Matteo Bernini

Arterial stiffness, intima-media thickness and carotid artery fibrosis in patients with primary aldosteronism

Objectives To evaluate vascular wall structure and conduit artery stiffness in patients with primary aldosteronism. Methods This observational study, conducted in a University Hypertension Center, evaluated the carotid wall by 2-D ultrasonography and ultrasonic tissue characterization, and analyzed arterial stiffness by applanation tonometer. Twenty-three consecutive patients with primary aldosteronism, 24 matched patients with essential hypertension and 15 controls were studied. Intima-media thickness and corrected integrated backscatter signal of the carotid arteries were evaluated. Radial and femoral pulse wave velocity and aortic augmentation index were also investigated. Results Intima-media thickness in patients with essential hypertension (0.69 ± 0.03 mm) was higher (P < 0.04) than that in controls (0.59 ± 0.02 mm). This finding was more evident in primary aldosteronism patients (0.84 ± 0.03 mm), in whom intima-media thickness was greater than that in controls (P < 0.0001) or in patients with essential hypertension (P < 0.01). Similarly, corrected integrated backscatter signal in patients with essential hypertension (−23.6 ± 0.35 dB) was higher (P < 0.0001) than that in controls (−26.2 ± 0.44 dB), but it was even more elevated in patients with primary aldosteronism (−22.1 ± 0.46 dB), who showed greater corrected integrated backscatter signal than was the case in patients with essential hypertension (P < 0.009) or in controls (P < 0.0001). Femoral pulse wave velocity was higher in primary aldosteronism patients (10.8 ± 0.57 m/s) than in patients with essential hypertension (9.1 ± 0.34 m/s, P < 0.03) or in controls (7.1 ± 0.51 m/s, P < 0.0001). Femoral pulse wave velocity was lower in controls than in patients with essential hypertension (P < 0.0001). The same pattern was observed for radial pulse wave velocity. Aortic augmentation index was higher in primary aldosteronism patients (28.2 ± 2.1%) than in patients with essential hypertension (26.0 ± 1.8%) or in controls (16.8 ± 2.0%, P < 0.001). Patients with essential hypertension likewise exhibited higher aortic augmentation index than controls (P < 0.001). Conclusion Aldosterone excess is responsible per se for vascular morphological (wall thickening and carotid artery fibrosis) and functional (central stiffness) damage.

Cholecalciferol administration blunts the systemic renin–angiotensin system in essential hypertensives with hypovitaminosis D

Introduction: Vitamin D plasma levels are negatively associated with blood pressure and cardiovascular mortality, and vitamin D supplementation reduces cardiovascular events. Renin–angiotensin system (RAS) suppression may be one of the mechanisms involved. However, there are no interventional prospective studies demonstrating a reduction in circulating RAS components after vitamin D treatment. Methods: Fifteen consecutive drug-free patients with essential hypertension and hypovitaminosis D underwent therapy with an oral dose of 25000 I.U. of cholecalciferol once a week for two months, while maintaining a constant-salt diet. In basal conditions and at the end of the study, RAS activity (plasma angiotensinogen, renin, PRA, angiotensin II, aldosterone and urinary angiotensinogen) was investigated, in addition to blood pressure and plasma vitamin D levels (25(OH)D). Results: After cholecalciferol administration, all patients exhibited normalized plasma 25(OH)D values. At the end of the study, a reduction (p < 0.05) in plasma renin and aldosterone, and a decrement, although not significant, of PRA and angiotensin II, was observed. No difference was found in plasma and urinary angiotensinogen or blood pressure values. Conclusions: Our data indicate that in essential hypertensives with hypovitaminosis D, pharmacological correction of vitamin D levels can blunt systemic RAS activity.

Plasma and urine aldosterone to plasma renin activity ratio in the diagnosis of primary aldosteronism.

Objective To establish the best cut-off value of the aldosterone (ALD)/plasma renin activity (PRA) ratio when screening patients for primary aldosteronism. One hundred and six patients with primary aldosteronism and 100 essential hypertensive patients were investigated in rigorous standardized conditions. Methods The ALD/PRA cut-off values were calculated from both the plasma and urine ALD/PRA ratio and analyzed by receiver operating characteristic (ROC) curve. In patients with PRA below 0.2 ng/ml/h [our radioimmunoassay detection limit], values were calculated both with PRA levels set at 0.2 ng/ml/h (‘adjusted’) and with PRA levels detected (‘unadjusted’) in the assay. Results ROC analysis on the ALD/PRA ratio indicated that the best performance was obtained when the plasma ALD (ng/dl)/PRA ratio was used in comparison with that observed in the urine ALD (μg/day)/PRA ratio. In patients with primary aldosteronism, as a whole group, the cut-off value of 69 corresponded to the best compromise value between sensitivity (96%) and specificity (85%), with and without PRA adjustment. In patients with aldosterone-producing adenoma, the cut-off to obtain 100% sensitivity with high specificity (85%) proved to be 69, with and without PRA adjustment. In patients with bilateral adrenal hyperplasia, both with and without PRA adjustment, the best compromise between sensitivity (94%) and specificity (86%) was a cut-off value of 71. Conclusion The best cut-off to identify patients with primary aldosteronism, corresponding to 69, was obtained by using the plasma ALD/PRA ratio. Adjustment of PRA to 0.2 ng/ml/h does not interfere with calculation of the plasma ALD/PRA ratio cut-off.

