-

els (17). The genotype GG was

identified as a high-producer genotype

whereas carriers of the GC and CC

genotypes showed lower IL-6 serum

levels.

The IL-6 c.174G/C polymorphismwas found to be associated to both

chronic (18) and aggressive periodon-

titis (19) as well as to the subgingival

colonization with periodontopatho-

gens (20). Furthermore, this polymor-

phism was found associated with

CHD (2123). Hence, IL-6 genotypesat promoter position 174 may beprognostic markers for CHD and

periodontitis and should be consid-

ered in multivariate risk factor

analyses.

So far, only one study from Fin-

land has investigated the role of den-

tal infection for new coronary events

among patients with proven coronary

artery disease (24). Therefore, the aim

of the present, prospective, longitudi-

nal study was to investigate whether

oral hygiene habits, severe periodonti-

tis, presence of periodontopathogens

in the subgingival biofilm, or certain

IL-6 c.174 genotypes represent inde-pendent risk factors for the incidence

of new cardiovascular events (com-

bined endpoint: myocardial infarction,

stroke/transient ischemic attack [TIA],

myocardial death) among inpatients

suffering from CHD.

Material and methods

Study population

At baseline, 942 consecutive German

patients of Caucasian origin from cen-

tral Germany admitted to the Depart-

ment of Internal Medicine III or

Department of Cardiothoracic Sur-

gery of the Martin Luther University

Halle-Wittenberg with angiographical-

ly proven CHD were prospectively

included from October 2009 to Febru-

ary 2011. The investigations were car-

ried out in accordance with the

ethical guidelines of the Declaration

of Helsinki and its amendment in

Tokyo and Venice. The study was

approved by the ethics committee of

the Martin Luther University Halle-

Wittenberg. Informed written consent

was obtained from each patient.

Inclusion criteria were age

18 years and known CHD asdefined by a stenosis of 50% of amain coronary artery by coronary

angiography or percutaneous coro-

nary intervention or coronary artery

bypass surgery. At least four own

teeth except for the third molars

needed to be present. Exclusion crite-

ria were pregnancy, antibiotic therapy

during the last 3 mo, subgingival scal-

ing and root planing during the last

6 mo or psychological reasons that

rendered study participation impracti-

cal. Patients with current alcohol or

drug abuse might be not completely

able to understand the aim of the

study and the necessity of an addi-

tional dental examination. If a drug

or alcohol abuse was known from

patients file or a patient reported

during the interview about a current

drug or alcohol abuse s/he was not

included in the study.

Ages, body mass index, current or

past diseases (e.g. diabetes mellitus,

hypertension and dyslipoproteinemia)

were assessed as part of the patients

medical history. Diabetes mellitus

was diagnosed when it was known

from the history and/or the patients

were receiving dietary or antidiabetic

drug therapy in the hospital, or had

a fasting blood glucose of 7 mM.Dyslipoproteinemia was assumed if

this had been prediagnosed, a ther-

apy with lipid-lowering agents was

being administered or a fasting cho-

lesterol of > 5.2 mM or low-densitylipoprotein cholesterol > 3.9 mM waspresent. Arterial hypertension was

defined as hypertension that was

diagnosed before the current hospital-

ization and/or the patient was taking

antihypertensive medication or when

a blood pressure of > 140/90 mmHgwas measured. Furthermore, patients

were asked about their smoking

behaviors. A person who smoked a

minimum of one cigarette per day

at the time of questioning was

considered a current smoker. For

quantification of cigarette smoking,

pack-year of each current smoker

was calculated. When calculating the

pack-year, former smokers were not

considered. Furthermore, all patients

underwent detailed clinical and bio-

chemical investigation. For instance,

serum parameters, including hemo-

globin (mM), IL-6 (pg/mL), CRP

(mg/dL) and creatinine (lM) wererecorded.

