Plasma levels of matrix metalloproteinase-9 are elevated in individuals with hypertensive crisis.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) participates in the degradation of components of the extracellular matrix and it is involved in vascular remodeling and vasomotor changes. The aim of this study was to investigate the plasma levels of MMP-9 in acute vascular alterations due to hypertensive crisis. METHODS: This cross-sectional study was performed in 40 normotensive (NT) and 58 controlled hypertensive subjects (CHyp) followed up in outpatient clinic. Moreover, 57 patients with hypertensive emergency (HypEmerg) and 43 in hypertensive urgency (HypUrg), seen in emergency department, were also included. Hypertensive crisis was divided into HypEmerg, which was characterized by levels of systolic blood pressure (BP) ≥ 180 mmHg and/or diastolic BP ≥ 120 mmHg complicated with target-organ damage (TOD), and HypUrg, defined by BP elevation without TOD. Univariate and multivariate regression analysis was performed to identify the influence of independent variables on MMP-9 levels. A p-value < 0.05 was considered statistically significant. RESULTS: The mean age was 43.5 years in the NT group (11 men); 57.7 years in the CHyp group (29 men); 59.4 years in the HypUrg group (21 men) and 62.4 years in the HypEmerg group (31 men). The age was statistically different in the NT group compared to other 3 groups. The mean BP was 116.5 ± 13.9/72.4 ± 10.6 mmHg for NT, 123.2 ± 12.6/79 ± 9.2 for CHyp, 194.1 ± 24.3/121.4 ± 17.3 for HypUrg and 191.6 ± 34.3/121.7 ± 18.8 mmHg for HypEmerg, respectively (p-value< 0.0001 between groups). MMP-9 levels were statistically different between the HypEmerg (2.31 ± 0.2 ng/mL) and HypUrg groups (2.17 ± 0.3 ng/mL) compared to the NT (1.94 ± 0.3 ng/mL) (p-value < 0.01 and p-value < 0.05, respectively) and CHyp groups (1.92 ± 0.2 ng/mL) (p-value < 0.01). Uric acid was the only independent variable for predicting MMP-9 levels (p-value = 0.001). CONCLUSION: MMP-9 concentrations are significantly higher in the hypertensive crisis groups (urgency and emergency) compared to the control groups. Therefore, MMP-9 may be a biomarker or mediator of pathophysiologic pathways in cases of acute elevations of blood pressure.

Effects of acute blood pressure elevation on biochemical-metabolic parameters in individuals with hypertensive crisis.

Hypertensive crisis is a common clinical situation that presents a high rate of morbidity and mortality and it is characterized by symptomatic rise of blood pressure (BP), systolic (SBP) ≥ 180 mmHg and/or diastolic (DBP) ≥ 120 mmHg. It is classified as emergency (HE) or hypertensive urgency (HU). There is no description of laboratory findings in patients who present acute BP elevation. Thus, this study had the objective to assess the biochemical-metabolic parameters of patients with HC. We studied 74 normotensive individuals (NT), 74 controlled hypertensive patients (ContrHT), 50 subjects with HU, and 78 with HE for evaluating biochemical-metabolic parameters. HE occurs in older individuals and more frequently in those with known hypertension. More patients with HE had dyslipidemia than those with HU (58% vs. 38%). The diastolic BP and heart rate were higher in the HE group (120 mmHg and 87 bpm) compared to ContrHT (71 mmHg and 71 bpm; p < 0.0001) and NT groups (75 mmHg and 68 bpm; p < 0.0001). Glycemia was higher in HE vs. NT and ContrHT (p < 0.05). HDL cholesterol was lower in HE than NT (p = 0.0088). Potassium was lower in HE vs. NT, ContrHT and HU groups (p < 0.05). Creatinine was higher in the HC group vs. NT and ContrHT (p < 0.05). The GFR was significantly lower in HE group vs. HU, ContrHT and NT (p < 0.001). In conclusion, individuals with HC show biochemical alterations when compared to ContrHT and NT. Acute BP elevations are associated with hyperglycemia, dyslipidemia, and higher potassium and creatinine levels and lower renal function. Abbreviations BMI = body mass index BP = blood pressure CH = hypertensive crisis ContrHT = controlled hypertensive DBP = diastolic blood pressure GFR = glomerular filtration rate HbA1c = glycated hemoglobin HDLc = high-density lipoprotein cholesterol HE = hypertensive emergency HPLC = high-performance liquid chromatography HR = heart rate HU = hypertensive urgency JNC 7 = VII Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure LDLc = low-density lipoprotein cholesterol MDRD = Modification of Diet in Renal Disease NT = normotensive RASB = renin-angiotensin system blockers SBP = systolic blood pressure TC = total cholesterol TG = triglycerides.

