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COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease, and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years.

Aim To evaluate the safety of four different dosages of alpha lipoic acid (400, 600, 800, and 1200 mg) as food supplement on adverse events related to alpha lipoic acid consumption and efficacy on glycemic status and lipid profile in subjects with euglycemia or dysglycemia. Methods We conducted a retrospective, observational study enrolling 322 patients, 83 taking 400 mg/day, 78 taking 600 mg/day, 80 taking 800 mg/day, and 81 taking 1200 mg/day alpha lipoic acid, respectively. Results In the groups treated with alpha lipoic acid 800 and 1200 mg/day, we registered a reduction of FPG, TC, LDL-C, and Tg compared to baseline (p < 0.05 for all with alpha lipoic acid 800 mg/day, and p < 0.01 for all with alpha lipoic acid 1200 mg/day). The values recorded in the group treated with alpha lipoic acid 1200 mg/day were significantly lower compared to the ones obtained with alpha lipoic acid 400 mg/day. Moreover, alpha lipoic acid 1200 mg/day reduced Hs-CRP levels compared to baseline and compared to 400 mg/day (p < 0.05 for both). In the group treated with alpha lipoic acid at 800 mg/day, 5 subjects with IFG and 1 subject with IGT returned euglycemic. In the group treated with alpha lipoic acid at 1200 mg/day, 11 subjects with IFG and 3 subjects with IGT returned euglycemic. Adverse events of patients during alpha lipoic acid treatment included nausea, vomiting, dizziness, cutaneous rash, hypoglycemia, and hypotension. Adverse events did not differ among the four groups. Conclusion The chronic use (4 years) of a food supplement containing alpha lipoic acid is well tolerated, without significant differences between lower and higher dosages and improves glycemic status and lipid profile but only if administered at high dosage.

Para garantizar la conservación y preservación del patrimonio inmueble de manera general, existen principios establecidos por el ICOMOS desde 1966, los mismos que incentivan a la creación de archivos documentales, que deben ser actualizados y que adquieren mayor importancia cuando se incluye como tema de estudio al patrimonio del siglo XX, el cual requiere ser conocido, comprendido y gestionado. Tras la conferencia realizada por la misma organización en Madrid, en 2011, se plantean criterios para identificar el valor y significado sociocultural de estos bienes en los cuales se destaca la importancia de generar inventarios que contengan información: técnica, métrica, histórica, gráfica, tecnológica, de uso, identificación, localización y contexto. Sin embargo, en la ciudad de Cuenca, los archivos documentales de arquitectura moderna se limitan a fichas de registro superficiales que exponen un contenido técnico y de gestión municipal, lo que ha ocasionado la falta de comunicación entre los organismos que velan por su protección generando una subutilización de recursos y profundizando la molestia de parte de los dueños por poseer un bien, que a su criterio no debería ser parte de un inventario patrimonial. Es por esta razón, que la presente investigación aborda un acercamiento a la arquitectura moderna a través de la adaptación de una metodología de documentación digital y tridimensional al contenido de una ficha de catalogación para arquitectura moderna, como caso estudio en la ciudad de Cuenca. De esta manera, los resultados cubren los requisitos para crear archivos documentales que permitan análisis comparativos para establecer una significancia del patrimonio moderno y demostrar la importancia de la valoración y difusión de este patrimonio y su aporte histórico a nivel local y nacional.Palabras clave: Patrimonio moderno, documentación digital, valoración, inventario. AbstractIn order to guarantee the conservation and preservation of the immovable heritage in general, there are principles established by ICOMOS since 1966, which encourage the creation of documentary files, that must be updated and become more important when the study of the 20th-century heritage is included, which requires to be known, understood and managed. After the conference held by the same organization in Madrid, 2011, criteria are proposed to identify the value and socio-cultural significance of these assets in which the importance of generating inventories containing: technical, metric, historical, graphic, technology, use, identification, location, and context information. However, in the city of Cuenca, the documentary files of modern architecture are limited to superficial registration cards that expose a technical and municipal management content, which has caused the lack of communication between the organizations that ensure their protection, generating an underutilization of resources and deepening the annoyance on the part of the owners for owning a property, who in their opinion should not be part of a heritage inventory. For this reason, the present research addresses an approach to modern architecture through the adaptation of a three-dimensional and digital documentation methodology to the content of a cataloging sheet for modern architecture, as a case study in Cuenca. In this way, the results cover the requirements to create documentary files that allow comparative analysis to establish a significance of modern heritage and demonstrate the importance of the valuation and dissemination of this heritage and its historical contribution at the local and national level.Keywords: Modern heritage, digital documentation, valuation, inventory.

BACKGROUND Patients with inherited haemorrhagic disorders may bleed during surgery. No questionnaire on bleeding diathesis has been yet validated for the preoperative period and current guidelines provide conflicting recommendations. AIM We aimed to assess if preoperative assessment with ISTH-BAT (International Society on Thrombosis and Haemostasis Bleeding Assesment Tool) and laboratory screening tests is useful to identify mild previously undiagnosed bleeding disorders (BDs) and to predict bleeding complications in selected patients undergoing elective surgery. METHODS Consecutive patients undergoing elective surgery received ISTH-BAT evaluation and laboratory screening for platelet count, Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT). Subjects with an abnormal ISTH-BAT and/or laboratory results underwent further testing, and they were compared with a 1:1 random gender-, age- and type of surgery- matched control group. RESULTS Overall, 1502 consecutive surgical patients (1186 adults, 316 children) were enrolled. Of these, 83 (5.5%, 95% confidence interval 4.4-6.8) patients (37 adults and 46 children) had an abnormal ISTH-BAT, and/or prolonged PT and/or prolonged aPTT and/or low platelet count; of them, one subject had low von Willebrand factor level, three Factor XII deficiency and four anticardiolipin and/or antiB2GPI antibodies. No major bleeding was reported in these 83 patients and their controls. CONCLUSION ISTH-BAT and laboratory screening tests do not accurately detect mild BDs in selected patients undergoing elective surgery.

