RU2705470C1 - Method for assessing the effectiveness of antihypertensive therapy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, cardiology. Patient undergoes manual isometric physical activity (IFA) at the first and subsequent visits to the doctor. One measures arterial pressure (AP) on two hands, selects the arm, on which the higher AP level – "dominant" – was determined. After 5 minutes, a maximum force in the patient's "dominant" arm is determined by means of a manual dynamometer. After 10 minutes AP is measured on the "dominant" arm immediately before the IFA test. Patient then compresses dynamometer for 3 minutes with force of 30 % of the maximum load. At end 3rd minutes of continuous compression of dynamometer fix AP level at load peak. Efficacy of the antihypertensive therapy is evaluated by the presented original mathematical formulas.

EFFECT: method enables assessing the effectiveness of the antihypertensive therapy without the ABPM, including concealed therapy inefficiency, preventing the occurrence of complications.

1 cl, 2 ex

Description

The invention relates to medicine, namely to cardiology, therapy, general practice, methods for assessing the effectiveness of treatment of patients with arterial hypertension (AH), including “hidden treatment inefficiency” (SNL), optimization (selection of treatment regimen, selection of drug doses) antihypertensive therapy (AHT) and cardiovascular risk management (SSR) in a patient with AH.

AH is one of the key factors in the development of cardiovascular diseases (CVD) in Russia: the prevalence of AH is on average 44% (from 18.3% among people aged 25-34 to 74.5% »among people 55-64 years old ) [Fighters SA. Balanova Yu.A., Shalnova S.A. et al. on behalf of the participants in the ESSE-RF study. Arterial hypertension among people 25-64 years old: prevalence, awareness, treatment and control. Cardiovascular Therapy and Prevention 2014; 14 (4): 4-14].

Effective drug treatment of hypertension is the main way to prevent the development of target organ damage (POM) and cardiovascular complications (CCO) in a patient suffering from hypertension [Williams B, Mancia G, Spiering W, et al. 2018 ESC / ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018; doi: 10.1093 / eurheartj / ehy339].

Such treatment is considered effective when the blood pressure drops below 140/90 mm Hg. (GFCF, 2004), and according to GFCF for 2018 - up to 120/80 mm Hg. In accordance with the recommendations of GFCF, normalization of blood pressure should be achieved as soon as possible, up to 2-3 months.

Despite the wide arsenal of antihypertensive drugs (AHP), the problem of insufficient effectiveness or SNL AH remains the most serious. In routine practice, the assessment of the achievement of the target level of blood pressure - the equivalent of effective treatment of hypertension in a patient is assessed by measuring the level of blood pressure (BP) by a doctor at the reception (clinical / office blood pressure). However, normal office BP can give the impression of false well-being. Relying only on the “office” measurement of blood pressure today, you can: skip the diagnosis of hypertension, and this is associated with a delay in the onset of treatment for the disease and a subsequent increase in the risk of developing CCO, or, conversely, diagnose “pseudohypertension”, which will entail unjustified prescribing of the patient [Schiffrin EL Campbell NR, Feldman RD, et al. Hypertension in Canada: past, present, and future. Ann Glob Health 2016; 82: 288-299].

Evaluation of the effectiveness of AHT in a patient based only on an office measurement may not always be accurate, especially in patients with an isolated increase in ambulatory blood pressure (latent hypertension), recorded only with 24-hour blood pressure monitoring (BPM), as well as in patients with white coat hypertension "(With elevated levels of office blood pressure and normal blood pressure outside the hospital - with BPA and self-monitoring), who may have the false impression of treatment effectiveness in the office measurement of blood pressure [Platonova EV, Gorbunov V.M. Use of outpatient blood pressure measurement methods to evaluate the effectiveness of antihypertensive therapy. Cardiovascular Therapy and Prevention, 2006; 5 (3): 101-110]. It is shown that underestimating the antihypertensive effect adversely affects the patient's adherence to treatment.