2 Reichert et al.

During the periodontal examina-

tion, patients were asked about the

frequency of tooth brushing per day

and whether they use dental floss or

interdental brushes to clean the inter-

dental spaces. The clinical assessment

involved determining the plaque index

(PI) (25) and assessing bleeding on

probing (BOP) (26). In both indexes,

four sites around each tooth (mesio-

buccal, mid-buccal, disto-buccal and

mid-lingual) were examined. The mea-

surements for both maximal clinical

probing depth (distance between gin-

gival margin and bottom of the

pocket) and maximum clinical attach-

ment loss (distance between cemento-

enamel junction and bottom of the

pocket) were taken using a pressure-

sensitive probe (DB764R; Aesculap

AG & Co. KG, Tuttlingen, Germany)

at six sites around each tooth (mesio-

buccal, mid-buccal, disto-buccal, me-

sio-lingual mid-lingual, disto-lingual).

For the diagnosis of periodontitis, we

used the published criteria for a two-

level periodontitis case definition for

risk factor research. Periodontitis was

defined as the presence of proximal

attachment loss of 3 mm in 2nonadjacent teeth. Severe periodonti-

tis was defined as the presence of

proximal attachment loss of 5 mmin at least 30% of the teeth (27).

A 1-year follow-up was performed

and the incidence of the combined

endpoint defined as myocardial infarc-

tion, stroke/TIA and death from car-

diovascular causes was calculated.

For acquiring follow-up data, a stan-

dardized questionnaire was sent out.

If patients did not return the

questionnaires, a telephone interview

was conducted with the patient or

patients relatives and physician, when

the patient was dead. At an unknown

current address or telephone number,

we contacted civil registration offices

and requested information about cur-

rent address or date of death. If the

patients death was already known,

for instance for individuals who died

in our hospital, we did not send out a

questionnaire. Instead, the informa-

tion about the cause and date of

death was obtained from electronic

patient files.

Determination of interleukin-6 c.174

G/C genotypes

The genomic DNA was obtained

from leukocytes in venous EDTA

blood using a commercial DNA

extraction kit (QIAamp; Qiagen,

Hilden, Germany) in accordance with

the manufacturers instructions.

Genotype analyses were carried out

using a commercial available polymer-

ase chain reaction (PCR)-SSP kit

(CTS-PCR-SSP Tray kit, Collabora-

tive Transplant Study, Department of

Transplantation Immunology of the

University Clinic of Heidelberg,

Germany) as described previously (28).

After agarose gel electrophoresis, the

results were evaluated visually. Bands

of 430 bp correspond to the various

IL-6 alleles. According to db single

nucleotide polymorphism, the identifi-

cation number of the single nucleotide

polymorphism was rs 1800793.

Molecular biological assessment of

periodontal bacteria in subgingival

pockets

Microbial samples were taken from

the deepest pocket of each quadrant

by inserting one sterile paper point

for 20 s. The four bacterial plaque

samples taken from each patient were

pooled in one tube. Aggregatibacter

actinomycetemcomitans, Porphyromon-

as gingivalis, Prevotella intermedia,

Tannerella forsythia, Treponema denti-

cola, Peptostreptococcus micros,

Fusobacterium nucleatum, Campylo-

bacter rectus, Eubacterium nodatum,

Eikenella corrodens and a combina-

tion of Capnocytophaga sputigena,

Capnocytophaga gingivalis and Capno-

cytophaga ochracea were specifically

assessed by PCR in a commercial lab-

oratory (micro-Ident plus test; HAIN-

Diagnostica, Nehren, Germany). The

procedure for detecting bacterial

DNA can be divided into three steps:

isolation of bacterial DNA, multiplex

amplification with biotinylated

species-specific primers by PCR, and

reverse hybridization. These steps

have been described in detail in a pre-

viously published paper of our group

(29). The detection limit for all bacte-

ria was 104 genome equivalents with

the exception of Aggregatibacter

actinomycetemcomitans with 103 gen-

ome equivalents. The numbers of

detected bacterial species per individ-

ual that were over the detection limit

were counted.

Statistical evaluation

Statistical analyses were carried out

using commercially available software

(SPSS v.19.0 package; IBM, Chicago,

IL, USA). Values of p 0.05 wereconsidered significant. The distribu-

tion of the IL-6 c.174GG, GC andCC among the inpatients with CHD

was tested according to the HardyWeinberg equilibrium.

