RU2248744C1 - Method for predicting complications in cardio-vascular system at applying substitution hormonal therapy - Google Patents

Abstract

FIELD: medicine, gynecology.

SUBSTANCE: the present innovation deals with treating women in climacteric period. For this purpose, before the onset of substitution hormonal therapy (SHT) it is necessary to investigate female antithrombogenic activity of vascular walls by detecting quantitative values of ADP-induced aggregation of thrombocytes, activity of antithrombin III in blood and fibrinolytic activity of blood both before and after "cuff test". Then one should determine the ratios of the mentioned values both before and after the above-mentioned test. Moreover, if the indices mentioned are lower against the norm by 20% it is possible to predict complications at carrying out SHT procedure. The method provides objective way to select women for whom SHT is useful except thromboembolic complications.

EFFECT: higher accuracy of prediction.

1 ex, 4 tbl

Description

The invention relates to medicine and can be used when using hormone replacement therapy (HRT) in women with natural menopause.

A known method for predicting complications of the cardiovascular system, which consists in conducting a comprehensive study of the mental status and spectral indicators of heart rate variability (RU 2195166 C1, publ. 12/27/2002).

The disadvantages of this method include the impossibility of predicting these complications before using HRT.

The objective of the invention is the creation of criteria for the selection of patients for hormone replacement therapy, especially in women in the menopause, as thromboembolic complications are possible with HRT.

The problem is solved in that in the method for predicting complications of the cardiovascular system before applying hormone replacement therapy (HRT), the antithrombogenic activity of the vascular wall in women is evaluated, for this purpose objective quantitative indicators of the antiplatelet, anticoagulant and fibrinolytic activity of the vascular wall with using a five-minute occlusion of the vessels of the forearm, caused by the application of the cuff of the sphygmomanometer on the shoulder of the subject (cuff sample), then determine the indices of antithrombogenic activity of the vascular wall, which is calculated as the ratio of these indicators before and after the specified cuff test, conduct a quantitative assessment of the degree of decrease in antithrombogenic activity of the vascular wall, while if these indices are reduced by more than 20% compared to the norm , women are not recommended to carry out HRT without the prophylactic use of antiplatelet agents, and with a decrease in indices of less than 20%, HRT is indicated.

The claimed method allows to prevent possible complications from the cardiovascular system as a result of the use of HRT in women in the menopause. The method is based on the assessment of the antithrombogenic activity of the vascular wall in women before the start of therapy, since the use of HRT in women with an initial decrease in the antithrombogenic activity of the vascular wall by more than 20% leads to its further deterioration and the development of diseases of the cardiovascular system associated with the pathology of hemostasis. Such patients are not recommended to perform HRT, since they have a multiple (2–25 times or more) increased risk of developing cardiovascular and thromboembolic complications (angina pectoris, heart attack, stroke, thromboembolism). If the initial decrease in antithrombogenic activity of the vascular wall does not exceed 20% compared with the norm, then HRT restores its indices to normal values with the subsequent maintenance of the achieved effect.

Antithrombogenic activity of the vascular wall is assessed by determining objective quantitative indicators of antiaggregation (ADP-induced platelet aggregation, where ADP is the abbreviation of adenazine diphosphate), anticoagulant (antithrombin III activity in the blood) and fibrinolytic (blood fibrinolytic activity) blood cell vascular activity .V. Baludy. Short-term (5 min) occlusion of the vessels of the forearm, caused by the application of the cuff of the sphygmomanometer on the shoulder of the subject, leads to the release of plasminogen activator, anti-aggregation factor and antithrombin III into the blood from the blood vessels of healthy people.

Then determine the indices of antithrombogenic activity of the vessel wall, calculated as the ratio of the above indicators before and after the cuff test, conduct a quantitative assessment of the degree of decrease in antithrombogenic activity of the vessel walls using these indices.

An example of a specific implementation of the method.

120 women aged 46-48 years were examined. All women were diagnosed with menopausal syndrome of varying severity. All women revealed a deviation of the antithrombogenic activity of the vascular wall from the standard values. The examined women received hormone replacement therapy with Divin (orally, 1 tablet per day, according to the calendar packaging 21 days, 7 days off). Women were observed for 8 years with periodic monitoring of the state of antithrombogenic activity of the vascular wall after 1 month, then every 3 months. The comparison group consisted of 40 healthy women.

All women were examined for gynecological and extragenital pathology. For various reasons, 10 patients refused the proposed therapy.

Statistical data processing was performed using variational statistical programs from Microsoft (Excel).

The results obtained after the first year of therapy allowed us to divide the examined women into two groups: in group A (n = 55 people), the treatment was effective (see Table 1), in group B (n = 65 people) - no (tab. 2). A study of the results showed that the effectiveness of therapy depends on the initial violations of the antithrombogenic activity of the vascular wall, and the change in the indices constituting the antithrombogenic activity of the vascular wall by 20% is critical.

As follows from the table. 3 data, the antithrombogenic activity of the vascular wall in women in group A remained within normal values for the next 7 years of observation, while no woman had cardiovascular diseases.

