Periapical Surgery Research Articles

Low Intensity Laser Therapy: A Review of Its Applications and Effectiveness in Health, General Dentistry and Endodontics

Aims: To evaluate the use of low-level laser therapy in endodontic treatment and its broader applicability in General Health and Dentistry. Study Design: Literature review. Place and Duration of Study: The study involved searching articles and book chapters in the Google Scholar and PubMed databases from 2018 to 2023, with the review concluding in 2024. Methodology: The review used descriptors from the Brazilian Health Sciences Descriptors database: Laser Therapy, Low-Level Light Therapy, Endodontic Treatment, Dentistry, and their Portuguese equivalents. A total of 34 articles were selected, focusing exclusively on low-level laser therapy and its applications. Articles not addressing this specific therapy were excluded. Results: Low-level laser therapy is frequently used as an adjunct in general health, dentistry and endodontic treatment. Clinical applications, such as postoperative pain control, root canal system disinfection, periapical surgery, and tissue repair, showed promising results. However, more theoretical and clinical evidence is still required to fully establish its efficacy. Further research is needed to strengthen the evidence base and optimize its clinical use. Conclusion: Low-level laser therapy offers a potential non-invasive treatment option in endodontics, with satisfactory outcomes in various clinical applications.

Periapical surgery and different root obturation protocols for upper central incisor: A finite elements analysis

BackgroundThe aim of this study was to determine the effect of root canal filling using different obturation materials combined with apicoectomy in upper central incisors under loading with 1 N and 100 N. The effect of incomplete root formation was also investigated. MethodsBased on a CBCT-scan, a model of an upper central incisor was created. The model was altered to simulate different clinical situations: root canal treatment, apicoectomy at two different lengths and with different obturation protocols, and immature root formation after trauma. In each model the tooth was loaded with 1 and 100 N, and peak Von Mises stress of bone and tooth, elastic strain of the periodontal ligament, as well as rotation and displacement of the tooth were measured. ResultsPeriapical surgery increases stress in dentin and the surrounding bone. Different obturation materials only produce minor differences in a coronally intact tooth. ConclusionsInterincisal angle or loading direction strongly affects all measured values and needs to be considered when planning periapical surgery or comparing finite element analysis. Immature roots show the highest stress values in this study, reaching half the yield strength of dentine.

Combined non-surgical and surgical management of misdiagnosed cutaneous sinus tract of endodontic origin – 15 months CBCT follow-up

Introduction and aim. An extraoral cutaneous sinus tract of endodontic origin represents a skin condition that appears due to an infection that could be primary or secondary to trauma accompanied by alveolar bony changes. It may be easily misdiagnosed and inappropriately treated due to lack of inadequate expertise on part of medical professionals followed by faulty treatment which can complicate the case further. Description of case. This case report intends to highlight a case of a sixteen-year-old male patient referred for an extraoral cutaneous sinus tract misdiagnosed and insufficiently treated by a general physician followed by general dentists for more than a month due to lack of proficiency in the field of endodontics. The clinical and radiographic examinations confirmed the pulpal origin due to trauma related to permanent mandibular incisors. A combination of non-surgical root canal therapy followed by periapical surgery was performed leading to a significant healing of the lesion. Conclusion. Accurate diagnosis is the key to treat draining sinus tracts of endodontic origin. Root canal treatment and endodontic surgery should be used judiciously for effectively eliminating the pathogens thus providing healing and repair mechanisms a chance to achieve the desired result.

Laser doppler flowmetry microcirculation assessment of a periapical cyst

The radicular cyst develops by necrosis in the center of a granulation lesion and expands by applying pressure to the surrounding tissues thus decreasing microcirculation in bone. Laser doppler flowmetry is a non-invasive method of measuring microcirculatory blood flow in tissue. Using laser doppler flowmetry Moor VMS-LDF1-HP and CP1T-HP probe combined with Moor VMS-PC software the microcirculation of the periapical lesion (cyst) was evaluated before surgical endodontic treatment. It was compared to a healthy endodontically treated tooth of the same type with no periapical lesions. Measurements were done with the help of a VMSLDF1-HP probe. Later the bony crypt of the cyst was evaluated for blood perfusions with the VP7BS-HP bone probeEvaluate tissue microcirculation of a periapical lesion before, after and during surgical endodontic treatmentLaser Doppler flowmetry shows that the cystic tooth has a decreased blood flow, decreased concentration, direct current, speed, and lower temperature compared to another endodontically treated lesion-free tooth of the same type. During periapical surgery, the direct laser blood flow evaluation of the surgical crypt shows different values of flux, speed, direct current, and concentration before and after cyst removal which could be attributed to the mechanical trauma (osmotic pressure), adrenaline in the local anaesthetic or laser irradiation of tissues.Laser Doppler flowmetry is a valuable method to perform tissue evaluation before, during and after treatment. It allows us to follow up on the healing and pathological dynamics of microcirculatory tissue changes as well as evaluate and compare different methods and materials for the treatment of apical periodontitis.

