RU2749293C1 - Method for determining probability of ischemic heart disease in young patients with abdominal obesity - Google Patents

Abstract

FIELD: medicine; cardiology.

SUBSTANCE: invention relates to the field of medicine, namely to cardiology, and concerns a method for determining the presence of ischemic heart disease (hereinafter – IHD) in young patients aged 25-44 years with abdominal obesity. In the patient’s blood serum, the concentration of leptin, adipsin and visphatin is determined, the values obtained are compared with the threshold value of the corresponding biomarker, equal to 3600 pg/ml for leptin, 4.2 mcg/ml for adipsin, and 8 ng/ml for visphatin. If at least two biomarker values deviate from the threshold values, a conclusion is made about the presence of ischemic heart disease in a young patient aged 25-44 years with abdominal obesity. At the same time, for leptin and adipsin, an increase in the concentration relatively to the threshold value is considered a deviation, and for visfatin, a decrease in the concentration relatively to the threshold value is considered a deviation.

EFFECT: invention provides for the creation of a non-invasive, affordable and inexpensive biochemical method for determining the probability of IHD in young patients with abdominal obesity, which can be used for effective early diagnostics.

1 cl, 2 tbl, 3 ex

Description

The invention relates to medicine, namely to cardiology, and can be used for early detection of coronary heart disease (CHD) in young people against the background of abdominal obesity.

Research in recent decades has shown that obesity is directly related to systemic inflammation and that visceral obesity increases the risk of cardiovascular disease, namely the risk of cerebrovascular disease and myocardial infarction.

Today, visceral adipose tissue is considered as an integral link between the formation of metabolic disorders and cardiovascular pathology. Many studies demonstrate that adipokine imbalance is highly associated with increased risks of cardiometabolic diseases and their complications (1-3).

Various techniques are used to diagnose myocardial ischemia: ECG recording at rest, Holter ECG monitoring, various stress tests (treadmill test and bicycle ergometry - VEM), pharmacological tests, stress echocardiography.

1. Electrocardiography at rest.

The essence of the method consists in registering electrical potentials that arise during the work of the heart and in their graphic display on a display or paper. The disadvantage of this method is the limitation of the possibility of detecting transient myocardial ischemia by recording an ECG at rest, the presence of false positive results in hypertrophy and dilatation of the left ventricle, electrolyte disturbances, cardiac arrhythmias and conduction disturbances, taking antiarrhythmic drugs, hyperventilation, etc.

2. Holter ECG monitoring.

The method is used to detect episodes of vasospastic or spontaneous ischemia, as well as asymptomatic myocardial ischemia. The value of this technique lies in the ability to identify myocardial ischemia in everyday life. The criterion for myocardial ischemia during Holter ECG monitoring is depression of the ST segment of the ischemic type by 1 mm or more with a duration of ST segment depression of at least 1 min and a time between separate episodes of at least 1 min.

The disadvantage of this method is the frequent presence of false positive results in patients without angina pectoris.

3. Load tests.

Stress tests provoke myocardial ischemia by increasing myocardial oxygen demand (treadmill test, VEM, dobutamine test) or reducing oxygen delivery to the myocardium (tests with dipyridamole and adenosine). This is a method for detecting transient myocardial ischemia in patients with suspected coronary artery disease or with an established diagnosis of it.

The disadvantages of the method include the relatively low sensitivity of the VEM test in IHD, the difficulty of performing the load on the bicycle ergometer for patients who have no experience in cycling, as well as for patients with orthopedic and neurological disorders or vascular diseases of the extremities.

4. Stress-Echo-KG.

Stress echocardiography is a combination of two-dimensional echocardiography and an exercise test. As a load, a treadmill or bicycle ergometer is used, as well as pharmacological drugs. This technique is suitable for the initially altered ECG (signs of left ventricular myocardial hypertrophy, intraventricular conduction disturbances, electrolyte disturbances, drug action, etc.).

The disadvantages of this method include the possibility of obtaining a fuzzy visualization of the left ventricle during physical activity, because Echocardiography is performed immediately after the end, and not at the height of the load. In addition, side effects may develop in the form of dizziness, rapid pulse, chest discomfort.

5. Coronary angiography (coronary angiography) is an X-ray examination using a contrast agent, which allows diagnosing all lesions of the coronary bed, including severe multivessel lesions, with high accuracy. Such an examination is considered the standard for the diagnosis of coronary artery disease, as it allows you to accurately establish the place and degree of spasm, stenosis or blockage of the coronary arteries of the heart.

