Effect of regulated vitamin D increase on vascular markers in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials.

AIM: The effect of increased vitamin D levels on vascular function in patients with chronic kidney disease (CKD) is controversial. This meta-analysis aimed to assess the effect of regulated vitamin D increase on vascular markers in patients with CKD. DATA SYNTHESIS: We searched PubMed, Web of Science, Embase and ClinicalTrials.gov from database inception up until July 21, 2023. We included randomized controlled trials assessing the effects of using vitamin D and its analogues on vascular function in patients with CKD. Fixed-effects and random-effects model analyses were performed using weighted mean difference effects for each trial by heterogeneity (I2) assessment. Primary outcomes encompassed blood flow-mediated dilation (FMD)、pulse wave velocity (PWV) and augmentation index (AIx). FINDINGS: From 1964 records we selected 12 trials, 5 (n = 331) on FMD, 8 (n = 626) on PWV and 4 (n = 393) on AIx. Vitamin D and VDRA supplementation failed to significantly improve FMD (WMD 1.68%; 95% CI -0.18 to 3.53; P = 0.08; I2 = 88%)、PWV (WMD -0.41 m/s; 95%CI -0.95 to 0.13; P = 0.14; I2 = 57%)and AIx (WMD -0.53%; 95%CI -1.69 to 0.63; P = 0.37; I2 = 0%). Subgroup analysis revealed that 2 µg paricalcitol significantly improved FMD (WMD 2.09%; 95%CI 1.28 to 2.90; P < 0.00001); I2 = 0%), as did cholecalciferol (WMD 5.49%; 95% CI 4.35 to 6.63; P < 0.00001). CONCLUSION: Supplementation vitamin D and VDRA are associated with improved vascular function as measured by FMD, but not arterial stiffness as measured by PWV and AIx, tentatively suggesting that regulating the increase of vitamin D could not potentially reduce the incidence of cardiovascular disease.

Pharmacological modulation of vascular ageing: A review from VascAgeNet.

Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation.

Carnosine Did Not Affect Vascular and Metabolic Outcomes in Patients with Prediabetes and Type 2 Diabetes: A 14-Week Randomized Controlled Trial.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in patients with prediabetes and type 2 diabetes mellitus (T2DM). Carnosine has been suggested as a potential approach to reduce ASCVD risk factors. However, there is a paucity of human data. Hence, we performed a 14-week double-blind randomized placebo-controlled trial to determine whether carnosine compared with placebo improves vascular and metabolic outcomes in individuals with prediabetes and T2DM. In total, 49 patients with prediabetes and T2DM with good glycemic control were randomly assigned either to receive 2 g/day carnosine or matching placebo. We evaluated endothelial dysfunction, arterial stiffness, lipid parameters, blood pressure, heart rate, hepatic and renal outcomes before and after the intervention. Carnosine supplementation had no effect on heart rate, peripheral and central blood pressure, endothelial function (logarithm of reactive hyperemia (LnRHI)), arterial stiffness (carotid femoral pulse wave velocity (CF PWV)), lipid parameters, liver fibroscan indicators, liver transient elastography, liver function tests, and renal outcomes compared to placebo. In conclusion, carnosine supplementation did not improve cardiovascular and cardiometabolic risk factors in adults with prediabetes and T2DM with good glycemic control. Therefore, it is improbable that carnosine supplementation would be a viable approach to mitigating the ASCVD risk in these populations. The trial was registered at clinicaltrials.gov (NCT02917928).

Efficacy of γ-linolenic acid, Vitis vinifera extract, and acetyl-L-carnitine combination therapy for improving arterial stiffness in Korean adults: Real-world evidence.

