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J Clin Periodontol 2008; 35 (Suppl. 8): 362–379 doi: 10.1111/j.1600-051X.2008.01281.

Cardiovascular disease and Gösta Rutger Persson1,2,3 and

Rigmor Elisabeth Persson1,3
Department of Periodontology, University of

periodontitis: an update on the Bern, Bern, Switzerland; 2Department of

Periodontology, University of Washington,
Seattle, WA, USA; 3Department of Oral

associations and risk Medicine, University of Washington, Seattle,


Persson GR, Persson RE. Cardiovascular disease and periodontitis: an update on the
associations and risk. J Clin Periodontol 2008; 35 (Suppl. 8): 362–379. doi: 10.1111/

Background: Associations between periodontitis and cardiovascular diseases have
been recognized.
Material and Methods: New literature since the last European Workshop on
Periodontology has been reviewed.
Results: The lack of reliable epidemiological data on disease prevalence makes an
assessment of the associations and risks between periodontitis and cardiovascular
diseases difficult. Two recent meta-analysis reports have identified associations
between periodontitis and cardiovascular diseases (odds ratios: 1.1–2.2). Different
surrogate markers for both disease entities, including serum biomarkers, have been
investigated. Brachial artery flow-mediated dilatation, and carotid intima media
thickness have in some studies been linked to periodontitis. Studies are needed to
confirm early results of improvements of such surrogate markers following periodontal
therapy. While intensive periodontal therapy may enhance inflammatory responses and
impair vascular functions, studies are needed to assess the outcome of periodontal
therapies in subjects with confirmed cardiovascular conditions. Tooth eradication may
also reduce the systemic inflammatory burden of individuals with severe periodontitis.
The role of confounders remain unclear.
Key words: acute coronary syndrome;
Conclusions: Periodontitis may contribute to cardiovascular disease and stroke in
atherosclerosis; infection; inflammation;
susceptible subjects. Properly powered longitudinal case–control and intervention periodontitis; review; stroke; therapy
trials are needed to identify how periodontitis and periodontal interventions may have
an impact on cardiovascular diseases. Accepted for publication 20 May 2008

Cardiovascular diseases comprise a vari- (Karchmer 1997). Cardiovascular dis- and thromboembolic events result from
ety of heart and vascular conditions eases are common in many adult popula- atherosclerosis and often in combination
including: ischaemia, atherosclerosis, per- tions (Rosamond et al. 2007). Over the with a superimposed coronary thrombosis.
ipheral artery disease, infective endocar- last 30 years, the greater life expectancy Development of atherosclerosis begins
ditis, and acute myocardial infarction and changes in diet and exercise habits already in the first or second decade of
have resulted in a higher prevalence of life, and with clinical manifestations
Conflict of interest and source of obesity, elevated levels of blood choles- many years later.
funding statement terol, hypertension, and diabetes mellitus A large number of surrogate endpoints
The Clinical Research Foundation for the which are all recognized cardiovascular of future cardiovascular diseases has been
Promotion of Oral Health (CRF) University risk factors. Smoking is another risk factor identified. This includes assessments of
of Berne, Switzerland has supported the in cardiovascular disease contributing to carotid intima media thickness (IMT),
review. The authors declare no conflict of the increasing incidence and mortality of flow-mediated dilatation of the brachial
interests. cardiovascular diseases (Kuller 2006). artery, serum biomarkers including high
The 6th European Workshop on Perio- Atherosclerosis, and myocardial density lipoprotein (HDL), low density
dontology was supported by an unrest- infarctions occur as a product of com- lipoprotein (LDL), cholesterol fibrinogen,
ricted educational grant from Straumann plex combinations of factors (Ross triglyceride, high sensitivity CRP,
AG. 1997). Myocardial infarctions, stroke, HbA1c, and systolic/diastolic blood pres-
362 r 2008 The Authors
Journal compilation r 2008 Blackwell Munksgaard
Periodontitis and cardiovascular diseases 363

sure. These surrogate measures, however, an association between periodontitis and routine measure of stroke risk. Carotid
only partly account for the occurrence of coronary heart disease [odds ratio (OR) artery calcification can be seen on
future cardiovascular diseases (EURO- 2.2, 95% CI 1.6–3.1, po0.001]. The panoramic dental radiographs and can
ASPIRE 1997). Currently, there are no prevalence of coronary heart disease in be related to a history of cerebral infarc-
recognized definitive diagnostic risk mar- the cross-sectional studies reviewed tion (Kumagai et al. 2007). Studies have
kers of cardiovascular diseases. (17,724 patients) was greater among demonstrated that the accuracy of
Diabetes mellitus constitutes another individuals with periodontitis than in panoramic radiographs against current
risk for cardiovascular disease and with subjects without periodontitis (OR 1.6, gold standard for the diagnosis of car-
a high mortality rate (Golden et al. 95% CI: 1.3–1.9, po0.001). otid coronary calcification (doppler
2007). Pro-inflammatory mediators Table 1 provides a summary based on sonography) is high (Ravon et al.
implicated in hyperglycemia has also studies on the associations and risks 2003). Patients presenting with evidence
been associated with periodontitis and between periodontitis and cardiovascu- of carotid calcification on panoramic
indicative of increased cardiovascular lar diseases. Meta-analysis of prospec- radiographs should be referred for cere-
disease risks (Janket et al. 2007). A tive and retrospective follow-up studies bro-vascular and cardiovascular evalua-
variety of processes may be responsible have shown that periodontal disease tion and treatment (Cohen et al. 2002).
for coronary artery abnormalities. This may only slightly increase the risk of
includes diet/overweight, metabolic dis- cardiovascular disease (Meurman et al.
ease, lack of exercise, stress, drugs, 2003, Bahekar et al. 2007, Mustapha
Role of infection and immune response in
socioeconomic status, gender, and et al. 2007). Furthermore, when adjust- periodontitis and cardiovascular disease
genetic factors. ing for demographic factors, studies
Many epidemiological studies have have shown that the association between The role of infection in acute coronary
identified statistically significant asso- periodontitis based on clinical attach- syndrome, stroke, and atherosclerosis is
ciations between established Perio- ment level measurements in relation to disputed. An infectious burden may be
dontitis and cardiovascular diseases coronary artery calcification (Agatason less significant in cardiovascular disease
(i.e. Mattila et al. 1989, DeStefano score) does not demonstrate a significant development than previously thought
et al. 1993, Beck et al. 1996). This asso- association between the two conditions (Steptoe et al. 2007). The hypothesis
ciation is not without dispute (Hujoel (Nakib et al. 2004). In contrast, others that different bacteria are involved in
et al. 2001, Beck et al. 2005). This have found a significant relationship the development of atherosclerosis may
review includes documents published between periodontal status based on also be an effect of the total infectious
between 2000 and December 2007, and clinical measures of probing pocket burden and not caused by a single
with focus on the last 3 years seeking depth/clinical attachment loss and acute bacterial infection (Espinola-Klein
explanatory factors to why patients with myocardial infarction (Cueto et al. et al. 2002, Honda et al. 2005). In the
periodontitis may be at an elevated risk 2005). Most studies provide odds ratios case of infective endocarditis, a specific
for cardiovascular diseases. A literature of periodontitis (defined by clinical microbial infection of the endothelial
search using Embase and Medline iden- measures of probing pocket depth and surface of the heart and heart valves is
tified more than 550 peer-reviewed clinical attachment levels) as a risk for more evident. A large number of differ-
publications on cardiovascular diseases cardiovascular disease at levels less than ent types of bacteria, fungi, and virus
and periodontitis and published in a ratio of 3:1. Studies resulting in higher have been identified in infective endo-
many different languages. Publications ORs have commonly used alveolar bone carditis of subjects age 601 (Karchmer
(4100) in the Italian, French, German, loss as the definition of periodontitis 1997, Baldassarri et al. 2004, Presterl
Polish, Russian, and in Chinese lan- rather than measures of probing pocket et al. 2005).
guages were excluded in this review depth and clinical attachment level Several studies have investigated the
and only literature in the English lan- (Persson et al. 2003a, Engebretson role of infection in cardiovascular
guage has been considered. et al. 2005, Geismar et al. 2006, Rech diseases.
et al. 2007). The study by Beck et al. Studies suggest that Chlamydia pneu-
(2005) confirmed that clinical signs moniae and Helicobacter pylori can be
Periodontitis-Cardiovascular (bleeding on probing, probing pocket linked to cardiovascular diseases (Liu et
Diseases – Association Studies depth, clinical attachment levels) are al. 2006, Miyazaki et al. 2006, Nyström-
The relationship between periodontitis not representative for the impact of Rosander et al. 2006, Atar et al. 2007).
and cardiovascular disease has been cumulative effects of periodontitis on Nevertheless, there is no common
summarized in two recent publications systemic health. Disparities in preva- agreement on the role of bacteria and
based on the principles of meta-analysis lence rates of periodontitis in study infection as a primary etiology for car-
(Bahekar et al. 2007, Mustapha et al. populations with different age groups, diovascular diseases. The infectious
2007). The analysis by Bahekar et al. ethnicity, and geographic location etiology of periodontitis is, however,
(2007) including five prospective cohort makes it difficult to assess the likelihood well established (Socransky & Haffajee
studies (86,092 patients) indicated that of an association between periodontitis 2005, Paster et al. 2006). Several studies
individuals with periodontitis had a 1.14 and cardiovascular diseases. assessing the presence of bacteria asso-
times higher risk of developing coronary Stroke is one of the major vascular ciated with periodontitis in specimens
heart disease than subjects without diseases. An association between cere- collected from the aorta or other blood
periodontitis [relative risk 1.14, 95% brovascular events and periodontitis has vessels have identified bacteria asso-
confidence interval (CI) 1.01–1.2, been identified in a few studies (Persson ciated with periodontitis in samples
po0.001]. The case–control studies et al. 2002, Grau et al. 2004). Doppler from aorta and heart valves. A summary
(1423 patients) showed greater odds of sonography of the carotid arteries is a of such reports is provided (Table 2).
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364 Persson & Persson