Metric demographic, clinical and

serological data were checked for

normal distribution using the

KolmogorovSmirnov test and theShapiroWilk test. As all metric valueswere not normally distributed, they

were plotted as median and 25th/75th

percentiles. For statistical evaluation,

the MannWhitney U test was used.Pack-year was calculated by multi-

plying the number of packs (one

pack = 20 cigarettes) of cigarettessmoked per day by the number of

years the person has smoked.

To evaluate adjusted odds ratios

for occurrence of severe periodontitis

among patients with CHD, a logistic

regression analysis was conducted

with respect of the cofactors age, gen-

der, body mass index, pack-year,

number of detected different bacterial

species per individual, frequency of

tooth brushing per day, use of floss/

interdental brushes and expression of

IL-6 c.174 G/C genotypes.For survival evaluation, Kaplan

Meier analyses with the log-rank test

were applied. Adjusted hazard ratios

were generated with Cox regression

and with respect of the variables age

gender, body mass index, pack-year,

hypertension, dyslipoproteinemia, dia-

betes, serum levels for IL-6, CRP,

hemoglobin and creatinine, IL-6 c.174 genotypes (GC+CC vs. GG),number of missing teeth, number of

detected different bacterial species per

individual, frequency of tooth

Periodontitis and cardiovascular events 3

brushing per day and use of floss/

interdental brushes were included in

one model.

Results

Periodontal, microbial and serologic

conditions in inpatients with

coronary heart disease

All baseline data are presented in

Table 1. The overall prevalence of

severe periodontitis among our

patients with CHD was almost 50%.

A median of 10 missing teeth (excep-

tion third molars) was recorded. The

median for the number of detected

bacterial species was 7. The majority

of patients with CHD (74.9%)

brushed their teeth more than once a

day but only 20.1% used floss and/or

interdental brushes. The overall med-

ian values for CRP and IL-6 were

above the reference values for healthy

persons.

The distribution of the IL-6 c.-174

genotypes GG, GC and CC fulfilled

the criteria of the HardyWeinberg

equilibrium. Of the patients, 70%

were carriers of IL-6 c.174 genotypesGC or CC.

Factors associated to the

occurrence of a severe periodontitis

among patients with coronary heart

disease

The age, male gender, the number of

detected oral species, and occurrence

of IL-6 c.174 GC or CC genotypeswere associated with an increased

adjusted odds ratio for severe peri-

odontitis whereas the use of floss/

interdental brushes was associated

with a lower adjusted odds ratio

(Table 2). Patients who used floss

and/or interdental brushes were signif-

icantly younger, more often females,

and had lower values for pack-years,

occurrence of a severe periodontitis,

missing teeth, PI and BOP in compar-

ison to patients with CHD, who did

not use any aids for interdental

hygiene (Table 3).

Association of severe periodontitis,

periodontal and microbial

conditions and IL-6 c.174

genotypes with the incidence of the

combined endpoint within the 1-year

follow-up period

A total of 942 patients with CHD

were prospectively included in the

longitudinal cohort study. For one

patient (0.1% dropout rate) we did

not obtain 1-year follow-up data.

During the mean follow-up of

54 11 wk, 20 (2.1%) myocardialinfarctions, 17 (1.8%) strokes/TIAs

and 32 (3.4%) cardiovascular deaths

were recorded. The total incidence of

the combined endpoint was 7.3%.

Bivariate analyses The KaplanMeier plot (Fig. 1) showed a signifi-

cantly lower incidence for the

combined endpoint among patients

who used dental floss/interdental

brushes than among individuals who

did not use these aids for oral hygiene

(1.6% vs. 8.8%, log-rank p = 0.001).Moreover, patients with CHD who

had only 010 missing teeth showed asignificantly lower incidence of the

combined endpoint than individuals

Table 1. Periodontal conditions, prevalence of internal diseases, biochemical parameters,

distribution of c.174 interleukin-6 genotypes among inpatients with coronary heart dis-ease

Variables

Stationary patients

with coronary

heart disease

n = 942

Demographic parameters

Age (years), median (25th/75th percentiles) 68.8 (59.5/74.9)

Males (%) 74.0

Pack-years, mean (SD) 3.0 (9.7)

