Franco Veglio

Università degli Studi di Torino, Torino, Piedmont, Italy

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Publications (279)760.08 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Context: Adrenal vein sampling (AVS) is the only reliable means to distinguish between aldosterone producing adenoma and bilateral adrenal hyperplasia, the two most common subtypes of primary aldosteronism (PA). AVS protocols are not standardized and vary widely between centers. Objective: To retrospectively investigate whether the presence of contralateral adrenal (CL) suppression of aldosterone secretion was associated with improved postoperative outcomes in patients who underwent unilateral adrenalectomy for PA. Setting: The study was carried out in 8 different referral centers in Italy, Germany and Japan. Patients: From 585 consecutive AVS in patients with confirmed PA, 234 procedures met the inclusion criteria and were used for the subsequent analyses. Results: Overall, 82% of patients displayed contralateral suppression. This percentage was significantly higher in ACTH stimulated compared to basal procedures (90% vs 77%). CL ratio was inversely correlated with aldosterone level at diagnosis and, amongst AVS parameters, with lateralization index (p=0.02 and 0.01, respectively). The absence of contralateral suppression was not associated with a lower rate of response to adrenalectomy in terms of both clinical and biochemical parameters and patients with CL suppression underwent a significantly larger reduction in aldosterone levels after adrenalectomy. Conclusions: For patients with lateralizing indices of > 4 (which comprised the great majority of subjects in this study), CL suppression should not be required to refer patients to adrenalectomy, since it is not associated with a larger blood pressure reduction after surgery and might exclude patients from curative surgery.
    The Journal of clinical endocrinology and metabolism. 08/2014;
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    ABSTRACT: The risk of thoracic aortic dissection is strictly related to the diameter of the ascending aorta. Arterial hypertension represents a major risk factor for the development of aortic dissection and is thought to be directly involved in the pathogenesis of aortic aneurysms. Recent studies have suggested a high prevalence of aortic root enlargement in the hypertensive population, but evidence of a direct link between blood pressure values and size of the aortic root has been inconclusive so far. The aim of the current study was to evaluate prevalence of aortic root dilatation (ARD) in the hypertensive population and to assess the correlates of this condition.
    Journal of hypertension. 06/2014;
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    ABSTRACT: Patients with autonomic failure experience orthostatic hypotension (OH) often leading to syncope. Arrhythmias may cause severe syncope, characterized by an increased risk of mortality. We report two cases of patients with primary autonomic neuropathy suffering from both severe OH and arrhythmic syncope.
    Clinical autonomic research : official journal of the Clinical Autonomic Research Society. 05/2014;
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    ABSTRACT: Primary aldosteronism comprises subtypes that need different therapeutic strategies. Adrenal vein sampling is recognised by Endocrine Society guidelines as the only reliable way to correctly diagnose the subtype of primary aldosteronism. Unfortunately, despite being the gold-standard procedure, no standardised procedure exists either in terms of performance or interpretation criteria. In this Personal View, we address several questions that clinicians are presented with when considering adrenal vein sampling. For each of these questions we provide responses based on the available evidence, and opinions based on our experience. In particular, we discuss the most appropriate way to prepare the patient, whether adrenal vein sampling can be avoided for some subgroups of patients, the use of ACTH (1-24) during the procedure, the most appropriate criteria for interpretation of adrenal vein cannulation and lateralisation, the use of contralateral suppression, and strategies to improve success rates of adrenal vein sampling in centres with little experience.
