Serum and saliva biomarkers in cardiovascular diseases and periodontitis- Smoking as a confounding factor

Posted 11.12.2018

Honored Professor Alpdogan Kantarci from The Forsyth Institute, Harvard School of Dental Medicine Affiliate, Cambridge, MA, United States, served as an opponent of DDS Laura Lahdentausta in her academic dissertation entitled “Serum and saliva biomarkers in cardiovascular diseases and periodontitis- Smoking as a confounding factor”. The dissertation was held in Biomedicum Helsinki 5th December 2018 and the PhD thesis was conducted in Department of Oral and Maxillofacial Diseases, University of Helsinki. Supervisors were adjunct Professor Pirkko Pussinen and Professor Timo Sorsa.

The PhD study consisted of three different study populations from which serum and saliva biomarker levels (MMP-8, MMP-9, TIMP-1, and MPO) were measured. Firstly, the Triangel data collected at Lund University Central Hospital in Sweden (n = 669) comprised ACS patients and healthy controls. Secondly, the case-control data collected from Ludwigshafen, Germany (n = 198), consisted of ischemic stroke patients and their controls whose oral status was estimated through a questionnaire and cumulative risk score (CRS) to assess their risk of having periodontitis determined from saliva molecules. Thirdly, the Parogene cohort (n = 508) consisted of patients with an indication of coronary angiography seen at Helsinki University Central Hospital in Finland. The clinical oral status was examined for patients in this cohort.

The data from this study indicate that saliva biomarkers distinguish periodontitis patients from controls, and cardiac status has a minor effect on the salivary periodontal diagnostics. Serum biomarkers designate the systemic state, and can be utilized in the diagnosis of CVD, including both ACS and ischemic stroke. This observation emerged from the Ludwigshafen study, where elevated serum biomarkers associated with ischemic stroke, while stroke-free healthy controls more frequently exhibited signs of current periodontitis reflected in elevated saliva biomarker levels. However, in the Parogene study periodontitis interfered in the diagnosis of ACS using serum MMP-9, indicating the systemic effect of periodontal disease. Finally, smoking complicates the use of saliva and serum biomarkers, whereby the smoking dimension (i.e., quantity, duration, and time since cessation) influences the biomarkers.

Overall, it was found that periodontitis and CVD associate with one another and the degradation of ECM remains crucial in both diseases. Thus, the same biomarkers can be utilized in the diagnosis of both diseases. However, the selection of sample material is crucial. Specifically, saliva is suitable for distinguishing periodontitis patients from controls, whereas serum biomarkers are suitable for CVD diagnostics. Smoking remains a factor that must be taken into account when using both serum and saliva biomarkers, such as MMP-8, MMP-9, TIMP-1, and MPO. To conclude, these biomarkers could be utilized by different healthcare professionals for screening, early diagnosis, and prevention aiming to improve patient quality of life.

Electronic link to thesis

On the picture from left to right: Ulvi K. Gürsoy (Un. of Turku), Mervi Gürsoy (Un. of Turku), Alpdogan Kantarci (Forsyth inst.), Laura Lahdentausta (Un. of Helsinki), Pirkko Pussinen (Un. of Helsinki), and Tulay Yucel-Lindberg (Karolinska inst.).

ScSP 2017 Congress Poster abstracts

Posted 08.01.2018



25-26 August 2017, Mariehamn, Åland Islands, Finland


Poster Abstracts


Ercan E1, Tunalı M2, Özdemir H3, Kasnak G4, Koyuncuoğlu C5, Kayıpmaz S1, Fıratlı E4

1 Karadeniz Techical University, Trabzon, Turkey
2 Bezmi Alem Vakıf University, İstanbul, Turkey
3 Osmangazi University, Eskişehir, Turkey
4 İstanbul University, İstanbul, Turkey
5 Aydın University, İstanbul, Turkey

Objective: The sinus augmentation procedure is a predictable approach for augmentation of the atrophic posterior maxilla. Autogenous grafts are the gold standard for sinus augmentation. Despite their osteogenic capacity, increased morbidity and limited availability make them less desirable. Titanium prepared PRF (T-PRF) was shown to induce bone regeneration. The post-operative sixth month results of three cases for sinus augmentation procedures with T-PRF and mini-screws were presented.
Methods: Three systemic healthy female patients were referred for dental implant placement. After local anesthesia full-thickness flap was elevated and a rectangular window was shaped on the buccal side of maxilla. The bone of the lateral window (which was still attached to the membrane) was moved from its lower edge to the inside and upwards. After the membrane was sufficiently exposed, the mini-screws of varying sizes were placed horizontally, above the lateral window, from outside to the inside to hold the membrane for reducing the ongoing pressure of membrane during healing period. The condensed T-PRF membranes were placed into the sinus cavity to completely fill the cavity. The remaining one T-PRF membrane was placed over the window. Flap was placed and sutured. The patient was evaluated by Cone Beam Computed Tomography (CBCT) at baseline and post-operatively.

