Pathogenetic Justification of a Method for Determining High Risk of Hypertensive Disease Through Digital Assessment of Hemodynamic Parameters and the Valsalva Maneuver

The dissertation is devoted to the development of a pathogenetically justified method for determining high risk of hypertensive disease and other diseases of the heart and blood vessels in practically healthy young males. The research is based on the assumption that at the preclinical stage of primary arterial hypertension, intermediate phenotypes reflecting increased predisposition to hypertensive disease are formed within the circulatory system. The methodology includes digital integral rheography of the body at rest and during performance of a functional test with the Valsalva maneuver, cluster analysis based on values of systolic and diastolic arterial pressure, mean arterial pressure, and heart rate, as well as discriminant analysis for constructing classification formulas.

Relevance of the topic. At the present time the population of developed countries, including Russia, suffers from a pandemic of hypertensive disease (primary arterial hypertension) (Belenkov Yu.N., Chazova I.E., Mychka V.B., 2004). In the Russian Federation primary arterial hypertension and complications of this disease are the most frequent causes of death among the most able-bodied segment of the population (Makolkin V.I., 2002). At the same time primary arterial hypertension in our days is characterized by:

1. Complications (acute myocardial infarction, cerebral circulation disorders) that increasingly develop at the first stage of arterial hypertension.

2. Accelerated development, that is, the emergence of sustained arterial hypertension of the third-fourth stage at middle age.

3. An increase in the frequency of cases of ineffectiveness of modern methods of pharmacotherapy (Frolova E.V., Plavinsky S.L., Moiseeva I.E., Kuznetsova O.Yu., Filatov V.N., 2004).

4. Disease risk amounting to 90 % in healthy individuals over 55 years of age.

5. Increasingly widespread lack of awareness of the disease and its high risk among a significant portion of the population.

In this connection the social imperative of individualized and targeted prevention of hypertensive disease at the preclinical stage of disease development becomes clear. A necessary condition for the effectiveness of such a system is the development of individualized methods of risk assessment for diseases of the heart and blood vessels (hypertensive disease in particular) using modern methods of investigation of systemic circulation and functional tests. Therefore, research aimed at the development of such methods may be considered relevant.

At the present time it has become definitively clear that primary arterial hypertension is a multifactorial disease (Boytsov S.A., 2002). As a multifactorial disease, hypertensive disease constitutes a systemic-level phenotype, being the result of genome expression specifically dependent on the action of factors of the modern post-industrial urbanized society. A number of these exogenous factors constitute conditions for the occurrence of the disease (its risk factors), including stressors as stimuli of persisting negative psychoemotional stress.

Taking into account the known fact of the predominant development of hypertensive disease in mature and elderly age, it should be presumed that at the preclinical stage of the disease, at levels of structural-functional organization close to the systemic level, intermediate phenotypes can be identified that correspond to increased predisposition to hypertensive disease, other diseases of the heart and blood vessels in subsequent periods of ontogeny.

Among the elements of such intermediate phenotypes, in particular, are high normal blood pressure (systolic arterial pressure 130-139 mm Hg, diastolic arterial pressure 85-89 mm Hg), an increase in minute blood circulation volume without a physiological decrease in total peripheral vascular resistance, resistance to insulin and pathological glucose tolerance, a tendency toward body mass increase within physiological limits and obesity, an increase in glomerular filtration rate and sodium reabsorption, dysautonomia with enhancement of systemic sympathetic regulatory influences, as well as an enhanced systemic response to the action of stressors of diverse origin (Baush E.A. et al., 2003). In this connection it appears possible to consider that high predisposition to hypertensive disease corresponds to certain peculiarities of systemic circulation, as well as to the character of the response of the values of its parameters to the action of stimuli of certain functional tests. This gives grounds for the relevance of the scientific task of pathogenic justification and practical development of methods for determining high risk of diseases of the heart and blood vessels in practically healthy subjects using functional tests.

The Valsalva maneuver is intended for assessment of the strength of the baroreflex response in practically healthy subjects and is contraindicated at any stage of primary arterial hypertension. The point is that an increase in arterial blood pressure in response to the action of maneuver stimuli at any degree of severity of hypertensive disease can cause cerebral circulation disorders as a consequence of exacerbation of arterial hypertension. It is known that predisposition to hypertensive disease in practically healthy individuals is characterized by enhanced reflexes involving higher sympathetic centers (Sliusarev et al., 2003). In this connection a corresponding character of sympathetic efferentation during realization of the baroreflex in response to the action of Valsalva maneuver stimuli should be presumed. The character of the response of systemic circulation to the action of Valsalva maneuver stimuli depending on predisposition to diseases of the heart and blood vessels in practically healthy individuals remains insufficiently studied to date. It may be considered that research aimed at the development of a method for determining high predisposition to diseases of the heart and blood vessels through continuous integral rheography of the body during performance of the Valsalva maneuver possesses relevance and scientific novelty.

At the present time a preclinical stage of primary arterial hypertension is identified, at which systolic arterial pressure is within the limits of 120-139 mm Hg, and diastolic arterial pressure is in the range of 80-89 mm Hg (Sliusarev et al., 2003). Clinical primary arterial hypertension is an absolute indication for modification of lifestyle and active application of preventive measures. It should be noted that an intensive search is underway for individualized preventive measures that would allow targeted prevention of hypertensive disease at the preclinical stage of its development (Britov A.N., 1997). At the same time the peculiarities of the response of systemic circulation to the action of stimuli of known functional tests, including the maneuver with performance of the Valsalva breathing exercise, remain unclear to this day. Determination of such peculiarities and development, based on the obtained facts, of a method for determining high predisposition to hypertensive disease possesses urgency as a relevant scientific task of applied orientation.

