Tiziano Perrone

Effect on the development of ankle edema of adding delapril to manidipine in patients with mild to moderate essential hypertension: A three-way crossover study

BACKGROUND Use of the combination of an angiotensin-converting enzyme inhibitor (ACEI) and a calcium channel blocker (CCB) is considered a rational approach in patients whose hypertension is not controlled by monotherapy, providing better blood pressure (BP) control than the individual components with a lower incidence of adverse effects. In particular, such combinations have been found to reduce the incidence of ankle edema, the most common adverse effect of dihydropyridine annhypertensives. OBJECTIVE The present study was undertaken to evaluate the effect on the development of ankle edema of adding the ACEI delapril to the CCB manidipine in patients with mild to moderate essential hypertension. METHODS Patients between the ages of 30 and 70 years who had mild to moderate hypertension (diastolic BP [DBP] >90 and <110 mm Hg) were included in the study. After a 4-week placebo run-in period, eligible patients were randomized to receive 6 weeks each of manidipine 10 mg/d, delapril 30 mg/d, and both in a crossover fashion. There was a 2-week washout period between treatments. Ankle edema was assessed based on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP). Sitting BP, AFV, and PSTP were measured at the end of the placebo run-in period and the end of each active-treatment period. RESULTS The study enrolled 40 patients with previously untreated hypertension (21 women, 19 men). Both manidipine and delapril monotherapy were associated with significant reductions from baseline in systolic BP (SBP) (mean [SD], -17.3 [4] and -14.8 [4] mm Hg, respectively; both, P<0.01) and DBP (-14.6 [3] and -12.9 [3] mm Hg; both, P<0.01). Compared with monotherapy, the combination of manidipine and delapril was associated with greater reductions from baseline in SBP (-21.8 [5] mm Hg; P<0.001) and DBP (-18.6 [4] mm Hg; P<0.001). Manidipme monotherapy was associated with significant increases from baseline in both AFV (7.9%; P<0.001) and PSTP (36.6%; P<0.01). Compared with manidipine alone, the combination of manidipine and delapril was associated with less pronounced increases in AFV (3.3%; P<0.05) and PSTP (10.4%; P<0.05). Ankle edema was clinically evident in 3 patients after receipt of manidipine monotherapy and in 1 patient after receipt of combination treatment. CONCLUSION In these patients with mild to moderate essential hypertension, the addition of delapril to manidipine partially counteracted the manidipine-induced microcirculatory changes responsible for ankle edema.

Effect of Telmisartan on Paroxysmal Atrial Fibrillation Recurrence in Hypertensive Patients With Normal or Increased Left Atrial Size

Hypertension is the most prevalent and potentially modifiable risk factor for atrial fibrillation (AF). In a previous secondary prevention study, the authors observed that the angiotensin II receptor blocker telmisartan was more effective than the calcium channel blocker amlodipine in preventing AF relapse in hypertensive patients with normal atrial size.

Ultrasonography modifications of visceral and subcutaneous adipose tissue after pioglitazone or glibenclamide therapy combined with rosuvastatin in type 2 diabetic patients not well controlled by metformin

