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Luiz Tadeu Giollo-Junior,1,2 Luciana Neves Cosenso-Martin,2 Valquiria da Silva Lopes,2 Manoel Paz Landim,2 Leticia Aparecida Barufi Fernandes,2 Kleber Aparecido de Oliveira,2 Amanda Oliva Spaziani,2 Aleandra Polegati Santos,2 Marco Antonio Silva,2 Juan Carlos Yugar-Toledo,2 Jose Fernando Vilela-Martin2 1General Hospital at Brazilian Army, Curitiba, Parana, Brazil; 2Hypertension Clinic - Internal Medicine Department, State Medical School in Sao Jose do Rio Preto (FAMERP), Sao Jose do Rio Preto, São Paulo, BrazilCorrespondence: Jose Fernando Vilela-Martin, Hypertension Clinic - Internal Medicine Department, State Medical School in Sao Jose do Rio Preto (FAMERP), Ave Brig. Faria Lima 5416, São Jose do Rio Preto, 15090-000, São Paulo, Brazil, Email vilelamartin@uol.com.brAbstract: 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.Keywords: resistant hypertension, blood pressure, central hemodynamic, arterial stiffness, non-pharmacological therapy

Elizabeth do Espirito Santo Cestario,1,&ast; Jose Fernando Vilela-Martin,1,&ast; Luciana Neves Cosenso-Martin,1 Tatiane Azevedo Rubio,1 Jessica Rodrigues Roma Uyemura,1 Valquiria da Silva Lopes,1 Letícia Aparecida Barufi Fernandes,1 Lucia Helena Bonalume Tacito,2 Heitor Moreno Junior,3 Juan Carlos Yugar-Toledo1,&ast; 1Hypertension Clinic, Internal Medicine Department, Medical School in São José Do Rio Preto (FAMERP), São Paulo, Brazil; 2Endocrinology Division, Internal Medicine Department, Medical School in São José Rio Preto (FAMERP), São Paulo, Brazil; 3Cardiovascular Pharmacology Laboratory, Faculty of Medical Sciences, State University of Campinas (UNICAMP), São Paulo, Brazil&ast;These authors contributed equally to this workCorrespondence: Jose Fernando Vilela-Martin, Ave Brig Faria Lima 5416, Sao Jose do Rio Preto, São Paulo, SP, 15090-000, Brazil, Tel +55 17 32015727, Email vilelamartin@uol.com.brIntroduction: 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.Keywords: resistant hypertension, natriuretic agents, dual blockade of the renin-angiotensin system, bisoprolol

Manoel Paz Landim, Luciana Neves Cosenso-Martin, Aleandra Polegati Santos, Jessica Rodrigues Roma Uyemura, Leticia Barufi Fernandes, Valquiria da Silva Lopes, Juan Carlos Yugar-Toledo, Jose Fernando Vilela-Martin Internal Medicine Department, State Medical School at Sao Jose do Rio Preto (FAMERP), Sao Jose do Rio Preto, Sao Paulo, BrazilCorrespondence: Jose Fernando Vilela-MartinInternal Medicine Department, State Medical School at Sao Jose do Rio Preto (FAMERP), Ave Brig Faria Lima 5416, Vila Sao Pedro, Sao Jose do Rio Preto, 15090-000, Sao Paulo, BrazilEmail vilelamartin@uol.com.brBackground: 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.Keywords: arterial hypertension, ambulatory blood pressure monitoring, left ventricular hypertrophy, albuminuria, stroke, coronary artery disease

João Marcos de Menezes Zanatta, Luciana Neves Cosenso-Martin, Valquíria da Silva Lopes, Jéssica Rodrigues Roma Uyemura, Aleandra Marton Polegati Santos, Manoel Ildefonso Paz Landim, Juan Carlos Yugar-Toledo, José Fernando Vilela-Martin Internal Medicine Department, State Medical School at Sao Jose Do Rio Preto (FAMERP), Sao Jose Do Rio Preto, Sao Paulo, BrazilCorrespondence: José Fernando Vilela-MartinInternal Medicine Department, State Medical School at Sao Jose Do Rio Preto (FAMERP), 5416 Avenida Brigadeiro Faria Lima, Sao Jose Do Rio Preto, SP, 15090-000, BrazilTel +55 17 3201-5727Email vilelamartin@uol.com.brAbstract: 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.Keywords: hypertension, resistant hypertension, medication adherence