Results: The post-operative healings were uneventful and morbidities were minimal. The average vertical bone gain was 2.66 (0.5-6.0) mm and the average bone volume increment was 0.93(0.505-1.245) cm3 according to CBCT analysis (baseline and post-op 6 months).

Conclusion: T-PRF may be a predictable autogenous alternative for autogenous bone graft.


Fábio Vidal, DDS, MSc, PhD1, Lucio Souza Gonçalves, DDS, MSc, PhD1, Rodrigo Carvalho de Souza, DDS, MSc, PhD1, Dennis de Carvalho Ferreira, DDS, MSc, PhD1, Ricardo Guimarães Fischer, DDS, MSc, PhD2

1. School of Dentistry, Estácio de Sá University, Rio de Janeiro, Brazil
2. School of Dentistry, Rio de Janeiro State University, Brazil

Objective: To compare the success of dental implants and bone augmentation procedures between non-HIV-infected and HIV-infected patients. The hypothesis is that well controlled HIV-infected patients can be eligible to implant therapy achieving similar outcomes than non-HIV-infected controls.
Methods: Thirteen non-HIV-infected and 13 HIV-infected patients were enrolled in this study and followed up to 156 months. Twenty five implants were planned for each group and bone augmentation procedures performed whenever necessary. Success was considered in the absence of early or late failure; surgical or restorative complications; bone loss; and mucositis/peri-implantitis. The two groups were compared regarding the individual-level characteristics (age, gender, smoking, dental floss use, mouthwash and periodontal diagnosis) and implant-level characteristics [peri-implant health, dental implant geometry, dental implant placement, prosthetic connection type, dental implant prosthesis type, periimplant keratinized mucosa, guided bone regeneration, membrane type, gengival bleeding index, visible biofilm, follow up, dental Implant length, dental implant torque and distance from the platform to the bone crest).
Results: All the implants placed healed uneventfully and were restored as planned. Comparisons between HIV-infected and non-HIV-infected patients regarding the individual-level characteristics did not demonstrate significant differences between group for all co-variables (p > 0.05). Comparisons of implant-level characteristics showed statistically significant differences between groups only for the variables dental implant prosthesis type (p = 0.021) and follow up (p = 0.011).
Conclusions: The findings suggest that well controled HIV-infected patients are eligible to undergo bone augmentation procedures and implant placement with similar long term outcomes when compared to non-HIV-infected patients.


Bulduklu A, Ozdemir H

University of Eskisehir Osmangazi, Turkey

Objective: The aim of this study is to evaluate the clinical value of periodontal bone defects determined by panoramic radiographs and dental tomography. And to question the reliability of digital radiographs that routinely aid diagnosis and treatment in the clinic by comparing the results
Material and Method: Eskişehir Osmangazi University Faculty of Dentistry Department of Periodontology October 2015 - April 2016 to date of patients who were placed among individuals diagnosed with chronic periodontitis and aggressive periodontitis were included in the study. Radiographic measurements the peak of the defect at the root of the alveolar crest (AC) projection was determined as the base of the apical contour (BD) defect at the root surface of the periodontal ligament. The enamel cementation (CEJ) is taken as a fixed coronal reference for these measurements. Radiographic measurements were made after the above lines were drawn. After radiographic measurements, clinical measurements were made correctly during flap surgery.
Results: According to the findings of this study, OPG and CBCT in the anterior region represented good clinical findings, whereas in the posterior region, measurements with CBCT were found to have excellent correlation in clinical measurements. In addition, CBCT represents better clinical measurements than OPG in evaluating all data.
Conclusion: It is more advantageous to use CBCT when it is aimed to make a more accurate judgment in clinically determined critical intrabony defects and to plan more radical treatment.


