Heart rate variability and perception of mental stress among medical students and residents at an emergency department.

BACKGROUND: When Medical Residents (MR) and Medical Students (MS) are assigned to the demanding environment of an Emergency they inevitably encounter stress. The aims of this study are to measure short-term heart rate variability (HRV) before and after shifts, estimate perceived stress levels, and assess the recovery patterns after their shifts. METHODS: We assessed HRV parameters in MS and MR using the wristband physiological monitor Polar® Verify Sense before and after day (DS) and night shifts (NS). Perceived stress levels were evaluated using the simplified State Trait Anxiety Inventory (STAI-S6) and the Subjective Units of Distress Scale. RESULTS: This study included 60 participants of which 55% were female with a mean age of 26 years. MS presented significant reduction in sympathetic nervous system index after DS [0.68 (0.01-2.42) vs -0.22 (-0.75-1.13), p < 0.01] and NS [0.87 (-0.28-1.45) vs 0.06 (-0.70-1.04), p < 0.01], while MR maintained the same levels of sympathetic activity [DS: 1.17 (0.04 -2.88) vs 0.93 (0.50-1.41), p = 0.14; NS: 1.37 (0.76-2.21) vs 1.29 (0.35-2.18), p = 0.40]. Psychological data from STAI-S6 showed statistically significant differences when comparing before and after DS in both groups, with more perceived stress after than before DS (MS: 12 ± 4 vs 14 ± 4, p = 0.04; MR: 14 ± 4 vs 16 ± 4, p = 0.04), which was not observed at NS (MS: 12 ± 3 vs 12 ± 3, p = 0.84; MR: 15 ± 3 vs 15 ± 4, p = 0.40). CONCLUSIONS: Short-term HRV recordings before and after day or night shifts among MR and MS revealed heightened sympathetic activity preceding each shift, with a more sustained increase observed in the MR population and more perceived stress after day shifts in both groups.

Whole-body vibration improves the functional parameters of individuals with metabolic syndrome: an exploratory study.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that increases the cardiovascular risk. Regular physical exercise can promote benefits, but the MetS individuals are demotivated to perform it. Thus, new possibilities are important as an alternative intervention. The whole-body vibration can be considered an exercise modality and would be a safe and low-cost strategy to improve functional parameters of individuals in different clinical conditions. The aim of this exploratory study was to assess effects of whole-body vibration on functional parameters of MetS individuals. The hypothesis of this work was that the whole-body vibration could improve the functionality of MetS individuals. METHODS: Twenty-two individuals performed the intervention. The vibration frequency varied from 5 to 14 Hz and the peak-to-peak displacements, from 2.5 to 7.5 mm. Each session consisted of one minute-bout of working time followed by a one minute-bout of passive rest in each peak-to-peak displacement for three-times. The whole-body vibration protocol was applied twice per week for 5 weeks. Data from the trunk flexion, gait speed, sit-to-stand test and handgrip strength were collected. Physiological parameters (blood pressure and heart rate) were also evaluated. The Wilcoxon Rank test and Student t-test were used. RESULTS: No significant changes (p > 0.05) were observed in physiological parameters (arterial blood pressure and heart rate). Significant improvements were found in trunk flexion (p = 0.01), gait speed (p = 0.02), sit-to-stand test (p = 0.005) and handgrip strength (p = 0.04) after the whole-body vibration. CONCLUSIONS: In conclusion, whole-body vibration may induce biological responses that improve functional parameters in participants with MetS without interfering in physiological parameters, comparing before and after a 5-week whole-body vibration protocol. TRIAL REGISTRATION: Register in the Registro Brasileiro de Ensaios Clínicos (ReBEC) with the number RBR 2bghmh (June 6th, 2016) and UTN: U1111-1181-1177. (virgula).

Effects of Vitamin D Supplementation on Central Hemodynamic Parameters and Autonomic Nervous System in Obese or Overweight Individuals. / Efeitos da Suplementação de Vitamina D sobre Parâmetros Hemodinâmicos Centrais e Sistema Nervoso Autônomo em Indivíduos com Obesidade ou Sobrepeso.

BACKGROUND: Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. OBJECTIVE: To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). METHODS: Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. RESULTS: The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). CONCLUSION: In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