In routine practice, the assessment of the achievement of the target level of blood pressure - the equivalent of effective treatment of hypertension in a patient is assessed by measuring the level of blood pressure (BP) by a doctor at the reception (clinical / office blood pressure). At the same time, assessing the effectiveness of AHT in a patient based only on an office measurement may not always be accurate, especially in patients with an isolated increase in ambulatory blood pressure (latent hypertension), recorded only with 24-hour blood pressure monitoring (BPM), as well as in patients with the “white coat” hypertension (with elevated levels of office blood pressure and normal blood pressure outside the hospital — with BPM and self-monitoring), which may give a false impression of treatment effectiveness during the office measurement of blood pressure [Platonova E.V., Gorbunov V.M. Use of outpatient blood pressure measurement methods to evaluate the effectiveness of antihypertensive therapy. Cardiovascular Therapy and Prevention, 2006; 5 (3): 101-110]. It is shown that underestimating the antihypertensive effect adversely affects the patient's adherence to treatment.

Normal office BP can give the impression of false well-being. The frequency of the SNL hypertension phenomenon varies in different studies from 17 to 60%. Among the predictors of SNL AH is the positive difference between the level of SBP, measured in orthostasis and office blood pressure, measured in the sitting position of the patient, as well as the variability of the average daily systolic blood pressure (SBP) [Smirnova MI, Oganov R.G., Gorbunov V.M. . and others. Latent inefficiency of treatment of arterial hypertension: frequency and predictors. Cardiovascular Therapy and Prevention, 2011; 10 (6): 11-17]. The presence of SNL AH increases the risk of patients with MTR by 76%.

At present, it is possible to detect SNF hypertension in case of BPM and patient self-monitoring of blood pressure at home [Smirnova MI, Platonova EM, Britov AN et al. Frequency and markers of latent arterial hypertension and latent inefficiency of treatment of arterial hypertension in workers of an industrial enterprise according to a routine examination. Rational pharmacotherapy in cardiology, 2014; 10 (5): 481-487]. These methods are complementary.

It is known that, unlike other methods of measuring blood pressure, BPM (office / clinical measurement or patient self-monitoring at home) objectively determines the true level of blood pressure and has clear advantages in assessing the effectiveness of antihypertensive drugs (AHP). Registration of blood pressure levels outside the walls of a hospital with outpatient BPM is rare, especially if the patient reaches the target level of "office" blood pressure. The described method of ABPM is the closest analogue of the claimed method for evaluating the effectiveness of antihypertensive drugs.

The disadvantages of SMAD are its complexity and cost. The method requires a differentiated approach, that is, assigning it to all patients treated for hypertension appears to be inappropriate [Smirnova M.I., Oganov R.G., Gorbunov V.M. and others. Latent inefficiency of treatment of arterial hypertension: frequency and predictors. Cardiovascular Therapy and Prevention, 2011; 10 (6): 11-17].

In addition, there are a number of contraindications for the ABM:

1. Dermatological diseases associated with skin lesions of the upper limb - lichen, fungus, etc.,

2. Blood diseases, for example, severe thrombocytopenia, hemorrhagic purpura, petechial rash, etc., characterized by the appearance of bruises at the slightest compression of the skin,

3. Injury to the upper limbs,

4. Vascular diseases with damage to arteries and veins of the upper extremities in exacerbation,

5. Mental illness of the patient associated with inability to self-care, with aggression and with other symptoms.

(https://sosudinfo.ru/arterii-i-veny/smad/)

At the same time, the role of office blood pressure measurement in assessing the effectiveness of AHT should not be neglected, on the contrary, it can be strengthened by using various tests that provoke the development of exercise hypertension, for example, by means of a test with manual isometric physical activity (IFN).