Aim To evaluate the safety of four different dosages of alpha lipoic acid (400, 600, 800, and 1200 mg) as food supplement on adverse events related to alpha lipoic acid consumption and efficacy on glycemic status and lipid profile in subjects with euglycemia or dysglycemia. Methods We conducted a retrospective, observational study enrolling 322 patients, 83 taking 400 mg/day, 78 taking 600 mg/day, 80 taking 800 mg/day, and 81 taking 1200 mg/day alpha lipoic acid, respectively. Results In the groups treated with alpha lipoic acid 800 and 1200 mg/day, we registered a reduction of FPG, TC, LDL-C, and Tg compared to baseline (p < 0.05 for all with alpha lipoic acid 800 mg/day, and p < 0.01 for all with alpha lipoic acid 1200 mg/day). The values recorded in the group treated with alpha lipoic acid 1200 mg/day were significantly lower compared to the ones obtained with alpha lipoic acid 400 mg/day. Moreover, alpha lipoic acid 1200 mg/day reduced Hs-CRP levels compared to baseline and compared to 400 mg/day (p < 0.05 for both). In the group treated with alpha lipoic acid at 800 mg/day, 5 subjects with IFG and 1 subject with IGT returned euglycemic. In the group treated with alpha lipoic acid at 1200 mg/day, 11 subjects with IFG and 3 subjects with IGT returned euglycemic. Adverse events of patients during alpha lipoic acid treatment included nausea, vomiting, dizziness, cutaneous rash, hypoglycemia, and hypotension. Adverse events did not differ among the four groups. Conclusion The chronic use (4 years) of a food supplement containing alpha lipoic acid is well tolerated, without significant differences between lower and higher dosages and improves glycemic status and lipid profile but only if administered at high dosage.

Aim: to evaluate the effects of abscisic acid (ABA), contained in dwarf peaches, on the regression of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) conditions. Materials and methods: sixty-five patients with IFG or IGT were randomized to take ABA or placebo for 3 months. We evaluated: fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbA1c), fasting plasma insulin (FPI), homeostatic model assessment of insulin resistance (HOMA-IR), lipid profile and high sensitivity C-reactive protein (Hs-CRP). At baseline, and after 3 months, all patients underwent an oral glucose tolerance test (OGTT), an euglycemic hyperinsulinemic clamp, and a glucagon test. Results: a significant reduction of HbA1c, FPG, PPG, FPI and HOMA-IR was observed in the ABA group. After 3 months, 26.7% of patients returned to a normal glycemic status in the ABA group versus zero patients in placebo group, 20.0% were classified as IFG and 53.3% as IGT in the nutraceutical group versus 33.3% and 63.3% in the placebo group. The M value was higher in the ABA group at the end of the treatment. Finally, Hs-CRP was reduced after 3 months of ABA consumption. Conclusions: abscisic acid can be effective in ameliorating glyco-metabolic compensation and in reducing inflammatory status in patients with IFG or IGT.

Background: Haemophilia is an inherited coagulopathy caused by the absence or dysfunction of clotting factor VIII or IX. Clinical manifestations are generally secondary to recurrent bleeding episodes mainly in the musculoskeletal system. Bleeding symptoms appear early in life and, when the disease is severe (when plasma factor VIII or IX activity is

Cardiovascular disease is a common cause of morbidity and mortality after solid organ transplantation, due to a combination of pre-existing cardiovascular risk factors and immunosuppressive drug toxicity. The prevalence of new-onset hypertension, dyslipidemia, diabetes mellitus, and metabolic syndrome was assessed after lung transplantation in a cohort of 67 patients (mean age: 48 ± 14 yr). The prevalence of hypertension increased from 19.4% to 70.1% at the three-yr follow-up visit (p

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 ...

Objective: The objective of this study was to compare valsartan or ramipril addition to amlodipine + hydrochlorothiazide (HCTZ) on blood pressure (BP) and left ventricular hypertrophy (LVH) in hypertensive diabetic patients with LVH. Research design and methods: 293 patients were treated with amlodipine 10 mg + HCTZ 12.5 combination and then randomized to receive valsartan 160 mg or ramipril 5 mg, in addition to the previous therapy, for 1 year. Main outcome measures: Clinic BP was measured every month; echocardiographic assessments were performed at the end of the placebo period, both before the randomization and after 1-year of triple combination therapy. Results: Both triple regimens similarly reduced SBP/DBP values (-13.5/10.9 mm Hg in the valsartan group and -13.4/10.4 mm Hg in the ramipril group). Triple combination including valsartan better reduced LVMI (-20.1%, p < 0.001), interventricular septal thickness (IVST) (-20.3%, p < 0.001) and left ventricular posterior wall thickness (PWT) (-16.3%, p

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...

We evaluated the effects of body weight (BW) loss on blood pressure (BP) in overweight non-obese patients with stage 1 hypertension. We enrolled 376 overweight (body mass index (BMI) >or=25 and