    The lancet. Diabetes & endocrinology. 05/2014;
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    ABSTRACT: Volume overload is typical of haemodialysis patients; correct volume status evaluation is crucial in achieving blood pressure homeostasis, hypertension management and good treatment planning. This study evaluates the effect of acute volume depletion on ultrasonographic parameters and suggests two of them as able to predict patients volume overload. 27 patients with end stage renal disease treated with haemodialysis underwent a complete echocardiographic exam before, after 90 min and at the end of the dialysis. Blood pressure levels significantly drop during the first 90 min of dialysis (139 ± 20 vs 126 ± 18; p < 0.0001), reaching a steady state with significantly lower values compared to baseline (130 ± 28; p = 0.02). LV and left atrial volume significantly decreased (baseline vs end dialysis 98 ± 32 vs 82 ± 31 p = 0.003 and 28 ± 10 vs. 21 ± 9 cc/m(2) p < 0.001). A significant reduction of systolic function (EF 61.6 % ± 9 vs 58.7 % ± 9 p = 0.04), of diastolic flow velocities (E/A 1.13 ± 0.37 vs. 0.87 ± 0.38 p < 0.001) and mitral annulus TDI tissue velocity (i.e. E' lat 10.6 ± 3 vs. 9.4 ± 3 cm/s; p 0.0001) were observed. Stroke work (SW) and LV end-diastolic diameter (LVEDd) indexed to height 2.7(LVEDdi) were able to predict volume overload: cut off values of respectively 13.5 mm/m(2.7) for LVEDdi and 173 cJ for SW were able to predict with a specificity of 100 % the presence of a volemic overload of at least 4 %. Blood pressure, cardiac morphology and function are significantly modified by acute volume depletion and such variations are strictly interrelated. SW and LVEDd/height(2.7) may identify ESRD patients carrying an higher volume load.
    High Blood Pressure & Cardiovascular Prevention 02/2014;
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    ABSTRACT: A correct diagnosis of primary aldosteronism (PA) requires adrenal venous sampling (AVS) for the classification of subtypes (bilateral hyperplasia, BAH, or adenoma, APA). Since such testing is not easily practicable, appropriate markers for the definition of subtypes are desirable. We hypothesized that an aldosterone excess was associated with abnormalities in urinary proteome, specific for PA subtypes. The project work was divided into 3 phases: (1) screening/identification by proteomic analysis and further characterization by RT-PCR and immunohistochemistry of the candidate protein; (2) clinical validation by quantitative ELISA assay of 57 (33 M, 24 F) PA patients and 50 normotensive controls (21 M, 29 F); (3) analysis of adrenal tissue of 8 individuals who had undergone adrenalectomy for APA or other adrenal tumors. The proteomic analysis showed a different expression of Serpin B3 Inhibitor-SCCA1 (SB3) in APA and BAH patients. Urine SB3 concentrations in normotensive controls, quantified by ELISA assay and normalized by urinary creatinine, resulted much lower in males (6.72 ng SB3 per mg creatinine, C.I. 4.43-10.19) than in females (20.56 ng SB3 per mg creatinine, C.I. 12.43-33.99, p < 0.00001). SB3 concentrations were not significantly different in males affected by different PA subtypes (BAH, n = 19 and APA, n = 14) compared with normotensive subjects (n = 21). In contrast, in PA females, SB3 was significantly higher in APA (n = 13) than in BAH patients (n = 11) or in normotensive controls (n = 29) (P < 0.01 and <0.05, respectively). Neither messenger RNA nor SB3 protein were identified in tissue obtained from adrenal tumors and from the surrounding normal gland. In conclusion urine SB3 concentrations are physiologically much lower in males than in females. Hypertensive women, affected by APA, present urinary SB3 concentrations significantly higher than women affected by BAH.
