RU2700889C1 - Method for determining the delayed development of the phenomenon of "escape" of the effectiveness of the antihypertensive therapy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to cardiology, and can be used to determine the delayed development of the phenomenon of "escape" of the effectiveness of antihypertensive therapy (AHT). Predictors of development of "escape" phenomenon are determined on the background of receiving effective AHT. Predictors are those of clinical systolic arterial pressure (SAP) in mm Hg and the pulse wave propagation speed on the carotid-femoral segment (cfPWPS) in m/s. Based on the obtained data, calculating the probability of the "escape" phenomenon of AHT (R) efficiency by formula: P=exp(-19.02+(0.24*cfPWPS)+(0.12*SAP))/(1+exp(-19.02+0.24*cfPWPS+0.12*SAP)). If the value P is more than 0.50, a high probability of development of the "escape" of the AHT efficiency in the first three months of its administration is determined. If P 0.50 and less than 0.50, a low probability of developing the phenomenon of "escape" the effectiveness of AHT in the first three months of admission is determined.

EFFECT: method enables predicting the probability of developing the phenomenon of "escape" the effectiveness of AHT in the first three months of admission in the patients with the initially achieved target clinical AP by predictors of developing the phenomenon of "escape" with underlying effective AHT.

1 cl, 2 ex

Description

The invention relates to medicine, namely to cardiology, and can be used to determine the likelihood of delayed development of the phenomenon of “slipping” of the effectiveness of antihypertensive therapy (AGT), associated with the risk of developing cardiovascular complications in patients with arterial hypertension (AH).

The uncontrolled course of arterial hypertension (AH) is a leading risk factor for the development of cardiovascular complications. Currently, despite the wide development of the Pharmaceutical Industry, and the existence of a large selection of antihypertensive drugs, the target level of blood pressure (BP) is achieved and stabilized in only a third of patients with hypertension.

According to modern domestic clinical guidelines for the diagnosis and treatment of hypertension, the target level of blood pressure is a value of less than 140/90 mm RT. Art., determined by clinical measurement. Achieving target blood pressure values allows us to ascertain the effectiveness of the prescribed AHT by the end of the course of selection or correction of therapy. Nevertheless, focusing only on these measurements of blood pressure, it is impossible to assess the delayed effectiveness of the prescribed therapy. The modern scientific literature describes the so-called phenomenon of “slipping” of the effectiveness of AHT, the development of which cannot be explained by the low patient adherence to treatment, the inefficiency of certain groups of antihypertensive drugs, and other classical reasons for the ineffective treatment of hypertension. This is taken into account in modern clinical practice, but it is possible to identify the inefficiency of AHT only at the next appearance at the doctor's office. Moreover, as a rule, the interval of preventive examinations is at least 3 months. Over this period of time, 33% of patients develop the phenomenon of "escape", which leads to an uncontrolled course of hypertension and an increased risk of cardiovascular complications. In addition, according to this patient management scheme, there is a need for outpatient examinations of a large number of patients with hypertension who do not need to be corrected for hypertension.

As an indirect assessment of the risk of the development of the “slipping away” phenomenon, one can also single out a number of factors that determine the apparent inefficiency of AHT. One of these is low adherence to treatment [E.V. Oshchepkova, L.G. Isaeva “Low adherence of patients with arterial hypertension to treatment: approaches to its improvement” Cardiology: a journal for practitioners. / Atmosphere / - 2003.- No. 3. - S. 33-36.]. One of the formulas for assessing adherence to treatment is as follows:

In connection with the use of a mathematical algorithm to calculate adherence to treatment, this method of assessing treatment failure is relatively objective.

However, a limitation in assessing adherence is the need to collect empty blisters from the taken tablets, and “manually count” their number. In addition, this method is usually retrospective, while it is much more important initially to have an idea about the possible development of therapy inefficiency at a remote stage of observation in a particular patient.

Another factor leading to the development of AHT inefficiency may be taking a single antihypertensive drug. The scientific literature describes the mechanism of the development of the phenomenon of “slipping away” in this case: in response to taking one antihypertensive drug, in patients with arterial hypertension, mechanisms are activated that prevent the decrease in blood pressure. [Makolkin V.I. Improving combination therapy is a way to improve the results of the treatment of arterial hypertension // breast cancer. 2007. No.16. S. 1238]

Nevertheless, according to the clinical recommendations for the diagnosis and treatment of hypertension, monotherapy of hypertension is indicated for a specific group of patients, and the appointment of multicomponent hypertension is unjustified and even dangerous due to the lack of evidence or the possibility of an excessive decrease in blood pressure. In addition, it cannot be unequivocally stated that all patients taking one antihypertensive drug will further develop its inefficiency.