Table 1. Studies assessing associations between cardiovascular diseases and periodontitis

Authors Study design Periodontal diagnosis Medical diagnosis Association

Mattila et al. Case–control study Total dental index: ACS consecutive cases, ACS-cholesterol (po0.001)
(1989) caries, periodontitis, peri-apical hospital confirmed cases ACS-detal index
lesions, abscess (14 criteria). (po0.01)
Subjects were assigned a score ACS-smoking (po0.01)
from 0 to 10 Odds ratio was not calculated
DeStefano Epidemiological Russell index Incidence of coronary heart CHD-gingivitis:
et al. (1993) study based on the Gingivitis disease (CHD) 1974–1987 OR 5 0.95, 95% CI: 0.5–1.8
NHANES I and the Periodontitis CHD-periodontitis:
(NHEFS) data OR 5 1.5, 95% CI: 0.8–3.0
CHD 5 CHD-Russell index:
OR 5 1.1, 95% CI: 0.9–1.3
Beck et al. A cohort study with Bone loss score based on Coronary heart disease OR 5 1.5
(1996) combined data from 5 different categories was including non-fatal 95% CI: 1.01 to 2.1
(1) the Normative assessed. More than 20% sites infarction, angina pectoris,
Aging Study, (2) the with bone loss 5 periodontitis and coronary heart disease
Dental Longitudinal death
Study (Veterans
Morrison A retrospective study Oral health/periodontitis Mortality experience in OR 5 2.2
et al. (1999) 1972–1993, the cornary heart disease 95% CI: 1.3 to 3.7
Nutrition Canadian
Persson et al. Cross-sectional study Composite of radiographic Self-reported history of OR 5 4.3 95% CI 2.4–7.9
(2002) of older subjects 651 evidence and probing pocket cardiovascular diseases
depth confirmed by medication
Lessem et al. Retrospective case Radiographic evidence of Heart transplant cases were 76% of cases had periodontitis
(2002) series alveolar bone loss searched through medical before heart transplantation.

Meurman Case–control study Revised version of the dental Serum samples of 256 High MDI/heart disease
et al. (2003) of 256 subjects with index as described by Mattila et patients with New York OR 5 1.3 95% CI: 1.2–1.5
heart disease and 250 al., 1989 and based on clinical Heart Association class II– Gingivitis/heart disease
controls and radiological dental IV heart disease (OR 5 3.4, 95% CI: CI 1.7–6.9)
examinations (MDI index)
Persson et al. Matched case– Alveolar bone loss X4 mm at Acute coronary syndrome All subjects:
(2003c) control study based approximal sites consecutive cases with Bone loss 450%
on consecutive cases Different proportional rates hospital diagnosis. Age, OR 5 14.1 95% CI: 5.5–28.2
of acute coronary from o10% to 450% of sites gender, smoking status, Bone loss 430% of sites
syndrome with alveolar bone loss socio-economic matched OR 5 12.95% CI: 4.7–35.3
controls through medical in non-smokers:
examination OR 5 5.9 95% CI: 1.4–24.4
Ravon et al. Case–control study Bone loss X4 mm at approximal Positve or negative duplex OR: 38.4, 95% CI: 10.6–138.7
(2003) sites at 430% of sites ultrasonography
Geerts et al. Case–control study Periodontitis defined by probing Hospital confirmed cases OR: 6.5, 95% CI 1.8–23.0)
(2004) 108 coronary heart pocket depth . One site or more with coronary heart disease A dose response curve for the
disease cases and 62 X5 mm in treatment PIRI index and coronary heart
healthy control New index for periodontal disease
subjects infection risk index (PIRI)
Nakib et al. Epidemiological Clinical attachment level Coronary artery calcification OR: 1.5, 95% CI: 0.5–4.2
(2004) study of 6931 X3 mm was used to define (Agatston score) Not statistically significant
subjects (1996–2000) periodontitis Adjusted for demographic
Shimazaki Case–control study Periodontal status of 1,111 374 Subjects without heart PPD definition:
et al. (2004) of 957 subjects males and 583 female Japanese disease as defined by ECG OR: 5 1.7 95% CI: 1.01–2.0
with X10 teeth was studied. analysis were studied CAL definition
OR: 1.7, 95% CI: 1.1–2.7)
Beck et al. Cross-sectional study Routine clinical data Coronary heart disease The study failed to identify an
(2005) and a subset of Subgingival samples (ACS) association between ACS and
participants in the Antibody titres to a selection of periodontitis based on clinic
Atherosclerosis Risk bacteria including: data. Microbiological data
in Communities A. actinomycetemcomitans, suggested significant odds ratios
(ARIC) Study C. ochracea for some bacteria (see text)
P. intermedia
T. denticola

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Periodontitis and cardiovascular diseases 365

Table 1. (Contd.)
Authors Study design Periodontal diagnosis Medical diagnosis Association