Aim To compare pioglitazone or glibenclamide alone and in combination with rosuvastatin on hepatic steatosis in type 2 diabetic patients. Materials and methods After 3 months of metformin, patients were randomized to add pioglitazone 15 mg twice a day or glibenclamide 5 mg twice a day for 6 months, and then rosuvastatin 5 mg was added for other 6 months. Patients underwent an ultrasound examination for evaluation of steatosis degree, subcutaneous adipose tissue, and visceral adipose tissue diameter, an euglycemic hyperinsulinemic clamp, and blood sample collection for evaluation of glycemic control, fasting plasma insulin, lipid profile, adipocytokines at randomization, and after 6 and 12 months. Results Both pioglitazone and glibenclamide improved glycemic control. Pioglitazone reduced fasting plasma insulin, whereas glibenclamide increased it. Pioglitazone increased the glucose infusion rate compared with glibenclamide. Pioglitazone, but not glibenclamide, improved the lipid profile, and, when rosuvastatin was added, there was a greater improvement with pioglitazone and rosuvastatin. Adiponectin was increased by pioglitazone (+0.5 &mgr;g/ml), with a further increase (+0.4 &mgr;g/ml) when rosuvastatin was added. A significant decrease in leptin (−3.1 ng/ml) and interleukin-6 (−0.4 pg/ml) was found only with pioglitazone; a similar trend (−2.5 ng/ml and −0.3 pg/ml, respectively) was maintained after the addition of rosuvastatin. Rosuvastatin+pioglitazone decreased tumor necrosis factor-&agr; (−0.3 ng/ml) and were superior to glibenclamide+rosuvastatin in reducing high-sensitivity C-reactive protein (−0.4 mg/l). Pioglitazone decreased ultrasound parameters, and the addition of rosuvastatin further decreased them both compared with randomization and glibenclamide. Conclusion Pioglitazone was more effective than glibenclamide in improving inflammation and hepatic steatosis indices.

Heart rate/blood pressure ratio as predictor of neuromediated syncope

BACKGROUND Predicting the occurrence of syncope in advance during tilt test could be useful to prepare the medical staff in preventing complications connected with this procedure, particularly in patients with no pre-syncopal symptoms. Our objective was to develop a simple algorithm able to predict the onset of neuromediated syncope during the tilt test. METHODS We analysed the trend in RR interval, blood pressures, the ratio of these two variables and their derivative, as possible predictors of neuromediated syncope during tilt test. We studied 145 patients: 72 tilt test positive (age 7-82 years, 23 male, 49 female) and 73 tilt test negative (age 8-82 years, 36 male, 37 female), coming at our attention for suspected syncope. We evaluated time of prediction, sensitivity, specificity and receiver-operating curves (ROC) of the trends in RR interval, blood pressure, their ratio and the derivative of their ratio, in predicting syncope. RESULTS The derivative of the ratio between RR interval and systolic blood pressure (dRR/SBP) was able to predict syncope 44.1 ± 6.6s in advance with a sensitivity of 86.2% and a specificity of 89.1%. Area under the curve of ROC was 0.877 (p<0.001). The method was able to predict syncope in all three forms of neuromediated syncope: cardioinhibitory, mixed and vasodepressor. Similar results were found using the pulse pressure (dRR/PP). CONCLUSIONS Using dRR/SBP or dRR/PP it is possible to predict the occurrence of syncope in advance during tilt test.

Effects of valsartan versus olmesartan addition to amlodipine/hydrochlorothiazide combination in treating stage 2 hypertensive patients

Objective: The objective of this study was to assess the effects of valsartan or olmesartan addition to dual therapy with amlodipine + hydrochlorothiazide (HCTZ) in the treatment of stage 2 hypertension. Research design and methods: 180 patients with diastolic blood pressure (DBP) ≥ 99 and < 110 mm Hg were treated with amlodipine 5 mg + HCTZ 12.5 mg combination. After 4 weeks, 149 patients whose blood pressure (BP) was not controlled, were randomized to the combination of valsartan 160 mg + amlodipine 5 mg + HCTZ 12.5 mg or olmesartan 20 mg + amlodipine 5 mg + HCTZ 12.5 mg for 4 weeks. Main outcome measures: At the end of each period, clinical and ambulatory BP measurements were recorded. Results: Both triple combinations produced greater ambulatory and clinical SBP/DBP reduction than dual therapy. However, mean reduction from baseline in the valsartan + amlodipine + HCTZ-treated patients was significantly greater than in the olmesartan + amlodipine + HCTZ-treated patients. Compared with dual therapy, the add-on effect of valsartan was significantly greater than that of olmesartan, the difference being more evident for nighttime SBP/DBP values (-3.3 (95% CI 0.44 – 3.51)/3.0 (95% CI 0.59 – 3.34) mm Hg, p < 0.01). Conclusions: The addition of valsartan to amlodipine + HCTZ produced greater BP reduction than the addition of olmesartan.