FUNDAMENTO: Estudos prévios têm sido inconsistentes em demonstrar efeitos cardiovasculares benéficos da suplementação de vitamina D. OBJETIVO: Avaliar efeitos da suplementação de vitamina D3 sobre parâmetros hemodinâmicos centrais e atividade autonômica em indivíduos obesos/sobrepeso e baixos níveis de vitamina D (<30ng/dl). MÉTODOS: Ensaio clínico prospectivo, randomizado, duplo-cego (NCT05689632), adultos 40-65 anos com índice de massa corporal ≥25<40 kg/m2. Hemodinâmica central avaliada por método oscilométrico (Mobil-O-Graph®), variabilidade da frequência cardíaca utilizando frequencímetro Polar (software Kubios®). Os pacientes (n=53) receberam placebo no grupo controle (CO, n=25) ou vitamina D3 (VD, n=28) 7000 UI/dia, avaliados antes (S0) e após 8 semanas (S8) com nível de significância de 0,05. RESULTADOS: Os grupos foram homogêneos na idade (51±6 vs. 52±6 anos, p=0,509) e níveis de vitamina D (22,8±4,9 vs. 21,7±4,5ng/ml, p=0,590). Na S8, o grupo VD apresentou níveis significativamente maiores de vitamina D (22,5 vs. 35,6ng/ml, p<0,001). Apenas o grupo VD mostrou redução significativa da pressão arterial sistólica (PAS; 123±15 vs. 119±14mmHg, p=0,019) e fosfatase alcalina (213±55 vs. 202±55mg/dl, p=0,012). O grupo CO mostrou elevação da pressão de aumento (AP: 9 vs. 12mmHg, p=0,028) e do índice de incremento (Aix: 26 vs. 35%, p=0,020), o que não foi observado no grupo VD (AP: 8 vs. 8mmHg, Aix: 26 vs. 25%, p>0,05). Grupo VD apresentou aumento no índice do sistema nervoso (iSN) parassimpático (-0,64±0,94 vs. -0,16±1,10, p=0,028) e no intervalo R-R (866±138 vs. 924±161ms, p=0,026). CONCLUSÃO: Nesta amostra, a suplementação diária de vitamina D durante oito semanas resultou em melhora dos níveis pressóricos, parâmetros hemodinâmicos centrais e do equilíbrio autonômico.

The effects of telmisartan and amlodipine in treatment-naïve and previously treated hypertensive patients: a subanalysis from a 4 × 4 factorial design study.

The subanalysis of a 4 × 4 factorial, 8-week study to evaluate the efficacy and tolerability of telmisartan (T) 40-80 mg/amlodipine (A) 5-10 mg used in treatment-naïve patients (n = 231) and patients previously treated with antihypertensive agents (n = 880). Similar blood pressure (BP) reductions were achieved with T + A, regardless of their pretreatment status. Highest reductions were achieved with T80 + A10 (treatment-naïve -26.5/-18.2 mm Hg and previously treated -25.6/-19.9 mm Hg). Most patients (treatment-naïve 72.4% and previously treated 77.6%), including those with added risk, achieved BP goal (<140/90 mm Hg) with T80 + A10. Tolerability was comparable in both groups.

Arterial Stiffness Associated with Sympathetic Hyperactivity in Obese Individuals with Moderate to Severe Obstructive Sleep Apnea.

INTRODUCTION: Obstructive Sleep Apnea (OSA) is a chronic disorder associated with several risk factors, and increased Body Mass Index (BMI) and waist circumference are correlated with it is severity. AIM: To evaluate vascular function, central hemodynamics, and autonomic modulation in obese individuals with moderate and severe OSA. METHODS: Individuals of both sexes, aged 40-70 years and BMI ≥ 30 and < 40 kg/m2, were submitted to assessment of heart rate variability, endothelial function by flow-mediated dilatation, central parameters by oscillometry and carotid ultrasound. The sleep study was performed through a portable home sleep test device (WatchPAT). RESULTS: Patients (n = 76) were divided according to Apnea-Hypopnea Index (AHI): absent-mild group (AHI < 15 events/h, n = 30) and Moderate-Severe (MS) group (AHI ≥ 15 events/h, n = 46). The Low/High Frequency (LF/HF) ratio (0.81 ± 0.48 vs 1.39 ± 1.08 ms2, p = 0.035), Pulse Wave Velocity (PWV; 6.9 ± 0.7 vs 7.7 ± 1.6m/s, p = 0.004), vascular age (48 ± 6 vs 53 ± 9 years, p = 0.05) and mean intima-media thickness (0.59 ± 0.08 vs 0.66 ± 0.13 mm, p = 0.011) were significantly higher in the MS group. AHI was significantly correlated with PWV (r = 0.26, p = 0.024) and LF/HF ratio (r = 0.40, p < 0.001). Only in the MS group, PWV was significantly correlated with SD2/SD1 ratio (r = 0.611, p ≤ 0.001), and flow-mediated dilation with central systolic blood pressure (r = 0.364, p = 0.018), even after adjustment for age and sex. CONCLUSION: In this sample of obese individuals, moderate to severe OSA was associated with sympathetic hyperactivity and evidence of accelerated vascular aging with arterial stiffness and subclinical atherosclerosis.

Acute Effects of Dietary Nitrate on Central Pressure and Endothelial Function in Hypertensive Patients: A Randomized, Placebo-Controlled Crossover Study. / Efeitos Agudos do Nitrato Dietético na Pressão Central e Desempenho Cardíaco em Hipertensos: Estudo Cruzado, Randomizado e Placebo-Controlado.

