Microcirculatory and tissue system as a marker of prenosological disorders of cardiovascular health in schoolchildren

Introduction

To date, research on the functioning of the blood microcirculation system remains a focus of scientific attention due to its involvement in many vital processes in the human body [1, 3, 5, 8]. Optical non-invasive diagnostic methods have already proven themselves effective in identifying disorders of peripheral blood flow associated with the development of cardiovascular diseases (arterial hypertension, coronary artery disease, stroke), type 2 diabetes mellitus, and other markers of metabolic syndrome [2, 4, 6, 9].

In the Russian Federation, within the framework of the national project "New Health Preservation Technologies" (2025-2030), the emphasis is on the development of preventive medicine technologies to ensure active and healthy longevity of citizens. Currently, in the RF, cardiovascular diseases (ranking 1st in the structure of overall morbidity in adults) continue to contribute significantly to mortality rates. Furthermore, the origins of cardiovascular pathology undoubtedly lie in childhood. The introduction of preventive medicine technologies in pediatrics should lead to significant results in preserving adult health in subsequent years [3, 5].

Objective

To study the state of the microcirculatory-tissue system in schoolchildren in order to determine prenosological screening markers of cardiovascular risk.

Materials and Methods

A comprehensive examination of 190 school-age children (14-17 years) was conducted at the Children's Health Center of the Smolensk Regional Children's Clinical Hospital as part of preventive check-ups for students from secondary educational institutions in Smolensk. Using random sampling, 82 schoolchildren were included in the study.

Depending on body mass index (BMI, kg/m²) and the level of ambulatory blood pressure (mean value of three BP measurements by the auscultatory method [1]), all examined schoolchildren were divided into 3 groups: Group 1 – 24 schoolchildren with BMI within ±1 SDS BMI (kg/m²) and normal ambulatory BP levels (systolic and diastolic BP did not exceed the 90th percentile for age, height, and sex); Group 2 – 36 schoolchildren with BMI within ≥ +1 SDS BMI (kg/m²) and normal ambulatory BP levels; Group 3 – 22 schoolchildren with BMI within ≥ +1 SDS BMI (kg/m²) and elevated systolic blood pressure (ambulatory BP exceeded the 90th percentile for age, height, and sex (14-15 years) or was equal to or greater than 135 mm Hg (16-17 years)).

The characteristics of the examined groups are presented in Table 1. There were no age or gender differences between the groups (Table 1).

Table 1. Characteristics of the Examined Groups

The comprehensive examination of schoolchildren included anthropometry (weight, height, BMI (kg/m²)); laser Doppler flowmetry and fluorescence spectroscopy of the skin in the forearm area using the "Lazma PF" analyzer (Russia) [7]. The following microcirculation parameters were assessed: M – arithmetic mean value of the microcirculation index (conventional units); M nutr. – mean value of nutritive blood flow (conv. units); σ – standard deviation of blood flow fluctuations from the mean value M (conv. units); Kv – coefficient of variation of blood flow fluctuations (%); An and Am – amplitudes of blood flow fluctuations (conv. units) due to neurogenic and myogenic mechanisms of vascular tone regulation, respectively; Ad and Ac – amplitudes of respiratory and cardiac blood flow fluctuations (conv. units); Fluxmotion Index (FMI = (Am + An) / (Ad + Ac), conv. units), characterizing the balance ratio between active and passive mechanisms of microcirculation regulation. Using laser fluorescence spectroscopy ("Lazma PF", Russia), the relative fluorescence amplitude of nicotinamide adenine dinucleotide (ANADN (A460/A365), conv. units) was assessed; as well as the Oxidative Metabolism Index (OMI, conv. units), linking the nutritive component of blood perfusion (microcirculation) (Mnutr.) and the fluorescence amplitude of the NADH coenzyme (ANADN). The microcirculation and oxidative metabolism studies were conducted under identical conditions for 4 minutes in the area of the right forearm.

Statistical processing of the research results was performed using the data analysis package of Microsoft Excel 2003, applying parametric (M, SD) and non-parametric (Me, 25th-75th perc.) statistics methods. Differences were considered statistically significant at p < 0.05.

Results and Discussion

Parameters characterizing the state of microcirculation (perfusion) and its variability in the examined children (Groups 1, 2, and 3) are presented in Table 2. It was revealed that schoolchildren with overweight/obesity and normal BP (Group 2) showed a trend towards an increase in the median perfusion (M, conv. units) compared to children in Group 1 (the increase in microcirculation occurred mainly due to an increase in M nutr. (an increase of 9.1%; p > 0.05). Against the background of increased perfusion, a significant decrease of 51.9% in the coefficient of variation of blood flow fluctuations (Kv (%)) was noted in children of Group 2 compared to children of Group 1 (decrease from 40.41% to 26.6%; p < 0.05). In schoolchildren of Group 3 with elevated systolic BP, a more significant increase in median perfusion (M, conv. units) was recorded compared to children in Groups 1 and 2 – by 29.6% and 23.0%, respectively (p < 0.05). The increase in microcirculation was also largely due to an increase in M nutr. (an increase of 53.3% compared to children in Group 1). A similar (as in children of Group 2) decrease in the coefficient of variation of blood flow fluctuations (Kv (%)) and blood flow variability (σ, conv. units) was observed in schoolchildren of Group 3 compared to children of Group 1 (p < 0.05).

