the effect of periodontal therapy on cardiovascular risk markers: a 6-month randomized clinical...

The effect of periodontal therapyon cardiovascular risk markers: a6-month randomized clinical trialCa�ula AL, Lira-Junior R, Tinoco EMB, Fischer RG. The effect of periodontaltherapy on cardiovascular risk markers: a 6-month randomized clinical trial. J ClinPeriodontol 2014; 41: 875–882. doi: 10.1111/jcpe.12290.

AbstractAim: To determine the influence of non-surgical mechanical periodontaltreatment on inflammatory markers related to risk for cardiovascular disease.Material and Methods: A total of 64 patients with severe chronic periodontitiswas randomly subjected to immediately periodontal treatment (test group,n = 32) or delayed periodontal treatment, without treatment during the studyperiod (control group, n = 32). Clinical periodontal and laboratory examinationswere performed at baseline (T0), 2 months (T2), and 6 months (T6) after the ini-tial examinations (Control group) or completion of periodontal treatment (Testgroup).Results: After 2 months of periodontal treatment there was a significant reduc-tion of erythrocyte sedimentation rate (ESR) and triglycerides (p = 0.002,p = 0.004, respectively) in the test group. Median values of C-reactive protein,ESR, total cholesterol, and triglycerides were reduced after 6 month of periodon-tal treatment in the test group (p < 0.001, p < 0.001, p < 0.001, and p = 0.015,respectively).Conclusions: The non-surgical periodontal treatment was effective in reducing thelevels of systemic inflammation markers and improved the lipid profile in subjectswith severe chronic periodontitis.

Andr�e Luis Ca�ula, RonaldoLira-Junior, Eduardo Muniz Barretto

Tinoco and Ricardo Guimar~aesFischer

Department of Periodontology, School of

Dentistry, Rio de Janeiro State University,

Rio de Janeiro, Brazil

Key words: cardiovascular disease;

C-reactive protein; erythrocyte sedimentation

rate; periodontitis; triglycerides

Accepted for publication 7 July 2014

Elevated inflammatory activity wasidentified as a major responsible forthe atherogenic process and endothe-lial dysfunction that may lead to car-diovascular disease (Ross 1999, Libby2002, 2006). Periodontitis is a chronic

inflammatory disease characterizedby bacterial infection and teeth sup-porting tissues destruction, able toinitiate and maintain high systemiclevels of various cytokines related toinflammatory response (Page & Sch-roeder 1976, Tonetti & Van Dyke2013). These cytokines, particularlytumour necrosis factor-a (TNF-a)and interleukin-6 (IL-6), trigger anincrease in hepatic synthesis andrapid secretion of intravascularplasma proteins, including C-reactiveprotein (CRP) and fibrinogen (Eber-sole & Cappelli 2000).

Several studies showed thatperiodontitis was linked with severalof these markers of inflammation(TNF-a, IL-6, CRP, and fibrino-gen) and many systemic changes,including dyslipidemias, which areknown risk factors for cardiovasculardisease (CVD) (Cutler et al. 1999,Loos et al. 2000, Noack et al. 2001,Buhlin et al. 2003, Craig et al. 2003,D’Aiuto et al. 2004, Joshipura et al.2004, Vidal et al. 2009). Two meta-analysis indicated evidences thatCRP and low-density lipoproteincholesterol are associated with CVD

Conflict of interest and source of

funding statement

The authors declare that there are noconflicts of interest in this study.No external funding, apart from thesupport of the authors’ institution,was available for this study.

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 875

J Clin Periodontol 2014; 41: 875–882 doi: 10.1111/jcpe.12290

events (Buckley et al. 2009, Ip et al.2009).

