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Influence of endogenous androgens on carotid wall in postmenopausal women.

ObjectiveThere is increasing evidence of a direct association between normal androgen levels and reduced cardiovascular morbidity and mortality in women. After menopause the influence of estrogens declines, whereas that of androgens increases. Therefore, we investigated the effects of androgens on atherosclerosis in postmenopausal women, by using carotid artery intimal-medial thickness as a marker of vascular damage. DesignBlood pressure, body mass index, waist-to-hip ratio, serum dehydroepiandrosterone sulfate, androstenedione, total and free testosterone, estrone, insulin, lipid profile, and glucose were evaluated in 44 women in stable physiological menopause. All subjects underwent carotid ultrasound (Biosound 2000 II s.a. high-resolution unit). ResultsSpearman correlation coefficients indicated that serum androstenedione and free testosterone were negatively associated with several carotid intimal-medial thickness measures with correlation coefficients (r) ranging from 0.477 to 0.397 (p < 0.01–0.04). Moreover, age-adjusted androstenedione and free testosterone highest tertiles showed intimal-medial thickness values significantly (p < 0.03–0.05) lower than the other tertiles. There was a favorable association between hormones and the most important cardiovascular risk factors. This association, however, did not reach statistical significance. Stepwise multiple regression analysis showed that the inverse relationships between the hormones (androstenedione and free testosterone) and several intimal-medial thickness measures were maintained (F: 4.15–6.07, p < 0.05–0.02) after adjustment for major cardiovascular risk factors. ConclusionsOur data demonstrate that in postmenopausal women endogenous steroid precursors and androgens are inversely related to carotid intimal-medial thickness, an established marker of atherosclerosis. In addition, these hormones show favorable associations with cardiovascular risk factors. Therefore, our study suggests that, after menopause, normal androgen levels may benefit the carotid artery wall.

Frequency of pheochromocytoma in adrenal incidentalomas and utility of the glucagon test for the diagnosis

To investigate the frequency of pheochromocytoma in patients with incidentally discovered adrenal masses (incidentalomas) and to evaluate the sensitivity, specificity and diagnostic accuracy of the Glucagon test in comparison with resting plasma catecholamines, 89 patients with adrenal incidentalomas (age range 23–80 yr; 41 males and 48 females) were studied. Fifty-seven patients were normotensive (SBP 130±1.8 mmHg; DBP 80±0.7 mmHg, mean±SE) and 32 had stable hypertension (SBP 155±3.3 mmHg, DBP 93±1.4 mmHg): no patient complained of typical signs or symptoms of pheochromocytoma. Resting plasma samples for noradrenaline and adrenaline determination and, at appropriate intervals, the Glucagon test (1 mg i.V.), were performed in all subjects. Diagnosis of pheochromocytoma was made on the basis of humoral evaluations and/or surgical intervention in 6 patients (6.7%), of whom 3 hypertensives and 3 normotensives. Resting plasma catecholamines revealed 5 out of 6 patients with pheochromocytoma: in 3 cases both catecholamines were above the normal range, in 1 only adrenaline was elevated and in 1 case only noradrenaline. Similarily, the glucagon test identified 5/6 pheochromocytomas: in 3 patients the response was abnormal for both catecholamines, in 1 only for adrenaline and in 1 case only for noradrenaline. The sensitivity, specificity, and diagnostic accuracy of resting plasma catecholamines and of the glucagon test were comparable: 83.3%, 96.3%, and 95.5%, respectively. In conclusion, the frequency of pheochromocytoma in adrenal incidentalomas is not negligible, and since the diagnostic accuracy of the Glucagon test is the same of that of resting plasma catecholamines, the former does not appear to offer additional advantages in the diagnosis of incidentally discovered pheochromocytomas.

Endogenous Digitalis-Like Factor and Ouabain Immunoreactivity in Adrenalectomized Patients and Normal Subjects After Acute and Prolonged Salt Loading

The aim of our study was to evaluate whether adrenals are involved in the secretion of endogenous digitalis-like factor(s) with polarity similar to (or less than) that of ouabain (EDLF-1), and whether acute plasma volume expansion is a physiological releasing stimulus for this factor(s) in humans. For this purpose, we measured the concentration of this substance(s) by a human placenta radioreceptor assay (RRA) and by the Du-Pont-NEN ouabain-EIA (immunoreactive ouabain, I-Oua) in plasma C18-extracts of eight normotensives and six patients with bilateral adrenalectomy before and after acute salt loading (2 lt 0.9% NaCl/2 h). The study was repeated after 2 weeks of increased sodium intake (200 mEq/day). Under basal conditions, EDLF-1 by RRA and I-Oua were similar in adrenalectomized patients and in controls and were not significantly modified by saline infusion. After 15 days of high sodium intake, basal plasma EDLF-1 and I-Oua were not significantly different from prediet levels, both in adrenalectomized patients and controls and were likewise unaffected by saline loading. Saline infusion, by contrast, significantly (P < or = .05) suppressed hematocrit and PRA and increased ANP both in controls and in patients, either before or after prolonged high dietary sodium. Plasma aldosterone (ALD) was similarly reduced (P < .001) in controls and, as expected, was undetectable in adrenalectomized patients. Our data indicate that in adrenalectomized patients circulating levels of EDLF-1 and I-Oua are similar to those of controls and that, in both groups, acute saline loading before and after sodium repletion does not influence circulating levels of these compounds. These findings suggest that, at least in humans, adrenals are not the main source of endogenous digitalis-like factor(s) with polarity similar to (or less than) that of ouabain, and that plasma volume expansion may be not a sufficient stimulus for the release of this factor(s).