    Molecular BioSystems 02/2014; · 3.35 Impact Factor
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    Journal of Clinical Hypertension 01/2014; · 2.36 Impact Factor
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    ABSTRACT: Aldosterone-producing adenomas (APAs) cause a sporadic form of primary aldosteronism and somatic mutations in the KCNJ5 gene, which encodes the G-protein-activated inward rectifier K(+) channel 4, GIRK4, account for ≈40% of APAs. Additional somatic APA mutations were identified recently in 2 other genes, ATP1A1 and ATP2B3, encoding Na(+)/K(+)-ATPase 1 and Ca(2+)-ATPase 3, respectively, at a combined prevalence of 6.8%. We have screened 112 APAs for mutations in known hotspots for genetic alterations associated with primary aldosteronism. Somatic mutations in ATP1A1, ATP2B3, and KCNJ5 were present in 6.3%, 0.9%, and 39.3% of APAs, respectively, and included 2 novel mutations (Na(+)/K(+)-ATPase p.Gly99Arg and GIRK4 p.Trp126Arg). CYP11B2 gene expression was higher in APAs harboring ATP1A1 and ATP2B3 mutations compared with those without these or KCNJ5 mutations. Overexpression of Na(+)/K(+)-ATPase p.Gly99Arg and GIRK4 p.Trp126Arg in HAC15 adrenal cells resulted in upregulation of CYP11B2 gene expression and its transcriptional regulator NR4A2. Structural modeling of the Na(+)/K(+)-ATPase showed that the Gly99Arg substitution most likely interferes with the gateway to the ion binding pocket. In vitro functional assays demonstrated that Gly99Arg displays severely impaired ATPase activity, a reduced apparent affinity for Na(+) activation of phosphorylation and K(+) inhibition of phosphorylation that indicate decreased Na(+) and K(+) binding, respectively. Moreover, whole cell patch-clamp studies established that overexpression of Na(+)/K(+)-ATPase Gly99Arg causes membrane voltage depolarization. In conclusion, somatic mutations are common in APAs that result in an increase in CYP11B2 gene expression and may account for the dysregulated aldosterone production in a subset of patients with sporadic primary aldosteronism.
    Hypertension 09/2013; · 6.87 Impact Factor
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    ABSTRACT: Objectives:to compare cardio- and cerebrovascular events in patients with primary aldosteronism (PA) and matched essential hypertensives (EH).Background:aldosterone plays a detrimental role on the cardiovascular system and PA patients display a higher risk of events compared to EH.Methods:We compared retrospectively the percentage of patients experiencing events at baseline and during a median follow-up of 12 years in 270 PA patients case-control matched 1:3 with EH patients, and in PA subtypes [aldosterone-producing adenoma, APA (n = 57); bilateral adrenal hyperplasia, BAH (n = 213)] versus matched EH.Results:a significantly higher number of PA patients experienced cardiovascular events over the entire period of the study (22.6% vs 12.7%, p<0.001). At diagnosis of PA a higher number of patients had experienced total events (14.1% vs 8.4% EH, p=0.007); further, during the follow-up period, PA patients had a higher rate of events (8.5% vs 4.3% EH, p=0.008). In particular, stroke and arrhythmias were more frequent in PA patients. During the follow-up a higher percentage of PA patients developed type 2 diabetes. Parameters that were independently associated with the occurrence of all events were age, duration of hypertension, systolic blood pressure, presence of diabetes mellitus and PA diagnosis. After division into PA subtypes, patients with either APA or BAH displayed a higher rate of events compared to matched EH.Conclusions:this study demonstrate in a large population of patients the pathogenetic role of aldosterone excess in the cardiovascular system and thus the importance of early diagnosis and targeted PA treatment.
    The Journal of clinical endocrinology and metabolism 09/2013; · 6.50 Impact Factor
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    ABSTRACT: According to recent hypertension guidelines, resistant hypertension is a clinical condition characterized by the presence of BP values above the recommended limits of the reference values (BP >140/90 mmHg). The prevalence of this clinical condition is about 10 % of the essential hypertensives. A proper diagnosis and management of resistant hypertension should go trough careful, mandatory clinical step, aimed at excluding the presence of pseudo-resistance hypertension. In this report, we summarized the practical recommendations are targeting both the general practitioner and the specialist who play an active role in the clinical management of patients with arterial hypertension.