Engebretson Case–control study Radiographic assessment of Ultrasound OR: 3.6, 95% CI: 1.4–9.7
et al. (2005) carotid calcification and alveolar Association between bone loss
bone loss and carotid artery plaque
Buhlin et al. Case–control study Assessments were performed Subjects treated for coronary Periodontal pockets and
(2005) Women only for: heart disease (angioplasty, coronary heart disease
Number of remaining teeth and by-pass grafting) OR: 3.8, 95% CI: 1.68–8.74),
pathological periodontal pockets Dentures and coronary heart
(X4 mm), Denture/no dentures disease: OR of 4.6 (0.99–21.28).
Vertical bone loss No relationship to vertical bone
Cueto et al. Case–control study Percentage of sites with clinical Medically confirmed acute Adjusted OR: 3.1
(2005) attachment loss and probing coronary syndrome
pocket depth were dichotomized
Holmlund Case–control study, Periodontal index scale 0–4 Subject self-report of a Periodontitis and myocardial
et al. (2006) referred dental dependent on extent of bone loss history of myocardial infarction
patients for (defined as 41/3 root length, infarction or high blood OR: 2.7,
periodontal care bleeding on probing and teeth pressure (not defined) 95% CI: 1.1–6.5
with furcation
Spahr et al. Case–control study CPITN index Angiography confirmed OR, 1.67
(2006) coronary heart disease and 95% CI, 1.08–2.58
controls with no medical
Geismar et al. Case–control study Full mouth periodontal exam. Routine serum assay. OR 5 6.6
(2006) Radiographic assessments Confirmed medical (95% CI: 1.9 to 25.6
conditions coronary disease Bone Loss
(0110) or health (n 5 140)
Rech et al. Case–control study Probing pocket depth 43 mm, ACS consecutive cases with OR 5 4.5
(2007) and/or bleeding on probing, and/ hospital diagnosis 95% CI: 1.3–15.6
or loss of clinical attachment,
and/or bone loss. Diagnosis
defined by clinicians unaware of
medical status
ACS, acute coronary syndrome; CHD, coronary heart disease; OR, odds ratio.

Streptococcal species have also been systematic reviews and meta-analysis of multi-organ failures (Taneva et al.
linked to acute coronary syndrome (Li published reports have identified that 2004). Age is an important factor asso-
et al. 2000, Herzberg et al. 2005, elevated antibody titres to bacteria asso- ciated with both periodontitis and cardi-
Nomura et al. 2006, Plummer & Dou- ciated with periodontitis can be linked to ovascular diseases. Studies in Mexico
glas 2006, Renvert et al. 2006). In oral cardiovascular disease risk (Meurman on the prevalence of periodontitis
biofilm formations, streptococci co- et al. 2003, Mustapha et al. 2007). among older subjects have revealed
aggregate with Gram-negative bacteria A summary of studies on serum anti- high prevalence rates of periodontitis
including Porphyromonas gingivalis body titres to bacteria associated with varying between 27% and 73%, and
and the same mechanism may be part periodontitis and cardiovascular disease depending on socioeconomic and geo-
of colonization of P. gingivalis on is presented (Table 4). High antibody graphic conditions. Furthermore, the
endothelial cells (Maeda et al. 2004). titers to A. actinomycetemcomitans spe- severity of periodontitis could be linked
Others have, however, failed to demon- cifically have been associated with cor- to high blood pressure and high body
strate that the counts of Aggregatibacter onary heart disease (Pussinen et al. mass index (BMI) (Borges-Yáñez et al.
actinomycetemcomitans, P. gingivalis, 2004a, b, 2005, 2007a, b, Beck et al. 2006). In a study of 1763 subjects
Parvimonas micra, Dialister pneumo- 2005, Vilkuna-Rautiainen et al. 2006). between age 38 and 88 in Japan, sub-
sintes, or Campylobacter rectus could Serum immunoglobulin A (IgA) and clinical aortic atherosclerosis as
be associated with cardiovascular dis- IgG antibody titres to A. actinomyce- assessed by magnetic resonance ima-
ease as defined by angiography (Non- temcomitans have also been linked to ging (MRI) appears to be present in
nenmacher et al. 2007). future stroke event (Pussinen et al. 50% of subjects and increasing with
2004a). age (Oyama et al. 2008). In a study of
people 80 years and older in an affluent
Sero-epidemiologic studies
part of central Stockholm, Sweden the
Traditional cardiovascular risk factors
A majority of medical studies suggest- prevalence of severe periodontitis in
ing an association between antibody older adults approached 50% (Holm-
titres against common pathogens and Pedersen et al. 2006). Similar high pre-
cardiovascular diseases including stroke Older patients often suffer from many valence rates of periodontitis in older
have particularly focused on C. pneu- diseases and many geriatric subjects subjects have been reported from Den-
moniae, and H. pylori (Table 3). Recent with acute coronary syndrome have mark (Krustrup & Petersen 2006). Thus
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366 Persson & Persson

Table 2. Examples of studies on the role of bacteria in periodontitis as link to cardiovascular disease
Authors Bacteria/type of study Study design Condition/result

Haraszthy A. actinomycdtemcomitas Case series with samples from 50 subjects 61% of 36 samples positive for bacteria
et al. (2000) P. gingivalis requiring endarterectomy. PCR analysis included one or more of the species studied.
P. intermedia 36% were positive for P. gingivalis
T. forsythia
Beck et al. See also text Table 1 case– Serum antibody titres to 17 different species in OR: A. actinomycetemcomitans 1.7(95% CI:
(2005) control study Beck et al periodontitis: ACS 1.2–2.7)
OR C. ochracea 2.0 (95%CI: 1.2 3.0)
OR: P. nigresens 1.7 (95% CI: 1.1–2.6)
Fiehn et al. A. actinomycetemcomitans 179 specimens of atherosclerotic plaque Viable oral bacteria could not be isolated from
(2005) C. rectus removed from carotid or femoral arteries were the atheromas.
P. gingivalis, studied by use of PCR techniques DNA of periodontal pathogens was detected in
P. intermedia, P. nigrescens atherosclerotic plaques. P. gingivalis was
T forsythia, and oral rarely found and P. intermedia more frequently
Kozarov et al. A. actinomycetemcomitans, 129 samples of DNA extracted from atheromas DNA from oral infectious agents is commonly
(2006) C. pneumoniae E. corrodens from 29 individuals were studied found in atheromas from young but especially
P. gingivalis P. intermedia from elderly subjects. The contribution of C.
S. aureus, S. epidermidis pneumoniae to inflammation may be minimal.
S.mutans, T. forsythia S. mutans was found in 20%, S. aureus in 5%
T. denticola S. epidermis in 10%, bacteroides species were
found in 17% of young and in 80% of older
Nomura et al. S. mutans Heart valve specimens from 52 patients and The serotype distribution in cardiovascular
(2006) atheromatous plaque specimens from 50 patients was significantly different from that in
patients were studied and dental plaque healthy subjects, suggesting that S. mutans
specimens from 41 patients before surgery serotype may be related to cardiovascular disease
Renvert et al. The subgingival pathogens were A total of 161 consecutive surviving cases The oral bacterial load of S. intermedius,
(2006) assayed by the checkerboard admitted with a diagnosis of acute coronary S. sanguinis, S. anginosus, T. forsythia,
DNA–DNA hybridization syndrome and 161 matched control subjects T. denticola, and P. gingivalis are concomitant
method. 40 species examined risk factors in ACS
Aimetti et al. T. forsythia, P. gingivalis, DNA was extracted from subgingival plaque Bacterial DNA was detected in 31 out of 33
(2007) T. denticola, P. intermedia, and samples and carotid atheromas from 33 endarterectomy specimens. None of the
A. actinomycetemcomitans subjects samples tested positive for DNA from
periodontal pathogens
Gotsman et al. P. gingivalis 201 patients with stable angina or ACS who Patients with ACS had significantly higher
(2007) underwent a periodontal assessment. Severity plaque scores, gingival index, and P. gingivalis
of coronary artery disease was determined by counts than stable patients
the number of obstructed coronary arteries
Nakano et al. S. mutans 35 heart valves and 27 atheromatous plaques S. mutans was detected in 69% of heart valves
(2006) were studied by PCR and in 74% of atheromatous plaques
Nakano et al. A. actinomycetemcomitans 60 heart valves, 10 with endocarditis, and 50 A. actinomycetemcomitans serotype e, and f
(2007) with valvular disease and dental plaque were was detected in both dental plaque and
analysed by PCR. Serotyping of A.a. was cardiovascular specimens
Pucar et al. A. actinomycetemcomitans, Patients with a diagnosis of coronary artery The absence of putative pathogenic bacteria in
(2007) C. pneumoniae disease were studied. Coronary arteries with internal mammary arteries, and their presence
P. intermedia, P. gingivalis atherosclerosis and 15 internal mammary in a high percentage of atherosclerotic
T. forsythia, and arteries without clinically assessable coronary arteries support the concept that
Cytomegalovirus atherosclerotic degeneration were investigated periodontal organisms are associated with the
development and progression of
Zaremba et al. A. actinomycetemcomitans The incidence of periodontal bacteria in A. actinomycetemcomitans in 1/20
(2007) C. rectus, F. nucleatum atherosclerotic plaque by DNA analysis from C. rectus in 4/20
P. gingivalis, P. intermedia 20 subjects was studied F. nucleatum 5/20
T .forsythia, T. denticola P. intermedia in 33%
P. gingivalis in 10/20
T. Denticola in 6/20
T. forsythia in 5/20
ACS, acute coronary syndrome; ELISA, enzyme linked immuno sorbent assay; OR, odds ratio; PCR, polymer chain reaction; P. intermedia,
Porphyromonas intermedia; P. gingivalis, Porphyromonas gingivalis; T. forsythia, Tannerella forsythia; S. mutans, Streptococcus mutans, T. denticola,
Tannerella denticola; A. actinomycetemcomitans, Aggregatibacter actinomycetemcomitans; C. rectus, Campylobacter rectus.

