Научная статья на тему 'The significance of inflammatory mediators in the clinical interpretation of patients with stable angina of II-III fc'

The significance of inflammatory mediators in the clinical interpretation of patients with stable angina of II-III fc Текст научной статьи по специальности «Клиническая медицина»

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ISCHEMIC HEART DISEASE / STABLE ANGINA / POSTINFARCTION CARDIOSCLEROSIS / INFLAMMATORY MARKERS / CYTOKINES

Аннотация научной статьи по клинической медицине, автор научной работы — Kasimova Mukhlisakhon Saidakbarkhodjayevna, Ismailova Adolat Abdurakhimovna, Tulabaeva Gavkhar Mirakbarovna

This article presents the results of a study on inflammatory mediators in patients with ishemic heart disease stable angina of II-III FC with postinfarction cardiosclerosis in anamnesis and without it. It had been fond significant higher levels of CRP and pro-inflammatory cytokines IL-6 and TFN-α in patients with stable angina with postinfarction cardiosclerosis in anamnesis. The relationship between these indicators revealed according to the correlation analysis.

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Текст научной работы на тему «The significance of inflammatory mediators in the clinical interpretation of patients with stable angina of II-III fc»

Such clinical forms of microspore can be accepted mistakenly for multiform exudative erythema, toxicodermia, pityriasis rosea of Jiber, allergic dermatitis, which it delays the term of establishment of diagnosis.

Conclusion

1. In the least suspicion to microsporia it is necessary to go to the specialist -dermatologist, which it allows to diagnose this

disease in a short time and to administer rational treatment in time.

2. Belated diagnostics and because of irrational therapy increases atypicalness of clinical manifestations leading to chronic course of mycosis and its dissemination. Such patients are the foci of unidentified infection and they increase unfavorable epidemiological condition.

References:

1. Abidova Z. M., Rakhimov I. R. Situation on dermatomycosis in the Republic during - 2009-2013 yy.//Dermato-venereology and esthetic medicine. - Tashkent, - 2014. - № 1. P. 172-173.

2. Egizbayev M. K., G. A. Tulepova G. A. The analysis of morbidity with contagious skin diseases in Southern Kazakhstan region of the Republic of Kazakhstan during 2000-2004 yy.//Progress in medical mycology. - Moscow, - 2006. - V. VIII. - P. 9-10.

3. Isayeva T. I. Clinical -epidemiological and medico- social aspects of microsporia in various climate - geographical conditions. Abstract of dissert. can. med. scien. - Moscow, - 2009. - P. 19.

4. Novikova L. A., Bakhmeteva E. M. Comparative analysis and clinical -epidemiological features of dermatomycosis among children. Voronej//Kashkinskiy chteniya. The thesis of lectures. - 2002. - P. 83.

5. Rukavishnikova V. M. Modern peculiarities of clinics and treatment of microsporia//Ward doctor. - 2001. - № 4. - P. 1-11.

6. Stepanova J. V./Clinical features and treatment of microsporia in present day conditions//Bulletin of dermatology and venereology. -2008. - № 6. - P. 85-88.

7. Fakhretdinova Kh., Medvedeva E. A. Dynamics of dermatomycosis in the Republic of Bashkortostan-in 1983-2003 yy.//Problems of medical mycology. - 2004. - V.6. - № 2. - P. 124-125.

8. Fedotov V.P, Kadenko O. A.. Actual problems of epidemiology and treatment of microsporia in children//«Up- to- date mycology in Russia». Thesis.lect. I -congress of mycologists of Russia. - Moscow, - 2002. - P. 325.

DOI: http://dx.doi.org/10.20534/ESR-16-9.10-100-103

Kasimova Mukhlisakhon Saidakbarkhodjayevna, Phd student of the Institute of Immunology of the Academy of Sciences of the Republic of Uzbekistan E-mail: [email protected] Ismailova Adolat Abdurakhimovna, Head of the Laboratory of immunopathology and immunopharmacology of the Institute of Immunology of the Academy of Sciences of the Republic of Uzbekistan, MD Tulabaeva Gavkhar Mirakbarovna, Head of the Department of Cardiology with the course of Gerontology of the Tashkent Institute of Postgraduate Medical Education, MD

The significance of inflammatory mediators in the clinical interpretation of patients with stable angina of II-III fc

Abstract: This article presents the results of a study on inflammatory mediators in patients with ishemic heart disease stable angina of II-III FC with postinfarction cardiosclerosis in anamnesis and without it. It had been fond significant higher levels of CRP and pro-inflammatory cytokines IL-6 and TFN-a in patients with stable angina with postinfarction cardiosclerosis in anamnesis. The relationship between these indicators revealed according to the correlation analysis.