The effect of periodontal treat-ment on systemic markers of inflam-mation is still conflicting. Somestudies showed that non-surgicalperiodontal treatment of chronicperiodontitis did not influence serumlevels of inflammatory markers (Ideet al. 2003, Yamazaki et al. 2005).In contrast, results of others studiesdescribed significant reductions insystemic markers of inflammation(Mattila et al. 2002, D’Aiuto et al.2005, Vidal et al. 2009, 2013, Bok-hari et al. 2012). Behle et al. (2009)observed that periodontal therapyresulted in an overall reduction ofsystemic inflammation, but therewas considerable inter-patient vari-ability in concentrations for most ofthe markers evaluated. The authorsstated that the failure to identify sig-nificant differences in the levels ofinflammatory markers after therapymay be partly attributed to a highbiological heterogeneity. Recently,D’Aiuto et al. (2013) performed asystematic review about the effect ofperiodontal treatment on CVD bio-markers and outcomes. The authorsconcluded there is moderate evi-dence that does not support a posi-tive effect of periodontal treatmenton lipid profile and there is a mod-erate positive effect in reducingserum CRP levels after periodontaltherapy.

Considering the possible associa-tion between periodontitis and CVD,potential benefits of periodontaltreatment to reduce cardiovascularrisk and inconsistency about thesebeneficial influences, studies on theeffect of periodontal therapy are stillnecessary. The aim of this researchwas to evaluate the influence of non-surgical mechanical periodontaltreatment on CRP serum level,erythrocyte sedimentation rate(ESR), and lipid profile in patientswith severe chronic periodontitis.

Material and Methods

Study population

The study design was a randomizedparallel clinical trial. The study pop-ulation consisted of 66 patients withsevere non-treated chronic periodon-titis, referred to the clinic of peri-odontology from the Military Dental

Clinic, Rio de Janeiro State FireDepartment (CBMERJ). All patientsgave written informed consent. Thestudy had been reviewed andapproved by the Ethics Committeein Research of Pedro Ernesto Uni-versity Hospital (HUPE) of the Riode Janeiro State University (UERJ).Each subject had at least 15 remain-ing teeth without untreated periapi-cal lesions, and with at least two ormore inter-proximal sites with clini-cal attachment loss (CAL) ≥ 6 mm,not in the same tooth, and the pres-ence of probing pocket depth(PPD) ≥ 5 mm in one or more inter-proximal sites, excluding thirdmolars (Page & Eke 2007).

Exclusion criteria were: (1)patients who require antibiotic pro-phylaxis, (2) patients with immuneor inflammatory conditions (arthri-tis, gastrointestinal disorder, bron-chitis), (3) patients who werepregnant or breastfeeding, (4)patients received periodontal treat-ment prior to 6 months before thestart of the study, and (5) patientsusing, or who received prior treat-ment (6 months) with medicines suchas antibiotics, anti-inflammatorydrugs, steroids, immunosuppressants,anticoagulants, and regulators ofcholesterol.

Sample size

Changes in CRP levels after 6 monthof periodontal treatment were estab-lished as primary outcome. Based ona = 0.05, mean difference of 0.5 mg/l(Paraskevas et al. 2008) and stan-dard deviation of �0.9, we shouldenrol 28 to achieve 80% of power.Assuming 20% of drop-out, 33patients per group were enrolled.

Medical history and physical exams

The medical history of each patientwas obtained through interviews andall participants underwent physicalexaminations. The information col-lected included: (1) sex, (2) age, (3)ethnicity, (4) educational level, (5)presence of systemic diseases, (6)habits of smoking, and (7) bodymass index (BMI).

Periodontal examination

Patients underwent a comprehensiveperiodontal examination including

PPD, CAL, bleeding on probing(BOP), and plaque index. The mea-surements were determinate at sixsites per tooth (mesiobuccal, midbuc-cal, distobuccal, mesiolingual, mid-lingual, and distolingual), excludingthird molars. The clinical examina-tion was performed by a single cali-brated examiner using a manualprobe (UNC-15, Hu-Friedy Manu-facturing Company, Inc., Chicago,IL, USA). To measure the degree ofintra-examiner reproducibility, aduplicate examination of periodontaldata was done, for which five indi-viduals not participating in the studywere examined according to themethodology used in the study andwere re-examined within 2 h afterthe first evaluation. The kappa coef-ficient was 0.78.