it is likely that many of these older between periodontitis and cardiovascu- 50% of subjects older than 60 years of
subjects also have significant severity lar disease in older subjects (Persson et age had periodontitis. In addition,
of cardiovascular disease. There are few al. 2002, Cueto et al. 2005). In the study approximately 55% had either a diag-
studies having assessed the association by Persson et al. (2002) approximately nosis ot atherosclerosis, or a history of
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Periodontitis and cardiovascular diseases 367

Table 3. The role of infection and antibody titres in subjects with cardiovascular disease in studies not assessing dental conditions (2006–2007)
Authors Bacteria Antibodies Disease Results Antibody function

Grabczewska, C. pneumonaie Serum IgG Unstable angina Antigen profile of importance, Not protective
et al. (2006) H. pylori antibodies by Case series suggesting specific role of Diagnostic of risk
ELISA antigen profile
Kaperonis C. pneumonia IgA and IgG Symptomatic and Detection of C. pneumonia and Not protective
et al. (2006) antibodies in non symptomatic elevated levels of serum Diagnostic of risk
serum subjects undergoing antibodies to C. pneumoniae
endartherectomy were correlated
Pitiriga et al. C .pneumoniae IgA and IgG titres Coronary artery Difference by IgA titres but not Not protective or irrelevant
(2006) defined by disease in subjects by IgG titres Diagnostic of risk
immuno- with our without
fluorescence disease
Völzke et al. Borrelia infection Serum IgG Cross-sectional study Elevated IgG titres linked to Not protective and suggesting
(2006) antibodies to of carotid intima artherosclerosis that Borrelia infection is a risk
Borrelia media thickness in regions with endemic lyme
definition of disease
Yavuz et al. C. pneumoniae IgA and IgG Atherosclerosis C. pneumoniae seropositivity Not protective and suggestive of
(2006) serum antibody severity associated with dyslipidemia, C. pneumoniae infective
titres and elevated IL-6 etiology
Buyukhatipoglu C. pneumoniae Serum IgG Atheroesclerosis in Correlation between extent of Not protective to C. pneumoniae
et al. (2007) Cytomegalovirus antibody titres haemodialysis carotid media thickening and and irrelevant to CMV
(CMV) subjects and controls IgG titres to C. pneumoniae but
not to CMV
Hagiwara C. pneumoniae Serum IgA and Severe carotid artery None of the different antibody Irrelevant to CVD and
et al. (2007) H. pylori IgG titres by stenosis a case series titres correlated with degree of periodontitis in Japanese
Cytomegalovirus ELISA of 50 Japanese stenosis subjects
Herpes simplex subjects
Jha et al. (2007) C. pneumoniae Serum IgA and Coronary artery Presence of C. pneumoniae and Not protective
IgG antibodies by disease in subjects elevated IgA1IgG titres linked Indicative of risk
ELISA with our without to coronary heart disease
Piechowski- C. pneumoniae Serum IgA and Young adults with Increased risk with elevated IgA Not protective
Jóżwiak et al. IgG antibodies by ischaemic stroke and titres to C. pneumoniae Diagnostic of risk
(2007) ELISA healthy controls OR: 9.6 95% CI: 4.8–18.3
irrelevant to IgG
Yoshikawa Helicobacter Serum IgG Early stage of Increased risk in both younger Not protective
et al. (2007) pylori antibodies by atherosclerosis in and older subjects Indicative of risk
ELISA subjects with disease
and in healthy
HSP, heat schock protein; C. pneumoniae, Chlamydia pneumoniae.

stroke, very high blood pressure, or periodontitis remain largely unknown and place of birth (Buhlin et al. 2005).
acute coronary syndrome. In another (Pilote et al. 2007). Data from the Other investigators have failed to iden-
study, an association between age and population-based study of health in tify gender differences in the association
dental conditions in relation to stroke Pomerania (SHIP) (1913 subjects), between periodontitis and cardiovascu-
has also been presented (Lee et al. have, however, identified an association lar diseases (Andriankaja et al. 2007).
2006). between tooth loss and left ventricular Thus, the role of female gender as effect
hypertrophy in women but not in men modifier in the association between
(Völzke et al. 2007). Similarly, Desvar- periodontitis and risk for cardiovascular
ieux et al. (2004) have reported that disease is unclear. It may, in part,
There is evidence to suggest that the measures of poor oral health including depend on the fact that women might
extent of atheroma assessed by intravas- tooth loss and periodontitis could be be less likely to survive a heart attack
cular ultrasound in women is less severe related to subclinical atherosclerosis in (Radovanovic et al. 2007).
and prevalent than in men and indepen- men but not in women. Clinical mea-
dent of other traditional cardiovascular sures of periodontitis (number of prob-
Socioeconomic factors
risk factors (blood pressure, serum LDL ing pocket depths X4 mm) have been
levels, and BMI) (Nicholls et al. 2007). associated with coronary heart disease The disease burden and loss of econom-
Gender-related risk factors and cardio- but only in women after controlling for ic output associated with chronic dis-
vascular disease outcomes in relation to age, smoking, BMI, diabetes, education, eases, mainly cardiovascular diseases,
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368 Persson & Persson

Table 4. The role of infection and antibody titres in subjects with periodontitis in relation to cardiovascular disease
Authors Bacteria Antibodies studied Disease Results Antibody function