Effects of Mindful Eating in Patients with Obesity and Binge Eating Disorder.

INTRODUCTION: Binge eating disorder (BED) is a psychiatric illness related to a high frequency of episodes of binge eating, loss of control, body image dissatisfaction, and suffering caused by overeating. It is estimated that 30% of patients with BED are affected by obesity. "Mindful eating" (ME) is a promising new eating technique that can improve self-control and good food choices, helping to increase awareness about the triggers of binge eating episodes and intuitive eating training. OBJECTIVES: To analyze the impact of ME on episodes of binge eating, body image dissatisfaction, quality of life, eating habits, and anthropometric data [weight, Body Mass Index (BMI), and waist circumference] in patients with obesity and BED. METHOD: This quantitative, prospective, longitudinal, and experimental study recruited 82 patients diagnosed with obesity and BED. The intervention was divided into eight individual weekly meetings, guided by ME sessions, nutritional educational dynamics, cooking workshops, food sensory analyses, and applications of questionnaires [Body Shape Questionnaire (BSQ); Binge Eating Scale (BES); Quality of Life Scale (WHOQOL-BREF)]. There was no dietary prescription for calories, carbohydrates, proteins, fats, and fiber. Patients were only encouraged to consume fewer ultra-processed foods and more natural and minimally processed foods. The meetings occurred from October to November 2023. STATISTICAL ANALYSIS: To carry out inferential statistics, the Shapiro-Wilk test was used to verify the normality of variable distribution. All variables were identified as non-normal distribution and were compared between the first and the eighth week using a two-tailed Wilcoxon test. Non-Gaussian data were represented by median ± interquartile range (IQR). Additionally, α < 0.05 and p < 0.05 were adopted. RESULTS: Significant reductions were found from the first to the eighth week for weight, BMI, waist circumference, episodes of binge eating, BSQ scale score, BES score, and total energy value (all p < 0.0001). In contrast, there was a significant increase in the WHOQOL-BREF score and daily water intake (p < 0.0001). CONCLUSIONS: ME improved anthropometric data, episodes of binge eating, body image dissatisfaction, eating habits, and quality of life in participants with obesity and BED in the short-term. However, an extension of the project will be necessary to analyze the impact of the intervention in the long-term.

The Impact of a Nutritional Intervention on Glycemic Control and Cardiovascular Risk Markers in Type 2 Diabetes.