The disadvantage of this method is its invasive nature and a high risk of developing various complications during the study. In addition, one should take into account the limitation of the availability of this method in real medical practice. The presence of such equipment is possible only in large specialized cardiovascular centers.

6. Computed tomography (CT) is a modern method of examining human internal organs using X-rays. To increase the information content, CT is performed using a contrast agent (in particular, when examining blood vessels and hollow organs).

The disadvantage of this method is its high cost and the availability of special equipment. As a rule, only large medical centers have such equipment. In addition, CT gives radiation exposure to tissues, so it cannot be used repeatedly.

7. Magnetic resonance imaging (MRI) is based on the principle of obtaining a data array and modeling on its basis a three-dimensional image of an organ using electromagnetic waves. Conducting MRI allows you to detect those changes in the vessels that occur during atherosclerosis and are inaccessible to other diagnostic methods: the presence of atherosclerotic plaques; their size, shape, stability; the degree of vasoconstriction at the site of the plaque; the prevalence of the process; the presence of blood clots; anomalies in the development of blood vessels.

The disadvantage of this method is the high cost and long research time. Such studies are carried out in specialized clinics with the participation of highly qualified specialists.

The disadvantage of this method is the analysis in a highly specific genetic laboratory using expensive equipment, the participation of highly qualified specialists to perform complex studies, which limits the implementation of this method in real clinical practice.

Despite significant advances in improving the diagnosis and treatment of coronary heart disease (CHD), the increase in cardiovascular disease (CVD) among young people is growing steadily around the world (4). This is mainly due to an increase in CVD risk factors. One of these risk factors is overweight, especially abdominal (visceral) obesity (AO) [5,6].

Much attention is paid to the concept according to which AO induces a chronic systemic inflammatory reaction of low severity, resulting from a combination of increased insulin resistance and increased production of inflammatory mediators due to an increase in the pool of visceral / abdominal adipocytes (7, 8).

The study of biomolecules secreted by visceral adipocytes during AO - adipokines and their effects is an important and rapidly developing area in modern medical science. Adipokines, being, among other things, endogenous biologically active mediators of inflammation secreted by visceral adipocytes, regulate intercellular and intersystem interactions, determine cell survival, stimulation or suppression of their growth, differentiation, functional activity of cells and the processes of their apoptosis. Adipokines ensure the coordination of the actions of the immune, endocrine and nervous systems under normal conditions and in response to pathological influences (9). Adipokines represent a wide range of different biomolecules, such as hormones (adiponectin, resistin, leptin, visfatin), pro-inflammatory cytokines (interleukins, IL-1β, IL-6, IL-8, monocyte-chemoattractant protein type 1, MCP-1, factor tumor necrosis alpha, TNF-α, lipocalin-2, omentin-1), molecules of the complement system (adipsin) and vascular hemostasis (type 1 plasminogen activator inhibitor, PAI-1) and others (10).

A known method for predicting the risk of metabolic syndrome in a patient with abdominal obesity, including the isolation of DNA lymphocytes from peripheral blood, followed by identification of T45G polymorphism of the adiponectin gene by polymerase chain reaction followed by restriction analysis. When the T45T genotype of the adiponectin gene is identified, the risk of developing metabolic syndrome is predicted. The method is specific and can be used for early prediction of the risk of developing metabolic syndrome in patients with abdominal obesity (11).

A known method for determining the risk factor of arterial hypertension in women with abdominal obesity by determining the level of high molecular weight adiponectin and when the level of high molecular weight adiponectin is less than 4.6 μg / ml is considered a risk factor for hypertension. The sensitivity of the method is 89.3%, the specificity is 88.1% (12).

The closest to the claimed method - the prototype, is a method for determining the risk of developing coronary heart disease by a biochemical study of blood serum, in which malondialdehyde, nitric oxide, phospholipase A2 and endotoxin are determined and with an increase in the level of malondialdehyde to 14.8 μmol / l or more , nitric oxide up to 122.3 μmol / L or more, phospholipase A2 up to 402.5 ng / ml or more, and endotoxin up to 3.1 EU / ml and more determine a high risk of developing coronary heart disease (13).

The disadvantage of this method is the analysis in a highly specific laboratory, the laboriousness of determining the biochemical markers recommended by the authors, which imposes restrictions on the implementation of this method in real clinical practice.

