CLINICAL RESEARCH
Gaurav Kumar, MDS,*
Sanjay Tewari, MDS,*
Mala Kamboj, MDS,*
Aparna Yadav, MD,*†
Paramjeet S. Gill, MD,*† and
Simmi Kharb, MD*†
SIGNIFICANCE
This prospective study
explores evidence of a
possible cause-and-effect
relationship between
endodontic infection and
systemic inflammatory burden
estimated by the difference in
the levels of serum
high-sensitivity C-reactive
protein and complete
hemogram parameters before
and after root canal treatment.
From the *Post Graduate Institute of
Dental Sciences, Rohtak, Haryana, India;
and †Post Graduate Institute of Medical
Sciences, Rohtak, Haryana, India
Address requests for reprints to Dr Sanjay
Tewari, Post Graduate Institute of Dental
Sciences, Rohtak, Haryana, India
124001.
E-mail address: tewarisanjayrohtak@
yahoo.co.in
0099-2399/$ - see front matter
Copyright © 2022 American Association
of Endodontists.
https://doi.org/10.1016/
j.joen.2022.05.003
1020 Kumar et al.
Comparative Evaluation of
Serum High-sensitivity
C-Reactive Protein and
Complete Hemogram Indices
in Subjects with and without
Apical Periodontitis:
A Prospective Interventional
Study
ABSTRACT
Introduction: This study aimed to compare the levels of high-sensitivity C-reactive protein
(hsCRP) and complete hemogram (CH) parameters before and after root canal treatment in
patients with apical periodontitis (AP) and healthy controls. Methods: Twenty-five patients
with asymptomatic AP in a single permanent tooth were recruited along with age- and sex-
matched healthy controls. Baseline serum hsCRP and CH parameters were recorded in both
groups. Root canal treatment was performed in teeth with AP, and biochemical parameters
were re-evaluated at the 6-month follow-up. Mann-Whitney and chi-square tests were used
to analyze data quantitatively and qualitatively, respectively. Spearman correlation was
applied to explore the relation between hsCRP with AP and periapical healing. Multivariate
linear regression tests were used to assess the effect of independent variables such as age,
sex, body mass index, and periapical index score on levels of hsCRP. Results: A baseline
comparison between patients with AP (3.37 6 2.69 mg/L) and controls (1.69 6 2.2 mg/L)
revealed a significant difference in hsCRP levels. However, all CH parameters were within the
reference range. A total of 22 patients in the AP group completed follow-up, and based on the
periapical index score and clinical presentations, 72.2% of patients were classified as healed.
At follow-up, hsCRP significantly reduced to 1.79 6 1.65 mg/L in the AP group. A significant
correlation between AP and hsCRP was observed. Conclusions: Patients with AP had a
significantly higher inflammatory burden than healthy controls, which significantly reduced
after root canal treatment. No significant change was detected in CH indices. (J Endod
2022;48:1020–1028.)
KEY WORDS
Apical periodontitis; hemogram; high-sensitivity C-reactive protein; neutrophil-lymphocyte
ratio; periapical healing; root canal treatment
Apical periodontitis (AP) is localized inflammation of periradicular tissue around the tooth1, which is usually
caused by a microbial infection of the dental pulp2. Contrary to its localized nature, there is a growing
body of evidence suggesting that AP may contribute to the total inflammatory burden of the body3. The
association of AP with altered metabolic control in diabetic patients4; endothelial dysfunction5;
unfavorable pregnancy outcomes6; and increased levels of numerous systemic markers, including high-
sensitivity C-reactive protein (hsCRP)7,8, interleukin (IL)-69, and tumor necrosis factor a10 has been
reported. However, there is a paucity of prospective studies on the topic. Root canal treatment is the
treatment of choice for AP. It involves the elimination of the microbial community within the confines of the
root canal and filling it with an inert material. The effect of root canal treatment on the systemic
inflammatory burden also remains unexplored so far, with very few studies reporting the effect of
JOE
Volume 48, Number 8, August 2022
endodontic treatment on markers of systemic
inflammation like C-reactive protein
(CRP)8,11,12, oxidative stress13, and
endothelial dysfunction14.
