Американский Научный Журнал THE ROLE OF INFLAMMATION AND COAGULATION CASCADE IN THE PATHOGENESIS OF ATRIAL FIBRILLATION (8-10)

Introduction: Atrial fibrillation (AF) is associated with prothrombotic or hypercoagulable states, various inflammation markers such as interleukin-6 (IL-6) and hsC-reactive protein (hsCRP) have also been associated with AF. The aim of this study is to investigate the relationship between inflammation markers and the prothrombotic state in the setting of AF and the impact on outcome in patients with AF. Methods: We observed 141 patients with non-valvular AF. As a control group patients similar in gender and age without AF were examined. Clinical, instrumental and laboratory tests were performed on the observed patients. The markers of the coagulation cascade (TF and F) and of inflammatory markers (hsCRP and IL-6) were studied additionally by ELISA on the analyzer "Stat Fax 303 Plus". Studies were conducted using SPSS 13.0 and EXCEL-2013. Results: The obtained results showed that compared to the control group, AF patients had significantly higher levels of IL-6 (p = 0.043), hsCRP (p = 0.002), TF (p = 0.026), and F (p = 0.025). Moreover, levels of hsCRP were higher among AF patients at "high" risk of stroke by CHA2DS2-VASc Score (p = 0.003). Besides, the levels of hsCRP and IL-6 were markedly elevated in patients with dilated left atrium (p = 0.001), poorly functioning left atrial appendage (p = 0.023) and longer duration of AF (p = 0.002). Conclusion: We have demonstrated that the increased plasma levels of IL-6 and hsCRP are related to indices of the coagulation cascade and contribute to structural atrial remodeling in patients with AF. Скачать в формате PDF
8 American Scientific Journal № ( 41) / 2020
МЕДИЦИНСКИЕ НАУКИ

THE ROLE OF INFLAMMATION AND COAGULATION CASCADE IN THE PATHOGENESIS OF
ATRIAL FIBRILLATION.

Hazarapetyan L.G.,
Grigoryan S.V.,
Sarksyan A.A.
Yerevan State Medical University after M.Heratsy ,
Research Inst itut e of Cardiology, Armenia
DOI: 10.31618/asj.2707 -9864.2020.3.41.32
Abstract . Introduction: Atrial fibrillation (AF) is associated with prothrombotic or hypercoagulable states,
various inf lammation markers such as interleukin -6 (IL -6) and hsC -reactive protein (hsCRP) have also been
associated with AF. The aim of this study is to investigate the relationship between inflammation markers and the
prothrombotic state in the setting of AF and th e impact on outcome in patients with AF.
Methods: We observed 141 patients with non -valvular AF. As a con trol group patients s imilar in gender and
age without AF were examined. Clinical, instrumental and laboratory tests were performed on the observed
pati ents. The markers of the coagulation cascade (TF and F) and of inflammatory markers (hsCRP and IL -6) were
studied additionally by ELISA on the analyzer "Stat Fax 303 Plus". Studies were conducted using SPSS 13.0 and
EXCEL -2013.
Results: The obtained resul ts showed that compared to the control group, AF patients had significantly higher
levels of IL -6 (p = 0. 043), hsCRP (p = 0.00 2), TF (p = 0.026), and F (p = 0.025). Moreover, levels of hsCRP were
higher among AF patients at "high" risk of stroke by CHA2DS2 -VASc Score (p = 0.003). Besides, the levels of
hsCRP and IL -6 were markedly elevated in patients with di lated left atrium (p = 0.001), poorly functioning left
atrial appendage (p = 0.023) and longer duration of AF (p = 0.002).
Conclusion: We have demonstr ated that the increased plasma levels of IL -6 and hsCRP are related to indices
of the coagulation cascade and contribute to st ructural atrial remodeling in patients with AF.
Keywords : Atrial fibrillation; high sensitive C reactive protein; Interleukine -6; tissue factor; fibrinogen