The objective of this study was to compare the effect on ankle edema of adding valsartan (V) or olmesartan (O) to amlodipine (A) in the treatment of hypertension.After a 4-week placebo period, 74 adult outpatients with essential hypertension (diastolic blood pressure [DBP]90 and110 mmHg, and systolic blood pressure [SBP]140 mmHg) were treated with A 10 mg once daily for 4 weeks. Thereafter, nonresponder patients (DBP90 mmHg and/or SBP140 mmHg; n=51) were randomized to receive additional V 160 mg once daily or O 20 mg once daily for 8 weeks in two crossover periods, each separated by a 4-week placebo period. Clinic blood pressure (BP), heart rate, and ankle/foot volume (AFV) were evaluated and blood samples were drawn to evaluate plasma norepinephrine (NE) levels.Both V/A and O/A induced a greater SBP/DBP reduction than A monotherapy (-26.4/-20.8 mmHg and -24.4/-19.1 mmHg, respectively; all P0.001 vs. baseline and P0.01 vs. A). A monotherapy increased AFV by 24%, P0.001 vs. baseline, while the addition of either V or A reduced such increases. However, with V/A the AFV increase (+9.7%, P0.05 vs. baseline, P0.01 vs. A) was lower than with O/A (+16.7%, P0.01 vs. baseline, P0.05 vs. A); the difference between the two combinations was significant. Plasma NE levels were significantly increased by A (+44.6%) and values did not change with the addition of V (+35.2%) or O (+33.7%). Plasma active renin (PAR) was unchanged by A but increased by V/A (+214.4%, P0.05 vs. baseline) and further by O/A (+325.6%, P0.01 vs. baseline; difference between the 2 combinations: P0.05). An inverse correlation was found between the AFV decrease and PAR increase (r=-0.31, P0.05).Adding V or O to A reduced ankle edema, but this effect was more pronounced with V. The greater degree of renin-angiotensin system activation observed with Ocould be related to such a difference.

Hypertension is one of the major risk factors associated with cardiovascular diseases. A range of blood pressure-lowering agents is available including diuretics, alpha- and beta-blockers, aldosterone antagonists, calcium-channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) and direct renin inhibitors (DRI). Most patients require two or more medications to control their blood pressures within normal ranges. When high blood pressure cannot be controlled by low-dose monotherapy, physicians employ either high-dose monotherapy or combination therapy. High-dose ARB monotherapy is more effective for reducing proteinuria against low-dose ARB monotherapy or CCBs. Combination therapy is recommended for hypertension patients to facilitate prompt maintenance of blood pressure. Single-pill combination therapy simplifies treatment and optimizes long-term compliance. Thiazide diuretics such as hydrochlorothiazide (HCTZ), alone or in combination are still widely used as first-line hypertension treatment. Recent studies have shown that double (CCB+ARBs) or triple (CCB+ARBs+HCTZ) combination therapies have a greater lowering efficacy and are better tolerated. Moreover, the use of DRIs has been patented and proven effective in selected categories of hypertensive patients with or without concomitant target organ damage (TOD).

ObjectivesThe aim of the present study was to verify whether angiotensin-II converting enzyme (ACE) inhibition is also effective in preventing relapses of lone atrial fibrillation (LAF), that is, in the absence of hypertension and/or heart disease.BackgroundSeveral studies have shown that ACE inhibitors are effective in preventing atrial fibrillation (AF) relapses in patients with arterial hypertension or several forms of heart disease, that is, in the presence of clinical conditions that are recognized as causing a higher risk of atrial arrhythmias.MethodsSixty-two patients admitted to the emergency department of our institution for a first-ever episode of LAF were enrolled in the study after excluding the presence of cardiac or extracardiac conditions known to be associated with an increased risk of AF, by medical history, physical examination, complete echocardiographic study, and the evaluation of blood pressure, thyroid function, urinary catecholamines, serum electrolytes, blood glucose, red blood cell count, and arterial blood gases. After cardioversion to sinus rhythm by intravenous propafenone, patients were randomized to either ramipril 5 mg/day (n = 31) or placebo (n = 31). Holter monitoring and clinical examination were performed every 3 months.ResultsAfter a 3-year follow-up, AF relapses were observed in 3 patients treated with ramipril and in 10 patients allocated to placebo (p < 0.03, Kaplan-Meier, log-rank test). During follow-up, none of the patients developed arterial hypertension or other cardiac or extracardiac condition known to be associated with increased risk of AF, that is, in all patients the diagnosis of LAF was confirmed.ConclusionsRamipril is effective in preventing relapses of LAF.

BACKGROUND This study compared the effect of antihypertensive treatment with valsartan or ramipril on atrial fibrillation (AF) recurrence, on P-wave dispersion, (PWD) and on serum procollagen type I carboxy terminal peptide (PIP). METHODS A total of 369 mild hypertensive (systolic blood pressure (SBP) >140 and/or 90 < diastolic blood pressure (DBP) < 110 mm Hg) outpatients in sinus rhythm but with at least two episodes of AF in the previous 6 months were randomized to valsartan (n = 122), ramipril (n = 124), or amlodipine (n = 123) for 1 year. Clinic blood pressure (BP) and a 24-h electrocardiogram (ECG) were evaluated monthly. Patients were asked to report any episode of symptomatic AF and to perform an ECG as early as possible. PWD and serum PIP levels were evaluated before and after each treatment period. RESULTS SBP and DBP were significantly reduced by the three treatments (P < 0.001). A total of 46 (47.4%) patients treated with amlodipine had a recurrence of AF as did 26 (27.9%) patients treated with ramipril (P < 0.01 vs. amlodipine) and 16 (16.1%) patients treated with valsartan (P < 0.01 vs. amlodipine and P < 0.05 vs. ramipril). The Kaplan-Meyer analysis showed a significant reduction of AF episodes in the valsartan group (P = 0.005 log-rank test) as well as in the ramipril group (P = 0.021), even if at a lesser degree. PWD values were significantly reduced by ramipril (-4.2 ms, P < 0.05) and even more by valsartan (-11.2 ms, P < 0.01), the difference being significant (P < 0.01). Serum PIP levels were reduced by ramipril (-49.7 microg, P < 0.001) and valsartan (-49.3 microg, P < 0.001). CONCLUSIONS Despite similar BP lowering, valsartan and ramipril were more effective than amlodipine in preventing new episodes of AF, but the effect of valsartan was greater than that of ramipril. This could be related to the greater PWD reduction observed with valsartan.