Furuichi et al. A. actinomycetem- Serum antibodies to Periodontitis and risk Significant association Elevated titres
(2003) comitans P. gingivalis markers for between antibody titer suggestive of CVD risk
P. gingivalis fimbriae, and whole cardiovascular disease levels and risk markers
cell P. gingivalis, and (CRP, lipidemia,blood for CVD
A. actinomycetem- pressure, body mass
comitans index, WBC counts
Pussinen et al. A. actinomycetem- Serum IgA and IgG Case–control study of No association for IgA or Infection by P. gingivalis
(2004b) comitans to these bacteria subjects with or without IgG titres to A. as assessed by serum
P. gingivalis myocardial infarction but actinomycetem-comitans titres may increase the
unknown dental status and myocardial risk for myocardial
infarction was found. No infarction
link between IgG titer
but for IgA titres to P.
gingivalis and
myocardial infarction
Beck et al. A. actinomycetem- Serum IgG antibody Periodontitis and See text: contradictory to Antibody titres to
(2005) comitans C. titres to 17 oral coronary heart disease previous report bacteria listed suggestive
ochraceae pathogens including of CVD risk. P.
P. intermedia P. gingivalis gingivalis was not
T. denticola included
V. parvula
Johansson A. actinomycetem- Serum antibodies to Stroke event but with no Elevated titres and Conflicting impact of
et al. (2005) comitans A.a. leukotoxin information on dental reduced risk in women antibody titres by gender
conditions but elevated titres and
risk for stroke in men
Pussinen et al. A. actinomycetem- Serum IgA and serum ACS incl. death. No A. actinomyceterm- High titres associated
(2005) comitans P. IgG titres to bacteria information on dental comitans high level IgA with risk of sub-clinical,
gingivalis listed conditions titres (OR: 2.0, 95% CI; and coronary disease
P. gingivalis (OR: 2.1,
95% CI: 2.1–3.4)
Vilkuna- Herpes simplex virus Serum IgA and IgG Relationship between Combined HSV and P. Enhanced CVD risk by
Rautiainen A. actinomycetem- titres serum titres to CVD risk gingivalis antibodies combined high titer
et al. (2006) comitans and markers of HDL, inversely correlated to levels and reduced HDL
P. gingivalis cholesterol HDL counts
Pussinen et al. A. actinomycetem- Serum IgA and serum Case–control study on Higher stroke risk in Antibody titer
(2007a) comitans IgG to bacteria listed stroke. No knowledge never smoking men for differences by gender
P. gingivalis about dental conditions elevated IgA titres. In and risk for stroke
women for IgG titres and
Yamazaki 12 different bacteria Serum IgG titres by Case–control study A high frequency of Elevated antibody titres
et al. (2007) including P. ELISA subjects with coronary antibody positivity for P. to high virulent
gingivalis 381 and P. heart diseases, or gingivalis Su63 but not P. gingivalis a risk for
gingivalis SU63 periodontitis, or healthy for FDC381 disease CVD
subjects subjects
Acs, acute coronarty syndrome; CVD, cardiovascular disease; HDL, high density lipoprotein; HSV, herpes simplex virus; A. actinomycetem,
Aggregatibacter actinomycetemcomitans; P. gingivalis, Porphyromonas gingivalis; T. denticola, Tannerella denticola.

account for around 80% of the total rate of ischemic coronary disease also Smoking
burden of chronic disease mortality in when adjusted for age (Chaix et al.
developing countries (Abegunde et al. 2007). Several studies have suggested Tobacco use is one of the most impor-
2007). Less affluent socioeconomic con- a robust association between severe tant causes of acute coronary syndrome
ditions in childhood may have a modest periodontitis and specific socioeco- globally, and especially in men (Teo
persisting influence on risk of coronary nomic factors including low education, et al. 2006). Data suggest that since a
heart disease later in life (Ramsay et al. low income, and belonging to disadvan- public smoking ban was introduced in
2007). Thus, age-adjusted odds of cor- taged neighbourhoods (Borrell et al. New York city the rate of hospital
onary heart disease were 2.2 times high- 2006a, b, Peres et al. 2007). There are admissions with a diagnosis of acute
er for low-income groups than for high- no studies that specifically have consid- coronary syndrome decreased by 8%.
income groups and with no gender dif- ered the relationship between socioeco- This was solely accounted for by the
ferences (Kivimäki et al. 2007). In a nomic status and periodontitis and impact of reduced smoking (Juster et al.
Swedish study comprising 4340,000 the impact of these factors on 2007). The early work on a relationship
subjects, data have suggested that socio- coronary heart disease, atherosclerosis, between periodontitis and cardiovascu-
economic factors affect the mortality or stroke. lar disease by DeStefano et al. (1993)
r 2008 The Authors
Journal compilation r 2008 Blackwell Munksgaard
Periodontitis and cardiovascular diseases 369

was criticized based on the management Data have also suggested a relation- model analysis based on 1400 subjects,
of the data in relation to smoking habits ship between elevated fasting serum the effects of stress associated with
as a confounding factor (Hujoel et al. triglyceride levels and measures of sys- financial strain and distress could be
2001). Thus, when adjusted for smoking temic inflammation including white linked to more severe periodontitis
Hujoel et al. (2001) failed to reach the blood cell (WBC) counts (Rivera et al. (Genco et al. 1999) and to poor treat-
same conclusions as DeStefano et al. 2007). The relationship between hyper- ment outcomes (Elter et al. 2002). Data
(1993). Data derived from large popula- triglyceridemia and low-grade inflam- have also suggested that subjects with
tion based case–control studies have mation defined by WBC counts might periodontitis and with inadequate stress
demonstrated that the association also be mediated by insulin resistance behaviour strategies (defensive coping)
between periodontitis and cardiovascu- (Onat et al. 2006, Shimazaki et al. are at greater risk for severe perio-
lar disease was identified independent 2007). dontitis (Wimmer et al. 2002, Ng &
from the possible confounding effect of A trend of a dose dependent relation- Leung 2006). Other studies have,
smoking (Persson et al. 2005b, Holm- ship between serum levels of metabolic however, found no significant associa-
lund et al. 2006, Andriankaja et al. markers including triglycerides, total tion between periodontitis and psycho-
2007). Additional studies are needed to cholesterol, LDL, HDL, and blood glu- social factors in older subjects (Persson
better understand the role of smoking in cose levels have been suggested in sub- et al. 2003b, Solis et al. 2004, Castro et
this potential link between periodontitis jects with severe periodontitis (Katz al. 2006). Differences in periodontitis
and cardiovascular diseases. et al. 2002, Nibali et al. 2007). and/or psychological status, age, and
ethnicity may explain these differences
Metabolic factors Hypertension in conclusions. The fact that stress has
been identified both in cardiovascular
BMI has been strongly linked to cardio- Recent evidence have linked perio- disease, and in dental studies suggests
vascular disease, and especially in relation dontitis with high blood pressure (Inoue that stress might be a risk factor for both
to coexisting diabetes mellitus (Balkau et et al. 2005, Borges-Yáñez et al. 2006). conditions and that stress may trigger an
al. 2007). An association between high Other measures of poor oral health inflammatory response expressed inde-
body weight measures early in life and an (tooth loss) have been associated with pendently in cardiovascular diseases and
increased risk for heart disease has been hypertension (Völzke et al. 2006). in periodontitis. Further studies are
reported (Lawlor & Leon 2005). Data Further studies are needed to confirm needed to assess the impact of stress
suggest that greater body weight has an this relationship as many adults suffer on the link between periodontitis and
influence on blood pressure and serum from high blood pressure and use med- cardiovascular diseases.
cholesterol levels, and that this may ication to control of blood pressure.
account for approximately 45% of the
increased risk of future coronary heart Stress
disease (Bogers et al. 2007). One mechanism how periodontitis may
Thus, the effects of increasing body Financial stress impacts on the indivi- be associated with cardiovascular dis-
weight, mostly in the western world, dual inflammatory burden resulting in eases is through bacteremia. The levels
could outweigh any effort made to elevated serum levels of several biomar- of streptococci spp. in blood samples
reduce cardiovascular risk by smoking kers [interleukin-1 (IL), -6, and higher following periodontal intervention may
cessation, or perhaps periodontal inter- serum high sensitivity CRP] (Gèmes be higher than for any other group of
vention. An association between a high et al. 2007). Older subjects with a major bacteria (Daly et al. 2001). This obser-
BMI and periodontitis has been demon- depression disorder have higher levels vation is important as streptococci might
strated (DallaVecchia et al. 2005, Saito of high sensitivity CRP and also present be specifically linked to a risk for car-
et al. 2005, Linden et al. 2007). When with severe coronary disease (Andrei diovascular diseases (Herzberg et al.
controlling for BMI periodontal condi- et al. 2007). Other studies have sug- 2005, Renvert et al. 2006). Data suggest
tions in women has been linked to gested that the association between that 80% of subjects present with posi-
coronary heart disease (Buhlin et al. stress and elevated tissue plasminogen tive bacterial cultures immediately fol-
2005). activator (t-PA) antigen levels may lowing subgingival debridement (Forner
LDL are involved in the transport represent one plausible mechanism et al. 2006a, b, Lafaurie et al. 2007).
cholesterol in the blood circulation and behind the accelerated rate of develop- Others have, however, shown that the
clearly implicated in the development ing a prothrombotic and increased mor- incidence of bacteremias following
and progression of atherosclerosis bidity and mortality in cardiovascular periodontal procedures are low (Kinane
resulting in heart attack, stroke, and diseases (Mausbach et al. 2007, Shakir et al. 2005) or almost non-measurable
peripheral vascular diseases. HDL have et al. 2007). (Hartzell et al. 2005). Thus, the role of
been implicated in the transport of cho- Studies of older depressed subjects bacteremia in the link between perio-
lesterol to the liver for its excretion or with elevated risk for cardiovascular dontitis and cardiovascular disease
re-utilization. Thus, the combination of disease have shown a hypocortisol remains unclear.
high LDL and low HDL levels are response to acute stress. This impaired
therefore predictive of cardiovascular cortisol response might contribute to
Blood markers of inflammation
disease (Barter et al. 2007). Thus high chronic inflammation reflected as ele-
LDL and low HDL would suggest a high vated high-sensitivity CRP values in IL-6 assessment
risk of cardiovascular disease and in depressed patients and result in an
contrast to low serum LDL and high increased cardiovascular disease risk IL-6 is a pro-inflammatory cytokine
serum HDL levels. (Taylor et al. 2006a). In an age adjusted secreted by T cells and macrophages to
r 2008 The Authors
Journal compilation r 2008 Blackwell Munksgaard
370 Persson & Persson

