Therapeutic Phlebotomy in Patients with Grade 1 Hypertension: A Randomized-Controlled Trial.

Aim: Study aim was to investigate the effects of therapeutic phlebotomy on ambulatory blood pressure in patients with grade 1 hypertension. Methods: In this randomized-controlled intervention study, patients with unmedicated hypertension grade 1 were randomized into an intervention group (phlebotomy group; 500 mL bloodletting at baseline and after 6 weeks) and a control group (waiting list) and followed up for 8 weeks. Primary endpoint was the 24-h ambulatory mean arterial pressure between the intervention and control groups after 8 weeks. Secondary outcome parameters included ambulatory/resting systolic/diastolic blood pressure, heart rate, and selected laboratory parameters (e.g., hemoglobin, hematocrit, erythrocytes, and ferritin). Resting systolic/diastolic blood pressure/heart rate and blood count were also assessed at 6 weeks before the second phlebotomy to ensure safety. A per-protocol analysis was performed. Results: Fifty-three hypertension participants (56.7 ± 10.5 years) were included in the analysis (n = 25 intervention group, n = 28 control group). The ambulatory measured mean arterial pressure decreased by -1.12 ± 5.16 mmHg in the intervention group and increased by 0.43 ± 3.82 mmHg in the control group (between-group difference: -1.55 ± 4.46, p = 0.22). Hemoglobin, hematocrit, erythrocytes, and ferritin showed more pronounced reductions in the intervention group in comparison with the control group, with significant between-group differences. Subgroup analysis showed trends regarding the effects on different groups classified by serum ferritin concentration, body mass index, age, and sex. Two adverse events (AEs) (anemia and dizziness) occurred in association with the phlebotomy, but no serious AEs. Conclusions: Study results showed that therapeutic phlebotomy resulted in only minimal reductions of 24-h ambulatory blood pressure measurement values in patients with unmedicated grade 1 hypertension. Further high-quality clinical studies are warranted, as this finding contradicts the results of other studies.

Plasma selenium and the risk of first stroke in adults with hypertension: a secondary analysis of the China Stroke Primary Prevention Trial.

BACKGROUND: Previous studies have indicated that selenium (Se) may play an important role in cardio-cerebrovascular disease. However, the relation between circulating selenium and risk of first stroke remains inconclusive. OBJECTIVES: We conducted a secondary analysis of the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, and aimed to investigate the correlation between Se concentration and first stroke risk in adults with hypertension and examine the potential effect modifiers. METHODS: In the CSPPT, a total of 20,702 adults with hypertension were randomly assigned to a double-blind daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study. RESULTS: During a median follow-up duration of 4.5 y (IQR: 4.2-4.6 y), there was a significant inverse association between plasma Se and the risk of first stroke (per SD increment; adjusted OR: 0.81; 95% CI: 0.68, 0.96) and ischemic stroke (per SD increment; adjusted OR: 0.76; 95% CI: 0.62, 0.93). Furthermore, a stronger inverse association between plasma Se and first stroke was observed in participants with higher folate concentrations at baseline [≥7.7 ng/mL (median), adjusted OR: 0.67; 95% CI: 0.54, 0.85, compared with <7.7 ng/mL, adjusted OR: 0.98; 95% CI: 0.80, 1.21; P-interaction = 0.008] and those with higher time-averaged systolic blood pressure (SBP) over the treatment period (≥140 mm Hg, adjusted OR: 0.71; 95% CI: 0.58, 0.86, compared with <140 mm Hg, adjusted OR: 0.96; 95% CI: 0.77, 1.20; P-interaction = 0.023). CONCLUSIONS: There was a significant inverse association between plasma Se and risk of first stroke in Chinese adults with hypertension, especially among those with higher baseline folate concentrations and those with higher time-averaged SBP over the treatment period. This trial was registered at clinicaltrials.gov as NCT00794885.

The Association between Plasma Concentration of Phytoestrogens and Hypertension within the Korean Multicenter Cancer Cohort.

In order to examine the association between plasma phytoestrogen concentration (genistein, daidzein, equol and enterolactone) and hypertension, we conducted a nested case-control study for 229 hypertension cases including 112 prehypertension and 159 healthy controls derived from the Korean Multi-center Cancer Cohort (KMCC). The concentration of plasma phytoestrogens was measured using time-resolved fluoroimmunoassay. We assessed the association between plasma phytoestrogens and hypertension using logistic regression models using odds ratio (OR) and 95% confidence interval (95%CI). The highest tertile of plasma equol and enterolactone concentration exhibited a significantly decreased risk of hypertension (equol, OR = 0.34, 95%CI 0.20-0.57; enterolactone, OR = 0.32, 95%CI 0.18-0.57), compared with the lowest tertile. Equol and enterolactone showed reduced ORs for prehypertension (the highest tertile relative to the lowest tertile, OR = 0.50, 95%CI 0.26-0.96; OR = 0.38, 95%CI 0.19-0.75, respectively) and hypertension (OR = 0.42, 95%CI 0.22-0.81; OR = 0.28, 95%CI 0.14-0.54, respectively). There was a stronger association in hypertension (the highest tertile relative to the lowest tertile in obesity vs. non-obesity; equol, OR = 0.06 vs. 0.63; enterolactone, OR = 0.07 vs. 0.46; both p-heterogeneity < 0.01). This study suggests that equol and enterolactone may contribute to prevent primarily prehypertension and hypertension, and control cardiovascular disease (CVD) based on the continuum of hypertension and CVD. Further study to assess hypertension risk based on useful biomarkers, including phytoestrogens, may contribute to primary prevention of hypertension.

