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.
Trang 1RESEARCH 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 (thuylabo@yahoo.com)
Date received: 03/11/2017 Date accepted: 18/12/2017
Trang 2SBJECTS 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
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
Trang 32 Serum levels of C3, C4
Table 1: Serum levels of C3 and C4
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
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,
IL-6 (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,
Trang 4since 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 (n = 37)
After treatment (n = 37)
p
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
Before treatment (n = 37)
After treatment (n = 37)
p
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
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]
Trang 5After 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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