stimulate immune response to tissue periodontitis (Loos et al. 2000, Ajwani Endothelial cell assessments
damage leading to inflammation and a et al. 2003, Craig et al. 2003, Saito et al.
potential risk marker of future cardio- 2003, Deliargyris et al. 2004, Persson Plasminogen activator inhibitor-1 (PAI-
vascular disease (i.e. Giannessi et al. et al. 2005a, Havemose-Poulsen et al. 1) is the principal inhibitor of tPA and
2007, Woodward et al. 2007). Several 2006, Salzberg et al. 2006). urokinase (uPA), and closely associated
studies have assessed the link between The number of remaining teeth and with increased risk for the development
periodontitis and serum IL-6 levels sug- clinical evidence of periodontitis has of atherosclerosis. In inflammatory con-
gesting that subjects with untreated been associated with an increased risk ditions in which fibrin is deposited in
periodontitis have elevated serum IL-6 for cardiovascular disease (Beck et al. tissues, PAI-1 appears to play a signifi-
levels (Loos et al. 2000, Ide et al. 2004, 1996, Elter et al. 2004, Geerts et al. cant role in the progression to fibrosis
Ioannidou et al. 2006b, Pussinen et al. 2004, Latronic et al. 2007), and includ- (Hoekstra et al. 2004). Increased PAI-1
2007a). There appears to be no studies ing sudden cardiac death (Karhunen concentrations are independent risk
assessing the additive effect of perio- et al. 2006). The presence of P.gingivalis, markers for major adverse cardiac
dontitis on IL-6 levels in subjects with Porphyromonas intermedia, C. rectus, events because of its role in fibrinolysis
diagnosed cardiovascular disease. It and Tannerella forsythia in subgingival (Marcucci et al. 2006). PA-1 behaves
should, however, be recognized that samples has also been associated with also as an acute phase protein and is
the relationship between cytokine serum elevated high sensitivity CRP levels regulated by IL-1 and by TNF-a (Iri-
levels (IL-6, and TNF-a) is disputed and (Noack et al. 2001). goyen et al. 1999). Elevated levels of
that several studies have not been able to Results from intervention studies PA-1 have been reported in subjects
associate levels of such cytokines to have suggested that within the first day with periodontitis (Montebugnoli et al.
cardiovascular events (Sukhija et al. of therapy serum high sensitivity CRP 2005, Bizzarro et al. 2007). This may
2007). values may significantly increase increase the potential risk for impaired
Conflicting results on changes in ser- (D’Aiuto et al. 2005a, b). Whether such fibrinolysis, a condition that may result
um IL-6 levels following periodontal sharp increases in serum high-sensitivity in a prothrombotic state and a potential
therapy have also been published CRP values suggest an acute cardiovas- risk for cardiovascular disease through
(improving: D’Aiuto et al. 2004; no cular disease risk remains unknown. It thrombosis.
effect: Ide et al. 2003, Yamazaki et al. might not be possible to reduce serum Periodontal intervention studies of
2005, Elter et al. 2006, Talbert et al. high sensitivity CRP values to levels subjects with periodontitis but no medi-
2006). Excluding subjects with a self- before the periodontal intervention cally confirmed status have demon-
reported history of cardiovascular, kid- 6 months following therapy (Tonetti strated that PA-1 increase occurs
ney, liver, or lung disease, it has been et al. 2007). shortly after therapy. Six months follow-
demonstrated that 24 h after intensive ing non-surgical periodontal therapy
periodontal intervention the treatment with adjunct local antibiotics, no differ-
WBC counts
resulted in an acute short-term systemic ence in PA-1 was noticed (Tonetti et al.
inflammatory response expressed as an Patients with acute coronary syndrome 2007). This was not consistent with the
increase in IL-6 levels (Tonetti et al. present with elevated WBC counts results of another intervention trial that
2007). (Avramakis et al. 2007). WBC counts included a decrease in PA-1 and TPA
within normal range in subjects with following tooth eradication (Taylor
periodontitis have been reported (Loos et al. 2006a, b). In the study by Taylor
CRP assessments
et al. 2000, Dietrich et al. 2002, et al. (2006a, b) subjects were confirmed
Measuring and determining the kinetics Montebugnoli et al. 2005). Others have as having one or more medically com-
of changes in serum of high sensitivity demonstrated that serum WBC counts promising medical conditions. This may
CRP has been proven to be useful in are associated with acute coronary syn- explain differences in the results
monitoring disease progression, or the drome but also that subjects confirmed obtained.
effectiveness in the treatment of dis- as not having cardiovascular disease but A number of non-invasive subclinical
eases that triggers a systemic inflamma- diagnosed with periodontitis present markers of cardiovascular disease exist.
tory response (Mora et al. 2006, with higher serum WBC counts than This includes: computed tomography of
Tsimikas et al. 2006, Bansal & Ridker periodontally healthy control subjects the coronary arteries, ultrasound of the
2007). A summary background, and (Persson et al. 2003a, 2005a, Buhlin carotid arteries, echocardiography,
conclusions from individual studies on et al. 2005, Bender et al. 2006, Renvert MRI, ankle-brachial index, microalbu-
high sensitivity CRP values and perio- et al. 2006). A significant decrease in minuria, flow-mediated dilation in the
dontitis are presented (Table 5). A WBC counts following periodontal ther- brachial artery, and pulse wave form
recent systematic review and meta-ana- apy in subjects with aggressive perio- analysis are not highly correlated with
lysis failed to support the hypothesis dontitis has been reported (Dietrich each other and do not include propensity
that periodontal treatment can reduce et al. 2002). Salivary matrix metallopro- for the important atherosclerotic phase
systemic high sensitivity CRP levels teinase-8 levels are associated with of plaque rupture, and do not fully
(Ioannidou et al. 2006a). periodontitis among subjects who also substitute for studies of clinical cardio-
The relationship reported between have cardiovascular disease (Furuholm vascular disease endpoints (Jacobs &
periodontitis and serum high sensitivity et al. 2006). Such leukocyte host immu- Crow 2007).
CRP is greatly affected by the type of nity driven proteolytic enzymes may be Endothelial dysfunction precedes
individuals recruited in the comparative part of a biological explanation to the clinical manifestation of atherosclerosis
studies, the control of systemic disease association between periodontitis and (Pellegrino et al. 2005). There is evi-
by other means, and the definition of cardiovascular diseases. dence to suggest that periodontitis may
r 2008 The Authors
Journal compilation r 2008 Blackwell Munksgaard
Periodontitis and cardiovascular diseases 371