Isometric loading is a physiological test designed to assess the functional state of the heart [Ogunlade O, Ayoka AO, Akintomide A, et al .. Non-Invasive Assessment of Cardiac Autonomic Functions in Healthy Young Adults in Ile-Ife, South-Western Nigeria. Int J Clin Cardiol, 2015; 2: 036]. Isometric loads are capable of simulating a “stress hypertension”, primarily an increase in SBP and heart rate (HR), which is associated with activation of the sympathoadrenal system (CAS) and an increase in blood levels of catecholamines [Krzeminski K, Cybulski A, Ziemba A, NazarK . Cardiovascular and hormonal responses to static handgrip in young and older healthy men. Eur J Appl Physiol. 2012; 112 (4): 1315-25].

A “loading” blood pressure that develops in response to physical activity is considered as a predictor of latent (“camouflage”) hypertension [Thanassoulis G, Lyass A, Benjamin EJ, et al. Relations of exercise blood pressure response to cardiovascular risk factors and vascular function in the Framingham Heart Study. Circulation 2012; 125: 2836-2843], predictor of hypertension in individuals with prehypertension [Schultz MG, Otahal P, Cleland VJ, et al. Exercise-induced hypertension, cardiovascular events, and mortality in patients undergoing exercise stress testing: a systematic review and meta-analysis. Am J Hypertens 2013; 26: 357-66] and the development of cardiovascular events (myocardial infarction, stroke, coronary heart disease) in patients with established hypertension [Schultz MG, Hare JL, Marwick TH, Stowasser M, Sharman JE. Masked hypertension is "unmasked" by low-intensity exercise blood pressure. Blood Press 2011; 20 (5): 284-9].

The technical result of the claimed method is the ability to timely assess the effectiveness of antihypertensive therapy, more effective prevention of MTR, the detection of SNF in hypertension through the use of a test with manual IFN. The proposed method for determining the effectiveness of AHT and detecting SNL in hypertension allows a more complete and accurate assessment of the clinical effect of treatment without using a device for BPM, which avoids the above disadvantages when using a device for measuring BPM and at the same time contributes to the timely identification of people with increased SSR, may also improve patient adherence to antihypertensive therapy _g

The claimed technical result is achieved due to patients performing a test with manual isometric physical activity (IFN).

The test with a manual IFN is informative, convenient to use, quickly activates the cardiovascular system, is easily performed by both the doctor and the patient, does not cause discomfort to the patient, and is affordable. When performing the test does not require additional time for patient education and additional space, the involvement of other specialists, except the attending physician. The IFN test can be performed at any time of the day, regardless of the patient's activity during the day.

The method is as follows

To solve the problem in the method of evaluating the effectiveness of AGT and detecting SNL in hypertension, a test with manual IFN was performed. Manual IFN was modeled by means of a manual dynamometer (a manual dynamometer of any manufacturer can be used for this).

The IFN test was performed during the patient’s visit to the clinic (usually this is the first half of the day), at least 30 minutes before the patient’s visit to the doctor, he did not take any stimulants that affect blood pressure levels (drugs, coffee, smoking) . Before starting the IFN test, the patient was in a sitting position for at least 5 minutes and was relaxed. Before starting the first test, “office” blood pressure was measured on two hands according to generally accepted rules with the aim of choosing a “dominant” hand (on which a higher level of blood pressure was determined); after 5 minutes, the maximum force in the patient’s “dominant” hand was determined by means of a manual dynamometer in order to calculate the level of estimated manual IFN, which is 30% of the individual maximum tolerance; after 10 minutes, blood pressure was measured on the "dominant" arm immediately before the test with IFN, then the patient in a sitting position for 3 minutes squeezed the dynamometer with a force of 30% of the individually tolerated maximum load and was fixed at the end of the 3rd minute of continuous squeezing of the dynamometer blood pressure at peak load. The applied test with manual IFN was standardized, each of the patients performed it at least four times, while taking into account the individual reaction of a particular patient. On repeated visits of the patient to the doctor, a test with manual IFN was performed on the patient's previously chosen “dominant” arm according to the scheme described above.

