[Interpretation and review of Clinical Practice Guidelines for Management of Hypertension in China (2020 edition) and exploration of traditional Chinese medicine for antihypertensive treatment].

Hypertension is the most important risk factor for cardiovascular disease-related deaths among urban and rural residents, and it has become a significant global public health issue. In October 2022, the Clinical Practice Guidelines for the Management of Hypertension in China(hereinafter referred to as the Practice Guidelines) were jointly released by the National Cardiovascular Center and other academic organizations. The Practice Guidelines sparked extensive discussions as they clearly lowered the diagnostic criteria for hypertension, raised the blood pressure targets for elderly patients, and proposed changes in the timing of early medication intervention. While these adjustments have some international evidence-based support, there is still debate regarding the cardiovascular benefits of intensified blood pressure control based on the existing level of evidence. Furthermore, whether the series of new standards proposed in the Practice Guidelines are suitable for the Chinese population and whether the hypertension control level in primary care in China can adapt to the new diagnostic and treatment standards require further in-depth research. In contrast to the strict blood pressure control concept emphasized in the Practice Guidelines, traditional Chinese medicine(TCM) emphasizes the concept of comprehensive prevention and treatment and holistic therapy in the treatment of hypertension, including prehypertension, hypertension, and target organ damage. In recent years, based on abundant clinical trial research and high-quality evidence-based support, the advantages of TCM in treating hypertension have gradually emerged. Previous studies by this research team have found that the pathogenesis of hypertension includes three major types: fire syndrome, fluid retention syndrome, and deficiency syndrome. TCM treatment of hypertension features stable blood pressure reduction, gentle blood pressure lowering, and long-lasting effects. In addition to blood pressure reduction, it also has effects such as reversing risk factors and protecting target organ damage. It demonstrates the characteristics of multiple targets, multiple components, and comprehensive regulation, and can be applied throughout the entire process of prevention and treatment, including prehypertension, hypertension, and target organ damage in the early, middle, and late stages of hypertension. Therefore, it has certain clinical application prospects.

A systematic review and meta-analysis of mindfulness-based stress reduction for arterial hypertension.

Arterial hypertension is a major public health issue. Non-pharmacological approaches like Mindfulness-Based Stress Reduction (MBSR) might be a promising addition to conventional therapy. This systematic review and meta-analysis aim to evaluate the effects of MBSR on systolic (SBP) and diastolic blood pressure (DBP) among individuals with prehypertension or hypertension. We searched Medline/PubMed, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials (RCTs) from their inception until August 1st 2021. RCTs were included that compared MBSR to any control intervention in participants with diagnosed prehypertension (120-139/80-89 mmHg) or hypertension (≥140/≥90 mmHg). Mean differences (MD) and 95% confidence intervals (CI) were calculated. Risk of Bias was assessed using the Cochrane tool. Seven RCTs with 429 participants were included. Very low quality of evidence was found for positive effects of MBSR on SBP (MD = -11.26 mmHg, 95%CI = -20.24 to -2.29, p = 0.01) but no evidence for effects on DBP levels (MD = -3.62 mmHg, 95%CI = -8.52 to 1.29, p = 0.15) compared to waitlist control. Compared to active control, very low quality of evidence was found for positive effects on DBP (MD = -5.51 mmHg, 95%CI = -10.93 to -0.09, p = 0.05) but no effects on SBP levels (MD = -4.33 mmHg, 95%CI = -12.04 to 3.38, p = 0.27). Overall, the studies showed a high degree of heterogeneity. The effects found were robust against selection, detection, and attrition bias. Only one RCT reported safety data. MBSR may be an option for lowering blood pressure in people with prehypertension to hypertension. More and larger high-quality studies are needed to substantiate our findings.

Efficacy of individualized homeopathic medicines in intervening with the progression of pre-hypertension to hypertension: A double-blind, randomized, placebo-controlled trial.

