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

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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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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Abstract 380: Favorable Effects of Flavonoids on Endothelial Function and Arterial Stiffness in Healthy Smokers

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.32.suppl_1.a380 ◽

2012 ◽

Vol 32 (suppl_1) ◽

Author(s):

Eleni Kokkou ◽

Gerasimos Siasos ◽

Dimitrios Tousoulis ◽

Evangelos Oikonomou ◽

Marilena Kollia ◽

...

Keyword(s):

Arterial Stiffness ◽

Cigarette Smoking ◽

Endothelial Function ◽

Vascular Function ◽

Augmentation Index ◽

Oral Treatment ◽

Grape Juice ◽

Arterial Tree ◽

Significant Difference ◽

Concord Grape

Background: Smoking is associated with impaired vascular function. Consumption of concord grape juice (CGJ), a rich source of flavonoids, has previously been shown to have antithrombotic and antioxidant effects and moreover can modify cardiovascular risk factors. In the present study we assessed the hypothesis that CGJ can improve endothelial function and arterial stiffness in healthy smokers. Methods: We studied the effect of a 2 weeks oral treatment with 7cc/Kg/day of CGJ (Welch’s 100% Concord Grape) in 20 healthy smokers (aged 26±5y) on two occasions (day 0: baseline and day 14). The study was carried out on two separate arms, one with CGJ and one with placebo, according to a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before (pSm) and immediately after (Sm0) cigarette smoking. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. 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: At baseline measurements, compared to pSm, cigarette smoking decreased FMD values (8.58±3.17% vs.5.65±1.98%, p<0.001) and moreover caused an increase in AIx (4.19±9.13% vs. 6.26±9.81%, p=0.013) and PWV (6.02±0.67m/sec vs. 6.21±0.68m/sec, p<0.046). Treatment with CGJ, improved pSm values of: FMD (7.87±2.79% vs. 9.43±2.62%, p=0.024), PWV (6.11±0.58m/sec vs. 5.70±0.6m/sec, p=0.013) and AIx (3.03±7.70% vs. -0.59±8.56%, p=0.016), while there was no statistically significant difference with placebo administration. Finally, compared with placebo, at day 14, treatment with CGJ, blunted the acute smoking-induced increase in PWV (placebo: from 5.67±0.64m/sec Psm to 6.00±0.78m/sec Sm0), (CGJ: from 6.00±0.73m/sec Psm to 6.23±0.66m/sec Sm0) (p=0.012). Conclusion: Concord grape juice contains specific flavonoids that may improve endothelium-dependent vasodilation and vascular elastic properties of the arterial tree in healthy smokers. Improved endothelial function and decreased arterial stiffness is a potential mechanism by which flavonoids may prevent cardiovascular events.

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Effect of Mineralocorticoid Receptor Blockade on Arterial Stiffness and Endothelial Function

Hypertension ◽

10.1161/hypertensionaha.120.16397 ◽

2021 ◽

Vol 77 (3) ◽

pp. 929-937

Author(s):

Atsushi Sakima ◽

Hisatomi Arima ◽

Tetsutaro Matayoshi ◽

Akio Ishida ◽

Yusuke Ohya

Keyword(s):

Arterial Stiffness ◽

Endothelial Function ◽

Mineralocorticoid Receptor ◽

Augmentation Index ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Blood Pressure Reduction ◽

Cochrane Central Register ◽

Flow Mediated Dilation ◽

Beneficial Effects

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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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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Residential Proximity to Greenness Mitigates the Hemodynamic Effects of Ambient Air Pollution

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00689.2020 ◽

2021 ◽

Author(s):

Daniel W. Riggs ◽

Ray Yeager ◽

Daniel J. Conklin ◽

Natasha DeJarnett ◽

Rachel J Keith ◽

...

Keyword(s):

Arterial Stiffness ◽

Pulse Pressure ◽

Vegetation Index ◽

Augmentation Index ◽

Systolic Pressure ◽

Ambient Air ◽

Ambient Air Pollution ◽

Linear Regression Models ◽

Residential Proximity ◽

Augmentation Pressure

Background: Residential proximity to greenness is associated with a lower risk of cardiovascular disease (CVD) and all-cause mortality. However, it is unclear whether the beneficial effects of greenness are linked to a reduction in the effects of ambient air pollutants. Methods and Results: We measured arterial stiffness in 73 participants with moderate to high CVD risk. Average levels of ambient PM2.5 and ozone were calculated from local monitoring stations. Residential greenness was estimated using satellite-derived normalized difference vegetation index (NDVI) for a 200m and 1km radius around each participant's home. Participants were 51% female; average age of 52 years; and, 79% had diagnosed hypertension. In multiple linear regression models, residential NDVI was negatively associated with augmentation index (-3.8% per 0.1 NDVI). Ambient levels of PM2.5 (per interquartile range (IQR) of 6.9 μg/m3) were positively associated with augmentation pressure (3.1 mmHg), pulse pressure (5.9 mmHg), and aortic systolic pressure (8.1 mmHg). Ozone (per IQR of 0.03 ppm) was positively associated with augmentation index (5.5%), augmentation pressure (3.1 mmHg), and aortic systolic pressure (10 mmHg). In areas of low greenness, both PM2.5 and ozone were positively associated with pulse pressure. Additionally, ozone was positively associated with augmentation pressure and systolic blood pressure. However, in areas of high greenness, there was no significant association between indices of arterial stiffness with either PM2.5 or ozone.Conclusions: Residential proximity to greenness is associated with lower values of arterial stiffness. Residential greenness may mitigate the adverse effects of PM2.5 and ozone on arterial stiffness.