Effects of strawberries on bone biomarkers in pre- and stage 1-hypertensive postmenopausal women: a secondary analysis.

Postmenopausal women experience an increase in bone remodeling with the rate of bone resorption superseding the rate of bone formation. This results in a net bone loss with a subsequent increased risk for osteoporosis and fractures. High blood pressure (BP) has been associated with loss of bone mineral density and increased propensity to fractures. Strawberries are rich in polyphenols, which have been shown to have anti-hypertensive and bone-protective properties. Thus, we examined whether daily intake of strawberries would positively affect biomarkers of bone metabolism in postmenopausal women with pre- and stage 1-hypertension. Participants (age: 59 ± 6 years; body mass index: 31.5 ± 4.1 kg m-2; systolic BP: 140 ± 13 mmHg) were randomly assigned to consume (1) 50 g of freeze-dried strawberry powder (FDSP), (2) 25 g FDSP + 25 g of placebo powder, or (3) 50 g placebo powder for eight weeks. Results indicate a significant time-by-treatment interaction (P = 0.04) for serum insulin-like growth factor (IGF)-1, a hormone that plays a major role in bone formation. Serum concentrations of bone-specific alkaline phosphatase, a marker of bone formation, and tartrate-resistant acid phosphatase-5b, a specific marker of bone resorption, were not affected by FDSP compared to placebo. Although not statistically significant, after eight weeks, osteocalcin increased in the 50 g FDSP group with a large effect size (d = 0.6) when compared to the placebo-control group. Adiponectin increased by 5% and 6% in the 25 g and 50 g FDSP groups, respectively, while it declined in the placebo-control group by 25% (P = 0.03 for time-by-treatment interaction). Our findings suggest that consumption of 25 g FDSP increases IGF-1 in postmenopausal women with pre- and stage 1-hypertension. However, further studies are needed to assert the effectiveness of a strawberry intervention for bone health.

Cyperus esculentus L. and Tetracarpidium conophorum Müll. Arg. Supplemented Diet Improved Testosterone Levels, Modulated Ectonucleotidases and Adenosine Deaminase Activities in Platelets from L-NAME-Stressed Rats.

In hypertensive individuals, platelet morphology and function have been discovered to be altered, and this has been linked to the development of vascular disease, including erectile dysfunction (ED). The impact of nutritional supplementation with Cyperus esculentus (tiger nut, TN) and Tetracarpidium conophorum (walnut, WN) on androgen levels, ectonucleotidases, and adenosine deaminase (ADA) activities in platelets from L-NAME (Nω-nitro-L-arginine methyl ester hydrochloride) challenged rats were investigated. We hypothesized that these nuts may show a protective effect on platelets aggregation and possibly enhance the sex hormones, thereby reverting vasoconstriction. Wistar rats (male; 250-300 g; n = 10) were grouped into seven groups as follows: basal diet control group (I); basal diet/L-NAME/Viagra (5 mg/kg/day) as positive control group (II); ED-induced group (basal diet/L-NAME) (III); diet supplemented processed TN (20%)/L-NAME (IV); diet supplemented raw TN (20%)/L-NAME (V); diet supplemented processed WN (20%)/L-NAME (VI); and diet supplemented raw WN (20%)/L-NAME (VII). The rats were given their regular diet for 2 weeks prior to actually receiving L-NAME (40 mg/kg/day) for ten days to induce hypertension. Platelet androgen levels, ectonucleotidases, and ADA were all measured. L-NAME considerably lowers testosterone levels (54.5 ± 2.2; p < 0.05). Supplementing the TN and WN diets revealed improved testosterone levels as compared to the control (306.7 ± 5.7), but luteinizing hormone levels remained unchanged. Compared to control groups, the L-NAME-treated group showed a rise in ATP (127.5%) hydrolysis and ADA (116.7%) activity, and also a decrease in ADP (76%) and AMP (45%) hydrolysis. Both TN and WN supplemented diets resulted in substantial (p < 0.05) reversal effects. Enhanced testosterone levels and modulation of the purinergic system in platelets by TN and WN could be one of the mechanisms by which they aid in vasoconstriction control.

Randomized trial of vitamin D versus placebo supplementation on markers of systemic inflammation in hypertensive patients.