The objective of the claimed invention is to provide a non-invasive, affordable and inexpensive laboratory method for determining the likelihood of coronary artery disease in young patients with abdominal obesity, which can be used for early primary prevention of coronary heart disease.

EFFECT: creation of a non-invasive, affordable and inexpensive biochemical method for determining the likelihood of CHD in young patients with abdominal obesity, which can be used for effective early diagnosis.

The task is achieved by the proposed method, which consists in the fact that in young patients (aged 18-44 years according to the WHO classification) with the presence of abdominal obesity (waist circumference (OT) more than 80 cm in women and more than 94 cm in men) in serum blood values of the following adipokines (biomarkers) are determined: leptin, adipsin and visfatin, then the obtained values are compared with the threshold value of the corresponding biomarker, and in the presence of two or more values that go beyond the threshold values of the corresponding biomarker, a conclusion is made on the likelihood of IHD in patients with abdominal obesity ... The method is carried out as follows.

In a young patient with abdominal obesity, blood is taken for biochemical research in the morning on an empty stomach from the cubital vein no earlier than 12 hours after the last meal. In blood serum, laboratory studies determine the concentration of leptin (pg / ml), adipsin (μg / ml), visfatin (ng / ml) and compare with the threshold numerical values of the concentrations of these biomarkers, equal for leptin - 3600 pg / ml, for adipsin - 4.2 μg / ml, for visfatin - 8 ng / ml and in the presence of at least two biomarker values, more or less (for visfatin) the threshold value of the corresponding biomarker, a conclusion is made about the likelihood of the patient having coronary heart disease.

The statistical analysis of the preliminary studies made it possible to determine the conditional threshold limit for each indicated indicator based on the construction of distribution histograms. The criterion for the inclusion of the patient in the examination was the age of 25-44 years and the presence of abdominal obesity, which is recorded with an OT of more than 80 cm in women and more than 94 cm in men.

The threshold value for leptin was 3600 pg / ml, for adipsin it was 4.2 μg / ml, for visfatin it was 8 ng / ml, since with an increase (leptin, adipsin) / decrease (visfatin) of these parameters, an increase in the number of patients with the presence of coronary heart disease.

The proposed method was developed on the basis of a study of a population sample of young patients (118 people) aged 25-44 years. 3 subgroups were formed:

1) persons with ischemic heart disease against the background of AO - 44 people,

2) control by age and sex of persons without coronary artery disease with AO - 44 people,

3) control by age and sex of persons without coronary artery disease and without AO - 30 people.

In all patients, blood for biochemical studies was taken in the morning on an empty stomach from the cubital vein no earlier than 12 hours after the last meal.

Simultaneous analysis of adipokine concentrations in blood serum was performed by multiplex analysis on a Luminex MAGPIX flow fluorometer using two panels (Millipore):

1) Panel HADK1MAG-61K MILLIPLEX MAP Human Adipokine Magnetic Bead Panel 1, including the determination of adipokines: adiponectin, adipsin, lipocalin-2, plasminogen activator inhibitor type 1 (PAI-1), resistin;

2) Panel HADK2MAG-61K MILLIPLEX MAP Human Adipokine Magnetic Bead Panel 2, including the determination of such adipokines as interleukins 1 beta (IL-1β), IL-6, IL-8, insulin, leptin, monocyte-chemoattractant protein type 1 (MCP -1), nerve growth factor (NGF), tumor necrosis factor alpha (TNF-α).

In addition, two adipokines - visfatin and omentin-1 - were determined in blood serum by enzyme-linked immunosorbent assay (ELISA) on an ELISA MULTISCAN analyzer using RayBiotech test systems.

Statistical processing of the results was performed using the SPSS for Windows program (version 17) with an estimate for each variable of the median (Me), lower and upper quartiles. Sample comparison methods and correlation analysis were used (Mann-Whitney U-test when comparing medians, Wilcoxon's test, One-Way ANOVA analysis using Dunnett's test for multiple comparisons. 95% level of statistical significance was used).

As a result, changes in the concentration of some adipokines were revealed in young people with early coronary artery disease in comparison with those without coronary artery disease (Table 1). It has been shown that in the group of persons without IHD, the levels of adipsin and leptin increase in the presence of abdominal obesity in patients, which is an important risk factor for the development of IHD. The level of such adipokine as visfatin, on the contrary, decreases in the group of persons with AO. Comparison of the level of these adipokines in the blood serum of young people without IHD and in the absence of AO with patients with IHD against the background of AO showed that the concentrations of adipsin and leptin in the blood were 1.32 and 4.9 times higher, respectively, and the level of visfatin , was 1.2 times lower, respectively. The levels of the studied human adipokines in the studied groups Me [25%; 75%] are presented in Table 1.