BACKGROUND: The diet's inorganic nitrate (NO3-) may provide a physiological substrate for reducing nitrate (NO2-) to NO independent of the endothelium. Studies suggest that inorganic NO3- has beneficial effects on cardiovascular health. OBJECTIVE: This study evaluated the acute effects of 500 mL nitrate-rich beetroot juice (BRJ; containing 11.5mmol NO3-) on blood pressure and endothelial function in treated hypertensive patients. METHODS: A randomized, placebo-controlled, crossover study was conducted in treated hypertensive patients (n=37; women=62%) who underwent clinical and nutritional evaluation and assessment of central hemodynamic parameters and microvascular reactivity. The significance level was p<0.05. RESULTS: The mean age was 59±7 years, and mean systolic and diastolic blood pressures were 142±10/83±9mmHg. There was a significant increase in the subendocardial viability ratio (SEVR; 149±25 vs. 165±30%, p<0.001) and reduction in ejection duration (ED; 37±4 vs. 34±4%, p<0.001) in the beetroot phase but no significant SEVR difference in the control phase. The % increase in perfusion (155 vs. 159 %, p=0.042) was significantly increased in the beetroot phase, which was not observed in the control phase. In the beetroot phase, the change in SEVR showed a significant correlation with the change in the area under the curve of post-occlusive reactive hyperemia (AUC-PORH) (r=0.45, p=0.012). The change in ED showed a significant correlation with the post-intervention perfusion peak (r=-0.37, p=0.031) and AUC-PORH (r=-0.36, p=0.046). CONCLUSIONS: The acute ingestion of BRJ by hypertensive patients resulted in an improvement of endothelial function, which was associated with higher subendocardial viability and performance in myocardial contraction.

FUNDAMENTO: O nitrato inorgânico (NO3­) da dieta pode fornecer substrato fisiológico para reduzir o nitrito (NO2­) a óxido nítrico (NO) independente do endotélio. Estudos sugerem que o NO3­ inorgânico tem efeitos benéficos na saúde cardiovascular. OBJETIVOS: Este estudo avaliou os efeitos agudos de 500 mL de suco de beterraba rico em nitrato (SB; contendo 11,5mmol NO3­) na pressão arterial e na função endotelial em pacientes hipertensos tratados. MÉTODOS: Estudo cruzado, randomizado, controlado por placebo foi realizado em pacientes hipertensos tratados (n=37; mulheres=62%) que foram submetidos à avaliação clínica e nutricional, avaliação dos parâmetros hemodinâmicos centrais e reatividade microvascular. O nível de significância foi p<0,05. RESULTADOS: A média de idade foi 59±7 anos e das pressões sistólica e diastólica foi de 142±10/83±9 mmHg. Houve aumento significativo na taxa de viabilidade subendocárdica (RVSE; 149±25 vs. 165±30%, p<0,001) e redução na duração da ejeção (DE; 37±4 vs. 34±4%, p<0,001) na fase beterraba, mas nenhuma diferença significativa de RVSE na fase controle. O % de aumento na perfusão (155 vs. 159%, p=0,042) cresceu significativamente na fase beterraba, o que não foi observado na fase controle. Na fase beterraba, a alteração da RVSE apresentou correlação significativa com a alteração da área sob a curva de hiperemia reativa pós-oclusiva (ASC-HRPO) (r=0,45, p=0,012). A mudança na DE mostrou uma correlação significativa com pico de perfusão pós-intervenção (r=-0,37, p=0,031) e ASC-HRPO (r=-0,36, p=0,046). CONCLUSÃO: A ingestão aguda de SB por pacientes hipertensos resultou em melhora da função endotelial, que foi associada à maior viabilidade subendocárdica e desempenho na contração miocárdica.

Highlights of mechanisms and treatment of obesity-related hypertension.

The prevalence of obesity has increased two to three times from 1975 to 2015. Large-scale epidemiological and longitudinal prospective studies link obesity with hypertension. Research suggests that excessive weight gain, particularly when associated with visceral adiposity, may account for as much as 65% to 75% of the risk of incident hypertension. Also, exercise and bariatric/metabolic surgery significantly lowers blood pressure, whereas weight gain increases blood pressure, thus establishing a firm link between these two factors. The mechanisms underpinning obesity-related hypertension are complex and multifaceted, and include, but are not limited to, renin-angiotensin-aldosterone system/sympathetic nervous system overactivation, overstimulation of adipokines, insulin resistance, immune dysfunction, structural/functional renal, cardiac, and adipocyte changes. Though weight loss is the mainstay of treatment for obesity-related hypertension, it is often not a feasible long-term solution. Therefore, it is recommended that aggressive treatment with multiple antihypertensive medications combined with diet and exercise be used to lower blood pressure and prevent complications. The research regarding the mechanisms and treatment of obesity-related hypertension has moved at a blistering pace over the past ten years. Therefore, the purpose of this expert review is two-fold: to discuss the pathophysiological mechanisms underlying obesity-related hypertension, and to revisit pharmacotherapies that have been shown to be efficacious in patients with obesity-related hypertension.

Effects of cycling bouts performed with different intensities and amounts of energy expended on central pressure and pulse wave reflection in normotensive and hypertensive men.

