American Journal Of Biomedical Science & Pharmaceutical Innovation
28
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VOLUME
Vol.05 Issue01 2025
PAGE NO.
28-31
10.37547/ajbspi/Volume05Issue01-07
Dynamics of immuno-inflammatory markers in patients
with chronic heart failure after myocardial infarction
during treatment with rosuvastatin
M.M. Abdurakhmanov
Bukhara State Medical Institute, Karakul College of Public Health named Abu Ali ibn Sino, Bukhara, Uzbekistan
A.N. Khamraev
Bukhara State Medical Institute, Karakul College of Public Health named Abu Ali ibn Sino, Bukhara, Uzbekistan
M.S. Radjabova
Bukhara State Medical Institute, Karakul College of Public Health named Abu Ali ibn Sino, Bukhara, Uzbekistan
Received:
26 October 2024;
Accepted:
29 December 2024;
Published:
30 January 2025
Abstract:
In the occurrence and progression of chronic heart failure (CHF), the role of pro- inflammatory cytokines
has been established: tumor necrosis factor-
α (TNF
-
α) and interleukin
-6 (IL-6), which induce the synthesis of C-
reactive protein (CRP), an increasing the level of these markers leads to the progression of CHF. It was determined
that with the development of the maladaptive phase of left ventricular remodeling, there is a sharp rise in the
level of pro- inflammatory cytokines and serum CRP, which are closely interrelated with the structural and
functional changes of the left ventricle in CHF. Against the background of taking rosuvastatin at a daily dose of 20
mg, there is a decrease in the levels of pro-inflammatory cytokines and serum CRP and a positive dynamics of
heart remodeling indicators.
Keywords:
Systemic inflammation, left ventricular remodeling, rosuvastatin, chronic heart failure.
Introduction:
In addition to the cardiac, hemodynamic
and neurohumoral concepts of progressive chronic
heart failure (CHF) has been developed the theory of
immune activation, according to that, endothelial
dysfunction is recognized as one of the main links in the
pathogenesis of CHF, induced by oxidative stress and
pro- inflammatory cytokines that suppress the
production of nitric oxide (NO) [1,3,7]. In the
occurrence and progression of CHF, the role of pro-
inflammatory cytokines has been established: tumor
necrosis factor-
α (TNF
-
α) and interleukin
-6 (IL-6) [4,9].
The biological effects of these cytokines
are largely similar: they induce the synthesis of C-
reactive protein (CRP), an increasing the level of those,
in turn, leads to the progression of CHF [6]. Many
authors suggest that pro- inflammatory cytokines play
an important role in the progression of CHF, mediating
the nature and intensity of myocardial and vascular
remodeling processes by regulating the level of
apoptosis of cardiomyocytes, which is currently
considered as a fundamental mechanism capable of
causing irreversible impairment of myocardial
contractile activity in CHF [5].
The aim of the study was to study the clinical and
laboratory significance of immuno- inflammatory
markers (CRP, IL-6 and TNF-
α) in patients with CHF
during the treatment with rosuvastatin.
METHODS
96 patients with CHF stages I
–
IIB and functional class I
–
IV were examined in the cardiology department of the
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American Journal of Applied Science and Technology (ISSN: 2771-2745)
Bukhara Regional Center of the Republican Scientific
Center for Medical Emergencies in Bukhara. There
were: 85 men and 11 women, aged 40 to
80 years (mean age 60.73 ± 9.86 years). Previously, all
patients had suffered a myocardial infarction (MI) of
various statutes of limitations - from 1 to 21 years
(average 10.61
± 7.26 years). Criteria for inclusion in the study: the
presence in patients of CHF of ischemic etiology. To
objectify FC CHF, a test with a 6- minute walk in a 35-
meter long corridor marked every 5 meters was carried
out and the clinical condition of patients was assessed
according to the modified V.Yu. Mareev in 2000 on the
clinical assessment scale (SHOKS) in CHF. Drug
treatment included angiotensin- converting enzyme
inhibitors, β
-blockers, diuretics, if necessary, nitrates,
cardiac glycosides. At the time of inclusion in the study,
patients did not take lipid-lowering drugs or stopped
taking them for various reasons at least 6 weeks before
the study. All patients were prescribed rosuvastatin
(Mertenil, Gedeon Richter company) at a daily dose of
20 mg once. The duration of therapy was 12 weeks,
after that all patients were re-examined. All of them
underwent a general clinical examination, which
included the collection of anamnesis and assessment of
objective data; complex ultrasound examination of the
heart.