The aim of this study was to compare the effect of valsartan/amlodipine and atenolol/amlodipine combination in preventing the recurrence of atrial fibrillation (AF) in hypertensive diabetic patients with a history of recent paroxysmal atrial fibrillation. Two hundred ninety-six hypertensive patients with well-controlled type 2 diabetes in sinus rhythm but with at least 2 ECG-documented episodes of AF in the previous 6 months were randomized to 160 mg of valsartan plus amlodipine (titrated from 2.5 to 10 mg) or to 100 mg of atenolol plus amlodipine (2.5 to 10 mg) in addition to their previous antiarrhythmic treatment (if any) and were followed up for 1 year. Blood pressure (BP) and a 24-hour ECG were evaluated monthly. The patients were asked to report any episode of symptomatic AF and to perform an ECG as early as possible. SBP/DBP values were significantly reduced after 12 months with valsartan/amlodipine (from 150.4/93.5 to 126.37/7.4 mm Hg, P < 0.001) and atenolol/amlodipine (from 151.1/94.2 to 127.1/77.9 mm Hg, P < 0.001), with no difference between the 2 regimens. At least 1 ECG-documented episode of AF was reported in 20.3% of the patients treated with valsartan/amlodipine and in 34.1% of those treated with atenolol/amlodipine, with a significant difference between treatments (P < 0.01). The positive effect of valsartan/amlodipine combination on AF recurrence was more evident in patients treated with amiodarone or propafenone than in patients treated with other antiarrhythmic drugs or without antiarrhythmic treatment. Despite similar BP reduction, valsartan/amlodipine combination was more effective in patients treated with amiodarone or propafenone than atenolol/amlodipine in preventing new episodes of AF in hypertensive diabetic patients.

Objective The aim of the study was to evaluate the effect of valsartan/amlodipine combination on insulin sensitivity in overweight-obese hypertensive patients. Methods After a 4-week placebo period, 58 overweight-obese (BMI ≥25 kg/m2) patients, with mild to moderate essential hypertension (DBP >95 and 140 mmHg) were treated with amlodipine 5 mg od or valsartan 160 mg od or amlodipine 5 mg plus valsartan 160 mg od for 8 weeks according to a randomized, open-label, blinded end-point, cross-over study. At the end of the placebo period and each treatment period, blood pressure (BP) and insulin sensitivity (IS) (by euglycemic hyperinsulinemic clamp technique) were evaluated. IS was expressed as the amount of glucose infused during the last 30 min (glucose infusion rate, GIR) in mg/kg/min. Results Valsartan/amlodipine combination produced a significantly greater decrease in SBP/DBP values (-22.3/16.7 mmHg, p

Objective To compare the effect of delapril/manidipine vs olmesartan/hydrochlorothiazide (HCTZ) combination on insulin sensitivity and plasma fibrinogen in obese hypertensive patients. Patients and Methods After a 4-week placebo period, 88 obese, hypertensive (DBP >95 and

We sought to compare the effect of manidipine versus hydrochlorothiazide (HCTZ) in addition to candesartan on the urinary albumin excretion rate (UAER) in hypertensive patients with type II diabetes and microalbuminuria.After a 2-week washout and run-in period, and 8-week monotherapy with candesartan 16 mg every day, 174 microalbuminuric diabetic hypertensive patients with uncontrolled blood pressure (BP) (130/80 mm Hg) were randomized to addition of manidipine 10 mg every day (n = 87) or HCTZ 12.5 mg every day (n = 87) for 24 weeks, with a titration after 4 weeks (manidipine or HCTZ dose-doubling) in nonresponder patients. Blood pressure, UAER, creatinine clearance, serum electrolytes, fasting plasma glycemia, and glycosylated hemoglobin were evaluated at baseline (end of run-in period), after candesartan monotherapy, and at the end of the combination treatment period.Both combinations produced greater systolic BP/diastolic BP reduction than candesartan monotherapy (-28/21 mm Hg versus -16/11 mm Hg and -28/20 mm Hg versus -15/11 mm Hg, respectively; all P.05 versus monotherapy), with no significant difference between the two combinations. The addition of manidipine produced a greater reduction in UAER than candesartan monotherapy (-55.4 mg/24 h v -36.1 mg/24 h, P.05), whereas the addition of HCTZ did not significantly modify UAER; the difference between the two combinations was statistically significant (P.05). Similarly, the percentage of patients moving to a normoalbuminuric state (UAER30 mg/24 h) was increased by the addition of manidipine to candesartan (from 35% to 64%, P.05), but not by the addition of HCTZ (from 34% to 39%, NS), with a statistical difference between the two combinations (P.05).These findings show that, despite equivalent reduction in BP, the addition of manidipine to candesartan further reduced the UAER, whereas the addition of HCTZ did not modify the UAER. This suggests that the antiproteinuric effect of manidipine is partially independent of BP reduction, and is attributable to mechanisms different from those mediated by angiotensin receptor blockade.

Aim of this study was to evaluate the effect of the telmisartan-amlodipine combination at different doses on urinary albumin excretion rate (UAER) in hypertensive diabetic patients with microalbuminuria.After a 2-week placebo period, 300 hypertensive patients with type 2 diabetes and microalbuminuria were treated with the 40 mg of telmisartan and 2.5 mg of amlodipine combination. After 4 weeks 210 patients whose blood pressure (BP) was not controlled (BP130/80 mm Hg) were randomized to two-dose titration regimens, one based on increasing doses of telmisartan (up to 160 mg daily) and fixed 2.5-mg dose of amlodipine, the other based on increasing doses of amlodipine (up to 10 mg daily) and fixed 40-mg dose of telmisartan. After 12 weeks the nonresponder patients were given transdermic clonidine (0.1mg/d). After 16 weeks the patients yet not controlled were discontinued, the others were followed for 48 weeks. Office BP, UAER, creatinine clearance, plasma potassium, fasting glycemia, and glycosylated hemoglobin were assessed at the end of the telmisartan (40 mg)/amlodipine (2.5 mg) treatment period and after 48 weeks of treatment.Similar decrease in systolic/diastolic BP values were obtained with both regimens (-24/-21, -23/-21, and -24/-21 mm Hg, all P.001 v baseline, with increasing telmisartan; -25/-22, -25/-21, and -25/-22 mm Hg, all P.001 v baseline with increasing amlodipine). Reductions of UAER were 47.5% (P.01), 65.3% (P.001), and 77% (P.0001) for telmisartan 80, 120, and 160 mg/amlodipine 2.5 mg daily, respectively, whereas reductions of UAER were 34% (P.03), 37% (P.03), and 33% (P.03) for amlodipine 5, 7.5, and 10 mg/telmisartan 40 mg daily, respectively, The difference between the two regimens was statistically significant (P.05, P.01, and P.001, respectively).These findings indicate that, at comparable levels of BP reduction, UAE decreased more in subjects treated with escalating doses of telmisartan.

