Effect of Mineralocorticoid Receptor Blockade on Arterial Stiffness and Endothelial Function

Although numerous studies have confirmed the beneficial effects of pharmacological therapy for arterial stiffness and endothelial dysfunction, which are predictors/therapeutic targets for cardiovascular diseases, only a few overall quantitative evaluations of MRAs (mineralocorticoid receptor antagonists) exist. We searched PubMed and Cochrane CENTRAL (Cochrane Central Register of Controlled Trials) for randomized trials evaluating MRA effects on arterial stiffness measured by pulse wave velocity (PWV) or augmentation index and endothelial function measured by flow-mediated dilation. Data from the included trials were pooled by using random-effects meta-analysis of the weighted mean difference (MD) between the comparator groups. The primary outcome was the MD of PWV. In 11 trials including 515 patients, the MRA treatment reduced the PWV when compared with control (MD, −0.75 m/s [95% CI, −1.12 to −0.39], P <0.00001), without heterogeneity. There were comparable effects of MRA on carotid-femoral PWV and those on other forms of PWV ( P =0.705 for heterogeneity). The effects of MRA on PWV were independent of blood pressure reduction related to the treatment according to meta-regression analysis. The MRA treatment reduced the augmentation index compared with control in 5 trials including 283 patients (MD, −6.74% [95% CI, −10.26 to −3.21], P =0.0002) and increased the flow-mediated dilation in 11 trials including 570 patients (MD, 1.18% [95% CI, 0.14 to 2.23], P =0.03). In conclusion, the current meta-analysis demonstrates the beneficial effects of MRA on PWV, augmentation index, and flow-mediated dilation.

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Abstract 4688: The Impact of Marfan Syndrome on Arterial Stiffness and Endothelial Function: The Role of Matrix Metalloproteinases

Circulation ◽

10.1161/circ.118.suppl_18.s_930-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Stella Brilli ◽

Dimitris Tousoulis ◽

Charalambos Antoniades ◽

George Hatzis ◽

Nikos Ioakeimidis ◽

...

Keyword(s):

Matrix Metalloproteinases ◽

Arterial Stiffness ◽

Endothelial Function ◽

Marfan Syndrome ◽

Augmentation Index ◽

Flow Mediated Dilation ◽

Arterial Tree ◽

Augmentation Pressure ◽

The Impact

Background: Marfan syndrome is characterised by high risk of aortic dissections and increased cardiovascular risk. However, the impact of Marfan syndrome on endothelial function and arterial stiffness is unclear, while the role of matrix metalloproteinases is unknown. We examined the impact of Marfan syndrome on the elastic properties of the arterial tree, and vascular endothelial function, and we evaluated the potential role of matrix metalloproteinases in these effects. Methods: The study population consisted of 17 subjects with Marfan syndrome, aged 26.6±2.3 years old, with BMI 20.5±1.03Kg/m2 and 22 healthy individuals matched for gender, age (26.4±0.78 years old, p=NS) and BMI (22.4±0.86 Kg/m2). Arterial stiffness was evaluated by measuring carotid-femoral pulse wave velocity (PWV), while augmentation pressure and augmentation index (AIx) were also determined, as measures of arterial wave reflections. Endothelial function was evaluated by determining flow mediated dilation (FMD) in the brachial artery while matrix metalloproteinase 9 (MMP-9) levels were determined by ELISA. Results: Patients with Marfan syndrome had significantly lower pulse pressure in the radial artery (41.0±1.07mmHg) compared to controls (51.3±4.4mmHg). In addition, patients had higher AIx (17.6±2.4%) and augmentation pressure (5.44±0.65mmHg) compared to controls (7.72±3.43% and 2.41±1.14mmHg respectively, p<0.05 for both). However, the difference in PWV between patients and controls did not reach statistical significance (6.33±0.33 vs 5.96±0.23m/s respectively, p=NS). Patients with Marfan syndrome had lower FMD (2.05±1.13%) and higher plasma MMP-9 (827±70ng/ml) compared to controls (6.8±2.3% p<0.05 and 326±50ng/ml, p<0.01). Conclusions: Marfan syndrome is associated with increased MMP-9 levels, as well as with elevated augmentation index and augmentation pressure compared to healthy individuals, matched for age, gender and body mass index. Moreover, flow-mediated dilation is also impaired in these subjects. These findings suggest that Marfan syndrome directly affects the elastic properties and endothelial function of the arterial tree, with matrix metalloproteinases being important mediators in the pathophysiology of this syndrome.