INTRODUCTION: Nutritional management plays a crucial role in treating patients with type 2 diabetes (T2D), working to prevent and control the progression of chronic non-communicable diseases. OBJECTIVES: To evaluate the effects of individualized nutritional interventions on weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglycerides (TGs), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR)} over 12 months and subsequently at follow-up (15 months). METHODS: This longitudinal experimental study (without randomization and blinding) enrolled 84 sedentary participants with T2D (both sexes, aged 18-80 years). They were divided into a control group of 40 participants who received only medical consultations, and an intervention group of 44 participants who received the same medical care along with a nutritional assessment. Consultations occurred quarterly from August 2020 to November 2022 (first-twelfth month), with six to nine patients per session. Subsequently, a follow-up was conducted from December 2022 to November 2023, during which the intervention group had only medical care (during the 12th-15th months). Personalized dietary planning was inspired by the Mediterranean/DASH diets adapted to Brazilian foods and socioeconomic cultures. STATISTICAL ANALYSIS: Normal variables were compared between groups for each time point and also within each group across different time points using a two-way ANOVA (repeated measures for intragroup) followed by the Sídák post hoc test. Non-normal variables were compared between groups for each time point using Kruskal-Wallis followed by the Dunn post hoc test, and within each group across different time points using Friedman followed by the Dunn post hoc test. Data with a Gaussian distribution were presented as mean ± standard deviation (SD), and data with a non-Gaussian distribution were presented as median ± interquartile range (IQR). For all cases, α < 0.05 and p < 0.05 were adopted. RESULTS: In the intervention group, significant reductions were observed between the first and twelfth month for all parameters (p < 0.05), (except for TC), along with an increase in HDL-C (p = 0.0105). Conversely, in the control group, there was a significant increase in HbA1c, weight, BMI, FBG, and WHR (p < 0.05) between the first and twelfth months. Regarding the comparison between groups, there was a significant difference for all analyzed parameters (p < 0.05) from the first to the twelfth month. In the follow-up, differences were also observed (p < 0.05), except for BMI (p > 0.05). CONCLUSION: The individualized nutritional intervention improved eating habits, anthropometric, biochemical, and cardiovascular markers in T2D over 12 months, with sustained results during follow-up. The dietary plan inspired by the Mediterranean and DASH diets demonstrated good adaptation to the Brazilian food culture and the patients' socioeconomic contexts. Consistent monitoring and personalized nutritional management are essential for optimizing long-term outcomes. However, more clinical trials are necessary in order to optimize the level of evidence for longitudinal interventions.

The Role of Heart Rate Variability (HRV) in Different Hypertensive Syndromes.

Cardiac innervation by the parasympathetic nervous system (PNS) and the sympathetic nervous system (SNS) modulates the heart rate (HR) (chronotropic activity) and the contraction of the cardiac muscle (inotropic activity). The peripheral vasculature is controlled only by the SNS, which is responsible for peripheral vascular resistance. This also mediates the baroreceptor reflex (BR), which in turn mediates blood pressure (BP). Hypertension (HTN) and the autonomic nervous system (ANS) are closely related, such that derangements can lead to vasomotor impairments and several comorbidities, including obesity, hypertension, resistant hypertension, and chronic kidney disease. Autonomic dysfunction is also associated with functional and structural changes in target organs (heart, brain, kidneys, and blood vessels), increasing cardiovascular risk. Heart rate variability (HRV) is a method of assessing cardiac autonomic modulation. This tool has been used for clinical evaluation and to address the effect of therapeutic interventions. The present review aims (a) to approach the heart rate (HR) as a CV risk factor in hypertensive patients; (b) to analyze the heart rate variability (HRV) as a "tool" to estimate the individual risk stratum for Pre-HTN (P-HTN), Controlled-HTN (C-HTN), Resistant and Refractory HTN (R-HTN and Rf-HTN, respectively), and hypertensive patients with chronic renal disease (HTN+CKD).

Nutritional Strategies for the Management of Type 2 Diabetes Mellitus: A Narrative Review.

BACKGROUND: Thinking about greater adherence to dietary planning, it is extremely important to be aware of all nutritional strategies and dietary prescriptions available in the literature, and of which of them is the most efficient for the management of T2DM. METHODS: A search was carried out in 2023 for randomized clinical trials, systematic reviews, meta-analyses, and guidelines in the following databases: Pubmed, Scielo, Web of Science, CrossRef and Google Scholar. In total, 202 articles were collected and analyzed. The period of publications was 1983-2023. RESULTS: There is still no consensus on what the best nutritional strategy or ideal dietary prescription is, and individuality is necessary. In any case, these references suggest that Mediterranean Diet may of greater interest for the management of T2DM, with the following recommended dietary prescription: 40-50% carbohydrates; 15-25% proteins; 25-35% fats (<7% saturated, 10% polyunsaturated, and 10% monounsaturated); at least 14 g of fiber for every 1000 kcal consumed; and <2300 mg sodium. CONCLUSIONS: Individuality is the gold standard for dietary prescriptions, however, the Mediterranean diet with low levels of carbohydrates and fats seems to be the most promising strategy for the management of T2DM.

