RU2722879C1 - Method for prediction of risk of premature aging of young and middle-aged men - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to gerontology, and can be used for prediction of risk of premature aging (PA) of young and middle-aged men. Proper biological age (PBA), as well as actual biological age (ABA) are determined with due allowance for fibroblast growth factor 21, systolic arterial pressure, respiratory arrest time, length of static balancing on one leg. Determining the difference between the ABA and the PBA values. If the value of the above difference is <3, a low risk of early aging of young and middle-aged men is predicted; if the value (ABA−PBA) is 3–9, an average risk is predicted, while the value (ABA−PBA) > 9 shows a high risk of PA of young and middle age.

EFFECT: method enables higher accuracy, specificity and sensitivity of predicting the risk of PA of young and middle age by evaluating a set of the most significant indicators.

1 cl, 1 tbl, 4 ex

Description

The invention relates to medicine, namely gerontology and can be used to predict the risk of premature aging (PS) of young and middle-aged men.

Correspondence of the calendar age in various individuals does not always mean the pattern of occurring age-related changes in organs and tissues. To this end, various methods are proposed for determining the actual biological age (FBV) to assess the psychological and physical condition and adaptive capabilities of a particular person. Despite the fact that there is no ideal method that takes into account changes in all body systems, it is necessary to actively identify individuals ahead of the pace of aging and take preventive measures to prevent age-related pathologies in young people.

The methodology for determining the biological age (BV) by the method proposed by S.G. Abramovich et al. Includes an assessment of the following indicators: cardiac output, heart economy index, vegetative index, general conjunctival index, systolic index, skin heat recovery time, duration of skin vessels spasm on norepinephrine, subjective health assessment using questionnaires, breath holding duration after deep breath, muscle strength of the hand, the duration of static balancing, the digital Wexler test [1]. The use of this technique is quite time-consuming and not suitable for routine use if it is necessary to quickly determine the compliance of BV with calendar age (CV) during mass examination.

An improved methodology for determining the BV of the above authors also includes the determination of many indicators: skin and hair aging coefficient, eye age, dental index, body mass index, systolic and diastolic blood pressure, heart function index, taste threshold for table salt, peak flow measurement, waist circumference, Bourdon test attention index and thermoregulation coefficient [2]. The authors propose the use of a number of methods that are not used in ordinary practice, which further complicates the conduct of such testing.

Methods for determining BV taking into account indicators of computer electroencephalography [3], echocardiography [4], spirography [5], blood analysis [6], mental and physical performance [7] and anthropometry [8] developed in the Laboratory of Ontogenesis of the Perm Medical Academy reflect only changes occurring in individual body systems. The most widespread in scientific research and practice in connection with accessibility and integrability is the method for predicting the risk of premature aging of the body, proposed by V.P. Voitenko and coauthors. In this case, systolic, diastolic and pulse arterial pressure, the speed of the pulse wave propagation through the arteries of the elastic and muscle type, vital capacity of the lungs, breath holding time on exhalation, accommodation, hearing acuity, static balancing on the left leg, body weight, subjective health assessment, are examined Wexler symbol-digital test [9]. This method has an inherent coefficient of determination equal to 0.63, the correlation of the calculated BV with HF is 0.78. In this regard, an improved method for determining BV was developed [10], according to which the pulse wave propagation velocity through the elastic and muscle type arteries and the time of breath holding on exhalation were replaced by measuring the QT interval. Thus, the authors claim an increase in the accuracy of determining the BV of patients (correlation of the calculated BV with CV) to 0.87.

As a prototype for the closest technical essence, we have chosen a method for predicting the risk of premature aging of the body, proposed by V.P. Voitenko and coauthors in a simplified version. This technique includes determining the actual biological age for men by determining systolic blood pressure, breath holding time on inhalation, the duration of static balancing on one leg, and the health self-esteem index (POP) using a questionnaire [9]. When determining the FBV in this way, complex diagnostic equipment is not required.