The following indicators were determined:
final systolic and diastolic dimensions (FDD, FSD, cm)
and volumes (FDV, FSV, ml) of the left ventricle (LV);
ejection fraction (EF, %); the thickness of the
interventricular septum in systole and diastole (IVSd,
IVSs, mm); thickness of the posterior wall in systole and
diastole (ThPWs, ThPWd, mm); the myocardial mass of
LV (MM, g); stroke volume (SV, ml); minute volume
(MV, ml/min). The relative thickness of wall (RTW) of
the LV was calculated using the formula: RTW = (IVSd +
ThPWd)/FDD. Systolic myocardial stress (MS in
dynes/cm2) was calculated using the formula: MS = BPs
× FSD/4 × ThPWs × ( 1 + ThPW/FSD), where BPs is
systolic blood pressure. To assess myocardial
contractile activity, the EF/MS index proposed by K.
Taniguchi and co-authors was used. (2000) , which
reflects the degree of adequacy of the global systolic
function of the heart to the test load with a given LV
geometry [10].Diastolic properties of LV were studied
using the study of transmitral diastolic flow (TMDF) by
determining the maximum TMDF velocity during early
LV filling (Ve, m/s), the maximum TMDF velocity during
late LV filling (Vа, m/s), the ratio of maximum velocities
flows in the period of early and late filling (E/A), time of
isovolumic relaxation of the left ventricle (TIR, ms). The
content of CRP (Vector-Best, Russia) and pro-
inflammatory cytokines: TNF-
α and IL
-6 (Protein
contour, St. Petersburg) were determined in the blood
serum of patients by enzyme immunoassay using
appropriate test systems. When examining a group of
healthy people, the average levels of IL-6 (7.27
± 0.42 pg/ml) and TNF-
α (4.62 ± 0.19 pg/ml) were
determined. Data analysis was carried out using
parametric and nonparametric statistical methods.
After a preliminary analysis of the distribution of the
studied features for normality, the mean value (M) and
standard error (m) were calculated. The significance of
the differences between the compared parameters
was calculated using the method of variation statistics
according to Student's t-test. The difference between
the compared indicators was taken as reliability p <
0.05. To identify correlations between the
differences and the parameters, a calculation was
carried out using the Pearson squares method. The
correlation between the estimated parameters was
considered reliability at p < 0.05.
RESULTS AND DISCUSSION
All patients were divided into 2 groups depending on
the severity of left ventricular remodeling according to
echocardiography, according to OSSN criteria (2010).
Group 1 included 67 (69%) patients with adaptive LV
remodeling (stages I
–
IIA), group 2 included 29 (31%)
patients with incompatible LV remodeling (stage IIB).
During the observation period, 6 (6.25%) adverse
cardiovascular events occurred. 2 patients of group 1
and 4 patients of group 2 died. The cause of death of
one patient from group 1 was complex arrhythmias, the
other - complications of myocardial infarction. In group
2, the cause of death was progressive heart failure.
From the presented data, it can be seen that patients
with maladaptive remodeling had significantly more
severe manifestations of CHF: a higher FC of circulatory
failure and a more significant decrease in exercise
tolerance. It was also noted that the development of
CHF is accompanied by a change primarily in the
geometry of the LV and an increase in the mass of the
LV myocardium. As CHF progressed, an increase in the
linear dimensions of the LV cavity was observed. In
patients with the development of maladaptive
remodeling, there was a decrease in the relative LV wall
thickness index, which indicates the development of
eccentric hypertrophy of LV and the progression of
maladaptive remodeling LV , the severity of which
increases with the increase in CHF FC. In patients with
adaptive LV remodeling, concentric hypertrophy of LV
prevailed (77%), and in 23% of cases in this group of
patients, the development of eccentric hypertrophy of
LV was noted. In the study of diastolic function, it was
found that the 1st type of diastolic dysfunction
American Journal of Applied Science and Technology
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American Journal of Applied Science and Technology (ISSN: 2771-2745)
prevailed in patients with adaptive LV remodeling, and
the 2nd type prevailed in patients with maladaptive LV
remodeling. Changes in the levels of the studied
cytokines in the blood serum and the concentration of
CRP in patients with CHF were characterized by their
significant increase with the progression of CHF (Table
1).
The maximum level of cytokines (TNF-
α
and IL-6) was found in patients with maladaptive left
ventricular remodeling. In patients with adaptive LV
remodeling, there was also an increase in the level of
TNF-
α in blood serum, but i
t was insignificant
compared to the group of healthy individuals. There
was no significant difference in the level of IL-6 with the
group of healthy subjects. The level of CRP in the blood
serum before treatment was increased both in group 1
and in group 2, and amounted to 25.99 ± 16.3 and 43.41
± 11.19 mg/l, respectively, which is significantly higher
than normal values.
Table 1.
Dynamics of inflammation markers and laboratory parameters before and after treatment with rosuvastatin
Note LDL - low density lipoproteins; TAG, triacyglycerides;
Significant difference (p < 0.05) from pre- treatment
scores; ** Significant difference (p < 0.05) from the
same indicator in group 1.