The periodontal PPD and CALwere stratified into three groupseach: (a) % of sites with PPD ≤3 mm, (b) % of sites with PPDfrom 4 to 5 mm, (c) % of sites withPPD ≥ 6 mm, (d) % of sites withCAL ≤ 3 mm, (e) % of sites withCAL from 4 to 5 mm, (f) % ofsites with CAL ≥ 6 mm. BOP wasregistered as the number of bleedingsites times 100 divided by the num-ber of examined sites. Plaque indexwas stratified into two groups each:(a) no visible plaque, (b) presenceof visible plaque.

Laboratorial exams

Venous blood samples (10 ml) werecollected in the morning of theperiodontal examination, after a12-h fasting period, in the labora-tory of the CBMERJ Hospital. Thelevels of CRP were determined inserum on an IMMULITE� Auto-mated Analyzer using the commer-cially available high sensitivityimmulite chemiluminescent enzymeimmunometric assay (Immulite�,Diagnostic Products Corp., LosAngeles, CA, USA). The ESR wasdetermined by Westergren method,manual system with the reading ofthe 1st. hour. Lipid profile wasdetermined by an automatedmethod, using the clinical analyzerapparatus Wiener lab. Metrolab2300 Plus Random Access (UV-VisMetrolab SA, Bernal, BuenosAires, Argentina). The laboratorystaff was blinded to the allocationgroup.

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

876 Ca�ula et al.

Experimental protocol

Patients were randomly allocated toone of two groups: Test Group(received periodontal treatmentimmediately, n = 32) or controlgroup (delayed periodontal treat-ment, without treatment during thestudy period, n = 32). The controlgroup received periodontal treatmentsimilar to the Test Group, but startedafter a period of 6 months. The mean(�SD) number of days from baselineto 2 months follow-up was 60.2(�11), range between 57–67 days,while the corresponding values frombaseline to 6 months were 183(�2.9), range 177–190 days.

To avoid the chance of havingmore patients in one group thananother, a randomization in blocks offour was performed using opaqueenvelopes placed in the IDs of thetreatment group (Test group and Con-trol group). The envelopes weresealed, shuffled, and then numbered insequential order from 1 to 4. Eachnew patient entering the study anenvelope was opened. This procedurewas repeated for each group of fourpatients. Thus, the numbers in thetwo groups would never differ bymore than half the length of the block.

Periodontal treatment consistedof four visits, scheduled weekly, withno restriction on duration. All treat-ment was performed by a singleoperator. Periodontal treatment con-sisted of instruction and monitoringof oral hygiene, supragingival andsubgingival scaling, and root plan-ning. It was performed manual andultrasonic instruments under localanaesthesia. For manual instrumen-tation, Gracey curettes (Hu-FriedyManufacturing Company, Inc., Chi-cago, IL, USA) and ultrasonicinstrumentation (Sonic Jet, DentalMedical Equipment Gnatus Ltda.Ribeirao Preto, Brazil) were usedunder local anaesthesia. Extractionof hopeless teeth and remainingroots was performed in the sameclinic session.

Clinical periodontal and labora-tory examinations were performedpre-treatment (T0) and at 2 and6 months (T2 and T6, respectively)after initial examination (controlgroup) or completion of periodontaltreatment (Test Group). The flowchart of the study is presented inFig. 1.

Statistical analysis

The data were processed and analy-sed using Statistical Package for theSocial Sciences (IBM SPSS 19.0,SPSS Inc., Chicago, IL, USA) ver-sion 19. Descriptive statistical analy-sis included medians and first andthird quartiles of quantitative vari-ables and frequency and percentagefor qualitative variables. The signifi-cance of differences of each parame-ter between the test and controlgroups, and among T0, T2, and T6periods was analysed by the non-parametric Wilcoxon test (Wilcoxonsigned rank test with continuity cor-rection). For categorical variables,we used chi-square test (Pearson’sChi-squared test with Yates’ conti-nuity correction). Spearman’s rankcorrelation was calculated for differ-ences in clinical and haematologicalvariables. Significance level wasdetermined at p < 0.05.