Luciana Neves Cosenso-Martin, Lais Yumi Takaoka, Jose Fernando Vilela-Martin Internal Medicine Division, State Medical School at Sao Jose do Rio Preto (FAMERP), Hospital de Base, Sao Jose do Rio Preto, Sao Paulo, BrazilCorrespondence: Jose Fernando Vilela-MartinState Medical School at Sao Jose do Rio Preto (FAMERP), Hospital de Base, Ave Brig. Faria Lima 5416, Sao Jose do Rio Preto, Sao Paulo 15090-000, BrazilTel +55 17 32015727Email vilelamartin@uol.com.brBackground: 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.Keywords: type 2 diabetes, hypertension, glycemic variability, vascular endothelium, dipeptidyl-peptidase IV inhibitors, arterial stiffness

José Fernando Vilela-Martin Internal Medicine Department, São José do Rio Preto State Medical School (FAMERP), São José do Rio Preto, Brazil Abstract: 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. Keywords: heart failure, vasopeptidase, natriuretic peptides, neprilysin, sacubitril, valsartan

Obesity is a complex chronic disease that affects millions of people worldwide. There is still significant stigma associated with it, which can lead to discrimination and create additional barriers for people who are already in treatment. On the other hand, it is noted that it can have serious implications for health and predisposition to noncommunicable chronic diseases. In this sense, the objective of this study was to carry out a narrative review involving all current elements for understanding, prevention, treatment, and debate of stigmas related to obesity. A search was conducted in 2024 for original articles, randomized or nonrandomized clinical trials, systematic reviews, meta-analyses, and guidelines in the following databases: Pubmed, Scielo, Web of Science, CrossRef, and Google Scholar. The publication period was from 2014 to 2024. Obesity is influenced by a complex combination of genetic, environmental, and psychological factors. It is encouraging to see that various emerging points have been identified across different fields such as histology, physiology, genetics, weight loss, and public policy. These obesity areas certainly warrant attention and future studies. Researchers can delve into these topics to deepen their understanding and potentially uncover novel insights. The management should be multifactorial and individualized for each patient. Public policies also play a crucial role in combating obesity, including health promotion, prevention of excessive weight gain, early diagnosis, and proper care of patients. It is crucial that society begins to see the disease as an extremely complex element and not as a moral failure or lack of willpower. This requires a change in the way people talk about obesity, as well as practices that support people instead of stigmatizing them. Obesity does not have a specific address, color, or race. It belongs to everyone and should be regarded as a global public health problem., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 Šídák 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.