    High Blood Pressure & Cardiovascular Prevention 08/2013;
  • Alberto Milan, Sara Abram, Franco Veglio
    JAMA The Journal of the American Medical Association 07/2013; 310(2):204-5. · 29.98 Impact Factor
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    ABSTRACT: Arterial hypertension and cancer are two of the most important causes of mortality in the world; correlations between these two clinical entities are complex and various. Cancer therapy using old (e.g. mitotic spindle poisons) as well as new (e.g. monoclonal antibody) drugs may cause arterial hypertension through different mechanisms; sometimes the increase of blood pressure levels may be responsible for chemotherapy withdrawal. Among newer cancer therapies, drugs interacting with the VEGF (vascular endothelial growth factors) pathways are the most frequently involved in hypertension development. On the other hand, many retrospective studies have suggested a relationship between antihypertensive treatment and risk of cancer, raising vast public concern. The purposes of this brief review have then been to analyse the role of chemotherapy in the pathogenesis of hypertension, to summarize the general rules of arterial hypertension management in this field and finally to evaluate the effects of antihypertensive therapy on cancer disease. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 06/2013; · 6.20 Impact Factor
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    ABSTRACT: The diagnosis of childhood hypertension based upon percentile tables proposed by the international guidelines is complex and often a cause of underdiagnosis, particularly among physicians who have not had specific training in the field of adolescent hypertension. The use of a simple and accurate screening test may improve hypertension diagnosis in adolescents. The aim of our study is to compare the different screening methods currently used in the literature to improve the diagnosis of childhood hypertension. We have conducted a cross-sectional population-based study of 1412 Caucasian adolescents among students of public junior high schools of Turin, Italy. In this population we have defined the hypertensive status with four different screening tests: BPHR, Somu's equations, Ardissino, and Kaelber methods. Finally, we compared the diagnostic accuracy of the 4 screening tests with the gold standard. Our analysis identifies in BPHR the test which combines ease of use and diagnostic accuracy.
    ISRN Hypertension. 06/2013; 2013.
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    ABSTRACT: AIM: To assess the procedure for measuring blood pressure (BP) among hospital nurses and to assess if a training program would improve technique and accuracy. METHODS: 160 nurses from Molinette Hospital were included in the study. The program was based upon theoretical and practical lessons. It was one day long and it was held by trained nurses and physicians who have practice in the Hypertension Unit. An evaluation of nurses' measuring technique and accuracy was performed before and after the program, by using a 9-item checklist. Moreover we calculated the differences between measured and effective BP values before and after the training program. RESULTS: At baseline evaluation, we observed inadequate performance on some points of clinical BP measurement technique, specifically: only 10 % of nurses inspected the arm diameter before placing the cuff, 4 % measured BP in both arms, 80 % placed the head of the stethoscope under the cuff, 43 % did not remove all clothing that covered the location of cuff placement, did not have the patient seat comfortably with his legs uncrossed and with his back and arms supported. After the training we found a significant improvement in the technique for all items. We didn't observe any significant difference of measurement knowledge between nurses working in different settings such as medical or surgical departments. CONCLUSIONS: Periodical education in BP measurement may be required, and this may significantly improve the technique and consequently the accuracy.
    High Blood Pressure & Cardiovascular Prevention 05/2013;
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    ABSTRACT: Primary aldosteronism (PA) is now recognized as the most frequent form of secondary arterial hypertension. The importance of a correct and prompt diagnosis of PA is determined by its relevant prevalence, its increased cardiovascular risk compared to essential hypertension and by the possibility of reversing this increased risk with a targeted therapy. Surgical treatment of unilateral forms of PA (mainly aldosterone-producing adenomas) is at present recommended in well-selected patients because of its cost-effectiveness. Therefore, subtype differentiation of PA forms is of fundamental importance, and available guidelines recommend contrast-enhanced CT-scanning and adrenal venous sampling (AVS) as the main diagnostic tests for this purpose. In this review, we discuss the value of adrenal non-invasive imaging and AVS, the recent advances in complementary tests and, finally, the available data on the outcome of surgical treatment for PA.