BACKGROUND AND AIMS: Animal and cell models indicated that vitamin D modulates inflammatory activity, which is considered relevant in the pathogenesis of arterial hypertension and cardiovascular diseases. We therefore aimed to investigate the effect of vitamin D supplementation on systemic markers of inflammation in a cohort of hypertensive patients. METHODS AND RESULTS: The Styrian Vitamin D Hypertension Trial is a single-centre, double-blind, placebo-controlled study conducted from 2011 to 2014 in Austria. We enrolled 200 study participants with arterial hypertension and 25-hydroxy-vitamin-D (25(OH)D) concentration below 30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D3 per day or placebo for 8 weeks. The present investigation is a post-hoc analysis using analysis of co-variance (ANCOVA). Outcome measures were biomarkers of inflammation including CRP, leukocytes including subtypes and leukocyte-to-lymphocyte ratio, leucine and kynurenic acid. A total of 187 participants (mean age 60.1 ± 11.3years; 47% women; mean baseline 25(OH)D 21.1 ± 5.6 ng/mL) completed the trial. ANCOVA revealed a mean treatment effect for none of the respective outcomes and no significant results were detected in various subgroup analyses. CONCLUSION: Vitamin D3 supplementation in hypertensive patients with insufficient 25(OH)D concentrations has no significant effect on lowering markers of systemic inflammation. Further studies investigating the effect of vitamin D on other inflammatory pathways and in populations with severe vitamin D deficiency and a significant inflammatory burden are required. REGISTRATION: ClinicalTrials.gov Identifier: NCT02136771; EudraCT No. 2009-018,125-70. Start Date: 2011-04-06.

Capnometric feedback training decreases 24-h blood pressure in hypertensive postmenopausal women.

BACKGROUND: High normal resting pCO2 is a risk factor for salt sensitivity of blood pressure (BP) in normotensive humans and has been associated with higher resting systolic BP in postmenopausal women. To date, however, no known studies have investigated the effects of regular practice of voluntary mild hypocapnic breathing on BP in hypertensive patients. The objective of the present research was to test the hypothesis that capnometric feedback training can decrease both resting pCO2 and 24-h BP in a series of mildly hypertensive postmenopausal women. METHODS: A small portable end tidal CO2 (etCO2) monitor was constructed and equipped with software that determined the difference between the momentary etCO2 and a pre-programmed criterion range. The monitor enabled auditory feedback for variations in CO2 outside the criterion range. 16 mildly hypertensive postmenopausal women were individually trained to sustain small decreases in etCO2 during six weekly sessions in the clinic and daily sessions at home. 24-h BP monitoring was conducted before and after the intervention, and in 16 prehypertensive postmenopausal women in a control group who did not engage in the capnometric training. RESULTS: Following the intervention, all 16 capnometric training participants showed decreases in resting etCO2 (- 4.3 ± 0.4 mmHg; p < .01) while 15 showed decreases in 24-h systolic BP (- 7.6 ± 2.0 mmHg; p < .01). No significant changes in either measure was observed in the control group. In addition, nighttime (- 9.5 ± 2.6; p < .01) and daytime (- 6.7 ± 0.2 mmHg) systolic BP were both decreased following capnometric training, while no significant changes in nighttime (- 2.8 ± 2.2 mmHg; p = .11) or daytime (- 0.7 ± 1.0 mmHg; p ≤ .247) systolic BP were observed in the control group. CONCLUSIONS: These findings support the hypothesis that regular practice of mild hypocapnic breathing that decreases resting etCO2 reliably decreases 24-h blood pressure in hypertensive postmenopausal women. The extent to which these effects persist beyond the training period or can be observed in other hypertensive subgroups remains to be investigated.

Time-Efficient Inspiratory Muscle Strength Training Lowers Blood Pressure and Improves Endothelial Function, NO Bioavailability, and Oxidative Stress in Midlife/Older Adults With Above-Normal Blood Pressure.

Background High-resistance inspiratory muscle strength training (IMST) is a novel, time-efficient physical training modality. Methods and Results We performed a double-blind, randomized, sham-controlled trial to investigate whether 6 weeks of IMST (30 breaths/day, 6 days/week) improves blood pressure, endothelial function, and arterial stiffness in midlife/older adults (aged 50-79 years) with systolic blood pressure ≥120 mm Hg, while also investigating potential mechanisms and long-lasting effects. Thirty-six participants completed high-resistance IMST (75% maximal inspiratory pressure, n=18) or low-resistance sham training (15% maximal inspiratory pressure, n=18). IMST was safe, well tolerated, and had excellent adherence (≈95% of training sessions completed). Casual systolic blood pressure decreased from 135±2 mm Hg to 126±3 mm Hg (P<0.01) with IMST, which was ≈75% sustained 6 weeks after IMST (P<0.01), whereas IMST modestly decreased casual diastolic blood pressure (79±2 mm Hg to 77±2 mm Hg, P=0.03); blood pressure was unaffected by sham training (all P>0.05). Twenty-four hour systolic blood pressure was lower after IMST versus sham training (P=0.01). Brachial artery flow-mediated dilation improved ≈45% with IMST (P<0.01) but was unchanged with sham training (P=0.73). Human umbilical vein endothelial cells cultured with subject serum sampled after versus before IMST exhibited increased NO bioavailability, greater endothelial NO synthase activation, and lower reactive oxygen species bioactivity (P<0.05). IMST decreased C-reactive protein (P=0.05) and altered select circulating metabolites (targeted plasma metabolomics) associated with cardiovascular function. Neither IMST nor sham training influenced arterial stiffness (P>0.05). Conclusions High-resistance IMST is a safe, highly adherable lifestyle intervention for improving blood pressure and endothelial function in midlife/older adults with above-normal initial systolic blood pressure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03266510.

