The content of immune markers of inflammation in patients with acute coronary syndrome and their clinical significance

The dissertation is devoted to the study of the levels of immune inflammatory markers in patients with acute coronary syndrome and to the evaluation of their clinical and prognostic significance. The work combines clinical observations with immunological laboratory studies performed using enzyme immunoassay. The study included patients with different variants of acute coronary syndrome, a group of patients with stable angina, and a group of apparently healthy donors. The clinical part of the work was carried out at the cardiological department and the intensive care unit of the Road Clinical Hospital at Yaroslavl Station of JSC "Russian Railways", while the immunological investigations were performed in the laboratory of the Yaroslavl State Medical Academy.

The aim of the study is a comprehensive evaluation of the levels of von Willebrand factor antigen, C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 in different variants of acute coronary syndrome, and of their predictive role with respect to the development of recurrent coronary events during a one-year follow-up. The objectives include the analysis of the concentration of each marker, comparison of the changes with the features of the clinical picture, assessment of the severity of the hospital period, and prediction of recurrent coronary events.

Acute coronary syndrome continues to be one of the most pressing problems in medicine. Its significance is determined by the early disability of patients and the high degree of risk of premature death [20,26]. Acute coronary syndrome refers to such exacerbations of ischemic heart disease as unstable angina and myocardial infarction with and without Q wave, the common morphological feature of which is damage to the surface of the atherosclerotic plaque and the formation of intracoronary thrombosis [14,32].

One of the key causes of acute coronary syndrome is endothelial dysfunction with activation of inflammatory reactions in the vascular wall [12,19,22,27,29,49]. von Willebrand factor is considered as a marker of endothelial dysfunction, although its independent role in the processes of vascular wall damage, the formation of the clinical picture, and the prognosis of acute coronary syndrome remains unclear. Individual reports indicate a possible predictive role of von Willebrand factor in coronary events [12,95].

Endothelial inflammation proceeds with the active participation of C-reactive protein. In recent years, a concept has emerged indicating that C-reactive protein is not only a marker of local or systemic inflammatory reaction, but also its modulator; therefore, reports on its concentration in different forms of acute coronary syndrome acquire special significance [86,102,225,268]. Nevertheless, no unambiguous position regarding its role has been found in the available literature.

The opinion on the role of cytokine activation in the development and course of intracoronary thrombosis is also equivocal. Interleukin-6 and tumor necrosis factor-alpha are assigned the greatest significance in cardiovascular pathology. However, the contradictory data on their levels and prognostic role in acute coronary syndrome also require further investigation.

The available literature lacks information on the comprehensive assessment of the above substances in different forms of acute coronary syndrome. The foregoing indicates the necessity of studying the role of each of them in the initiation and course of acute coronary syndrome and their predictive significance.

AIM OF THE STUDY

To investigate the levels of von Willebrand factor antigen, C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 in different variants of acute coronary syndrome in order to evaluate their clinical significance and to predict the development of recurrent coronary events during a one-year follow-up period.

OBJECTIVES OF THE STUDY

1. To evaluate the level of von Willebrand factor antigen in the blood serum of patients with acute coronary syndrome and its clinical significance.

2. To establish the clinical and diagnostic role of C-reactive protein in different variants of acute coronary syndrome.

3. To investigate the level of tumor necrosis factor-alpha in the blood serum and its diagnostic and prognostic significance in acute coronary syndrome.

4. To evaluate the level of interleukin-6 in the blood serum in acute coronary syndrome and to compare the identified changes with the features of the clinical picture of the disease.

5. To study the predictive role of von Willebrand factor antigen, C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 in the development of recurrent coronary events during a one-year follow-up in patients with acute coronary syndrome.

SCIENTIFIC NOVELTY

For the first time in acute coronary syndrome, a comprehensive study of the immune inflammatory markers—von Willebrand factor antigen, C-reactive protein, tumor necrosis factor-alpha, and interleukin-6—was carried out by means of enzyme immunoassay in comparison with stable angina and a group of apparently healthy donors.

A comparison was performed between the variants of the course of acute coronary syndrome and the pattern of changes in the concentration of the studied parameters.

The differing predictive significance of von Willebrand factor antigen, C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 with respect to the development of recurrent coronary events during a one-year follow-up was established in patients with acute coronary syndrome.

PRACTICAL SIGNIFICANCE

The determination of von Willebrand factor antigen, C-reactive protein, and interleukin-6 in blood serum should be included in the comprehensive examination of patients with acute coronary syndrome in order to assess the severity of the hospital period and to predict the development of recurrent coronary events.

MAIN STATEMENTS OF THE DISSERTATION PRESENTED FOR DEFENSE

1. In acute coronary syndrome, an increased level of von Willebrand factor antigen is observed, and its high titers are associated with necrotic changes in the myocardium and an unfavorable course of the hospital period.

2. An elevated level of C-reactive protein, detected in patients with acute coronary syndrome, is associated with a severe course of the hospital period.

3. Tumor necrosis factor-alpha and interleukin-6 have diagnostic and prognostic significance in the development of acute coronary syndrome, confirmed by clinical and immunological correlations.

4. The studied parameters—von Willebrand factor antigen, C-reactive protein, tumor necrosis factor-alpha, and interleukin-6—play differing predictive roles with respect to the development of recurrent coronary events during a one-year follow-up.

IMPLEMENTATION OF THE SET OBJECTIVES

The clinical part of the work was carried out on the basis of the intensive care unit and the cardiological department of the Road Clinical Hospital at Yaroslavl Station of the non-state healthcare institution of the open joint-stock company "Russian Railways" (Head Physician: Candidate of Medical Sciences M.S. Mogutov). The special immunological methods of investigation were carried out on the basis of the laboratory at the course of clinical laboratory diagnostics (Head: Doctor of Medical Sciences, Professor A.A. Baranov) of the Yaroslavl State Medical Academy (Rector: Academician of the Russian Academy of Medical Sciences, Professor Yu.V. Novikov).

APPROBATION AND IMPLEMENTATION OF THE RESULTS

The research materials are used in the educational process at the Department of Therapy of the Pediatric Faculty. The results of the work are applied in the practical activity of the intensive care unit and the cardiological department of the Road Clinical Hospital at Yaroslavl Station.

The main statements and results of the research were reported at: the VII All-Russian Forum named after Academician V.I. Ioffe with international participation "Days of Immunology in Saint Petersburg" (Saint Petersburg, June 23-26, 2003), June 25, 2003; the V Regional Scientific and Practical Conference of Students, Postgraduates, and Young Scientists of Higher Education Institutions "Yaroslavl Region. Our Society in the Third Millennium" (Yaroslavl, May 22, 2004), May 22, 2004; the Scientific and Practical Conference "The Problem of Thrombosis in Rheumatology", dedicated to the 60th anniversary of the Russian Academy of Medical Sciences (Moscow, November 24-26, 2004), November 26, 2004.

Ten works have been published on the topic of the dissertation, of which five are in central press.

SCOPE OF THE WORK

The dissertation is set out on 136 pages of typewritten text and consists of an introduction, a literature review, four chapters of the results of original research, a discussion of the obtained data, conclusions, practical recommendations, and a bibliography comprising 270 sources, of which 70 are Russian and 200 are foreign works. The dissertation is illustrated with 22 tables and 16 figures.