Primary aldosteronism (PA) has been considered a rare cause of hypertension. The introduction of the aldosterone/renin ratio (ARR) as a screening test has led to an increase in the detection rate. The aim of this study was to evaluate the prevalence of PA among unselected hypertensive patients by using an ARR >25 as a screening test. We studied 3,000 consecutive unselected hypertensive patients. Blood samples for the determination of plasma renin activity (PRA), aldosterone (ALD) and electrolytes were drawn in the morning, and patients with an ARR >25 underwent intravenous saline infusion as a confirmatory test. Adrenal CT and a dexamethasone suppression test were performed in patients with confirmed PA. Patients with a positive dexamethasone test underwent genetic testing for glucocorticoid-remediable aldosteronism (GRA). Out of 3,000 hypertensives, 684 (22.8%) showed an ARR >25 and 177 of them (5.9% of the whole population) had a positive saline loading test. Only 44 of them (24.8%) were hypokalemic. CT was performed in all the patients with confirmed PA and 53 of them (29.9%) had a solitary adrenal macroadenoma, 112 (63.3%) had bilateral adrenal enlargement and 12 (6.8%) had normal appearing adrenal glands. Of 177 patients given dexamethasone to identify GRA, 8 (4.5%) showed aldosterone suppression but only one (0.1%) tested positive for the chimeric gene. In conclusion, our findings indicate that standardized application of an ARR >25 to unselected hypertensive patients, followed by i.v. saline loading as a confirmatory test, can result in the detection of a large number of patients with PA (5.9% of the studied population), most of whom are normokalemic. Bilateral adrenal hypertrophy represents the more common form of PA.

Background This study compares the effects of telmisartan hydrochlorothiazide (HCTZ) combination versus nifedipine GITS on ambulatory blood pressure (BP) and sympathetic activity, in patients with mild-to-moderate hypertension. Methods One hundred twenty-four outpatients with sitting diastolic BP ≥95 mm Hg and

The aim of this study was to compare the effects of benazepril and amlodipine in monotherapy versus in combination with plasma t-PA and PAI-1 activity in hypertensive type-2 diabetic patients. After an initial 6-week wash-out, single-blind placebo period, 38 patients, 17 men and 21 females, were randomly assigned to receive benazepril 10 mg o.d. or amlodipine 5 mg o.d. or their combination o.d. at the same dosage for 6 weeks in three crossover periods each separated by a 2-week placebo wash-out period (3×3 latin square). At the end of the placebo run-in period and of each treatment period, BP, plasma PAI-1 and tPA activity were evaluated. Both benazepril and amlodipine were similarly effective in reducing systolic blood pressure (SBP) (−17.6 mmHg with benazepril and −19.8 mmHg with amlodipine; P

Background: Failure to achieve good blood pressure (BP) control is probably the most important reason for high rates of morbidity and mortality in patients with hypertension. Combination therapy has been shown to increase the percentage of patients in whom BP control is achieved. One combination is a calcium channel blocker (CCB) and an angiotensin-converting enzyme inhibitor (ACE-I). Objective: The aim of this study was to assess the effects of the fixed combination of the CCB manidipine and the ACE-I delapril in the treatment of hypertensive patients already given monotherapy with either component but with poor results (ie, insufficient BP control or adverse events [AEs]). Methods: In this Phase III, multicenter, open-label, clinical trial, patients with mild to moderate hypertension were assigned to 1 of 2 groups. Group 1 comprised patients whose diastolic BP (DBP) was >90 mm Hg or who experienced AEs with manidipine 20 mg once daily. Group 2 comprised patients who had a DBP >90 mm Hg or who experienced AEs with delapril 30 mg BID. In both groups, patients aged

To compare the effects of valsartan and atenolol on sexual activity and plasma testosterone in newly diagnosed, previously untreated, essential hypertensive male subjects.One hundred and ten hypertensive men, aged 40-49 years, homogeneous for marital status and without any previous sexual dysfunction were randomly treated with valsartan 80 mg daily (o.d.) or atenolol 50 mg o.d. for 16 weeks according to a double-blind, parallel-arm study design. After 8 weeks the dose was doubled in the non-responders (diastolic blood pressure90 mmHg). Clinical evaluation was performed after 8 weeks and 16 weeks of treatment and included blood pressure and plasma testosterone measurements and the compilation of a questionnaire about sexual activity (sexual intercourse episodes/month).Despite similar blood pressure lowering, atenolol significantly reduced sexual activity (from 6.0 sexual intercourse episodes/month to 4.2 sexual intercourse episodes/month, P0.01 vs placebo), whereas valsartan increased it, although not significantly (from 5.8 sexual intercourse episodes/month to 7.4 sexual intercourse episodes/month, P = 0.058), compared with placebo, but significantly compared with the atenolol group ( P0.05). Testosterone was reduced by atenolol (from 18.2 nmol/l to 13.8 nmol/l, P0.01 vs baseline) but was not affected by valsartan (from 17.6 nmol/l to 18.3 nmol/l).These results suggest that atenolol induces a worsening of sexual activity and a reduction of testosterone, whereas valsartan does not worsen sexual activity and does not change testosterone levels.