Correlation analysis of the studied parameters with some risk factors for the development of coronary heart disease showed that the greatest number of connections was found for adipsin. The results of the correlation analysis of the studied adipokines and risk factors for coronary artery disease are presented in Table 2.

Thus, adipsin, together with a protein that stimulates acetylation, promotes the flow of glucose into adipocytes and enhances the synthesis of triglycerides in them, regulating the serum levels of these metabolites (14). This fact is confirmed by the revealed correlations between the concentration of adipsin and the level of triglycerides (r = 0.566).

Thus, the claimed method provides a quick detection of the presence of coronary artery disease in a patient for further development of tactics of preventive and therapeutic measures.

The invention is illustrated by the following clinical examples.

Example 1.

Patient S. (No. 263), age 41 years old, OT 85. Clinically and instrumental confirmation of the diagnosis "Certain ischemic heart disease". The diagnosis was made if the following criteria were met: a past large-focal myocardial infarction (MI) (ECG), exertional angina (Rose's questionnaire), ischemic ECG changes without left ventricular hypertrophy, rhythm and conduction disturbances (ECG).

A biochemical analysis of blood serum was carried out for the content of the following biomarkers:

Leptin - 4086 pg / ml

Adipsin - 4.21 μg / ml

Visfatin - 6.30 ng / ml The obtained values were compared with the threshold values of these biomarkers:

Leptin - more than 3600 pg / ml

Adipsin - more than 4.2 μg / ml

Visfatin - less than 8.0 ng / ml

From the studied complex of biomarkers in the patient, three indicators went beyond the threshold values of the corresponding biomarkers, which indicates the likelihood of the presence of coronary artery disease.

Example 2.

Patient A. (No. 362), age 31 years old, from 58 cm. Clinically and instrumentally, there is no ischemic heart disease.

A biochemical analysis of blood serum was carried out for the content of the following biomarkers:

Leptin - 852.9 pg / ml

Adipsin - 3.84 mcg / ml

Visfatin - 9.94 ng / ml

The obtained values were compared with the threshold values:

Leptin - more than 3600 pg / ml

Adipsin - more than 4.2 μg / ml

Visfatin - less than 8.0 ng / ml

From the studied complex of biomarkers in the patient, all indicators did not go beyond the threshold values, which indicates the absence of coronary artery disease.

Example 3.

Patient M. (No. 765), age 44 years old, from 84 cm - abdominal obesity. Clinically, laboratory and instrumental: there is no diagnosis of coronary heart disease.

A biochemical analysis of blood serum was carried out for the content of the following biomarkers:

Leptin - 1775 pg / ml

Adipsin - 3.93 mcg / ml

Visfatin - 8.44 ng / ml

The obtained values were compared with the threshold values of these biomarkers:

Leptin - more than 3600 pg / ml

Adipsin - more than 4.2 μg / ml

Visfatin - less than 8.0 ng / ml

From the studied complex of biomarkers in the patient, all indicators did not go beyond the threshold values of the analyzed biomarkers, which indicates the absence of coronary artery disease.

The proposed method makes it possible to determine the likelihood of coronary heart disease in young people with abdominal obesity. This method is non-invasive, safe, does not require large financial costs, and can be performed in a clinical biochemical laboratory.

In addition, this method will allow at an early stage to determine the possibility of developing coronary artery disease, to accelerate the pace of additional examination and the choice of treatment tactics for the patient.

Information sources

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Claims (1)

A method for determining the presence of coronary heart disease in young patients with abdominal obesity, including determining target biomarkers in the blood serum with subsequent comparison of these values with the threshold values of the corresponding biomarkers, characterized in that the concentration of leptin, adipsin and visfatin is determined in the patient's blood serum, the obtained values compared with the threshold value of the corresponding biomarker, equal for leptin - 3600 pg / ml, for adipsin - 4.2 μg / ml, for visfatin - 8 ng / ml, and if at least two biomarker values deviate from the threshold values, a conclusion is made about the presence of ischemic heart disease in a young patient aged 25-44 with abdominal obesity, while for leptin and adipsin, an increase in concentration relative to the threshold value is considered a deviation, and for visfatin - a decrease in concentration relative to the threshold value.