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Sant'Ambrogio di Torino, Italy

Angeli F.,Hospital S.M. della Misericordia | Angeli E.,Hospital San Giovanni Battista | Verdecchia P.,Hospital of Assisi
International Journal of Molecular Sciences | Year: 2015

Hypertensive disorders of pregnancy are a major cause of poor outcome, including placental abruption, organ failure, cerebrovascular accident and disseminated intravascular coagulation. These disorders are associated with increased fetal risk of intrauterine growth restriction, intrauterine death and prematurity. Electrocardiography (ECG) recently emerged as a useful tool to evaluate cardiovascular complications during pregnancy. Specifically, left atrial abnormalities detected by standard ECG are associated with a fourfold increased risk of developing hypertensive disorders during pregnancy. The mechanisms linking left atrial abnormality on ECG with hypertensive disorders are still elusive. Several mechanisms, possibly reflected by abnormal left atrial activation on ECG, has been suggested. These include increased reactivity to angiotensin II and up-regulation of angiotensin type 1 receptors, with activation of autoantibodies targeting these receptors. © 2015 by the authors; licensee MDPI, Basel, Switzerland.

Staessen J.A.,Catholic University of Leuven | Staessen J.A.,Maastricht University | Thijs L.,Catholic University of Leuven | Stolarz-Skrzypek K.,Jagiellonian University | And 18 more authors.
Trials | Year: 2011

Background: The Ouabain and Adducin for Specific Intervention on Sodium in Hypertension (OASIS-HT) Trial was a phase-2 dose-finding study of rostafuroxin, a digitoxygenin derivative, which selectively antagonizes the effects of endogenous ouabain (EO) on Na+,K+-ATPase and mutated adducin. Rostafuroxin lowered blood pressure (BP) in some animal models and in humans.Methods: OASIS-HT consisted of 5 concurrently running double-blind cross-over studies. After 4 weeks without treatment, 435 patients with uncomplicated systolic hypertension (140-169 mm Hg) were randomized to rostafuroxin (0.05, 0.15, 0.5, 1.5 or 5.0 mg/d) or matching placebo, each treatment period lasting 5 weeks. The primary endpoint was the reduction in systolic office BP. Among the secondary endpoints were diastolic office BP, 24-h ambulatory BP, plasma EO concentration and renin activity, 24-h urinary sodium and aldosterone excretion, and safety. ANOVA considered treatment sequence (fixed effect), subjects nested within sequence (random), period (fixed), and treatment (fixed).Results: Among 410 analyzable patients (40.5% women; mean age, 48.4 years), the differences in the primary endpoint (rostafuroxin minus placebo) ranged from -0.18 mm Hg (P = 0.90) on 0.15 mg/d rostafuroxin to 2.72 mm Hg (P = 0.04) on 0.05 mg/d. In the 5 dosage arms combined, the treatment effects averaged 1.30 mm Hg (P = 0.03) for systolic office BP; 0.70 mm Hg (P = 0.08) for diastolic office BP; 0.36 mm Hg (P = 0.49) for 24-h systolic BP; and 0.05 mm Hg (P = 0.88) for 24-h diastolic BP. In the 2 treatment groups combined, systolic (-1.36 mm Hg) and diastolic (-0.97 mm Hg) office BPs decreased from week 5 to 10 (P for period effect ≤0.028), but carry-over effects were not significant (P ≥ 0.11). All other endpoints were not different on rostafuroxin and placebo. Minor side-effects occurred with similarly low frequency on rostafuroxin and placebo.Conclusions: In 5 concurrently running double-blind cross-over studies rostafuroxin did not reduce BP at any dose.Trial Registration: ClinicalTrials (NCT): NCT00415038. © 2011 Staessen et al; licensee BioMed Central Ltd.

Angeli F.,Preventive Cardiology | Angeli E.,Hospital San Giovanni Battista | Cavallini C.,Preventive Cardiology | Ambrosio G.,University of Perugia | And 3 more authors.
Maturitas | Year: 2010