Atherosclerosis is associated with various cardiovascular diseases (CVDs). Measurement of arterial stiffness using pulse wave velocity (PWV) enables assessment of atherosclerosis progression in individuals. The authors screened patients with asymptomatic atherosclerosis, based on the PWV findings, to evaluate appropriate early interventions and assess the efficacy of γ-linolenic acid, Vitis vinifera extract, and acetyl-L-carnitine triple combination therapy in atherosclerosis prevention. This retrospective study analyzed the medical records of adult patients between March 2007 and April 2019, with presenting complaints of fatigue and lethargy. Among patients with vascular stiffness beyond their biological age on brachial-ankle PWV (baPWV) testing, those with ≥80% compliance for three drugs were allocated to the experimental group. Those with compliance of <80% for any one drug were allocated to the control group to assess changes in arterial stiffness, fasting plasma glucose (FPG), lipid level, and blood pressure (BP). After 1 year of triple-combination therapy, there were significant decreases in right and left baPWV (1537.16 ± 274.84 and 1519.00 ± 289.32 cm/s, respectively) as compared to baseline (1633.15 ± 271. 20 and 1598.64 ± 267.95 cm/s, respectively; p < .001). There was no difference in baPWV between sexes. Moreover, neither group showed significant changes in FPG and lipid levels. When triple-combination therapy combining γ-linolenic acid, V. vinifera extract, and acetyl-L-carnitine was administered to patients with high arterial stiffness relative to their age, as assessed by baPWV, the experimental group showed a decrease in arterial stiffness in both sexes.

Dietary Intake and Arterial Stiffness in Children and Adolescents: A Systematic Review.

Arterial stiffness is a risk factor for cardiovascular disease that is affected by diet. However, research understanding how these dietary risk factors are related to arterial stiffness during childhood is limited. The purpose of this review was to determine whether various dietary factors were associated with arterial stiffness in the pediatric population. Five databases were systematically searched. Intervention studies, cross-sectional and cohort studies were included that investigated nutrient or food intake and outcomes of arterial stiffness, primarily measured by pulse wave velocity (PWV) and augmentation index (AIx), in the pediatric population (aged 0-18 years). A final 19 studies (six intervention and 13 observational) were included. Only two intervention studies, including a vitamin D and omega-3 supplementation trial, found protective effects on PWV and AIx in adolescents. Findings from observational studies were overall inconsistent and varied. There was limited evidence to indicate a protective effect of a healthy dietary pattern on arterial stiffness and an adverse effect of total fat intake, sodium intake and fast-food consumption. Overall, results indicated that some dietary factors may be associated with arterial stiffness in pediatric populations; however, inconsistencies were observed across all study designs. Further longitudinal and intervention studies are warranted to confirm the potential associations found in this review.

Effect of Menaquinone-7 Supplementation on Arterial Stiffness in Chronic Hemodialysis Patients: A Multicenter Randomized Controlled Trial.

BACKGROUND: There is a very high prevalence of subclinical vitamin K deficiency in patients requiring hemodialysis (HD), and this problem is associated with vascular calcification and arterial stiffness. Vitamin K2 (MK-7) supplementation can improve vitamin K status in HD patients. However, the benefits of vitamin K supplementation on arterial stiffness have still not been established. The present study was conducted to evaluate the efficacy of menaquinone-7 (MK-7) supplementation on arterial stiffness in chronic HD patients. METHODS: This open-label multicenter randomized clinical trial was conducted in 96 HD patients who had arterial stiffness, defined by high carotid femoral pulse wave velocity (cfPWV ≥ 10 m/s). The patients were randomly assigned to receive oral MK-7 (375 mcg once daily) for 24 weeks (n = 50) or standard care (control group; n = 46). The change in cfPWV was the primary outcome. RESULTS: Baseline parameters were comparable between the two groups. There was no significant difference in the change in cPWV at 24 weeks between the MK-7 group and standard care [-6.0% (-20.2, 2.3) vs. -6.8% (-19.0, 7.3), p = 0.24]. However, we found that MK-7 significantly decreased cPWV in patients with diabetes [-10.0% (-15.9, -0.8) vs. 3.8% (-5.8, 11.6), p = 0.008]. In addition, the MK-7 group had a lower rate of arterial stiffness progression, compared to controls (30.2% vs. 39.5%, p = 0.37), especially in diabetes patients (21.4% vs. 72.7%, p = 0.01). No serious adverse events were observed during the 24 weeks. CONCLUSION: Vitamin K supplements provided a beneficial impact in lowering the rate of arterial stiffness progression in chronic hemodialysis patients with diabetes. Possible benefits on cardiovascular outcomes require further investigation.

A Critical Review on Vasoactive Nutrients for the Management of Endothelial Dysfunction and Arterial Stiffness in Individuals under Cardiovascular Risk.