Corresponding values of arterial blood pressure within its normal range are not the only data of medical examination that indicate high risk of hypertensive disease, as well as other diseases of the heart and blood vessels in subsequent periods of ontogeny. This risk is directly associated with values of heart rate, pulse and diastolic arterial pressure, as well as with values of the entire spectrum of characteristics of systemic circulation (Weiger B.X. et al., 2001). In this connection a rational presumption appears that cluster analysis based on values of systolic, diastolic, and mean arterial pressure, as well as heart rate, will allow identification of a group of subjects with the greatest predisposition to hypertensive disease, as well as to other diseases of the heart and blood vessels. The scientific task of identifying such a group through cluster analysis is considered relevant, as it will allow selection of a contingent with high risk of hypertensive disease in the nearest periods of ontogeny. Selection of such a contingent will make it possible to develop methods for determining high risk of cardiovascular pathology based on the use of modern digital methods of investigation of systemic circulation and application of non-ergometric tests to the action of stimuli of functional tests and to the action of Valsalva maneuver stimuli in particular. Pathogenetic justification and detailed technical development of such a method will constitute a novel solution to the relevant scientific task of identifying high risk of hypertensive disease and other diseases of the heart and blood vessels in subsequent periods of ontogeny in practically healthy individuals.

The goal of the research is to provide a pathogenic justification and technical development of a method for determining high risk of diseases of the heart and blood vessels in practically healthy male individuals of young age through digital integral rheography of the body during performance of a functional test with the Valsalva maneuver.

Research tasks:

1. Through cluster analysis based on values of systolic and diastolic arterial pressure, mean arterial pressure, and heart rate, to identify from the general group of practically healthy young males a group of subjects with the greatest predisposition to hypertensive disease and a group of individuals with a lower level of such predisposition.

2. To identify peculiarities of the response of systemic circulation parameter values to the action of stimuli of the functional test with performance of the Valsalva maneuver depending on predisposition to hypertensive disease in subjects of young age, male sex, and without overt pathology.

3. Based on values of changes in systemic circulation parameters under the action of stimuli of the functional test with performance of the Valsalva maneuver and through discriminant analysis, to obtain calculation formulas for a classification index for determining high risk of hypertensive disease in practically healthy subjects of young sex and young age.

Scientific novelty of the research. Peculiarities of the response of systemic circulation parameter values to the action of stimuli of the functional test with performance of the Valsalva maneuver depending on predisposition to hypertensive disease have been identified in practically healthy young males. Calculation formulas for a classification index for determining high risk of hypertensive disease in practically healthy subjects of young sex and young age have been obtained.

Practical value. The results of the research will allow a novel solution to the relevant practical task of preventive medicine, namely, determination of high risk of hypertensive disease in practically healthy young males. The results are used in the practical work of the Clinical Pathophysiology Laboratory of the Military Medical Academy during examination of practically healthy individuals for determination of the risk of the most frequent diseases of humans in subsequent periods of ontogeny.

Basic provisions submitted for defense:

1. Cluster analysis depending on values of systolic and diastolic arterial pressure, heart rate values, and mean arterial pressure divides the entire group of practically healthy males of young age into two clusters. One of the clusters is characterized by higher mean values of the given systemic circulation parameters and the greatest frequency of familial association with patients suffering from hypertensive disease as markers of greater predisposition to hypertensive disease in subsequent periods of ontogeny.

2. At rest, the peculiarities of systemic circulation in high predisposition to hypertensive disease in practically healthy young males are: a) increase in heart rate and stroke volume within physiological limits; b) the greatest determinacy of stroke volume values by values of total peripheral vascular resistance; c) absence of negative influences of heart rate and total peripheral vascular resistance values on mean arterial pressure values.

3. In high predisposition to hypertensive disease, the baroreflex response of systemic circulation in the fourth phase of the maneuver with performance of the Valsalva breathing exercise is expressed to a greater degree than in low predisposition. This is evidenced by: a) greater, than in low predisposition, values of increase in total peripheral vascular resistance and stroke volume; b) baroreflex decrease in heart rate, which is absent in low predisposition, in response to enhancement of cardiac pump function and increase in mean arterial pressure; c) absence of increase in total peripheral vascular resistance due to a more pronounced dynamic arterial hyperemia at greater enhancement of cardiac pump function.

Implementation of the work. The results of the work are used in the practical work of the Clinical Pathophysiology Laboratory of the Military Medical Academy during examination of practically healthy individuals for determination of the risk of the most frequent diseases of humans in subsequent periods of ontogeny.

Public presentation. The basic provisions of the dissertation research were reported at the All-Russian conference with international participation "Actual Problems of Clinical Pathophysiology" (Saint Petersburg, 2004), at the All-Russian Scientific Conference "Psychophysiology of Professional Activity of Man" (Saint Petersburg, 2004), and at a meeting of the Saint Petersburg Society of Pathophysiologists (2002).

Structure and volume of the dissertation.

The dissertation consists of an introduction, a literature review, materials and methods of research, results of original research, discussion of the obtained results, conclusions, practical recommendations, and bibliographic lists.