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

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Georgia Siasou ◽  
Gerasimos Siasos ◽  
Marilita M Moschos ◽  
Nikolaos Gouliopoulos ◽  
Evangelos Oikonomou ◽  
...  

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.

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Stella Brilli ◽  
Dimitris Tousoulis ◽  
Charalambos Antoniades ◽  
George Hatzis ◽  
Nikos Ioakeimidis ◽  
...  

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.


2013 ◽  
Vol 2013 ◽  
pp. 1-5
Author(s):  
Andrew J. Degnan ◽  
Nandini Shah ◽  
David M. Carty ◽  
John R. Petrie ◽  
Christian Delles ◽  
...  

Background. Peripheral arterial tonometry (PAT) is a novel, non-invasive and operator-independent method for simultaneous assessment of endothelial function and arterial stiffness. We examined the repeatability of PAT in females and the influence of the estrous cycle. Methods. In 14 healthy female and five healthy male control subjects, PAT was performed on three separate occasions with 10 days between visits. Reactive hyperemia index (RHI), a measure of endothelial function, and peripheral augmentation index (AIx), a measure of arterial stiffness, were determined with the EndoPAT-2000 system. Intraclass correlation coefficient (ICC) was calculated as a measure of repeatability. Results. In both female and male groups, RHI and AIx did not differ between the three measurements (all n.s. by 1-way ANOVA). In females, reanalyzing the data after taking phase of estrous cycle into account had no effect on the results. Repeatability for RHI and AIx in females (ICC for RHI = 0.43, ICC for AIx = 0.78) was similar to that in male subjects (ICC for RHI = 0.42, ICC for AIx = 0.63). Conclusions. PAT measurements were not affected by the estrous cycle in females, and repeatability was comparable to that in males. This should facilitate inclusion of female subjects into vascular function studies using PAT.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Anastasiou ◽  
E Oikonomou ◽  
G Vogiatzi ◽  
G Siasos ◽  
Z Flora ◽  
...  

Abstract Introduction Both anthracyclines and trastuzumab are key regiments for the treatment of breast cancer, but their concurrent use is contraindicated because of their cardiotoxicity. Their effects on vascular function have been less well studied. Purpose We explored the effects of the anthracycline-based chemotherapy followed by trastuzumab-based treatment on endothelial function and arterial stiffness in patients with breast cancer. Methods 46 female patients (54.56±11.5 years old) with breast cancer scheduled for anthracycline-based chemotherapy followed by the combination of trastuzumab and taxane were enrolled. Trastuzumab was continued until the completion of one-year treatment. All participants underwent assessment of the brachial flow mediated dilatation (FMD), endothelial independent dilatation (EID), carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) at baseline (BL), at the end of anthracycline treatment (FU1), 3 months following initiation of trastuzumab with taxane (FU2) and at the completion of treatment with trastuzumab (FU3). Results Over the follow-up period (15 months) there was significant deterioration in FMD (p=0.04) (Table 1, Figure 1). Importantly, while there was no significant difference in FMD between BL vs FU1 (p=0.6), FMD has been significantly deteriorated over the treatment with trastuzumab with taxane FU1 vs FU2 (p=0.01) and FU2 vs FU3 (p=0.01) (Table 1, Figure 1). EID did not change over the follow-up period (Figure 1). Similarly, PWV has been significantly increased over the follow up period (p=0.03). There was no significant difference in PWV BL vs FU1 (p=0.1), however PWV has been significantly increased over the treatment with trastuzumab with taxane FU1 vs FU 2 (p=0.02) and FU2 vs FU3 (p=0.01) (Table 1, Figure 1). A similar pattern of impairment was observed with AIx (Table 1, Figure 1). Conclusion We report a significant adverse effect of the anthracycline- and trastuzumab-based therapy on the arterial stiffness and endothelial function. This effect is more considerable after the exposure to trastuzumab. Figure 1. Changes of FMD, PWV, Alx, EID during FU Funding Acknowledgement Type of funding source: None


2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Eleni Kokkou ◽  
Gerasimos Siasos ◽  
Dimitrios Tousoulis ◽  
Evangelos Oikonomou ◽  
Marilena Kollia ◽  
...  

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.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Oikonomou ◽  
E Bourouki ◽  
M Moschos ◽  
G Siasos ◽  
G Siasou ◽  
...  