Keywords: ischemic heart disease, stable angina, postinfarction cardiosclerosis, inflammatory markers, cytokines.

Topicality. The cardiovascular disease for the past 50 years, firmly holds the primacy among the causes of death in the developed world [7]. The most common form of chronic ischemic heart disease (IHD) is stable angina (SA) [14]. The atherosclerosis ofthe coronary arteries is the pathological basis of coronary heart disease. The local and systemic signs of nonspecific inflammatory process in atherosclerosis observed at an early stage lesion of blood vessel walls. It is known that arteriosclerosis — is a chronic inflammatory process, and even at the early stages of atherogenesis — intra- and

extracellular lipid sediments and the formation of lipid spots inflammatory cells already present (macrophages and T lymphocytes) [2]. These cells, activating, secrete large amounts of cytokines, chemo-kines, and matrix metalloproteinases that cause the progression of atherosclerotic foci [2; 6].

Among the basic mechanisms of pathogenesis of atherosclerosis of arterial vessels the importance given to the inflammatory process, which, according to P. Libby theory, accompanies all its stages [10]. It is known that cytokines have regulatory multidirectional im-

The significance of inflammatory mediators in the clinical interpretation of patients with stable angina of II-III fc

pact on the atherosclerotic process. Thus, pro-inflammatory cytokines (TNF -a, IL-1p, IL-6, IL-8) are considered as atherogenic and anti-inflammatory cytokines (IL-4 and IL-10)-like antiatherogenic mediators [9]. The major pro-inflammatory cytokines are TNF-a, IL-1 and IL-6, IL-8. The tumor necrosis factor-a (TNF-a) — is a proinflammatory cytokine with expressed proinflammatory properties. It is playing a crucial role in the development of inflammation. It is an active participant in the immune response, is involved in regulation of cell apoptosis [12].

The IL-6 as a pro-inflammatory cytokine plays an important role in systemic inflammation, it is a major activator of protein synthesis of liver acute phase. According to the authors of [8], the content of IL-6 in the blood serum increases in obesity and atherosclerosis, and also shows the value of IL-6 as a predictor of the development of clinical manifestations of atherosclerotic vascular lesions in healthy individuals without any signs of the disease [13].

Also, the reality of atherosclerosis inflammatory theory is confirmed by the discovery in the blood of patients with cardiovascular disease elevated levels of systemic inflammatory response markers such as high sensitive C-reactive protein (hs-CRP) [5]. We detected a moderate positive association between CRP levels early and long-term risk of adverse outcomes in patients with ACS. Given that CRP studied as a marker of inflammation in IHD better than the other markers such as IL-6, TNF-a, fibrinogen, et al., Some may have a greater prognostic value [3; 4]. In connection with this, now is the urgent question of studying and comparing the predictive value of not only CRP, but also other markers of inflammation in patients with IHD.

Purpose. The study of inflammatory mediators in patients with IHD with SA of II-III functional class (FC), with postinfarction cardio sclerosis (PICS) and without it.

Materials and methods.

The study included 34 IHD patients with SA of II-III FC at the age of 23 to 70 years (mean age 57,5±1,57 years). Of these, 12 (35%) men (average age of 56,8±2,1 years) and 22 (65%) women (mean age 58.9±2.1 years). The duration of the disease IHD at the time of inclusion of patients in the study was an average of 10,9±1,42 years. Hypertensive heart disease was observed in history in 27 (79%) patients. Based on the clinical data, all patients were divided into 2 groups: the I group — consisted of 24 IHD patients with SA of II-III FC; The II group — was presented by 10 IHD patients with SA of II-III FC with PICS (the prescription of myocardial infarction > 6 months or more). The diagnosis of SA

of II-III FC was verified according veloergometry, as recommended by the GFCF/WHO (2004), the classification of the Canadian Society of Cardiovascular Diseases (1989). The patients' gathering was carried out on the basis of the paid cardiology department of City Clinical Hospital № 7 in 2013. The diagnosis of myocardial infarction was established on the GFCF and ICD-10 recommendations, taking into account medical history, ECG, EhoCG. The control group consisted of 25 healthy individuals (men and women), mean age of 56,2 ± 1,53 years.

The criteria for inclusion in the study were men and women up to 70 years; the presence of ischemic heart disease: stable angina of II-III FC confirmed clinically (the characteristic pain) and treadmill test data (segment depression ST> 1 mm length> 0,08c); the presence of myocardial infarction (patients of group II) — prescription of myocardial infarction> 6 months, confirmed with the data of ECG and echocardiography (hypokinesis zones); informed consent. The study excluded patients with complex disorders of rhythm and conduction of the heart; chronic heart failure of III-IV FC (NYHA); acute myocardial infarction; Resting heart rate before treatment <60 beats per minute; renal and hepatic failure; thyroid dysfunction, diabetes mellitus type 2 in the stage of severe decompensation requiring insulin treatment; oncological and immunological diseases.