Background: Although repolarization abnormalities on ECG are frequent in post-menopausal hypertensive women, their prognostic value in these women is uncertain. Methods: We analyzed 908 hypertensive post-menopausal women consecutively included in the PIUMA (Progetto Ipertensione Umbria Monitoraggio Ambulatoriale) study. The median duration of follow-up was 8.6 years (range: 1-21). All women were untreated at entry. Drug treatment during follow-up was adjusted to single individuals. Standard 12-lead ECG was carried out at entry. The Minnesota Coding was used to define minor and major ("typical strain") repolarization abnormalities. Design: prospective observational study in essential hypertension. Results: Mean age at entry was 60 years. At baseline, ECG was normal in 707 women, minor ST-T changes were noted in 152 women, and a typical strain pattern was present in 49 subjects. Predictors of typical strain were age, diabetes and systolic blood pressure (BP). During follow-up there were 119 new cardiovascular (CV) events and 75 all-cause deaths. Typical strain was associated with a threefold higher risk of CV disease (HR: 3.16; 95% CI: 1.59-6.31; p = 0.001) after adjustment for the significant influence of age, diabetes, serum creatinine, systolic BP and HDL-cholesterol. Women with minor LV repolarization abnormalities showed a non-significant excess risk of CV disease when compared with women with normal LV repolarization (HR: 1.25; 95% CI: 0.69-2.26; p = 0.467). Similar results were obtained for all-cause mortality. Conclusions: Typical strain pattern, an easily detectable marker of altered LV repolarization, identifies post-menopausal hypertensive women at increased risk of CV disease and all-cause mortality. © 2010 Elsevier Ireland Ltd.

Krengli M.,University of Piemonte Orientale | Calvo F.A.,University Hospital Gregorio Maranon | Sedlmayer F.,Paracelsus Medical University | Sole C.V.,University Hospital Gregorio Maranon | And 23 more authors.
Strahlentherapie und Onkologie | Year: 2013

Background: A joint analysis of clinical data from centres within the European section of the International Society of Intraoperative Radiation Therapy (ISIORT-Europe) was undertaken in order to define the range of intraoperative radiotherapy (IORT) techniques and indications encompassed by its member institutions. Materials and methods: In 2007, the ISIORT-Europe centres were invited to record demographic, clinical and technical data relating to their IORT procedures in a joint online database. Retrospective data entry was possible. Results: The survey encompassed 21 centres and data from 3754 IORT procedures performed between 1992 and 2011. The average annual number of patients treated per institution was 42, with three centres treating more than 100 patients per year. The most frequent tumour was breast cancer with 2395 cases (63.8 %), followed by rectal cancer (598 cases, 15.9 %), sarcoma (221 cases, 5.9 %), prostate cancer (108 cases, 2.9 %) and pancreatic cancer (80 cases, 2.1 %). Clinical details and IORT technical data from these five tumour types are reported. Conclusion: This is the first report on a large cohort of patients treated with IORT in Europe. It gives a picture of patient selection methods and treatment modalities, with emphasis on the main tumour types that are typically treated by this technique and may benefit from it. © 2013 Springer Heidelberg Berlin.

Angeli F.,Hospital S Maria della Misericordia | Angeli E.,Hospital San Giovanni Battista | Ambrosio G.,University of Perugia | Mazzotta G.,University of Perugia | And 3 more authors.
American Journal of Hypertension | Year: 2011

BackgroundElevated neutrophil count, a marker of systemic inflammation, has been suggested as a prognostic marker of cardiovascular disease in postmenopausal women with hypertension. We tested the hypothesis that an association exists between elevated neutrophil count and increased arterial stiffness, as reflected by a wide pulse pressure (PP), in this population of women. We also tested PP as predictor of cardiovascular adverse events in this population.MethodsWe analyzed data relating to 886 postmenopausal women with hypertension, consecutively enrolled in a prospective registry. Ambulatory blood pressure monitoring was carried out at entry in all the subjects. The median duration of follow-up was 7.4 years (range: 1-21 years).ResultsThere was a direct relationship between neutrophil count and 24-h ambulatory PP (P <0.0001) and this association remained significant after adjusting for age, serum glucose, and left ventricular (LV) hypertrophy at electrocardiogram (ECG) (all P <0.01). During follow-up there were 121 first-time major cardiovascular (CV) events. The rate (× 100 patient-years) of CV events was 1.02, 1.36, and 3.75, respectively in the three tertiles of the distribution of 24-h PP (P <0.0001). In a multivariate analysis, 24-h ambulatory PP and neutrophil count were independent predictors of total CV events after adjusting for the influence of other risk markers. In particular, for each 10mmHg increase in 24-h PP, there was a 73% higher risk for total CV events (P = 0.015). Office-recorded PP did not achieve significance when forced in the same model.ConclusionsIncreased arterial stiffness, as reflected in high values of 24-h ambulatory PP, is an adverse prognostic marker in postmenopausal women with hypertension, possibly as an additional correlate of systemic inflammation. © 2011 American Journal of Hypertension, Ltd.

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