Formula for calculating the actual biological age (FBV) for men:

FBV = 26.985 + 0.215 ⋅ CAD-0.149 HFA + 0.723 ⋅ POP-0.151 Б SB, where

GARDEN - the value of systolic blood pressure, mm Hg;

HFA - the value of the breath-holding time on inhalation, s;

SB - the value of the time of static balancing on one leg, sec.

POPs - self-assessment index of health in points;

Formula for calculating proper biological age (DBV) for men:

DBV = 0.629 KB + 18.56

Depending on the deviation of the calculated FBV from DBV, the following ranks are distinguished:

I rank: from (-15) to (-9) years, which corresponds to a sharply slowed down rate of aging;

II rank: from (-8.9) to (-3) years, which corresponds to a slowed down rate of aging;

III rank: from (-2.9) to (+2.9) years, which means an approximate correspondence between BV and KV;

IV rank: from (+3) to + (8.9) years, which corresponds to the accelerated rate of aging;

V rank: from (+9) to + (15) years, which corresponds to a sharply accelerated rate of aging [12].

The disadvantages of the method selected as a prototype include insufficiently high accuracy of estimation of the FBV: the determination coefficient in men is 76.2% [11], the low specificity and sensitivity, which, according to our own data, are 80% and 79%, respectively.

The technical result of the invention is to increase the accuracy of the method, its specificity and sensitivity.

We chose men as the object of study, due to the fact that the relationship between CV and aging markers in women is less than in men. This indicates a slowdown in the rate of aging in women, which may be due to gender differences, social and economic factors [12]. The choice of the age of men to study (young and middle age) was determined by the fact that when detecting premature aging in the subjects, the ongoing processes can be reversible and timely correction can increase their life expectancy and reduce early mortality.

The technical result of the invention is achieved by the fact that a method for predicting the risk of premature aging of young and middle-aged men is to determine the actual biological age (PBF), taking into account the measured parameters of the subject — fibroblast growth factor 21, systolic blood pressure, breath holding time, and duration static balancing on one leg, with the subsequent calculation of the FBV of the subject according to the formula:

FBV = 15.948 + 0.746⋅ln (FGF 21) + 0.301⋅SAD - 0.193⋅ZVV - 0.152⋅SB,

where FBV - the actual biological age, years;

FGF 21 - the value of fibroblast growth factor 21, ng / l;

GARDEN - the value of systolic blood pressure, mm Hg;

HFA - the value of the breath-holding time on inhalation, s;

SB - the value of the time of static balancing on one leg, s,

Then determine the proper biological age (DBV) of the subject according to the formula:

DBV = 0.629⋅KV + 18.56, where DBV is the proper biological age, KB is the calendar age with subsequent determination of the difference between the obtained values of the BBV and DBV. If the difference between the obtained values (PBW and DBV) is <3, a low risk of premature aging of young and middle-aged men is predicted, which corresponds to the first risk group for PS of the body. With a value of (FBV-DBV) of 3–9, the average risk of PS of young and middle-aged men is predicted, which corresponds to the second risk group for PS of the body. With a value of (FBV-DBV)> 9, a high risk of PS, young and middle-aged men is predicted, which corresponds to the third risk group for PS of the body.

The inventive method is as follows:

To determine the actual biological age, a study of the following indicators is carried out:

1. Determination of the concentration of fibroblast growth factor 21 (FGF-21) in serum is carried out by enzyme-linked immunosorbent assay using the BCM Diagnostics sets SK00145-01 (BCM Diagnostics, USA), in ng / l.

2. Systolic blood pressure (SBP) is measured according to the generally accepted auscultatory technique of N. S. Korotkov on his right hand, in a sitting position, three times, with an interval of 5 min, in mm RT. Art. Take into account the results of the measurement at which the blood pressure has the smallest value (in mm RT. Art.).

3. The breath holding time on exhalation (the duration of the breath holding after deep inhalation and deep exhalation) is measured three times using a stopwatch with a 5-minute interval. Take into account the largest value (in seconds).