CONTEXT: Pre-hypertension remains a significant public health challenge and appropriate intervention is required to stop its progression to hypertension and/or cardiovascular diseases. OBJECTIVE: To study the effects of individualized homeopathic medicines (IH) against placebo in intervening with the progression of pre-hypertension to hypertension. DESIGN: Double-blind, randomized, two parallel arms, placebo-controlled trial. SETTING: Outpatient departments of D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, India. PATIENTS: Ninety-two patients suffering from pre-hypertension; randomized to receive either IH (n = 46) or identical-looking placebo (n = 46). INTERVENTIONS: IH or placebo in the mutual context of lifestyle modification (LSM) advices including dietary approaches to stop hypertension (DASH) and brisk exercises. MAIN OUTCOME MEASURES: Primary - systolic and diastolic blood pressure (SBP and DBP); secondary - Measure Yourself Medical Outcome Profile version 2.0 (MYMOP-2) scores; all measured at baseline, and every month, up to 3 months. RESULTS: After 3 months of intervention, the number of patients having progression from pre-hypertension to hypertension between groups were similar without any significant differences in between (all P>0.05). Reduction in BP and MYMOP-2 scores were non-significantly higher (all P>0.05) in the IH group than placebo with small effect sizes. Lycopodium clavatum, Thuja occidentalis and Natrum muriaticum were the most frequently prescribed medicines. No harms or serious adverse events were reported from either group. Thus, there was a small, but non-significant direction of effect favoring homeopathy, which ultimately rendered the trial as inconclusive. [Trial registration: CTRI/2018/10/016,026; UTN: U1111-1221-8251].

Efficacy of Khar-i-khasak (Tribulus terrestris Linn.) in prehypertension: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Prehypertension is a state of above-normal blood pressure that does not meet the criteria for the diagnosis of hypertension and its prevalence estimated in population-based samples ranges from 22 to 52%. It conveys potentially many deleterious consequences such as high risk of progression to hypertension and cardiovascular disease later in life. OBJECTIVES: The present study was conducted to evaluate the blood pressure-lowering effect of Khar-i-khasak (Tribulus terrestris Linn.) in prehypertensive individuals. METHODS: This randomized, double-blind, placebo-controlled, clinical trial was conducted at the National Institute of Unani Medicine, Hospital, Bengaluru, after approval by the Institutional Ethics Committee. Prehypertensive individuals over 18 years of age were enrolled after obtaining their written informed consent and were randomly allocated to the test or placebo group. The test and placebo groups were administered powdered dried fruits of Khar-i-khasak (6g) and matched placebo (6g) in three divided doses for two months respectively. The efficacy assessment was determined by changes in systolic and diastolic blood pressures. RESULTS: Both systolic and diastolic blood pressure showed a significant decline in the test group (p<0.001) as compared to the placebo group. The average decline in systolic/diastolic blood pressure was -7.7/5.5 mmHg in the test group and -1.9/0.2 mmHg in the placebo group. During the post-therapy follow-up period, no prehypertensive developed full-blown hypertension in either group. Safety parameters were found to be within normal limits. CONCLUSIONS: The test drug Khar-i-khasak (T. terrestris Linn.) was found to be effective and safe in lowering blood pressure compared to placebo in prehypertensive individuals.

Sex May Modulate the Effects of Combined Polyphenol Extract and L-citrulline Supplementation on Ambulatory Blood Pressure in Adults with Prehypertension: A Randomized Controlled Trial.

Increased blood pressure (BP), vascular dysfunction and inflammation are involved in the etiology of cardiovascular disease (CVD). Although several dietary components such as polyphenols and L-citrulline may help to control BP, their combined impact on ambulatory BP in individuals at risk of CVD remains unknown. The objective of this research was to investigate the short-term impact of supplementation with a combination of polyphenol extract and L-citrulline on ambulatory BP, endothelial function and inflammation. In a randomized double-blind parallel trial, 73 men and women with prehypertension were supplemented with a placebo (cellulose, n = 34, Plac) or 548 mg/day of polyphenols and 2 g/day of L-citrulline (n = 35, Suppl) for 6 weeks. The primary outcome of this study was the difference between groups in 24-h ambulatory diastolic BP (DBP) at week six. Secondary outcomes were a difference between groups at week six in ambulatory systolic BP (SBP), casual BP, serum lipids and high-sensitivity C-reactive protein (hs-CRP) concentrations and skin advanced glycation end products (AGEs). Potential interaction of treatment with sex was examined. Suppl had no impact on mean ambulatory SBP and DBP (p > 0.10 vs. placebo). Daytime and 24-h SBP were reduced with Suppl in women (p ≤ 0.01), but not in men (p ≥ 0.27). A non-significant reduction in AGEs was observed after Suppl compared to Plac among all participants (p = 0.07) and there was no difference in the concentrations of blood lipids (p > 0.20) or CRP (p = 0.36) between treatments at week six. Therefore, supplementation with polyphenol extract and L-citrulline for 6 weeks has no impact on ambulatory BP, blood lipids and CRP in adults with prehypertension. However, the polyphenol extract/L-citrulline supplement may reduce ambulatory SBP in women, but not in men. These preliminary results need further research efforts towards further documenting this sex-dependent BP response to supplementation with polyphenols and L-citrulline.