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Effects of qigong on systolic and diastolic blood pressure lowering: a systematic review with meta-analysis and trial sequential analysis

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-020-03172-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Siew Mooi Ching ◽

Naidu Ragubathi Mokshashri ◽

Maharajan Mari Kannan ◽

Kai Wei Lee ◽

Nurin Amalina Sallahuddin ◽

...

Keyword(s):

Blood Pressure ◽

Diastolic Blood Pressure ◽

Sequential Analysis ◽

Controlled Trial ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Blood Pressure Reduction ◽

Trial Sequential Analysis ◽

Control Group ◽

Cochrane Central Register

Abstract Background The benefits of qigong for systolic and diastolic blood pressure (BP) reduction have been noted in previously published systematic reviews; however, the data on its effectiveness has been at best scarce. We aimed to update the evidence of qigong on blood pressure reduction after taking into consideration the risks of random error and reliability of data in the cumulative meta-analysis using trial sequential analysis (TSA). Methods Included trials were assessed using Cochrane risk of bias instrument. We performed meta-analysis with random-effects model and random errors were evaluated with TSA. We performed the search for the eligible randomized controlled trial (RCT) through Medline, Cinahl, Cochrane Central Register of Controlled Trials and also PubMed. Results A total of 370 subjects sourced from seven eligible RCTs were entered into the analysis. The pooled results demonstrated the significant reduction with the use of qigong of the systolic blood pressure [weighted mean difference (WMD), − 10.66 mmHg (95% confidence interval (CI) = − 17.69,-3.62, p < 0.001] and diastolic BP [WMD, − 6.76 mmHg, 95% CI = − 12.22, − 1.30, p < 0.001] as compared to the control group. Conclusions Significant reductions in BP is seen with the use of qigong as compared with the control group, suggesting that qigong may be used as a complementary therapy in the somewhat complicated management of hypertension.

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The Effects of Ischemic Preconditioning Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6690691 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Xufang Gu ◽

Zhichao Liu ◽

Shengwei Gao ◽

Li Ma ◽

Jinhong Chen ◽

...

Keyword(s):

Endothelial Function ◽

Ischemic Preconditioning ◽

Meta Analysis ◽

Cochrane Library ◽

Flow Mediated Dilation ◽

Vascular Endothelial ◽

Brachial Artery Diameter ◽

Beneficial Effects ◽

The Relationship

Objective. Ischemic preconditioning (IPC) has gradually been promoted in clinical practice to lower the risk of cardiovascular surgery and postoperative complications. We investigated the role of IPC on vascular endothelial function and the relationship between IPC, flow-mediated dilation (FMD), and brachial artery diameter (BAD). Methods. Systematic searches were conducted in PubMed, Medline, Cochrane Library, Embase, and Scopus databases from their inception to March 20, 2020. This research included randomized controlled trials (RCTs) with adults, and the values of FMD and BAD were considered as the primary outcomes. Ten studies comprising 292 participants were included in the meta-analysis. Results. Regarding FMD, we observed beneficial effects of IPC on endothelial function (standardized mean difference (SMD): 1.82; 95% confidence interval (CI): 0.64, 3.01; p < 0.001 ; I2 = 89.9%). However, the available evidence did not indicate that IPC affected BAD (SMD: 0.08; 95% CI: −0.03, 0.18; p > 0.05 ; I2 = 76.5%). Conclusions. Our meta-analysis indicated a significant effect of IPC on the endothelial function of the blood vessels, affecting FMD but not BAD.

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Convalescent plasma therapy for COVID-19 patients: a protocol of a prospective meta-analysis of randomized controlled trials

Trials ◽

10.1186/s13063-021-05066-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Lajos Szakó ◽

Nelli Farkas ◽

Szabolcs Kiss ◽

Szilárd Váncsa ◽

Noémi Zádori ◽

...