Results

From a total of 66 participantsinvited to participate in the study,two withdrew before starting thetreatment phase. Thus, 64 partici-pants completed the study and wereincluded in the analysis. Therewere no significant differences inparticipant characteristics betweengroups at baseline (T0). The sample

characterization, which presents thefrequencies, percentages, averages,and standard deviations of thedemographic and medical character-istics, is presented in Table 1. Thepatients did not change their medica-tions or their smoking habit duringthe study.

Periodontal conditions were simi-lar on baseline in the test and con-trol groups (Table 2). However,there was a significant difference inall periodontal parameters betweenthe test and control groups at 2 and6 months after treatment (T2 andT6). When comparing the medianvalues of periodontal parametersbetween T0/T2 and T0/T6 in the testgroup, we observed statistically sig-nificant improvement in almost allvalues, except the percentage of siteswith CAL 4–5 mm, which showedno significant difference (p = 0.342and p = 0.466 between T0/T2 andT0/T6). However, when comparingmedian values of periodontal param-eters in the control group, weobserved statistically significantworsening of almost all values,except the percentage of sites withCAL ≥ 6 mm (p = 0.776) betweenT0/T2, and the percentage of siteswith CAL ≥ 6 mm (p = 0.47) andpercentage of sites withPPD ≥ 6 mm (p = 0.49) between T0/T6 (Table 2). In the period between

Assessment for eligibility(n = 66)

Enrollment Exclusion (n =2)• Withdrew (n = 2)

Randomization (n = 64)

Test group (n = 32) Control group (n = 32)

Allocation

Lost to follow-up (n = 0) Lost to follow-up (n = 0)

Follow-up

Analyzed (n = 32) Analyzed (n = 32)

Analysis

Fig. 1. Flow chart of the study.


Periodontal therapy reduces CVD risk markers 877

T0 and T2, five control patients haddiscomfort and pain symptoms andwere undergoing dental extraction(lost a total of six teeth with mobil-ity grade 3). There was no tooth lossbetween T2 and T6 in two groups.

Haematological data are pre-sented in Table 3. At the pre-treat-ment (T0), there was no significantdifference between groups for CRPlevel, ESR, and lipid profile. How-ever, there was a significant differenceafter treatment between the test andcontrol groups for the median valuesof CRP and ESR at T2 [0.19 (CI 95%0.1–0.32) difference, p = 0.001 and3.5 (1.1–6.2) difference, p = 0.003,respectively] and for median values ofCRP, ESR, and total cholesterol, inT6 [0.7 (0.51–0.83) difference,p < 0.001; 7.0 (5.8–10.4) difference,p < 0.001; and 10.0 (4.7–38.6) differ-ence, p = 0.021, respectively]. Whencomparing median values of haema-tological data in the test group, weobserved statistically significantimprovement between T0/T2, of thevalues of ESR and triglycerides [2.5(1.2–5.0) difference, p = 0.002 and23.0 (2.0–75.8) difference, p = 0.004,respectively]. Reduction in the med-ian levels of CRP, ESR, total choles-terol, and triglycerides, between T0/T6 was observed in the test group[0.46 (0.21–0.73) difference,p < 0.001; 5.0 (4.0–7.9) difference,p < 0.001; 20.5 (10.9–30.4) difference,p < 0.001; and 23.5 (3.1–72.7) differ-ence, p = 0.015, respectively]. The

LDL cholesterol showed a trendtowards reduction [3.5 (�0.2–12.8)difference, p = 0.06]. When compar-ing median values of haematologicaldata in the control group betweenT0/T2 and T0/T6, we observed a sta-tistically significant increase in thevalues of CRP [0.14 (0.06–0.2) differ-ence, p = 0.003 and 0.24 (0.1–0.5) dif-ference, p < 0.001, respectively] andESR [1.0 (0.2–4.1) difference,p = 0.007 and 2.0 (1.4–6.1) difference,p = 0.001, respectively].