The proposed method was tested in a group of patients with hypertension (n = 44) aged 37 to 72 years (average age 56.4 ± 7.9 years) with I and II degree of increase in blood pressure (blood pressure level ≥140 / 90 and <180/110 mmHg.). The study excluded patients with severe hypertension (SBP levels ≥180 mm Hg and / or DBP ≥110 mm Hg) and secondary hypertension, as well as patients suffering from morbid obesity (with a BMI ≥ 40 kg / m ² ).

In parallel with the test with manual IFN, the patients were monitored for 24-hour (24-hour) blood pressure monitoring (BPM) using a CardioTens apparatus (Meditech, Hungary). Blood pressure and heart rate were measured in the "day" period (7: 00-23: 00) with intervals of 15 minutes and in the "night" period (23: 00-7: 00) with intervals of 30 minutes. Each patient performed four to six procedures of BPM.

To determine the possibility of using the test with a manual IFN to assess the effectiveness of the prescribed AHT, we studied the nature of the SBP reaction in response to IFN taking into account the SBP values in the clinical measurement of blood pressure and BPM. Patients performed 165 tests with manual IFN.

AHT was considered effective when reaching the target SBP values while sitting with an “office” measurement (<140 mmHg), and the measurement of SBP sitting in front of the IFN (<140 mmHg). In the control monitoring of ABPM, effective AGT was considered the average SBP per day (≤135 mm Hg) and 24 hours (<130 mm Hg).

As a result, three groups of patients were formed:

- 1 group - patients (n = 93) with no antihypertensive effect - exceeding the achievement of target levels in terms of indicators: SBP during clinical measurement and before IFN (≥140 mm Hg), mean daytime SBP (> 135 mm RT. Art.) and in 24 hours (> 130 mm Hg) according to the BPMS;

- group 2 - patients (n = 26) who did not have a definite antihypertensive effect during therapy: SBP exceeded the target level in the clinical measurement and before IFN (≥140 mm Hg), but the target values were achieved according to the BPM the average GARDEN per day (≤135 mm Hg) and 24 hours (≤130 mm Hg);

- group 3 - patients (n = 46) who achieved therapy with the target levels of SBP in terms of parameters: SBP during clinical measurement and before IFN (<140 mmHg), mean daytime SBP (≤135 mm Hg) and in 24 hours (≤130 mm Hg) according to the Smad.

In order to assess the effectiveness of AHT in hypertension through a test with manual IFN at the first and subsequent visits to the doctor, linear regression modeling was performed, which allowed to distinguish the following types of antihypertensive effect of the therapy:

"Defined antihypertensive effect":

"Uncertain antihypertensive effect":

"The absence of antihypertensive effect":

Where:

GARDEN _PIKINF-2 - GARDEN at the peak of IFN, during treatment, at the last visit to the doctor;

GARDEN peak IFN _-1 - GARDEN at the peak of IFN, before treatment, at a previous visit to the doctor;

GARDEN _doINF-1 - GARDEN before IFN, before treatment, at a previous visit to the doctor;

GARDEN _doINF-2 - GARDEN before IFN, during treatment, at the last visit to the doctor.

It was found that in order to evaluate the effectiveness of AGP, to detect SNL in hypertension and to optimize AGT, it is advisable to study changes in blood pressure levels in a test with manual IFN. The developed criteria for evaluating the effectiveness of AGT, taking into account the results of IFN samples, can be used in practice as an alternative to ABPM.