The effects of soursop supplementation on blood pressure, serum uric acid, and kidney function in a prehypertensive population in accordance with the 2017 ACC/AHA guideline.

Soursop consumption is beneficial to health, but there have been few clinical studies observing its benefit in human subjects. We investigated the effects of soursop supplementation on blood pressure (BP), serum uric acid (SUA), and kidney function. A total of 143 subjects were included in this randomized controlled trial. Subjects were selected from a prehypertension population dataset (n = 4190) in the "Mlati Study Database" in 2007 (using the Joint National Committee (JNC) 7 guideline). After 10 years, 143 samples showed essential prehypertension combined with high-normal SUA levels. Subjects were randomly allocated into two groups, i.e., the treatment and control group. For a 3-month period, the treatment group was given 2 × 100 g soursop fruit juice per day and the control group was not treated. Using the JNC 7 guideline, the treatment group showed a significantly lower mean systolic BP after being adjusted by three times of examinations (baseline, week 6 and 12) compared with the control group. Furthermore, the control group was more likely to have prehypertension, hypertension, and high-normal and high SUA levels after 6 weeks, as well as after 12 weeks, compared with the treatment group. An additional analysis using the 2017 ACC/AHA guideline for subjects with stage 1 hypertension showed results similar to that using the JNC 7 guideline. Moreover, it indicated that mean of both systolic and diastolic BP of the treatment group was significantly lower compared with the control group after 12 weeks of treatment. We conclude that soursop supplementation can lower BP and SUA levels.

Beneficial effects of Codonopsis lanceolata extract on systolic blood pressure levels in prehypertensive adults: A double-blind, randomized controlled trial.

Codonopsis lanceolata (CL) extract was shown to have antihypertensive effects in hypertensive rats. This randomized controlled trial was designed to investigate the ability of CL extract to prevent hypertension (HTN) in prehypertensive subjects. Eighty subjects aged 19-60 years with a systolic blood pressure (BP) of 120-139 mmHg and a diastolic BP of 80-89 mmHg were recruited over 3 months. Subjects were randomized 1:1 to a CL group and a placebo (PL) group and administered CL extract and starch, respectively, for 6 weeks. (BP) was measured and blood sampled at baseline and at the end of the trial. Relative to baseline, systolic BP was significantly decreased, and catalase activity was significantly increased following CL treatment in both the elevated systolic BP and stage 1 HTN subgroups. In the elevated systolic BP subgroup, serum nitrite concentration relative to baseline was significantly increased in CL compared to PL treated subjects (p = .038). In subjects with stage 1 HTN, high sensitivity C-reactive protein (p = .020) and malondialdehyde (p = .039) showed significantly greater reductions from baseline in the CL than in the PL group. In summary, CL was effective in preventing endothelial dysfunction, inflammation, and lipid peroxidation in prehypertensive subjects, with these effects differing according to baseline systolic BP levels.

Effects of Grape Seed Proanthocyanidin Extract on Vascular Endothelial Function in Participants with Prehypertension: A Randomized, Double-Blind, Placebo-Controlled Study.

This study aimed to investigate the effects of grape seed proanthocyanidin extract (GSPE) on blood pressure and vascular endothelial function in middle-aged Japanese adults with prehypertension. We conducted a randomized, double-blind, placebo-controlled study on 6 men and 24 women aged 40-64 years old. The participants were randomized to receive tablets containing either low-dose (200 mg/day) or high-dose (400 mg/day) GSPE, or placebo, for 12 weeks. Systolic and diastolic blood pressures (SBP and DBP, respectively), brachial flow-mediated dilation (FMD), and other cardiovascular parameters were measured before and after 4, 8, and 12 weeks of treatment. The mean SBP in the high-dose group significantly decreased by 13 mmHg after 12 weeks (P = 0.028), although FMD did not change. In an ad hoc analysis of non-smoking participants (n = 21), the mean SBP, DBP, stiffness parameter ß, distensibility, incremental elastic modulus (Einc), and pulse wave velocity (PWV) also significantly improved in the high-dose group after 12 weeks. Changes in Einc and PWV from baseline to 12 weeks were significantly greater in the high-dose group than in the placebo group (Einc, P = 0.023; PWV, P = 0.03). GSPE consumption could help maintain vascular elasticity and normal blood pressure in this population.