The Effect of Transcutaneous Electrical Nerve Stimulation in Peripheral and Central Hemodynamic Parameters on Resistant Hypertension: A Case Report.

Resistant hypertension (RH) is characterized by being difficult to control, even with the use of various antihypertensive drugs and is associated with target organ lesions and other comorbidities. Thus, new treatment alternatives such as transcutaneous electrical nerve stimulation (TENS) can offer benefits to resistant hypertensive patients by reducing blood pressure (BP) in a non-invasive way and without the need for the association of more antihypertensive drugs. In this case, a patient with RH was submitted to three weekly applications of TENS on the stellate ganglion lasting 40 min each for 1 month. Peripheral and central hemodynamic assessments were performed by 24-h ambulatory BP monitoring (ABPM) before and after TENS applications. After completion of the TENS applications, significant reductions in office systolic (SBP) and diastolic BP (DBP) were observed. There was also a decrease in peripheral SBP and DBP in the 24-h ABPM and sleep and SBP during wakefulness. Additionally, central parameters including central SBP and pulse wave velocity presented a significant reduction in the 24-h ABPM, during the wakefulness and sleep. TENS is able to attenuate the sympathetic hyperactivity present in RH cases and decrease the peripheral and central hemodynamic parameters of a resistant hypertensive patient.

Carotid intima-media thickness is associated with cognitive deficiency in hypertensive patients with elevated central systolic blood pressure.

BACKGROUND: The role of hypertension in the loss of cognitive function is controversial. Relationships between hypertension and increases in cerebral vascular resistance, diffused lesions and multiple lacunar infarcts of the white matter are well known. Thus, the objectives of this study were: to evaluate the relationship between hypertension and cognitive dysfunction (CD), identify risk factors and determine the association between early markers of vascular disease and CD in hypertensive individuals. METHODS: Two hundred individuals aged between 40 and 80 years old were evaluated in this cross-sectional prospective study. Fifty participants were controls (CT). The remaining 150 hypertensive patients were subdivided into two groups, those with CD (HCD) and those without CD (HNCD). All participants underwent clinical evaluations and biochemical blood tests were performed. CD was investigated using the Mini Mental State Examination (MMSE) following the guidelines for its use in Brazil. The impact of hypertension on the arterial bed was assessed by identifying and measuring changes in the intima-media thickness (IMT) by vascular ultrasonography of the carotid arteries and analyses of the central blood pressure and Augmentation Index by applanation tonometry of the radial artery. RESULTS: There were no significant differences in the total cholesterol, high-density lipoprotein cholesterol and triglycerides plasma concentrations between the three groups. The serum creatinine and estimated glomerular filtration rate were within normal ranges for all three groups. A significantly lower MMSE score was recorded for the HCD Group compared to the HNCD and CT Groups (p-value < 0.05).The IMT was significantly different between the HNCD and HCD Groups (p-value = 0.0124). A significant difference in the IMT was also observed between hypertensive patients and the CT Group (p-value < 0.0001). Age, low-density cholesterol, high-density cholesterol, triglycerides and IMT increased the Odds Ratio for cognitive dysfunction.The central systolic pressure was significantly higher in the HCD and HNCD Groups compared to CT Group (p-value < 0.0001). CONCLUSIONS: Hypertensive patients with CD have changes in the vascular morphology characterized by an increased carotid IMT, enhanced atherosclerotic lipid profile and impaired hemodynamic functional manifested by elevated central systolic blood pressure.

Effect of Sequential Nephron Blockade versus Dual Renin-Angiotensin System Blockade Plus Bisoprolol in the Treatment of Resistant Hypertension, a Randomized Controlled Trial (Resistant Hypertension on Treatment - ResHypOT).