Leukocyte-Platelet-Rich Fibrin in Bone Regeneration after Periapical Surgery: A 30-Month Follow-Up Clinical Report

Aim and background: Periapical lesions, which occur due to the infection and necrosis of dental pulp, are a significant dental pathology that poses risks to oral and systemic health. These lesions often require interventions such as root canal treatment or periapical surgery. Recent research has focused on the effectiveness of biocompatible materials, including mineral trioxide aggregate, bioceramics, and leukocyte-platelet-rich fibrin (L’PRF), in improving healing outcomes. This report presents the application of leukocyte-platelet-rich fibrin (L’PRF) derived from the patient’s autologous blood to enhance bone healing. Case description: A 61-year-old woman with well-controlled hypertension and good oral hygiene visited the dental clinic due to a painless swelling near her upper left central incisor. After examination, it was determined that she had a periapical granuloma. The patient underwent successful root canal retreatment and apical surgery, during which leukocyte-platelet-rich fibrin was applied. After 30 months, she experienced significant improvement with no symptoms and substantial bone regeneration. Conclusion: Clinical evidence and this case study indicate that leukocyte-platelet-rich fibrin (L’PRF) may enhance healing post periapical surgery. Further research, including more extensive and longer-term randomized trials, must confirm L’PRF’s effectiveness and refine treatment protocols. Clinical significance: L’PRF enhances bone healing post periapical surgery. Clinicians should consider integrating L’PRF in periapical surgeries, ensure diligent follow-up, and inform patients of its long-term advantages. Further randomized trials are needed to refine L’PRF clinical guidelines.

Research protocol to identify the effect of concentrated growth factors on healing of apicomarginal defects

Periapical periodontitis can cause damage to both the tooth and the periodontium, thereby affecting the life quality of patients. Traditional periapical surgery takes a long time to heal, and postoperative pain and swelling are obvious. Seeking a good treatment strategy for faster and better healing of periapical periodontitis is an urgent issue that needs to be addressed. Concentrated growth factor (CGF) is considered an ideal biomaterial for retaining abundant and denser growth factors in accelerating bone formation. To investigate the effect of CGF on healing of apicomarginal defects, this prospective study aims to enroll 72 patients with periapical periodontitis in their anterior teeth or premolars who have undergone comprehensive root canal treatment. The patients will be randomly allocated into the following four groups: control group, which will receive apical surgery alone (including apicoectomy, inflammation debridement, and retrofilling of the root apex); bone group, which will undergo apical surgery in conjunction with the use of bone substitute; CGF group, which will undergo apical surgery in conjunction with the use of CGF; and CGF+bone group, which will undergo apical surgery in conjunction with the use of bone substitute and CGF gel. Each group will comprise 18 patients, and all surgeries will be conducted by the same proficient surgeon. The participants will undergo a 1-year follow-up with the assistance of a physician, including questionnaire data and daily records of pain and swelling at 2, 6, and 12 h and 7 days after the surgery. Cone-beam computed tomography images will be taken before the surgery, immediately after the surgery, and at 3, 6, and 12 months after the surgery. This study aims to explore the therapeutic effect of CGF on apicomarginal defects, in order to help clinical doctors find better treatment methods.

Analysis of the Prognostic Factors That Influence the Outcome of Periapical Surgery, including Biomimetic Membranes for Tissue Regeneration: A Review.