The Effects of a New Generation of Nutraceutical Compounds on Lipid Profile and Glycaemia in Subjects with Pre-hypertension.

INTRODUCION: Treatment strategies for patients with pre-hypertension and low-moderate cardiovascular (CV) risk may include nutraceutical compounds (NCs). AIM: To investigate the efficacy and safety of a new-generation of NC in lowering BP values and improving metabolic profile, in a group of hyper-cholesterolemic subjects with pre-hypertension. METHODS: 131 subjects with pre-hypertension (systolic BP 130-139 mmHg and/or diastolic BP 85-89 mmHg) without organ damage and history of CV diseases were enrolled. 66 subjects were treated with a once-daily oral formulation of a NC (red yeast rice, Berberine, Coenzyme Q10, folic acid and chrome) added to diet for 3 months, while 65 patients followed a diet only. Differences in serum total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDLC and HDLC), triglycerides (TG), glycemia, creatine phosphokinase (CPK), aspartate aminotransferase (AST) alanine aminotransferase (ALT) and body mass index (BMI) were evaluated. RESULTS: At the end of treatment, significant reductions of TC, LDLC, TG glucose levels were observed in both treatment groups, while HDLC values increased in the active treatment group only. A greater reduction of TC, LDLC and glycemia was observed in the treatment group. TG levels were not different within the two groups. BP and BMI levels remained unchanged, as well AST, ALT; CPK slightly increased in both groups, but it remained in the normal range. CONCLUSIONS: In patients with pre-hypertension, NC supplementation was safe, well tolerated and effective in improving lipid pattern and glucose levels and in preventing the progression to overt hypertension.

Grape Seed Extract Supplementation Attenuates the Blood Pressure Response to Exercise in Prehypertensive Men.

We tested the hypothesis that exaggerated pressor responses observed in prehypertensive males (N = 9) during dynamic exercise are attenuated following acute dietary supplementation with grape seed extract (GSE) (i.e., a single dose). Effects of placebo and GSE (300 mg) on systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), cardiac output (CO), stroke volume (SV), total vascular conductance (TVC), and rate × pressure product (RPP) in response to two submaximal cycling workloads (40% and 60% VO2peak) were compared 2 h after ingestion of GSE or placebo on different days, 1 week apart. Endothelial function was also evaluated using flow-mediated dilation (FMD). Placebo treatment had no effect on any of the variables. GSE supplementation attenuated MAP at both workloads (40% VO2peak: 115 ± 1 vs. 112 ± 2 mmHg; 60% VO2peak: 126 ± 2 vs. 123 ± 2 mmHg) and RPP at the lower workload. Conversely, SV, CO, and TVC were augmented during both workloads. FMD was augmented by GSE (18.9 ± 2.0 vs. 12.4% ± 2.0%). These findings indicate that in exercising prehypertensive males, a single dose of GSE reduces blood pressure, peripheral vasoconstriction, and work of the heart and enhances O2 delivery; effects that may be due, in part, to endothelium-dependent vasodilation. We propose that acute GSE treatment represents an intervention that may minimize potential increases in the risk of cardiovascular events during dynamic exercise in prehypertensives.

Consumption of Fruitflow® lowers blood pressure in pre-hypertensive males: a randomised, placebo controlled, double blind, cross-over study.

In order to investigate whether the angiotensin converting enzyme-inhibitory tomato extract Fruitflow® would lower blood pressure after consumption, we conducted a randomised, double-blinded, placebo-controlled human intervention study, involving 12 pre-hypertensive people in a crossover design. Consuming a single dose of 150 mg Fruitflow® resulted in a significant reduction in 24-hour average blood pressure as well as average wake-period and sleep-period SBP, compared to placebo. Other parameters related to blood pressure, such as 24-hour average mean arterial pressure, pulse pressure, heart rate, central aortic systolic pressure and radial augmentation index were also reduced. In addition, the platelet aggregation response to ADP, measured 24 hours after consuming Fruitflow®, fell significantly compared to baseline, and compared to placebo. This pilot study clearly shows the beneficial effects of Fruitflow® on two important cardiovascular risk factors, high blood pressure and platelet hyperactivity.