Time course of antiproteinuric effect of aliskiren in arterial hypertension associated with type 2 diabetes and microalbuminuria

Objective: The aim was to compare the antiproteinuric effect of aliskiren and ramipril in hypertensive patients with type 2 diabetes and microalbuminuria. Research design and methods: A total of 138 patients were treated with aliskiren 300 mg/day or ramipril 10 mg/day for 12 weeks and checked after 1, 2, 4, 8 and 12 weeks and 2 and 4 weeks after treatment withdrawal. Main outcome measures: Clinic and ambulatory BP, urinary albumin excretion rate (UAER) and plasma aldosterone were measured. Results: Both aliskiren and ramipril induced a similar lowering in clinic and ambulatory BP (p < 0.001 vs baseline). However, such a lowering persisted longer after stopping aliskiren than after stopping ramipril regimen. Both treatments reduced UAER, but the decrease in UAER associated with aliskiren was more pronounced, the difference vs ramipril being maximal at week 12 (−42 vs −15%, p < 0.01). Two weeks after stopping therapy, UAER remained below baseline values with aliskiren, but not in the ramipril group. Plasma aldosterone decreased in the aliskiren group, whereas in the ramipril group it decreased until week 8 and thereafter increased toward baseline values. Conclusions: Aliskiren has a greater and more prolonged antiproteinuric effect than R; it might partly be related to a higher degree of intrarenal renin–angiotensin–aldosterone system blockade.

Lung US features of severe interstitial pneumonia: case report and review of the literature

BackgroundChlamydia pneumonia is reported to account for a relatively large number of cases of CAP. In elderly patients in particular, the clinical presentation can be a severe form of diffuse interstitial pneumonia. The chest X-ray presentation is aspecific. Lung US can show a typical pattern of diffuse interstitial lung syndrome; in some cases, like the present one, the association of multiple B lines with a coarse and thickened pleural line points to a more likely diagnosis of interstitial pneumonia.Case reportWe present the case of an 87-year-old woman with severe interstitial chlamydial pneumonia, for whom lung US was very useful for directing diagnosis and for follow-up during therapy.ConclusionsThe use of lung US in the diagnosis of interstitial syndrome is likely to improve the care of patients in whom the diagnosis is a consideration; it offers better characterization than a chest X-ray and is free from CT radiation. Furthermore, the concept of using lung US for monitoring a patient is one of the major innovations that has emerged from recent studies.SommarioBackgroundChlamydia pneumoniae è riconosciuto come agente eziologico largamente rappresentato nelle polmoniti acquisite in comunità (CAP); nei soggetti più anziani può associarsi a gravi forme di polmonite interstiziale diffusa. La presentazione radiologica è aspecifica. L’ecografia polmonare può mostrare un quadro tipico di sindrome interstiziale diffusa; in alcuni casi, quale il nostro, l’associazione di multiple linee B con il reperto di una linea pleurica irregolare ed ispessita, può suggerire una più verosimile diagnosi di polmonite interstiziale.Caso clinicopresentiamo il caso di una paziente di 87 anni, ricoverata nel nostro reparto per grave polmonite interstiziale da Chlamydia, in cui il ruolo dell’ecografia polmonare si è dimostrato fondamentale nella diagnosi e nel follow-up in corso di terapia mirata.Conclusionil’ecografia polmonare può migliorare la gestione clinica del paziente con probabile diagnosi di polmonite interstiziale, per miglior caratterizzazione del quadro rispetto alla radiografia del torace, evitando il danno da radiazioni proprio della TC. L’utilità dell’ecografia polmonare nel monitoraggio del paziente durante terapia emerge sempre con più chiarezza in letteratura.