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Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial function, inflammatory parameters, and platelet function in patients with acute coronary syndrome undergoing coronary artery stenting: a randomized, blinded, parallel study

European Heart Journal ◽

10.1093/eurheartj/ehz917 ◽

2020 ◽

Vol 41 (33) ◽

pp. 3144-3152 ◽

Cited By ~ 12

Author(s):

Boris Schnorbus ◽

Andreas Daiber ◽

Kerstin Jurk ◽

Silke Warnke ◽

Jochem Koenig ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Endothelial Function ◽

Adenosine Diphosphate ◽

Platelet Inhibition ◽

Clinical Parameter ◽

Mean Difference ◽

Low Flow ◽

Flow Mediated Dilation ◽

Coronary Syndrome ◽

The Impact

Abstract Aims In a randomized, parallel, blinded study, we investigate the impact of clopidogrel, prasugrel, or ticagrelor on peripheral endothelial function in patients undergoing stenting for an acute coronary syndrome. Methods and results The primary endpoint of the study was the change in endothelium-dependent flow-mediated dilation (FMD) following stenting. A total of 90 patients (age 62 ± 9 years, 81 males, 22 diabetics, 49 non-ST elevation myocardial infarctions) were enrolled. There were no significant differences among groups in any clinical parameter. Acutely before stenting, all three drugs improved FMD without differences between groups (P = 0.73). Stenting blunted FMD in the clopidogrel and ticagrelor group (both P < 0.01), but not in the prasugrel group. During follow-up, prasugrel was superior to clopidogrel [mean difference 2.13, 95% confidence interval (CI) 0.68–3.58; P = 0.0047] and ticagrelor (mean difference 1.57, 95% CI 0.31–2.83; P = 0.0155), but this difference was limited to patients who received the study therapy 2 h before stenting. Ticagrelor was not significantly superior to clopidogrel (mean difference 0.55, 95% CI −0.73 to 1.82; P = 0.39). No significant differences were seen among groups for low-flow-mediated dilation. Plasma interleukin (IL)-6 (P = 0.02 and P = 0.01, respectively) and platelet aggregation reactivity in response to adenosine diphosphate (P = 0.002 and P = 0.035) were lower in the prasugrel compared to clopidogrel and ticagrelor group. Conclusion As compared to ticagrelor and clopidogrel, therapy with prasugrel in patients undergoing stenting for an acute coronary syndrome is associated with improved endothelial function, stronger platelet inhibition, and reduced IL-6 levels, all of which may have prognostic implications. This effect was lost in patients who received the study medication immediately after stenting. EUDRACT-No 2011-005305-73

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THE IMPACT OF NATURAL CHIOS MASTIC SUPPLEMENTATION ON ENDOTHELIAL FUNCTION AND ARTERIAL STIFFNESS IN SMOKERS

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(17)35410-4 ◽

2017 ◽

Vol 69 (11) ◽

pp. 2021

Author(s):

Vasiliki Tsigkou ◽

Gerasimos Siasos ◽

Evangelos Oikonomou ◽

Konstantinos Mourouzis ◽

George-Angelo Papamikroulis ◽

...

Keyword(s):

Arterial Stiffness ◽

Endothelial Function ◽

The Impact

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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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Effects of dark chocolate and cocoa consumption on endothelial function and arterial stiffness in overweight adults

British Journal Of Nutrition ◽

10.1017/s0007114513002912 ◽

2013 ◽

Vol 111 (4) ◽

pp. 653-661 ◽

Cited By ~ 68

Author(s):

Sheila G. West ◽

Molly D. McIntyre ◽

Matthew J. Piotrowski ◽

Nathalie Poupin ◽

Debra L. Miller ◽

...

Keyword(s):

Arterial Stiffness ◽

Endothelial Function ◽

Augmentation Index ◽

Saturated Fat ◽

Dark Chocolate ◽

Control Treatment ◽

Resistance Arteries ◽

Basal Diameter ◽

Total Fat ◽

Overweight Adults

The consumption of cocoa and dark chocolate is associated with a lower risk of CVD, and improvements in endothelial function may mediate this relationship. Less is known about the effects of cocoa/chocolate on the augmentation index (AI), a measure of vascular stiffness and vascular tone in the peripheral arterioles. We enrolled thirty middle-aged, overweight adults in a randomised, placebo-controlled, 4-week, cross-over study. During the active treatment (cocoa) period, the participants consumed 37 g/d of dark chocolate and a sugar-free cocoa beverage (total cocoa = 22 g/d, total flavanols (TF) = 814 mg/d). Colour-matched controls included a low-flavanol chocolate bar and a cocoa-free beverage with no added sugar (TF = 3 mg/d). Treatments were matched for total fat, saturated fat, carbohydrates and protein. The cocoa treatment significantly increased the basal diameter and peak diameter of the brachial artery by 6 % (+2 mm) and basal blood flow volume by 22 %. Substantial decreases in the AI, a measure of arterial stiffness, were observed in only women. Flow-mediated dilation and the reactive hyperaemia index remained unchanged. The consumption of cocoa had no effect on fasting blood measures, while the control treatment increased fasting insulin concentration and insulin resistance (P= 0·01). Fasting blood pressure (BP) remained unchanged, although the acute consumption of cocoa increased resting BP by 4 mmHg. In summary, the high-flavanol cocoa and dark chocolate treatment was associated with enhanced vasodilation in both conduit and resistance arteries and was accompanied by significant reductions in arterial stiffness in women.

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