Features of blood pressure variability and arterial stiffness in hypertensive men with androgen defi ciency

Male sex has long been argued as a strong risk factor for arterial hypertension. Noteworthy is that available data support the negative impact of low testosterone on male cardiovascular health. Objective. This study was designed to assess characteristics of circadian blood pressure and arterial stiffness in hypertensive men with and without testosterone defi ciency. Materials and methods. A total of 60 male hypertensive patients aged above 45 years were screened on androgen defi ciency symptoms via Male andropause symptoms self-assessment questionnaire (MASSQ). 42 subjects with suspected low testosterone level were recruited into the study for subsequent total testosterone (TT) measurement. 24 h BP monitoring was carried out for all participants. Aortic stiffness was assessed using BPLab Vasotens System (cuff-based oscillometry method). Results. 43 % of patients had biochemically confi rmed low testosterone level. The total score of MASSQ in this group was signifi cantly higher compared to patients with normal testosterone. The decreasing of TT concentration with age was detected. The low TT group was characterized by signifi cantly higher values of 24 h systolic blood pressure (SBP) and pulse pressure (PP) values. The lower testosterone appears to be associated with prevalence of “non-dipper” pattern. The results of the multiple regression analysis revealed the relationship between plasma testosterone levels and SBP values in both study groups, while the relationship between testosterone and DBP values was not signifi cant. A signifi cant relationship was also found in each group between TT and PWV. Conclusion. The study revealed the high prevalence of androgen defi ciency among hypertensive middle-aged men. These patients are characterized by higher BP values compared to those with normal TT levels in the same age range. Low TT concentration may be considered also as the contributor of increased arterial stiffness in hypertensive males.

Висновки.L ast years the interest to the problem of hormonal changes in the development of cardiovascular disorders markedly increased.Male sex has long been argued as a strong risk factor for arterial hypertension.The functional activity of the entire endocrine system changes with aging, and it is of interest to study the male age-related androgen defi ciency syndrome in cardiovascular diseases (CVD).However serum testosterone level is not accepted as a traditional risk factor, the natural aging process faces with gradual decreasing of androgen concentration [14].Baltimore Aging Study has shown that 20 % of men over 60 years, 30 % over 70 years and 50 % over 80 years have low level of total testosterone [8].
There is an increasing number of evidence regarding the negative impact of low testosterone on male cardiovascular health [2].Testosterone may act as a biomarker of general health disorders, similar to other hormones that are biomarkers of illness, such as thyroid hormone, which declines with illness severity and predicts mortality [12,13].Many co-morbidities and prescribed medications can affect testosterone levels resulting in a wide range of nonspecifi c clinical signs and symptoms of androgen defi ciency [3].Nowadays there is thoroughly studied the role of androgenic status in the maintenance of cardiovascular health in adult male.Higher physiological testosterone levels are now getting attention as a benefi cial modulator of traditional cardiovascular risk factors [5,10].
Within the last decade the prospective population-based studies demonstrated the association of low testosterone levels with an increased risk of major coronary events and signifi cant correlation between poor androgenic status and cardiovascular mortality [4].Despite the growing number of observations of the impact of low androgens levels to development, progressing and outcomes of CVD the controversies regarding the exact laboratory defi nition of testosterone defi ciency still exist.
A large number of researches have shown the crucial role of preclinical organ damage to determine individual cardiovascular risk.Accelerated arterial stiffness is considered as a novel predictor of cardiovascular events and all-cause mortality, and can be evaluated with pulse wave velocity (PWV) [6], ambulatory arterial stiffness index (AASI) [1] and augmentation index (AIx) [11].Cause-and-affect relationship between testosterone level and arterial stiffness is yet to be established.Numerous studies describe arterial stiffness in various subpopulations, but there are no evaluations of PWV, AASI, and AIx in hypertensive patients according to androgenic status.