Pathophysiological conditions such as endothelial dysfunction and arterial stiffness, characterized by low nitric oxide bioavailability, deficient endothelium-dependent vasodilation and heart effort, predispose individuals to atherosclerotic lesions and cardiac events. Nitrate (NO3-), L-arginine, L-citrulline and potassium (K+) can mitigate arterial dysfunction and stiffness by intensifying NO bioavailability. Dietary compounds such as L-arginine, L-citrulline, NO3- and K+ exert vasoactive effects as demonstrated in clinical interventions by noninvasive flow-mediated vasodilation (FMD) and pulse-wave velocity (PWV) prognostic techniques. Daily L-arginine intakes ranging from 4.5 to 21 g lead to increased FMD and reduced PWV responses. Isolated L-citrulline intake of at least 5.6 g has a better effect compared to watermelon extract, which is only effective on endothelial function when supplemented for longer than 6 weeks and contains at least 6 g of L-citrulline. NO3- supplementation employing beetroot at doses greater than 370 mg promotes hemodynamic effects through the NO3--NO2-/NO pathway, a well-documented effect. A potassium intake of 1.5 g/day can restore endothelial function and arterial mobility, where decreased vascular tone takes place via ATPase pump/hyperpolarization and natriuresis, leading to muscle relaxation and NO release. These dietary interventions, alone or synergically, can ameliorate endothelial dysfunction and should be considered as adjuvant therapies in cardiovascular diseases.

Cinnamomum cassia on Arterial Stiffness and Endothelial Dysfunction in Type 2 Diabetes Mellitus: Outcomes of a Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Cinnamomum cassia is a medicinal plant whose use has demonstrated benefits on body weight, blood pressure, glucose, and lipids. This study aimed to evaluate the effect of C. cassia on arterial stiffness and endothelial dysfunction (ED) in patients with type 2 diabetes mellitus (T2DM). A randomized, double-blind, placebo-controlled clinical trial was carried out in 18 subjects aged 40-65 years, with a diagnosis of T2DM of one year or less since diagnosis and treated with Metformin 850 mg daily. Patients were randomly assigned to receive either C. cassia or a placebo in 1000 mg capsules, thrice a day, before each meal for 12 weeks. At baseline and after 12 weeks of intervention, brachial-ankle pulse wave velocity and Flow Mediated Dilation were measured, as well as body weight, body mass index (BMI), blood pressure (BP), fasting glucose (FG), glycated hemoglobin A1c (HbA1c), total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and very low density lipoprotein cholesterol, respectively, triglycerides, creatinine, and transaminases. The Mann-Whitney U test for differences between groups and the Wilcoxon signed-rank test for intragroup differences were used, and a P ≤ .05 was considered statistically significant. After C. cassia administration, statistically significant reductions in body weight (81.4 ± 10.4 kg vs. 79.9 ± 9.0 kg, P = .037), BMI (30.6 ± 4.2 kg/m2 vs. 30.1 ± 4.2 kg/m2, P = .018), and HbA1c (53 ± 5.4 mmol/mol vs. 45 ± 2.1 mmol/mol, P = .036) were observed. No changes statistically significant on arterial stiffness, ED, FG, BP, and lipids were observed. C. cassia administration decreases body weight, BMI, and HbA1c without statistically significant changes on arterial stiffness, ED, FG, BP, and lipids. CTR Number: NCT04259606.

Acute effects of nitrate and breakfast on working memory, cerebral blood flow, arterial stiffness, and psychological factors in adolescents: Study protocol for a randomised crossover trial.