    Current Hypertension Reviews 05/2013; 9(2):156-65.
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    ABSTRACT: BACKGROUND:: Aortic root dilatation (ARD) and arterial hypertension represent two important risk factors for aortic dissection: prevalence of observed ARD is increasing - up to 12% in the latest available reports. A recently published work tested on a good number of healthy individuals new reference ranges for aortic root dimensions, suggesting new reference values with corrections for age, gender, height (pHeight) or body surface area (pBSA). AIM:: The aim of the study was to evaluate the prevalence of ARD in hypertensive patients using various criteria. METHODS:: A total of 1076 untreated and treated essential hypertensive patients (mean age, 52.5 ± 2 years) were considered for this analysis. We measured proximal aortic diameters using ultrasound imaging (echocardiography). ARD was defined in three ways. First, when the observed aortic diameter was larger than that predicted for age, sex, and BSA (pBSA), second when larger than predicted by height (pHeight), and third when the aortic diameter to BSA ratio (ASi) was at least 2.1 cm/m. RESULTS:: A total of 237 patients (22% of the study population) showed at least one among the three different criteria defining aortic dilatation. Prevalence of ARD, considering singularly each one of the criteria, varied between 12.8% (pBSA) and 16.9% (pHeight). CONCLUSION:: Our study demonstrated a prevalence of ARD higher than previously reported. Our data suggest, therefore, the necessity of a correct choice of the diagnostic criterion that has to be applied in the single patient for definition of ARD. In particular, using the criterion pHeight in obese patients, we may avoid underdiagnosis of this condition.
    Journal of Hypertension 03/2013; · 4.22 Impact Factor
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    ABSTRACT: Primary aldosteronism is characterised by the dysregulation of aldosterone production and comprises both sporadic forms, caused by an aldosterone-producing adenoma or bilateral adrenal hyperplasia, and familial forms (familial hyperaldosteronism typesI, II and III). The two principal physiological regulators of aldosterone synthesis are angiotensinII and serum K + , which reverse the high resting K + conductance and hyperpolarized membrane potential of adrenal glomerulosa cells. The resulting membrane depolarization causes the opening of voltage-gated Ca 2+ channels and an increase in intracellular Ca 2+ that stimulates aldosterone biosynthesis. Point mutations in the KCNJ5 gene, which encodes the G-protein-activated inward rectifier K + channel4 (GIRK4), have been implicated in the pathogenesis of both sporadic and familial forms of primary aldosteronism. These mutations interfere with the selectivity filter of GIRK4 causing Na + entry, cell depolarization and Ca 2+ channel opening, resulting in constitutive aldosterone production. Seven families with familial hyperaldosteronism caused by KCNJ5 germline mutations have so far been described, and multicentre studies have reported KCNJ5 mutations in approximately 40% of sporadic aldosterone-producing adenomas. Herein, we review the role of GIRK4 in adrenal pathophysiology and provide an overview of the clinical and biochemical phenotypes resulting from KCNJ5 mutations in patients with sporadic and familial primary aldosteronism.