There was no significant correla-tion between PPD and BOP reduc-tions and haematological changes atT2 in the test group. However, therewas a significant correlation betweenCAL decrease and a decline in trigly-cerides at T2 in the test group(q = 0.395, p < 0.05). At T6, therewere significant correlations betweenPPD reduction and a decrease inESR (q = 0.502, p = 0.003) andbetween CAL improvement andCRP decrease in the test group(q = 0.371, p < 0.05). No significantcorrelation was observed betweenPPD, CAL, and BOP alterationsand haematological changes at T2and T6 in the control group.

Correlations among CRP, TC,HDL, and LDL at baseline (T0), 2(T2) and 6 months (T6) after peri-odontal treatment are described inTable 4. There was a statistically sig-nificant correlation between TC andLDL at T0, T2, and T6 and betweenTC and triglycerides at T0 and T2.

Discussion

The aim of this study was to evalu-ate the effect of non-surgical peri-odontal treatment on markers ofcardiovascular disease (CRP, ESR,and lipid profile). The results ofnon-surgical treatment are in accor-dance with the classical studies(Badersten et al. 1981, 1984, 1987).We found that periodontal treatmentwas effective in improving the peri-odontal parameters and reducingCRP level, ESR, total cholesterol,and triglycerides after 6 months.

Inflammation is important in allphases of CVD, including initiationof atherogenic process, as well as theacute rupture of atherosclerotic pla-que (Ridker 2003). Low-gradeinflammation is a marker for subse-quent CVD (Ridker et al. 1998) andC-reactive protein is an acute-phaseprotein that has been shown to be asimple, reliable, and reproduciblemarker of underlying systemicinflammation and a strong predictorof myocardial infarction and stroke(Willerson & Ridker 2004). ESR isan indicator of red cell aggregationand thus of blood viscosity, and it isa simple and inexpensive laboratorytest. ESR is an independent, long-term predictor of coronary heart dis-ease (Andresdottir et al. 2003). Lipidprofile is also associated with coro-nary heart disease (Sarwar et al.2007).

Elevated levels of CRP havebeen observed in periodontalpatients (Paraskevas et al. 2008).The elevation of CRP level isconsidered a risk factor for athero-sclerosis and cardiovascular disease(Buckley et al. 2009). In the presentstudy, no significant changes inCRP levels were observed within2 months, however, a significantreduction was observed in CRPafter 6 months of treatment (p <0.0001). These results are similar tothose found by D’Aiuto et al.(2004). Mattila et al. (2002) havealso found that treating periodonti-tis decreases CRP level. The authorsconcluded that it possibly reducesCVD risk. Ide et al. (2003) andYamazaki et al. (2005) did not findsignificant effect of periodontaltherapy on CRP level. They evalu-ated CRP levels, respectively, after6 weeks and 3 months followingcompletion of treatment which

Table 1. Medical and demographic characteristics of the test and control groups

Variable Test (n = 32) Control (n = 32) p

Age (years) 44.4 (38; 50) 44.0 (38.5; 51.5) 0.89BMI (kg/m2) 26.5 (25; 28.2) 26.4 (24.1; 29.2) 0.75Ethnicity [n (%)]White 13 (40.6%) 15 (46.9%) 0.85Pardo (brown-skinned, mixed-race) 12 (37.5%) 10 (31.2%)Black 7 (21.9%) 7 (21.9%)Gender [n (%)]Men 20 (62.5%) 19 (59.4%) 1.00Women 12 (37.5%) 13 (40.6%)Education Level [n (%)]Fundamental 15 (46.9%) 9 (28.1%) 0.20Medium 16 (50.0%) 21 (65.6%)Superior 1 (3.1%) 2 (6.2%)Smoking [n (%)]Smokers 4 (12.5%) 6 (18.8%) 0.16Ex-smokers 13 (40.6%) 6 (18.8%)Non-smokers 15 (46.9%) 20 (62.5%)Diabetes [n (%)] 5 (15.6%) 7 (21.9%) 0.37Arterial hypertension [n (%)] 7 (21.9%) 3 (9.4%) 0.15

Results are expressed as median (first quartile; third quartile) and frequency (percentage).


878 Ca�ula et al.

could indicate that the time to bio-chemical changes occurred could beinsufficient (Ide et al. 2003). On theother hand, Vidal et al. (2009) havefound that 3 months after periodon-tal treatment the CRP level wasreduced.