17-hydroxyprogesterone response to ACTH in bilateral and monolateral adrenal incidentalomas

The aim of our study was to assess the frequency of 21-hydroxylase deficiency, a cause of congenital adrenal hyperplasia (CAH), in incidentally discovered asymptomatic adrenal masses (incidentalomas) and to compare the prevalence of this enzymatic disorder in monolateral (M) and bilateral (B) forms. Twenty-seven patients with incidentalomas (12 M and 15 B) and 16 sex and age-matched controls (C) received synthetic adrenocorticotropin (ACTH, 250 μg iv). Plasma 17-OHprogesterone (17-OHP) and Cortisol were collected in basal conditions and after 30, 60, 90 minutes. Basal plasma 17-OHP in C [1.25±0.15 (0.61) ng/ml, mean±SE (SD)] was not significantly different from that in patients with M [0.85±0.13 (0.44) ng/ml] or B [0.94±0.23 (0.90) ng/ml] incidentalomas. After ACTH, 17-OHP levels significantly (p<0.05) increased in C, in M and B incidentalomas. However, the rise in plasma 17-OHP in C both in terms of peak [2.5±0.28 (1.1) ng/ml] and of AUC values [174+16 (64) ng/ml/min] was significantly lower than that observed in M [peak 6.32±1.66 (5.7) ng/ml, p<0.01; AUC 410±111 (385.5) ng/ml/min, p<0.01] and in B [peak 8.84±1.98 (7.65) ng/ml, p<0.001; AUC 613±149 (579.3), ng/ml/min, p<0.001] incidentalomas. Individual data indicated that while 17-OHP response to ACTH in C never reached 5 ng/ml (cut-off for normal response), 16 out of 27 patients with incidentalomas (59.2%) exceeded this value. Moreover, the abnormal response was more frequently observed in B (66.6%) than in M (50%) incidentalomas. Basal and stimulated plasma Cortisol did not differ among the three groups. In conclusion, our data indicate that in adrenal incidentalomas the endocrine pattern of 21-hydroxylase deficiency is very common and that this enzymatic defect is more frequent in bilateral than in monolateral lesions.

Relationship between wave reflection and renal damage in hypertensive patients: a retrospective analysis

Objective: Arterial stiffening has harmful effects; peripheral pulse wave reflections deleteriously increase central pressure, but on the contrary they could also possibly be protective, as the pulse is transmitted to the microcirculation to a lesser extent. The aim of this study was, therefore, to explore the relationship between wave reflection and small vessel damage in the kidney. Methods: In 216 hypertensive patients, data on renal resistive index, obtained by Doppler ultrasound sampling of the interlobar arteries, as well as augmentation index (AIx) and carotid-to-femoral pulse wave velocity (PWV), were retrospectively analyzed. Reflection magnitude was computed through a triangular flow estimate. Results: AIx and reflection magnitude were positively correlated with resistive index; age, BMI, central pulse pressure, and cholesterol, but not AIx or reflection magnitude, were predictors of resistive index in multivariate analyses. Crossing tertiles of PWV and AIx, resistive index did not differ between patients with high AIx and low PWV (n = 25; 0.632 (0.064)) and those with low AIx and high PWV (n = 17; 0.645 (0.053)), despite a difference in reflection magnitude (74.9 (6.7) vs. 51.2 (7.3)%; P < 0.001). Conclusion: Pressure wave reflection is positively correlated with resistive index in a hypertensive population. No negative relationship was found even adjusting for confounders or when it was examined separately from the influence of arterial stiffness. These findings do not support the hypothesis of peripheral wave reflections having a significant protective role for the microcirculation of a low resistance vascular bed such as the kidney.

[PP.19.24] DETERMINANTS OF INAPPROPRIATELY HIGH PULSE WAVE VELOCITY IN HYPERTENSIVE PATIENTS: A RETROSPECTIVE CROSS-SECTIONAL COHORT STUDY

Objective: Age and blood pressure (BP) are known to be the main determinants of large artery stiffness. However other factors may lead to an inappropriately high pulse wave velocity (PWV) on top of these two factors. We investigated the determinants of inappropriately high PWV in hypertensive patients, and their possible role in causing organ damage accrual. Design and method: Hypertensive patients were selected among those attending a visit in our Hypertension Outpatient Clinic and undergoing carotid-femoral PWV by applanation tonometry, and cardiac and carotid ultrasound during a 5-year period (2006–2011). Inappropriately high pulse wave velocity (PWV) was calculated as the ratio between the observed value and the values predicted according to the formula derived from international reference values stratified by age and mean BP (oPWV/pPWV). Results: 731 hypertensive patients were selected (age 30–88 years, 42% women, 57% taking BP-lowering drugs). Median oPWV/pPWV was 102% (range 61–196%). In a multiple linear regression model, independent determinants of oPWV/pPWV were: daylight hours (beta -1.72, p < 0.001), age (beta -0.73, p < 0.001), BMI (beta 0.49, p = 0.01), blood glucose (beta 0.18, p < 0.001), mean BP (beta = -0.25, p = 0.002) and heart rate (beta = 0.22, p = 0.003). Though oPWV/pPWV was significantly higher in men and current smokers, the association disappeared in the multiple regression model. There was no association between oPWV/pPWV and any BP-lowering drug class. oPWV/pPWV was not associated with left ventricular mass. Conversely, oPWV/pPWV was an independent determinant of the presence of carotid plaques (beta 7.35, 5–95%CL 2.36–12.34). Conclusions: In hypertensive patients, inappropriately elevated PWV is associated more tightly than observed PWV to younger age and high blood glucose, thus it might help to better depict vascular aging in younger hypertensives and in those with metabolic alterations. A more advanced atherosclerotic process might also contribute to excess aortic stiffness. Whether an inappropriately high PWV translates into an increased cardiovascular risk should be determined in longitudinal studies.