Introduction: Hypertension is the most important modifiable risk factor for cardiovascular disease and a leading public health concern. Objectives: The primary aim was to compare sequential nephron blockade (SNB) versus dual renin-angiotensin system blockade (DRASB) plus bisoprolol in patients with resistant hypertension to observe reductions in systolic and diastolic blood pressure (SBP and DBP) levels after 20 weeks of treatment. Material and Methods: This trial was an open-label, prospective, randomized, parallel-group, clinical study with optional drug up-titration. Participants were evaluated during five visits at 28-day intervals. Results: The mean age was 55.5 years in the SNB and 58.4 years in the DRASB + bisoprolol group (p=NS). Significant office BP reductions were observed in both groups. SNB group, SBP decreased from 174.5±21.0 to 127.0±14.74 mmHg (p<0.0001), and DBP decreased from 105.3±15.5 to 78.11±9.28 mmHg (p<0.0001). DRASB group, SBP decreased from 178.4±21.08 to 134.4 ± 23.25 mmHg (p<0.0001) and DBP decreased from 102.7±11.07 to 77.33±13.75 mmHg (p<0.0001). Ambulatory blood pressure monitoring (ABPM) showed also significant SBP and DBP reductions in both groups (p<0.0001). Conclusion: In patients with RHTN adherent to treatment, SNB and DRASB plus bisoprolol showed excellent therapeutic efficacy, although SNB was associated with earlier SBP reduction.

Predictive Factors for Target Organ Injuries in Hypertensive Individuals.

BACKGROUND: The causal relationship between systemic arterial hypertension and target organ damage (TOD) is well known, as well as the association with cardiovascular risk factors (CV). Ambulatory blood pressure monitoring (ABPM) is important in monitoring hypertension and assessing the risk of TOD. OBJECTIVE: To evaluate the relationship between blood pressure (BP) and clinical and biochemical parameters in the development of TOD in hypertensive patients. METHODS: This was a retrospective cohort study with 162 hypertensive patients followed for an average period of 13 years. The TOD investigated were left ventricular hypertrophy (LVH), microalbuminuria, coronary artery disease (CAD) and stroke. Blood pressure was assessed by ABPM and LVH using echocardiogram and electrocardiogram, respectively. Biochemical-metabolic tests and 24-hour microalbuminuria were performed at baseline and follow-up. The P-value <0.05 was considered significant. RESULTS: The average age was 69±11.8 years, with a predominance of women (64.8%), white ethnicity (79.6%) and diabetics (78.4%). ABPM showed a significant reduction in BP values during follow-up, although without association with TOD (microalbuminuria, stroke, and CAD), except for LVH that showed a correlation with sleep BP ≥120/70 mmHg (P=0.044). The most frequent TODs were LVH (29.6%), microalbuminuria (26.5%), CAD (19.8%) and stroke (17.3%). In the follow-up, there was an association between LVH and diabetes; microalbuminuria was associated with diabetes and triglycerides; stroke was associated with HDL-cholesterol (HDL-c), microalbuminuria and carotid disease. CAD showed a relationship with age and HDL-c. CONCLUSION: Predictive factors for TOD are age, microalbuminuria, diabetes, HDL-c, triglycerides and carotid disease. Nocturnal BP is correlated with LVH. The absence of a relationship between ABPM and other TODs can be explained by the use of effective drugs, improvement of metabolic and blood pressure parameters.

Evidence of Nonadherence in Cases of Pseudoresistant Hypertension.

Resistant hypertension (RH) is characterized by the use of three or more antihypertensive drugs without reaching the goal of controlling blood pressure (BP). For a definitive diagnosis of RH, it is necessary to exclude causes of pseudoresistance, including the white-coat effect, errors in BP measurement, secondary hypertension, therapeutic inertia, and poor adherence to lifestyle changes and pharmacological treatment. Herein, we report the history of a patient with long-standing uncontrolled BP, even when using seven antihypertensive drugs. Causes of secondary hypertension that justified the high BP levels were investigated, in addition to the other causes of pseudo-RH. In view of the difficult-to-control BP situation, it was decided to hospitalize the patient for better investigation. After 5 days, he had BP control with practically the same medications previously used. Finally, all factors related to the presence of pseudo-RH are discussed, especially poor adherence to treatment. Poor adherence to antihypertensive treatment is common in daily medical practice, and its investigation is of fundamental importance for better management of BP.