Mechanism of Radix Astragali and Radix Salviae Miltiorrhizae Ameliorates Hypertensive Renal Damage.

Hypertensive-induced renal damage (HRD) is an important public health and socioeconomic problem worldwide. The herb pair Radix Astragali- (RA-) Radix Salviae Miltiorrhizae (RS) is a common prescribed herbal formula for the treatment of HRD. However, the underlying mechanisms are unclear. The purpose of our study is to explore the mechanism of combination of Radix Astragali (RA) and Radix Salviae Miltiorrhizae (RS) ameliorating HRD by regulation of the renal sympathetic nerve. Thirty 24-week-old spontaneously hypertensive rats (SHRs) as the experimental group were randomly divided into the RA group, the RS group, the RA+RS group, the valsartan group, and the SHR group and six age-matched Wistar Kyoto rats (WKY) as the control group. After 4 weeks of corresponding drug administration, venipuncture was done to collect blood and prepare serum for analysis. A color Doppler ultrasound diagnostic instrument was used to observe renal hemodynamics. Enzyme-linked immunosorbent assay was used to detect norepinephrine (NE), epinephrine (E), angiotensin II (Ang II), and B-type brain natriuretic peptide (BNP). Simultaneously, the kidneys were removed immediately and observed under a transmission electron microscope to observe the ultrastructural changes. And the concentration of transforming growth factor-ß1 (TGF-ß1), angiotensin type 1 receptor (AT1), and nitric oxide (NO) was detected by immunohistochemistry. Our results showed that renal ultrasonography of rats showed no significant difference in renal size among groups. The RA+RS group had obviously decreased vascular resistance index. The levels of NE, E, BNP, Ang II, AT1, and TGF-ß1 were decreased (P < 0.05), and the density of NO was increased. Pathological damage of the kidney was alleviated. In conclusion, the results of the present study suggested sympathetic overexpression in the pathogenesis of HRD. The combination of RA and RS may inhibit the hyperexcitability of sympathetic nerves and maintain the normal physiological structure and function of kidney tissue and has a protective effect on the cardiovascular system.

Choline Metabolites, Hydroxybutyrate and HDL after Dietary Fiber Supplementation in Overweight/Obese Hypertensive Women: A Metabolomic Study.

Metabolomics has been increasingly used to evaluate metabolic changes associated with morbidities. The objective of this study is to assess the metabolic profile before and after intervention with mixed dietary fiber in overweight and obese hypertensive women. This is an intervention study, and the sample consists of 14 women aged 28 to 58 years. An intervention with 12 g of mixed soluble and insoluble fiber is performed for a period of eight weeks. Serum metabolites are identified using a Bruker 1H NMR spectrometer at 400 MHz. Multivariate data analysis, including principal component analysis (PCA), is used to differentiate the two groups. After supplementation with dietary fiber, there is a significant increase in the peak intensity values of the metabolites HDL-C (0.0010*), choline (0.0012*) and hydroxybutyrate (0.0010*) as well as a decrease in systolic (0.0013*) and diastolic (0.0026*) blood pressure. The analysis of the metabolomic profile allows the identification of metabolites that have been associated in the literature with hypertension and excess weight (choline, hydroxybutyrate and amino acids) and with fiber intake (choline, hydroxybutyrate and amino acids) in addition to an increase in HDL-C. The increase in the detection of the described metabolites possibly occurs due to the presence of pathologies and the use of fiber in the intervention, which also contributes to elevated HDL-c and reduced blood pressure.

Ruta Montana Evokes Antihypertensive Activity Through an Increase of Prostaglandins Release in L-NAME-Induced Hypertensive Rats.

AIMS: The aim of the study was to experimentally investigate the antihypertensive effect of Ruta Montana. BACKGROUND: Ruta montana L. is traditionally used in Moroccan herbal medicine to treat hypertension. This study aimed to experimentally evaluate the hypotensive and vasoactive properties of this plant. OBJECTIVE: The objective of the study was to evaluate the effect of the aqueous extract of Ruta Montana on blood pressure parameters in LNAME-induced hypertensive rats and to determine the vasorelaxant activity of this aqueous extract. METHODS: The antihypertensive effect of the aqueous extract obtained from Ruta montana aerial parts (RMAPAE) (200 mg/kg) was evaluated in normal and anesthetized hypertensive rats. Blood pressure parameters (systolic blood pressure (SBP), mean blood pressure (MBP) and diastolic blood pressure (DBP)) and heart rate were measured using a tail-cuff and a computer-assisted monitoring device. The acute and chronic effect of RMAPAE was recorded for 6 hours for the acute experiment and for 7 days for the sub-chronic test. In the other set, the vasorelaxant effect of RMAPAE on the contractile response was observed in the isolated thoracic aorta. RESULTS: The results indicated that the RMAPAE extract significantly decreased SBP, MBP, DBP and heart rate in L-NAME-induced hypertensive rats. Furthermore, RMAPAE was demonstrated to induce a dose-dependent relaxation in the aorta precontracted with Epinephrine or KCl. More interestingly, this vasorelaxant activity of RMAPAE seems to be probably mediated through the prostaglandins pathway. CONCLUSION: The present study illustrates the beneficial action of Ruta montana on hypertension and supports its use as an antihypertensive agent.