Cardiovascular changes in patients with primary aldosteronism after surgical or medical treatment

Background: Data on the cardiovascular middle-term follow-up of patients with primary aldosteronism (PA) are scanty. Aim: To detect the cardiovascular effects of surgery in patients with aldosterone (ALD)-producing adenoma (APA) and of pharmacotherapy in those with bilateral adrenal hyperplasia (BAH), a prospective study involving 60 consecutive patients with PA was performed. Material/methods: Clinical, biochemical, and cardiovascular assessment was obtained before and after (31.5±4.4 months) surgery or proper medical treatment (32.1 ±5.0 months) in 19 and 41 patients, respectively. Results: As expected, plasma ALD normalized in all operated patients, while in the other group it did not change. Systolic and diastolic blood pressure decreased (p<0.001) after both treatments. However, absolute and percentage reduction was significantly more pronounced (p<0.01) in operated than in non-operated patients. Left ventricular (LV) mass showed significant reduction after surgery (LV mass g/m2, p<0.0007; LV mass g/m2.7, p<0.01), but no change after medical treatment, so that the differences between absolute and percentage values at follow-up were statistically significant (p<0.01) between groups. Basal LV mass/m2.7 was positively associated with age (p<0.009), body mass index (p<0.0008), drug number (p<0.03), and ALD/plasma renin activity ratio (p<0.01). Allocating the patients according to plasma ALD and cardiac parameters, patients who presented ALD reduction during the study also had a decrement in cardiac mass (p<0.04). Conclusions: Our data indicate that in patients with PA the removal of ALD excess by surgery in APA is effective in reducing blood pressure and in improving cardiac parameters, while anti-hypertensive therapy in BAH shows less positive impact on cardiovascular system.

Cardiac remodeling in patients with primary aldosteronism

Objective: To evaluate the morpho-functional changes of the myocardium in patients with primary aldosteronism (PA). Design: An observational study in a university referral center for blood pressure diseases. Patients: Twenty-three patients with PA, 24 patients with essential hypertension (EH), and 15 normotensive controls (C) underwent conventional echocardiography with integrated backscatter (IBS) and tissue Doppler imaging (TDI) analysis. The corrected IBS (C-IBS) values and the systo-diastolic variation of IBS (CV-IBS) were performed at both interventricular septum and the posterior wall levels. TDI myocardial systolic (Sm), early diastolic (Em), and late diastolic (Am) velocities of both left ventricular walls were also determined. Results: In PA patients, septal and posterior wall CV-IBS were significantly lower than C (p<0.0001) and EH patients (p<0.001). In EH, CV-IBS was significantly lower than C (p<0.001). Patients with PA exhibited lower Sm, lower Em, and higher Am, and a subsequently reduced Em/Am ratio than C (p<0.001 for all) and EH (p<0.01 for all) at interventricular septum and lateral wall levels. In the latter, Sm, Em, and Em/Am ratio were lower and Am was higher than C (p<0.001 for all). In PA and EH patients, CV-IBS at both septum (r=−0.66, p<0.001) and posterior wall levels (r=−0.67, p<0.001) and Sm peak of both septum (r=−0.52, p<0.001) and lateral wall (r=−0.55, p<0.001) were inversely related to plasma aldosterone. Conclusions: Patients with PA showed myocardial wall remodeling characterized by increased myocardial fibrosis and early left ventricular systodiastolic function abnormalities.

Effect of acute and chronic vitamin D administration on systemic renin angiotensin system in essential hypertensives and controls

Aim: To investigate the systemic renin-an-giotensin system (RAS) in essential hypertensives (EH) and controls (C) after short- and long-term vitamin D receptor activation. Design: Ten consecutive EH (under controlled low-salt diet) and 10 C underwent calcitriol administration (0.25 µg bid) for 1 week (Group A). Eighteen consecutive EH under angiotensin II receptor antagonist therapy received a single oral dose of 300,000 IU of cholecalciferol and were followed up for 8 weeks (Group B). Methods: In basal conditions and at the end of the study (1 week in Group A and 8 weeks in Group B), plasma renin activity (PRA), plasma active renin, aldosterone, and angiotensin II were evaluated, as well as blood pressure, plasma 25-hy-droxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], and PTH. Results: In Group A, plasma 25(OH)D levels in EH and C were below the normal range, although lower levels were found in the former. No association between basal plasma 25(OH)D or 1,25(OH)2D levels and blood pressure values or RAS components was observed either in the whole group or in the two subgroups. Calcitriol administration did not affect any RAS parameter either in EH or in C. In Group B, cholecalciferol significantly increased 25(OH)D and 1,25(OH)2D levels without interfering with the angiotensin II receptor antagonist-induced increase in RAS components. No correlation was found between plasma 25(OH)D or 1,25(OH)2D levels and blood pressure values or RAS parameters before and after cholecalciferol administration. Conclusions: The present data suggest that, in our experimental conditions, vitamin D receptor activation is unable to influence systemic RAS activity.