The phenomenon of “slipping” of the effectiveness of AGT when prescribing drugs from the ACE inhibitor and ARA-II groups is widely known. [Malay L.N., Miroshnichenko A.N., Sharykin B.V., Konurovsky V.V. To the 110th anniversary of the discovery of renin. Clash of the Titans: ACE inhibitors and sartans. Rational Pharmacotherapy in Cardiology. 2009; 5 (4): 85-92.].

Nevertheless, as in the previous case, this method is not informative, since focusing on the fact of taking drugs from these groups does not always mean the mandatory development of their inefficiency at a distant stage.

A known method for detecting latent inefficiency in the treatment of arterial hypertension in patients with achieved target clinical blood pressure. The patient is identified: gender, age, body mass index, diastolic blood pressure in orthostasis, the number of antihypertensive drugs taken, the reception / absence of an angiotensin II receptor antagonist. Based on these characteristics, the value of the latent inefficiency coefficient of treatment of hypertension (KSNL) is calculated. If KSNL is equal to or greater than 0.1144, the patient is diagnosed with a high probability of latent treatment failure of hypertension. And if KSNL is less than 0.1144, then the probability of latent treatment inefficiency is considered low.

(RF patent No. 2659642, IPC АВВ 5/00, publ. 03.07.2018, Bull. No. 19)

However, this method does not take into account the possibility of the development of AHT inefficiency at a remote stage of observation, which makes it necessary to conduct repeated medical examinations of all patients with the same period of time (both those who underwent BPM and patients who did not pass the study). This fact significantly increases the load on the medical staff. In other words, patients who initially have low CVL may have high chances of the “slipping away” phenomenon, i.e. the development of treatment inefficiency at a distant stage, which is not taken into account in the proposed method, and, due to uncontrolled blood pressure levels, can lead to an increase in cardiovascular risk. In addition, the formula for calculating CSNL itself, which has 6 variables and 7 coefficients, is not convenient for use in real doctor’s practice due to the complexity and duration of the calculation.

The closest analogue is the calculation of the probability of the development of the phenomenon of “slipping” of the effectiveness of antihypertensive therapy by determining and analyzing the values of the predictor indicators of the phenomenon of “slipping” according to the proposed algorithm. A number of predictors of the development of the phenomenon of “slipping away” of antihypertensive therapy are described, which initially made it possible to achieve target blood pressure values [Mikhailova OO, “The Role of Indices of the Daily Profile of Blood Pressure, Structural and Functional State of the Vascular Wall, the Presence and Severity of Obstructive Sleep Apnea Syndrome in Predicting the Phenomenon” "Slipping" of the effectiveness of antihypertensive therapy ", The dissertation for the degree of candidate of medical sciences. -M, 2018 - 143 s]. These predictors include:

- initial levels of systolic blood pressure according to clinical measurements, self-monitoring and daily monitoring of blood pressure;

- pulse blood pressure

- carotid-femoral pulse wave propagation velocity

- brachial artery stiffness index ASI

Moreover, taking into account a rather large number of predictor indicators, it becomes obvious that determining each of them and using the obtained data in clinical practice is not only laborious, but also requires a special set of equipment to determine the likelihood of the development of the “slip away” phenomenon.

The objective of the invention is to create an effective and informative way to determine the likelihood of delayed development of the phenomenon of "slipping away" the effectiveness of antihypertensive therapy, which allows clinically acceptable sensitivity and specificity to predict the ineffectiveness of antihypertensive therapy in the first three months of its administration in patients with initially achieved target clinical blood pressure, and optimally plan the timing their repeated appearances to the doctor to assess the need for AHT correction and control the risk of developing ser cardiovascular complications in patients with arterial hypertension (AH).

The technical result consists in increasing the efficiency and information content of the method for assessing the need for correction of antihypertensive therapy and controlling the risk of developing cardiovascular complications in patients with arterial hypertension.