Ectopic ACTH syndrome of different origin-Diagnostic approach and clinical outcome. Experience of one Clinical Centre.

PURPOSE: Ectopic Cushing Syndrome (EAS) is a rare condition responsible for about 5-20% of all Cushing syndrome cases. It increases the mortality of affected patients thus finding and removal of the ACTH-producing source allows for curing or reduction of symptoms and serum cortisol levels. The aim of this study is to present a 20-year experience in the diagnosis and clinical course of patients with EAS in a single Clinical Centre in Southern Poland as well as a comparison of clinical course and outcomes depending on the source of ectopic ACTH production-especially neuroendocrine tumors with other neoplasms. METHODS: Twenty-four patients were involved in the clinical study with EAS diagnosed at the Department of Endocrinology between years 2000 and 2018. The diagnosis of EAS was based on the clinical presentation, hypercortisolemia with high ACTH levels, high dose dexamethasone suppression test and/or corticotropin-releasing hormone tests. To find the source of ACTH various imaging studies were performed. RESULTS: Half of the patients were diagnosed with neuroendocrine tumors, whereby muscle weakness was the leading symptom. Typical cushingoid appearance was seen in merely a few patients, and weight loss was more common than weight gain. Patients with neuroendocrine tumors had significantly higher midnight cortisol levels than the rest of the group. Among patients with infections, we observed a significantly higher concentrations of cortisol 2400 levels in gastroenteropancreatic neuroendocrine tumors. Chromogranin A correlated significantly with potassium in patients with neuroendocrine tumors and there was a significant correlation between ACTH level and severity of hypokalemia. CONCLUSION: EAS is not common, but if it occurs it increases the mortality of patients; therefore, it should be taken into consideration in the case of coexistence of severe hypokalemia with hypertension and muscle weakness, especially when weight loss occurs. Because the diagnosis of gastroenteropancreatic neuroendocrine tumor worsens the prognosis-special attention should be paid to these patients.

[Analysis of the biochemical, anthropometric profile, and of antioxidant micronutrient ingestion in patients with resistant arterial hypertension]. / Análisis del perfil bioquímico y antropométrico, y de la ingesta de micronutrientes antioxidantes en pacientes con hipertensión arterial resistente.

INTRODUCTION: Introduction: resistant arterial hypertension (HAR) is associated with a high risk for cardiovascular events due to oxidative stress. Research has shown the beneficial effects of dietary antioxidants on cardiovascular health. Objective: to analyze and correlate the biochemical, anthropometric profile and intake of antioxidant micronutrients of patients with HAR. Material and methods: the patients underwent a biochemical assessment, and an anthropometric assessment to calculate body mass index (IMC), waist circumference (PCI), hip circumference (PCA), waist-to-hip ratio (ICC), and micronutrient intake assessment: vitamin A, vitamin C, vitamin E, selenium and zinc, estimated by a semi-quantitative food frequency questionnaire and 24-hour recall. The statistical analysis was performed using the SPSS Statistics 20 software. A p-value < 0.05 was considered significant. Results: sixty individuals with HAR were studied, with a mean age of 62.83 ± 10.73 years. Mean IMC was 31.01 ± 5.60 kg/m², PCI, 98.12 ± 15.04 cm, PCA, 110.55 ± 13.16 cm, and ICC, 0.879 ± 0.084. Regarding the biochemical profile, mean total colesterol was 187.65 ± 48.29 mg/dL, triglycerides, 136.38 ± 99.91 mg/dL; HDL-col, 49.00 ± 10.99 mg/dL; LDL-col, 112.01 ± 41.89 mg/dL; glucose, 105.37 ± 14.81 mg/dL, and glycated hemoglobin, 6.29 ± 1.76 %. The average daily intake of antioxidants was: vitamin A, 241.47 ± 191.87 µg/d; vitamin C, 147.02 ± 192.94 mg/d; vitamin E, 1.99 ± 1.82 mg/d; selenium, 36.80 ± 34.56 µg/d, and zinc, 99.91 ± 6.64 mg/d, where 91.38 %, 46.55 %, 93.10 %, 67.24 %, and 46.55 % of the sample were below the recommended intakes, respectively. Conclusion: inadequate antioxidant intake was observed in these patients with HAR, with a high prevalence of obesity, especially visceral adiposity and alterations in lipid profile, conditions that require a greater usage of these micronutrients. We suggest there is a need for dietary planning for these patients to improve their quality of life and their response to antihypertensive treatment.