Effect of oral magnesium supplementation on the transcription of TRPM6, TRPM7, and SLC41A1 in individuals newly diagnosed of pre-hypertension. A randomized, double-blind, placebo-controlled trial.

A stringent regulation of influx and efflux of magnesium by cation transporters seems to play an important role in the regulation of blood pressure (BP). With this regard, we evaluate the effect of oral magnesium supplementation on the transcription of TRPM6, TRPM7, and SLC41A1, in individuals with incident pre-hypertension (preHTN). For such purpose, we conducted a randomized, double-blind, placebo-controlled trial that compared 18 individuals who received oral magnesium lactate (360 mg elemental magnesium) versus 18 individuals who received placebo, during 4 months. Diagnosis of hypertension or normal BP, diabetes, alcohol intake, chronic diarrhea, use of diuretics, intake of magnesium supplementation, and reduced renal function were exclusion criteria. Regarding the transcription analysis of TRPM6, TRPM7, and SLC41A1 using RT-qPCR, leukocyte-rich plasma was obtained and total RNA was isolated with the kit Direct-zol™ RNA MiniPrep (Zymo). The leukocyte TRPM6 mRNA relative expression showed a significant increase (2.1 ± 1.37 and 0.8 ± 0.4, P<0.05), whereas the mRNA relative expression of both leukocyte TRPM7 (0.8 ± 1.1 and 0.9 ± 0.6, pNS) and SLC41A1 (0.9 ± 1.0 and 0.7 ± 0.6, pNS) showed no significant differences, between the magnesium and placebo groups, respectively. Oral magnesium supplementation increases the leukocyte TRPM6 mRNA relative expression, in subjects with new diagnosis of preHTN.

Randomised, double-blind, placebo-controlled, assessment of the efficacy and safety of dietary supplements in prehypertension.

We aimed to evaluate efficacy and tolerability of a protocol including lifestyle modifications and a novel combination of dietary supplements in prehypertension. A prospective, double-blind, randomised, placebo-controlled trial was conducted in 176 subjects (103 men, aged 52±10 years), with blood pressure (BP) of 130-139 mm Hg systolic and/or 85-89 mm Hg diastolic entered. After a single-blind run-in period, participants were randomised to twice daily placebo (n=88) or a commercially available combination pill (n=88). Primary endpoints were the differences in clinic BP between the two groups at the end of the trial. Secondary endpoints included intragroup differences in clinic BP during the study period and response rates (that is, BP <130/85 mm Hg or a BP reduction >5 mm Hg on week 12). Baseline characteristics were similar among the treatment groups. At 12 weeks, the supplement group had lower systolic BP (124±9 versus 132±7 mm Hg, P<0.0001) and similar diastolic BP (81±8 versus 82±7 mm Hg, P=0.382) compared to the placebo group. With respect to baseline measures, changes in BP with supplements were statistically significant for systolic (-9.3±4.2 mm Hg, P<0.0001) and diastolic values (-4.2±3.6 mm Hg, P<0.0001). Changes versus baseline in systolic and diastolic BP, conversely, were not different on placebo. The overall response rate at week 12 was significantly greater with supplements than placebo (58% (51 of 88) and 25% (22 of 88), respectively, P<0.0001). This randomised trial shows that combination of supplements with BP-lowering effect is an effective additional treatment to conventional lifestyle modifications for a better control of systolic BP in prehypertension.

Whey protein lowers blood pressure and improves endothelial function and lipid biomarkers in adults with prehypertension and mild hypertension: results from the chronic Whey2Go randomized controlled trial.