CRP is an acute-phase protein
produced by the liver in response to the
stimulus causing inflammation. It activates the
adaptive immune system by acting as a
pattern recognition molecule15. hsCRP is a
highly sensitive assay to detect CRP and is
considered a reliable marker for predicting
future cardiovascular diseases, such as
atherosclerosis16. In addition, it has been
studied for its role as a marker in many other
systemic illnesses, including stroke17, cancer18
and fibromyalgia19. Evidence of elevated CRP
levels caused by oral diseases such as
periodontitis, alveolar abscess, and
pericoronitis was first furnished by Boucher
et al20. Since then, numerous studies have
found increased CRP in the serum of patients
with periodontitis21. However, very few and
primarily cross-sectional studies have
evaluated the effect of AP on serum CRP
levels22. Although these studies suggest an
association of AP with increased levels of CRP,
the cause-effect relationship has not been
assessed yet because of the lack of
intervention studies23. Only recently has an
interventional study evaluated the levels of
hsCRP before and after root canal treatment in
patients with AP12. However, the lack of a
control group and a small sample size of 15
patients limit the generalization of the result.
The complete hemogram (CH) is a
routine biochemical test that provides valuable
information regarding the initiation and
progression of numerous pathophysiological
conditions24. CH indices including the
neutrophil-lymphocyte ratio (NLR), the mean
platelet volume (MPV), and the platelet-
lymphocyte ratio (PLR) are well-recognized
inflammatory markers used in varied diseases
as prognostic tools25. NLR is considered a
valuable marker of systemic inflammation and
a prognostic marker for numerous conditions
such as malignancy, cardiovascular disease,
and rheumatoid arthritis26. Its use as a marker
of oral inflammation is reported with marginal
periodontitis27. In an animal study, a significant
increase in lymphocytes in the presence of an
endodontic infection was observed28, whereas
a cross-sectional study in human subjects with
AP failed to find any difference in the neutrophil
count but reported a higher value of NLR in
patients with AP compared with healthy
control8. However, no prospective study has
attempted to study the association of CH
parameters such as NLR with endodontic
conditions and treatment outcomes. Thus, the
present study was designed to investigate
JOE
Volume 48, Number 8, August 2022
(1) the difference in the serum hsCRP level
and CH indices in patients with AP and
healthy controls and
(2) the effect of root canal treatment on
these parameters in patients with AP.
MATERIALS AND METHODS
The ethical approval for the study was
obtained from the Biomedical and Health
Research Ethics Committee of the Post
Graduate Institute of Dental Sciences, Rohtak,
Haryana, India (PGIDS/BHRC/20/4), and the
study protocol was registered with the
clinicaltrials.gov database (NCT04980768).
Sample Size
Considering the mean difference in the serum
hsCRP level between patients with AP
(2.88 6 1.06 mg/L)12 and healthy controls
(1.75 6 1.23 mg/L)8 from previous studies, the
effect size of 0.984 was calculated using
G*Power 3.1 statistical software (Heinrich-
Heine, Dusseldorf, Germany). A sample of 19
patients was then calculated with 90% power
and an alpha level of 5%. However,
considering attrition during follow-up, 25
subjects were recruited in both groups.
Study Population
Patients were enrolled between January and
March 2021. A total of 25 patients with AP (5
anterior teeth, 1 premolar, and 17 molars)
between 18 and 40 years of age were recruited
from the pool of patients reporting to the Out
Patient Department of Conservative Dentistry
and Endodontics, Post Graduate Institute of
Dental Sciences. The inclusion criteria were
patients diagnosed with apical periodontitis
with periapical index (PAI) scores 329 in a
single permanent tooth and pulp necrosis
verified by cold and electric pulp tests. Patients
were excluded if they were obese (body mass
index .30 kg/m2), smokers, pregnant, or
immunocompromised; had a medical history
of diabetes; or had any other systemic
inflammatory condition. Patients with marginal
periodontitis, moderate and severe gingivitis30,
teeth with a fracture, previous endodontic
treatment, or other ongoing dental treatment
were also excluded. A total of 25 healthy
controls were also randomly recruited and
matched in terms of age, sex, and physical
characteristics with the AP group.
