Clinical significance of endocrine disorders in the development of early vascular aging in males with abdominal obesity and concomitant arterial hypertension: An observational cohort study

Abstract

Background. Visceral obesity is a risk factor in the development of metabolic and endocrine disorders leading to arterial hypertension and cardiovascular complications. Their early predictors include increased vascular stiffness and early vascular aging. The current literature lacks studies into the effects of changes in testosterone, cortisol, and aldosterone levels in serum on vascular stiffness and the development of early vascular aging in patients with visceral obesity. Objective. To determine the relationship between hypercortisolemia, hyperaldosteronemia, and hypotestosteronemia and vascular stiffness and the presence of early vascular aging in male patients with visceral obesity. Methods. An observational cohort study of 78 males aged 35–45 years (mean age 38.1 ± 6.5 years) diagnosed with abdominal obesity and grade 1 arterial hypertension was conducted. The mean waist circumference ranged 105.5 ± 6.9 cm; systolic and diastolic blood pressure ranged 152.5 ± 5.0 and 92.5 ± 5.0 mm Hg, respectively. The vascular age of the studied patients (n = 78) comprised 44.1 ± 6.2 years, which was statistically higher than their passport age (р < 0.001). The studied patients were divided into subgroups according to both total testosterone (< 12.1 nmol/l in subgroup 1A (n = 49) and ≥ 12.1 nmol/L in subgroup 1B (n = 29)) and cortisol in the evening saliva portion (> 4.5 nmol/L in subgroup 2A (n = 24) and ≤ 4.5 nmol/L in subgroup 2B (n = 24)). All the patients completed the study. To assess the hormonal status, the total testosterone sex steroid-binding globulin (SSBP) and insulin in morning serum samples were investigated. Insulin resistance was assessed based on the NOMA-IR index. The concentration of total testosterone was determined by enhanced chemiluminescence (Ortho-Clinical Diagnostics, J&J); the SSBP and insulin levels were determined by delayed fluorescence. Aldosterone content was determined by radioimmunoassay; free cortisol and testosterone were measured by luminescent LIA. Free and bioavailable testosterone concentrations in serum were calculated using an online calculator (issam.ch/freetesto.htm). The cardio-ankle vascular index (CAVI) was determined using a VaSera VS-15000N device, which automatically calculated the vascular age. Statistical analysis was performed using the Statistica 10.0 Windows package (StatSoft, Inc., USA). Results. The vascular age of patients with hypogonadism was statistically significantly ( р < 0.001) higher than their passport age and the vascular age in males without hypogonadism. The CAVI and vascular age were also statistically significantly higher in males with functional hypercorticism (р < 0.001) compared with a subgroup of patients without hypercorticism. The vascular age and CAVI increased with an increase in the salivary cortisol concentration 2200 (r = 0.5; р < 0.05) and decreased with an increase in the salivary cortisol level 900 (r = –0.5; р < 0.05). These parameters decreased with an increase in serum aldosterone obtained in the morning (r = –0.4; p < 0.05) and increased with an increase in serum aldosterone in the evening (r = 0.4; p < 0.05). In 23% (n = 18), an inversion of the daily rhythm of cortisol production was observed; in these patients, salivary cortisol levels of 2200 exceeded salivary cortisol levels of 900. The vascular age of patients with the inversion of cortisol production (49.4 ± 4.4 years) was statistically significantly ( р < 0.001) different from that of patients with normal changes in salivary cortisol concentrations (41.9 ± 4.9 years). CAVI was also higher (р < 0.001) in males with inverted fluctuations in salivary cortisol levels (7.51 ± 0.62) compared to those with normal diurnal rhythm (6.45 ± 0.69). The results of aldosterone evaluation revealed that 17% of the patients (n = 13) had higher aldosterone levels in the evening serum portion compared to the morning serum portion. In these patients, the vascular age (45.8 ± 5.1 years) was higher ( р < 0.001) than that in males with normal physiologic changes in aldosterone levels (41.6 ± 5.7 years). A similar pattern was observed when comparing vascular stiffness indices. Thus, the CAVI in men with inverted changes in aldosterone concentration (6.9 ± 0.8) was significantly higher ( р < 0.001), compared to that in men with physiological changes in blood aldosterone levels (6.4 ± 0.8). Conclusion. Endocrinologic disorders in male patients with visceral obesity and concomitant arterial hypertension (functional hypogonadism, functional hypercorticism, inverted daily rhythms of cortisol and aldosterone production) contribute to the development of early vascular aging by increasing vascular stiffness.