Immunological studies were performed in the laboratory of im-munopathology and immunepharmacology of the Institute Immunology of the Academy of Sciences of Uzbekistan. The cytokines IL-6 and TNF-a were determined in serum by ELISA method using sets produced by "Vector-Best" LTD (Novosibirsk, Russia) on the enzyme immunoassay analyzer «StatFax — 2100" (USA). The statistic processing of the results was performed using Applied software for statistical data processing Statistica® version 6.0. The significance of differences between treatment groups was evaluated by Student's t test. Differences compared values recognized statistically significant at p<0,05. The correlation analysis was held with the help of Spearman's coefficient calculation.

Results and discussion

Essential to the development of atherosclerosis and occurring on its basis of IHD is attached immunological reactions [12]. To evaluate the clinical significance of immune responses in the development of coronary artery disease were studied indicators hs-CRP, fibrinogen, leukocytes and ESR in IHD patients with PICS history and without it (figure 1).

Figure 1. The level of inflammatory markers in patients with stable angina with the presence of PICS and without P <0.05 compared with the control group

The study of clinical and laboratory parameters in patients with SA showed that the level of hs-CRP in the control group was significantly lower than in the main group. Since the average value of hs-CRP in the control group was 1,2±0,70 mg/l, despite the fact that, in groups of patients with cardiovascular continuum on the background of PICS 7.38±2,08 mg/l, and in patients with cardiovascular continuum without PICS 4,94 ± 0,37 mg/l. As can be seen, the largest index of hs-CRP was observed in the group of patients with SA with PICS, which significantly exceeded the level of hs-CRP in the control group to 6.15 times (p <0.05). It was also on the differences between hs-CRP groups: in the group of patients with PICS hs-CRP was increased in 1.5-times, compared with patients without it. According to a meta-analysis conducted by Li-ping H in 2010., Early CRP is a predictor of poor outcome in patients with ACS. We detected a moderate positive association between CRP levels early and long-term risk of adverse outcomes in patients with ACS. [11]. According to the results of our research important

The Table 1 shows the mean value of IL-6 in control group was 3.42 ± 0.28 pg/ml, while in patients without PICS it was 12,9 ± 1,19 pg/ml. while in patients with a history of PICS presence it was 15.42 ± 2.22 pg/ml. A significantly high level of IL-6 determined in angina patients compared with controls (p<0,001). Increasing the content of this cytokine in 4.5 times compared with the control group occurred in the serum of patients with SA of II-III FC amid myocardial infarction. In patients without a history of myocardial infarction IL-6 level was raised to 3.7 times compared with the control group. Comparing the two groups of patients with angina pectoris is observed between 1.2 times increase in patients with a history of presence PICS. By diversity cell sources and the target product of the biological action of IL-6 is one of the most active cytokines involved in the immune response and inflammatory reactions. According to the authors of [8], the content of IL-6 in the blood serum increases in obesity and atherosclerosis, and found an association of high concentrations of IL-6 with impaired contractile function of the heart in patients with chronic heart failure [15]. Our results are consistent with the literature, which was carried out the correlation between the performance of CRP, IL-6, TNF-alpha and the severity of coronary atherosclerosis as a result of coronary angiography.

The results of the study of pro-inflammatory cytokine TNF-alpha showed 4,58 ± 0,81 pg/ml in the control group, in the group of patients with SA without PICS in anamnesis noted 9.73 ± 0,63 pg/ml and higher the level observed in patients with the presence of a history of PICS, which amounted to 11,43 ± 1,69 pg/ml. Determining the concentration of TNF-a in the serum of patients with coronary artery disease showed its significant increase in comparison with the control group (p<0,001). For example in patients with SA without PICS level of TNF-a has been increased by 2.1 times, and in patients with previous myocardial infarction greater than 2.4 times compared to the control group. A comparison group of SA between them there was an increase of 1.17 times in patients with a history of PICS. TNF-a is synthesized primarily in monocytes and mac-

clinical and diagnostic marker for coronary artery disease is the hs-CRP. Its level in patients with previous myocardial infarction was significantly higher compared to other groups, which confirms the relationship of CRP concentration to severity of angina.

According to received data level of white blood cells had no significant difference between the groups, but in the group of patients with SA with PICS noted most increased value ofleukocytes. The Indicators of fibrinogen and ESR in patients with angina is not particularly differ from the control group data.