The learning curve of sonographic inferior vena cava evaluation by novice medical students: the Pavia experience

PurposeThe sonographic evaluation of inferior vena cava diameters and its collapsibility—that is also defined as the caval index—has become a popular way to easily obtain a noninvasive estimate of central venous pressure. This is generally considered an easy sonographic task to perform, and according to the American College of Emergency Physicians (ACEP) Guidelines 25 repetitions of this procedure should be sufficient to reach proficiency. However, little is known about the learning process for this sonographic technique. Therefore, we designed this study to investigate the learning curve of inferior vena cava evaluation.MethodsWe enrolled a sample of ten ultrasound-naïve medical students who received a preliminary training provided by two Junior Emergency Medicine Residents. Following training, each student performed the sonographic task on 25 different patients who were hospitalized in the internal medicine ward. The students’ performance was compared with the results obtained by a consultant in internal medicine with extensive experience in point-of-care ultrasound, who repeated the procedure on the same patients (gold standard). In detail, we evaluated the time to complete the task, the quality of the obtained images, and the ability to visually estimate and measure the caval index.ResultsAlthough most students (9/10) reached the pre-defined level of competence, their overall performance was inferior to the one achieved by the gold standard, with little improvement over time. However, repetition was associated with progressive shortening of the time needed to achieve readable images.ConclusionsOverall, these findings suggest that, although allowing to obtain a pre-defined competence, 25 repetitions are not enough to reach a good level of proficiency for this technique, that needs a longer training to be achieved.SommarioScopoLo studio ecografico della vena cava inferiore con la misurazione dei diametri e la valutazione della sua collassabilità agli atti respiratori, noto come caval index, si è diffuso come un semplice metodo per stimare in modo non invasivo la pressione venosa centrale. Generalmente questo task ecografico è considerato di semplice esecuzione, e, secondo linee guida dell’American College of Emergency Physicians (ACEP) 25 ripetizioni di questa procedura sarebbero sufficienti a raggiungere la proficiency. Tuttavia, la curva di apprendimento per questa tecnica è stata scarsamente studiata. Per questo abbiamo realizzato questo studio, al fine di analizzare il processo di apprendimento per lo studio ecografico della vena cava inferiore.MetodiAbbiamo arruolato un campione di 10 studenti di Medicina senza precedenti esperienze in ecografia. Gli studenti hanno dapprima ricevuto un training preliminare da parte di Specializzandi di Medicina d’Emergenza-Urgenza, e, successivamente, hanno eseguito il task ecografico su 25 pazienti ricoverati presso il reparto di Medicina Interna. Le performance degli studenti sono state confrontate con quelle di un medico strutturato di Medicina Interna con lunga esperienza in ecografia point-of-care, che ha ripetuto la procedura sugli stessi pazienti, fungendo quindi da gold-standard. I parametri analizzati sono stati il tempo per completare la procedura, la qualità delle immagini ottenute e la capacità di stimare visivamente e misurare il caval index.RisultatiAnche se la maggior parte degli studenti (9/10) hanno raggiunto il livello predefinito di competenza, le loro performance sono state sommariamente inferiori rispetto a quelle del gold-standard, registrando un piccolo trend di miglioramento nei tempi medi per l’esecuzione del task ecografico.ConclusioniQuesti risultati suggeriscono che, sebbene 25 ripetizioni consentano ad un soggetto inesperto di ottenere un livello pre-definito di competenza, non sembrano però essere sufficienti a raggiungere la proficiency necessaria per questa tecnica, che necessita di un training più lungo.

[OP.7A.06] TREATING HYPERTENSIVE CRISES BETWEEN GUIDELINES AND REAL-WORLD: AN ANTI-HYPERTENSIVE ROLE OF ANTI-ANXIETY DRUGS?