We have established a relationship bet- ween the levels
of pro-inflammatory cytokines in the blood serum and
the morpho-functional parameters of the left ventricle.
In the group of patients with maladaptive remodeling,
a correlation between TNF-
α and myocardial mass was
noted (r = 0.65; p < 0.05); MS (r = 0.63; p < 0.05); with
the state of diastolic function: peak E and E/A (r = 0.72;
p < 0.05, r = 0.58; p < 0.05).
There was no connection with EF, but there was a
correlation with the EF/MS index, which characterizes
the specific contractility of the myocardium (r = 0.46; p
< 0.05). In patients with adaptive LV remodeling, IL-6
correlated with MS (r = 0.39; p < 0.05) and LV wall
thickness (r = 0.75; p < 0.05), while TNF-
α correlated
with LDL (r = 0.41; p < 0.05) and TAG (r = 0.38; p < 0.05).
Thereafter, the results of this study demonstrated that
the levels of pro- inflammatory cytokines in the serum
of patients with CHF are associated with the
development and severity of clinical manifestations of
CHF. A previously undescribed abrupt increase in
serum pro- inflammatory cytokines was found in
patients with maladaptive LV remodeling.
Against the background of taking rosuvastatin at a daily
dose of 20 mg, a positive trend in the clinical
manifestations of CHF was noted, which was
characterized by a significant decrease in the FC of CHF
and an increase in exercise tolerance according to the
test with a 6-minute walk in both group 1 and group 2.
There was a significant decrease in myocardial mass,
and a decrease in FDV and FSV. An improvement in
myocardial contractility was noted, and the EF/MS
index increased by 14.2 and 36.0% in patients with
adaptive and maladaptive remodeling, respectively. A
positive change in the structural and functional state of
the left ventricle was accompanied by an improvement
in the diastolic function of the left ventricle in the form
of a positive change in the structure of diastolic filling
(E/A) in both groups.
After 12 weeks of the study, in patients with both
adaptive and maladaptive LV remodeling, against the
background of clinical improvement, a significant
decrease in the concentration of CRP and pro-
inflammatory cytokines (IL-6, TNF-
α) in the blood
serum was noted. All patients at the time of inclusion
in the study according to the SCORE scale for assessing
the risk of death from cardiovascular diseases were in
the high and very high-risk group. In 62% of patients,
after 3 months from the start of treatment with
rosuvastatin at a daily dose of 20 mg, the target LDL
level (< 2.5 mmol / l) was achieved.
Our data are largely consistent with the literature data
on the adverse effect of pro- inflammatory cytokines on
the initiation, becoming and progression of LV ischemic
dysfunction [8]. They also indicate a close relationship
American Journal of Applied Science and Technology
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American Journal of Applied Science and Technology (ISSN: 2771-2745)
between the processes of LV remodeling in CHF and the
mechanisms of the immune response, which is
activated in this disease. The detected significant
abrupt increase in the levels of pro-inflammatory
cytokines and CRP during the development of the
maladaptive phase of heart remodeling can serve as a
criterion for the severity of CHF and become the
starting point in the clinician's reasoning about the
intensity (aggressiveness) of the therapeutic effect. The
results of our study showed that rosuvastatin therapy
is not only accompanied by a hypolipidemic effect, but
also leads to a significant decrease in the concentration
of pro-inflammatory cytokines in the blood serum and
CRP in patients with CHF of ischemic etiology. In our
study, the level of CRP significantly decreased during
treatment with rosuvastatin in both groups, which
indicates a decrease in inflammation and is associated
with a decrease in cardiac decompensation and,
accordingly, the risk of an unfavorable course.
This is consistent with the results of a number of
studies, which also noted a correlation between the
level of pro- inflammatory cytokines and the severity of
clinical manifestations of CHF, a decrease in life
expectancy, and a decrease in their concentration
during treatment is associated with clinical
improvement [2].
Thus, after 12 weeks, most patients reach- ed the
target level of blood lipids, but even more important to
us is the pronounced effect of this treatment on the
level of pro-inflammatory cytokines and CRP, which
may contribute to the inhibition of the development of
the disease.
CONCLUSION
1.
The development of the maladaptive phase of
LV remodeling is accompanied by a sharp rising the
level of pro-inflammatory cytokines and CRP in the
blood serum.
2.
There is a significant correlation of pro-
inflammatory cytokines with structural and functional
changes in the heart in CHF.
3.
Treatment with rosuvastatin (Mertenil drug) at
a dose of 20 mg in patients with CHF of ischemic
etiology is accompanied by a decrease in the level of
pro-inflammatory cytokines (TNF-
α, IL
-6), serum CRP
and an improvement in the structural and functional
state of the LV in patients with CHF of ischemic
etiology.
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