OBJECTIVE: This study investigated pulse wave analysis in normotensive and hypertensive men after cycling bouts with different intensities and amounts of energy expended. METHODS: Twenty-four men were assigned into normotensive (n = 14; age: 40.7 ± 2.8 years; 24-h ambulatory SBP/DBP:121 ± 2/74 ± 1 mmHg) and hypertensive (n = 10; age: 39.2 ± 2.3 years; 24-h ambulatory SBP/DBP:139 ± 3/86 ± 2 mmHg) groups. Participants undertook a maximal cardiopulmonary exercise test, a nonexercise control session (CTL) and three cycling bouts [two prolonged bouts expending 300 kcal at 50% (i.e. P-MOD) and 70% (i.e. P-VIG) oxygen uptake reserve (VO2R) and one short bout expending 150 kcal at 50% VO2R (i.e. S-MOD)] performed in a randomized order. Central SBP (cSBP), pulse pressure (cPP), augmentation pressure, augmentation index (AIx), heart rate (HR) and AIx adjusted for HR (AIx@75) were determined 10 min before, and 30- and 70-min postintervention. RESULTS: Compared to CTL, only the P-VIG changed the cSBP [70-min (Δ -11.7 mmHg)], cPP [70-min (Δ:-7.4 mmHg)], augmentation pressure [30-min (Δ:-5.7 mmHg); 70-min (Δ:-7.3 mmHg)], AIx [30-min (Δ:-15.3 %); 70-min (Δ:-16.4 %)], AIx@75 [30-min (Δ:-12.8 %); 70-min (Δ:-13.9 %)] and HR [70-min (Δ: 9.9 bpm)] in the hypertensive group. However, all exercise bouts mitigated the increased cSBP responses post-CTL in the hypertensive group. CONCLUSION: The present study provides evidence that vigorous-intensity aerobic exercise reduces acute central pressure and pulse wave reflection in hypertensive men.

Effects of Oral Magnesium Supplementation on Vascular Function: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: The effects of magnesium (Mg) supplementation on vascular function have been evaluated in some randomized controlled trials (RCT) but their results are conflicting. AIM: A systematic review and meta-analysis were conducted to summarize the effects of oral Mg supplementation on vascular function in RCT. METHODS: The databases MEDLINE (PubMed), Embase, Web of Science and Cochrane Library were accessed from inception to May 27, 2019. Intergroup differences (treatment vs. control group) related to changes in flow-mediated dilation (FMD) and pulse wave velocity (PWV), expressed as mean and standard deviation, were used to evaluate the effect of Mg supplementation on these outcomes. The results of the meta-analysis were expressed using a random-effects model. The heterogeneity between studies was evaluated using the I2 statistic. RESULTS: The oral supplementation of Mg had no significant effect on FMD (mean difference 2.13; 95% CI - 0.56, 4.82; p = 0.12) and PWV (mean difference - 0.54, 95% CI - 1.45, 0.36, p = 0.24). Heterogeneity for both outcomes (FMD and PWV) was high (I2 = 99%, p < 0.001). However, in subgroup analyses, oral Mg significantly improved FMD in studies longer than 6 months, in unhealthy subjects, in individuals older than 50 years, or in those with body mass index (BMI) ≥ 25 kg/m2. The reduced number of RCT and the heterogeneity among them were the main limitations. CONCLUSIONS: This meta-analysis suggest that oral Mg supplementation may improve endothelial function when conducted at least for 6 months and in unhealthy, overweight or older individuals. Registration number: PROSPERO CRD42019111462.

Microvascular Reactivity in Hypertensive Patients with High Body Adiposity. / Estudo da Reatividade Microvascular em Pacientes Hipertensos com Adiposidade Corporal Elevada.

BACKGROUND: Several anthropometric indexes have been proposed to determine the association between overweight and cardiovascular risk factors. OBJECTIVE: To evaluate the relationship between body adiposity and microvascular reactivity in hypertensive patients under antihypertensive therapy. METHODS: Treated hypertensive patients aged 40 to 70 were submitted to evaluation of anthropometric indexes: conicity (CI), body adiposity (BAI), visceral adiposity (VAI) and waist-to-height ratio (WHtR). Participants were divided by the terciles of fat percentage (%F) obtained by bioelectrical impedance. The patients underwent microvascular reactivity test (Laser Speckle Contrast Image) and pulse wave velocity (PWV) measurement. The p value <0.05 was considered statistically significant. RESULTS: The variation of the area under the curve (AUC) of the skin perfusion was lower in the upper tercile (97±57% vs. 67±36%; p=0.027). %F showed significant correlation with WHtR (r=0.77; p<0.001), VAI (r=0.41; p=0.018), CI (r=0.60; p<0.001), BAI (r=0.65; p<0.001) in men and only with WHtR (r=0.55; p<0.001) and BAI (r=0.60; p<0.001) in women. In linear regression, AUC was independently associated with %F (ß=-3.15; p=0.04) in women and with blood glucose (ß=-1.15; p=0.02) in men. There was no difference in PWV measurements. CONCLUSION: Anthropometric indices were more associated with %F in men. Higher body adiposity was associated with lower microvascular reactivity, which was more evident in women. There was no difference in arterial stiffness, which may have been influenced by antihypertensive treatment.