Table 5. Selection of studies assessing serum (high sensitivity) C-reactive protein (C-rp) values and periodontal condition under different
Publication Study design Results and author conclusions Reviewer conclusion

Iwamoto et al. Case series: 15 subjects with chronic Levels of TNF-a, hs-CRP, and Effective reduction of TNF-a, hsC-RP,
(2003) periodontitis receiving subgingival adiponection were studied before and 1 (C-rp from a mean of 1.7–0.9 mg/l).
debridement and antibiotics month after treatment including Large individual variation
Saito et al. Case series: 179 Japanese men aged ABL around posterior teeth associated Subjects in the highest tertile of
(2003) 50–54 years old, with at least 10 teeth, with elevated C-rp in Japanese men, alveolar bone loss had an increased risk
were examined as part of a suggesting an association between for C-rp elevation 4 or 5 1.3 mg/l
comprehensive health examination periodontal disease and increased risk (OR 5 8.20; 95% CI: 1.6–40.7,
of type 2 diabetes and CVD p 5 0.01)
Seinost et al. Case–control study: 61 subjects of3 Change in serum CRP following Healthy subjects 0.8 mg/l (SD  0.8).
(2005) months duration including debridement treatment Periodontitis subjects before treatment
and antibiotics in treatment group 1.7 mg/l (SD  1.6)
Periodontitis subjects after treatment
1.1 (SD10.9)
Best et al. Case–control study: 1131 older subjects Periodontal disease and infection may Periodontitis in the presence of
(2005) with or without periodontitis/positive be modifiable risk indicators to elevated periodontitis (BANA test) is linked to
bacterial enzyme test (BANA test) and levels of CRP in older people elevated TNF-a, and IL-6 levels in
serum markers of inflammation: older subjects. This may specifically
CRP, Il-6, TNF-a suggest the link between periodontitis
and cardiovascular diseased susceptible
D’Aiuto et al. Longitudinal case–control study: 24 CRP reductions significant to the Small study groups (subgroups).
(2005a, b) subject in CTR, 21 subject on SC and control only in non-smokers Mean reduction in CRP in test groups
20 subj ect on SC1local antibiotics 0.5 mg/l
period: 2 months
Yamazaki Case–control1intervention study of 24 Trend toward higher CRP levels in Limited effect by periodontal therapy
et al. (2005) periodontitis subjects receiving non- patients at baseline compared with on IL-6, TNF-a, and serum CRP levels.
surgical periodontal therapy control subjects. Decrease after Periodontal therapy did not reduce
treatment was not significant CVD risk as defined by surrogate
Briggs et al. Case–control study 92 periodontitis Median CRP in periodontitis subjects Periodontitis and risk for coronary heart
(2006) cases and 79 healthy controls 2.1 and 1.4 mg/l in controls. Mean age disease
was 58 years OR 5 3 1, 95% CI: 1.0–9.2 (po0.05)
C-rp (high/low): Periodontitis
OR 0.1, 95% CI: 0.5–2.5 NS
Elter et al. Case series; 22 systemically healthy Change in high sensitivity CRP over 1 Pretreatment 3.6 mg/l (SD19.5)
(2006) subjects treated for chronic month was monitored Post treatment 3.3 mg/l 8 SD15.1).
periodontitis. Data from before and Mean decrease: 0.3 mg/l
after debridement
Franek et al. Case–control study subject with kidney Patients with kidney disease and severe The chronic kidney disease was
(2006) disease with (17) or without kidney periodontitis had mean CRP 5 13.2 mg/ responsible for CRP values and
disease (27) l. Patients with kidney disease without periodontitis contributed a minor
periodontitis had CRP means 10.4 mg/l element
po0.05) confirmed by multiple
regression analysis
Salzberg et al. Case–control study Patients with aggressive periodontitis Aggressive periodontitis may induce a
(2006) Serum samples were collected from 93 have statistically significant elevations severe host inflammatory response that
patients with generalized aggressive in serum CRP levels compared with can be linked to systemic disease
periodontitis and from 91 healthy subjects without periodontitis
Blum et al. Case–control study 919 subjects with Mean hs CRP levels decreased from Small study group. Decrease in CRP on
(2007) or without severe periodontitis 2.97–2.3 mg/l (p 5 0.01) average 0.7 mg/l
Kshirsagar Cross-sectional study: 5537 subjects Severe periodontitis was linked to low No observed association of severe
et al. (2007) chronic hemodialysis patients with or serum albumin (OR 5 8.2; 95% CI: periodontitis with CRP was found
without periodontitis 1.6–41.8; p 5 0.01) but not to RP values
IS, intervention study; SD, subgingival debridement.

promote endothelial dysfunction as therapy may improve brachial artery IMT

assessed by flow mediated dilatation of flow rate in subjects with periodontitis
the artery (Amar et al. 2003). This has but with no medically confirmed diag- Cross-sectional and prospective evidence
not been confirmed by brachial ankle nosis of cardiovascular disease (Merca- correlates IMT with cardiovascular
pulse velocity assessments in subjects noglu et al. 2004, Seinost et al. 2005, disease. B-mode ultrasound measure-
with periodontitis (Miyaki et al. 2006). Elter et al. 2006, Blum et al. 2007, ment of the inner layers of the carotid
Some studies suggest that periodontal Tonetti et al. 2007). wall, provides a well-validated index of
r 2008 The Authors
Journal compilation r 2008 Blackwell Munksgaard
372 Persson & Persson