INTRODUCCIÓN: Introducción: la hipertensión arterial resistente (HAR) se asocia a un alto riesgo de eventos cardiovasculares debido al estrés oxidativo. Los estudios han demostrado los efectos beneficiosos de los antioxidantes dietéticos sobre la salud cardiovascular. Objetivo: analizar y correlacionar el perfil bioquímico y antropométrico, y la ingesta de micronutrientes antioxidantes en pacientes con HAR. Material y métodos: los pacientes se sometieron a una evaluación bioquímica y antropométrica para calcular el índice de masa corporal (IMC), el perímetro de la cintura (PCI), el perímetro de la cadera (PCA), el índice cintura-cadera (ICC) y la ingesta de micronutrientes ­vitaminas A, C y E, selenio y zinc­ utilizando una encuesta de frecuencia de consumo alimentario y el recordatorio de 24 horas. El análisis estadístico se realizó utilizando el software SPSS Statistics 20, con un valor de p < 0,05 como significativo. Resultados: estudiamos a 60 individuos con HAR de 62,83 ± 10,73 años. El IMC medio fue de 31,01 ± 5,60 kg/m²; el PCI de 98,12 ± 15,04 cm, el PCA de 110,55 ± 13,16 cm y el ICC de 0,879 ± 0,084. Respecto al perfil bioquímico, el colesterol total medio fue de 187,65 ± 48,29 mg/dL, los triglicéridos de 136,38 ± 99,91 mg/dL, el HDL-col de 49,00 ± 10,99 mg/dL, el LDL-col de 112,01 ± 41,89 mg/dL, la glucemia de 105,37 ± 14,81 mg/dL y la hemoglobina glucosilada del 6,29 ± 1,76 %. La ingesta de antioxidantes fue: vitamina A: 241,47 ± 191,87 µg/d; vitamina C: 147,02 ± 192,94 mg/d; vitamina E: 1,99 ± 1,82 mg/d; selenio: 36,80 ± 34,56 µg/d, y zinc: 9,91 ± 6,64 mg/d, y el 91,38 %, 46,55 %, 93,10 %, 67,24 % y 46,55 % de la muestra se encontraron por debajo de lo recomendado, respectivamente. Conclusión: se observó una ingesta insuficiente de antioxidantes en los pacientes con HAR, que presentan una alta prevalencia de obesidad, especialmente de adiposidad visceral y alteraciones del perfil lipídico, afecciones que requieren un mayor uso de estos micronutrientes. Se sugiere la necesidad de una planificación dietética dirigida a estos pacientes para mejorar la calidad de vida y la respuesta al tratamiento antihipertensivo.

Heat-sensitive moxibustion self-administration in patients in the community with primary hypertension: A protocol for a multi-center, pragmatic, non-randomized trial.

BACKGROUND: Although the efficacy of antihypertensive drugs has been well established for primary hypertension, their effectiveness is always limited by side effects and poor compliance. Heat-sensitive moxibustion is an innovative acupoint stimulation therapy that is promising as a community health care intervention for hypertension. AIMS: This study aims to evaluate the pragmatic effectiveness and safety of heat-sensitive moxibustion self-administration by patients in the community with primary hypertension. METHODS: This study will adopt a multi-center, pragmatic, nonrandomized design. Six hundred patients with primary hypertension will be recruited from 4 communities. Each patient will choose to either receive heat-sensitive moxibustion self-administration + original antihypertensive drugs or maintain their original antihypertensive drugs without heat-sensitive moxibustion for 1 year. EXPECTED OUTCOMES: The primary outcome will be changes in systolic and diastolic blood pressures and the percentage changes in the doses of antihypertensive drugs. The secondary outcomes will be changes in quality of life assessed by a validated patient-reported outcome scale and the levels of fasting blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, urinary albumin, and serum creatinine. The proportion of patients with poor compliance with the heat-sensitive moxibustion regimen will also be evaluated as a secondary outcome. The safety of heat-sensitive moxibustion will be considered by analyzing the incidence of all and serious adverse events and their correlation with heat-sensitive moxibustion. DISCUSSION: The findings of this study will provide pragmatic evidence for heat-sensitive moxibustion self-administration in patients in the community with primary hypertension and may also establish an ethical basis for further randomized controlled trials. TRIAL REGISTRATION: The protocol of this trial was registered in ClinicalTrials.gov at May 11, 2020 (No. NCT04381520).

Effects of whey protein on glycemic control and serum lipoproteins in patients with metabolic syndrome and related conditions: a systematic review and meta-analysis of randomized controlled clinical trials.

BACKGROUND: This systematic review and meta-analysis aimed to assess the effects of whey protein on serum lipoproteins and glycemic status in patients with metabolic syndrome (MetS) and related disorders. METHODS: Online databases, such as Web of Science, Cochrane Library, PubMed and Scopus were systematically searched by two independent authors from inception until 30th April 2020 for English randomized clinical trials investigating the efficacy of whey protein administration in subjects with Mets or related conditions on the parameters of glycemic and lipid control compared to certain control. In order to evaluate the included studies' methodological quality, Cochrane Collaboration risk of bias tool was applied. Using Cochrane's Q test and I-square (I2) statistic, the included trials' heterogeneity was also examined. Using a random-effects model, data were pooled, and weighted mean difference (WMD) was considered as the overall effect size. RESULTS: Twenty-two studies were selected to be included in this meta-analysis. Consumption of whey protein resulted in significant reduction of HbA1c (WMD: -0.15; 95% CI: - 0.29, - 0.01) insulin (WMD: -0.94; 95% CI: - 1.68, - 0.21) and homeostasis model assessment-estimated insulin resistance (HOMA-IR) (WMD: -0.20; 95% CI: - 0.36, - 0.05). A significant reduction in triglycerides levels (WMD: -17.12; 95% CI: - 26.52, - 7.72), total cholesterol (WMD: -10.88; 95% CI -18.60, - 3.17), LDL-cholesterol levels (WMD: -8.47 95% CI: - 16.59, - 0.36) and total cholesterol/HDL-cholesterol ratio (WMD: -0.26; 95% CI: - 0.41, - 0.10) was found as well. CONCLUSIONS: This meta-analysis suggests that supplementation with whey protein had beneficial effect on several indicators of glycemic control and lipid parameters in patients with MetS and related conditions.