BACKGROUND: Inorganic nitrate has been shown to acutely improve working memory in adults, potentially by altering cerebral and peripheral vasculature. However, this remains unknown in adolescents. Furthermore, breakfast is important for overall health and psychological well-being. Therefore, this study will investigate the acute effects of nitrate and breakfast on working memory performance, task-related cerebral blood flow (CBF), arterial stiffness, and psychological outcomes in Swedish adolescents. METHODS: This randomised crossover trial will recruit at least 43 adolescents (13-15 years old). There will be three experimental breakfast conditions: (1) none, (2) low-nitrate (normal breakfast), and (3) high-nitrate (concentrated beetroot juice with normal breakfast). Working memory (n-back tests), CBF (task-related changes in oxygenated and deoxygenated haemoglobin in the prefrontal cortex), and arterial stiffness (pulse wave velocity and augmentation index) will be measured twice, immediately after breakfast and 130 min later. Measures of psychological factors and salivary nitrate/nitrite will be assessed once before the conditions and at two-time points after the conditions. DISCUSSION: This study will provide insight into the acute effects of nitrate and breakfast on working memory in adolescents and to what extent any such effects can be explained by changes in CBF. This study will also shed light upon whether oral intake of nitrate may acutely improve arterial stiffness and psychological well-being, in adolescents. Consequently, results will indicate if nitrate intake from beetroot juice or if breakfast itself could acutely improve cognitive, vascular, and psychological health in adolescents, which can affect academic performance and have implications for policies regarding school meals. TRIAL REGISTRATION: The trial has been prospectively registered on 21/02/2022 at https://doi.org/10.1186/ISRCTN16596056. Trial number: ISRCTN16596056.

The Influence of Dietary Interventions on Arterial Stiffness in Overweight and Obese Subjects.

Arterial stiffness is often increased in overweight/obese subjects before the development of hypertension. It is also one of the earliest indicators of increased cardiovascular disease risk and can be considered a good predictor of the development of subclinical cardiovascular dysfunction. Arterial stiffness is a significant prognostic factor influencing cardiovascular risk, which dietary habits can modify. Obese patients should use the caloric-restricted diet because it augments aortic distensibility, diminishes pulse wave velocity (PWV), and increases the activity of endothelial nitric oxide synthases. High intake of saturated fatty acids (SFA), trans fats, and cholesterol, typical for the Western diet, impairs endothelial function and raises brachial-ankle PWV. The replacement of SFA with monounsaturated (MUFA) or polyunsaturated fatty acids (PUFA) derived from seafood and plants diminishes the risk of arterial stiffness. The dairy product intake (excluding butter) decreases PWV in the general population. The high-sucrose diet causes toxic hyperglycemia and increases arterial stiffness. Complex carbohydrates with a low glycemic index (including isomaltose) should be recommended to keep vascular health. The high sodium intake (>10 g/day), particularly associated with low potassium consumption, has a deleterious effect on arterial stiffness (↑ baPWV). Since vegetables and fruits are good sources of vitamins and phytochemicals, they should be recommended in patients with high PWV. Thus, the dietary recommendation to prevent arterial stiffness should be similar to the Mediterranean diet, which is rich in dairy products, plant oils, and fish, with a minimal red meat intake and five servings of fruits and vegetables daily.

Association of arterial stiffness with all-cause and cause-specific mortality in the diabetic population: A national cohort study.

Background: Estimated pulse wave velocity (ePWV) has been proposed as a potential alternative to carotid-femoral pulse wave velocity to assess the degree of aortic stiffness, and may predict cardiovascular disease (CVD) outcomes and mortality in the general population. However, whether arterial stiffness estimated by ePWV predicts all-cause and cause-specific mortality in patients with diabetes mellitus (DM) has not been reported. Methods: This was a prospective cohort study with data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 and followed up until the end of December 2019. 5,235U.S. adults with DM (age≥20years) were included in the study. Arterial stiffness was estimated by ePWV. Survey-weighted Cox proportional hazards models were performed to assess the hazard ratios (HRs), and 95% confidence intervals (CIs) for the associations of ePWV with all-cause and cause-specific mortality. Meanwhile, the generalized additive model was used to visually assess the dose-dependent relationship between ePWV and mortality. As a complementary analysis, the relationship between mean blood pressure (MBP) and risk of mortality was also examined. Multiple imputations accounted for missing data. Results: For the 5,235 DM patients, the weighted mean age was 57.4 years, and 51.07% were male. During a median follow-up period of 115 months (interquartile range 81-155 months; 53,159 person-years), 1,604 all-cause deaths were recorded. In the fully adjusted Cox regression model, every 1 m/s increase in ePWV was associated with 56% (HR 1.56; 95% CI, 1.44 to 1.69) increase in the risk of all-cause. In addition, a nonlinear relationship between ePWV and all-cause mortality was observed (P for non-linear=0.033). Similar results were obtained after subgroup analysis and multiple imputations. Besides, the risk of most cause-specific mortality, except for accident and renal disease-specific mortality, increased from 53% to 102% for every 1 m/s increase in ePWV. Conclusions: In the diabetic population, ePWV is independently associated with all-cause and most cause-specific mortality risks. ePWV may be a useful tool for assessing mortality risk.

Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial.

Many animal studies have shown that oral administration of the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) prevents the reduction of NAD+ levels in organs and tissues, helping alleviate aging-related diseases. However, there are very few clinical reports of NMN supplementation in humans. Thus, this study aimed to investigate the influence of a 12-week NMN oral supplementation on biochemical and metabolic health parameters. A 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. A total of 36 healthy middle-aged participants received one capsule of either 125 mg NMN or placebo twice a day. Among the NAD+ metabolites, the levels of nicotinamide in the serum were significantly higher in the NMN intake group than in the placebo group. Pulse wave velocity values indicating arterial stiffness tended to decrease in the NMN intake group. However, no significant difference was found between the two groups. Long-term NMN supplementation at 250 mg/day was well tolerated and did not cause adverse events. NMN safely and effectively elevated NAD+ metabolism in healthy middle-aged adults. Additionally, NMN supplementation showed potential in alleviating arterial stiffness.

Effect of vitamin K supplementation on serum calcification propensity and arterial stiffness in vitamin K-deficient kidney transplant recipients: A double-blind, randomized, placebo-controlled clinical trial.

Vitamin K deficiency is common among kidney transplant recipients (KTRs) and likely contributes to progressive vascular calcification and stiffness. In this single-center, randomized, double-blind, placebo-controlled trial, we aimed to investigate the effects of vitamin K supplementation on the primary end point, serum calcification propensity (calciprotein particle maturation time, T50), and secondary end points arterial stiffness (pulse wave velocity [PWV]) and vitamin K status in 40 vitamin K-deficient KTRs (plasma dephosphorylated uncarboxylated matrix Gla protein [dp-ucMGP] ≥500 pmol/L). Participants (35% female; age, 57 ± 13 years) were randomized 1:1 to vitamin K2 (menaquinone-7, 360 µg/day) or placebo for 12 weeks. Vitamin K supplementation had no effect on calcification propensity (change in T50 vs baseline +2.3 ± 27.4 minutes) compared with placebo (+0.8 ± 34.4 minutes; Pbetween group = .88) but prevented progression of PWV (change vs baseline -0.06 ± 0.26 m/s) compared with placebo (+0.27 ± 0.43 m/s; Pbetween group = .010). Vitamin K supplementation strongly improved vitamin K status (change in dp-ucMGP vs baseline -385 [-631 to -269] pmol/L) compared with placebo (+39 [-188 to +183] pmol/L; Pbetween group < .001), although most patients remained vitamin K-deficient. In conclusion, vitamin K supplementation did not alter serum calcification propensity but prevented progression of arterial stiffness, suggesting that vitamin K has vascular effects independent of calciprotein particles. These results set the stage for longer-term intervention studies with vitamin K supplementation in KTRs. TRIAL REGISTRY: EU Clinical Trials Register (EudraCT Number: 2019-004906-88) and the Dutch Trial Register (NTR number: NL7687).

Comparing the effects of different exercises on blood pressure and arterial stiffness in postmenopausal women: A systematic review and meta-analysis.