4. The time of static balancing on one leg is determined using a stopwatch when the subject is standing on his left foot, without shoes, eyes are closed, hands are lowered down and pressed to the hips (without prior training). Take into account the best result (the longest standing time on one leg in seconds) from three attempts with a 5-minute interval.

5. The PBF of the subject is calculated by the formula:

FBV = 15.948 + 0.746⋅ln (FGF 21) + 0.301 ⋅ SAD - 0.193 Д HFA - 0.152 Б SB, where FBV - actual biological age, years; FGF 21 - the value of fibroblast growth factor 21, ng / l; GARDEN - the value of systolic blood pressure, mm. Hg; HFA - the value of the breath-holding time on inhalation, s; SB - the value of the time of static balancing, s.

6. DBV of the subject is calculated by the formula:

DBV = 0.629⋅KV + 18.56, where DBV is the proper biological age, KB is the calendar age.

7. Determine the difference between the obtained values of the PBW and DBV.

8. When the difference between the obtained values (PBW and DBV) is <3, a low risk of premature aging of men of young and middle age is predicted, which corresponds to the first risk group for PS of the body, with a value of (PCB-DBV) of 3-9, the average risk of PS is predicted young and middle-aged men, which corresponds to the second risk group for PS of the body; with a value of (FBV-DBV)> 9, a high risk of PS, young and middle-aged men is predicted, which corresponds to the third risk group for PS of the body.

Significant distinguishing features and a causal relationship between them and the achieved result:

additional determination of fibroblast growth factor 21 with the subsequent calculation of the actual biological age of the subject according to the formula:

FBV = 15.948 + 0.746⋅ln (FGF 21) + 0.301⋅SAD-0.193⋅ZDV-0.152⋅SB,

where FBV - the actual biological age, years;

FGF 21 - individual value of fibroblast growth factor 21, ng / l;

GARDEN - individual value of systolic blood pressure, mm Hg;

HFA - individual value of the breath-holding time on inhalation, s;

SB - individual value of the time of static balancing on one leg, s,

then determine the proper biological age of the subject according to the formula:

DBV = 0.629⋅KV + 18.56, where DBV is the proper biological age, KB is the calendar age, with subsequent determination of the difference between the obtained values of the proper biological age and when the difference between the obtained values (PBV and DBV) <3, low risk is predicted premature aging of young and middle-aged men, which corresponds to the first risk group for PS of the body, with a value (FBV-DBV) of 3-9, the average risk of PS for young and middle-aged men is predicted, which corresponds to the second risk group for PS in the body; with a value of (FBV-DBV)> 9, a high risk of PS, young and middle-aged men is predicted, which corresponds to the third risk group for PS of the body.

Fibroblast growth factor 21 is a circulating protein with antihyperglycemic, lipolytic and geroprotective properties. Its level rises with coronary heart disease, type 2 diabetes mellitus, obesity, atherosclerosis, non-alcoholic fatty liver disease, chronic renal failure, which are typical for people of an older age group. Identification of an elevated level of this factor indicates the presence and / or possible development of the above diseases. The establishment of such diagnoses at a young and middle age indicates the formation of premature aging in them. When conducting a correlation analysis, it was found that the levels of fibroblast 21 growth factor are statistically significantly correlated with indicators characterizing aging - glucose, cholesterol, cholesterol, high, low and very low density lipoproteins, triglycerides, C-reactive protein, body mass index, signs left ventricular hypertrophy according to ECG (table 1).

In this regard, we hypothesized that there is a relationship between the values of fibroblast growth factor 21 and signs of aging, so this indicator can be used in calculating the actual biological age.

This assumption was confirmed by testing in 99 subjects.

The correlation of the calculated FBV with the calendar age was 0.98 for young and middle-aged men, and 0.76 in the prototype. In the regression analysis, informativeness (determination coefficient R ² = 0.984> 0.5) and adequacy (F = 1422.8; p = 3.8⋅10 ^-83 , i.e., the significance level according to the F-criterion is significantly less than 0, were established). 05).