A detailed medical examination and
tests by consultant physicians were
considered to rule out any acute or chronic
systemic inflammatory conditions, including
nephrotic syndrome, chronic renal failure,
cardiovascular disease, and type 1 or type 2
Serum hsCRP and CH Indices in Subjects with and without AP
diabetes mellitus31. All eligible and consenting
individuals signed a written informed consent
form after a detailed explanation of the
procedure, and the associated risks and
benefits were expounded to them. This was
followed by clinical examination of the oral
cavity, oral hygiene practice, and oral
prophylaxis. All patients underwent panoramic
radiographic examination to rule out AP in
more than 1 tooth. In addition, the pulp
sensibility tests, such as cold and electric tests,
along with percussion and palpation of the
affected tooth were performed. Standard
exposure parameters were used for periapical
radiographic examinations.
Periodontal clinical parameters,
including probing depths, the clinical
attachment level, and bleeding on probing at
the base of the crevice, excluding third molars,
were evaluated at 6 sites in all teeth. A manual
periodontal probe (UNC 15; Hu-Friedy,
Chicago, IL) was used for the periodontal
assessment. In addition, baseline evaluation of
hsCRP and CH parameters were performed
for all subjects participating in the study
followed by root canal treatment for patients
with AP.
Blood Samples and Laboratory
Analysis
Fasting blood samples were obtained by
venipuncture of the antecubital vein by a
trained phlebotomist 7 days after oral hygiene
practice and oral prophylaxis. The blood
sample was collected in 2 separate vacuum
blood collection tubes, 1 containing EDTA for
anticoagulation (K2-EDTA 1.8 mg/mL per
tube) and the other without any additive for
serum separation. Samples were submitted to
the clinical laboratory of the Department of
Microbiology, Post Graduate Institute of
Medical Sciences and the Department of Oral
Pathology, Post Graduate Institute of Dental
Sciences for the quantitative analysis of hsCRP
and CH analysis, respectively. The CH was
analyzed using a fully automatic hematology
analyzer (PROKAN; Shenzhen Prokan
Electronics Inc, Shenzhen, China), and an
enzyme-linked immunosorbent assay (ELISA)
kit (CalBiotech, El Cajon, CA) was used for
hsCRP assessment.
Technique for ELISA
ELISA is a sandwich enzyme immunoassay.
The whole blood sample was kept at 4 C and
centrifuged for 15 minutes at 6000 rpm for
serum separation. Serum was stored in
aliquots at 280 C until use. A serum hsCRP
assay kit was used. A monoclonal antibody
specific for these markers was precoated on
1021
FIGURE 1 – The study flowchart.

the microplate. The standard and sample were enzyme-linked polyclonal antibody specific for incubation period, amplifier solution was
pipetted into wells, and the immobilized hsCRP was added to the wells after washing added to the wells, and the color developed in
antibody bound any marker present. An away any unbound substances. After an proportion to the amount of hsCRP bound in

1022 Kumar et al. JOE
Volume 48, Number 8, August 2022

TABLE 1 - The Demographic Features of Participants swelling, sinus, and tenderness to palpation/
percussion were criteria for clinical success.
P
Variables Group 1 (AP) Group 2 (control) value
Statistical Analysis
Age 26.20 6 7.94 27.12 6 5.126 .326
Sex, n (%) Male: 15 (60) Male: 15 (60) .774 All statistical analyses were 2-tailed with a
Female: 10 (40) Female:10 (40) significance level set at .05. SPSS statistical
Body mass index 22.92 6 2.89 22.60 6 2.34 .801 software (v.20; SPSS/IBM, Armonk, NY) was
used for analyses. Nonparametric tests were
applied because data were nonnormally
distributed on evaluation with the Kolmogorov-
Smirnov test. The Mann-Whitney U test for
the initial stage. The intensity of the color was Follow-up continuous variables and the chi-square test
measured. Follow-up evaluation including a reassessment
for categoric variables were applied. The
of hsCRP, CH indices, and periapical healing
Spearman correlation test was used to analyze
was performed at 6 months. The control group
the relation between hsCRP, PAI score, NLR,
Root Canal Treatment was not subjected to additional biochemical
and periapical healing. Changes in parameters
Local anesthesia (2% lidocaine with tests for ethical reasons.