Keyword(s):

Confidence Interval ◽

Randomized Controlled Trials ◽

Organ Failure ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Plasma Therapy ◽

Monthly Basis ◽

Randomized Controlled

Abstract Background Coronavirus disease 2019 (COVID-19) is an infection with possible serious consequences. The plasma of recovered patients might serve as treatment, which we aim to assess in the form of a prospective meta-analysis focusing on mortality, multi-organ failure, duration of intensive care unit stay, and adverse events. Methods A systematic search was conducted to find relevant registered randomized controlled trials in five trial registries. A comprehensive search will be done continuously on a monthly basis in MEDLINE (via PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to find the results of previously registered randomized controlled trials. The selection will be done by two independent authors. Data extraction will be carried out by two other independent reviewers. Disagreements will be resolved by a third investigator. An update of the search of the registries and the first search of the databases will be done on the 21st of July. Data synthesis will be performed following the recommendations of the Cochrane Collaboration. In the case of dichotomous outcomes (mortality and organ failure), we will calculate pooled risk ratios with a 95% confidence interval (CI) from two-by-two tables (treatment Y/N, outcome Y/N). Data from models with multivariate adjustment (hazard ratios, odds ratio, risk ratio) will be preferred for the analysis. P less than 0.05 will be considered statistically significant. In the case of ICU stay, weighted mean difference with a 95% confidence interval will be calculated. Heterogeneity will be tested with I2, and χ2 tests. Meta-analysis will be performed if at least 3 studies report on the same outcome and population. Discussion Convalescent plasma therapy is a considerable alternative in COVID-19, which we aim to investigate in a prospective meta-analysis.

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Effects of statin therapy on augmentation index as a measure of arterial stiffness: A systematic review and meta-analysis

International Journal of Cardiology ◽

10.1016/j.ijcard.2016.03.010 ◽

2016 ◽

Vol 212 ◽

pp. 160-168 ◽

Cited By ~ 25

Author(s):

Amirhossein Sahebkar ◽

Ivan Pećin ◽

Eugenia Tedeschi-Reiner ◽

Giuseppe Derosa ◽

Pamela Maffioli ◽

...

Keyword(s):

Systematic Review ◽

Arterial Stiffness ◽

Statin Therapy ◽

Augmentation Index ◽

Meta Analysis

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Abstract 12770: The Significant Role of Endothelium and Arterial Wall Properties in Patients With Pseudoexfoliative Glaucoma

Circulation ◽

10.1161/circ.132.suppl_3.12770 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Georgia Siasou ◽

Gerasimos Siasos ◽

Marilita M Moschos ◽

Nikolaos Gouliopoulos ◽

Evangelos Oikonomou ◽

...

Keyword(s):

Arterial Stiffness ◽

Endothelial Function ◽

Significant Role ◽

Vascular Function ◽

Arterial Wall ◽

Augmentation Index ◽

Open Angle Glaucoma ◽

Anterior Segment ◽

Pseudoexfoliative Glaucoma

Introduction: Primary open-angle glaucoma (POAG) is one of the most prevalent causes of irreversible blindness and is associated with endothelial dysfunction and arterial stiffness. Pseudoexfoliative glaucoma (PEG) is another type of glaucoma observed in pseudoexfoliation syndrome. It is characterized by the deposition of pseudoexfoliative material not only to the anterior segment of the eye, but also to the vessels, heart and other organs. Hypothesis: Endothelial function and arterial stiffness are impaired in patients with POAG and PEG supporting the significant role of vascular function impairment in the progression of the disease. Methods: Forty four POAG patients, 22 PEG and 38 healthy subjects (Cl) were included in this study. All subjects were free of cardiovascular or inflammatory diseases. Endothelial function was evaluated by flow-mediated dilatation (FMD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as a measure of arterial wave reflections Results: Between the three study groups CL, POAG, PEG there was no difference in age (67±10years vs. 70±9years vs. 66±12yeras, p=0.12) or prevalence of male sex (70% vs. 57% vs. 50%, p=0.21). Importantly, there was a linear impairment of FMD (7.35±2.77% vs. 6.58±3.18% vs. 4.88±3.29%, p=0.006), PWV (7.98±1.56m/sec vs. 9.20±1.84m/sec vs. 9.22±2.16m/sec, p=0.004) and AIx (21.29±8.77% vs. 25.14±5.71% vs. 28.20±8.75%, p=0.002) from CL to POAG and PEG. Interestingly post hoc test after Scheffe correction revealed also that PEG subjects had not only significantly impaired FMD, compared to control subjects, but also compared to POAG subjects (4.88±3.29% vs. 6.58±3.18%, p=0.02). Conclusions: Endothelial function and arterial stiffness are significantly impaired in patients with pseudoexfoliative glaucoma. These findings shed some light in the pathophysiology of pseudoexfoliative glaucoma and support the theory that pseudoexfoliative fibrils may also accumulate and damage the arterial wall.