Thus, the set of essential distinguishing features is new and, compared with the prototype method, increases the accuracy, sensitivity and specificity of predicting the risk of premature aging in men of young and middle age.

We give examples of specific performance of the proposed method:

Example 1. Surveyed A., 42 years old.

According to the claimed method:

FBV = 15.948 + 0.746⋅ln (350.21) + 0.301⋅147-0.193⋅24-0.152⋅31 = 52.746

DBV = 0.629⋅42 + 18.56 = 44.978

FBV-DBV = 7.768

According to the prototype method:

FBV = 26.985 + 0.215⋅147-0.149⋅24 + 0.723⋅6-0.151⋅31 = 54.671

DBV = 0.629⋅42 + 18.56 = 44.978

FBV-DBV = 9.693

Thus, in subject A., 42 years old, according to our method, they predict the average risk of premature aging, which corresponds to the second risk group for PS of the body; by the method of the prototype - a high risk of PS, which corresponds to the third risk group of PS of the body.

Example 2. Surveyed M., 45 years old.

According to the claimed method:

FBV = 15.948 + 0.746⋅ln (380.98) + 0.301⋅137-0.193⋅35-0.152⋅39 = 46.427

DBV = 0.629⋅45 + 18.56 = 46.865

FBV-DBV = -0.438

According to the prototype method:

FBV = 26.985 + 0.215⋅137-0.149⋅35 + 0.723⋅5-0.151⋅39 = 48.951

DBV = 0.629⋅45 + 18.56 = 46.865

FBV-DBV = 2,086

Thus, in examined M., 45 years old, according to both methods, a low risk of premature aging is predicted, which corresponds to the first risk group for PS of the body.

Example 3. Surveyed V., 46 years old.

According to the claimed method:

FBV = 15.948 + 0.746⋅ln (243.68) + 0.301⋅160-0.193⋅25-0.152⋅27 = 56.961

DBV = 0.629⋅46 + 18.56 = 47.494

FBV-DBV = 9,467

According to the prototype method:

FBV = 26.985 + 0.215⋅160-0.149⋅25 + 0.723⋅9-0.151⋅27 = 60.09

DBV = 0.629⋅45 + 18.56 = 46.865

FBV-DBV = 13,225

Thus, in subject V., 45 years old, both methods predict a high risk of PS, which corresponds to the third risk group for PS of the body.

Example 4. Surveyed S., 45 years.

According to the claimed method:

FBV = 15.948 + 0.746⋅ln (380.98) + 0.301⋅137-0.193⋅35-0.152⋅39 = 46.427

DBV = 0.629⋅45 + 18.56 = 46.865

FBV-DBV = -0.438

According to the prototype method:

FBV = 26.985 + 0.215⋅137-0.149⋅35 + 0.723⋅7-0.151⋅39 = 50.397

DBV = 0.629⋅45 + 18.56 = 46.865

FBV-DBV = 3,532

Thus, in subject S., 45 years of age according to our method, they predict a low risk of premature aging, which corresponds to the first risk group for PS of the body; according to the prototype method, the average risk of PS, which corresponds to the second risk group of PS of the body.

The accuracy of the proposed method, component 88%, is calculated by the formula:

TS - the accuracy of the method;

PI - true positive results;

IO - truly negative results;

LP - false positive results;

ON - false negative results.

The accuracy of the prototype method, component 79%, is calculated by the formula:

TP - the accuracy of the prototype method;

PI - true positive results;

LP - false positive results;

IO - truly negative results;

LO - false negative results.

The sensitivity of the method, comprising 87%, was calculated by us according to the formula:

ES - the sensitivity of the method;

PI - true positive results;

LO - false negative results.

The sensitivity of the prototype method, component 79%, was calculated by us according to the formula:

PE - prototype sensitivity;

PI - true positive results;

LO - false negative results.