By the next step, we carried out the immunological characteristics of patients with SA with the presence PICS in anamnesis and without it. In the literature a lot of data on changes in IL-6 and TNF-alpha in patients with coronary artery disease, but so far there is no final opinion on the role of these cytokines and lacking the practical aspects of their interpretation. So we had the interest to study the IL-6 and TNF-alpha in patients with SA with the presence PICS anamnesis and without it (Table 1).

rophages, as well as in mast cells, fibroblasts, endothelial cells. It stimulates the expression of interleukin-1p production, IL-6, IL-8, also affects the functional properties of the endothelium to affect coagulation gives lipid metabolism by stimulating the processes of atherogenesis [12]. We found that IHD patients with SA of II-III FC significant largest increase in TNF-a observed in patients with PICS.

Therefore, the immunological characteristics of patients, showed that the presence of IHD with preserved PICS high importance not only of clinical laboratory parameters of inflammation, and immunological inflammatory mediators. Comparison of IL-6 and TNF-a in the groups of patients with coronary artery disease showed a significant higher their content in patients with SA and myocardial infarction.

In the correlation analysis, wich was conducted in patients with SA postinfarction cardiosclerosis, was revealed a direct significant relationship between indicators of IL-6 and TNF-a (r=0,6; p<0,05), IL-6, and erythrocyte sedimentation rate (r=0,6; p<0,05) and inverse relationship between indicators of fibrinogen and TNF-a; and hs-CRP and fibrinogen (r= -0,57; p<0,05, r= -0,8; p<0,01, respectively). In the group ofpatients with stable stenocardia A significant positive correlation relationship between indicators of IL-6 and fibrinogen (r=0,47; p<0,05). Also were found on the average power of the inverse correlation between IL-6 and hs-CRP (r= -0.5), but it was not accurate p>0.05.

Conclusion

1. Studies showed activation of proinflammatory cytokines in the group of patients with stable angina of II-III FC with PICS and the group without a history of PICS, but reliable high value identified cytokine status in patients with PICS.

2. Also, a high degree of inflammation in patients with stable angina PICS history (the level ofhs-CRP, IL-6 and TNF-alpha, and others.) Than in patients without PICS characterizes the level of CRP, which was significantly higher in the group of patients with stable stenocardia of II-III FC with previous myocardial infarction.

Table 1. - The level of pro-inflammatory cytokines in patients with stable stenocardia in combination with PICS and without it, M ± m

IL-6 (pg/ml) TFN-a (pg/ml)

control (n=25) 3,42±0,28 4,58±0,81

Patients with IHD (n=24) 12,9±1,19* 9,73±0,63*

Patient with IHD on the PICS background (n=10) 15,42±2,22* 11,43±1,69*

P<0,001 compared with the control group.

Use of essentiale Forte n in complex treatment of Antiphospholipid syndrome in women

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DOI: http://dx.doi.org/10.20534/ESR-16-9.10-103-105

Maniyozova Gulnoza Murodovna, the Andizhan State medical institute, the senior research assistant the competitor of chair of obstetrics and gynecology, Uzbekistan Negmatshaeva Habiba Nabievna, Andijan State Medical Institute, docent of department of Obstetrics and Gynecology, Uzbekistan.

E-mail: [email protected]

Use of essentiale Forte n in complex treatment of Antiphospholipid syndrome in women

Abstract: Research of autoimmune response impacts (formation of antibodies to certain proper phospholipids) on implantation, growth, fetal and fetus development processes, gestation course and outcome of labor is taking on special significance in studying function of immune-associated processes and in pathogenesis habitual noncarrying of pregnancy.

Keywords: Antiphospholipid syndrome; Reproductive losses; Autoimmune response; Essential's phospholipid.

Introduction: Obstetric complications developing at antiphospholipid syndrome are serious medical-social problem. Seeking of the treatment methods sets conditions for urgency of the article reviewed. Essentiale forte N is widely applied for treatment of women with reproductive losses and coagulation system changes. However mechanism of action of preparations containing proteolytic enzymes is unclear, there are no well-grounded indications for their application and objective monitoring of treatment efficiency [1; 2; 3].

Antiphospholipid antibodies have multifarious influence on haemostasis system by damaging its entire protective links: endo-

thelial barrier, function of natural anticoagulants, and endogenous fibrinolysis by activating platelet link of haemostasis and procoagulant factors.

At present specialists of all medical sectors are involved in studying ofAPS. It's time to apply this knowledge in interpretation of diversified clinical picture of APS, studying critical conditions, recurrent thromboses which contribute to progress of obstetric and perinatal complications [2; 4; 5].

As far as pregnancy progression with diseases proceeding with haemostasis system disturbance the risk of blood clot development in vessels of placenta, fetus, maternal body increases.

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