Along with shared risk factors for cardiovascular disease (CVD) in men and women, women have a unique risk factor: the development of estrogen deficiency in postmenopausal period [1, 2]. Available contemporary data on the mechanisms of estrogenic influence on cardiovascular system indicate the complexity and multidirectional nature of their biological effects, provided by their impact on metabolic risk factors [3, 4], along with other direct impacts on the vascular wall [5‐7]. Estrogens cause vasodilation by affecting the synthesis of nitric oxide (NO) and prostacyclin, reducing synthesis of endothelin-1, and promoting the opening of calcium channels in the cell membranes of vascular smooth muscle cells [8].

The effect of estrogen deficiency on CVD development can be mediated by various mechanisms. On one hand, age-related estrogen deficiency promotes the redistribution of adipose tissue resulting in abdominal obesity, development of insulin resistance, and occurrence of adverse metabolic changes, all of which create the basis for the formation of menopausal metabolic syndrome [9, 10].

On the other hand, the consequence of estrogen deficiency is an imbalance of vasoactive mediators with a predominance of vasoconstrictor production and a decrease in the secretion of vasodilators. As a result, the conditions are created for the development of endothelial dysfunction and changes in elastic properties of the vascular wall [7, 11].

Structural and functional changes of the vascular wall in women occur already at the very early stages of reproductive aging. They accelerate significantly after the onset of menopause, which is largely due to the loss of protective effect of female sex hormones on the cardiovascular system [11‐13].

In most studies, the menopause onset has been associated with an imbalance among the production of vasoconstrictor and vasodilating factors: a decrease in endothelium-dependent vasodilation, related to insufficient NO production [14], and increase in vasoconstrictor factors [5, 11, 15].

Currently, non-invasive methods for assessing early structural and functional changes in the vascular wall are actively studied. Such methods include ultrasound examination of the carotid arteries, evaluation of endothelial function and coronary calcification, characterization of the central pulse wave, and investigation of the vascular wall for arterial stiffness. All of the above belong to subclinical vascular CVD markers, enabling the assessment of the vascular wall condition at different stages of CVD continuum [16, 17].

An emergence of applanation tonometry made it possible to evaluate arterial stiffness and central hemodynamic parameters non-invasively, which considerably expanded the information that had been provided previously by invasive methods used for studying these parameters during cardiac catheterization. The development of techniques, combining the brachial artery blood pressure (BP) measurements with a cuff and the analysis of the central pulse wave, permitted to evaluate the functional parameters of the arterial wall via the method of outpatient daily monitoring [16, 17], which expanded the possibilities of early cardiovascular screening of the patients at risk for CVD.

The phenomenon of pulse pressure amplification (PPA) from the central arteries to the peripheral arteries, mainly because of a rise in systolic pressure, makes it incorrect to use pulse pressure in the brachial artery as a substitute for pulse pressure in aorta.

Taking into account that central aortic pressure (CAP) reflects blood flow in the coronary and cerebral vasculatures to a greater extent and is a more significant predictor of cardiovascular complications, the assessment of central pulse wave parameters has additional advantages for characterizing the state of the cardiovascular system than assessment of arterial stiffness indicators alone [17].

Whereas a few studies have assessed CAP parameters and reflected pulse wave in women at different phases of their reproductive aging [18‐20], none investigated the daily profile of CAP and reflected pulse wave parameters in women undergoing different stages of the menopause. Our preliminary results established an association of menopause phases with some hemodynamic parameters (CAP parameters, vascular stiffness, and reflected pulse wave) [21]. Nonetheless, an impact of some cardiovascular risk factors (e.g., hypertension and obesity), as well as complex structure of revealed association deserves further comprehensive investigation.

The objective of our study was to assess daily variability in CAP and daily profile of amplification and augmentation of pulse blood pressure (PBP) in women at different menopause phases, with regards to the presence, or absence, of some cardiovascular risk factors, such as hypertension and obesity.

We compared the absolute values of the SBP, PBP, CASP, CAPP and the PPA phenomenon among women during their perimenopause (Group 1) and early postmenopause (Group 2), separately for daytime and nighttime hours. A comparison of the daily BP profile indicators in the brachial artery vs. aorta with simultaneous non-invasive 24-h BP monitoring in women undergoing different phases of the menopause is presented in Table 2.

The dynamics of SBP and PBP during the 24-h period in women of both groups matched the changes in similar indicators measured in the brachial artery. For postmenopausal women, we discovered higher values of SBP and PBP both in the brachial artery and aorta during the 24-h period, in daytime hours (when staying awake) and at night (during sleep), compared with women undergoing menopausal transition.

For women of both groups, our results demonstrated that CAPP at night declined less than peripheral PBP; while in women of Group 2, the decrease of CAPP at night was less pronounced than in Group 1. The reduction in CAPP at night was 2.1 ± 1.1 mmHg in Group 1 and 1.2 ± 1.0 mmHg in Group 2 (p = 0.001). The decline in peripheral PBP at night in women of Group 1 was 4.7 ± 1.4 mmHg, while in women of Group 2, it was 4.6 ± 1.2 mmHg (p = 0.452).

With similar changes in the 24-h BP profile in women of both groups, a smaller decline in central PBP at night may indicate a greater CASP augmentation during this time of the day.

In connection with revealed disproportionality in the degree of a night-time decline in peripheral and central BP, we analyzed AIxao (Table 2). To diminish the dependence of AIxao on the heart rate, the normalized value of the former, corresponding to the heart rate of 75 beats per minute, was calculated. Thus, we leveled off the effect of different heart rate values on the studied parameter in daytime and nighttime hours.