BACKGROUND: Cardiovascular diseases (CVDs) are the greatest cause of death globally, and their reduction is a key public-health target. High blood pressure (BP) affects 1 in 3 people in the United Kingdom, and previous studies have shown that milk consumption is associated with lower BP. OBJECTIVE: We investigated whether intact milk proteins lower 24-h ambulatory blood pressure (AMBP) and other risk markers of CVD. DESIGN: The trial was a double-blinded, randomized, 3-way-crossover, controlled intervention study. Forty-two participants were randomly assigned to consume 2 × 28 g whey protein/d, 2 × 28 g Ca caseinate/d, or 2 × 27 g maltodextrin (control)/d for 8 wk separated by a 4-wk washout. The effects of these interventions were examined with the use of a linear mixed-model ANOVA. RESULTS: Thirty-eight participants completed the study. Significant reductions in 24-h BP [for systolic blood pressure (SBP): -3.9 mm Hg; for diastolic blood pressure (DBP): -2.5 mm Hg; P = 0.050 for both)] were observed after whey-protein consumption compared with control intake. After whey-protein supplementation compared with control intake, peripheral and central systolic pressures [-5.7 mm Hg (P = 0.007) and -5.4 mm Hg (P = 0.012), respectively] and mean pressures [-3.7 mm Hg (P = 0.025) and -4.0 mm Hg (P = 0.019), respectively] were also lowered. Flow-mediated dilation (FMD) increased significantly after both whey-protein and calcium-caseinate intakes compared with control intake [1.31% (P < 0.001) and 0.83% (P = 0.003), respectively]. Although both whey protein and calcium caseinate significantly lowered total cholesterol [-0.26 mmol/L (P = 0.013) and -0.20 mmol/L (P = 0.042), respectively], only whey protein decreased triacylglycerol (-0.23 mmol/L; P = 0.025) compared with the effect of the control. Soluble intercellular adhesion molecule 1 and soluble vascular cell adhesion molecule 1 were reduced after whey protein consumption (P = 0.011) and after calcium-caseinate consumption (P = 0.039), respectively, compared with after control intake. CONCLUSIONS: The consumption of unhydrolyzed milk proteins (56 g/d) for 8 wk improved vascular reactivity, biomarkers of endothelial function, and lipid risk factors. Whey-protein supplementation also lowered 24-h ambulatory SBP and DBP. These results may have important implications for public health. This trial was registered at clinicaltrials.gov as NCT02090842.

Effects of Potassium Magnesium Citrate Supplementation on 24-Hour Ambulatory Blood Pressure and Oxidative Stress Marker in Prehypertensive and Hypertensive Subjects.

Diet rich in fruits, vegetables, and dairy products, known as the Dietary Approaches to Stop Hypertension (DASH) diet, is known to reduce blood pressure (BP) in hypertensive patients. More recently, the DASH diet was shown to reduce oxidative stress in hypertensive and nonhypertensive humans. However, the main nutritional components responsible for these beneficial effects of the DASH diet remain unknown. Because the DASH diet is rich in potassium (K), magnesium (Mg), and alkali, we performed a randomized, double-blinded, placebo-controlled study to compare effects of potassium magnesium citrate (KMgCit), potassium chloride (KCl), and potassium citrate (KCit) to allow dissociation of the three components of K, Mg, and citrate on 24-hour ambulatory BP and urinary 8-isoprostane in hypertensive and prehypertensive subjects, using a randomized crossover design. We found that KCl supplementation for 4 weeks induced a significant reduction in nighttime SBP compared with placebo (116 ± 12 vs 121 ± 15 mm Hg, respectively, p <0.01 vs placebo), whereas KMgCit and KCit had no significant effect in the same subjects (118 ± 11 and 119 ± 13 mm Hg, respectively, p >0.1 vs placebo). In contrast, urinary 8-isoprostane was significantly reduced with KMgCit powder compared with placebo (13.5 ± 5.7 vs 21.1 ± 10.5 ng/mgCr, respectively, p <0.001), whereas KCl and KCit had no effect (21.4 ± 9.1 and 18.3 ± 8.4, respectively, p >0.1 vs placebo). In conclusion, our study demonstrated differential effects of KCl and KMgCit supplementation on BP and the oxidative stress marker in prehypertensive and hypertensive subjects. Clinical significance of the antioxidative effect of KMgCit remains to be determined in future studies.

Research protocol: effect of natural S-equol on blood pressure and vascular function--a six-month randomized controlled trial among equol non-producers of postmenopausal women with prehypertension or untreated stage 1 hypertension.