FUNDAMENTO: Diversos índices antropométricos têm sido propostos para determinar a associação entre excesso de peso e fatores de risco cardiovascular. OBJETIVO: Avaliar a relação entre adiposidade corporal e reatividade microvascular em pacientes hipertensos sob terapia anti-hipertensiva. MÉTODOS: Pacientes hipertensos tratados de 40 a 70 anos foram submetidos à avaliação de índices antropométricos: conicidade (IC), adiposidade corporal (IAC), adiposidade visceral (IAV) e relação cintura-estatura (RCE). Os participantes foram divididos pelos tercis de percentual de gordura (%G) obtido pela bioimpedância elétrica (BIA) e submetidos a teste de reatividade microvascular (laser speckle contrast image), medida da velocidade da onda de pulso (VOP). O valor de p < 0,05 foi considerado estatisticamente significativo. RESULTADOS: A variação da área sob a curva (ASC) da perfusão cutânea foi inferior no tercil superior (97 ± 57% vs. 67 ± 36%; p = 0,027). O %G apresentou correlação significativa com RCE (r = 0,77; p < 0,001), IAV (r = 0,41; p = 0,018), IC (r = 0,60; p < 0,001) e IAC (r = 0,65; p < 0,001) nos homens e somente com RCE (r = 0,55; p < 0,001) e IAC (r = 0,60; p < 0,001) nas mulheres. Na regressão linear, a ASC mostrou associação independente com o %G (ß =­3,15; p = 0,04) nas mulheres e com a glicemia (ß = ­1,15; p = 0,02) nos homens. Não houve diferença nas medidas de VOP. CONCLUSÃO: Os índices antropométricos de obesidade foram mais associados ao %G nos homens. A maior adiposidade corporal foi relacionada com menor reatividade microvascular, o que foi mais evidente nas mulheres. Não houve diferença na rigidez arterial, o que pode ter sido influenciado pelo tratamento anti-hipertensivo.

Efeitos da Suplementação de Vitamina D sobre Parâmetros Hemodinâmicos Centrais e Sistema Nervoso Autônomo em Indivíduos com Obesidade ou Sobrepeso / Effects of Vitamin D Supplementation on Central Hemodynamic Parameters and Autonomic Nervous System in Obese or Overweight Individuals

Resumo Fundamento Estudos prévios têm sido inconsistentes em demonstrar efeitos cardiovasculares benéficos da suplementação de vitamina D. Objetivo Avaliar efeitos da suplementação de vitamina D3 sobre parâmetros hemodinâmicos centrais e atividade autonômica em indivíduos obesos/sobrepeso e baixos níveis de vitamina D (<30ng/dl). Métodos Ensaio clínico prospectivo, randomizado, duplo-cego (NCT 05689632), adultos 40-65 anos com índice de massa corporal ≥25<40 kg/m2. Hemodinâmica central avaliada por método oscilométrico (Mobil-O-Graph®), variabilidade da frequência cardíaca utilizando frequencímetro Polar (software Kubios®). Os pacientes (n=53) receberam placebo no grupo controle (CO, n=25) ou vitamina D3 (VD, n=28) 7000 UI/dia, avaliados antes (S0) e após 8 semanas (S8) com nível de significância de 0,05. Resultados Os grupos foram homogêneos na idade (51±6 vs. 52±6 anos, p=0,509) e níveis de vitamina D (22,8±4,9 vs. 21,7±4,5ng/ml, p=0,590). Na S8, o grupo VD apresentou níveis significativamente maiores de vitamina D (22,5 vs. 35,6ng/ml, p<0,001). Apenas o grupo VD mostrou redução significativa da pressão arterial sistólica (PAS; 123±15 vs. 119±14mmHg, p=0,019) e fosfatase alcalina (213±55 vs. 202±55mg/dl, p=0,012). O grupo CO mostrou elevação da pressão de aumento (AP: 9 vs. 12mmHg, p=0,028) e do índice de incremento (Aix: 26 vs. 35%, p=0,020), o que não foi observado no grupo VD (AP: 8 vs. 8mmHg, Aix: 26 vs. 25%, p>0,05). Grupo VD apresentou aumento no índice do sistema nervoso (iSN) parassimpático (-0,64±0,94 vs. -0,16±1,10, p=0,028) e no intervalo R-R (866±138 vs. 924±161ms, p=0,026). Conclusão Nesta amostra, a suplementação diária de vitamina D durante oito semanas resultou em melhora dos níveis pressóricos, parâmetros hemodinâmicos centrais e do equilíbrio autonômico.

Abstract Background Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. Objective To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). Methods Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT 05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. Results The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). Conclusion In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

Association of urinary sodium/potassium ratio with structural and functional vascular changes in non-diabetic hypertensive patients.

Studies aiming to associate the sodium/potassium (Na/K) ratio with hypertension use 24-hour urinary excretion as a daily marker of ingestion. The objective of this study was to evaluate the association between urinary Na/K ratio and structural and functional vascular alterations in non-diabetic hypertensive patients. In hypertensive patients (n = 72), aged between 40 and 70 years, both sexes (61% women), in use of hydrochlorothiazide, we measured blood pressure, 24-hour urine sample collection, assessment of carotid-femoral pulse wave velocity (cf-PWV, Complior), central hemodynamic parameters (SphygmoCor), and post-occlusive reactive hyperemia (PORH). The participants were divided according to the tertile of 24-hour urinary Na/K ratio. Each group contained 24 patients. Systolic blood pressure was higher in T2 (133 ± 9 vs 140 ± 9 mmHg, P = .029). C-reactive protein (CRP) presented higher values in T3 as compared to T1 [0.20(0.10-0.34) vs 1.19 (0.96-1.42) mg/dL, P < .001]. Higher values in T3 were also observed for aortic systolic pressure (aoSP) [119(114-130) vs 135(125-147) mmHg, P = .002] and cf-PWV (9.2 ± 1.6 vs 11.1 ± 1.5 m/s, P < .001). The urinary Na/K ratio presented significant correlations with proteinuria (r = .27, P = .023), CRP (r = .77, P < .001), cf-PWV (r = .41, P < .001), and post-occlusive reactive hyperemia on cutaneous vascular conductance (PORH CVC) (r = -.23, P = .047). By multivariate linear regression, it was detected an independent and significant association of cf-PWV with urinary Na/K ratio (R2  = 0.17, P < .001) and PORH CVC with CRP (R2  = 0.30, P = .010). Our data indicated that increased urinary Na/K ratio in non-diabetic hypertensive patients was associated with higher degree of inflammation, raised peripheral and central pressure levels, and changes suggestive of endothelial dysfunction and arterial stiffness.