This study compared the effects of losartan and perindopril on plasma plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in hypertensive type 2 diabetic patients.We studied 85 nonsmoking outpatients, aged 46 to 64 years, with mild to moderate essential hypertension (diastolic blood pressure [BP]90 and110 mm Hg) and well controlled type 2 diabetes mellitus. After a 4-week washout placebo period, patients were randomized to received perindopril 4 mg once daily (n = 42) or losartan 50 mg once daily (n = 43) for 12 weeks according to a double-blind, parallel-group design. At the end of the placebo and active treatment periods, BP was measured and plasma PAI-1 and fibrinogen were evaluated.Both perindopril and losartan reduced systolic and diastolic BP values (-16/15 mm Hg and -15/14, respectively; P.001 v placebo), with no difference between the two treatments. Plasma PAI-1 was reduced by perindopril (-10 ng/dL, P = .028 v placebo) but not by losartan (+4 ng/dL, NS), the difference between the two treatments being statistically significant (P.01). Plasma fibrinogen showed no significant change with both drugs, although a decreasing trend was noted with perindopril.These findings indicate that perindopril but not losartan decreases PAI-1 in hypertensive type 2 diabetic patients, which suggests that the PAI-1 lowering effect is unrelated with AT, receptor blockade and could rather be due to the fact that the endothelial receptors that mediate PAI-1 expression in response to angiotensin II are not type 1 receptor subtypes. Different effects of the two drugs on the bradykinin system might also be implicated.

Background: The angiotensin II (AII) receptor antagonists are effective agents for the treatment of mild to moderate hypertension. Agents within this drug class differ with respect to their pharmacologic and pharmacokinetic properties, which may translate into differences in antihypertensive effect. Objective: The purpose of this study was to compare the antihypertensive efficacy of the AII receptor antagonists losartan, valsartan, and telmisartan using 24-hour ambulatory blood pressure monitoring (ABPM). Methods: Outpatients aged 40 to 60 years with mild to moderate hypertension (sitting diastolic blood pressure [DBP] ≥95 mm Hg and ≤115 mm Hg) were enrolled. After a 4-week placebo washout period, patients were randomized to receive losartan 50 mg, valsartan 80 mg, telmisartan 40 mg, or placebo once daily for 4 weeks according to a 4-period crossover design. Each treatment period was separated by a 2-week placebo washout period. Every 2 weeks, 24-hour ABPM was performed. To assess the homogeneity of blood pressure (BP) control, the trough-to-peak (T/P) ratio and the smoothness index (SI) for systolic blood pressure (SBP) and DBP were calculated. Results: After 2 and 4 weeks of treatment, all 3 agents produced significant reductions in 24-hour, daytime, and nighttime SBP and DBP, compared with placebo ( P P P 50%. The SI for SBP and DBP was significantly higher with valsartan than with losartan and telmisartan both at 2 weeks ( P P P P Conclusions: In the present study, treatment with valsartan resulted in an earlier, greater, and smoother antihypertensive effect compared with treatment with losartan or telmisartan; this differential effect was likely due to differences in the pharmacologic properties of these agents. Analysis of SI revealed a qualitative difference in the antihypertensive action of telmisartan at the beginning of treatment.

The aim of this study was to compare the effects of trandolapril and losartan on plasminogen activator inhibitor type 1 (PAI-1) levels and insulin sensitivity in hypertensive postmenopausal women. We studied 89 hypertensive (diastolic blood pressure >90 and

Background: Ankle edema is one of the most common side effects of antihypertensive treatment with calcium channel blockers (CCBs). The incidence of edema is higher with dihydropyridines than with verapamil or diltiazem. Objective: The aim of this study was to compare the effect of antihypertensive treatment with the new CCB lercanidipine versus nifedipine gastrointestinal therapeutic system (GITS) on ankle-foot volume (AFV) and on pretibial subcutaneous tissue pressure (PSTP), considered objective measures of CCB-induced ankle edema. Methods: Patients with mild to moderate hypertension (diastolic >90 mm Hg and Results: Sixty patients (34 men and 26 women) aged 36 to 70 years were enrolled. Lercanidipine and nifedipine GITS produced similar reductions in systolic and diastolic BP (lercanidipine, −18.7/11.8 mm Hg; nifedipine GITS, −18.8/11.5 mm Hg; P P 2 O) compared with nifedipine GITS (AFV, 284.2 mL; PSTP, 1.8 cm H 2 O). In both treatment groups, correlation analysis showed an inverse relationship, although to a different degree, between AFV and PSTP changes, but not between absolute values of AFV and PSTP during treatment. AFV increase was greater and PSTP increase was lower with increasing age, which suggests a role for age in the type of tissue response to a stimulus for edema formation. No relationship was found between AFV and PSTP changes and BP reduction. Conclusions: These data suggest that lercanidipine produces significantly less increases in AFV and PSTP, 2 objective measures of edema formation, than nifedipine GITS.