including hsCRP, NLR, and PAI score were
1:100,000 epinephrine) was administered also calculated, and the correlation between
followed by access cavity preparation under Assessment of Treatment Outcome them was investigated. Multivariate binomial
rubber dam isolation. Root canal orifices were Treatment outcome was assessed using a logistic regression was applied to assess the
explored and negotiated with #10 and #15 K- combination of PAI scores on radiographs and effect of predictor variables (age, sex, white
files. The working length was measured using clinical signs and symptoms32. Two blood cell [WBC] count, platelet count, NLR,
an apex locator (Root ZX; J Morita, Kyoto, independent and calibrated observers PLR, MPV, hsCRP, and PAI score at baseline)
Japan) and confirmed by radiography. Next, assigned PAI scores to all teeth. In the case of on the dependent variable (periapical healing).
root canal preparation was performed multirooted teeth, each root was assigned a The goodness of fit of the regression model
following the crown-down technique using separate score, and the highest score was was verified with the Hosmer-Lemeshow
rotary endodontic files (Navigator Evo, Medin, considered for final evaluation. Patients with a statistic. Multiple linear regression was also
Czech Republic). Irrigation was performed PAI score of 3 (changes in bone structure with applied to assess the effect of independent
intermittently with 27-G side-vented needles some diffuse demineralization), 4 (apical variables (age, sex, BMI, PAI score, and
using 3% sodium hypochlorite (Parcan; periodontitis with the well-defined radiolucent presence/absence of AP) on the hsCRP level
Septodont, Maharashtra, India). After the final area), and 5 (severe apical periodontitis, with (dependent variable) and the change in hsCRP
irrigation with 5 mL distilled water, root canals exacerbating features) were only considered level in the intervention group.
were dried with paper points and obturated healed when it changed to either score 2 (small
with laterally condensed gutta-percha (Meta changes in bone structure with no
Biomed Co Ltd, Chungcheongbuk-do, demineralization) or 1 (normal periapical RESULTS
Korea) and zinc oxide eugenol sealer. The structures). The PAI scores at 6 months were
A total of 25 patients with AP and 25 healthy
final coronal restoration was performed with further dichotomized into healed (PAI 2) and
controls (15 men and 10 women) were
composite resin (Filtek P60; 3M ESPE, St nonhealed (PAI 3). Clinical signs and
recruited for the study. In the AP group, 3
Paul, MN). symptoms including the absence of pain,
patients were lost to follow-up (Fig. 1). The
demographic details are outlined in Table 1.
There was a statistically significant difference in
TABLE 2 - A Comparison of the Laboratory Parameters of Participants in the Apical Periodontitis (AP) and Control the mean levels of hsCRP of 1.66 mg/L
Groups between the control (1.69 6 2.20 mg/L) and
AP (3.37 6 2.69 mg/L) groups at baseline
Group 1 (AP) Group 2 (Table 2). CH parameters, WBC count, MPV,
Before treatment Posttreatment (Control) and the platelet count were within the
reference range with a nonsignificant
Variables (n 5 25) (n 5 22) (n 5 25) difference (P . .05) between the groups at
WBC count (10 /L) 9
7.55 6 1.41 6.90 6 1.53 6.90 6 1.36 baseline. NLR was significantly higher in the AP
Neutrophil 1.86 6 1.25* 1.99 6 0.77† 1.34 6 0.47 group at baseline. At the 6-month follow-up
lymphocyte ratio after root canal treatment in the AP group, the
Platelet count 236.44 6 82.46 218.45 6 95.96 249.44 6 50.65 mean hsCRP level was significantly reduced by
Mean platelet 9.82 6 0.95 10.11 6 0.97‡ 9.56 6 0.60
1.56 mg/L from baseline (P , .05) (Table 2).