LC-MS-Based Lipidomic Analysis of Serum Samples from Spontaneously Hypertensive Rats Treated with an Extract of Acanthopanax sessiliflorus Fruits.

Recently, lipidomics has revealed that many diseases are highly associated with altered lipid metabolism, as in the case of hypertension affecting serum lipid metabolism. In this study, an LC-MS-based lipidomic approach was used to profile serum lipids in spontaneously hypertensive rats (SHRs) treated with an extract of Acanthopanax sessiliflorus fruits (ASF), to elucidate the serum lipid metabolism alteration by hypertension and the treatment of a drug or ASF. First, UPLC-QTOF/MS profiled a total of 208 lipids from six pooled samples of normal controls, SHR, SHR + 100 mg/kg of drug, and SHR + ASF 200, 400, or 600 mg/kg. These six groups were differentiated by the PCA and sPLS-DA, and 120 lipid species were identified as differentially regulated lipids (DRLs) by ANOVA (p values < 0.05). Second, UPLC-QqQ/MS was used for the target profiling of 120 DRLs from individual samples of the six groups. Using an ANOVA, 67 lipids (38 TGs, 4 DGs, 17 PCs, 2 PEs, and 6 LPCs) were selected as validated DRLs. The mostly altered lipids, such as TG (62:13), TG (60:13), PC (34:4), PC (36:5), and PC (38:2), were decreased in SHR compared to the normal control, and received little by treatment with ASF. These results demonstrated the correlation between hypertension and serum lipid metabolism. Furthermore, both drug and ASF treatment similarly altered the lipid profiles of SHRs. Finally, we found that DRLs have the potential to help us to interpret the lipid metabolism of hypertension.

Identifying Interactions between Dietary Sodium, Potassium, Sodium-Potassium Ratios, and FGF5 rs16998073 Variants and Their Associated Risk for Hypertension in Korean Adults.

Hypertension is affected by both genetic and dietary factors. This study aimed to examine the interaction between dietary sodium/potassium intake, sodium-potassium ratios, and FGF5 rs16998073 and link these with increased risk for developing hypertension. Using data from the Health Examinee (HEXA) Study of the Korean Genome and Epidemiologic Study (KoGES), we were able to identify a total of 17,736 middle-aged Korean adults who could be included in our genome-wide association study (GWAS) to confirm any associations between hypertension and the FGF5 rs16998073 variant. GWAS analysis revealed that the FGF5 rs16698073 variant demonstrated the strongest association with hypertension in this population. Multivariable logistic regression was used to examine the relationship between dietary intake of sodium, potassium, and sodium-potassium ratios and the FGF5 rs16998073 genotypes (AA, AT, TT) and any increased risk of hypertension. Carriers with at least one minor T allele for FGF5 rs16998073 were shown to be at significantly higher risk for developing hypertension. Male TT carriers with a daily sodium intake ≥2000 mg also demonstrated an increased risk for developing hypertension compared to the male AA carriers with daily sodium intake <2000 mg (adjusted odds ratio (AOR) = 2.41, 95% confidence intervals (CIs) = 1.84-3.15, p-interaction < 0.0001). Female AA carriers with a daily potassium intake ≥3500 mg showed a reduced risk for hypertension when compared to female AA carriers with a daily potassium intake <3500 mg (AOR = 0.75. 95% CIs = 0.58-0.95, p-interaction < 0.0001). Male TT carriers in the mid-tertile for sodium-potassium ratio values showed the highest odds ratio for hypertension when compared to male AA carriers in the lowest-tertile for sodium-potassium ratio values (AOR = 3.03, 95% CIs = 2.14-4.29, p-interaction < 0.0001). This study confirmed that FGF5 rs16998073 variants do place their carriers (men and women) at increased risk for developing hypertension. In addition, we showed that high daily intake of sodium exerted a synergistic effect for hypertension when combined with FGF5 rs16998073 variants in both genders and that dietary sodium, potassium, and sodium-potassium ratios all interact with FGF5 rs16998073 and alter the risk of developing hypertension in carriers of either gender among Koreans.

Association Between Blood Lead Level and Uncontrolled Hypertension in the US Population (NHANES 1999-2016).