The present study aimed to compare the efficacy of different exercises on systolic blood pressure (SBP), diastolic blood pressure (DBP), and aortic pulse wave velocity (PWV) in postmenopausal women. We searched the China National Knowledge Infrastructure (CNKI), Wanfang database, Web of Science, PubMed, and Cochrane library databases, up to July 2022. The randomized controlled trials (RCTs) were selected following the inclusion criteria. We assessed study quality with the PEDro scale. The Stata software was used for statistical analysis. Twenty-three papers (26 RCTs) and 729 participants were included. Meta-analysis demonstrated that exercise decreased SBP (WMD = -6.74 mmHg, 95%CI: -9.08, -4.41, p = 0.000), DBP (WMD = -4.13 mmHg, 95%CI: -5.78, -2.48, p = 0.000) and aortic PWV (WMD = -0.79 m/s, 95%CI: -1.02, -0.56, p = 0.000). Aerobic exercise can significantly decrease SBP (WMD = -7.97 mmHg, 95%CI: -12.99, -2.60, p = 0.003) and DBP (WMD = -5.97 mmHg, 95%CI: -8.55, -3.39, p = 0.000). Resistance exercise can significantly decrease SBP (WMD = -5.62 mmHg, 95%CI: -9.00, -2.23, p = 0.001), DBP (WMD = -1.87 mmHg, 95%CI: -2.75, -0.99, p = 0.000) and aortic PWV (WMD = -0.67 m/s，95%CI: -0.98, -0.36, p = 0.000). Combined aerobic and resistance exercise can significantly decrease SBP (WMD = -5.42 mmHg, 95%CI: -10.17, -0.68, p = 0.025). The efficacy of mind-body exercise (Tai Chi/Yoga) on SBP, DBP, and aortic PWV were not obvious (p > 0.05). Exercise significantly improved SBP, DBP, and aortic PWV in postmenopausal women. Aerobic exercise decreased SBP and DBP. Resistance exercise decreased SBP, DBP, and aortic PWV. Additionally, further research is required to confirm the efficacy of mind-body exercise (Tai Chi/Yoga) on blood pressure and arterial stiffness.

Changes in Intestinal Flora From Chronic Renal Failure Complicated With Coronary Heart Disease and its Correlation With Arterial Stiffness Index.

Context: One common and serious cardiovascular complication of chronic renal failure (CRF) is coronary heart disease (CHD). CRF can lead to an imbalance of patients' gut microbiota, and changes in intestinal flora might heavily affect CRF's development. Objective: The study intended to investigate the changes in intestinal flora of patients with CRF complicated with CHD and their relationship with ASI to understand the association of those changes and ASI with CRF comorbid with CHD, with the goal of offering a reliable clinical basis for active prevention and treatment of CRF and CHD in the future. Design: The research team designed a prospective controlled study. Setting: The study took place at the Affiliated Hospital of Hebei University in Baoding, Hebei, China. Participants: Participants were 86 patients with both CRF and CHD and 72 patients with CHD only who had been admitted to the hospital between October 2019 and January 2021. Intervention: The intervention group included participants who had received a diagnosis of CRF complicated with CHD and the control group included participants who had received a diagnosis of CHD only. Outcome Measures: The research team counted participants' intestinal flora and measured their ambulatory blood pressure and arterial stiffness index (ASI) to analyze the correlation of the ASI with the intestinal flora and the related factors impacting CHD in patients with CRF. Results: The monitoring of participants' ambulatory blood pressures showed that the intervention group's day systolic blood pressure (dSBP) and 24h SBP were significantly higher, while the group's day diastolic blood pressure (dDBP) and 24h DBP were significantly lower than those of the control group. The intervention group's levels of lactobacillus, bacteroidaceae, and bifidobacterium were significantly lower than those of the control group, and those intestinal flora were negatively correlated with ASI. The intervention group's levels of Escherichia coli and yeasts were significantly higher than those of the control group, and those intestinal flora were positively correlated with ASI. A significant relationship existed between lactobacillus and yeast and the occurrence of CHD in the CRF participants. Conclusions: Patients with both CRF and CHD have an obvious intestinal-flora imbalance, and the imbalance is strongly bound up with their ASI, which is of great reference significance for novel therapy of such patients and for the clinical application of ASI.

Dietary intake of anthocyanins improves arterial stiffness, but not endothelial function, in volunteers with excess weight: A randomized clinical trial.