The specificity of the proposed method, component 100%, is calculated by the formula:

SS - specificity of the method

IO - true negative results;

LP - false positive results;

The specificity of the prototype method, component 80%, is calculated by the formula:

SP - the specificity of the prototype

IO - true negative results;

LP - false positive results;

Thus, compared with the prototype, the claimed method increases the objectivity of determining the actual biological age of the subjects, which, in turn, increases the accuracy of predicting the risk of premature aging in men of young and middle age by 9%, sensitivity - by 8%, specificity - by 20 %

When identifying persons with signs of premature aging, they need to conduct further diagnostic and therapeutic measures.

Literature:

1. Abramovich S.G. Method for determining the biological age of a person / S.G. Abramovich, A.A. Fedotchenko, I.M. Mikhalevich, A.V. Koryakina // Siberian Medical Journal (Irkutsk). 1999. V. 16. No. 1. S. 45-47.

2. Abramovich S.G. Method for determining the biological age and rate of human aging / S.G. Abramovich, I.M. Mikhalevich, A.V. Shcherbakova, N.A. Kholmogorov, E.M. Larionova, E.O. Korovina, E.V. Barkhatova // Clinical medicine. 2008.V. 86. No. 9. S. 54-56.

3. Belozerova L. M. Assessment of biological age by computer electroencephalography / L.M. Belozerova // Successes of gerontology. 2013.V. 26. No. 4. S. 666-670.

4. Belozerova L.M. Evaluation of biological age by echocardiography / L.M. Belozerova // Successes of gerontology. 2006. No.19. S. 90-92.

5. Belozerova L.M. Method for determining the biological age of spirography / L.M. Belozerova, T.V. Odegova // Clinical Gerontology. - 2006. - T. 12, No. 3. - S. 53 - 56.

6. Belozerova L.M. Determination of biological age by blood analysis / L.M. Belozerova // Clinical Gerontology. - 2006. - T. 12, No. 3. - S. 50-52.

7. Belozerova L.M. Methods for determining the biological age of mental and physical performance. - Perm, 2000 .-- 60 p.

8. A method for determining the biological age of a person [Text]: US Pat. 2228137 ROS. Federation: IPC: 7 A61B 5/16 A

9. Voitenko V.P. Determination of biological age as a problem of mathematical modeling of aging processes / V.P. Voitenko // Fourth All-Union Congress of Gerontologists and Geriatricians: abstract. doc. - К., 1982. - T. 1. - P. 73.

10. Gavrilov I.V., Meshchaninov V.N., Tkachenko E.L., Lukash V.A., Sazonov S.V., Leontiev S.L., Sedov S.G. A method for determining biological age in men. Patent No. 2617313, 07/18/2016

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Claims (12)

A method for predicting the risk of premature aging (PS) of young and middle-aged men, which consists in determining the actual biological age (PBF), taking into account the measured parameters of the subject - systolic blood pressure, breath holding time on inspiration, as well as the duration of static balancing on one leg, and due biological age (DBV) of the subject according to the formula: DBV = 0.629⋅KV + 18.56, where DBV is the proper biological age, KV - calendar age, with the subsequent determination of the difference between the obtained values of FBV and DBV, which is used to predict the risk of premature aging (PS) of young and middle-aged men, characterized in that they additionally determine the growth factor of fibroblast 21 with the subsequent calculation of the FBV of the subject according to the formula: FBV = 15.948 + 0.746⋅ln (FGF 21) + 0.301⋅SAD-0.193⋅ZDV-0.152⋅SB, where FBV - the actual biological age, years; FGF 21 - the value of fibroblast growth factor 21, ng / l; GARDEN - the value of systolic blood pressure, mm Hg; HFA - the value of the breath-holding time on inhalation, s; SB - the value of the duration of static balancing on one leg, s, and with a difference value between the obtained values (PBW and DBV) <3, a low risk of premature aging of young and middle-aged men is predicted, which corresponds to the first risk group for PS in the body, with a value (PBV-DBV) of 3–9, the average risk of PS in young men and middle age, which corresponds to the second risk group for PS of the body; with a value (FBV-DBV)> 9, a high risk of PS of men of young and middle age is predicted, which corresponds to the third risk group of PS of the body.