Alfakry H 1, Orlandi M 2, Parkar M 3, Tervahartiala M 1, Pussinen PJ 1, Sorsa T 1, Tsimikas S 4, Deanfield JE 5, D’Aiuto F 2

1. Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
2. Periodontology Unit, Department of Clinical Research, UCL Eastman Dental Institute, London, UK
3. Cell Biology, UCL Institute of Ophthalmology, London, UK
4. University of California, San Diego, La Jolla, California, USA
5. Vascular Physiology Unit, Institute of Cardiovascular Science, UCL, London, UK

Periodontal treatment triggers acute and chronic inflammatory changes associated with endothelial function. It is not known whether these changes are reflected by endotoxin or biomarkers of neutrophilic activity. The aim of the present study was to assess the impact of periodontal treatment on circulating biomarkers of neutrophil activity.
120 participants suffering from severe generalized periodontitis were randomized to receive either intensive periodontal therapy (IPT, N=61) or control treatment (CPT, N=59). Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery. Serum sample concentrations were collected at baseline, and at 1, 7, 30, 60 and 180 days. Neutrophil matrix metalloproteinase (MMP)-8 was determined by a time-resolved immunofluorometric assay (IFMA), and tissue inhibitor of MMP-1 (TIMP-1), myeloperoxidase (MPO) interleukin-6 (IL-6) levels were measured by ELISA. C-reactive protein (CRP) was quantified by immunoturbidimetry and endotoxin activity (LPS) by limulus amebocyte lysate (LAL) assay.
Acute vascular dysfunction observed at 24 hrs following IPT was associated with elevated neutrophil activity (increased MMP-8 and MPO levels, p<0.01 and decreased TIMP-1, p<0.01) as well as with elevated endotoxin activity (p<0.01) when compared to CPT. Most of these markers returned to baseline values within one month following IPT. Improvement of FMD at 6 months was associated with a reduction in neutrophilic enzyme activity ratio (MMP-8/TIMP-1 ratio, p<0.05) and with an elevation in MMP-8 inhibitor (TIMP-1, P<0.05).
After acute impairment biomarkers of neutrophilic activity display 6 months delayed improvement in subjects with severe periodontitis following IPT compared with CPT.


Tunalı M¹, Ercan E², Uzun B.C³, Koyuncuoğlu C⁴, Kasnak G⁵, Özdemir H⁶, Öncü E⁷, Fıratlı E⁵.
1. Bezmialem Vakıf University School of Dentistry Department of Periodontology, İstanbul, Türkiye.
2. Karadeniz Technical University School of Dentistry Department of Periodontology, Trabzon, Türkiye.
3. Ministry of Health Hospital, Department of Periodontology, Manisa, Türkiye.
4. İstanbul Aydın University School of Dentistry Department of Periodontology, İstanbul, Türkiye.
5. İstanbul School of Dentistry Department of Periodontology, İstanbul, Türkiye.
6. Osmangazi University School of Dentistry Department of Periodontology, Eskişehir, Türkiye.
7. Necmettin University School of Dentistry Department of Periodontology, Konya, Türkiye.

Objectives: Several surgical techniques have been proposed to treat single and multiple gingival recessions. Aberrant frenum and muscle attachments can contribute to the progression of recession by generating tension on the marginal tissues. Despite Semilunar Flap technique is advantageous for elimination of frenum and muscle attachments in single gingival recessions, it cannot be a solution for multiple gingival recessions. The previously introduced Modified Semilunar technique can be used in a very limited number of cases, because significantly reduce the blood supply to tissues. Web Coronally Advanced Flap (WCAF) is described for the treatment of multiple recession defects. WCAF is also advantageous for elimination of multiple frenum and muscle attachments without significantly reduce marginal tissues blood supply.
Methods: Four patients were referred to our clinic with a total of 20 multiple Miller Class I/II gingival recessions represented that exposed root surfaces showed abrasion defects. Recessions were treated with titanium prepared platelet rich fibrin (T-PRF) membrane and WCAF technique. The following clinical measurements were taken before the surgery and at 1 month, 3 months and 6 months follow-up examination: probing depth (PD), clinical attachment level (CAL), amount of keratinized tissue (KT), and recession depth (RD).
Results: After 6 months, mean root coverage was 92.36%. Furthermore, the mean amount of KT increased statistically.
Conclusion: Within the limits of this case series study, the results demonstrated that T-PRF membrane combined with a WCAF surgery is safe and effective in a treatment of multiple Miller Class I/II gingival recession defects.

Swedish Society of Periodontology Winter Course by Prof. Jan Lindhe

Posted 20.12.2017

Members of ScSp are eligible for registration at member-price; simply mention your ScSP membership during registration.