Objective
This study was designed to assess characteristics of circadian blood pressure and arterial stiffness in hypertensive men with and without testosterone defi ciency.

Materials and methods
A total of 60 male hypertensive patients aged above 45 years were exposed to perform Male andropause symptoms self-assessment questionnaire (MASSQ) [9].42 subjects with more then 40 points of MASSQ were supposed to have mild-to-moderate androgen defi ciency and were recruited into the study.Patients with BMI >28 kg/m 2 , prior history of hypogonadism, medical or surgical treatment for any prostatic disease, major cardiovascular events and diabetes mellitus were excluded.Signed informed consent was obtained from all patients.The subsequent total testosterone (TT) concentration was evaluated using immunoassay.TT was measured in the morning (between 7 a. m. and 11 a. m.) after an overnight fast.As the cut-off the value of 350 ng/dL was used to defi ne androgen defi ciency [7].The patients with TT levels below 230 ng/dL were not included into this study because of requirement of testosterone replacement therapy.24 h BP monitoring was carried out for all participants.Aortic stiffness was assessed using BPLab Vasotens System (cuff-based oscillometry method).Pulse wave analysis was evaluated due to the non-invasive measurement of aortic pulse wave velocity (PWVao), augmentation index (AIx) adjusted to the 75 beats per minute of heart rate and subendocardial viability ratio (SEVR).
Statistical analysis of the data was performed using Statistica 6.0 for Windows.Multiple regression analysis was used to assess the causality of androgen defi ciency in hypertension and changes of arterial stiffness.The results are expressed as means±SD.The level of signifi cance was taken as p<0.05.

Results
The general characteristics of the two groups are shown in Table 1.
Eighteen patients (43 %) had biochemically confi rmed low testosterone level.Furthermore, the total score of MASSQ in participants of this group was signifi cantly higher compared to patients with normal testosterone.The most usual manifestations of androgen decline were physical exhaustion and decrease in ability to perform sexually.
Patients with testosterone defi ciency were more aged.The TT level seemed to be lower with increasing of age, and this decline becomes evident after the age of 64.The decreasing of TT concentration with age is shown in Fig. 1.
The low TT group was characterized with signifi cantly higher values of 24 h systolic blood pressure (SBP) and pulse pressure (PP) values.Therewith it was noticed that the difference in SBP was more representative for values SBP during the active period.The difference between diastolic blood pressure (DBP) values between groups was non-signifi cant.The circadian BP profi le of non-dipper was prevalent in androgen defi cient patients (51 %).
The pulse wave form assessment showed that pulse pressure amplifi cation tends to be higher and wave refl ection tends to be lower in participants with testosterone insuffi ciency (Fig. 2).
Based on the idea that testosterone defi ciency can affect BP and arterial stiffness and although on the possibility of reverse causality multiple regression analysis was performed with testosterone as an independent variable and BP and arterial stiffness parameters as dependent variables.
The results of the multiple regression analysis using TT as an independent variable and SBP, DBP, PWV and SEVR as dependent variables are demonstrated in Table 2.This analysis revealed the relationship between plasma testosterone levels and SBP values in both study groups, while the relationship between testosterone and DBP values was not signifi cant.A signifi cant relationship was also found in each group between TT and PWV.
Discussion.The present research demonstrated the prevalence of androgen defi ciency among male patients with arterial hypertension and confi rmed the gradual decline of TT level with increasing of age.These fi ndings are in accordance to many prospective cross-sectional and longitudinal studies, such as Massachusetts Male Aging Study that also indicated a decrease of TT in the process of aging [10].Hypertensive patients with low TT level are characterized by higher 24 h SBP and PP; herewith the most prevalent circadian BP profi le is non-dipper.At the same time, the assessment of aortic stiffness parameters has shown the signifi cant relationship

Fig. 1 .
Fig. 1.The distribution of TT concentration according to the age.

Table 1 Main characteristics of the study population
Note: * -p≤0.05 between groups with and without androgen defi ciency.