The objective of this study was to analyze the prognostic factors that influence the outcome of periapical surgery. A systematic search of the literature was carried out using PubMed and Scopus databases between January 2000 and December 2023 with no language limitations. The PICO question of the present systematic review was: What prognostic factors may influence the outcome of periapical surgery? The most relevant randomized controlled clinical trials (RCTs), prospective clinical trials, retrospective studies, and meta-analyses (n = 44) were selected from 134 articles. The reviewed literature evidenced that bone-lesion healing could significantly be improved by the absence of deep periodontal pockets (>4 mm), localization in anterior teeth, the absence of pain and/or preoperative symptoms, a size of bone lesion < 5 mm, the use of ultrasound, the correct placement of retrograde filling material, and the use of different biomimetic membranes for guided tissue regeneration (GTR). Some preoperative and intraoperative factors could significantly improve the prognosis of periapical surgery. However, these results were not conclusive, and further high-quality research is required.

Comparative Evaluation of Solite RS3 and HyFlex Remover Retreatment Files in Conserving Remaining Dentin Thickness During Endodontic Retreatment Using Cone Beam Computed Tomography: An In Vitro Analysis.

Introduction Non-surgical retreatment is seen as a conservative choice for dealing with recurrent infections, instead of opting for periapical surgery. The retreatment processes should be promptly and efficiently carried out, utilizing a suitable armamentarium. The objective of this experiment is to evaluate the quantity of root dentin that remains following the removal of gutta-percha (GP) from the root canal employing two distinct retreatment files. Materials and methods Sixty single-rooted teeth were selected for the examination. The process of shaping and cleaning was performed using the step-back approach, with a master apical file size of 40. The smear layer was effectively eliminated by rinsing with a solution of 3% sodium hypochlorite and 17% ethylenediaminetetraacetic acid. Paper points were employed to desiccate the canals. The obturation process involved the utilization of the lateral compaction technique with the AH Plus sealer (Dentsply Sirona, NC, USA). The teeth were classified into two groups: Group I (n=30) underwent retreatment using HyFlex Remover (Coletene India, Pvt., Ltd.), whereas Group II (n=30) received therapy with Solite RS3 retreatment files (Solite Dental in Chennai, India). The remaining dentin thickness (RDT) was assessed by cone beam computed tomography at levels 3, 6, and 9 mm from the cemento enamel junction after the removal of GP. The acquired data underwent examination using an independent t-test to determine statistical significance. Results The findings demonstrate that the utilization of Solite RS3 files led to a higher level of dentin thickness remaining at 3 mm, 6 mm, and 9 mm on the mesial side in comparison to HyFlex Remover retreatment files. The observed difference was found to be statistically significant at a significance level of p<0.05 on the mesial side. Nevertheless, there was no notable disparity seen between the two file types at these three levels on the distal side (p>0.05). Conclusion Based on the obtained results of the study, it can be concluded that Solite RS3 files show promise in preserving the RDT. However, further studies encompassing diverse parameters are needed to establish a conclusive and definitive conclusion.

Root End Resection in Periapical Surgeries: A Contention of Opinion Between an Oral Surgeon and an Endodontist.

Root End Resection in Periapical Surgeries: A Contention of Opinion Between an Oral Surgeon and an Endodontist.

Management of type III Dens Invaginatus with a periapical lesion in a maxillary lateral incisor: A case report

Dens Invaginatus (DI) is a developmental abnormality, usually affecting the maxillary incisor teeth, particularly lateral incisors. These cases usually present technical difficulties concerning their management owing to their aberrant canal morphology. Conventional root canal therapy, periapical surgery, and extraction have been reported as treatment modalities for such anomalies. The following case report depicts surgical endodontic management of an Oehler’s Type III DI involving a maxillary lateral incisor associated with periapical lesion aided by cone beam computed tomography (CBCT) and with the use of mineral trioxide aggregate (MTA), hydroxyapatite bone graft and platelet-rich fibrin (PRF) membrane. At 12 months post-treatment, the patient did not report any eventful episodes, and the size of the periapical lesion was markedly reduced.