Normalization of catecholamine production following resection of phaeochromocytoma positively influences carotid vascular remodelling

OBJECTIVE To evaluate the influence of plasma catecholamines on the vascular structure in humans, the effects of catecholamine normalization on the carotid wall of patients with phaeochromocytoma (PHEO) were investigated. A prospective study in patients with PHEO before and after (first follow-up: 20.5+/-1.8 months, second follow-up: 31.5+/-2.2 months) successful surgery was conducted in the University Referral Center for Blood Pressure Diseases. Ten consecutive patients with PHEOs and ten age- and blood pressure-matched controls were investigated. Intima-media thickness (IMT) by two-dimensional conventional ultrasonography and corrected ultrasonic integrated backscatter signal (C-IBS) analysis of carotid arteries were investigated in basal conditions and after mass removal. RESULTS In PHEOs, at variance with the expected reduction in metanephrines and catecholamines, no variation in body weight, blood pressure and lipid profile was observed after operation. IMT and C-IBS values in patients with PHEO were greater (at least P<0.01) than in controls. At long-term follow-up after surgery, a significant reduction in mean carotid IMT (P<0.0009) and C-IBS (P<0.009) values was observed. A significant correlation (r=0.54, P<0.03) was found between absolute reduction in C-IBS values and absolute decrement in urinary normetanephrine levels. CONCLUSIONS Our study shows that normalization of catecholamine levels after the removal of PHEO improves carotid IMT and reduces carotid wall fibrosis even without influencing blood pressure and lipid profile. These findings confirm that high catecholamine tone in humans directly influences vascular remodelling of carotid arteries.

A case of pheochromocytoma presenting as secondary hyperaldosteronism, hyperparathyroidism, diabetes and proteinuric renal disease

A 35-year-old woman was admitted to the Nephrology and Dialysis Unit of Pisa University for hypertension, hypokalaemia, renal impairment, proteinuria and hyperglycaemia. plasma renin activity (PRA) and plasma aldosterone were elevated, but Doppler ultrasound and angio-computed tomography (CT) of renal arteries were normal. Abdomen CT revealed only a left adrenal mass, and measurement of catecholamines suggested the diagnosis of pheochromocytoma. Biochemical findings suggestive of hyperparathyroidism were also detected, but a multiple endocrine disorder was excluded by genetic analysis. Pathology examination confirmed the pheochromocytoma and immunohistochemistry also showed positivity for parathyroid hormone. After surgery, disappearance of the symptoms and normalization of all haemodynamic and humoral parameters was observed. This is a rare case of pheochromocytoma responsible for secondary hyperaldosteronism, hyperparathyroidism, proteinuric renal disease and diabetes mellitus.

Sporadic or familial head neck paragangliomas enrolled in a single center: Clinical presentation and genotype/phenotype correlations

The purpose of this study was to investigate clinical features and prevalence of germline mutations of patients with head/neck paragangliomas.

Acute and Subacute Effect of Rheopheresis on Microvascular Endothelial Function in Patients Suffering From Age‐related Macular Degeneration

This study was performed on seven patients affected by the atrophic form of age‐related macular degeneration (AF‐ARMD). The patients under investigation belonged to a larger study aimed at evaluating the efficacy of rheopheresis treatment (RT) on the visual function of AF‐ARMD patients. Following the protocol of the larger study, patients received RT twice a week, every two weeks, for a total of ten treatments, as well as high‐dose supplementation with zinc and vitamins A, E and beta‐carotene. Recruited patients underwent skin laser Doppler flowmetry coupled with skin iontophoresis of the endothelium‐dependent vasodilator acetylcholine (ACh) and a test of skin post‐ischemic reactive hyperemia, before and after the first RT (time 1: all seven patients) and the fifth RT (time 2: six patients). A significantly higher absolute (anova for repeated measures) and relative (percentage change from the baseline) skin blood flux response (SBFR) to ACh iontophoresis was observed after RT, compared to before RT at time 1 (679 ± 43% and 436 ± 78%, respectively; P < 0.05), as well as before RT at time 2 compared to before RT at time 1 (683 ± 74% and 436 ± 78%, respectively; P < 0.05). Absolute and relative SBFR to ischemia did not differ either after RT compared to before RT at time 1, or before RT at time 2 compared to before RT at time 1. These findings are consistent with an acute and subacute beneficial effect of RT on skin microvascular endothelial function in the studied AF‐ARMD patients.