Recent meta-analysis demon-strated a reduction in CRP afterperiodontal treatment of about0.50 mg/l (p < 0.05) (Paraskevaset al. 2008, Demmer et al. 2013, Tee-uw et al. 2014). The magnitude ofchange in CRP after treatment inpresent study is similar to that one(0.46 mg/l 6 months after therapy,p < 0.001). A slight increase in CRPlevels (10%) was also observed incontrol group, mainly after2 months without periodontal treat-ment. The reason for this observa-tion is not clear. However, it mayobserved that this increase was fol-lowed by worsening in some peri-odontal parameters, as shown inTable 2. Moreover, a previous studyfrom our group, in refractory hyper-tensive patients, also found a smallincrease in CRP levels in the controlgroup, after 3 months without peri-odontal treatment (Vidal et al.2009).

Some prospective studies haveshown increased ESR as an indepen-dent risk factor for cardiovasculardisease (Danesh et al. 2000, Erikssenet al. 2000, Andresdottir et al. 2003).Hutter et al. (2001) showed a trendto higher ESR values in moderateand severe periodontitis compared tocontrol (p = 0.023). They alsoshowed that gender is an importantcovariate for the ESR. The results ofour study show a significant reduc-tion of ESR at 2 and 6 months post-treatment for men (p = 0.004,p < 0.001, respectively) and onlyafter 6 months for women(p = 0.001). These results are consis-tent with the findings of Ribeiroet al. (2005) who observed adecrease in ESR, 3 months afterperiodontal therapy.

Hypercholesterolaemia is one ofthe most important established riskfactors for atherosclerosis (Thomaset al. 1966). The effects of peri-odontal therapy on lipid markerswas assessed by D’Aiuto et al.(2006) who observed a significantreduction in plasma levels of differ-ent lipids (total cholesterol of 209to 197 mg/dl, p = 0.0384, and LDLT

able

2.

Medianvalues

(firstandthirdquartiles)ofclinicalparametersofparticipants

inthetest

andcontrolgroupsatbaseline(T0)and2(T2)and6(T6)monthspost-treatm

ent

Variable

T0

T2

T0/T2-t

T0/T2-c

T6

T0/T6-t

T0/T6-c

Test

Control

pa

Test

Control

pa

pb

pc

Test

Control

pa

pd

pe

No.Teeth

23.5

(20.5;26)

24(20.5;26.5)

0.53

22.5

(18.5;26)

24(20.5;26.5)

0.20

0.01

0.05

22.5

(18.5;26)

24.5

(20.5;26.5)

0.20

0.013

0.05

CAL

≤3mm

(%sites)

54.0

(34.5;67.5)

50(25.5;61.5)

0.35

65.5

(46.5;85.5)

48(25;58.5)

0.003

<0.001

0.006

68(45.5;86.5)

48.5

(25;58)

0.001

<0.001

<0.001

CAL

4-5

mm

(%sites)

29.5

(21;36.5)

32.5

(24;42)

0.25

30(11.5;41)

35(25.5;42.5)

0.04

0.34

0.005

28(10;38.5)

33.5

(26;43)

0.034

0.47

0.001

CAL

≥6mm

(%sites)

16(7.5;25.5)

17(7;31)

0.94

4.5

(1;11)

17(7;33.5)

0.004

<0.001

0.78

4(0;9)

17(7;36)

0.002

<0001

0.5

PPD

1-3mm

(%sites)

64(49.5;78)

62(50;76.5)

0.73

86.5

(78.5;93.5)

60(40.5;74)

<0.001

<0.001

0.008

89(81;95)

59.5

(38.5;74)

<0.001

<0.001

<0.001

PPD

4-5mm

(%sites)

24(17;36.5)

29(18;39.5)

0.30

11.5

(6.5;18.5)

31.5

(18;42.5)

<0.001

<0.001

0.001

10.5

(5;18.5)

32.5

(22;43)

<0.001

<0.001

<0.001

PPD

≥6mm

(%sites)

7(4;15.5)

7(4;15.5)

