ClinicalTrials.gov: NCT02145611, registered on 11 Jun 2013.

BackgroundVildagliptin, a DPP-4 inhibitor widely used for the treatment of type 2 diabetes mellitus (T2DM), shows beneficial effects on endothelial function. This study aims to evaluate the effect of vildagliptin on endothelial function and arterial stiffness in patients with T2DM and hypertension.MethodsFifty over 35-year-old patients with T2DM and hypertension, without cardiovascular disease, will be randomly allocated to two groups: group 1 will receive vildagliptin added-on to metformin and group 2, glibenclamide added-on to metformin. Biochemical tests (glycemia, glycated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, triglycerides, creatinine, alanine aminotransferase, ultrasensitive C-reactive protein, and microalbuminuria), 24-h non-invasive ambulatory blood pressure monitoring, and assessment of endothelial function and arterial stiffness will be performed in both groups before and after 12 weeks of treatment. The endothelial function will be assessed by peripheral arterial tonometry, which measures the reactive hyperemia index (vasodilation), and arterial stiffness will be evaluated by applanation tonometry. All analysis will be performed using SPSS Statistical Software. For all analysis, a 2-sided P < 0.05 will be considered statistically significant.ResultsThe study started in December 2013 and patient recruitment is programed until October 2015. The expected results are that vildagliptin will improve the endothelial function in patients with T2DM and hypertension compared to glibenclamide treatment, independently of glycemic control.ConclusionsIt is expected that this DPP-4 inhibitor will improve endothelial function in patients with T2 DM.Trial registration: Clinical Trials NCT02145611, registered on 11 Jun 2013

CONTEXT AND OBJECTIVES: Assessment of central blood pressure (BP) has grown substantially over recent years because evidence has shown that central BP is more relevant to cardiovascular outcomes than peripheral BP. Thus, different classes of antihypertensive drugs have different effects on central BP despite similar reductions in brachial BP. The aim of this study was to investigate the effect of nebivolol, a β-blocker with vasodilator properties, on the biochemical and hemodynamic parameters of hypertensive patients. DESIGN AND SETTING: Experimental single cohort study conducted in the outpatient clinic of a university hospital. METHODS: Twenty-six patients were recruited. All of them underwent biochemical and hemodynamic evaluation (BP, heart rate (HR), central BP and augmentation index) before and after 3 months of using nebivolol. RESULTS: 88.5% of the patients were male; their mean age was 49.7 ± 9.3 years and most of them were overweight (29.6 ± 3.1 kg/m 2 ) with large abdominal waist (102.1 ± 7.2 cm). There were significant decreases in peripheral systolic BP (P = 0.0020), diastolic BP (P = 0.0049), HR (P < 0.0001) and central BP (129.9 ± 12.3 versus 122.3 ± 10.3 mmHg; P = 0.0083) after treatment, in comparison with the baseline values. There was no statistical difference in the augmentation index or in the biochemical parameters, from before to after the treatment. CONCLUSIONS: Nebivolol use seems to be associated with significant reduction of central BP in stage I hypertensive patients, in addition to reductions in brachial systolic and diastolic BP. RESUMO CONTEXTO E OBJETIVOS:A avaliação da pressão arterial central (PAc) tem crescido substancialmente nos últimos anos porque as evidências mostraram que PAc central é mais relevante para os desfechos cardiovasculares do que pressão arterial (PA) periférica. Assim, diferentes classes de anti-hipertensivos têm efeitos diferentes sobre PAc apesar de reduções semelhantes na PA braquial. O objetivo foi investigar o efeito do nebivolol, β-bloqueador com propriedades vasodilatadoras, nos parâmetros bioquímicos e hemodinâmicos de pacientes hipertensos. TIPO DE ESTUDO E LOCAL: Estudo de coorte única experimental realizado em ambulatório de hospital universitário. MÉTODOS: Todos os 26 pacientes recrutados foram submetidos à avaliação bioquímica e hemodinâmica (PA, frequência cardíaca, FC, PAc, augmentation index) antes e após três meses usando nebivolol. RESULTADOS: 88,5% dos indivíduos eram do sexo masculino, com média de idade de 49,7 ± 9,3 anos, predominância de sobrepeso (29,6 ± 3,1 kg/m 2 ) e aumento da cintura abdominal (102,1 ± 7,2 cm). Houve diminuição significativa da PA sistólica periférica (P = 0,0020) e diastólica (P = 0,0049), da FC (P < 0,0001) e da PAc (129,9 ± 12,3 x 122,3 ± 10,3 mmHg, P = 0,0083) após o tratamento em comparação aos valores basais. Não houve diferença no augmentation index, nem nos parâmetros bioquímicos antes e após o período de tratamento. CONCLUSÕES: O uso de nebivolol parece estar associado à redução significativa da PA...

Hypertension and type 2 diabetes mellitus (DM) are among the main risk factors for the development of cardiovascular disease. Pharmacotherapy for DM should not only improve blood glucose control, but also provide beneficial glucose-independent cardiovascular effects. The central systolic blood pressure (SBP) has become more important than the brachial SBP in the assessment of cardiovascular risk.This case report describes the effect of vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, on the central SBP in a 54-year-old woman with hypertension and DM. She was submitted to applanation tonometry (AT) before and after vildagliptin association. AT of the radial artery is a non-invasive method that indirectly assesses arterial stiffness by calculating the central SBP and the augmentation index (AIx).After 3 months of follow-up using vildagliptin, central SBP and AIx were improved. Moreover, she presented better glycemic control.This case suggests an effect of DPP-4 inhibitor on arterial stiffness parameter (central SBP) in a hypertensive and diabetic patient, which shows a glucose-independent beneficial cardiovascular effect of this group of drugs.