The aim of this study was to assess the effects of adding losartan to lisinopril on 24-hour blood pressure (BP) values and on the reninangiotensin system (RAS) in patients with hypertension whose condition was not controlled by lisinopril monotherapy. We studied 52 patients with essential hypertension (27 men, 25 women; mean age, 56 ± 6 years) with sitting diastolic blood pressure (DBF) > 90 mm Hg after 4 weeks of monotherapy with lisinopril 10 mg once daily. The patients were randomly allocated to receive either losartan 50 mg once daily in addition to lisinopril 10 mg once daily or a double dose of lisinopril (20 mg once daily) for 4 weeks, according to a doublemasked, crossover design. At the end of each treatment period, casual BP and heart rate were measured, noninvasive 24-hour ambulatory blood pressure monitoring was performed, and a blood sample was obtained to measure plasma renin activity (PRA) and angiotensin (Ang) I and II levels. The combined administration of losartan 50 mg and lisinopril 10 mg produced a greater reduction in both ambulatory and casual systolic BP and DBP values compared with lisinopril 20 mg. The additive BP-lowering effect of the combination therapy occurred during both the 24-hour period and the single daytime and nighttime subperiods, without interfering with the normal circadian BP pattern. Furthermore, the losartanlisinopril combination increased PRA and Ang I more than lisinopril 20 mg and decreased the losartan-induced peak value of Ang II. Results of this study suggest that the addition of losartan to lisinopril therapy was more effective in decreasing BP and increasing PRA and Ang I than doubling the lisinopril dose; therefore, a more complete RAS blockade might improve BP control in patients with hypertension.

The aim of this prospective, randomized, open-label, masked, endpoint, crossover study was to compare the antihypertensive efficacy of valsartan with that of losartan—angiotensin II (Ang II) receptor antagonists with different pharmacologic profiles—in patients with mild-to-moderate essential hypertension. After an initial 2-week placebo washout period, 40 patients (24 men and 16 women, aged 39 to 58 years) were assigned randomly to receive valsartan 80 mg or losartan 50 mg once daily for 4 weeks. After an intermediate 2-week placebo washout period, patients were switched to the alternative regimen for an additional 4 weeks. After the initial placebo washout period and every 2 weeks thereafter, 24-hour ambulatory blood pressure monitoring (ABPM) was performed using a noninvasive device, and casual blood pressure (BP) and heart rate were measured. Both losartan and valsartan had a clear-cut antihypertensive effect. However, valsartan showed significantly better antihypertensive efficacy compared with that of losartan, as demonstrated by (1) the 24-hour, daytime, and nighttime ABPM values, which were significantly lower ( P

The aim of this study was to compare the effects of long-term monotherapy with four different beta-blockers on plasma lipids in hypercholesterolemic hypertensive patients. We studied 152 subjects with essential hypertension [diastolic blood pressure (DBP) >90 mm Hg], total cholesterol (TC) >240 and

Prostaglandins (PGs) are thought to play a role in the genesis of cough induced by angiotensin-converting enzyme (ACE) inhibitors, whereas inhibition of PG synthesis can reduce or abolish the incidence of this side effect. Experimental and clinical data suggest that nifedipine, a dihydropyridine calcium channel blocker, can inhibit PG synthesis. Therefore, the aim of the present study was to determine whether treatment with amlodipine would also reduce cough induced by an ACE inhibitor and to compare the efficacy of amlodipine with that of indomethacin, a known inhibitor of PG synthesis. Thirty-three patients with hypertension who developed cough during chronic benazepril therapy were allocated randomly to receive slow-release nifedipine gastrointestinal therapeutic system (GITS) 30 mg once daily, amlodipine 5 mg once daily, indomethacin 50 mg twice daily, or placebo twice daily for 2 weeks. This was according to a double-masked, double-dummy, crossover, Latin square design. At the end of each phase, cough was assessed by means of a self-administered questionnaire with an ordinal 10-point visual analogue scale for rating daily cough intensity and frequency. Indomethacin eliminated or markedly reduced cough induced by the ACE inhibitor, whereas nifedipine GITS and amlodipine reduced it to a lesser degree. These findings suggest that PGs play a role in cough caused by ACE inhibitors and that a dihydropyridine calcium channel blocker can reduce the occurrence of this side effect.

To evaluate the effect of manidipine 10 mg on 24-hour ambulatory blood pressure (BP) and heart rate (HR) in very elderly hypertensive patients, 54 patients aged 76-89 years (mean age 81.8 years) with systolic blood pressure (SBP) > 160 mmHg and diastolic blood pressure (DBP) > 90 mmHg were studied. After a 4-week placebo washout period, patients were randomized to receive manidipine 10 mg or placebo, both administered once daily for 8 weeks. Patients were checked after the initial run-in placebo phase and every 4 weeks thereafter. At each visit casual BP and HR were measured. At the end of the placebo period and after 8 weeks of active treatment, noninvasive 24-hour ambulatory blood pressure measurement (ABPM) was performed. Manidipine significantly lowered casual sitting and standing SBP (P < 0.001) and DBP (P < 0.001) at the trough level. ABPM showed a significant decrease in 24-hour SBP and DBP values (P < 0.001), daytime SBP and DBP (P < 0.001), and night-time SBP (P < 0.001) and DBP (P < 0.005). In addition, ABPM confirmed a consistent antihypertensive activity throughout the 24-hour dosing interval, without effect on the circadian BP profile. The trough/peak ratio was 0.67 for SBP and 0.59 DBP. No statistically significant change in HR was observed. The treatment was well tolerated, and there were no serious side effects. In conclusion, in very elderly hypertensive patients, once-daily administration of manidipine 10 mg was well tolerated and effective in reducing casual as well ambulatory BP.

The effect of sustained-release (SR) diltiazem 300 mg on 24-hour ambulatory blood pressure (BP), heart rate (HR), and left ventricular mass was evaluated in 35 elderly patients aged 75 to 84 years with mild-to-moderate essential hypertension, defined as sitting systolic blood pressure (SBP) >160 mm Hg and diastolic blood pressure (DBP) >90 mm Hg but

AIM: To evaluate heart rate and its relationship with some established cardiovascular risk factors in normotensive and hypertensive individuals. METHODS: We studied 881 1 men, 696 with essential hypertension and 8115 with normal blood pressure, stratified in four age groups: 20-29, 30-39, 40-49 and 50-59 years. Clinical evaluation included measures of heart rate (by pulse palpation), blood pressure (by mercury sphygmomanometer), total cholesterol, triglycerides, blood glucose and fibrinogen, and details of medical history and personal habits, with particular regard to smoking habits. RESULTS: Heart rate, which was significantly higher in hypertensive than in normotensive individuals, showed no significant change with age in the normotensive group, but a slight decline with increasing age in those with hypertension. In the normotensive group, heart rate was significantly higher in smokers than in non-smokers and ex-smokers, and showed no significant variation with increasing age, independently of smoking habits. Among those with hypertension, heart rate was not statistically different in smokers, non-smokers and ex-smokers, and showed a moderate decrease with age in non-smokers and ex-smokers, but did not change with age in smokers. CONCLUSIONS: Both ageing and smoking habits have different effects on heart rate in normotensive and hypertensive individuals.