sub-clinical atheroma (Simon et al. dontitis fail to identify an association 2007, O’Donnell et al. 2007, Yoshie
2002, de Groot et al. 2004). Perio- between periodontitis and cardiovascu- et al. 2007).
dontitis has also been associated with lar disease (Beck et al. 2005). Such The research on serum markers of
IMT (Beck et al. 2001). A relationship findings might discourage from inter- inflammation in both cardiovascular
between periodontal microbiology and vention studies attempting at reducing and periodontal research is extensive.
subclinical atherosclerosis assessed by the extent of bleeding on probing and The literature clearly demonstrates that
IMT has been documented (Desvarieux probing pocket depths and thereby redu- elevated proinflammatory cytokines are
et al. 2005). There are no studies that cing the risk of cardiovascular disease. present in both cardiovascular diseases
have assessed the impact on IMT as a Thus the strength of an association as well as in periodontitis. It appears
result of periodontal interventions. between periodontitis and cardiovascu- that Il-6, PA-1, and WBC counts are
lar disease based on epidemiological, closely related to periodontitis whereas
and cross-sectional studies varies based the levels of serum hs C-rp are not
on data from studies of different popula- conclusive.
Discussion tion of subjects. Future studies assessing C. pneumoniae is perhaps one of the
During the last two decades, there has the association between periodontitis few bacteria that might be associated
been an increasing interest in the impact and cardiovascular diseases must also with an increased risk for cardiovascular
of oral health, specifically periodontitis, consider the prevalence of both disease disease. There are, however, few studies
on cardiovascular diseases. In one meta- entities. Available studies suggest that demonstrating that C. pneumoniae may
analysis the findings resulted in a con- periodontitis prevalence in older subjects be present in periodontal plaque sam-
clusion that periodontitis and poor oral is high (Terpenning et al. 2001, Persson ples. (Tran et al. 1997, Mäntylä et al.
health overall indeed contribute to the et al. 2002, Persson et al. 2003d, Holm- 2004). There are few studies having
pathogenesis of cardiovascular disease Pedersen et al. 2006, Krustrup & Petersen assessed the relationship between the
(Meurman et al. 2004). Furthermore, 2006). The aspect of aging as factor in periodontal infection and acute coronary
another meta-analysis identified that the link between periodontitis and cardi- syndrome at the time of diagnosis
the level of systemic bacterial exposure ovascular diseases including stroke must demonstrating that subjects with perio-
from periodontitis is the biologically be considered in future studies. dontitis and acute coronary syndrome
pertinent exposure with regard to ather- Poor oral health in general has also have higher counts of key pathogens in
osclerotic risk (Mustapha et al. 2007). directly been linked to cardiovascular periodontal pockets than found in sub-
This conclusion can be illustrated by the disease (i.e. Mattila et al. 1989, Meur- jects who were medically confirmed as
only existing study that has assessed the man et al. 2003, Karhunen et al. 2006). being healthy (Renvert et al. 2006).
subgingival microbiota in subjects with The finding that tooth clearance is effi- Stress, socioeconomic and dietary
acute coronary syndrome shortly after cacious in reducing levels of serum factors are approaching the level of
being released from the hospital. The markers of inflammation (Taylor et al. etiological important factors both in
study demonstrated that significantly 2006a, b, Ellis et al. 2007) must be cardiovascular disease and periodontitis.
higher levels of 19/40 bacterial species further investigated. In fact, the findings In fact, dietary factors are also about to
could be identified in subgingival sam- from these two studies suggest that the become etiological and involved in sev-
ples from subjects with a recent history old concept of tooth clearance as a eral diseases including cardiovascular
of acute coronary syndrome in compar- means to reduce the risk or severity disease and periodontitis (Kaput et al.
ison to subjects confirmed not to have of inflammatory diseases should be 2005).
cardiovascular disease (Renvert et al. revisited. This may further specifically The data on periodontal intervention
2006). Thus the role of periodontal relate to older people who may have and immediate increases in serum mar-
infections as a causative factor in the poor oral health status and chronic kers of inflammation may suggest that
link to cardiovascular disease must be inflammatory diseases such as rheuma- intensive periodontal therapy may result
further explored. toid arthritis. Other studies have, in serious adverse events (Tonetti et al.
The meta-analysis by Bahekar et al. however, demonstrated that edentulous- 2007). There is only one recent study
(2007) has demonstrated that having ness does not change IMT and that tooth that has addressed the outcome of perio-
periodontitis might enhance the risk for loss and long-term periodontitis are dontal intervention in subjects with
cardiovascular disease but that this related to subclinical atherosclerosis heart disease suggesting that periodontal
risk is not robust. Some studies have but only in men (Desvarieux et al. intervention may not induce more ser-
provided high ODs between perio- 2004). ious adverse events than what might be
dontitis and cardiovascular diseases (i.e. New diagnostic and monitoring meth- expected in the community over a 25
Meurman et al. 2003, Persson et al. ods using validated surrogate markers months period (Beck et al. 2008).
2003a, Buhlin et al. 2005, Engebretson will open new perspectives in the Furthermore the study demonstrated
et al. 2005, Geismar et al. 2006, Rech assessment of periodontal treatment out- that non-surgical routine periodontal
et al. 2007). These studies have used comes and independent of any relation- therapy did not reduce the risk of serious
alveolar bone loss as a cumulative ship to other systemic diseases (i.e. cardiovascular events.
expression of chronic periodontitis Dietrich et al. 2002, Ioannidou et al. Given the chronic nature of both
rather than a temporal expression of 2006b, Jacobs & Crow 2007). In the periodontitis and cardiovascular dis-
inflammation (i.e. bleeding on probing future, genetics marker may also pro- eases, intervention at a time when
and probing pocket depth). Concur- vide useful tools to assess associations already one or both disease entities are
rently, others have shown that probing and risks between periodontitis and car- diagnosed, periodontal intervention may
pocket depth and clinical attachment diovascular diseases (Loos et al. 2005, not reduce future cardiovascular events,
levels as diagnostic markers of perio- Hart & Atkinson 2007, Kinane et al. or reduce symptoms of cardiovascular
r 2008 The Authors
Journal compilation r 2008 Blackwell Munksgaard
Periodontitis and cardiovascular diseases 373

disease. Preventive care may, in fact, be matory markers in elderly patients with heart Relationship of periodontal disease to carotid
the most important effort in reducing the failure. Psychosomatics 48, 319–324. artery intima-media wall thickness: the ather-
risk for cardiovascular disease by main- Andriankaja, O. M., Genco, R. J., Dorn, J., osclerosis risk in communities (ARIC) study.
taining healthy oral conditions. Dmochowski, J., Hovey, K., Falkner, K. L. Arteriosclerosis Thrombosis and Vascular
& Trevisan, M. (2007) Periodontal disease Biology 21, 1816–1822.
and risk of myocardial infarction: the role of Beck, J., Garcia, R., Heiss, G., Vokonas, P. S. &
gender and smoking. European Journal of Offenbacher, S. (1996) Periodontal disease
Conclusions Epidemiology 22, 699–705. and cardiovascular disease. Journal of Perio-
Atar, S., Tolstrup, K., Cercek, B. & Siegel, R. J. dontology 67, 1123–1137.
Available data suggest that periodontitis (2007) Chlamydia pneumoniae antibody Bender, J. S., Thang, H. & Glogauer, M. (2006)
may have overall health consequences. titers and cardiac calcifications: a cross-sec- Novel rinse assay for the quantification of
The term ‘‘cardiovascular diseases’’ is a tional serological-echocardiographic correla- oral neutrophils and the monitoring of
broad term and efforts are needed to tive study. Israel Medical Association chronic periodontal disease. Journal of Perio-
specifically identify which cardiovascu- Journal 9, 517–520. dontal Research 41, 214–220.
lar diseases (i.e. stroke, acute coronary Avramakis, G., Papadimitraki, E., Papakonstan- Best, L. G., Zhang, Y., Lee, E. T., Yeh, J. L.,
syndrome, atherosclerosis) can be dinou, D., Liakou, K., Zidianakis, M., Der- Cowan, L., Palmieri, V., Roman, M., Dever-
linked to periodontitis. Until the precise mitzakis, A., Mikhailidis, D. P. & Ganotakis, eux, R. B., Fabsitz, R. R., Tracy, R. P.,
E. S. (2007) Platelets and white blood cell Robbins, D., Davidson, M., Ahmed, A. &
biological mechanisms how perio-
subpopulations among patients with myocar- Howard, B. V. (2005) C-reactive protein as a
dontitis influences cardiovascular dis- dial infarction and unstable angina. Platelets predictor of cardiovascular risk in a popula-
ease are known intervention studies 18, 16–23. tion with a high prevalence of diabetes:
should be reviewed with caution. Bahekar, A. A., Singh, S., Saha, S., Molnar, J. & the Strong Heart Study. Circulation 112,
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Clinical Relevance Principal findings: The review studies are not conclusive. It appears
Scientific rationale for the study: revealed that a large number of bio- that patients with severe periodontitis
Many studies have suggested an asso- logical, social and risk behavioral are at risk of developing cardiovas-
ciation between cardiovascular dis- factors are shared in periodontitis cular disease and dental clinician
ease and periodontitis. The scientific and cardiovascular diseases. Specifi- should consult cardiovascular exper-
rationale for the present review was to cally, inflammatory markers have tise in the management of such
identify factors that during the last been studied. patients.
three years have been identified as Practical implications: Practical
possible explanations to such an asso- implications remain difficult to pre-
ciation. sent due to the fact that intervention

r 2008 The Authors

Journal compilation r 2008 Blackwell Munksgaard