**3. Results and discussion**

Characteristics of clinical and anamnestic data of examined patients are presented in **Table 1**. The data presented in the table show that the age of the patients in Groups 2 and 3 significantly differed from Group 1 (p < 0.005; p < 0.001, respectively). There were no significant differences in smoking and body mass index (BMI) in all groups, or duration of AH in the groups with AH. The percentage of family history of AH in the groups with AH did not differ, but was significantly lower in the control group of healthy patients. Regarding the grade of AH, the maximum percentage of patients with grade 1 AH was in Group 2 and the maximum percentage of patients with grade 3 AH was in Group 3. In addition, patients in group with AH and OP had significantly longer postmenopausal period compared to the 1st group of patients (p < 0.001).

According to ABPM, a significant difference in the parameters was observed for the levels of 24-hour systolic BP (SBP 24) and diastolic BP (DBP 24) between healthy subjects in Group 1 and patients in Group 2, as well as for the levels of SBP 24 variability and nighttime DBP between patients in Groups 2 and 3 (p < 0.01). The absence of other significant changes in ABPM parameters can be explained by sufficient adherence of patients with AH to antihypertensive therapy. The characteristics of structural


*\*\*\*p < 0.001 – comparison between groups 1 and 2.*

*##p < 0.01 – comparison between groups 2 and 3.*

*p – comparison between groups 1 and 3.*

#### **Table 1.**

*Clinical and anamnestic characteristics in groups of examined patients.*


*p < 0.05 – comparison between groups 2 and 3.*

*##p < 0.01 – comparison between groups 2 and 3.*

*p – comparison between groups 1 and 3.*

#### **Table 2.**

*Structural and functional characteristics of the vascular wall and bone tissue in the groups of examined patients (M ± SD).*

and functional parameters of vascular wall and bone tissue in the groups of examined patients are presented in **Table 2**.

According to the results presented in **Table 2**, PWV-R/L is significantly higher in the groups of patients with AH compared to the control group. The maximum values were registered in Group 3, which significantly exceeded parameters in Groups 1 and 2, which is compliant with the data of other researchers who registered increase in the rigidity of the vascular wall in postmenopausal women [2, 3].

IMT of the common carotid artery (IMT CCA) d/s maximum values were observed in Group 3 of patients with AH and OP, which significantly exceeded the values in Group 1. T-Score and AC were naturally significantly reduced in Group 3 of patients with AH and OP compared to Groups 1 and 2. Correlation analysis of parameters presented in the table showed moderate relationships in Group 2 – PWV-R with IMT CCA d (r = 0.415, p < 0.06); in Group 3 – AC with PWV-R (r = 0.871, p < 0.06) and IMT CCA d (r = −0.673, p < 0.002).

We decided to study common relationships between the studied parameters by determining their relationships with the biochemical parameters of the lipid profile, inflammatory response, and endothelial dysfunction of the vascular wall, as well as parameters of hormonal and mineral-vitamin metabolism.

Laboratory biochemical parameters in the examined groups of patients are presented in **Table 3**.

According to the table, there is a persistent tendency to increase in the levels of total cholesterol and its atherogenic fractions in the groups with AH compared to the control group of patients. There is a clear tendency to increase in myeloperoxidase as a parameter reflecting increased peroxidation process in Group 3 of patients with AH and OP compared to Groups 1 and 2.

According to the results of vascular inflammatory response markers, the levels of hs-CRP, HYC, and IL-8 were significantly higher in Group 3. A tendency to increase in the levels of endothelin-1 and significant increase in nitrites in Group 3 indicate significant endothelial dysfunction in patients with AH and OP. Results in the study of the parameters of hormonal and mineral-vitamin metabolism showed the maximum


*Characteristics of Pathogenetic Links in Vascular Remodeling and Bone Tissue Destruction… DOI: http://dx.doi.org/10.5772/intechopen.107444*

*\* p < 0.05.*

*\*\*\*p < 0.001 – icomparison between groups 1 and 2.*

*# p < 0.05 – comparison between groups 2 and 3.*

*p – comparison between groups 1 and 3.*

#### **Table 3.**

*Characteristics of biochemical parameters in the examined groups of patients (M ± SD).*

levels of parathyroid hormone (p < 0.029) and decreased levels of estrogens, progesterone, testosterone, a tendency to decrease in calcitonin, total and ionized calcium and significantly low levels of vitamin D (p < 0.001) in Group 3 of patients. Our results are consistent with published data and reflect the severity of changes in the parameters of biochemical markers in different groups of patients [2, 3].

The study showed multiple multidirectional moderate correlations (r = 0.452, p < 0.05) between the presented structural, functional, and biochemical parameters; in Group 3, negative correlations were observed between the peak of T-Score and age, PWV-L/R, 24-hour and night SBP and DBP, duration of menopause, IL-6, hs-CRP and HYC, as well as between PWV-L and estradiol; positive correlations between T-Score and progesterone and between PWV-R/L and IL-6, LDL-cholesterol, hs-CRP, TNF-α, endothelin-1, mean 24-hour SBP, in daily variability of SBP and DBP.