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Endothelial Function and Arterial Stiffness Should Be Measured to Comprehensively Assess Obstructive Sleep Apnea in Clinical Practice

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.716916 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jinmei Luo ◽

Xiaona Wang ◽

Zijian Guo ◽

Yi Xiao ◽

Wenhao Cao ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Arterial Stiffness ◽

Endothelial Function ◽

Augmentation Index ◽

Reactive Hyperemia ◽

Control Group ◽

Apnea Hypopnea Index ◽

Obstructive Sleep ◽

Tnf Α

Objective: An effective clinical tool to assess endothelial function and arterial stiffness in patients with obstructive sleep apnea (OSA) is lacking. This study evaluated the clinical significance of subclinical markers for OSA management in males without serious complications.Patients/Methods: Males without serious complications were consecutively recruited. Clinical data, biomarker tests, reactive hyperemia index (RHI), and augmentation index at 75 beats/min (AIx75) measured by peripheral arterial tonometry were collected. An apnea hypopnea index (AHI) cutoff of ≥15 events/h divided the patients into two groups.Results: Of the 75 subjects, 42 had an AHI ≥15 events/h. Patients with an AHI ≥15 events/h had higher high-sensitivity C-reactive protein, tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor, and AIx75 values than the control group but no statistical difference in RHI was observed. After controlling for confounders, TNF-α was negatively correlated with the average oxygen saturation (r = −0.258, P = 0.043). RHI was correlated with the rapid eye movement (REM) stage percentage (r = 0.306, P = 0.016) but not with AHI (P > 0.05). AIx75 was positively correlated with the arousal index (r = 0.289, P = 0.023) but not with AHI (r = 0.248, P = 0.052).Conclusions: In males with OSA without severe complications, TNF-α and AIx75 are independently related to OSA. The role of RHI in OSA management requires further elucidation. These markers combined can comprehensively evaluate OSA patients to provide more evidence for the primary prevention of coronary heart disease and treatment response assessment.

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Eating and arterial endothelial function: a meta-analysis of the acute effects of meal consumption on flow-mediated dilation

Obesity Reviews ◽

10.1111/obr.12454 ◽

2016 ◽

Vol 17 (11) ◽

pp. 1080-1090 ◽

Cited By ~ 13

Author(s):

N. J. Thom ◽

A. R. Early ◽

B. E. Hunt ◽

R. A. Harris ◽

M. P. Herring

Keyword(s):

Endothelial Function ◽

Meta Analysis ◽

Flow Mediated Dilation ◽

Acute Effects ◽

Meal Consumption

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The Efficacy of Stretching Exercises on Arterial Stiffness in Middle-Aged and Older Adults: A Meta-Analysis of Randomized and Non-Randomized Controlled Trials

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17165643 ◽

2020 ◽

Vol 17 (16) ◽

pp. 5643 ◽

Cited By ~ 2

Author(s):

Michitaka Kato ◽

Fumi Nihei Green ◽

Kazuki Hotta ◽

Toshiya Tsukamoto ◽

Yasunari Kurita ◽

...

Keyword(s):