Objective: Current ESH Guidelines are extensively devoted to diagnosis, management and follow-up of arterial hypertension in the “chronic” setting, whereas less attention is given to the acute management of hypertensive crises, a group of potentially life-threatening complications. Moreover, epidemiological data concerning hypertensive crises are limited. Design and method: During 2014, 457 consecutive patients with an initial systolic blood pressure (SBP) >170 mmHg and/or diastolic blood pressure (DBP) >110 mmHg were enrolled after being admitted to an Emergency Department (ED) serving a population of more than 50000 inhabitants, Results: Hypertensive crises represented 0.95% of the total number of ED admissions (n = 48054). Hypertensive emergencies (i.e. hypertensive crises associated with organ damage), were 113/457 (25%), the remaining 344/457 (75%) being hypertensive urgencies. Global mortality rate was 0.87%, (4% in the subset of hypertensive emergencies). Female patients were the majority in both hypertensive urgencies (65.1%) and emergencies (53.1%). Mean age was 68.5 years (range: 23–97). The presence of hypertension (either treated or untreated) was already known in 67.1% of cases. Treatment was associated with significant blood pressure reduction in both urgencies (SBP = −42.1 mmHg, DBP = −19.4 mmHg) and emergencies (SBP = −40.5 mmHg, DBP = −21 mmHg; p < 0.001 for both) in a relatively short time span (<5 hours). As expected, acute treatment of hypertensive emergencies was based on a combination of diuretics, nitrates, labetalol and urapidil. In contrast, in hypertensive urgencies the most commonly prescribed drugs were clonidine (44.3%) and diazepam (36.3%). Although not recognized as an antihypertensive drug, diazepam is widely used in the management of hypertensive crises. Notably, diazepam-treated patients achieved a similar extent of blood pressure reduction when compared with patients not receiving antianxiety treatment. Moreover, diazepam administration was associated with a faster reduction in blood pressure and a significantly lower number of associated anti-hypertensive drugs (0.7 vs 1.2; p < 0.01). During a 11-month follow-up, re-admissions caused by hypertensive crises were 63 (13.8%), without any difference related to diazepam treatment. Conclusions: Anti-anxiety drugs are commonly used in hypertensive crises, showing an interesting role in “real-world” treatment. Further studies are warranted to better define their role as “anti-hypertensive” drugs.

NT-proBNP and the risk of incident hypertension: is change over time a better predictor than baseline value?

I n many different areas of cardiovascular physiology [1], cardiac biomarkers have been shown to be very useful tools in evaluating cardiac (dys)function [2], assessing diagnosis [3,4], guiding subsequent management [5], stratifying prognosis [6], as well as assessing total cardiovascular risk [7]. Moreover, they significantly contribute to our knowledge of mechanisms of disease genesis and progression. In this area, the release of natriuretic peptides has been extensively studied in the past decades, and B-type natriuretic peptide (BNP) has been defined as a ‘window’ to the cardiovascular system [8], able to help clinicians in diagnosis, follow-up, and prognostication [9–11]. This is the case not only for heart failure [12,13] but also for specific cardiac diseases, such as amyloid cardiomyopathy [14–17], congenital heart disease [18], hypertrophic cardiomyopathy [19], pulmonary embolism [20], and many other conditions [21]. In the setting of arterial hypertension, the role of natriuretic peptides is complex. On the one hand, a higher serum concentration of BNP is a rather robust marker of pressureinduced cardiac damage [22], on the one hand a reduced risk of hypertension has been associated with genetically elevated concentrations of either BNP or the N-terminal fragment of proBNP (NT-proBNP) [23,24]. Among many others, the main effects of BNP are vasodilation as well as natriuresis, both representing key mechanisms in arterial pressure control and in the cardio-renal cross-talk. Opposite effects are exerted by the renin–angiotensin–aldosterone system, and it has been recently shown that natriuretic peptides buffer renal vascular hypertension via reninindependent effects [25]. BNP is released by ventricular