Body mass index (kg/m2), median (25th/75th percentiles) 28.1 (25.3/30.8)

Prevalence of internal diseases

Diabetes (%) 34.2

Hypertension (%) 87.6

Dyslipoproteinemia (%) 58.7

Oral care habits and periodontal conditions

Frequency of tooth brushing per day (%)

Once a day 23.9

More than once a day 74.9

Use of interdental floss/brush (%) 20.1

No periodontitis (%) 2.1

All periodontitis cases (%)a 97.9

Severe periodontitis cases (%)b 47.7

Plaque index (%), median (25th/75th percentiles) 0.8 (0.5/1.4)

Bleeding index (%), median (25th/75th percentiles) 5.6 (1.8/12.1)

Number of missing teeth, median (25th/75th percentiles) 10.0 (5.0/18.0)

Number of detected oral species, median

(25th/75th percentiles)

7.0 (5.0/8.0)

Serological parameters

C-reactive protein (mg/dL), median (25th/75th percentiles)

Reference: < 0.58.9 (3.6/32.1)

Interleukin 6 (pg/mL)

Median (25th/75th percentiles)

Reference: < 6.4

7.4 (3.6/15.7)

Creatinine (lM), median (25th/75th percentiles)Reference: males: < 102; females: < 88

87.0 (72.0/106.3)

Hemoglobin (mM)

Median (25th/75th percentiles)

Reference: males 8.711.2; females: 7.39.9

8.3 (7.2/9.1)

IL-6 c.174 G>C genotypes (rs 1800793) (%)GG 29.8

GC 49.3

CC 20.95

aAttachment loss of 3 mm in at least two non-adjacent teeth.bAttachment loss of 5 mm in 30% of teeth present.

4 Reichert et al.

who had 1124 missing teeth (4.9%vs. 9.8%, log-rank p = 0.004) (Fig. 2).The incidence for the combined end-

point tended to be higher in patients

with severe periodontitis than in indi-

viduals who did not have severe peri-

odontitis (8.9% vs. 5.9%, log-rank

p = 0.095). There was no significantdifference regarding the incidence of

the combined endpoint in patients

where none to five various bacterial

species were detected in comparison

to those with six to 11 bacteria (7.9%

vs. 7.0%, log-rank p = 0.515). IL-6c.174 genotypes were not signifi-

cantly associated with different inci-

dence rates of the combined endpoint

(GG 6.1%, GC 7.1%, CC 9.6%,

log-rank p = 0.340).

Multivariate analysis To generate

adjusted hazard ratios the influence of

severe periodontitis, oral hygiene hab-

its, number of missing teeth and

expression of IL-6 c.174 genotypeson the cardiovascular endpoint, was

investigated with Cox regression with

respect to known confounders for

both, periodontitis and CHD. Only

the use of dental floss/interdental

brushes was associated with a signifi-

cantly decreased adjusted hazard ratio

for the combined endpoint (Table 4).

Discussion

Periodontitis, periodontopathogens,

oral hygiene habits, number of miss-

ing teeth and polymorphisms in genes

of cytokines such as IL-6 might be

indicative for new cardiovascular

events among patients who suffer

from CHD. If such associations were

identified, the diagnosis and therapy

of periodontal diseases would need to

be regularly integrated into cardiac

rehabilitation programs to reduce the

risk for such events.

The purpose of the present study

was to evaluate the impact of these

periodontal and genetic conditions on

further cardiovascular events (com-

bined endpoint: myocardial infarction,

stroke/TIA, myocardial death) within

a 1-year follow-up period among

inpatients with proven CHD. The

hazard ratios should be controlled for

known confounders for both peri-

odontitis and CHD.

Both the overall prevalence of peri-

odontitis (97.9%) and prevalence of a

severe periodontitis (47.7%) among

our patients with CHD (Table 1) were

slightly higher than the epidemiologic

data obtained in the fourth German

Dental Health Survey (DMS IV). In

that study, the overall prevalence of

periodontitis was 87.8% (Community

Periodontal Index [CPI] Code 3 or 4)

among individuals aged from 65 to

74 years and 39.9% had a severe peri-

odontitis (CPI Code 4) (30). In con-

trast, the number of missing teeth

(except for the third molars) was not

higher among our patients with CHD

(14.0 vs. 14.2) (31).