Background This study aims to explore whether higher blood lead levels (BLL) may be associated with failure to control blood pressure and subsequent uncontrolled hypertension. Methods and Results We used serial cross-sectional waves of the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016. 30 762 subjects aged 20 years and above were included. Uncontrolled hypertension was defined as systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg. We estimated odds ratios (ORs) of quartiles of BLL for any hypertension and uncontrolled hypertension by sex using logistic regression, adjusted for demographics, smoking status, serum cotinine, alcohol intake, body mass index, and menopause status in women. The weighted prevalence of hypertension was 46.7%, of which 80.1% were uncontrolled. Men, younger ages, ethnic minorities, people with lower income, never and current smokers, and people with higher BLL were less likely to have their hypertension controlled. In men, compared with the lowest quartile of BLL (<0.94 µg/dL), the highest 2 quartiles (0.94-1.50 µg/dL, 1.50-2.30 µg/dL) were associated with hypertension (Q2: OR, 1.12; 95% CI, 0.96-1.30; Q3: OR, 1.16; 95% CI, 1.01-1.34; Q4: OR, 1.25; 95% CI, 1.08-1.45), but not in women. In hypertensive men, higher BLL was related to uncontrolled hypertension compared with the lowest quartile (Q2: OR, 1.34; 95% CI, 0.98-1.85; Q3: OR, 1.70; 95% CI, 1.26-2.30; Q4: OR, 1.96; 95% CI, 1.45-2.65). In women, the relationship was similar (Q2: OR, 1.26; 95% CI, 0.95-1.67; Q3: OR, 1.48; 95% CI, 1.10-2.00; Q4: 1.70; 95% CI, 1.26-2.30). Conclusions BLL is associated with higher prevalence of hypertension and uncontrolled hypertension, with more pronounced association in men.

Comprehensive characterisation of phenolics from Nitraria sibirica leaf extracts by UHPLC-quadrupole-orbitrap- MS and evaluation of their anti-hypertensive activity.

ETHNOPHARMACOLOGICAL RELEVANCE: For more than ten scores years, the leaves and fruits of Nitraria sibirica have been used as a natural remedy for indigestion, irregular manes, and hypertension in the Middle East and Central Asia, especially, are recommended for hypertension treatment in the northwest region, China. AIM OF THE STUDY: we aimed to support the traditional usage of N. sibirica leaves as pharmaceuticals or dietary supplements in treatment of hypertension by investigating their chemical constituents and anti-hypertensive activity. METHODS: We identified the chemical composition of N. sibirica leaves ethanolic purified extract (NSL-EPE) using UHPLC-quadrupole-orbitrap-MS, and quantified the main chemical constituents by an analytical method established and validated. We also evaluated anti-hypertensive activity of NSL-EPE using spontaneously hypertensive rats (SHR): blood pressure was measured weekly by non-invasive blood pressure (NIBP) measurements; hemodynamic parameters, biochemical and clinical chemistry variables in plasma, serum and kidney tissue were measured after 10 weeks of treatment with NSL-EPE as well. RESULTS: UHPLC-quadrupole-orbitrap-MS analysis identified 52 compounds, of which 40 compounds were reported for the first time in N. sibirica. 11 phenolic compounds further quantitatively analyzed, among which the most abundant compound was found to be clovin (8.8%). Systolic blood pressure decreased progressively from the second treatment week compared to that in non-treated SHRs. The plasma endothelin, aldosterone, angiotensin II levels were significantly increased, while the level of NOX was significantly decreased; glutathione to oxidized glutathione ratio, superoxide dismutase and total catalase levels in the kidney tissue were markedly accelerated, while malondialdehyde level was significantly reduced in NSL-EPE treated SHRs. Moreover, the serum cholesterol, triglyceride, blood uria nitrogen and creatinine were attenuated in NSL-EPE treated SHRs (P < 0.05), but in sharp contrast to those values in the water-treated SHRs. CONCLUSION: This study screened out leading compounds from N. sibirica and offered a new understanding of the antihypertensive properties of N. sibirica leaves, by which inhibit oxidative stress-induced endothelial dysfunction and improve lipid profiles.

Impact of pulsed electromagnetic field therapy on vascular function and blood pressure in hypertensive individuals.

The present study investigated the impact of 12 weeks of pulsed electromagnetic field (PEMF) therapy on peripheral vascular function, blood pressure (BP), and nitric oxide in hypertensive individuals. Thirty hypertensive individuals (SBP > 130 mm Hg and/or MAP > 100 mm Hg) were assigned to either PEMF group (n = 15) or control group (n = 15). During pre-assessment, participants underwent measures of flow-mediated dilation (FMD), BP, and blood draw for nitric oxide (NO). Subsequently, they received PEMF therapy 3x/day for 12 weeks and, at conclusion, returned to the laboratory for post-assessment. Fifteen participants from the PEMF group and 11 participants from the control group successfully completed the study protocol. After therapy, the PEMF group demonstrated significant improvements in FMD and FMDNOR (normalized to hyperemia), but the control group did not (P = .05 and P = .04, respectively). Moreover, SBP, DBP, and MAP were reduced, but the control group did not (P = .04, .04, and .03, respectively). There were no significant alterations in NO in both groups (P > .05). Twelve weeks of PEMF therapy may improve BP and vascular function in hypertensive individuals. Additional studies are needed to identify the mechanisms by which PEMF affects endothelial function.