0.60

0(0;1.5)

7(4;15)

<0.001

<0.001

0.5

0(0;1)

7.0

(4;15.5)

<0.001

<0.001

0.5

BOP(%

)55(38;68)

42.5

(26.5;62)

0.06

9(0;20)

41.5

(29.5;68.5)

<0.001

<0.001

0.002

7.5

(0.5;20)

40.0

(32.5;69.5)

<0.001

<0.001

<0.001

Plaque(%

)45(31;62.5)

41.5

(24.5;55.5)

0.15

5(0;23)

40.5

(28.5;55)

<0.001

<0.001

0.019

12.5

(4.5;21)

43.5

(29;54.5)

<0.001

<0.001

0.002

pa=statisticaldifference

betweentest

andcontrolgroupsatT0,T2,andT6,calculatedbytheWilcoxonsigned

ranktest

withcontinuitycorrection;pb=

statisticaldifference

betweenT0

andT2forthetest

group,calculatedbytheWilcoxonsigned

ranktest

withcontinuitycorrection;Pc=statisticaldifference

betweenT0andT2forthecontrolgroup,calculatedbytheWil-

coxonsigned

ranktest

withcontinuitycorrection;Pd=statisticaldifference

betweenT0andT6,forthetest


ranktest

withcontinuitycorrection;

Pe=statisticaldifference

betweenT0andT6,forthecontrolgroup,calculatedbytheWilcoxonsigned

ranktest

withcontinuitycorrection.



from 132 to 116 mg/dl, p = 0.0082),through periodontal therapy associ-ated with locally applied minocy-cline, 6 months after treatment. Ozet al. (2007) achieved the sameresult (total cholesterol of 244 to213 mg/dl, p = 0.02, and LDL of155 to 115 mg/dl, p < 0.001) after3 months, with mechanical debride-ment alone. In both studies, therewere no significant changes in tri-glyceride level. However, Kamilet al. (2011) observed no significantdifferences in serum lipid markersafter 3 months of periodontal treat-ment. L€osche et al. (2005) alsofound no significant changes after3 months of periodontal treatmentin patients with periodontitis andcomparatively lower values of LDLat baseline (median 114 mg/dl).L€osche (2007) later suggested thatthe effect of periodontal therapy onLDL seems to be more evident inhigher baseline levels comparedwith lower baseline levels of LDL.In this study, we observed a signifi-cant reduction in total cholesterolafter 6 months (p = 0.001). Therewas also a tendency to decreasedlevels of LDL in the period of6 months (p = 0.054). It was veri-fied a significant reduction in trigly-cerides 2 and 6 months afterperiodontal treatment in the testgroup (p = 0.004 and p = 0.015,respectively).

According with the results of thepresent study, periodontal treatmentmay reduce low-grade systemicinflammatory markers and lipid pro-file, but these results should be inter-preted with caution because of thelarge amount of co-variables. Otherinterventional studies are required toassess the potential systemic effectsof periodontal therapy and its bene-fits in reducing cardiovascular risk.A recent pilot study showed thatperiodontal treatment may reducesystemic blood pressure and left ven-tricular mass (Vidal et al. 2013), butit is still necessary to demonstratelong-term results, beyond theimprovement of the inflammatoryprofile, in real cardiovascular end-points.

The non-surgical periodontaltreatment was effective in reducingthe levels of markers of systemicinflammation and improves the lipidprofile in subjects with severechronic periodontitis.T

able

3.

Medianvalues

(firstandthirdquartiles)ofandCRP,ESR,andlipid

profile

oftest

andcontrolgroups,before

treatm

ent(T0)and2(T2)and6(T6)monthspost-treatm

ent

Variable

T0

T2

T0/T2-t

T0/T2-c

T6

T0/T6-t

T0/T6-c

Test

Control

pa

Test

Control

pa

pb

pc

Test

Control

pa

pd

pe

CRP(m

g/l)

1.0

(0.7;1.2)

1.0

(0.7;1)

0.94

0.9

(0.7;1)

1.1

(0.9;1.2)

0.001

0.26

0.003

0.5

(0.33;0.8)