The results of the study showed that if the SBP while sitting at the office measurement and before the IFN was <130 mm Hg and at the peak of IFN <150 mm Hg, then during the ABPM these figures corresponded to the SBP average daily <135 mm Hg. and SBP average of 24 hours <130 mm Hg, which is the norm. Analysis of the level of SBP at the peak of IFN of low / moderate intensity in patients with hypertension who achieve a “definite antihypertensive effect” against the background of AGT - target levels of SBP by indicators (clinical SBP and before IFN <140 mm Hg, mean SBP in daytime ≤135 and for 24 hours ≤130 mm Hg), allowed us to propose the criteria for “exercise hypertension”: this is a clinical GARDEN at the peak of IFN≥150 mm Hg. (in this case, the CAD at the "office" measurement at rest and before IFN> 130 mm Hg). The detection of “exercise hypertension” during the test with IFN correlates with the presence of hypertension according to the ABPM.

Examples of specific performance of the method:

Example 1

A 45-year-old patient, diagnosed with grade 2 hypertension, took antihypertensive therapy with effect control after 2 weeks; "Office" GARDEN at the 1st visit to the doctor - 168 mm Hg and at the 2nd visit to the doctor after 1 month - 170 mm Hg. Levels of GARDEN before the test with manual IFN: at the 1st visit to the doctor - 166 mm Hg. and at the 2nd visit to the doctor - 168 mm Hg. The levels of SBP at the peak of the test with manual IFN were at the 1st visit of the patient to the doctor - 182 mm Hg and at the 2nd visit of the patient to the doctor - 186 mmHg

The patient underwent BPA after 2 weeks of AGT (at the 2nd visit to the doctor): the average SBP in the daytime was 170 mm Hg. and in 24 hours - 158 mm Hg.

Thus, in a patient:

The GARDEN of peak IFN _-2 (GARDEN at the peak of IFN, during treatment) was 186 mm Hg;

GARDEN peak IFN _-1 (GARDEN at the peak of IFN before treatment) was 182 mm Hg;

GARDEN _doIFN-2 (GARDEN before IFN during treatment) was 168 mm Hg.

In the patient against the background of AHT, “absence of antihypertensive effect” was recorded:

186 mmHg GARDEN _{PIK IFIF-2} ≥182 mmHg GARDEN _{PIK IFN-1} ,

168 mmHg GARDEN _doIFN-2 > 130 mm Hg

AGT was changed for the patient with an assessment of the effect after 2 weeks (3rd visit): the “office” CAD at the 2nd visit to the doctor was 170 mmHg. and on the 3rd visit to the doctor - 130 mm Hg. Levels of GARDEN before the test with manual IFN: on the 2nd visit to the doctor - 168 mm Hg. and at the 3rd visit to the doctor - 130 mmHg. The level of GARDEN at the peak of the test with manual IFN at the 2nd visit to the doctor was 186 mmHg. and on the 3rd visit to the doctor - 144 mm Hg.

The patient underwent BPA after 2 weeks of AHT (on the 3rd visit to the doctor): the average SBP in the daytime is 134 mm Hg. and in 24 hours 128 mm Hg.

Thus, in a patient:

The GARDEN of peak IFN _-2 (GARDEN at the peak of IFN, against the background of treatment - the 3rd visit to the doctor) was 144 mm Hg;

GARDEN peak IFN _-1 (GARDEN at the peak of IFN before treatment - 2nd visit to the doctor) was 186 mm Hg;

GARDEN _doIFN-2 (GARDEN before IFN during treatment - 3rd visit to the doctor) was 128 mm Hg;

GARDEN _doIFN-1 (GARDEN before IFN before treatment - 2nd visit to the doctor) was 168 mm Hg.

In a patient with AGT, a “definite antihypertensive effect” was recorded:

144 mmHg GARDEN _{PIK IFIF-2} <186 mmHg GARDEN _{PIK IFN-1} ,

144 mmHg GARDEN _PIK IFN -2≤168 mm Hg GARDEN _doIFN-1 ,

130 mmHg GARDEN _doIFN-2 ≤130 mm Hg

Example 2

A 55-year-old patient, diagnosed with grade 1 hypertension, took antihypertensive therapy with effect control after 2 weeks; "Office" GARDEN at the 1st visit to the doctor - 150 mm Hg and at the 2nd visit to the doctor after 1 month - 142 mm Hg. Levels of GARDEN before the test with manual IFN: at the 1st visit to the doctor - 148 mm Hg. and at the 2nd visit to the doctor - 142 mmHg. The levels of SBP at the peak of the test with manual IFN were at the 1st visit of the patient to the doctor - 160 mmHg. and at the 2nd visit of the patient to the doctor - 152 mm Hg.