Introduction : Atrial fibrillation (AF) is the most
commonly sustained arrhyt hmia and at the same ti me
the most heterogeneous arrhythmia with regard to the
individual spectrum of resulting symptoms. AF is
associated with atrial st ructural changes that may have
an inflammatory basis [1, 2, 3, 4, 5, and 6 ]. The role of
inflammation i n the pathogenesis of AF has not yet
been evaluated but inflammatory mechanisms may
form a basis for new agents more likely to prevent
recurrent episodes of AF. There has recently been much
interest in the relationship between systemic
inflammation and coa gulati on cascade in patients with
AF [7, 8, and 9]. AF is also associated with a
prothrombotic or hypercoagulable state and there is a
plausible evidence linking inflammation to the
initiation and perpetuation of AF and AF -related
thrombosis. Several proth rombot ic factors have been
found to be elevated in AF, indicating abnormal
thrombogenesis. Over the last years we suggested the
link between inflammatory processes and development
of AF. Classical markers of inflammation such as hsC -
reactive protein (hsCRP ) and proinflammation
cytokine Interleukin –6 (IL -6) were found elevated in
patients with AF. Tissue Factor (TF) is the principal
initiator of the coagul ation cascade. In this way TF
promotes blood coagulation and is involved in
inflammation and angiogenes is [10 , 11, 12, and 13].
The aim of this study is to investigate the relationship
between inflammation markers and the prothrombotic
state in the setting of AF, including the impact of this
interaction on clinical presentation and outcome in
patients with AF.
Material and methods . We observed 141 patients
with non -valvular AF. There were 84 males (59.2%),
57 females (40.8. %), mean age 59, 73 ± 6, 49, th e
duration of AF is 14, 36 ± 12 7 months. Among the
examined patients, 129 (92.4%) were diagnosed of
isc hemic heart disease, arterial hypertension was
observed in 78 patients (56.1%). Heart failure (NYHA
functional class I -II) was detected in 104 patients
(76.4%) and NYHA (functional class III) - in 33
patients (23.6%). The exclusion criteria were:
ventricul ar ar rhythmia (more than 30 per hour by
Lown) ventricular tachycardia, acute coronary
syndrome, heart failure (functional class more than III
by NYHA), bronchial asthma, diabetes, and acute
inflammatory disease within the last 4 months,
cardiomyopathy, myo cardi tis, valvular heart disease,
the thyroid gland dysfunction. Clinical examination of
patients included a study of medical history, physical,
laborat ory and instrumental examination. As a control
group similar in gender and age composition 48
patients w ith I HD and AH without AF were examined.
Clinical and instrumental characteristics of patients
with AF were performed in Table 1.
The program of invest igation included general
clinical examination of patients: electrocardiogram,
echocardiography and commo n bio chemical blood
tests. The level of the prothrombotic state, including
markers of the coagulation cascade (TF and F) and
levels of inflammatory mark ers (hsCRP and IL -6) were
studied additionally and were determined by ELISA on
the analyzer "Stat Fax 30 3 Plu s». Studies were
conducted on the basis of simple randomized protocols,
using the universal statistical packages SPSS 13.0 and