Utilising blood-derived products for guided tissue regeneration in periradicular surgery: a systematic review and meta-analysis

Background Since 1982, guided tissue regeneration (GTR) has become increasingly popular. The recent progress in GTR research focuses on the application of blood-derived products. However, no comprehensive systematic review has been conducted to assess its effectiveness specifically in periradicular surgery. Therefore, the aim of this review was to analyse the outcomes of periradicular with GTR using blood-derived products compared to standard periradicular surgery. Methods This review was based on randomised controlled trials comparing periradicular surgery in conjunction with GTR with blood-derived products and the standard periapical surgery. The databases searched included Embase, MEDLINE, Cochrane CENTRAL, and Dentistry and Oral Sciences Source, with the most recent search conducted on December 16th, 2022. Additionally, reference lists of similar systematic reviews were examined, while international trials registries and repositories were consulted for unpublished studies. Two blinded independent reviewers carried out the screening and the included studies underwent critical appraisal. The findings are reported in accordance with the PRISMA guidelines. Results A total of 261 publications were initially reviewed based on their title and abstract, resulting in seventeen studies that underwent full-text screening. At this stage, 14 studies were excluded, leaving three randomised controlled trials to be included. These trials involved a total of 85 patients. A meta-analysis was conducted for the outcome of healing. The overall treatment effect was 0.78 (95% CI 0.18 to 3.34), indicating a preference towards the control group. Conclusion Based on a meta-analysis of three studies, there was no statistically significant distinction observed in terms of healing between the GTR involving blood-derived products and standard procedure groups. However, critical appraisal revealed indirectness and imprecision, resulting in a certainty rating of 'low'. Thus, additional robust evidence is necessary to support the utilisation of blood-derived products in GTR techniques to enhance periradicular surgery outcomes. Systematic review registration number PROSPERO CRD42020222663.

Surgical Management of Radicular Cyst with the Application of a Natural Platelet Concentrate and Ostoden: A Case Report

ABSTRACT The most frequent cystic lesions that affect the jaw are radicular cysts. The current case report describes the surgical management of a radicular cyst in the periapical region of maxillary central and lateral incisors, and highlights the efficacy of natural platelet concentrate [platelet-rich fibrin (PRF)] along with Ostoden bone graft material used for postoperative healing. A 46-year-old male patient presented to the department with swelling in the palatal aspect of the maxillary anterior region. On radiographic examination, a radiolucent periapical lesion was evident in relation to the left maxillary central and lateral incisor. In the maxillary anterior region, root canal therapy was performed, followed by periapical surgery, and PRF with Ostoden bone graft was placed in the surgical site to initiate the healing at a faster rate. The patient was recalled at follow-ups after 7 days, 3, 6, and 9 months. No symptoms such as pain, inflammation, or discomfort were observed during the review period.

Twelve Years Success of Radiographical Assessment and Clinical Review of Post Periapical Surgery of a Tooth with Canal Calcificification (Case Study)

This case report deliberates on the modification of the treatment plan for a young female patient having a history of trauma to her anterior tooth for two years duration. The patient didn’t pay attention to the trauma at that time and she barely remember about it, until she gets in pain. In this case study we will highlight on the treatment options and how to save the tooth. Different modality of treatment has been raised to study the possibility of the survival of this tooth since the patient doesn’t want to lose it.

Intentional Replantation with Simultaneous Periapical Surgery- A Case Report with One Year of Follow-Up

Intentional Replantation with Simultaneous Periapical Surgery- A Case Report with One Year of Follow-Up

A Narrative on Inflammatory Biomarkers in Endodontics

ABSTRACT One of the most common diseases causing the destruction of enamel and remaining tooth structure is dental caries which further leads to pulpal and periapical inflammation if not treated. As tools for revealing important factors in identifying targets disease and pathophysiology for the evolution of prevention and treatment strategies, molecular and cellular biology plays a pivotal role. Finding an accurate diagnosis that will serve as the foundation for effective treatment continues to be one of the key issues in endodontics. Inflammatory biomarkers play a diverse and broad role in endodontics, with the potential to become a key factor in determining treatment plans by assisting in diagnosis and prognosis. Inflammatory biomarkers have the potential to become a key factor in determining treatment plans by assisting in diagnosis and prognosis. Endodontists are still divided on issues such as vital pulp therapy versus traditional root canal therapy and retreatment versus periapical surgery. Furthermore, clinical challenges such as determining the appropriate tissue fluid to analyse, establishing a precise inflammatory threshold, and delivering results at the chairside must be overcome. Endodontists may soon be able to use chairside genetic tests to make more informed treatment decisions for their patients.