Evaluation of 1-Year Follow-up of Patients Included in the Registry of Clinical Practice in Patients at High Cardiovascular Risk (REACT). / Avaliação do Seguimento de 1 Ano dos Pacientes Incluídos no Registro da Prática Clínica em Pacientes de Alto Risco Cardiovascular (REACT).

BACKGROUND: In clinical practice, there is evidence of failure to prescribe evidence-based therapies for patients at high cardiovascular risk. However, in Brazil, data on 1-year outcomes of these patients remain insufficient. OBJECTIVES: To describe the use of evidence-based therapies and the occurrence of major cardiovascular outcomes and their major predictors in a 12-month follow-up of a Brazilian multicenter registry of patients at high cardiovascular risk. METHODS: This prospective observational study documented the outpatient clinical practice of managing patients over 45 years of age and of high cardiovascular risk in both primary and secondary prevention. Patients were followed-up for 1 year, and the prescription of evidence-based therapies and the occurrence of major cardiovascular events (myocardial infarction, stroke, cardiac arrest, and cardiovascular death) were assessed. P-values < 0.05 were considered statistically significant. RESULTS: From July 2010 to August 2014, a total of 5076 individuals were enrolled in 48 centers, 91% of the 4975 eligible patients were followed-up in cardiology centers, and 68.6% were in secondary prevention. At 1 year, the concomitant use of antiplatelet agents, statins, and angiotensin-converting enzyme inhibitors reduced from 28.3% to 24.2% (p < 0.001). Major cardiovascular event rate was 5.46%, and the identified predictors were age, patients in secondary prevention, and diabetic nephropathy. CONCLUSIONS: In this large national registry of patients at high cardiovascular risk, risk predictors similar to those of international registries were identified, but medical prescription adherence to evidence-based therapies was inferior and significantly worsened at 1 year. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

FUNDAMENTO: Na prática clínica, há evidências de falhas na prescrição de terapias baseadas em evidências para pacientes de alto risco cardiovascular. Entretanto, no Brasil, ainda são insuficientes os dados sobre a evolução ao longo de 1 ano desses pacientes. OBJETIVOS: Descrição no acompanhamento de 12 meses da utilização de terapias baseadas em evidência e da ocorrência de desfechos cardiovasculares maiores e seus principais preditores em um registro brasileiro multicêntrico de pacientes de alto risco cardiovascular. MÉTODOS: Estudo observacional prospectivo que documentou a prática clínica ambulatorial de indivíduos acima de 45 anos e de alto risco cardiovascular tanto em prevenção primária como secundária. Os pacientes foram seguidos por 1 ano e avaliou-se a prescrição de terapias baseadas em evidência e a ocorrência de eventos cardiovasculares maiores (infarto agudo do miocárdio [IAM], acidente vascular cerebral [AVC], parada cardíaca e mortalidade por causa cardiovascular). Valores de p < 0,05 foram considerados estatisticamente significantes. RESULTADOS: De julho de 2010 até agosto de 2014, 5.076 indivíduos foram incluídos em 48 centros, sendo 91% dos 4.975 pacientes elegíveis acompanhados em centros de cardiologia e 68,6% em prevenção secundária. Em 1 ano, o uso concomitante de antiplaquetários, estatinas e inibidores da enzima conversora de angiotensina (IECA) reduziu de 28,3% para 24,2% (valor de p < 0,001). A taxa de eventos cardiovasculares maiores foi de 5,46%, e os preditores identificados foram: idade, pacientes em prevenção secundária e nefropatia diabética. CONCLUSÕES: Neste grande registro nacional de pacientes de alto risco cardiovascular, foram identificados preditores de risco semelhantes aos registros internacionais, porém a adesão da prescrição médica a terapias baseadas em evidência esteve abaixo dos dados da literatura internacional e apresentou piora significativa em 1 ano. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

Randomized Study Comparing Vildagliptin vs Glibenclamide on Glucose Variability and Endothelial Function in Patients with Type 2 Diabetes Mellitus and Hypertension.