BACKGROUND: Although higher habitual soy intake is associated with lower blood pressure (BP) and stroke incidence, clinical trials using soy protein or isoflavones on cardiovascular risks yielded inconsistent results. The discrepancies are hypothesized to be due to the individuals' intestinal bacterial capacity to metabolite isoflavones daidzein into equol. Animal and in vitro studies have revealed that equol has stronger estrogen-like and anti-oxidative activity than isoflavones and possesses natriuretic and vasorelaxant properties which may play an important role in the prevention of hypertension. However, no clinical trial has examined the effect of equol on BP. We thus propose a 24-week randomized controlled trial to test the effectiveness of natural S-equol on BP and vascular function among equol non-producers. METHODS/DESIGN: This will be a 6-month double-blind, randomized, placebo-controlled trial among 207 non-equol producing postmenopausal women with prehypertension or early untreated hypertension. Eligible participants who have completed a 2-week run-in will be randomized to either one of the 3 groups: placebo group, low-equol group (10 mg/d) and high equol group (20 mg/d). The outcome measures will be conducted at baseline and at the end of the trial including 24 h ambulatory BP, endothelial function (by ultrasound determined brachial flow mediated dilation), arterial stiffness (by pulse wave analysis) and other cardiovascular risk factors (lipid profile, glycemic control and inflammatory biomarkers). Urinary isoflavones will be tested for compliance assessment. One way analysis of variance will be applied to compare the 6-month changes in ambulatory BP or parameters of vascular function among the 3 treatment groups. DISCUSSION: This study will be performed in community subjects. If the antihypertensive effect of equol is proven, the provision of natural equol to those high risk adults who are unable to produce equol will have enormous public health implications for the primary and secondary prevention of hypertension and cardiovascular diseases on a population basis. The research efforts will also have significant implications for industry in the provision of suitable soy products for the prevention of hypertension and its related complications. TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov with identifier of NCT02515682 .

Blood pressure-lowering effect of Korean red ginseng associated with decreased circulating Lp-PLA2 activity and lysophosphatidylcholines and increased dihydrobiopterin level in prehypertensive subjects.

We evaluated the effects of red ginseng consumption on blood pressure (BP) and the fasting plasma metabolome. This randomized, double-blind, placebo-controlled study included nonobese, nondiabetic, prehypertensive subjects consuming 10 capsules daily containing 5 g red ginseng (n=31) or placebo (n=31). Fasting plasma metabolome profiles were obtained using ultra performance liquid chromatography-linear trap quadrupole Orbitrap MS. After 12 weeks, participants consuming red ginseng showed reductions of 6.5 and 5.0 mm Hg in systolic and diastolic BP, respectively. Compared with controls, those consuming red ginseng showed greater reductions in changed values of systolic BP, diastolic BP and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, after adjusting for baseline values. In addition, the red ginseng group showed a greater increase in dihydrobiopterin levels and greater decrease in palmitic amide and lysophosphatidylcholines (lysoPCs). The change in diastolic BP positively correlated with changes in lysoPCs and Lp-PLA2 activity. The BP-lowering effect of red ginseng is associated with decreased Lp-PLA2 and lysoPCs and increased dihydrobiopterin levels in prehypertensive subjects (ClinicalTrials.gov: NCT02326766).

Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study.

Taurine, the most abundant, semiessential, sulfur-containing amino acid, is well known to lower blood pressure (BP) in hypertensive animal models. However, no rigorous clinical trial has validated whether this beneficial effect of taurine occurs in human hypertension or prehypertension, a key stage in the development of hypertension. In this randomized, double-blind, placebo-controlled study, we assessed the effects of taurine intervention on BP and vascular function in prehypertension. We randomly assigned 120 eligible prehypertensive individuals to receive either taurine supplementation (1.6 g per day) or a placebo for 12 weeks. Taurine supplementation significantly decreased the clinic and 24-hour ambulatory BPs, especially in those with high-normal BP. Mean clinic systolic BP reduction for taurine/placebo was 7.2/2.6 mm Hg, and diastolic BP was 4.7/1.3 mm Hg. Mean ambulatory systolic BP reduction for taurine/placebo was 3.8/0.3 mm Hg, and diastolic BP was 3.5/0.6 mm Hg. In addition, taurine supplementation significantly improved endothelium-dependent and endothelium-independent vasodilation and increased plasma H2S and taurine concentrations. Furthermore, changes in BP were negatively correlated with both the plasma H2S and taurine levels in taurine-treated prehypertensive individuals. To further elucidate the hypotensive mechanism, experimental studies were performed both in vivo and in vitro. The results showed that taurine treatment upregulated the expression of hydrogen sulfide-synthesizing enzymes and reduced agonist-induced vascular reactivity through the inhibition of transient receptor potential channel subtype 3-mediated calcium influx in human and mouse mesenteric arteries. In conclusion, the antihypertensive effect of chronic taurine supplementation shows promise in the treatment of prehypertension through improvement of vascular function.