BACKGROUND: 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. HYPOTHESIS: Telmisartan may be more effective than amlodipine in preventing AF recurrence in hypertensive patients with paroxysmal AF and normal or increased left atrial dimension (LAD). METHODS: The authors assigned 378 mild hypertensive outpatients in sinus rhythm, but with ≥2 episodes of AF in the previous 6 months, to 1 of 2 groups. Group 1 comprised patients with LAD 40 mm and 45 mm and

The time to achieve a blood pressure (BP) goalor =130/85 mmHg with a combination versus a conventional monotherapy approach was evaluated in 308 hypertensive patients with metabolic syndrome. They were randomized to valsartan (V) 8 mg/amlodipine (A) 5 mg combination or to V 160 mg monotherapy for 12 weeks and every 2 weeks, there was a titration in nonresponder patients: in the combination group V/A was progressively increased to V 160/A 5 mg; V160/A 7.5 mg; V160/A 10 mg; V 240/A 10 mg, and V 320/A 10 mg. In the monotherapy group, the regimen was progressively modified as following: V 240 mg; V 320 mg; V 320/A 5 mg; V 320/A 7.5 mg, and V 320/A 10 mg. The mean time to achieve the BP goal was shorter in patients randomized to combination therapy compared to those randomized to conventional monotherapy (4.7 +/- 2.7 weeks vs. 7.1 +/- 3.9 weeks, respectively, p0.001). The percentage of patients who achieved target BP in the combination approach group statistically exceeded that of the monotherapy treated one already after 2 weeks of treatment (30.5 vs. 14.9%, p0.01) and again after 4, 6, 8, and 10 weeks of treatment. Only at 12 weeks the percentage of normalized patients was similar in the two treatment groups (78.8% vs. 75.3%, ns). These results suggest that initial therapy with a V/A combination approach may be more quickly effective than a conventional sequential monotherapy approach in achieving target BP in hypertensive patients with metabolic syndrome.

The renin-angiotensin-aldosterone system (RAAS), an important regulator of blood pressure and mediator of hypertension-related complications, is a prime target for cardiovascular drug therapy. Angiotensin-converting enzyme inhibitors (ACEIs) were the first drugs to be used to block the RAAS. Angiotensin II receptor blockers (ARBs) have also been shown to be equally effective for treatment. Although these drugs are highly effective and are widely used in the management of hypertension, current treatment regimens with ACEIs and ARBs are unable to completely suppress the RAAS. Combinations of ACEIs and ARBs have been shown to be superior than to either agent alone for some, but certainly not all, composite cardiovascular and kidney outcomes, but dual RAAS blockade with the combination of an ACEI and an ARB is sometimes associated with an increase in the risk for adverse events, primarily hyperkalemia and worsening renal function. The recent introduction of the direct renin inhibitor, aliskiren, has made available new combination strategies to obtain a more complete blockade of the RAAS with fewer adverse events. Renin system blockade with aliskiren and another RAAS agent has been, and still is, the subject of many large-scale clinical trials and furthermore, is already available in some countries as a fixed combination.

The treatment of moderate or severe hypertension in most cases requires the contemporaneous use of multiple antihypertensive agents. The most available two-drug combinations have an agent that addresses renin secretion and another one that is statistically more effective in renin-independent hypertension. The practice of combining agents that counteract different mechanisms is the most likely explanation for the fact that most available two-drug combinations have an agent that addresses renin secretion (beta-blocker, angiotensin converting enzyme inhibitor, angiotensin II receptor blocker or direct renin inhibitor) and another one that is more effective in renin-independent hypertension (diuretic, dihydropyridine or non-dihydropyridine calcium channel blocker). Based on these considerations, addition of hydrochlorothiazide to the combination of an antagonist of the renin-angiotensin system with a calcium channel blocker would constitute a logical approach. Inclusion of a diuretic in the triple combination is based on the evidence that these agents are effective and cheap, enhance the effect of other antihypertensive agents, and add a specific effect to individuals with salt-sensitivity of blood pressure. The benefit of triple combination therapy with amlodipine, valsartan and hydrochlorothiazide over its dual component therapies has been demonstrated, and the use of a single pill will simplify therapy resulting in better blood pressure control.

Angiotensin II is a vasoactive hormone of the renin-angiotensin system and plays an important role in the pathophysiology of several organ damages. Angiotensin II receptor blockers have been shown to be effective in treating both hypertension and connected organ damages. It is well known that although the angiotensin II receptor blockers have structural and pharmacokinetic differences, few pharmacological differences separate them. One of these is the degree of binding to the angiotensin II receptor type 1 compared with the angiotensin II receptor type 2; olmesartan medoxomil exhibits more than a 12,500-fold greater affinity for the angiotensin II receptor type 1 receptor than for the angiotensin II receptor type 2, making it theoretically the second most potent agent. However, olmesartan's excellent receptor interaction is based on the combination of several specific pharmacokinetic factors. Potential advantages of this drug include once-daily dosing, a very low incidence of significant adverse reactions and/or events and a well-tolerated side effect profile. Nowadays, we have a lot of information about the pharmacology, antihypertensive efficacy and safety of olmesartan medoxomil, to further extend many clinical studies are still continuing to evaluate the potential benefits of high dosages and/or combination of this molecule.