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.

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.

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.

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.

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.

Beneficial Effects of Dietary Nitrate on Endothelial Function and Blood Pressure Levels.

Poor eating habits may represent cardiovascular risk factors since high intake of fat and saturated fatty acids contributes to dyslipidemia, obesity, diabetes mellitus, and hypertension. Thus, nutritional interventions are recognized as important strategies for primary prevention of hypertension and as adjuvants to pharmacological therapies to reduce cardiovascular risk. The DASH (Dietary Approach to Stop Hypertension) plan is one of the most effective strategies for the prevention and nonpharmacological management of hypertension. The beneficial effects of DASH diet on blood pressure might be related to the high inorganic nitrate content of some food products included in this meal plan. The beetroot and other food plants considered as nitrate sources account for approximately 60-80% of the daily nitrate exposure in the western population. The increased levels of nitrite by nitrate intake seem to have beneficial effects in many of the physiological and clinical settings. Several clinical trials are being conducted to determine the broad therapeutic potential of increasing the bioavailability of nitrite in human health and disease, including studies related to vascular aging. In conclusion, the dietary inorganic nitrate seems to represent a promising complementary therapy to support hypertension treatment with benefits for cardiovascular health.

Alterações cardiometabólicas em mulheres hipertensas com obesidade abdominal / Cardiometabolic disorders in Hypertensive women with abdominal obesity

Fundamentos: Estudos mostram o aumento da circunferência abdominal como indicador relevante de riscocardiovascular (RCV) aumentado.Objetivo: Identificar alterações cardíacas estruturais e funcionais em mulheres hipertensas não diabéticas comobesidade abdominal (OA). Métodos: Estudo transversal com 120 mulheres hipertensas, de 40-65 anos, estratificadas em: grupo sem obesidadeabdominal (SOA, n=42) e com obesidade abdominal (COA, n=78), sendo circunferência abdominal < ou ≥88 cm, respectivamente. Realizou-se avaliação clínica, exames bioquímicos, ecoDopplercardiograma e ultrassonografia de carótida.Resultados: A média de idade foi 53±1 anos nos grupos. A pressão arterial (PA) sistólica, embora maior no grupo COA, não atingiu significância estatística (145±2mmHg vs. 140±2mmHg, p=0,098). Grupo COA apresentou maiorPA diastólica (90±1mmHg vs. 85±1mmHg, p <0,05), maior número de critérios (3,1±0,1 vs. 1,4±0,1, p<0,001) e prevalência de síndrome metabólica (62,8% vs. 11,9%, p<0,001). Apesar de glicemias normais, pacientes COA apresentaram índices mais altos de HOMA-IR (2,62±0,22 vs. 1,61±0,17 p<0,01) e HOMA-beta (358±57 vs. 200±22, p<0,05). Na avaliação ecocardiográfica, a função sistólica foi semelhante nos grupos, mas o grupo COA apresentou evidências de disfunção diastólica pelo Doppler tissular e prevalência maior de hipertrofia ventricular esquerda (29,2% vs. 2,4%), sem diferença entre a espessura médio-intimal da carótida.Conclusões: Nesta amostra de hipertensas não diabéticas, a obesidade abdominal foi associada com maiores níveis de pressão arterial diastólica, redução da sensibilidade à insulina e alterações cardíacas, especialmente hipertrofia ventricular esquerda e disfunção diastólica. Contudo, não houve evidência de aterosclerose carotídea subclínica nas hipertensas com e sem obesidade abdominal.

Background: Studies show increased waist circumference as a relevant indicator of increased cardiovascular risk (CVR). Objective: To identify structural and functional cardiac abnormalities in nondiabetic hypertensive women with abdominal obesity (AO). Methods: Cross-sectional study with 120 hypertensive women, aged 40-65, stratified into: group with no abdominal obesity (NAO,n=42) and with abdominal obesity (QAO, n=78), and waist circumference < or ≥88cm, respectively. Clinical evaluation, biochemical tests, Doppler echocardiography and carotid ultrasound were conducted. Results: Average age was 53±1 in the groups. Although the systolic blood pressure (BP) was higher in the WAO group, it did not reach statistical significance (145±2mmHg vs. 140±2mmHg, p=0.098). The WAO group had higher diastolic BP (90±1mmHg vs. 85±1mmHg, p<0.05), greater number of criteria (3.1±0.1 vs. 1.4±0.1, p<0.001) and prevalence of metabolic syndrome (62.8% vs.11.9%; p<0.001). Despite normal blood glucose levels, WAO patients had higher HOMA-IR levels (2.62±0.22 vs. 1.61±0.17 p<0.01) and HOMA-beta levels (358±57 vs. 200±22, p<0.05). In the echocardiographic evaluation, systolic function was similar in bothgroups, but the WAO group presented evidence of diastolic dysfunction by tissue Doppler and higher prevalence of left ventricular hypertrophy (29.2% vs. 2.4%), with no difference between the carotid artery intima-media thickness.Conclusions: In this sample of nondiabetic hypertensive women, abdominal obesity was associated with higher levels of diastolic blood pressure, reduced insulin sensitivity and cardiac issues, especially left ventricular hypertrophy and diastolic dysfunction.However, there was no evidence of subclinical carotid atherosclerosis in hypertensive patients with and without abdominal obesity.

Characterisation of hypertensive patients with improved endothelial function after dark chocolate consumption.

Recent findings indicate an inverse relationship between cardiovascular disease and consumption of flavonoids. We aimed to identify clinical and vascular parameters of treated hypertensive who present beneficial effects of dark chocolate for one-week period on vascular function. Twenty-one hypertensive subjects, aged 40-65 years, were included in a prospective study with measurement of blood pressure (BP), brachial flow-mediated dilatation (FMD), peripheral arterial tonometry, and central hemodynamic parameters. These tests were repeated after seven days of eating dark chocolate 75 g/day. Patients were divided according to the response in FMD: responders (n = 12) and nonresponders (n = 9). The responder group presented lower age (54 ± 7 versus 61 ± 6 years, P = 0.037), Framingham risk score (FRS) (2.5 ± 1.8 versus 8.1 ± 5.1%, P = 0.017), values of peripheral (55 ± 9 versus 63 ± 5 mmHg, P = 0.041), and central pulse pressure (PP) (44 ± 10 versus 54 ± 6 mmHg, P = 0.021). FMD response showed negative correlation with FRS (r = -0.60, P = 0.014), baseline FMD (r = -0.54, P = 0.011), baseline reactive hyperemia index (RHI; r = -0.56, P = 0.008), and central PP (r = -0.43, P = 0.05). However, after linear regression analysis, only FRS and baseline RHI were associated with FMD response. In conclusion, one-week dark chocolate intake significantly improved endothelial function and reduced BP in younger hypertensive with impaired endothelial function in spite of lower cardiovascular risk.