The Role of Renin-Angiotensin-Aldosterone System and Its New Components in Arterial Stiffness and Vascular Aging.

Many cardiovascular diseases present renin-angiotensin-aldosterone system (RAAS) hyperactivity as an important pathophysiological mechanism to be target in the therapeutic approaches. Moreover, arterial stiffness is currently considered as a new independent risk factor for cardiovascular disease in different clinical conditions, including hypertension and chronic kidney disease. In fact, excessive stimulation of angiotensin type 1 (AT1) receptors, as well as mineralocorticoid receptors, results in cellular growth, oxidative stress and vascular inflammation, which may lead to arterial stiffness and accelerate the process of vascular aging. In the last decades, a vasoprotective axis of the RAAS has been discovered, and now it is well established that new components with antioxidant and anti-inflammatory properties play important roles promoting vasodilation, natriuresis and reducing collagen deposition, thus attenuating arterial stiffness and improving endothelial function. In this review, we will focus on these pathophysiological mechanisms and the relevance of RAAS inhibition by different strategies to increase arterial compliance and to decelerate vascular aging.

Efeitos Agudos do Nitrato Dietético na Pressão Central e Desempenho Cardíaco em Hipertensos: Estudo Cruzado, Randomizado e Placebo-Controlado / Acute Effects of Dietary Nitrate on Central Pressure and Endothelial Function in Hypertensive Patients: A Randomized, Placebo-Controlled Crossover Study

Resumo Fundamento O nitrato inorgânico (NO3-) da dieta pode fornecer substrato fisiológico para reduzir o nitrito (NO2-) a óxido nítrico (NO) independente do endotélio. Estudos sugerem que o NO3- inorgânico tem efeitos benéficos na saúde cardiovascular. Objetivos Este estudo avaliou os efeitos agudos de 500 mL de suco de beterraba rico em nitrato (SB; contendo 11,5mmol NO3-) na pressão arterial e na função endotelial em pacientes hipertensos tratados. Métodos Estudo cruzado, randomizado, controlado por placebo foi realizado em pacientes hipertensos tratados (n=37; mulheres=62%) que foram submetidos à avaliação clínica e nutricional, avaliação dos parâmetros hemodinâmicos centrais e reatividade microvascular. O nível de significância foi p<0,05. Resultados A média de idade foi 59±7 anos e das pressões sistólica e diastólica foi de 142±10/83±9 mmHg. Houve aumento significativo na taxa de viabilidade subendocárdica (RVSE; 149±25 vs. 165±30%, p<0,001) e redução na duração da ejeção (DE; 37±4 vs. 34±4%, p<0,001) na fase beterraba, mas nenhuma diferença significativa de RVSE na fase controle. O % de aumento na perfusão (155 vs. 159%, p=0,042) cresceu significativamente na fase beterraba, o que não foi observado na fase controle. Na fase beterraba, a alteração da RVSE apresentou correlação significativa com a alteração da área sob a curva de hiperemia reativa pós-oclusiva (ASC-HRPO) (r=0,45, p=0,012). A mudança na DE mostrou uma correlação significativa com pico de perfusão pós-intervenção (r=-0,37, p=0,031) e ASC-HRPO (r=-0,36, p=0,046). Conclusão A ingestão aguda de SB por pacientes hipertensos resultou em melhora da função endotelial, que foi associada à maior viabilidade subendocárdica e desempenho na contração miocárdica.

Abstract Background The diet's inorganic nitrate (NO3-) may provide a physiological substrate for reducing nitrate (NO2-) to NO independent of the endothelium. Studies suggest that inorganic NO3- has beneficial effects on cardiovascular health. Objective This study evaluated the acute effects of 500 mL nitrate-rich beetroot juice (BRJ; containing 11.5mmol NO3-) on blood pressure and endothelial function in treated hypertensive patients. Methods A randomized, placebo-controlled, crossover study was conducted in treated hypertensive patients (n=37; women=62%) who underwent clinical and nutritional evaluation and assessment of central hemodynamic parameters and microvascular reactivity. The significance level was p<0.05. Results The mean age was 59±7 years, and mean systolic and diastolic blood pressures were 142±10/83±9mmHg. There was a significant increase in the subendocardial viability ratio (SEVR; 149±25 vs. 165±30%, p<0.001) and reduction in ejection duration (ED; 37±4 vs. 34±4%, p<0.001) in the beetroot phase but no significant SEVR difference in the control phase. The % increase in perfusion (155 vs. 159 %, p=0.042) was significantly increased in the beetroot phase, which was not observed in the control phase. In the beetroot phase, the change in SEVR showed a significant correlation with the change in the area under the curve of post-occlusive reactive hyperemia (AUC-PORH) (r=0.45, p=0.012). The change in ED showed a significant correlation with the post-intervention perfusion peak (r=-0.37, p=0.031) and AUC-PORH (r=-0.36, p=0.046). Conclusions The acute ingestion of BRJ by hypertensive patients resulted in an improvement of endothelial function, which was associated with higher subendocardial viability and performance in myocardial contraction.

