Research on changes in levels of non specific inflammatory markers in patients with acute coronary syndrome

Journal of military pharmaco-medicine no1-2018

RESEARCH ON CHANGES IN LEVELS OF NON-SPECIFIC
INFLAMMATORY MARKERS IN PATIENTS WITH ACUTE
CORONARY SYNDROME
Nguyen Thi Thanh Thuy*; Pham Nguyen Vinh**; Pham Manh Hung***
SUMMARY
Objectives: To investigate serum levels of some inflammatory markers (CRP-hs, C3, C4, and
Interleukin (IL)-6 in patients with acute coronary syndrome (ACS). Subjects and Methods:
Serum levels of CRP-hs, C3, C4, and IL-6 in blood samples taken from 100 patients with ACS
(on hospital admission, and at 6 months after treatment) and 50 healthy people (served as
normal controls) were quantified using immuno-chemiluminescense technique. Results: Serum
levels of CRP-hs, C3, C4, and IL-6 were significantly higher in patients with ACS compared to
those in controls. After 6 months of conventional treatment, CRP-hs and IL-6 levels significantly
decreased compared to those before treatment. Conclusions: Serum level of IL-6 và CRP-hs in
patients with ACS reflected the treatment response, and thus, may serve as biomarkers for
treatment evaluation in patients with ACS
* Keywords: Coronary artery disease; Acute coronary syndrome; Inflammatory markers.

INTRODUCTIONS
Coronary artery disease (CAD) is one
of the diseases that has increased in
prevalence and become more common in
developed as well as developing
countries, including Vietnam. The disease
is believed to account for a large number
of death in hospital inpatients. CAD
includes ACS and stable coronary artery
disease. Pathogenesis of CAD involves
artherosclerosis with damaged vessel wall
of the coronary arteries, leading to vessel

occlusion by thrombosis, and eventually,
myocardial infarction [3, 8].
Recent data showed that inflammation
plays an important role in initiation as well

as progression of ACS [6, 7]; investigation
of level of inflammatory markers in serum
of patients with ACS would be of importance
in elucidating the pathogenesis of the
disease. Among the inflammatory markers,
CRP-hs has been proven to be associated
with the risk of cardiovascular events. In
addition to CRP, however, some other
inflammatory markers may be involved in
pathogenesis of the disease. In the present
study, we investigated the changes in
serum level of complement C3, C4 and IL-6
in patients with acute coronary syndrome
after treament, in order to determine a
relationship between the inflammatory
markers and the disease progression.

* Institute of Heart , Hochiminh City
** Pham Ngoc Thach Medical College
*** Vietnam General Association of Medicine and Pharmacy
Corresponding author: Nguyen Thi Thanh Thuy ()
Date received: 03/11/2017
Date accepted: 18/12/2017

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Journal of military pharmaco-medicine no1-2018
SBJECTS AND METHODS
1. Subjects.
The study has been carried out on 100
patients with ACS, who hospitalized and
treated at Institute of Heart, Hochiminh
City during the period from October 2011
to October 2013, and 50 healthy people
without ACS who have undergone medical
examination at the Hospital at the same
period of time, serving as controls.
* Inclusion criteria for patients:
- Patients who were confirmatorily
diagnosed to have ACS, and were
indicated to undergo emergent coronary
intervention.
- Patients who had one or more occluded
coronary artery branches and were
indicated to undergo coronary artery
bypass surgery or coronary intervention.
- Patients with ACS who were indicated
to undergo treatment by internal medicine.
* Exclusion criteria for patients:
- Patients who were infected.
- Patients who had concurrent
inflammatory diseases, such as arthritis,
goute, bronchitis, etc.
* Selection criteria for controls: Healthy

people who had periodical medical
examination at the hospital during the
period of the study, without cardiovascular
diseases.
2. Methods.
* Study design:
This is a prospective study, in which
the patients’ samples were taken 2 times:
first time at hospital admission, and second
164

time at 6 months after treatment, either by
internal medicine or coronary intervention.
- Group 1: 100 patients with CAD.
- Group 2: 50 healthy people without
cardiovascular diseases, serving as control
group.
Among the CAD patients, 37 patients
were followed for 6 months after treatment
at Institute of Heart Diseases, Hochiminh
City.
* Studied parameters:
- Serum level of inflammatory
markers C3, C4, IL-6, and CRP-hs at
hospital admission, measured by
immunochemiluminescence assay (for
C3, C4 and IL-6) or immunoturbidimetric
method (for CRP-hs), using reagents from
Roche Diagnostics.
- Data analysis: by STATA 12 statistical

software.
RESULTS AND DISCUSSIONS
1. Patients’ characteristics.
Among 100 CAD patients involved in
the study, 66 (66%) were male. The
average age of the patients was 63.67 ±
11.7, which was believed to be the age of
most prevalent of CAD, according to
recent papers [9, 10].
Among 37 patients being followed up
after treatment, the average age of the
patients was 63.0 ± 11.29, with 24/37
(65%) were male. 15/37 patients
(40.54%) had elevated ST on ECG; 18/37
patients (48.65%) had non-ST elevation,
and 4/37 patients (10.8%) had ACS.