BACKGROUND: Glucose variability (GV) is considered an important factor for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). High GV causes endothelial dysfunction and increased oxidative stress. Dipeptidyl peptidase-4 (DPP-4) inhibitors may improve endothelial function and decrease GV. The aim of this study was to investigate the effects of vildagliptin, a DPP-4 inhibitor, compared with glibenclamide in GV and endothelial function in patients with T2DM and arterial hypertension. METHODS: This is a prospective, randomized, open and drug-controlled study. Fifty patients older than 35 years with T2DM and hypertension without CVD were randomized to receive vildagliptin (n=25) or glibenclamide (n=25), both in added-on metformin. Laboratory tests and analysis of endothelial function were performed before and 12 weeks after treatment. Endothelial function, defined by reactive hyperemia index (RHI), was analyzed by peripheral artery tonometry (endo-PAT2000). GV was evaluated by capillary glucose with intermittent monitoring device, six measurements per day, for three days, before and after treatment. The median of standard deviation (SD) of mean blood glucose (MBG) was used to evaluate GV. RESULTS: GV decreased in the vildagliptin group (35.2 to 30.7, P=0.037) but did not change with glibenclamide (37.6 to 37.5, P=0.765). Glycated hemoglobin was similar in both groups. MBG decreased only in glibenclamide group, without difference with vildagliptin group (P=0.374). There were no changes in the RHI in both groups and there was no correlation between GV and RHI (P=0.658). CONCLUSION: Vildagliptin reduces GV; however, the action on endothelial function was not demonstrated. In addition, there was no correlation between GV and endothelial function.

Effect of vildagliptin versus glibenclamide on endothelial function and arterial stiffness in patients with type 2 diabetes and hypertension: a randomized controlled trial.

AIMS: Several trials have reported that dipeptidyl peptidase-4 (DPP-4) inhibitors, used to treat type 2 diabetes (T2DM), improve endothelial function. The current study investigated the effects of vildagliptin, a DPP-4 inhibitor, compared to glibenclamide on endothelial function, arterial stiffness, and blood pressure in patients with T2DM and hypertension. METHODS: Patients aged over 35 years with T2DM and hypertension, but without cardiovascular disease, were randomly allocated to treatment with vildagliptin (n = 25) or glibenclamide (n = 25). Both groups took metformin. Endothelial function was evaluated by peripheral artery tonometry (Endo-PAT 2000) to calculate the reactive hyperemia index (RHI) and arterial stiffness. Primary outcome was change in the RHI after 12 weeks of treatment. Twenty-four-hour non-invasive ambulatory blood pressure monitoring was performed using a Mobil-O-Graph® 24-h PWA monitor. Arterial stiffness was assessed using the augmentation index corrected for 75 bpm (AIx75), pulse wave velocity (PWV) and central systolic blood pressure (cSBP). RESULTS: There were no changes in the RHI in the vildagliptin group (before 2.35 ± 0.59; after 2.24 ± 0.60; p value = NS) or in the glibenclamide group (before 2.36 ± 0.52; after 2.34 ± 0.50; p value = NS), with no differences between groups (p value = NS). There was also no difference between vildagliptin and glibenclamide treatment in respect to AIx75 (p value = NS), cSBP (p value = NS) or PWV (p value = NS). CONCLUSIONS: Vildagliptin and glibenclamide similarly do not change the endothelial function and arterial stiffness after 12 weeks of treatment in diabetic and hypertensive patients without cardiovascular disease. Thus, vildagliptin has a neutral effect on vascular function. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02145611, registered on 11 Jun 2013.

Resistant Hypertension On Treatment (ResHypOT): sequential nephron blockade compared to dual blockade of the renin-angiotensin-aldosterone system plus bisoprolol in the treatment of resistant arterial hypertension - study protocol for a randomized controlled trial.

BACKGROUND: Resistant 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/DESIGN: This 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. DISCUSSION: In 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 REGISTRATION: Sequential 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.

Spotlight on valsartan-sacubitril fixed-dose combination for heart failure: the evidence to date.

Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin-angiotensin-aldosterone system. Neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds. The inhibition of neprilysin has been a therapeutic target for several drugs tested in cardiovascular disease, mainly for heart failure and/or hypertension. However, side effects and a lack of efficacy led to discontinuation of their development. LCZ696 is a first-in-class neprilysin- and angiotensin-receptor inhibitor that has been developed for use in heart failure. This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan). The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease.

HIPERTENSÃO E DIABETES: CONCEITOS ATUAIS NA TERAPÊUTICA / HYPERTENSION AND DIABETES: CURRENT CONCEPTS IN THERAPEUTICS

Diabetes mellitus tipo 2 (DM) cursa com alta prevalência na população, acometendo cerca de 9,3% da população mundial (463 milhões de indivíduos). Devido ao crescimento dos casos e envelhecimento populacional, estima-se que o número de diabéticos será superior a 628 milhões em 2045. Dados de 2013 estimam que 6,2% da população brasileira acima dos 18 anos de idade tenham diabetes. Rápida urbanização, transição epidemiológica, fator nutricional, estilo de vida sedentário, excesso de peso, crescimento e envelhecimento populacional são fatores associados ao aumento da prevalência. Geralmente, ao tempo do diagnóstico do DM, a hipertensão arterial sistêmica (HAS) está presente em 50% dos diabéticos. O artigo discute aspectos relacionados à fisiopatogenia do diabetes e hipertensão, as metas de pressão arterial e as principais abordagens terapêuticas no tratamento da hipertensão arterial no paciente diabético, de acordo com as diretrizes mais recentes

Type 2 Diabetes mellitus presents high prevalence in the population, responding for about 9.3% in the world population (463 million individuals). Due to cases increase and aging, it is estimated that the number of diabetic subjects will be higher than 628 million in 2045. Data of 2013 show that 6,2% of Brazilian population higher 18 years-old have diabetes. Fast urbanization, epidemiological transition, nutritional factor, physical inactivity, overweight, population growth and aging are factors associated to increase of prevalence. Generally, when of diabetes diagnosis, hypertension is present in 50% of diabetic individuals. The article discusses aspects of pathophysiology of hypertension and diabetes, the targets of blood pressure and the principal therapeutic approaches of treatment of hypertension in the diabetic patient, in according to recenter guidelines

Chlorthalidone Plus Amiloride Reduces the Central Systolic Blood Pressure in Stage 1 Hypertension Patients.

BACKGROUND: Hypertension reduction strategies use blood pressure in the brachial artery as the primary endpoint. Individuals who achieve the target blood pressure reduction with antihypertensive treatment have residual cardiovascular risk attributed to the difference in pressure between the aorta and brachial artery. Antihypertensive treatment affects the intrinsic properties of the vascular wall and arterial stiffness markers and consequently the central pressure. Recent publications stress the importance of adequate control of the central compared to peripheral blood pressure. Related clinical implications suggest that individuals with normal peripheral but high central blood pressure should not receive antihypertensive drugs that act on the central pressure. Therefore, they are at greater cardiovascular risk. The aim of the study was to evaluate the effect of treatment with a thiazide diuretic versus losartan on the central blood pressure in stage 1 hypertensive patients. METHODS: Twenty-five patients were randomized to the chlorthalidone 25 mg/amiloride 5 mg group (q.d.) and 25 patients received losartan 50 mg (b.i.d). The central systolic blood pressure (CSBP) and augmentation index (AIx 75) were assessed using applanation tonometry. The paired t-test was used to compare the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), CSBP and AIx 75 between the thiazide and losartan groups at baseline and after 6 months of treatment. RESULTS: Significant reductions in CSBP (123.3 ± 14.2 vs. 113.4 ± 111.4, P = 0.0103) and AIx 75 (87.7 ± 9.6 vs. 83.8 ± 8.9, P = 0.0289) were observed after 6 months of drug treatment with chlorthalidone 25 mg/amiloride 5 mg (q.d.). The administration of losartan 50 mg (b.i.d) did not reduce the CSBP and there were insignificant changes in the AIx 75. CONCLUSIONS: Six-month treatment of chlorthalidone/amiloride but not losartan reduces the CSBP and AIx 75 in adults with stage 1 hypertension.