In the table. Figure 4 shows the dynamics of the antithrombogenic activity of the vascular wall in women of group B. In these women, despite a significant increase in the functional activity of the vascular wall after 1 year of divina therapy, a marked decrease in the antithrombogenic activity of the vascular wall was observed in the next 7 years of observation.

After 2 years of therapy, the indices of antithrombogenic activity returned to their original values, and after 8 years of therapy, the above activity decreased by 50% compared with the control values. Against the background of the above changes in the functional activity of vascular endothelium, 4 women were diagnosed with myocardial infarction, 2 - stroke, 25 - angina pectoris, and 1 - thromboembolism.

Thus, with a decrease in the antithrombogenic activity of the vascular wall by no more than 20%, HRT leads to the normalization of its parameters during the first year of treatment with the subsequent maintenance of the achieved effect. With a decrease of more than 20%, HRT contributes to an insignificant improvement during the first year of treatment, however, a marked decrease in the functional activity of the vascular wall is noted in the future, which leads to the development of pathologies such as coronary heart disease, stroke, thromboembolism.

Table 1
Dynamics of antithrombogenic activity of the vascular wall under the influence of divina therapy in group A during the first year of observation Index (Index) Comparison group Initial data The duration of therapy (months) 1 3 6 nine 12 ATIII s 1.28 ± 0.04 1.13 ± 0.16 1.13 ± 0.11 1.17 ± 0.12 1.21 ± 0.11 1.24 ± 0.13 1.26 ± 0.11 FAK,% 1.56 ± 0.05 1.30 ± 0.01 1.36 ± 0.02 1.39 ± 0.01 1.44 ± 0.01 1.46 ± 0.01 1.53 ± 0.05 ADP-induced platelet aggregation,% 0.82 ± 0.04 0.98 ± 0.05 0.98 ± 0.07 0.92 ± 0.06 0.89 ± 0.06 0.82 ± 0.06 0.81 ± 0.08

table 2
Dynamics of antithrombogenic activity of the vascular wall under the influence of divina therapy in group B during the first year of observation Index (Index) Comparison group Initial data The duration of therapy (months) 1 3 6 nine 12 ATIII s 1.28 ± 0.04 1.00 ± 0.04 1.00 ± 0.06 1.00 ± 0.06 1.07 ± 0.08 1.11 ± 0.06 1.12 ± 0.06 FAK,% 1.56 ± 0.05 1.07 ± 0.02 1.07 ± 0.09 1.12 ± 0.07 1.18 ± 0.07 1.26 ± 0.06 1.31 ± 0.06 ADP-induced platelet aggregation,% 0.82 ± 0.04 1.22 ± 0.09 1.24 ± 0.07 1.15 ± 0.07 1.15 ± 0.05 1.11 ± 0.07 1.11 ± 0.09

Table 3
Dynamics of antithrombogenic activity of the vascular wall under the influence of divina therapy in group A during 8 years of observation Index (Index) The duration of therapy (years) 1 2 3 4 5 6 7 8 ATIII s 1.26 ± 0.11 1.28 ± 0.13 1.28 ± 0.12 1.27 ± 0.11 1.28 ±
0.13 1.29 ±
0.15 1.28 ±
0.11 1.29 ± 0.13 FAK,% 1.53 ± 0.05 1.55 ± 0.03 1.58 ± 0.04 1.61 ± 0.05 1.59 ±
0,03 1.59 ±
0.04 1.61 ±
0.05 1.59 ± 0.04 ADP-induced platelet aggregation,% 0.81 ± 0.08 0.82 ± 0.05 0.81 ± 0.06 0.81 ± 0.06 0.83 ±
0.05 0.83 ±
0.06 0.82 ±
0.06 0.81 ± 0.07

Table 4
Dynamics of antithrombogenic activity of the vascular wall under the influence of divina therapy in group B during 8 years of observation Indicator
(index) The duration of therapy (years) 1 2 3 4 5 6 7 8 ATIII s 1.12 ± 0.06 1.01 ± 0.08 1.01 ± 0.07 0.91 ± 0.06 0.87 ±
0,07 0.90 ±
0.06 0.70 ±
0.05 0.70 ± 0.05 FAK,% 1.09 ± 0.09 1.03 ± 0.03 1.01 ± 0.05 0.98 ± 0.05 0.92 ±
0.05 0.93 ±
0,03 0.93 ±
0.04 0.91 ± 0.04 ADP-induced platelet aggregation,% 1.11 ± 0.09 1.20 ± 0.05 1.25 ± 0.07 1.24 ± 0.09 1.27 ±
0.05 1.26 ±
0,07 1.29 ±
0,07 1.28 ± 0.05

Claims (1)

A method for predicting complications of the cardiovascular system when using hormone replacement therapy (HRT) in women, characterized in that prior to HRT, the antithrombogenic activity of the vascular wall is examined, determining the parameters of ADP-induced platelet aggregation, blood antithrombin III activity and blood fibrinolytic activity and the ratio of these indicators before and after the “cuff test,” and with a decrease in the indices reflecting these relations by more than 20% compared with the norm, predict lodging from the cardiovascular system.