Introduction: Equations can calculate pulse wave velocity (ePWV) from blood pressure values (BP) and age. The ePWV predicts cardiovascular events beyond carotid-femoral PWV. We aimed to evaluate the correlation between four different equations to calculate ePWV., Methods: The ePWV was estimated utilizing mean BP (MBP) from office BP (MBPOBP) or 24-hour ambulatory BP (MBP24-hBP). We separated the whole sample into two groups: individuals with risk factors and healthy individuals. The e-PWV was calculated as follows: [Formula: see text] [Formula: see text] We calculated the concordance correlation coefficient (Pc) between e1-PWVOBP vs e2-PWVOBP, e1-PWV24-hBP vs e2-PWV24-hBP, and mean values of e1-PWVOBP, e2-PWVOBP, e1-PWV24-hBP and e2-PWV24-hBP. The multilevel regression model determined how much the ePWVs are influenced by age and MBP values., Results: We analyzed data from 1541 individuals; 1374 ones with risk factors and 167 healthy ones. The values are presented for the entire sample, for risk-factor patients and for healthy individuals respectively. The correlation between e1-PWVOBP with e2-PWVOBP and e1-PWV24-hBP with e2-PWV24-hBP was almost perfect. The Pc for e1-PWVOBP vs e2-PWVOBP was 0.996 (0.995-0.996), 0.996 (0.995-0.996), and 0.994 (0.992-0.995); furthermore, it was 0.994 (0.993-0.995), 0.994 (0.994-0.995), 0.987 (0.983-0.990) to the e1-PWV24-hBP vs e2-PWV24-hBP. There were no significant differences between mean values (m/s) for e1-PWVOBP vs e2-PWVOBP 8.98±1.9 vs 8.97±1.8; p = 0.88, 9.14±1.8 vs 9.13±1.8; p = 0.88, and 7.57±1.3 vs 7.65±1.3; p = 0.5; mean values are also similar for e1-PWV24-hBP vs e2-PWV24-hBP, 8.36±1.7 vs 8.46±1.6; p = 0.09, 8.50±1.7 vs 8.58±1.7; p = 0.21 and 7.26±1.3 vs 7.39±1.2; p = 0.34. The multiple linear regression showed that age, MBP, and age2 predicted more than 99.5% of all four e-PWV., Conclusion: Our data presents a nearly perfect correlation between the values of two equations to calculate the estimated PWV, whether utilizing office or ambulatory blood pressure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

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.

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).

Introduction: Hypertension and kidney function are closely related. However, there are few studies on renal function during acute elevation of blood pressure (BP), denominated hypertensive crisis (HC)., Objectives: To evaluate the relationship between renal function and inflammatory cytokines in HC, subdivided into hypertensive urgency (HUrg) and emergency (HEmerg)., Materials and Methods: This cross-sectional study was carried out in 74 normotensive (NT) and 74 controlled hypertensive individuals (ContrHT) followed up in outpatient care. Additionally, 78 subjects with hypertensive emergency (HEmerg) and 50 in hypertensive urgency (HUrg), attended in emergency room, were also evaluated. Hypertensive crisis was classified into HEmerg, defined by systolic blood pressure (BP) ≥ 180 mmHg and/or diastolic BP ≥ 120 mmHg in presence of target-organ damage (TOD), and HypUrg, clinical situation with BP elevation without TOD. The glomerular filtration rate (eGFR) was estimated, and cytokine levels were measured. Statistical analysis was performed using the Kruskal-Wallis or Mann-Whitney test and Spearman's correlation, with significant differences p -value < 0.05., Results: The median age was 53.5 years in the NT group (52 female), 61 years in the ContrHT group (52 female), and 62.5 years in the HC group (63 female) ( p -value < 0.0001). The median BP was 118.5/75 mmHg for NT, 113.5/71 for ContrHT, and 198.5/120 mmHg for HC, respectively ( p -value < 0.0001 among groups). BP and heart rate levels were significantly higher in the HC group compared to the NT and ContrHT groups ( P < 0.001 for all). The eGFR was significantly lower in HC group compared to the NT and ContrHT groups. The cytokine levels were higher in the HEmerg and HUrg groups compared to ContrHT group ( P < 0.0001, except for IL-1β in HUrg vs. ContrHT), without difference between the acute elevation of BP groups. Thus, all cytokines were significantly elevated in patients with HC compared to the control groups (NT and ContrHT). There was a negative correlation between eGFR and the cytokines (IL-1β, IL-6, IL-8, IL-10, and TNF-α) in the HC group., Conclusion: Elevated inflammatory cytokines are associated with reduced eGFR in individuals with HC compared to control groups, suggesting that the inflammatory process participates in the pathogenesis of acute elevations of BP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Andrade, Aguiar, Mansor, Valente, Souza, Lopes, Fernandes, Godoy, Yugar-Toledo, Cosenso-Martin and Vilela-Martin.)