Effects of Rubus occidentalis extract on blood pressure in patients with prehypertension: Randomized, double-blinded, placebo-controlled clinical trial.

OBJECTIVE: Black raspberry (Rubus occidentalis) is known for improving vascular function. However, there has been no study evaluating its effects on 24-h systolic and diastolic blood pressure in prehypertensive patients. The aim of this study was to examine those effects. METHODS: Patients with prehypertension (N = 45) were prospectively randomized into a moderate-dose black raspberry group (n = 15, 1500 mg/d), a high-dose black raspberry group (n = 15, 2500 mg/d), or a placebo group (n = 15) during an 8-wk follow-up period. Raspberries were consumed in the form of a dried powder extract that was fashioned into capsules. The capsules contained 187.5 and 312.5 mg of raspberry powder, which was equivalent to 1500 and 2500 mg raspberries. Ambulatory 24-h blood pressure (BP); central BP; pulse-wave velocity; abdominal visceral fat; serum renin; angiotensin-converting enzyme; and inflammatory cytokines such as interleukin-6, tumor necrosis factor-α, C-reactive protein, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and plasminogen activator inhibitor-1 were measured at baseline and at 8-wk follow-up. RESULTS: High-dose black raspberry significantly reduced 24-h systolic blood pressure (SBP; 3.3 ± 10 mm Hg versus -6.7 ± 11.8 mm Hg; P < 0.05) and nighttime SBP (5.4 ± 10.6 mm Hg versus -4.5 ± 11.3 mm Hg; P < 0.05) compared with controls during the 8-wk follow-up. Black raspberry powder did not produce any significant changes in most of the parameters other than BP. CONCLUSION: The use of black raspberry significantly lowered 24-h BP in prehypertensive patients during the 8-wk follow-up. Black raspberry used as a dietary supplement could be beneficial in reducing SBP in prehypertensive patients.

Effects of grape seed extract beverage on blood pressure and metabolic indices in individuals with pre-hypertension: a randomised, double-blinded, two-arm, parallel, placebo-controlled trial.

The aim of the present study was to test grape seed extract (GSE) as a functional ingredient to lower blood pressure (BP) in individuals with pre-hypertension. A single-centre, randomised, two-arm, double-blinded, placebo-controlled, 12-week, parallel study was conducted in middle-aged adults with pre-hypertension. A total of thirty-six subjects were randomised (1:1) to Placebo (n 18) or GSE (n 18) groups; twenty-nine of them completed all the protocol-specified procedures (Placebo, n 17; GSE, n 12). Subjects consumed a juice (167 kJ (40 kcal)) containing 0 mg (Placebo) or 300 mg/d GSE (150 mg) twice daily for 6 weeks preceded by a 2-week Placebo run-in and followed by 4-week no-beverage follow-up. Compliance was monitored. BP was measured at screening, 0, 6 and 10 weeks of intervention and blood samples were collected at 0, 3, 6 and 10 weeks of intervention. GSE significantly reduced systolic BP (SBP) by 5·6 % (P=0·012) and diastolic BP (DBP) by 4·7 % (P=0·049) after 6 weeks of intervention period, which was significantly different (SBP; P=0·03) or tended to be different (DBP; P=0·08) from Placebo. BP returned to baseline after the 4-week discontinuation period of GSE beverage. Subjects with higher initial BP experienced greater BP reduction; nearly double the effect size. Fasting insulin and insulin sensitivity tended to improve after 6 weeks of GSE beverage supplementation (P=0·09 and 0·07, respectively); no significant changes were observed with fasting plasma lipids, glucose, oxidised LDL, flow-mediated dilation or vascular adhesion molecules. Total plasma phenolic acid concentrations were 1·6 times higher after 6 weeks of GSE v. Placebo. GSE was found to be safe and to improve BP in people with pre-hypertension, supporting the use of GSE as a functional ingredient in a low-energy beverage for BP control.