An in-vitro comparison of bond strength of three different root end filling materials with Universal testing machine

Bacterial infection is widely known cause of apical periodontitis. Failure of conventional root canal treatment indicates the periapical surgery, this procedure requires root end resection. For the long term success of periapical surgery, root end filling materials are used. To compare the push-out bond strength of Portland cement, ProRoot MTA and Biodentine used as root-end filling materials using Universal Testing Machine. From the middle part of each root, three dentinal slices were made to produce 93 slices which were divided into 3 groups. In Group A: ProRoot MTA, In Group B: Biodentine and In group C: Portland cement were used and were further divided in subgroups based on soaking time in PBS solution i.e. 24hrs and 7 days before assessing the push out bond strength using Universal Testing Machine. The mode of bond failure of material to root dentin was analyzed using microscope. Data was analyzed using ANOVA and post-hoc tukey’s test. After 24hrs, there was statistically non-significant difference but After 7 days, ProRoot MTA showed significantly higher bond strength as compared to other tested groups. While analyzing the mode of bond failure, ProRoot MTA had adhesive failure, Biodentine had cohesive failure and Portland cement had mixed type of bond failure. All the tested materials showed comparable bond strength but ProRoot MTA had highest bond strength to root dentin among the other tested materials.

The Effectiveness of Autologous Platelet Concentrates in the Clinical and Radiographic Healing after Endodontic Surgery: A Systematic Review.

Regenerative techniques are increasingly applied in endodontic surgery, but different materials may have varying impacts on soft and hard tissue healing. This systematic review aims to evaluate the effectiveness of autologous platelet concentrates (APCs) in clinical and radiographic healing after endodontic surgery. The data for this systematic review were processed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for improving the reporting of systematic reviews and meta-analyses. A literature search was conducted until October 2023 on PubMed, Scopus, and Cochrane Databases. Randomized controlled trials and controlled clinical trials addressing the use of APCs in patients who presented persistent periapical lesions and needed periapical surgery were included. Dual publications, narrative reviews, systematic reviews, case series, questionnaires, animal studies, case reports, letters to the editor, in vitro studies, and abstracts were excluded. In total, the search resulted in 14 papers. Clinical and radiographical findings were reported, showing that when APCs were used, patients exhibited less pain and swelling and a greater reduction of apical radiolucency after 12 months follow-up on average. However, the moderate/high risk of bias of included studies and their high heterogeneity, do not allow one to draw definitive conclusions on the effectiveness of APC after endodontic surgery.

Comparative evaluation of platelet-rich plasma + β-tricalcium phosphate and platelet-rich fibrin + β-tricalcium phosphate for healing periapical lesions, using cone beam computed tomography - an in vivo study.

Platelet concentrates are currently being researched for their potential to enhance bone formation. The aim of this study is to quantitatively evaluate and compare bone regeneration in periapical lesions using a combination of platelet-rich plasma (PRP) + β-tricalcium phosphate (β-TCP) and platelet-rich fibrin (PRF) + β-TCP. Ten subjects with periapical lesions measuring 10-20 mm in relation to maxillary incisors indicated for periapical surgery were selected. Pre-operative bone density values at the periapical region were measured using CBCT. Root canal treatment was completed appropriately in all cases. Under adequate local anesthesia, periapical surgery was performed. The 10 subjects were distributed into two groups of 5 subjects in each group. Group I: Periapical bone defect filled with PRP + β-TCP and Group II: Periapical bone defect filled with PRF + β-TCP. The mucoperiosteal flaps were repositioned and sutured. Bone density evaluation of the periapical region was done 6 months and 1 year after surgery using cone beam computed tomography (CBCT). The Hounsfield unit (HU) values obtained were subjected to statistical analysis by Independent samples t-test for inter-group comparison. The intra-group comparison was done by repeated measure ANOVA and Bonferroni post hoc tests. In Group I and Group II, a statistically significant difference was observed at the end of 6 months and 1 year, when compared to the pre-operative values (P=0.000). There was no statistically significant difference in bone density values between the PRP + β-TCP and PRF + β-TCPgroups at both 6 months and 1-year post-operative observation periods. PRP + β-TCP and PRF + β-TCP were equally effective in promoting bone regeneration and can be considered valuable bioactive surgical additives for enhancement of healing in periapical bone defects.