BackgroundResistant hypertension is characterized when the blood pressure (BP) remains above the recommended goal after taking three antihypertensive drugs with synergistic actions at their maximum recommended tolerated doses, preferably including a diuretic. Identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether acting on the control of intravascular volume or sodium balance, or acting on the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney.Methods/designThis is a randomized, open-label, clinical trial is designed to compare sequential nephron blockade and its contribution to the intravascular volume component with dual blockade of the RAAS plus bisoprolol and the importance of serum renin in maintaining BP levels. The trial has two arms: sequential nephron blockade versus dual blockade of the RAAS (with an angiotensin converting enzyme (ACE) inhibitor plus a beta-blocker) both added-on to a thiazide diuretic, a calcium-channel blocker and an angiotensin receptor-1 blocker (ARB). Sequential nephron blockade consists in a progressive increase in sodium depletion using a thiazide diuretic, an aldosterone-receptor blocker, furosemide and, finally, amiloride.On the other hand, the dual blockade of the RAAS consists of the progressive addition of an ACE inhibitor until the maximum dose and then the administration of a beta-blocker until the maximum dose. The primary outcomes will be reductions in the systolic BP, diastolic BP, mean BP and pulse pressure (PP) after 20 weeks of treatment. The secondary outcomes will evaluate treatment safety and tolerability, biochemical changes, evaluation of renal function and recognition of hypotension (ambulatory BP monitoring (ABPM)). The sample size was calculated assuming an alpha error of 5% to reject the null hypothesis with a statistical power of 80% giving a total of 40 individuals per group.DiscussionIn recent years, the cost of resistant hypertension (RH) treatment has increased. Thus, identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether by acting on the control of intravascular volume or sodium balance, or by acting on the effects of the RAAS on the kidney.Trial registrationSequential Nephron Blockade vs. Dual Blockade Renin-angiotensin System + Bisoprolol in Resistant Arterial Hypertension (ResHypOT). ClinicalTrials.gov, ID: NCT02832973. Registered on 14 July 2016. First received: 12 June 2016. Last updated: 18 July 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2343-3) contains supplementary material, which is available to authorized users.

The pathophysiological mechanism of resistant hypertension (RH) is related to increased vascular smooth muscle tone and blood volume, exacerbation of the activity of the sympathetic system and hyperactivity of the renin-angiotensin-aldosterone system (RAAS), all of which are important regulatory mechanisms of blood pressure. Hypertension is associated with reduced endothelial homeostasis, and thus the best treatment would not only reduce blood pressure but also reverse endothelial injury. RH is associated with more serious vascular dysfunction, assessed by endothelium-dependent vasodilation and the presence of serum biomarkers. Arterial stiffness also constitutes an important independent factor that can determine risk of cardiovascular events in patients with RH; it is an important indicator of vascular changes, and is associated with cardiovascular mortality. Arterial stiffness can be assessed by 3 measures: central blood pressure, augmentation index (AIx) and pulse wave velocity (PWV). PWV is a recognized as main marker of the severity of vascular injury. The increase in central blood pressure caused by backward (reflected) waves can be evaluated as an index derived from an analysis of the central aortic blood pressure curve known as the AIx, and depends on the magnitude and time of the reflected waves and indirectly on heart frequency and arterial stiffness. The evaluation of patients with RH is focused on the identification of causes of hypertension guided by the clinical features of hypertension and metabolic, vascular, endocrine and family history.

BackgroundResistant hypertension (RH) treatment requires an adequate and intense therapeutic approach. However, the results are not always satisfactory despite intensive treatment. Of the different pathophysiological mechanisms involved in the pathogenesis of RH, sympathetic overstimulation and therapies that block the sympathetic system have been widely studied. These approaches, however, are invasive and expensive. Another possible approach is by transcutaneous electrical nerve stimulation (TENS), a noninvasive method that modulates activity by using low-frequency transcutaneous electrical stimulation to inhibit primary afferent pathways. Thus, the current study will evaluate the effect of applying TENS in the cervicothoracic region of subjects with RH and will seek to develop a new low-cost and readily available therapy to treat this group of hypertensive individuals.Methods/designThis is a randomized, single blind (subject), parallel-assignment study controlled with a sham group and including participants aged 40 to 70 years with resistant hypertension. The trial has two arms: the treatment and control (sham group). The treatment group will be submitted to the stimulation procedure (TENS). The sham group will not be submitted to stimulation. The primary outcomes will be a reduction in the peripheral blood pressure and adverse events. The secondary outcomes will be a reduction the central blood pressure. The study will last 30 days. The sample size was calculated assuming an alpha error of 5 % to reject the null hypothesis with a statistical power of 80 %, thereby resulting in 28 participants per group (intervention versus sham).DiscussionIn recent decades, RH has become very common and costly. Adequate control requires several drugs, and in many cases, treatment is not successful. Sympathetic nervous system inhibition by renal denervation and central inhibition have significant effects in reducing BP; however, these treatments are costly and invasive. Another type of sympathetic nervous system inhibition can also be noninvasively achieved by electric current. Therefore, the application of TENS may be a new therapeutic option for treating resistant hypertensive individuals.Trial RegistrationClinical Trials NCT02365974Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1302-8) contains supplementary material, which is available to authorized users.

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