Evidence has shown that women with type 2 diabetes mellitus (T2DM) have a greater risk of cardiovascular complications compared with men, but this sex difference is not clearly understood. This study assessed the microvascular function and circulatory biomarkers in postmenopausal women (PMW) with T2DM compared with diabetic men and their non-diabetic counterparts. Sixty participants were divided into nondiabetic PMW, PMW with T2DM, non-diabetic men, and diabetic men. Microvascular function was assessed using non-invasive equipment (EndoPAT®) and reported as reactive hyperemia index (RHI). Anthropometric and cardiovascular parameters were also measured. Two-way ANOVA was performed using sex (women or men) and T2DM (non-diabetic and diabetic) as the two factors. RHI impairment (1.97±0.14) was detected in diabetic PMW compared with women without T2DM (2.5±0.13) accompanied by lower adiponectin levels (T2DM: 9.3±1.2 and CTL: 13.8±1.8 ug/mL, P<0.05). An increase in the Nε-carboxymethyllysine (CML), nitrate/nitrite, and C-reactive protein (CRP) levels were observed in diabetic PMW compared to the other groups. Although a poor glycemia control was seen in diabetic men, neither RHI nor circulatory biomarkers were affected by T2DM. Multiple linear regression stratified by sex and T2DM identified some variables with RHI only in PMW with T2DM: HbA1c (P=0.003), body mass index (P=0.029), CML (P=0.032), and CRP (P=0.006). Diabetic PMW were more susceptible to the deleterious effects of hyperglycemia than men, showing microvascular dysfunction with high levels of pro-inflammatory mediators (CML and CRP) and a lower adiponectin concentration.

Aims: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of JNC 7 Stage I hypertension in patients with type 2 diabetes mellitus., Methods: In an a priori subgroup analysis of a randomized, double-blind, controlled trial, volunteers aged 30-70 years, with stage I hypertension and diabetes mellitus, were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 47) or 50 mg of losartan (N = 50), and followed for 18 months in 21 clinical centers. If BP remained uncontrolled after three months, study medication dose was doubled, and if uncontrolled after six months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg BID) were added as open label drugs in a progressive fashion., Results: Systolic BP decreased to a greater extent in participants allocated to diuretics compared to losartan (P < 0.001). After 18 months of follow-up, systolic BP was 128.4 ± 10.3 mmHg in the diuretic group versus 133.5 ± 8.0 in the losartan group (P < 0.01). In the diuretic group, 36 out of 43 participants (83.7%) had a JNC 7 normal BP, compared to 31/47 (66%) in the losartan group (P = 0.089). Serum cholesterol was higher in the diuretic arm at the end of the trial. Other biochemical parameters and reports of adverse events did not differ by treatment., Conclusions: Treatment of hypertension based on a combination of chlorthalidone and amiloride is more effective for BP lowering compared to losartan in patients with diabetes mellitus and hypertension., Trial Registration: Clinical trials registration number: NCT00971165.

Objectives: This observational, cross-sectional study based aimed to test whether heart failure (HF)-disease management program (DMP) components are influencing care and clinical decision-making in Brazil., Methods: The survey respondents were cardiologists recommended by experts in the field and invited to participate in the survey via printed form or email. The survey consisted of 29 questions addressing site demographics, public versus private infrastructure, HF baseline data of patients, clinical management of HF, performance indicators, and perceptions about HF treatment., Results: Data were obtained from 98 centers (58% public and 42% private practice) distributed across Brazil. Public HF-DMPs compared to private HF-DMP were associated with a higher percentage of HF-DMP-dedicated services (79% vs 24%; OR: 12, 95% CI: 94-34), multidisciplinary HF (MHF)-DMP [84% vs 65%; OR: 3; 95% CI: 1-8), HF educational programs (49% vs 18%; OR: 4; 95% CI: 1-2), written instructions before hospital discharge (83% vs 76%; OR: 1; 95% CI: 0-5), rehabilitation (69% vs 39%; OR: 3; 95% CI: 1-9), monitoring (44% vs 29%; OR: 2; 95% CI: 1-5), guideline-directed medical therapy-HF use (94% vs 85%; OR: 3; 95% CI: 0-15), and less B-type natriuretic peptide (BNP) dosage (73% vs 88%; OR: 3; 95% CI: 1-9), and key performance indicators (37% vs 60%; OR: 3; 95% CI: 1-7). In comparison to non- MHF-DMP, MHF-DMP was associated with more educational initiatives (42% vs 6%; OR: 12; 95% CI: 1-97), written instructions (83% vs 68%; OR: 2: 95% CI: 1-7), rehabilitation (69% vs 17%; OR: 11; 95% CI: 3-44), monitoring (47% vs 6%; OR: 14; 95% CI: 2-115), GDMT-HF (92% vs 83%; OR: 3; 95% CI: 0-15). In addition, there were less use of BNP as a biomarker (70% vs 84%; OR: 2; 95% CI: 1-8) and key performance indicators (35% vs 51%; OR: 2; 95% CI: 91,6) in the non-MHF group. Physicians considered changing or introducing new medications mostly when patients were hospitalized or when observing worsening disease and/or symptoms. Adherence to drug treatment and non-drug treatment factors were the greatest medical problems associated with HF treatment., Conclusion: HF-DMPs are highly heterogeneous. New strategies for HF care should consider the present study highlights and clinical decision-making processes to improve HF patient care.