Potential Role of Endothelin in Early Vascular Aging.

Early vascular aging is a process associated with gradual alterations in the vessels, regarding their structure and function, taking a more rapid course than normal biological aging in the arteries. In the presence of cardiovascular disease, these age-associated alterations are accelerated, contributing in the appearance or the progression of cardiovascular disease, such as high blood pressure, dyslipidemia, smoking and diabetes. Endothelin-1 (ET-1) is the most abundant and important endothelin produced by vascular cells. ET-1 exerts its biological actions through the activation of two receptors: ETA and ETB. Many important functions are mediated by the activation of these receptors, such as cardiovascular remodeling, vasoconstriction, cell proliferation and differentiation, production of extracellular matrix, and water and sodium secretion control. ETA receptor seems to participate in the pathogenesis and development of diseases, such as diabetes, atherosclerosis, systemic and pulmonary hypertension, and cardiac remodeling after myocardial ischemia, whereas ETB receptor seems to prevent the overstimulation of ETA receptor, acting as a clearance receptor. Increased ET-1 system activity may contribute to vascular dysfunction in aging via multiple pathways, such as direct hemodynamic effects, vascular oxidative stress, inflammatory activity, mitogenic stimulation of the vascular smooth muscle cells and fibrotic processes. Endothelin receptor antagonists were considered to be used for the treatment of some diseases like hypertension, diabetes and chronic kidney disease. However, besides pulmonary hypertension, this class is not in clinical use because of the side effects and the availability of safer drugs for the treatment of these diseases.

Omega-3 fatty acids supplementation improves endothelial function and arterial stiffness in hypertensive patients with hypertriglyceridemia and high cardiovascular risk.

Association between hypertriglyceridemia and cardiovascular (CV) disease is still controversial. The purpose of this study was to compare omega-3 and ciprofibrate effects on the vascular structure and function in low and high CV risk hypertensive patients with hypertriglyceridemia. Twenty-nine adults with triglycerides 150-499 mg/dL were divided into low (<7.5%) and high (≥7.5%) CV risk, randomized to receive omega-3 fatty acids 1800 mg/d or ciprofibrate 100 mg/d for 12 weeks. Treatment was switched after 8-week washout. Clinical evaluation and vascular tests were assessed at baseline and after intervention. Peripheral (131 ± 3 to 125 ± 3 mm Hg, P < .05) and aortic (124 ± 3 to 118 ± 2 mg/dL, P < .05) systolic blood pressure were decreased by ciprofibrate in low-risk patients. In high-risk patients, pulse wave velocity was reduced (10.4 ± 0.4 to 9.4 ± 0.3 m/s, P < .05) and flow-mediated dilation was increased (11.1 ± 1.6 to 13.5 ± 1.2%, P < .05) by omega-3. In conclusion, omega-3 improved arterial stiffness and endothelial function, pointing out the beneficial effect of this therapy on vascular aging, in high-risk patients.

Twenty-four hour Blood Pressure in Obese Patients with Moderate-to-Severe Obstructive Sleep Apnea.

BACKGROUND: Obesity, systemic arterial hypertension (SAH) and obstructive sleep apnea (OSA) are closely related. Up to 70% of patients with OSA may be asymptomatic, and there is evidence that these patients have cardiovascular disease, especially nocturnal SAH. OBJECTIVES: The aim of this study was to evaluate 24-hour blood pressure circadian variation in asymptomatic, obese individuals with moderate-to-severe OSA and compare it with that in individuals with mild OSA or without OSA. METHODS: Eighty-six obese subjects aged between 30 and 55 years (BMI 30-39 kg/m2), with casual blood pressure < 140/90 mmHg and without comorbidities were recruited. Eighty-one patients underwent clinical and anthropometric assessment, ambulatory blood pressure monitoring (ABPM), and Watch-PAT. Participants were divided into two groups, based on the apnea-hypopnea index (AHI): group 1, with AHI < 15 events/hour, and group 2 with AHI ≥ 15 events/hour. RESULTS: Compared with group 1, group 2 had higher neck circumference and waist-hip circumference (40.5 ± 3.2 cm vs. 38.0 ± 3.7 cm, p = 0.002, and 0.94 ± 0.05 vs. 0.89 ± 0.05, p = 0.001, respectively), higher systolic and diastolic blood pressure measured by the 24-h ABPM (122 ± 6 vs 118 ± 8 mmHg, p = 0.014, and 78 ± 6 vs 73 ± 7 mmHg, p = 0.008, respectively), and higher nocturnal diastolic pressure load (44,6 ± 25,9% vs 31,3 ± 27,3%, p = 0,041). Moreover, there was a positive correlation between nocturnal diastolic blood pressure and AHI (r = 0.43, p < 0.05). CONCLUSIONS: Asymptomatic obese subjects with moderate-to-severe OSA have higher systolic and diastolic blood pressure at 24 hours compared with those with absent / mild OSA, despite normal casual blood pressure between the groups. These results indicate that ABPM may be useful in the evaluation of asymptomatic obese patients with moderate-to-severe OSA.