Table 2. Comparative Characteristics of the State of Microcirculation (Perfusion) and Its Variability in the Examined Children (1st, 2nd, and 3rd Groups)

Parameters characterizing the regulation of microcirculation (perfusion) in children of Groups 1, 2, and 3 are presented in Table 3. In schoolchildren with overweight/obesity and normal BP (Group 2), a feature of microcirculation regulation compared to children in Group 1 is a decrease in the amplitude of respiratory and cardiac blood flow fluctuations (Ad – by a factor of 2.31 (p < 0.05); Ac – by a factor of 1.95 (p < 0.05)). A similar trend in microcirculation regulation (decrease in the amplitude of respiratory and cardiac blood flow fluctuations) was also recorded in children of Group 3 compared to children of Group 1 (Table 3). Furthermore, in schoolchildren of Group 3 with elevated systolic BP, a significant increase in the median amplitude of neurogenic (An by a factor of 1.86) and myogenic (Am by a factor of 1.63) mechanisms of blood flow regulation was recorded (p < 0.05) compared to children in Group 1; similar features of microcirculatory blood flow regulation were noted in schoolchildren of Group 3 compared to children of Group 2 (Table 3). It should be separately noted that in schoolchildren of Group 3, a more pronounced dependence of vascular tone regulation on the nervous and muscular components was recorded compared to children in Groups 1 and 2; this is evidenced by an increase in the median FMI in schoolchildren of Group 3 by a factor of 1.83 compared to the FMI of children in Group 1 (p < 0.05) and by a factor of 1.47 (p < 0.05) compared to the FMI of children in Group 2.

Table 3. Indicators of Microcirculation Regulation in the Examined Children (1st, 2nd, and 3rd Groups)

Table 4. Oxidative Metabolism Indicators in the Examined Children (1st, 2nd, and 3rd Groups)

Analysis of oxidative metabolism indicators showed that children in Group 2 exhibited a trend (p > 0.05) towards an increase in OMI compared to children in Group 1. Meanwhile, schoolchildren in Group 3 showed a significant increase in OMI by a factor of 2.1 (p < 0.05) compared to children in Group 1, against the background of an increase in the fluorescence amplitude of nicotinamide adenine dinucleotide (ANADN) and M nutr. (Tables 2, 4). The integral complex indicator OMI reflects the state of metabolic processes in the skin, including consideration of microcirculatory blood flow. In this regard, in the second stage, based on the analysis of oxidative metabolism data (OMI, conv. units) from schoolchildren in Group 1, normative parameters characterizing the functional state of the microcirculatory-tissue system (FS MTS) were proposed for further assessment of its structure in children of Groups 2 and 3.

Considering the recommendations of the "Lazma PF" analyzer manual [7] and the OMI values obtained in the study for children in Group 1 (25th–75th perc., conv. units), it is proposed to distinguish 4 types of FS MTS in schoolchildren aged 14-17 years:

• "Active" FS MTS, if the OMI value (conv. units) is in the range from 0.68 to 1.12 (25th and 75th percentiles of OMI in schoolchildren of Group 1);

• "Increased Activity" FS MTS, if the OMI value (conv. units) equals or exceeds the upper limit of the specified value (1.12 and above);

• FS MTS in the "Compensation" stage, if the OMI value (conv. units) is reduced by up to 20% relative to the lower limit of the control values (from 0.68 (inclusive) to 0.54);

• FS MTS in the "Decompensation" stage, if the OMI value is reduced by 20% or more relative to the lower limit of the control values (0.54 and below).

Table 5. Structure of the Functional State of the Microcirculatory-Tissue System (FS MTS) in the Examined Children (1st, 2nd, and 3rd Groups)

Analysis of the structure of the functional state of the microcirculatory-tissue system (FS MTS) in the examined children revealed that in children of Group 2, "Increased Activity" FS MTS was recorded 1.8 times more often (p < 0.05) than in children of Group 1; and 11.1% of children in Group 2 already had "Decompensation" FS MTS (Table 5). In schoolchildren of Group 3 compared to children of Group 2, "Active" FS MTS, indicating the preservation of compensatory-adaptive mechanisms at the microcirculatory level, was recorded 7.8 times less frequently. At the same time, 72.7% of children in Group 3 had "Increased Activity" FS MTS, and "Compensation" FS MTS was detected significantly more often than in children of Groups 1 and 2 (Table 5).

A comprehensive summary analysis of the features of the functional state of the microcirculatory-tissue system in schoolchildren of Groups 2 and 3 compared to children of Group 1 is presented in Table 6.

Table 6. Stage-by-Stage Summary Analysis of the Features of the Functional State of the Microcirculatory-Tissue System in Schoolchildren of the 2nd and 3rd Groups Compared with Children of the 1st Group

The research results showed that the functional state of the microcirculatory-tissue system closely correlates with the state of the cardiovascular system and, accordingly, can be used as one of the diagnostic markers of preclinical impairments of cardiovascular health in schoolchildren.

Conclusion

Thus, the results of the study on the state of microcirculation, its variability, and regulation in schoolchildren indicate the dependence of these parameters on both body mass index and the level of ambulatory (systolic) blood pressure. In schoolchildren with elevated ambulatory BP against the background of excess body fat, the features of FS MTS were: a significant increase in perfusion (microcirculation) against the background of reduced variability and enhanced active mechanisms of blood flow regulation, characterized by the predominance of sympathetic influences; as well as an increase in the intensity of oxidative metabolism at the microcirculatory level.

Based on the results of laser Doppler flowmetry and laser fluorescence spectroscopy ("Lazma PF"), the prenosological screening diagnostic markers of cardiovascular risk in schoolchildren with overweight/obesity should be considered "increased activity" of FS MTS against the background of high values of the Fluxmotion Index (indicating increased sympathetic influences on microcirculatory blood flow).