volume (fL)
hsCRP (mg/L) 3.37 6 2.69§ 1.79 6 1.65k 1.69 6 2.2 The 6-month success rate was 100% based
PAI 3.88 6 0.60 2.32 6 0.839k — on clinical signs and symptoms. However,
radiographic success was 72.2%, with 16 and
hsCRP, high-sensitivity C-reactive protein; PAI, periapical index; WBC, white blood cell. 6 patients classified as healed (Fig. 2) and
*Statistically significant versus controls (P 5 .024). nonhealed, respectively. Table 3 outlines the
†
Statistically significant versus controls (P 5 .001).
‡
Statistically significant versus controls (P 5 .030).
biochemical parameters and PAI score
§
Statistically significant versus controls (P 5 .007). difference between the healed and nonhealed
k
Statistically significant versus before treatment for AP (P 5 .000). patients. The mean PAI score reduced from

JOE
Volume 48, Number 8, August 2022 Serum hsCRP and CH Indices in Subjects with and without AP 1023
FIGURE 2 – (A and B ) Preoperative and (C and D ) 6-month follow-up radiographs showing periapical healing.
3.88 at baseline to 2.32 at follow-up, which
was statistically significant (P , .05).
The risk factors for developing future
cardiovascular events were categorized into
no (,1 mg/L), intermediate (1–3 mg/L), and
high (.3 mg/L) risk based on the levels of
hsCRP (Table 4). In the control group, the
proportions of subjects categorized as no,
intermediate, and high risk were 56%, 24%,
and 20%, respectively. In the AP group, there
were more patients in the high-risk (44%)
category than intermediate and no (28% each)
risk (Table 4). However, this difference was
nonsignificant (P . .05). At the 6-month follow-
up after root canal treatment, 50% of patients
from both the high- (n 5 5) and intermediate-
risk (n 5 3) categories lowered their
cardiovascular disease risk status. One patient
from the low-risk category was reassigned to
1024 Kumar et al.
the intermediate-risk category after an increase
in hsCRP.
None of the factors (age, sex, WBC
count, platelet count, NLR, PLR, MPV, hsCRP,
and PAI score at baseline) analyzed in the
binary logistic regression analysis had a
significant effect on success. The linear
regression results were nonsignificant with
respect to independent variables on the levels
of hsCRP at baseline and at follow-up in the AP
group. A significant correlation between AP
and baseline hsCRP was observed (P , .05),
whereas a nonsignificant correlation was
observed with the severity of AP (PAI score)
and hsCRP as well as with NLR (P . .05). At
the 6-month follow-up in the AP group, the
correlation between hsCRP and PAI score/
healing was nonsignificant (P . .05). In
addition, a nonsignificant correlation between
the change in PAI score and the change in
hsCRP level in the AP group (P . .05) was
observed.
DISCUSSION
The immune response in AP is mediated by
inflammatory markers that may also add to the
overall inflammatory burden of the body,
leading to the development or progression of
systemic conditions22. However, this
association is observed mainly in a cross-
sectional study, which is limited by its nature in
establishing a cause-effect relation16 and
temporality23. A prospective study in which
patients are followed before and after the
endodontic intervention is required to satisfy
Hill’s criteria of causation33. Therefore, this
study was designed to assess the effect of AP
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Volume 48, Number 8, August 2022
TABLE 3 - A Comparison of the Laboratory Parameters and Periapical Index (PAI) Score of Participants in the Apical
Periodontitis Group with Healed and Nonhealed Periapical Lesions at the 6-Month Follow-up
Variables Healed (n 5 16)
WBC count (109/L) 6.81 6 1.73
Neutrophil 2.08 6 0.80
lymphocyte ratio
Platelet count 227 6 86.10
Mean platelet 9.96 6 0.55
volume (fL)
hsCRP (mg/L) 1.66 6 1.86
PAI 1.87 6 0.34
hsCRP, high-sensitivity C-reactive protein; WBC, white blood cell.