The patient underwent BPA after 2 weeks of AGT (at the 2nd visit to the doctor): the average SBP in the daytime was 134 mmHg. and in 24 hours - 128 mm Hg.

Thus, in a patient:

GARDEN peak IFN _-2 (GARDEN at the peak of IFN, during treatment - the 2nd visit to the doctor) was 152 mm Hg;

GARDEN peak IFN _-1 (GARDEN at the peak of IFN before treatment - the first visit to the doctor) was 160 mm Hg;

GARDEN _doIFN-1 (GARDEN before IFN before treatment - the first visit to the doctor) was 148 mm Hg;

GARDEN _doIFN-2 (GARDEN before IFN during treatment - 2nd visit to the doctor) was 142 mm Hg.

In a patient with AGT, an “indeterminate antihypertensive effect” was recorded:

152 mmHg GARDEN _{PIK IFN-2} <160 mm Hg GARDEN _{PIK IFN-1} ,

152 mmHg GARDEN _{PIK IFN-2} ≤148 mmHg GARDEN _doIFN-1 ,

142 mmHg GARDEN _doIFN-2 > 130 mmHg.

The above examples prove the feasibility of using the claimed method for evaluating the effectiveness of antihypertensive therapy through a test with manual IFN in patients with hypertension. The claimed method is able to replace the monitoring of blood pressure, without actually conducting a BPA, to evaluate the effectiveness of antihypertensive therapy, preventing the occurrence of CCO. to detect SNL in hypertension can replace the repeated use of SMAD in patients with hypertension.

Claims (10)

A method for evaluating the effectiveness of antihypertensive therapy, including measuring systolic blood pressure (BP), characterized in that the patient is tested with manual isometric physical activity (IFN) at the first and subsequent visits to the doctor, for which blood pressure is measured on two hands, a hand is selected, which was determined a higher level of blood pressure - "dominant", after 5 minutes using a manual dynamometer determine the maximum force in the "dominant" hand of the patient, after 10 minutes measure blood pressure on the "dominant" hand directly But before performing the IFN test, then the patient squeezes the dynamometer for 3 minutes with a force of 30% of the maximum load, at the end of the 3rd minute of continuous squeezing of the dynamometer, the blood pressure level at the peak of the load is recorded and the effectiveness of antihypertensive therapy is assessed as: “Defined antihypertensive effect "at GARDEN _{peak IFN-2} <GARDEN _{peak IFN-1} , GARDEN _{peak IFN-2} ≤GARDEN _doIFN-1 , GARDEN _doIFN-2 ≤130 mm Hg; "Uncertain antihypertensive effect" with GARDEN _{PIK IFN-2} <GARDEN _{PIK IFN-1} , GARDEN _{PIK IFN-2} ≤GARDEN _doIFN-1 , GARDEN _doIFN-2 > 130 mm Hg; "The absence of antihypertensive effect" with GARDEN _{PIK IFN-2} ≥GARDEN PIK _IFN-1 , GARDEN _doIFN-2 > 130 mmHg, where GARDEN peak IFN _-2 - GARDEN at the peak of IFN, during treatment, at the last visit to the doctor; GARDEN peak IFN _-1 - GARDEN at the peak of IFN, before treatment, at a previous visit to the doctor; GARDEN _doIFN-1 - GARDEN before IFN, before treatment, at a previous visit to the doctor; GARDEN _doIFN-2 - GARDEN before IFN, during treatment, at the last visit to the doctor.