Older Adults ◽

Arterial Stiffness ◽

Endothelial Function ◽

Meta Analysis ◽

Controlled Trials ◽

Vascular Endothelial ◽

Vascular Endothelial Function ◽

Middle Aged ◽

Randomized Controlled ◽

Stretching Exercises

Background: Aerobic exercise is known to reduce arterial stiffness; however, high-intensity resistance exercise is associated with increased arterial stiffness. Stretching exercises are another exercise modality, and their effect on arterial stiffness remains unclear. The purpose of this study was to determine whether stretching exercises reduce arterial stiffness in middle-aged and older adults, performing the first meta-analysis of currently available studies. Methods: We searched the literature for randomized controlled trials (RCTs) and non-RCTs published up to January 2020 describing middle-aged and older adults who participated in a stretching intervention vs. controls without exercise training. The primary and secondary outcomes were changes in arterial stiffness and vascular endothelial function and hemodynamic status. Pooled mean differences (MDs) and standard MDs (SMDs) with 95% confidence intervals (CIs) between the intervention and control groups were calculated using a random effects model. Results: We identified 69 trials and, after an assessment of relevance, eight trials, including a combined total of 213 subjects, were analyzed. Muscle stretching exercises were shown to significantly reduce arterial stiffness and improve vascular endothelial function (SMD: −1.00, 95% CI: −1.57 to −0.44, p = 0.0004; SMD: 1.15, 95% CI: 0.26 to 2.03, p = 0.01, respectively). Resting heart rate (HR) and diastolic blood pressure (DBP) decreased significantly after stretching exercise intervention (MD: −0.95 beats/min, 95% CI: −1.67 to −0.23 beats/min, p = 0.009; MD: −2.72 mm Hg, 95% CI: −4.01 to −1.43 mm Hg, p < 0.0001, respectively) Conclusions: Our analyses suggest that stretching exercises reduce arterial stiffness, HR, and DBP, and improve vascular endothelial function in middle-aged and older adults.

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Endothelial Function in Patients with Essential Thrombocytosis.

Blood ◽

10.1182/blood.v106.11.3983.3983 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3983-3983

Author(s):

Maya Koren-Michowitz ◽

Batia Avni ◽

Irma Zur ◽

Yulia Volcheck ◽

Naomi Rahimi-Levene ◽

...

Keyword(s):

Platelet Count ◽

Arterial Stiffness ◽

Endothelial Function ◽

Arterial Thrombosis ◽

Pulse Wave ◽

Augmentation Index ◽

Smoking History ◽

Essential Thrombocytosis ◽

The Difference ◽

Analysis System

Abstract Essential thrombocytosis (ET) is a myeloproliferative disorder whose main complication is thrombothic events. Reduction of platelet count is associated with a decrease in the risk for thrombosis. Recently it was shown that although anagrelide and hydroxyurea lower platelet counts to the same extent, hydroxyurea decreased the rate of arterial thrombosis and increased the rate of venous thrombosis compared to anagrelide. The reason for the different effects is unknown. The endothelium has important antithrombotic properties. Therefore, we hypothesized that hydroxyurea and anagrelide may have different effects on endothelial function in patients with ET. Thirty patients with ET were studied; 12 treated with anagrelide and 18 with hydroxyurea. Endothelial function was assessed using a semi-automated pulse wave analysis system (SphygmoCor PVX, AtCor Medical, Sydney Australia). Pulse wave is recorded at the radial artery. Using a validated transfer function, the following variables are determined: central systolic blood pressure (CSBP); augmentation index (AIx), a reflection of arterial stiffness; augmentation index adjusted for heart rate (AIx@75). Measurements were taken at baseline, after inhalation of terbutaline 500 mcg (representing endothelial dependent vasodilation due to NO synthesis), and after sublingual nitroglycerine 400 mcg (representing endothelial independent vasodilation). The difference between baseline AIx and maximum response after terbutaline and nitroglycerine are given as EDV (endothelial dependent vasodilation) and EIV (endothelial independent vasodilation), respectively. There was no difference between the two groups of patients with regard to disease duration, age, gender, prior thrombotic events and risk factors for atherosclerosis including BMI, hyperlipidemia, diabetes mellitus, smoking history and hypertension. Mean Hct and platelet count was the same in both groups of patients. However, WBC and neutrophil counts were lower in patients treated with hydroxyurea compared to the patients treated with anagrelide (WBC 6.2±1.4 K/μl vs. 8.4±3.4 K/μl, p=0.07, neutrophils 4.0±1.2 K/μl vs. 6.3±2.9 K/μl, p=0.05). Parameters of arterial stiffness and endothelial function did not differ significantly between the two groups of patients (Table 1). There was no correlation between platelet count and endothelial function, however a correlation between CSBP and age was found (R= 0.615 p<0.001). In conclusion: our preliminary results do not support a different effect for hydroxyurea and anagrelide on arterial stiffness and endothelial function in patients with ET. In accordance with previous reports we found a lower neutrophil count in the group of patients on hydroxyurea therapy. This may affect the interaction between neutrophils and the vessel wall thereby decreasing the rate of arterial thrombosis. Table 1 Therapy (N) Anagrelide (12) Hydroxyurea (18) CSBP mmHg 120±14 122±21 AIx % 26±12 33±11 AIx@75 % 25±10 27±10 EDV % −2±8.6 0.6±7.5 EIV % −11±9 −15±7

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