Bold value signifies significant difference between two groups.
and root canal treatment on the combination of
inflammatory markers derived from CH
parameters and serum levels of hsCRP before
and after root canal treatment. The results of
this study show that mean hsCRP levels are
significantly higher in patients with AP, which
are significantly reduced after root canal
treatment. The hemogram indices were within
the normal range in both subjects with and
without AP.
One of the significant drawbacks in the
literature evaluating the association between
AP and inflammatory markers is the presence
of confounders. Because levels of
inflammatory markers are prone to change
because of the slightest change in lifestyle34,
complete elimination of confounders may not
be possible. However, strict inclusion criteria
like a single tooth with AP and the absence of
any local or systemic inflammatory state
combined with patient education and lifestyle
monitoring allowed us to control confounders
in the present study. Previous studies have
reported higher levels of hsCRP in patients
with marginal periodontitis; therefore, they
were excluded from the present study.
Gingivitis was eliminated by scaling, and blood
samples were obtained after 1 week of the
treatment. Root canal treatment was
performed by a single operator using a
standardized protocol, and all biochemical
tests were performed at a single laboratory to
reduce methodological variations.
TABLE 4 - The Proportion of Subjects Classified in 3 Categories of Risk for Future Cardiovascular Events Based on the
Level of Serum High-sensitivity C-Reactive Protein in Both Groups
Groups No risk (,1 mg/L)
Control (n 5 25) 56 (14)
Apical periodontitis 28 (7)
(before treatment)
(n 5 25)
Apical periodontitis 39.13 (9)
(after treatment)
(n 5 22)
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Volume 48, Number 8, August 2022
P extrapolating their results. Nonetheless, the
Nonhealed (n 5 6) value
7.15 6 0.90 .407
1.75 6 0.71 .329
195 6 124.82 .231
10.51 6 1.66 .641
2.14 6 0.95 .098
3.50 6 0.54 .000
A significantly higher level of hsCRP was
found in patients with AP (3.36 mg/L) than in
healthy controls (1.69 mg/L), which is
consistent with the findings of previous
studies7,8. In addition, a significant correlation
was found between hsCRP and AP. However,
the correlation with the severity of AP was
nonsignificant. This is in contrast to the finding
of Sirin et al8, who reported a moderate
correlation between AP severity and hsCRP
level. The inclusion of multiple teeth with AP
(22%) and a higher proportion of teeth with a
PAI score of 5 (21%) in the previous study
compared with the inclusion of only a single
tooth with AP and a small proportion of teeth
with a PAI score of 5 (16%) in the present study
may have attributed to this finding.
The possible mechanism for increased
CRP levels in patients with periapical lesions is
not clear; however, it can be hypothesized that
infected pulp activates immune cells that
release numerous inflammatory mediators
such as interleukins (IL-1 and IL-6), tumor
necrosis factor a, and interferons35. IL-6, 1 of
the proinflammatory cytokines released in the
periapical region, induces secretion of CRP by
hepatocytes. This assumes significance
because raised CRP levels are strongly
associated with the risk of developing
cardiovascular disease. A recent study
reported a significant association of
endodontic inflammatory conditions with a first
myocardial infarction36. However, this study
Intermediate risk High risk
(1–3 mg/L) (.3 mg/L)
24 (6) 20 (5)
28 (7) 44 (11)
34.79 (8) 26.08 (5)
Serum hsCRP and CH Indices in Subjects with and without AP
had limitations (eg, it included patients with
wide variations in their oral and systemic
health), so caution is advised while
fact that AP leads to increased levels of
important systemic markers including hsCRP
calls for its early and sound clinical
management to minimize its repercussions on
general health.