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).

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.

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.

Background: To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood pressure (BP) in adults with prehypertension., Methods: The PREVER-prevention trial was a randomized, parallel, double-blinded, placebo-controlled trial, with 18 months of follow-up, conducted at 21 academic medical centers in Brazil. Of 1772 individuals evaluated for eligibility, 730 volunteers with prehypertension who were aged 30-70 years, and who did not reach optimal blood pressure after 3 months of lifestyle intervention, were randomized to a fixed association of chlorthalidone 12.5 mg and amiloride 2.5 mg or placebo once a day. The main outcomes were the percentage of participants who achieved an optimal level of BP., Results: A total of 372 participants were randomly allocated to diuretics and 358 to placebo. After 18 months of treatment, optimal BP was noted in 25.6% of the diuretic group and 19.3% in the placebo group (P < 0.05). The mean net reduction in SBP and DBP for the diuretic group compared with placebo was 2.8 mmHg (95% CI 1.1 to 4.5) and 1.1 mmHg (95% CI -0.09 to 2.4), respectively. Most participants in the active treatment group (74.5%) and in the placebo group (80.7%) continued to have BP in the prehypertension range or progressed to hypertension., Conclusion: Low-dose diuretic therapy increased the probability of individuals with prehypertension to achieve optimal BP but most of those treated continued to have a BP in the prehypertension range or progressed to having overt hypertension.

Purpose of Review: Resistant hypertension (RHTN) is a condition in which besides the antihypertensive therapy using at least three different drugs (including a diuretics), brachial blood pressure does not reach the target (e.g., 140/90 mmHg)., Recent Findings: Despite the diversity of clinical presentations, we divide RHTN in two major groups according to blood pressure and number of drugs taken: controlled (C-RHTN) and uncontrolled (UC-RHTN) resistant hypertension, with refractory hypertension (RfHTN) included in the latter subgroup. Both C-RHTN and UC-RHTN are heterogenic and complex syndromes. To better approach this matter, the some pathophysiological mechanisms (increased volemia, hyperactivity, plasma cortisol, adipocitokines, and other pro-inflammatory factors), have a pivotal clinical role. Some features (African ethnic, obesity, age > 60, LV hypertrophy, and vascular stiffness) increase the risk of refractoriness as well as worst prognosis. Based on increased target organ damage, cardiovascular risk and events will be addressed in this review. Our conclusion is that although both C-RHTN and UC-RHTN are extreme phenotypes of hard-to-control BP, some mechanisms of the disease and clinical expressions are distinct. According to these differences, "UC-RHTN and C-RHTN are not in the same bag."

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.

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.

Background: Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER-Prevention) trial aimed to evaluate the efficacy and safety of a low-dose diuretic for the prevention of hypertension and end-organ damage., Methods and Results: This randomized, parallel, double-blind, placebo-controlled trial was conducted in 21 Brazilian academic medical centers. Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new-onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms. The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo (hazard ratio 0.56, 95% CI 0.38-0.82), resulting in a cumulative incidence of 11.7% in the diuretic arm versus 19.5% in the placebo arm (P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow-Lyon voltage and voltage-duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02)., Conclusions: A combination of low-dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension., Clinical Trial Registration: URL: http://www.ClinicalTrials.gov, www.ensaiosclinicos.gov. Unique identifiers: NCT00970931, RBR-74rr6s., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

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.