The differences regarding the preva-

lence of periodontitis among patients

with CHD in comparison to the DMS

IV data should be interpreted with

caution, however, and we cannot con-

clude from these data that the preva-

lence of periodontal disease is higher

among patients with CHD in general.

For instance, CPI codes were only

recorded on index teeth and a pocket

depth on 45 mm (Code 3) wasdefined as periodontitis. In the present

Table 2. Logistic regression analysis for the occurrence of a severe periodontitisa among

patients with cardiovascular heart disease

Confounding variables

Odds

ratio

95%

lower

CI

upper p values

Age 1.02 1.01 1.04 0.002

Male gender 1.42 1.03 1.95 0.03

Body mass index 0.99 0.96 1.02 0.44

Pack-years 1.03 1.01 1.05 0.002

Frequency of tooth brushing per day 0.87 0.68 1.11 0.26

Use of floss/interdental brushes 0.50 0.35 0.71 < 0.001Number of detected bacterial various

species per individual

1.14 1.08 1.21 < 0.001

Diabetes 1.22 0.91 1.64 0.18

IL-6 c.174 GC or CC vs. GG 1.11 0.83 1.49 0.009

aAttachment loss of 5 mm in 30% of teeth present.

Table 3. Demographic, general and periodontal conditions in patients with coronary heart

diseases in depending on the use of aids for approximal hygiene

Variable

No use of floss/

interdental brushes

n = 753

Use of floss/

interdental brushes

n = 189 p

Age (years), median


69.2 (59.7/75.5) 67.3 (59.2/72.0) 0.006c

Males (%) 74.0 30.7 < 0.001b

Pack-years, mean (SD) 3.3 (10.4) 1.5 (5.9) 0.045c

Body mass index (kg/m2), median


28.1 (25.2/30.8) 27.9 (25.4/30.5) 0.649c

Severe periodontitis (%)a 51.9 30.7 < 0.001b

Missing teeth (exception third

molars), median (25th/75th

percentiles)

12.0 (6.0/20.0) 7.0 (3.1/10.0) < 0.0001c

Plaque index (%), median


0.9 (0.6/1.6) 0.6 (0.4/0.8) < 0.0001c

Bleeding upon probing (%),

median (25th/75th percentiles)

6.3 (2.2/12.5) 3.5 (0.9//6.9) < 0.0001c

Number of bacterial species per

individual, median (25th/75th

percentiles)

7 (5.0/8.0) 7 (4.0/8.0) 0.963c

aSevere periodontitis: Attachment loss of 5 mm in 30% of teeth present.bChi-squared test with Yates correction.cMannWhitney U-test.


study, the threshold for diagnosis of a

periodontitis case was a clinical

attachment loss of at least 3 mm in at

least two nonadjacent teeth. More-

over, all teeth were investigated.

As only 20 (2.1%) of our study

patients with CHD did not have peri-

odontitis, a separate statistical evalua-

tion for this cohort would not be

meaningful. Therefore, this group was

added to patients who had no severe

periodontitis.

Our main results showed a signifi-

cantly decreased adjusted HR for the

combined endpoint among patients

who used dental floss/interdental

brushes for oral hygiene (Table 4).

According to our results this associa-

tion might be due to the favorable

effect of proper oral hygiene in the

plaque and bleeding index, number of

missing teeth and prevalence of severe

periodontitis (Table 3). The inverse

association between use of floss/inter-

dental brushes and prevalence of a

severe periodontitis was additionally

confirmed in a binary logistic regres-

sion model (Table 2). The long-term

effect of effective plaque control on

periodontitis and tooth mortality has

already been demonstrated (32). The

use of aids for cleaning interdental

spaces as an adjunct to brushing was

found to remove more dental plaque

than brushing alone (33). In contrast

to our results, a Scottish health survey

(34) obtained (Table 4) an inverse

association between the frequency of

dental brushing and the risk of CHD.

The use of floss/interdental brushes,

however, was not evaluated.