Oral magnesium supplementation improves endothelial function and attenuates subclinical atherosclerosis in thiazide-treated hypertensive women.

BACKGROUND: Epidemiological studies demonstrate an inverse association between serum magnesium and incidence of cardiovascular disease. Diuretics commonly cause hypomagneseamia. METHOD: We evaluated effects of magnesium supplementation on blood pressure (BP) and vascular function in thiazide-treated hypertensive women in a randomized, double-blind, clinical trial. Hypertensive women (40-65 years) on hydrochlorothiazide and mean 24-h BP at least 130/80 mmHg were divided into placebo and supplementation (magnesium chelate 600 mg/day) groups. Patients were evaluated for nutritional and biochemical parameters, office and ambulatory blood pressure monitoring, brachial flow-mediated dilatation (FMD), peripheral arterial tonometry, assessment of carotid intima-media thickness, central hemodynamic parameters and pulse wave velocity at inclusion and after 6-month follow-up. RESULTS: The magnesium group had a significant reduction in SBP (144 ±â€Š17 vs. 134 ±â€Š14 mmHg, P = 0.036) and DBP (88 ±â€Š9 vs. 81 ±â€Š8 mmHg, P = 0.005) at 6 months, without effect on plasma glucose, lipids, or arterial stiffness parameters. The placebo group showed a significant increase in carotid intima-media thickness (0.78 ±â€Š0.13 vs. 0.89 ±â€Š0.14 mm, P = 0.033) without change in the magnesium group (0.79 ±â€Š0.16 vs. 0.79 ±â€Š0.19 mm, P = 0.716) after 6 months. The magnesium group demonstrated a significant increase in variation of FMD vs. the placebo group (+3.7 ±â€Š2.1 vs. 2.4 ±â€Š1.2%, P = 0.015). There was a significant correlation between the intracellular magnesium variation and FMD (r = 0.44, P = 0.011). CONCLUSION: Magnesium supplementation was associated with better BP control, improved endothelial function and amelioration of subclinical atherosclerosis in these thiazide-treated hypertensive women.

QUALITY OF LIFE OF PATIENTS WITH METABOLIC SYNDROME IS IMPROVED AFTER WHOLE BODY VIBRATION EXERCISES.

BACKGROUND: Whole body vibration exercises (WBVE) improve the quality of life (QoL) of different populations. Metabolic syndrome patients (MetS) may be favored by physical activity. Questionnaires are used to assess the QoL. The aim was to evaluate the QoL of patients with MetS that have undergone WBVE with a brief WHOQOL (WHOQOL-BREF). MATERIAL AND METHODS: MetS patients were randomly divided into three groups: (i) control group (CG), (ii) treated with WBVE once per week (WBVE1) and (iii) treated with WBVE twice per week (WBVE2). In the first session, the patient was sat in a chair in front of the platform with the feet on its base in 3 peak to peak displacements (2.5, 5.0 and 7.5 mm) and frequency of 5 Hz was used. From the second to the last session, patients were subjected to the same protocol, however they were standing on the base of the platform and the frequency was increased up to 14 Hz. The patients fulfilled the WHOQOL-BREF before the first and after the last sessions. Cronbach coefficients were determined to each domain of the WHOQOL-BREF and test Wilcoxon (p<0.05) was used. RESULTS: The patients of the WBVE1 group had improvements in the physical, psychological and environment domains while in the WBVE2, the improvements were in the physical and social relationships domain of the WHOQOL-BREF. CONCLUSION: It was observed that the WBVE in a protocol (one or two times per week) with a progressive and increased frequency improves the QoL of patients with MetS in different domains of the WHOQOL-BREF.

[The "LOTHAR" study: evaluation of efficacy and tolerability of the fixed combination of amlodipine and losartan in the treatment of essential hypertension]. / Estudo "LOTHAR": avaliação de eficácia e tolerabilidade da combinação fixa de anlodipino e losartana no tratamento da hipertensão arterial primária.

OBJECTIVE: The LOTHAR study evaluated medium and long term (one year) efficacy, tolerability and metabolic effects of the fixed combination of amlodipine and losartan compared to amlodipine or losartan alone. METHODS: Brazilian multicenter, randomized, double-blind and comparative trial performed with 198 patients in stage 1 and 2 essential hypertension. RESULTS: The fixed combination has a high antihypertensive efficacy that is sustained in the long term with very low percentage of loss of blood pressure control. This percentage is incidentally lower than that of the two monotherapy comparative regimens. In the long term, more than 60% of the patients treated with the fixed combination remained with DBP < or = 85 mmHg, and the antihypertensive effect, when assessed by ABPM persisted for 24 hours with a trough-to-peak ratio of 76.7%. The frequency of adverse events was quite low in this group, and the long-term incidence of leg edema was approximately four-fold lower than that observed with amlodipine alone. The fixed combination did not change glucose and lipid metabolism in the medium or in the long term. CONCLUSION: Based on these results, we can say that the combination of amlodipine and losartan--the first fixed combination of a calcium channel blocker and an angiotensin II receptor blocker available in the pharmaceutical market, is an excellent option for the treatment of a wide range of hypertensive patients.