Purpose: To investigate the effect of transcutaneous electrical nerve stimulation (TENS) on the arterial stiffness in healthy young adult and middle-aged men using the augmentation index (AI-x) and hemodynamic measures., Methods: Twenty-four men (12 aged 27·25 ± 5·53 years and 12 aged 54·83 ± 5·10 years) were randomly allocated to two subgroups: TENS or placebo in ganglion region for 45 min. The AI-x and hemodynamic measures [late systolic blood pressure (SBP), central blood pressure (CBP), difference between P1 and P2 (ΔP) and tension time index (TTI)] were determined before and after protocols., Results: TENS resulted in reduction of SBP in younger adults (TENSpre: 111 ± 2; post: 105 ± 2·2 mm Hg; PLACEBOpre: 113 ± 1·8; post: 114 ± 2·5 mm Hg; GEE, P<0·01), whereas no difference was found in middle-aged group. TENS also resulted in reduction of AI-x younger adults group (TENSpre: 56 ± 2·8; post: 53 ± 2%; PLACEBOpre: 55 ± 3; post: 58 ± 2·5%; GEE, P<0·01). ΔP and TTI were significantly decreased after the application of TENS in both groups, but significantly greater reductions in TTI and the SBP/CBP ratio were found in the group of younger adults., Conclusions: The acute application of ganglion TENS attenuated arterial stiffness in younger adults as well as hemodynamic measures in the middle-aged group. This method could emerge as effective therapy for the management of arterial blood pressure., (© 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Objectives: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of stage I hypertension., Methods: In a randomized, double-blind, controlled trial, 655 participants were followed for 18 months in 21 Brazilian academic centers. Trial participants were adult volunteers aged 30-70 years with stage I hypertension (BP 140-159 or 90-99 mmHg) following 3 months of a lifestyle intervention. Participants were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 333) or 50 mg of losartan (N = 322). If BP remained uncontrolled after 3 months, study medication dose was doubled, and if uncontrolled after 6 months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg twice daily) were added as open-label drugs in a progressive fashion. At the end of follow-up, 609 (93%) participants were evaluated., Results: The difference in SBP during 18 months of follow-up was 2.3 (95% confidence interval: 1.2 to 3.3) mmHg favoring chlorthalidone/amiloride. Compared with those randomized to diuretic, more participants allocated to losartan had their initial dose doubled and more of them used add-on antihypertensive medication. Levels of blood glucose, glycosilated hemoglobin, and incidence of diabetes were no different between the two treatment groups. Serum potassium was lower and serum cholesterol was higher in the diuretic arm. Microalbuminuria tended to be higher in patients with diabetes allocated to losartan (28.5 ± 40.4 versus 16.2 ± 26.7 mg, P = 0.09)., Conclusion: Treatment with a combination of chlorthalidone and amiloride compared with losartan yielded a greater reduction in BP., Clinical Trials Registration Number: NCT00971165.

Background: Resistant 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/design: This 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)., Discussion: In 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 Registration: Clinical Trials NCT02365974.

Introduction: Prehypertension is considered a precursor of systemic arterial hypertension and a predictor of morbidity-mortality due to cardiovascular diseases, which are the main causes of death in Brazil and the world. Thus, early diagnosis and the adoption of therapeutic measures in cases of prehypertension can reduce cardiovascular risk. The aim of the present study was to perform a selective review of the literature to identify and discuss early endothelial changes in individuals with pre-hypertension., Results and Discussion: The findings indicate an increase in ET-1-mediated vasoconstrictor tone in prehypertension, with endothelial-dependent vasodilatation impairment. Moreover, significantly high levels of angiotensin, arginine and vasopressin were found in this group of patients. A reduction in endothelial fibrinolytic capacity was another important change found in patients with prehypertention and was associated with an increased risk for atherothrombotic events., Conclusion: The present findings demonstrate endothelial changes in individuals with prehypertension that contribute to the development of arterial hypertension as well as a high risk for cardiovascular events, underscoring the importance of the early adoption of optimized therapeutic measures for this population.