A systematic search of the literature by
Georgiou et al22 found only 8 intervention
studies that evaluated the effect of
inflammatory markers before and after
treatment in patients with AP. However,
treatments were not standardized and ranged
from antibiotic prescription to surgical
endodontic treatment and extractions. Root
canal treatment was performed in only 4
studies11,13,37,38 and in 1 study13 it was
performed in all included patients, potentially
introducing a source of bias. The markers
evaluated in these studies were immune
complex and complement factor 337,38,
reactive oxygen species13, and CRP11. There
was significant heterogeneity in terms of the
time point for the evaluation of these markers
after treatment, ranging from 7–365 days after
treatment. The results of these studies were
mixed, with 2 reporting no difference in the
levels of markers11,37 and the other 2 reporting
significant differences before and after
treatment13,38. CRP was studied in an
intervention study design by 2 studies in the
past with significant differences in the study
design and methodology. The results of both
these studies were contrasting, with no
significant difference noted using the rapid
chairside method and a significant difference
reported by another study using ELISA. Also,
periodontal health was not controlled in the
previous study, root canal treatment was
performed for only 1 patient, and re-evaluation
was performed only after 7 days. In the present
study, a significant reduction in hsCRP levels
was observed after root canal treatment,
which is consistent with the findings of a
previous study12. Periapical healing was
assessed using a combination of radiographic
and clinical findings. The PAI score was relied
on for grading radiographic success, whereas
the absence of signs and symptoms was used
to assess clinical success. At the 6-month
follow-up, the success rate was 73.9%, which
is expectedly lower because periapical healing
takes up to 4 years to heal in some cases
completely.
The risk status of patients with AP was
higher for future cardiovascular events
because a higher proportion of patients were in
an intermediate- and high-risk group
compared with healthy controls. The risk was
reduced in 50% of patients. The risk status
1025
reduction was more apparent in the high-risk
group after root canal treatment. For the
majority of patients, the risk status remains
unchanged. The previous study also reported
an unchanged risk status after root canal
treatment in about one third of the total
patients. However, root canal treatment led to
the lowering of the hsCRP level in most
patients (87%) to some extent in the present
study, highlighting the possible causal role of
endodontic infection in the overall inflammatory
burden. A large-scale study may be required in
the future to corroborate these findings.
The CH indices were within the
reference range in both groups. This is in
contrast to the findings of previous studies that
have reported a significant difference in some
parameters. For example, in animal studies, a
significant difference in the leukocyte,
neutrophil, and lymphocyte counts was
observed between rats with and without
AP24,28. However, in 1 study, the difference
was only significant with rats having multiple
teeth with AP and not with rats having a single
AP28. In a case-control study, all blood
parameters were similar across groups,
including controls and patients with varied
numbers and severity of AP, except for the
NLR value, which was significantly higher
(2.46 6 1.34) in patients with at least 1 tooth
with a PAI score of 5 compared with controls
without AP (1.85 6 0.80)8. Although NLR was
higher in patients with AP in the present study,
it was within the reference range of 339. The
different results of the present study can also
be explained by the inclusion of only 1 tooth
with varying severity of AP.
Although strict criteria for enrollment
minimized the chances of confounding results,
values of hsCRP can be affected by a range of
factors, such as insomnia, depression,
nutritional deficiencies, and chronic parasitic
infections40, that are very difficult to control.
However, an attempt was made to mitigate
these effects by following strict eligibility criteria
for patient recruitment, meticulous selection of
matched controls, and limited methodological
variations. The small sample size and relatively
smaller follow-up period may be some of the
drawbacks of this study. Also, the inclusion of
hospital-based controls may be a source of
selection bias because they may have
underlying diseases or conditions unrelated to
AP. Furthermore, only CH parameters and
hsCRP were evaluated, leaving some other
important markers of systemic inflammation
such as oxidative stress unanalyzed. Also,
because only a single tooth with AP was
included, the cumulative effect of multiple teeth
with AP may be studied in future studies.
Future research should also focus on the
assessment of the levels of different
inflammatory markers in patients with varied
systemic conditions and AP. Well-planned
intervention studies are also required to
establish a temporal relation between systemic
disease and AP. Furthermore, these findings
suggest the inclusion of endodontic diagnosis
and a treatment protocol for the management
of AP in cardiac patients to minimize the
systemic inflammatory burden.
ACKNOWLEDGMENTS
The authors acknowledge the support of the
Multi-disciplinary Research Unit, Post
Graduate Institute of Medical Sciences,
Rohtak. Haryana, India.
The authors deny any conflicts of
interest related to this study.

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