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    ABSTRACT: OBJECTIVES:: The objectives of this study were to evaluate the prevalence of dilatation of proximal ascending aorta (pAA) in essential hypertensive patients and the association between pAA dilatation, arterial stiffness and left ventricular hypertrophy. BACKGROUND:: Few data are available regarding patients with pAA dilatation in arterial hypertension. It is not known whether pAA dilatation may be related to increased left ventricular mass and what the relation with central hemodynamics and arterial stiffness would be. METHODS:: A total of 345 untreated and treated essential hypertensive patients (mean age, 54.3 ± 11 years) were considered for this analysis. We measured pulsatile hemodynamic parameters directly using tonometry, and the proximal aortic diameters through ultrasound imaging (echocardiography). RESULTS:: Prevalence of pAA dilatation was 17%. Peripheral hemodynamic parameters were similar in patients with and without ascending aorta dilatation. We observed a slight increase of central systolic (129.81 ± 15.4 vs. 125.02 ± 14.7 mmHg; P = 0.02) and pulse pressure (45.02 ± 10.4 vs. 42 ± 9.54 mmHg; P = 0.02) in patients with pAA dilatation. Pulse wave velocity (9.26 ± 2.33 vs. 7.70 ± 1.69 m/s; P < 0.0001), as well as the augmentation index (25.86 ± 10.2 vs. 19.41 ± 9.52%; P < 0.0001), was significantly greater in patients with pAA dilatation. Finally, left ventricular hypertrophy was thrice as frequent (32.8 vs. 13.4%; P < 0.0001) compared to hypertensive patients without aortic dilatation. CONCLUSION:: This study shows a high prevalence (17%) of ascending aortic dilatation in patients affected by essential hypertension, without further complications. Dilatation of the ascending aorta is associated both to an increased left ventricular mass and arterial stiffness.
    Journal of Hypertension 01/2013; 31(1):109-116. · 4.22 Impact Factor
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    ABSTRACT: Primary aldosteronism is characterised by the dysregulation of aldosterone production and comprises both sporadic forms, caused by an aldosterone-producing adenoma or bilateral adrenal hyperplasia, and familial forms (familial hyperaldosteronism types I, II and III). The two principal physiological regulators of aldosterone synthesis are angiotensin II and serum K(+), which reverse the high resting K(+) conductance and hyperpolarized membrane potential of adrenal glomerulosa cells. The resulting membrane depolarization causes the opening of voltage-gated Ca(2+) channels and an increase in intracellular Ca(2+) that stimulates aldosterone biosynthesis. Point mutations in the KCNJ5 gene, which encodes the G-protein-activated inward rectifier K(+) channel 4 (GIRK4), have been implicated in the pathogenesis of both sporadic and familial forms of primary aldosteronism. These mutations interfere with the selectivity filter of GIRK4 causing Na(+) entry, cell depolarization and Ca(2+) channel opening, resulting in constitutive aldosterone production. Seven families with familial hyperaldosteronism caused by KCNJ5 germline mutations have so far been described, and multicentre studies have reported KCNJ5 mutations in approximately 40% of sporadic aldosterone-producing adenomas. Herein, we review the role of GIRK4 in adrenal pathophysiology and provide an overview of the clinical and biochemical phenotypes resulting from KCNJ5 mutations in patients with sporadic and familial primary aldosteronism.
    Nature Reviews Endocrinology 12/2012; · 11.03 Impact Factor
  • Journal of Clinical Hypertension 10/2012; 14(10):729-30. · 2.36 Impact Factor

Publication Stats

3k Citations
760.08 Total Impact Points

Institutions

  • 1988–2014
    • Università degli Studi di Torino
      • • Department of Medical Science
      • • Dipartimento di Scienze Chirurgiche
      • • Dipartimento di Scienze Cliniche e Biologiche
      Torino, Piedmont, Italy
  • 2012
    • Georgia Health Sciences University
      • Department of Physiology
      Augusta, GA, United States
  • 2007–2010
    • Università Politecnica delle Marche
      • Department of Clinical and Experimental Medicine
      Ancona, The Marches, Italy
  • 2009
    • Ospedale San Giovanni Battista, ACISMOM
      Torino, Piedmont, Italy
  • 2008
    • Università degli Studi del Sannio
      Benevento, Campania, Italy
  • 2006–2008
    • University of Padova
      • Department of Medicine DIMED
      Padua, Veneto, Italy
  • 1994–2008
    • University of Camerino
      • • Dipartimento di Medicina Sperimentale e Sanità Pubblica
      • • Dipartimento di Scienze Chimiche
      Camerino, The Marches, Italy
  • 1995–1999
    • Sapienza University of Rome
      • Department of Cardiovascular, Respiratory, Nephrologic and Geriatric Sciences
      Roma, Latium, Italy