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.

Background: The absence of nocturnal blood pressure dipping (ND) identified by 24-h ambulatory blood pressure monitoring (ABPM) correlates with a worse cardiovascular prognosis. The renin-angiotensin system influences blood pressure levels and the occurrence of target organ damage (TOD). Thus, the aim of this study was to correlate the angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism with the 24-h blood pressure profile and TOD in hypertensive individuals., Methods: 155 non-diabetic hypertensive individuals on antihypertensive treatment underwent ABPM. Peripheral blood samples were drawn for biochemistry and genetic analysis of the ACE I/D polymorphism by polymerase chain reaction. ND was defined as ≥10 % differences in the mean systolic blood pressure (BP) during wakefulness and sleep., Results: There were no differences in clinical or biochemical variables or TOD in respect to ND status, except for higher BP levels during sleep (p < 0.001) in non-dippers. There was significant difference in the prevalence of left ventricular hypertrophy (LVH) between ACE genotypes (II: 13.0 %; ID: 34.1 %; DD: 46.5 %; p value = 0.024) with an increased risk in carriers of the DD genotype (OR = 5.80; IC 95 % 1.50-22.44; p value = 0.011). Carriers of the D allele had higher systolic BP during wakefulness and by ABPM (p < 0.05), higher left ventricular mass (117.3 ± 50.0 vs. 100.3 ± 25.7; p value = 0.017) and higher prevalence of LVH (37.4 vs. 12.5 %; OR = 4.14; 95 % IC: 1.17-14.65; p value = 0.028), compared to the II genotype., Conclusions: The DD genotype is associated with a higher prevalence of LVH. The presence of the D allele appears to be associated with higher mean 24-h and wake systolic BP measured by ABPM in hypertensive patients under antihypertensive treatment.

Background: Vildagliptin, 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., Methods: Fifty 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., Results: The 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., Conclusions: It 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.

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.

Cardiovascular diseases are the leading cause of deaths. Also, cardiovascular risk factors start the atherosclerotic process, which leads to cardiovascular diseases. Nowadays, periodontal disease can also be considered another cardiovascular risk factor. It involves inflammatory, immunological and humoral activities, which induce the production of proinflammatory cytokines and the destruction of the epithelium. This allows the entry of endotoxins and exotoxins in the bloodstream, which may contribute to atherogenesis and thromboembolic events. There is also direct invasion of the vessel wall by oral pathogens, triggering an inflammatory response that produces endothelial dysfunction. In hypertension, changes in microcirculation can cause ischemia in the periodontium, which favors periodontal disease. Moreover, endothelial dysfunction promotes the formation of atherosclerotic plaque and the development of lesions in target organs. Periodontitis has also been associated with insulin resistance and a higher risk for the metabolic syndrome, which is characterized by oxidative stress. This seems to act as a common link to explain the relationship between each component of the metabolic syndrome (including hypertension) and periodontitis. This article will discuss clinical and experimental evidence, as well as possible pathophysiologic mechanisms and links involved in the relationship among periodontal disease, hypertension and cardiovascular disease.