Although our data suggest a direct

link between oral hygiene and the

incidence of the combined endpoint,

further confounders should be dis-

cussed. For instance, patients who

used aids for interdental hygiene were

significantly younger, more often were

females and had a lower smoke

exposure than their counterparts who

did not clean the interdental spaces

(Table 3). These confounders might

influence the risk for further cardio-

vascular events. It is also conceivable

that patients with a proper interdental

hygiene were in better general health

and more motivated and/or able to

use floss/interdental brushes regularly.

Furthermore, good oral care habits

such as use of aids for interdental

hygiene might reflect a higher health

consciousness in general. Despite this

uncertainty regarding the underlying

biologic effect of oral hygiene to the

incidence of new cardiovascular

events, the use of interdental brushes/

dental floss might be recommended,

in particular, to patients with CHD.

The hypothesis that interdental

cleaning per se reduces the risk of

new cardiovascular events should be

examined in an interventional study.

0.8

0.6

0.4

0.2

0.0

0 20 40 60 100Wk of follow up

Co

mb

ined

en

dp

oin

t

80

1.0

NoYes

Use of dentalfloss/interdental

brushes

Fig. 1. KaplanMeier plot for combined endpoint (stroke/transient ischemic attack, car-

diovascular death, myocardial infarction) according to the use of aids for interdental

hygiene (use of floss/interdental brushes vs. no use of floss interdental brushes).

010 missing teeth1124 missing teeth

0.8

0.6

0.4

0.2

0

0.0

20 40 60 100Wk of follow up

Co

mb

ined

en

dp

oin

t

80

1.0

Fig. 2. KaplanMeier plot for combined endpoint (myocardial infarction, stroke/transient

ischemic attack, myocardial death) according to the number of missing teeth (010 missing

teeth vs. 1124 missing teeth).

6 Reichert et al.

Although oral hygiene habits were

associated to both, the prevalence of

a severe periodontitis (Table 2) and

incidence of the cardiovascular end-

point (Table 4) we found only a trend

but not a significant association

between severe periodontitis and the

incidence of the combined endpoint at

all. In contrast to our result, a previ-

ous study (24) showed a significant

positive association between dental

infection and the risk of new coronary

events among patients with proven

coronary artery disease. In particular,

differences in the study design (e.g.

number of studied individuals, follow-

up intervals and definition of the end-

point, including cofactors) might be

responsible for these inconsistent

results. For instance, in a previous

study (24) only 214 individuals were

investigated but the follow-up period

was 7 years. The endpoint was

defined as incidence of fatal and non-

fatal coronary events and overall

mortality but incidence of TIA/stroke

was not investigated. Moreover, in

comparison to our multivariate Cox

regression the socioeconomic status,

the number of previous myocardial

infarctions, and serum lipids were

included as confounding variables.

A Swedish longitudinal study (35)

reported a dose-dependent relation-

ship between number of teeth and

all-cause and cardiovascular disease

mortality. The authors assumed that

severe tooth loss might be an indica-

tor for life-long dental infections,

which could represent an important

risk factor for atherosclerotic vascular

changes. The results of that study are

partially confirmed by our findings

because, according to the log-rank

test (Fig. 2), the incidence of the com-

bined endpoint was associated with

the number of missing teeth. How-

ever, this was not significant in the

multivariate model (Table 4).

The positive association between

the periodontal pathogen burden and

the prevalence of CHD obtained in a

previous cross-sectional controlled

study (9) could not be confirmed by

our results. According to our findings,

the number of detected bacterial spe-

cies per individual was indeed associ-

ated to the prevalence of a severe

periodontitis (Table 2) but not to the

incidence of the combined endpoint

(Table 4).

This different result in comparison

to the preceding study (9) could be

due to differences in study designs

(cross-sectional vs. longitudinal) or

the different methods for detecting

periodontopathogens and thus differ-

ent detection limits.

There was trend for a positive asso-

ciation between the individual expres-

sion of the genotypes IL-6 c.-174 GC

or CC and the prevalence of a severe

periodontitis among patients with

CHD (Table 2). However, although

our patients who were carriers of IL-6

c.174 CC or GC genotypes usuallymet the combined endpoint, this was

not significant after both log-rank test

and Cox regression. Therefore, our

results did not support previous cross-

sectional studies and meta-analyses,

which identified the IL-6 c.174 G/Cpolymorphism as indicative for car-

diovascular diseases (2123,36).