Back in 1935, Allen et al. showed that estrogens dilate blood vessels, improve blood circulation, and normalize cardiac function, and in 1957, Popovici et al. stated that a decrease in estrogen levels resulted in decrease in acetylcholine, which in turn resulted in coronary and arterial ischemic syndrome. Modern data convincingly prove the existence of the relationships between the levels of sex hormones both with CVD and bone destructive processes, and prolonged vascular inflammatory response is considered a pathogenetically associated link in this relationship.

The risks of the development and progression of destructive changes were calculated using logistic regression for the group of AH with osteopenia and OP in postmenopausal period. Thus, for the patients with AH and osteopenia, statistically significant parameter associated with the risk of OP was PWV-R index, which increase by 1 point was associated with 3.8-time increase in the risk of OP (odds ratio (OR) 3.8, 95% confidence interval (CI) 1.81–7.97). There were no reliable relationships between biochemical parameters and the risk of OP at this stage of the study in this group.

In the group of AH with OP, risks of progression of the bone destructive process were observed with changes in certain biochemical markers. Thus, the risk of OP increased: by 2.5 times with increase in IL-6 by 1 pg./mL (OR 1.037 CI 1.01; 1.065, p = 0.048), by 2 times with increase in TNF-α by 1 pg./mL (OR 1.99 CI 1.107; 0.58, p = 0.022), by 6.5% with decrease in estrogen by 1 nmol/L (OR 0.967 CI 0.935; 1.00, p = 0.052), by 18% with increase in HYC by 1 μmol/L (OR 1.18 CI 1.023; 1.361, p = 0.023), by 65% with decrease in progesterone by 1 nmol/L (OR 0.348 95% CI 0.164; 0.739, p = 0.006), by 3.7% with increase in parathyroid hormone by 1 pg./mL (OR 1.037 95% CI 1.01; 1.065, p = 0.009), by 13.6% with increase in IL-8 by 1 pg./ml (OR 1.136 95% CI 1.016; 61.27, p = 0.025), by 54% with decrease in IL-10 by 1 pg./mL (OR 0.459 95% CI 0.252; 0.837, p = 0.011). As for functional parameters, the risk of OP increased by 6 times with increase in PWV by 1 m/s (OR 6.06 95% CI 2.203; 16.69, p = 0.00048).

The characteristics of OR that maximally determine the risk of OP in the groups of AH with osteopenia and OP are presented in **Figures 1** and **2**. According to the data presented in **Figure 1**, in the group of OP, the most reliable parameter that determined the risk of OP was PWV-R value. According to the data presented in **Figure 2**, increased levels of parathyroid hormone and inflammatory markers IL-6 and 8, TNF-α, hs-CRP, as well as decreased levels of progesterone and anti-inflammatory IL-10, were most actively involved in the aggravation of pre-existing destruction of bone tissue.

In addition, during the receiver operating characteristic (ROC) analysis in the group of patients with AH and OP, cut-off points for increased risk of OP progression were determined; for example, with decrease in progesterone levels below 0.93 nmol/L, the risk of OP increases by 9 times (sensitivity 76.9%, specificity 85.7); *Characteristics of Pathogenetic Links in Vascular Remodeling and Bone Tissue Destruction… DOI: http://dx.doi.org/10.5772/intechopen.107444*

#### **Figure 1.**

*The odds ratios that maximally determine the risk of osteoporosis in hypertensive patients with osteopenia.*

#### **Figure 2.**

*The odds ratios that maximize the risk of osteoporosis progression in hypertensive patients with pre-existing osteoporosis.*

with increase in parathyroid hormone levels over 28.14 pg./mL, the risk of OP increases by 3.7% (sensitivity 68.6%, specificity 69.2%); with increase in IL-8 over 10.25 pg./mL, the risk of OP increases by 13.6% (sensitivity 71.4%, specificity 64.1); with decrease in IL-10 levels below 3.465 pg./mL, the risk of OP increases by 54.1% (sensitivity 66.7%, specificity 62.9%). As for functional parameters, with increase in PWV-R index over 12.05 m/s, the risk of OP increases by 6 times (sensitivity 87.1%, specificity 89.3).

The results of the discriminant analysis clarified that the most significant parameters for the progression of OP in Group 3 of patients were progesterone, parathyroid hormone, IL-8, and PWV-R. The model obtained as a result of the discriminant function calculations is statistically significant (the Wilks' lambda is 0.201, p < 0.001) with a canonical correlation coefficient of 0.894.

At the same time, the greatest diagnostic contribution to the progression of OP is made by the level of progesterone (standardized coefficient 0.843). The standardized coefficients of parathyroid hormone (0.523), IL-8 (0.367) and PWV-RC (0.413) indicate approximately the same diagnostic significance of these variables. The equation

of the resulting discriminant function is as follows: F = −2.618 + 42.951\* progesterone +1.293\* parathyroid hormone +0.749\* IL-8 + 1.025\* PWV-R.

The specificity of this model was 100%, the sensitivity was 92%; 96% of the original observations were classified correctly. To enable classification, centroids were calculated for each group and a cut-off point that allows for more accurate identification of group membership. The mean value of the function for Group 1 was −1.915, for Group 2 - 1.992; the cut-off point (or threshold value) was equal to the function value of 0.039.