American Scientific Journal № ( 41) / 2020 9

EXCEL -2013. Results: The analysis of the data
showed the significant differences between the levels
of hsCRP and IL -6 among patie nts with AF and the
control group (1.2±0.60 vs. 5. 7± 1.4 p = 0.002 and 1.2±
0.8 vs. 2.6± 1.1 p = 0.043 accordingly). HsCRP is an
acute -phase prote in that is why it is likely to react more
quickly to the appearance of AF. In all likelihood the
inflamm ation markers such as hsCRP and IL -6 markers
of inflammation can be considered as risk factors for
the occurrence and recurrence of AF. At the same time ,
the state of coagulation cascade of blood is of particular
importance for the appearance of AF. Tissue Fact or
(TF), formerly known as thromboplastin, is the key
initiator of the coagulation cascade. TF expression and
activity can be induced in endothelia l cells, vascular
smooth muscle cells, and monocytes by various stimuli
such as cytokines, growth factor s, an d biogenic amines.
We revealed that in patients with AF, TF is improved
as compared to the similar patients without AF (1300±
50.vs 600±11.9 p = 0. 026). The similar pattern was also
observed when comparing the concentrations of
fibrinogen F in AF pati ents with control group (13. ±
2.4 vs9.08± 1.4 p = 0.025). Moreover, we found a direct
correlation between the activity of thromboplastin and
the left a trium structural and functional changes (r=
0.643). Table 2 shows the results of concentration of
some i nflam matory markers and coagulation cascade
agents in patients with AF and the similar patients
without AF as a control group (table 2).
Thus, our obtai ned results showed that compared
to the control group, AF patients had significantly
higher levels of IL -6 (p = 0.043), hsCRP (p = 0.002),
TF (p = 0.026), and F (p = 0.025). Moreover, plasma
levels of hsCRP were higher among AF patients at
"high" risk of s troke by CHA2DS2 -VASc Score (p =
0.003). Besides the levels of hsCRP and IL -6 are
markedly elevated in p atien ts with dilated left atrium (p
= 0.001), poorly functioning left atrial appendage (p =
0.023) and longer duration of AF (p = 0.002).
Conclusion: Th us, as a classic inflammatory
marker hsCRP is the major acute phase protein and a
sensitive indicator of infl ammation. HsCRP elevation
may be a non -specific response to any environmental
stimulus, also it may be not directly or indirectly related
to the pa thogenesis of AF. Its synthesis by the liver is
regulated to a large extent by the pro -inflammatory
cyto kine (such as IL -6), and probably acting on
distance to the blood vessel wall to produce elevations
in conventional cardiovascular risk factors and the
coagulation cascade agents such as TF and F. That is
why we have demonstrated that the increased plasma
levels of IL -6 and hsCRP are related to indices of the
coagulation cascade and may contribute to structural
atrial remodeling in patients with AF.
Decla ration of interest
The authors report no conflicts of interest. The
authors alone a re responsible for th e content and
writing of this article.

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10 American Scientific Journal № ( 41) / 2020
Tables
Table 1.
Characteristics of the average values of some parameters of patients with AF
Indice s Mean values+standards deviation
Age (years) 59,7 ± 6,49
Duration AF (months) 14,4 ± 12,7
LAD (mm) 42,28 ± 3,68
LVEDD (mm) 56, 69 ± 3, 84
EF (%) 46, 63 ± 5, 48
IVST (mm) 12.44 ± 2, 50
Note: LAD -left atrium diameters; LVEDD -left ventricular end -diastolic diameter; EF – ejection fraction; IVST -
interventricul ar septum thickness;
Table 2.
The levels of inflammation markers and coagulation cascade agents in AF patients and the control grou p
Indices Control group n=48 AF group n=141

TF pg/ml 600±11.9 1300± 50.* p = 0.026
IL-6 pg/ml 1.2± 0.8 2.6± 1.1* p = 0.043
hsCRP mg/l 1.2±0.60 5,7± 1.4* p = 0.002
F mgmol/l 9.08± 1.4 13. ± 2.4* p = 0.025
Notes: TF – tissue factor; F – fibrinogen; hsCRP – hsC reactive protein; IL -6 – cytokine interleukin -6.
Hazarapetyan L.G.
Grigoryan S.V.

QUANTUM BIOPHYSI CS IN CONVALESCENCE OF NOSOLOGICAL FORMS
(ON THE EXAMPLE OF MULTIPLE SCLEROSIS).
PREPARATION AND STORAGE OF ENTANGLED STATES IN NONLINEAR CRYSTALS

Vlasov Yan Vladimirovich* 1,
Ardatov Sergey Vladimirovich 2,
Antipova Tatyana Alexandrovna 3,
Sineok Evgeniya V italyevna 4,
Ardatova Anastasia Sergeevna 5,
Gavrilov Vladimir Yurievich 6

1 ORCID: 0000 -0002 -9471 -9088
Sama ra state medical University of the Russian Federation.
Professor of the Department of neurology and neurosurgery.
President of the "All -Russian public organization of disabled people with multiple sclerosis". 2 ORCID: 0000 -0002 -2644 -5353
Samara state medic al University of the Russian Federation.
Associate Professor of the Department of traumatology,
orthopedics and extreme surgery nam ed after academician A. F. Krasnov.
Head of the Department of traumatology and orthopedics №1 of SamSMU clinics. 3 ORCID: 000 0-0001 -5499 -2170
Samara state medical University of the Russian Federation.
Associate Professor of the Department of medical physic s,
mathematics and i nformatics.