Journal of military pharmaco-medicine no1-2018
2. Serum levels of C3, C4.
Table 1: Serum levels of C3 and C4.
Patients group (n = 100)

Control group (n = 50)

p

Mean ± SD

Mean ± SD

C3 (mg/dL)

130.326 ± 26.4

99.056 ± 17.9

< 0.001

C4 (mg/dL)

31.41 ± 9.01

22.332 ± 7.4

< 0.001

Serum levels of C3 and C4 in patient group were significantly higher than those in
control group (p < 0.001)
3. Serum levels of IL-6 and CRP-hs.
The levels of IL-6 and CRP-hs in serum samples from the CAD patients did not
show a standard Gauss’s distribution pattern. The median and 25, 75 percentile values
of the IL-6 and CRP-hs levels were presented in table 2.
Table 2: Serum levels of IL-6 and CRP-hs.

IL-6 (pg/mL)
CRP-hs (mg/L)

Patient group (n = 100)

Control group (n = 50)

p

Median [25%; 75%]

Median [25%; 75%]

13.885 [6.11; 42.105]

1.5 [1.5; 1.65]

< 0.001

7.6 [2.5; 31.25]

0.8 [0.3; 1.3]

< 0.001

Median values of CRP and IL-6 levels in serum from patients were significantly
higher than those from controls (p < 0.001).
4. Relationship between levels of
inflammatory markers C3, C4, IL-6 and
CRP and patients’ status.
There was a significant relationship
between serum levels of CRP and C4, IL6 (p < 0.001). However, no relationship
between CRP and C3 levels was observed
(p = 0.065).
It was revealed by our data presented

in this study that levels of C3, C4, IL-6
and CRP significantly elevated in patients
with ACS, and there was close relationship
between these parameters. These results
were in agreement with data published
previously [8, 9]; particularly, the increase

of serum IL-6 was also recently reported
by Vu Tien Thang [5]. IL-6 is a
proinflammatory cytokine which has been
intensively studied in recent years. Serum
level of IL-6 is elevated in various
inflammatory diseases, including infection.
Although not a specific marker for ACS,
the elevation of IL-6 may suggest a close
relationship between inflammatory response
and ACS. By deeper researching, several
authors have proposed a hypothesis that
the inflammatory factors present in ACS
may lead to artherosclerotic plaque rupture,
which eventually causes myocardial infarction.
However, conclusive studies are needed,
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Journal of military pharmaco-medicine no1-2018
since the myocardial ischemia as well as
necrosis caused by myocardial infarction
may trigger an inflammatory response. On
the other hand, it was believed by several

other authors that changes in level of

some inflammatory markers may help
evaluating the disease's progression as
well as prognosis, and thus, determination
of inflammatory markers in serum maybe
helpful in management of ACS [11].

5. Serum levels of C3, C4 before and after treatment.
Table 3: Serum levels of C3 and C4.
Before treatment

After treatment

p

(n = 37)

(n = 37)

C3 (mg/dL)

133.86 ± 28.08

132.73 ± 22.4

0.7430

C4 (mg/dL)

32.7 ± 10.3

31.8 ± 7.8

0.3869

Serum levels of C3 and C4 after treatment and those before treatment were not
significantly different (p = 0.7430 and 0.3869 for C3 and C4 levels, respectively).
6. Serum levels of IL-6 and CRP-hs before and after treatment.
Table 4: Serum levels of IL-6 and CRP-hs.

IL-6 (pg/mL)
CRP-hs (mg/L)

Before treatment

After treatment

(n = 37)

(n = 37)

Median [25%; 75%]

Median [25%; 75%]

16.59 [7.42; 45.69]

3.99 [2.89; 6.29]

< 0.001

8.7 [3.4; 26.5]

1.3 [0.8; 3.5]

< 0.001

Serum levels of IL-6 and CRP-hs after
treatment significantly lower than those
before treatment (p < 0.001), which was
in agreement with data from Vu Tien
Thang [4]. A significant decrease in IL-6,
CRP levels after treatment which was not
similarly observed with C3 and C4 levels
suggested a more specific association of
IL-6 and CRP-hs levels in ACS than C3
and C4, and this requires further studies
for more conclusive data.
Regarding the sources and roles of
inflammatory factors, IL-6 stimulates
166

p

hepatocytes to produce acute phase
proteins, including CRP, during the acute
phase of inflammatory repsonse. IL-6 level
is early elevated in most patients. Previous
studies indicated that serum IL-6 level

elevated during the first days and then quickly
declined; meanwhile, CRP level elevated
later and remained high for longer time.
Serum C3 and C4 levels elevated during
acute phase and declined after treatment,
yet not significantly. The increase in CRP,
IL-6, C3 and C4 levels was in agreement
with data previously published [8, 12].


Journal of military pharmaco-medicine no1-2018
After 6 months of treatment, a decline
of all investigated inflammatory markers
was observed in all ACS patient groups.
The severity of inflammation was likely to
decrease due to effective anti-inflammatory
therapy using both statin and aspirin.
CONCLUSIONS
- There was a significant elevation in
serum levels of C3, C4, IL-6 and CRP in
patients with acute coronary syndrome
- There was a significant relationship
between the elevation of C4, IL-6 level
and that of CRP, but not with the elevation
of C3 and CRP.
- After treatment, IL-6 and CRP-hs
levels significantly declined, but C3 and
C4 levels did not.
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