The technical result is achieved by the fact that in the claimed method for determining the delayed development of the phenomenon of "slipping" the effectiveness of antihypertensive therapy, including determining predictors of the development of the phenomenon of "slipping" while taking effective AGT, according to the invention, the values of clinical systolic blood pressure (SAD) are determined as predictors in mmHg and the propagation velocity of the pulse wave on the carotid-femoral segment (kfSRPV) in m / s, and on the basis of the data obtained, the probability of the phenomenon of “slipping” of the effectiveness of AGT (P) is calculated by the formula:

P = exp (-19.02+ (0.24 * kfSRPV) + (0.12 * kfSRV)) / (1 + exp (-19.02 + 0.24 * kfSRV + 0.12 * CAD)), and with a value of P more than 0.50 determine a high probability of development the phenomenon of "slipping" of the effectiveness of AGT in the first three months of its intake, with a value of P 0.50 and less than 0.50 determine the low probability of the development of the phenomenon of "slipping" of the effectiveness of AGT in the first three months of its administration.

These two independent predictors make it possible to calculate with the greatest accuracy and minimum laboriousness the probability of the development of the phenomenon of “slipping” of the effectiveness of antihypertensive therapy in the first three months after selecting an effective combination of AHT, which makes it possible to use them in an outpatient setting.

The method is as follows.

To assess the likelihood of the development of the “slipping away” phenomenon of the initially effective AGT, it is necessary to determine the values of 2 predictors of this phenomenon while taking effective AGT. These predictors include: clinical systolic blood pressure (SBP) and pulse wave propagation velocity on the carotid-femoral segment (cfSRPV).

1. Clinical measurement of blood pressure should be performed according to the recommendations for the diagnosis and treatment of hypertension, namely:

- position of the patient - sitting, hand on the table at heart level.

- the shoulder cuff is superimposed 2 cm above the elbow, the size of the cuff should correspond to the size of the arm.

- blood pressure measurement is performed by a doctor or nurse after a 5-minute rest. It excludes the use of coffee, tea, smoking 1 hour before the measurement.

- at the initial medical examination, blood pressure measurements are carried out 2-3 times on each arm, with an interval of at least 1 minute. In the subsequent blood pressure is determined on the arm where it was higher with the same magnification.

To process the data of clinical blood pressure, the average value of blood pressure is selected from 3 received.

2. Definition of carotid-femoral PWV

Measurement of cfSPRV is carried out by the method of applanation tonometry, in accordance with the recommendations for standardization of measurements set forth in the Consensus of experts on arterial stiffness.

To calculate the carotid-femoral pulse wave propagation velocity (cfSRPV), a pulse-wave transducer records the pulse wave of the right common carotid artery (at the level of the upper edge of the thyroid cartilage) and the right femoral artery (at the point of exit from the pupartic ligament). The distance from the jugular notch of the sternum to the point of pulsation of the femoral artery in the inguinal region is taken as the path length (D) made by the pulse wave. The time (t) during which the pulse wave travels this path is automatically calculated by the device. kfSRPV is determined by the device as the ratio of the path length (D) to the pulse wave delay time (t). If the measurements do not meet the quality criteria, the study is repeated.

Taking these two predictors into account is determined by their simplicity of determination at the level of the outpatient unit, and the sensitivity and specificity of the test (64.2% and 72.5%, respectively) are high enough to testify in favor of the predictive significance of the result.

After determining the 2 above indicators, their values are substituted into the following formula to determine the likelihood of the development of the phenomenon of "slipping" of the effectiveness of AGT (P):

P = exp (-19.02+ (0.24 * kfSRPV) + (0.12 * CAD)) / (1 + exp (-19.02 + 0.24 * kfSRPV + 0.12 * CAD)), where:

kfSRPV - pulse wave propagation velocity on the carotid-femoral segment, m / s; GARDEN - systolic blood pressure, mmHg

If the probability value is more than 0.50 against the background of taking effective AHT, the patient has the potential possibility of developing the phenomenon of “slipping” of the effectiveness of therapy in the first three months of taking it. This group of patients is recommended daily BP self-monitoring during the first three months of receiving initially effective AGT, as well as a doctor’s visit on demand (if blood pressure is exceeded> 135/85 mm Hg at home, for 3 or more days in a row ), and / or 1 and 3 months after the start of taking this AGT.