Limitations of the study

The present study is a longitudinal

cohort study to investigate predictors

for new cardiovascular events among

patients with CHD. Therefore, a gen-

der- and age-matched non-CHD con-

trol group was not included and the

prevalence of a severe periodontitis

among patients with CHD was com-

pared with data obtained in the

fourth German Dental Health Survey

(DMS IV). Not surprisingly, the com-

parison of patients with CHD to

matched controls without CHD

would extend conclusions. The pres-

ent study does not provide informa-

tion about whether use of aids for

interdental hygiene among individuals

without CHD reduced the risk for

CHD events at all.

In the study 118 patients were

included who reported in the inter-

view about a previous periodontitis

therapy earlier than 6 mo before den-

tal examination. Previous periodontal

therapy might lower the risk for new

cardiovascular events. Moreover,

patients with CHD were heteroge-

neous regarding their status of inter-

nal diseases. For instance, patients

with diabetes who had not yet started

any diabetic control measures were

included.

It is feasible that patients with

CHD where the concomitant internal

diseases were well treated have a

Table 4. Cox regression for the incidence of the combined endpoint (myocardial infarction,

stroke/transient ischemic attack, myocardial death) within the 1-year follow-up period

among patients with coronary heart disease. Significant data are highlighted in bold print.

Confounding variables

Hazard

ratio

95%

lower

CI

upper p values

Age 0.99 0.97 1.02 0.52

Male gender 0.65 0.37 1.16 0.15

Body mass index 0.95 0.89 1.00 0.07

Pack-years 0.99 0.96 1.02 0.43

Hypertension 0.96 0.45 2.02 0.91

Dyslipoproteinemia 0.86 0.53 1.41 0.55

Hemoglobin 0.97 0.78 1.20 0.77

Diabetes 1.51 0.90 2.56 0.12

IL-6 1.00 0.99 1.01 0.29

C-reactive protein 1.00 0.99 1.00 0.71

Creatinine 1.00 1.00 1.00 0.13

Severe periodontitisa 1.20 0.68 2.09 0.53

IL-6 c.174 GC or CC vs. GG 1.41 0.79 2.49 0.24Missing teeth 0.99 0.96 1.03 0.74

Plaque index 1.25 0.89 1.77 0.20

Number of detected various bacterial

species per individual

0.91 0.82 1.01 0.07

Frequency of tooth brushing per day 1.14 0.74 1.78 0.56

Use of floss/interdental brushes 0.19 0.06 0.63 0.01

CI, confidence interval; IL, interleukin.aSevere periodontitis: Attachment loss of 5 mm in 30% of teeth present.


lower risk for further CHD events

than patients with untreated internal

diseases.

We investigated Caucasian patients

from central Germany. As the distri-

bution of gene polymorphisms is also

different with respect to ethnicity, our

results regarding the IL-6 polymor-

phism cannot be transferred to groups

with other ethnic affiliations.

With multivariate analyses, we tried

to identify independent risk indicators

for the incidence of the cardiovascular

endpoint. However, the results depend

very strongly on the type and number

of included confounding variables and

duration of follow-up. This could

explain different results in comparison

to other investigations.

In summary, the use of dental floss

and/or interdental brushes was signifi-

cantly associated with an adjusted

decreased HR for new cardiovascular

events among patients with CHD

within a 1-year follow-up period

whereas severe periodontitis, number

of missing teeth, the amount of

detected bacterial species and certain

IL-6 c.174 genotypes were not.Whether the use of aids for oral

hygiene actually reduces the incidence

of new cardiovascular events should be

investigated in an interventional study.

Acknowledgements

We would like to thank all patients

for their cooperation in this study.

Source of funding

The study was supported by a grant of

the Deutsche Herzstiftung, Frankfurt

am Main, Germany (F/34/08) and by

an unrestricted grant from HAIN-

Diagnostica, Nehren, (Germany).

Conflict of interest

The authors declare that they have no

conflict of interest.

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