Introduction: Metabolic syndrome (MS) is a set of cardiovascular risk factors and type 2 diabetes, responsible for a 2.5-fold increased cardiovascular mortality and a 5-fold higher risk of developing diabetes., Objectives: 1-to evaluate the prevalence of MS in individuals over 18 years associated with age, gender, socioeconomic status, educational levels, body mass index (BMI), HOMA index and physical activity; moreover, to compare it to other studies; 2-to compare the prevalence of elevated blood pressure (BP), high triglycerides and plasma glucose levels, low HDL cholesterol and high waist circumference among individuals with MS also according to gender; 3-to determine the number of risk factors in subjects with MS and prevalence of complications in individuals with and without MS aged over 40 years., Methods: A cross-sectional study of 1369 Individuals, 667 males (48.7%) and 702 females (51.3%) was considered to evaluate the prevalence of MS and associated factors in the population., Results: The study showed that 22.7% (95% CI: 19.4% to 26.0%) of the population has MS, which increases with age, higher BMI and sedentary lifestyle. There was no significant difference between genders until age ≥70 years and social classes. Higher prevalence of MS was observed in lower educational levels and higher prevalence of HOMA positive among individuals with MS. The most prevalent risk factors were elevated blood pressure (85%), low HDL cholesterol (83.1%) and increased waist circumference (82.5%). The prevalence of elevated BP, low HDL cholesterol and plasma glucose levels did not show significant difference between genders. Individuals with MS had higher risk of cardiovascular complications over 40 years., Conclusion: The prevalence of MS found is similar to that in developed countries, being influenced by age, body mass index, educational levels, physical activity, and leading to a higher prevalence of cardiovascular complications after the 4th decade of life.

Heart Failure (HF) is a progressive and fatal disorder, which ranks among the major public health problems in Brazil and worldwide. However, survival for patients who developed the syndrome after myocardial infarction (MI) enhanced significantly, as a result of an improvement of pharmacological therapies. A medical breakthrough was the discovery that remodelling of the left ventricle (LV) may be limited by the blockade of the renin-angiotensin system (RAS), at the level of angiotensin converting enzyme (ACE) and binding of angiotensin (Ang) II to its AT1 receptor. This review shows that the therapeutic effects of both ACE inhibitors and the angiotensin receptor blockers (ARB) go beyond the interference in the biochemical pathway ACE-Ang II AT1-receptor. Such effects are also related to the potentiation of bradykinin and increased beneficial effects mediated by the AT2 receptor. Therefore, the results of five randomized trials were presented, which evaluated the use of losartan, valsartan or candesartan, considering their effects on survival and risk of clinical deterioration in patients with symptomatic HF after MI. These studies confirmed the advantage of ARBs over inhibitors in case of cough, rashes and angioneurotic edema, despite similar adverse effects, such as hyperkalemia, renal failure and hypotension. Thus, in this article we have discussed with patents that ACE inhibitors also appear as the first option as RAS inhibitors in search of relevant results for the patient, allowing the alternative use of ARBs to those patients with intolerance.

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/m2) 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.

Hypertensive crisis (HC) stands out as a form of acute elevation of blood pressure (BP). It can manifest itself as hypertensive emergency (HE) or hypertensive urgency (HU), which is usually accompanied with levels of diastolic BP ≥120 mmHg. Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism may influence manifestations of HC. Thus, this study evaluated the influence of ACE I/D polymorphism in individuals with HC. A total of 187 patients admitted with HC (HU [n=69] and HE [n=118]) and 75 normotensive individuals were included in the study. Peripheral blood was drawn for a biochemical and genetic analysis of the ACE I/D polymorphism by Polymerase Chain Reaction. HC group showed higher systolic BP, body mass index (BMI), glycemia, creatinine, and lower high-density lipoprotein (HDL) cholesterol compared with normotensive individuals. The use of renin-angiotensin system (RAS) blockers was more frequent in the HU group than in the HE group (p=0.020). The II genotype was more predominant in normotensive and HU individuals than among HE individuals (18.7%, 11.6%, and 2.5%, respectively; p=0.004). Higher BMI and glycemia were associated with HC in the logistic regression model. ACE II genotype (odds ratio [OR] 0.14; 95% confidence interval [CI] 0.04-0.51) and HDL cholesterol were protective for the development of HE. ACE II genotype was present in the HU group, compared with the HE group (OR 0.18; 95% CI 0.04-0.88). This study shows an association between the low prevalence of ACE I/D polymorphism II genotype and a greater occurrence of HE in Brazilian individuals. The lower blockage of RAS, which was detected in the HE group, may interact with the low frequency of II genotype, conferring an increased risk for HE.

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.