Excess body weight has been associated with endothelial dysfunction and increased arterial stiffness. Foods rich in polyphenols and anthocyanins such as açaí-juçara (Euterpe edulis Martius) fruit may have protective vascular effects. Thus, we examined the effect of dietary intake of anthocyanins (açaí-juçara fruit) on endothelial function (flow-mediated dilation [FMD]) and arterial stiffness (pulse wave velocity [PWV]) in individuals with excess body weight. Fifty-five individuals with BMI ≥25 kg/m2 were randomized into non-anthocyanin (N-ATH, n = 25) or anthocyanin (ATH, n = 30) intake groups. A 12-week individualized diet plan (20% reduction in total energy intake) was prescribed and included daily intake of açaí-juçara 200 g (anthocyanins 293.6 mg) in the ATH diet plan. We evaluated anthropometric and biochemical parameters, FMD, PWV, and peripheral vascular resistance (PVR). A GEE (Bonferroni post-hoc) was used (p ≤ 0.05). No change in FMD was observed. However, PWV showed a reduction from baseline in the ATH (p = 0.002) and vs. N-ATH (p = 0.036). Both groups showed reduced peripheral vascular resistance (N-ATH, p = 0.005; ATH, p = 0.040) with no significant differences between them. In conclusion, dietary intake of anthocyanins proved effective in protecting against arterial stiffness (by PWV) in individuals with excess weight. PVR was reduced in both diet groups regardless of dietary intake of anthocyanins.

Wild Watermelon-Extracted Juice Ingestion Reduces Peripheral Arterial Stiffness with an Increase in Nitric Oxide Production: A Randomized Crossover Pilot Study.

Wild watermelon contains various nutrients, but the effect of its acute ingestion on arterial stiffness is unclear. This study aimed to investigate whether a single bout of acute ingestion of wild watermelon-extracted juice decreased arterial stiffness concomitant with an increase in nitric oxide (NO) production. Twelve healthy young female participants were tested under two conditions in a randomized, double-blind crossover study: (1) a beverage containing 90 g of wild watermelon extract and (2) a control beverage: a placebo. Pulse wave velocity (PWV), an index of arterial stiffness, blood flow, and plasma nitrate/nitrite (NOx) levels were measured in the supine position at 30, 60, and 90 min after the intake of each beverage. The changes in femoral-ankle PWV were significantly reduced after wild watermelon-extracted juice intake compared to those in the placebo group. Additionally, the changes in blood flow in the posterior tibial artery and plasma NOx levels after intake of wild watermelon-extracted juice were significantly increased compared to those in the placebo group. These data show that acute ingestion of wild watermelon-extracted juice reduces peripheral (lower limb) arterial stiffness and increases NO bioavailability. To confirm these associations, more detailed investigations of the nutrients that influence these effects should be conducted.

Green tea could improve elderly hypertension by modulating arterial stiffness, the activity of the renin/angiotensin/aldosterone axis, and the sodium-potassium pumps in old male rats.

Hypertension is a major health problem common in the elderly people. Green tea is a popular beverage recommended in folk medicine for lowering blood pressure. However, the molecular mechanisms involved in the antihypertensive effects of green tea are not fully understood. Therefore, the aim of this study was to investigate the antihypertensive effects of green tea on high-salt diet-induced hypertension in old male rats. Forty old male rats were divided into five groups: control, hypertensive, and hypertensive-green tea (2, 4, and 6 g/kg). Heart rate (HR) and systolic blood pressure (SBP) were measured. Cardiac and renal histology were also performed. Lipid profile, NO, angiotensin II (Ang II), and aldosterone were determined, and the expression of eNOS, ATIR and ATIIR, aldosterone receptor, and Atp1a1 were measured. Green tea could significantly decrease HR and SBP, lipid profiles, renin-angiotensin II-aldosterone system activity, and Ang II signaling in kidney tissue of hypertensive rats (p < .01). It also increased Atp1a1, Nrf2, and eNOS expression along with antioxidant enzymes activity and NO concentration (p < .05) and decreased NF-ĸB and iNOS expression and IL-1ß levels in the heart, kidneys, and aorta of rats with hypertension. It can be concluded that green tea can improve salt-induced blood pressure by modulating the function of the renin-angiotensin-aldosterone system, enhancing the synthesis of nitric oxide in the endothelium, increasing antioxidant activity and suppressing inflammation in the heart and kidney, improving the expression of the sodium-potassium pump, and reduction in serum lipids and glucose in aged male rats. PRACTICAL APPLICATIONS: The results of this study showed that green tea could improve hypertension in elderly rats by modulating (1) the expression of the sodium-potassium pump in the heart, kidney, and aortic tissues, (2) the activity of the renin-angiotensin II-aldosterone system in kidney, (3) enhancing antioxidant and anti-inflammatory activities in the heart, aorta, and kidneys, (4) enhancing the synthesis of nitric oxide in the endothelium, and (5) lowering lipid profile. The results of these studies show that the consumption of green tea and its products can be a good candidate for the prevention of cardiovascular diseases such as hypertension in the elderly. In addition, attention to its bioactive compounds can be considered by researchers as an independent therapeutic strategy or adjunctive therapy for the treatment of hypertension.

Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women.

Aging and menopause are associated with decreased nitric oxide bioavailability due to reduced L-arginine (L-ARG) levels contributing to endothelial dysfunction (ED). ED precedes arterial stiffness and hypertension development, a major risk factor for cardiovascular disease. This study investigated the effects of L-citrulline (L-CIT) on endothelial function, aortic stiffness, and resting brachial and aortic blood pressures (BP) in hypertensive postmenopausal women. Twenty-five postmenopausal women were randomized to 4 weeks of L-CIT (10 g) or placebo (PL). Serum L-ARG, brachial artery flow-mediated dilation (FMD), aortic stiffness (carotid-femoral pulse wave velocity, cfPWV), and resting brachial and aortic BP were assessed at 0 and 4 weeks. L-CIT supplementation increased L-ARG levels (Δ13 ± 2 vs. Δ−2 ± 2 µmol/L, p < 0.01) and FMD (Δ1.4 ± 2.0% vs. Δ−0.5 ± 1.7%, p = 0.03) compared to PL. Resting aortic diastolic BP (Δ−2 ± 4 vs. Δ2 ± 5 mmHg, p = 0.01) and mean arterial pressure (Δ−2 ± 4 vs. Δ2 ± 6 mmHg, p = 0.04) were significantly decreased after 4 weeks of L-CIT compared to PL. Although not statistically significant (p = 0.07), cfPWV decreased after L-CIT supplementation by ~0.66 m/s. These findings suggest that L-CIT supplementation improves endothelial function and aortic BP via increased L-ARG availability.

Reversal Of Arterial Disease by modulating Magnesium and Phosphate (ROADMAP-study): rationale and design of a randomized controlled trial assessing the effects of magnesium citrate supplementation and phosphate-binding therapy on arterial stiffness in moderate chronic kidney disease.

BACKGROUND: Arterial stiffness and calcification propensity are associated with high cardiovascular risk and increased mortality in chronic kidney disease (CKD). Both magnesium and phosphate are recognized as modulators of vascular calcification and chronic inflammation, both features of CKD that contribute to arterial stiffness. In this paper, we outline the rationale and design of a randomized controlled trial (RCT) investigating whether 24 weeks of oral magnesium supplementation with or without additional phosphate-binding therapy can improve arterial stiffness and calcification propensity in patients with stage 3-4 CKD. METHODS: In this multi-center, placebo-controlled RCT, a total of 180 participants with an estimated glomerular filtration rate of 15 to 50 ml/min/1.73 m2 without phosphate binder therapy will be recruited. During the 24 weeks intervention, participants will be randomized to one of four intervention groups to receive either magnesium citrate (350 mg elemental magnesium/day) or placebo, with or without the addition of the phosphate binder sucroferric oxyhydroxide (1000 mg/day). Primary outcome of the study is the change of arterial stiffness measured by the carotid-femoral pulse wave velocity over 24 weeks. Secondary outcomes include markers of calcification and inflammation, among others calcification propensity (T50) and high-sensitivity C-reactive protein. As explorative endpoints, repeated 18F-FDG and 18F-NaF PET-scans will be performed in a subset of participants (n = 40). Measurements of primary and secondary endpoints are performed at baseline, 12 and 24 weeks. DISCUSSION: The combined intervention of magnesium citrate supplementation and phosphate-lowering therapy with sucroferric oxyhydroxide, in stage 3-4 CKD patients without overt hyperphosphatemia, aims to modulate the complex and deregulated mineral metabolism leading to vascular calcification and arterial stiffness and to establish to what extent this is mediated by T50 changes. The results of this combined intervention may contribute to future early interventions for CKD patients to reduce the risk of CVD and mortality. TRIAL REGISTRATION: Netherlands Trial Register, NL8252 (registered December 2019), EU clinical Trial Register 2019-001306-23 (registered November 2019).