Comparison of Marginal Adaptation, Surface Hardness and Bond Strength of Resected and Retrofilled Calcium Silicate-based Cements Used in Endodontic Surgery: An In Vitro Study.

This study compared the effects of orthograde and retrograde methods on marginal adaptation, surface hardness, and push-out bond strength (POBS) of three calcium silicate-based used in endodontic surgery. Ninety single-rooted human mandibular premolars were randomly assigned into six groups (n = 15/group): groups I and II, ProRoot mineral trioxide aggregate (MTA) with orthograde and retrograde methods; groups III and IV, Biodentine (BD) with orthograde and retrograde methods; groups V and VI, iRoot BP Plus (BP-RPM) with orthograde and retrograde methods. After obturation, the apical 3 mm of each root was sectioned into two 1-mm-thick root slices and evaluated for marginal adaptation using a scanning electron microscope, surface hardness using Vickers hardness tester and POBS using a universal testing machine. Orthograde placement had a higher maximum gap width than retrograde placement (p < 0.05), but there was no significant difference among the tested materials (p > 0.05). Biodentine exhibited lower surface hardness than ProRoot MTA and iRoot BP Plus (p < 0.05), but there was no significant difference between ProRoot MTA and iRoot BP Plus (p > 0.05). Orthograde placement had higher POBS compared with retrograde placement (p < 0.05). Biodentine had higher POBS than iRoot BP Plus (p < 0.05), but no significant difference from ProRoot MTA (p > 0.05). The failure mode was mainly mixed for all the tested materials regardless of material type or placement technique. The retrograde method had better marginal adaptation; however, the orthograde method provided better dislodgement resistance. Biodentine had lower surface hardness than MTA and iRoot BP Plus with both techniques, whereas iRoot BP Plus demonstrated lower dislodging resistance than BD. The current findings suggest that orthograde technique, a simpler periapical surgery, with ProRoot MTA provides potentially better surface hardness and POBS than BD and iRoot BP Plus in single-canal teeth.

Successful endodontic treatment reduces serum levels of cardiovascular disease risk biomarkers-high-sensitivity C-reactive protein, asymmetric dimethylarginine, and matrix metalloprotease-2.

To investigate serum biomarkers of inflammation 2 years following non-surgical root canal re-treatment (Re-RCT) and peri-apical surgery (PS). The results were correlated with signs and symptoms, treatment outcome, metabolic syndrome factors, infection with severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 (COVID-19) infection and COVID-19 vaccination. Subjects from our previous study were recalled for 2 years post-treatment follow-up. Changes to the patient's history (medical, dental, social) were noted. Periapical health of the treated teeth was examined both clinically and radiographically. Blood pressure, fasting HbA1C and low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides and total cholesterol (TC) levels were measured. Serum inflammatory marker levels were assayed using a Bio-Rad Bio-Plex 200 analyser and values at different time points within the same group were compared using a Wilcoxon signed-rank test and differences between groups with a Mann-Whitney test. Linear associations were tested using Pearson's correlations. The recall percentage at 2 years was 56.9% (n = 37), with a 100% radiographic success rate using periapical radiographs. In total, 21 cases (56.8%) were completely healed, and 16 cases (43.2%) were healing. Higher matrix metalloprotease 2 (MMP2) levels were present in the healing group compared to the healed group. Serum levels of high-sensitivity C-reactive protein (hs-CRP), asymmetric dimethylarginine (ADMA) and MMP-2 were significantly reduced (p ≤ .001) whereas other biomarkers showed significant increases at 2 year compared to pre-operative levels, while FGF-23 and ICAM-1 were not significantly increased. HbA1C (p = .015), TC (p = .003), LDL (p = .003) and HDL (p = .003) reduced significantly at 2 years post-treatment compared to their preoperative levels. COVID infection showed a significant association with MMP-9 (p = .048). hs-CRP, ADMA and MMP-2 can be regarded as prognostic biomarkers of successful Re-RCT and PS as they reduced at 2 year recall in cases which showed evidence of clinical and radiographic success. The successful treatment of chronic apical periodontitis is correlated with improvements in metabolic syndrome indicators, better glycemic control, and reduction at 2 year of some systemic inflammatory markers which are related to risks of cardiovascular disease events.