If the probability of the development of the “escape” phenomenon is 0.50 or less, the course of hypertension is considered favorable, with a well-controlled level of blood pressure that is within the target values. This group of patients is recommended once a week to carry out self-monitoring of blood pressure and observation by a cardiologist according to the generally accepted scheme: with appearances to the doctor 1 time in 6 months.

Clinical example No. 1

Patient A., 60 years old, suffers from hypertension, with maximum blood pressure in life - 190/110 mm Hg. At the initial appearance to the doctor, blood pressure was 160/100 mm Hg. The doctor of the clinic selected the following scheme of antihypertensive therapy: perindopril 10 mg / day, indapamide 1.5 mg / day, bisoprolol 2.5 mg / day. On this background, the target level of clinical blood pressure was achieved: average numbers - 130/80 mm Hg. When determining kfSRPV against the background of taking this AGT regimen, a significantly increased stiffness of the vascular wall was determined - 16.0 m / s.

After a month of taking the initially effective AHT, the patient came to the doctor with complaints about the frequent need for additional short-acting antihypertensive drugs due to almost daily increases in blood pressure to 150/100 mm Hg. in the last 2 weeks.

When calculating the likelihood of the phenomenon of “slipping” according to the above formula, using the initial data of the clinical GARDEN and kfSRPV, its value was 0.60, which corresponds to the increased risk of developing inefficiency of the prescribed AHT in the first three months of its administration. Thus, the probability value of the “slipping away” phenomenon in this example corresponds to the demonstrated delayed AGT inefficiency at the doctor’s examination after 1 month of taking it.

Clinical example No. 2

Patient Yu., 48 years old, first noted an elevated blood pressure level with random self-measurement - 3 years ago. Permanent antihypertensive therapy does not receive. The maximum blood pressure in life is 180/100 mm Hg. At the doctor’s appointment, blood pressure was 170/100 mm Hg. The following AHT regimen was selected: losartan 100 mg / day, hydrochlorothiazide 25 mg / day. After 3 weeks of taking this treatment regimen, its effectiveness was ascertained: the target level of blood pressure was achieved, which, on clinical measurement, averaged 136/84 mm Hg, kfSRPV against the background of the therapy being taken - 10.0 m / s.

After three months of taking initially effective AGT, the patient came to the doctor for a routine examination. No active complaints. According to the diary of self-monitoring of blood pressure: the level of home blood pressure over the past period of time did not exceed 135/85 mm Hg. In clinical measurement, blood pressure was 130/80 mm Hg.

When calculating the likelihood of the phenomenon of “slipping away” using the above formula, using the initial data of the clinical CAD and cfRS, its value was 0.42, which corresponds to the lack of potential for the development of inefficiency of the prescribed AHT in the first three months of its administration. Thus, the probability value of the “slipping away” phenomenon in this example corresponds to the demonstrated delayed effectiveness of AGT at the doctor’s examination after 3 months of taking it.

The proposed method will increase the effectiveness of the treatment of arterial hypertension at the outpatient stage, without the expected increase in the load on the medical staff of the outpatient unit due to a more differentiated approach to planning repeated examinations. Effective treatment of arterial hypertension, due to the prevention or identification of the phenomenon of “slipping away” and timely correction of antihypertensive therapy, will ultimately help reduce the incidence of cardiovascular complications in patients with hypertension and cardiovascular mortality in general.

Claims (7)

A method for determining the likelihood of delayed development of the phenomenon of "escape" of the effectiveness of antihypertensive therapy (AGT), including the definition of predictors of the development of the phenomenon of "slipping away" on the background of taking effective AGT, characterized in that as predictors determine the values of clinical systolic blood pressure (SBP) in mm Hg and the propagation velocity of the pulse wave on the carotid-femoral segment (kfSRPV) in m / s, on the basis of the data obtained, the probability of the development of the phenomenon of “slipping” of the effectiveness of AGT (P) is calculated by the formula: P = exp (-19.02+ (0.24 * kfSRPV) + (0.12 * CAD)) / (1 + exp (-19.02 + 0.24 * kfSRPV + 0.12 * CAD)), and with a P value of more than 0.50, a high probability of the development of the phenomenon of "slipping" of the effectiveness of AGT in the first three months of its administration is determined, with a P value of 0.50 and less than 0.50, a low probability of developing the phenomenon of “slipping” of the effectiveness of AGT in the first three months of its administration is determined.