1.2

(1;1.3)

<0.001

<0.001

<0.001

ESR

(mm/h)

12(8;17.5)

12(6.5;14.5)

0.25

9.5

(6;11.5)

13(11.5;17.5)

0.003

0.002

0.007

7(5.5;9)

14(12;17.5)

<0.001

<0.001

0.001

TC

(mg/dl)

200.5

(163;217.5)

189(165;213)

0.75

183.5

(164.5;219)

188.5

(169;214)

0.43

0.26

0.42

180(147;198.5)

190(169;213)

0.021

<0.001

0.91

HDL-C

(mg/dl)

46(37.5;51)

46(38.5;51.5)

0.65

49(40;52)

49.5

(45;52)

0.72

0.3

0.29

49.5

(43.5;53)

45(40.5;50)

0.20

0.13

1.00

LDL-C

(mg/dl)

116.5

(92;138.5)

108(90.5;135)

0.37

110(82;128)

109.5

(92;132.5)

0.72

0.61

0.79

113(89.5;128)

109(90.5;123.5)

0.92

0.06

0.48

Triglycerides

(mg/dl)

139(84;187.5)

102(77;217)

0.64

116(78.5;170.5)

111(89.5;205.5)

0.25

0.004

0.62

115.5

(74.5;156.5)

123(99;203.5)

0.22

0.015

0.52

CRP,C-reactiveprotein;ESR,erythrocyte

sedim

entationrate;TC,totalcholesterol;HDL-C

,HDLcholesterol;LDL-C

,LDLcholesterol.

pa=statisticaldifference

betweentest

andcontrolgroupsatT0,T2,andT6,calculatedbytheWilcoxonsigned

ranktest

withcontinuitycorrection;pb=

statisticaldifference

betweenT0

andT2forthetest


ranktest

withcontinuitycorrection;Pc=statisticaldifference

betweenT0andT2forthecontrolgroup,calculatedbytheWil-

coxonsigned

ranktest

withcontinuitycorrection;Pd=statisticaldifference

betweenT0andT6,forthetest


ranktest

withcontinuitycorrection;

Pe=statisticaldifference

betweenT0andT6,thecontrolgroup,calculatedbytheWilcoxonsigned

ranktest

withcontinuitycorrection.


880 Ca�ula et al.

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Table 4. Correlation of haematological variables at baseline (T0), 2 months (T2), and 6 months (T6) after periodontal treatment.

TC HDL LDL Triglycerides

T0 T2 T6 T0 T2 T6 T0 T2 T6 T0 T2 T6

CRP �0.141 0.086 �0.149 �0.024 �0.237 0.208 �0.070 �0.015 �0.058 �0.057 �0.087 0.239TC – – – �0.149 0.071 �0.028 0.643* 0.421* 0.642* 0.568* 0.485* 0.332HDL – – – – – – �0.200 �0.181 �0.053 �0.260* 0.067 0.043LDL – – – – – – – – – 0.078 �0.194 0.201

CRP, C-reactive protein; TC, total cholesterol; HDL-C, HDL cholesterol; LDL-C, LDL cholesterol.*p < 0.05.



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Address:Ricardo G. FischerFaculdade de OdontologiaRio de Janeiro State UniversityBoulevard 28 de Setembro 157, 2o Andar,Vila IsabelRio de Janeiro, RJ. Cep 20551-030, BrazilE-mail: [email protected]

Clinical Relevance

Scientific rationale for the study:Evidences showed that periodontaldisease is associated with cardio-vascular disease. C-reactive protein,erythrocyte sedimentation rate, andlipid profile are risk markers ofcardiovascular disease. Periodontal

therapy may reduce these risk mark-ers and thus improve cardiovascularrisk profile.Principal findings: Periodontal ther-apy significantly reduced C-reactiveprotein, erythrocyte sedimentation,and significantly improved lipid pro-file.

Practical implications: Treatmentof periodontal disease may reducecardiovascular risk markers. Den-tists should be aware of the poten-tial of periodontal therapy inimproving cardiovascular risk pro-file.


882 Ca�ula et al.

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