In women of the early postmenopausal stage, compared with those in perimenopause, we detected lower PPA values over 24-h period, at night, and a clear trend of its decrease in daytime hours.

Analyzing 24-h AIxao dynamics, we noticed its higher nighttime values, compared with daytime monitoring period, with more pronounced changes detected in women of the early postmenopausal stage.

Twenty-four-hour changes in amplification and augmentation of pulse pressure in subgroups 1a and 2a are presented in Table 3.

The discovered dynamics in the 24-h PPA profiles of healthy women (subgroups 1a and 2a) matched the identified changes in groups of climacteric women (Groups 1 and 2): the CAPP at night declined less than the peripheral BP, measured on the brachial artery, and the PPA at night was less pronounced than in daytime hours.

The decrease of peripheral PBP at night in women was 5.4 ± 1.6 mmHg in the subgroup 1a and 5.6 ± 1.6 mmHg in the subgroup 2a (p = 0.259). Despite the absence of significant differences in the degree of the CAPP decrease, women in subgroup 2a showed a clear tendency towards a smaller CAPP decline at night than subjects in the subgroup 1a (2.4 ± 1.2 vs. 2.8 ± 1.2 mmHg, p = 0.086).

The 24-h AIxao dynamics indicated its higher nighttime values ​​in both groups, whereas more pronounced changes were noted in postmenopausal women.

Thus, in women of early postmenopausal phase, compared with those undergoing menopausal transition, we detected a decrease in 24-h and nighttime PPA profiles, and a clear trend of PPA decline in daytime hours as well, combined with higher augmentation index values ​​ during the day, night, and over a 24-h monitoring period. Analyses of 24-h PPA and AIxao profiles in women of both groups demonstrated PPA reduction accompanied by its higher values at night, compared with daytime hours, with more distinct changes noted in women of the early postmenopausal period.

We conducted multiple logistic regression analysis, in which the menopausal status was used for dependent variable. Body mass index and all indicators of a 24-h BP monitoring in the brachial artery and aorta in women of Groups 1 and 2 were included in the regression model as independent variables. The outcomes of logistic regression analysis are presented in Table 4. General characteristics of the calculated logistic regression equation included adjusted R² = 0.49, log-likelihood = − 50.3, chi-square (19) = 97.6, p < 0.001. We conducted multiple regression analysis, in which the menopausal status was used for dependent variable. For each independent trait, a standardized value of the regression coefficient (beta) was calculated. The beta coefficients for various parameters were as follows: 0.652 (p = 0.007) for CAPP, 0.609 (p = 0.044) for AIxao, − 0.580 (p = 0.081) for PPA, 0.028 (p = 0.204) for CASP, 0.215 (p = 0.385) for SBP, and 0.205 (p = 0.326) for PBP. General characteristics of the obtained multiple regression equation included adjusted R² = 0.80, F(13.69) = 26.9, p < 0.001.

The phenomenon of pulse pressure amplification from central to peripheral arteries implies that PBP use in brachial artery as a substitute for PBP in aorta is quite inadequate. It was previously shown that CAP (especially CAPP), along with augmentation index, correlate with the degree of transformation in large arteries and pulse wave velocity as a conventional indicator of the vascular wall stiffness [27, 28].

Previously conducted studies have shown comparable circadian rhythms for both central blood pressure and peripheral blood pressure; while less pronounced decrease in central SBP was observed, compared with the peripheral SBP at night in menopausal women. However, the mechanisms explaining this phenomenon remain insufficiently studied [29].

It could be assumed that age-related estrogen deficiency, leading to structural and functional changes in the vascular wall, may affect the amplification and augmentation of pulse pressure.

The research conducted by Kuznetsova et al. [26] included women of an age range comparable to our study. However, the study carried out on women in this age range requires detailing their menopausal status (the period of the menopausal transition or early postmenopause), which was demonstrated by our results. Besides, the research of Kuznetsova et al. [26], in contrast to our study, involved solely healthy volunteers, thus excluding various additional risk factors, largely associated with the menopause.

It can be assumed that higher CAPP values, combined with a lower PPA and an amplitude increase of the reflected pulse wave, determine the pulse wave damaging effect on the blood vessels of the target organs and, therefore, may be associated with increased risk of cardiovascular complications, as was shown in a number of studies [28, 30].

We were interested in the effect of the menopause per se on the discovered phenomenon of disproportionality in augmentation and amplification of pulse pressure in menopausal women. The data in Tables 1 and 2 clearly imply that body mass index and all indicators of a 24-h BP monitoring in the brachial artery and aorta differed significantly among the groups of women at various climacteric phases. Therefore, the association between the body mass index and the studied indicators of a 24-h BP monitoring comes as no surprise. However, after the inclusion of the body mass index in the regression model, the association of climacteric phases with the aortic augmentation index persists throughout the 24-h cycle, whereas no significant relationship between the pulse pressure amplification and menopausal status was established (Table 4). The implications of this outcome are especially interesting, given that previous studies have shown a positive effect of the menopausal hormone therapy on amplification increase and pulse pressure augmentation decrease in postmenopausal women [31].

The value of the augmentation index could be potentially considered as a criterion for the magnitude of a cardiovascular risk. An increase in the amplitude of the reflected central pulse wave leads to a significant increase in the afterload, myocardial hypertrophy, augmented oxygen demand, and a decrease in the efficiency of subendocardial blood flow [30].