Abstract Background Pseudoexfoliative glaucoma (PEX) is a type of glaucoma characterized by the secretion of a grey-white, fibrogranular material in several tissues. Microparticles are shed membrane vesicles released from a variety of cell types in response to cellular activation or apoptosis and correlate with the pathogenesis of cardiovascular diseases. Endothelial MPs may be used as biomarkers of endothelial function. Purpose To evaluated the role of endothelial dysfunction, arterial stiffness and systemic inflammation in patients with PEX compared to patients with Primary open angle glaucoma (POAG) and control subjects as well as the possible pathophysiologic role of a specific microparticle profile associated with endothelial damage. Methods We enrolled 29 subjects with PEX, 57 subjects with POAG and 44 control subjects. Endothelial function was evaluated by flow-mediated dilation (FMD). Pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as a measure of arterial wave reflections. Growth differentiation factor-15 (GDF-15) and intercellular adhesion molecule1 (ICAM1) were measured to evaluate systemic inflammatory status. Total circulating MPs and EMPs were isolated and analysed by flow cytometry, utilizing specific labels for EMPs (CD 144+) and Annexin V staining for phospatidylserine bearing-MPs (AnnexinV + MPs). Results There was a linear impairment in FMD (p=0.005), PWV (p=0.007) and Aix (p=0.02) and a stepwise increase in GDF-15 (p=0.001) and sICAM-1 levels (p=0.08) between the three study groups (control, POAG, PEX). Interestingly, the PEX subjects expressed greater levels of total circulating MPs (Annexin V+) [1698 (1199–5894) MPs/μL vs. 1641 (1470–2705) MPs/μL. vs 493 (417–1512) MPs/μL, p=0.004] and EMPs (CD144+)[1412 (645–1760) MPs/μL3 vs 1380 (498–2496) MPs/μL vs 34 (184–870) MPs/μL, p<0.001] compared to POAG and control subjects. Conclusion Pseudoexfoliative glaucoma is associated with impaired endothelial function, arterial wall properties and vascular inflammation with a parallel increase in EMPs. Our findings indicate the significant role of endothelial damage in the progress of glaucomatous disease especially in subjects with pseudoexfoliative glaucoma.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jinmei Luo ◽  
Xiaona Wang ◽  
Zijian Guo ◽  
Yi Xiao ◽  
Wenhao Cao ◽  
...  

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 &gt; 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.


Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Sangeetha D Nathaniel ◽  
Shane McGinty ◽  
David G Edwards ◽  
William B Farquhar ◽  
Melissa A Witman ◽  
...  

The mechanisms for the benefits of Angiotensin Receptor Neprilysin inhibitor (ARNi) in heart failure patients with reduced ejection fraction (HFrEF) are likely beyond blood pressure (BP) reduction. Vascular function, a prognostic marker in HFrEF, improves with ARNi in animal models. Improvements in vascular function may contribute to benefits from ARNi in HFrEF; however, this has yet to be demonstrated in humans. The purpose of the study was to test the hypothesis that arterial stiffness and endothelial function would improve after 12 weeks of ARNi in HFrEF. Methods: HFrEF participants with NYHA class II-III were enrolled from local cardiology clinics and completed experimental visits at baseline and 12 weeks later: 13 participants were prescribed ARNi by their cardiologist [62±10 years, Men: 10, BMI: 30±5 kg/m 2 , EF: 28±6 %; Non-ischemic cardiomyopathy (NICM): 8], 10 participants continued on conventional treatment [CON: 60±7 years, Men: 6, BMI: 31±6 kg/m 2 , EF: 31±5 % and NICM: 4; all P=NS]. During each experimental visit, arterial stiffness was assessed via carotid-femoral pulse wave velocity (PWV; Sphygmocor PVx system) and endothelial function by brachial artery flow-mediated dilation (FMD) using standard techniques. Statistical analyses were performed using 2x2 repeated-measures ANOVA. Results: Baseline mean BP (MAP) was similar between ARNi (93±14 mmHg) and CON (85 ± 10 mmHg; P=0.13); MAP tended to decrease after 12 weeks of ARNi (88 ± 11 mmHg; P=0.08) but not CON (90 ± 17 mmHg; P=0.14) (ANOVA interaction P=0.03). PWV tended to be higher at baseline in ARNi (8.8 ± 2.5 m/s) compared to CON (7.0 ± 2.5 m/s; P=0.09); PWV decreased after 12 weeks of ARNi (7.0 ± 1.7 m/s; P<0.01) and was unchanged in CON (7.4 ± 2.4 m/s; P=0.33) (ANOVA interaction P<0.01). When controlling for MAP, the effect of ARNi on PWV remained (P<0.01). At baseline, FMD was similar between ARNi (2.81 ± 2.05%) and CON (4.75 ± 3.75%; P=0.13); however, FMD increased after 12 weeks of ARNi (5.73 ± 1.87%; P<0.001) but not in CON (5.37 ± 3.38%; P=0.33) (ANOVA time P<0.001, interaction P=0.01). Conclusion: ARNi improves arterial stiffness and endothelial function in HFrEF. Understanding the mechanisms of ARNi in HFrEF is crucial as it may pave the way for better interventions in other cardiovascular diseases.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Oikonomou ◽  
G Siasos ◽  
G Marinos ◽  
M Zaromitidou ◽  
D Athanasiou ◽  
...  

Abstract Background Regular physical activity is recommended for health improvement. However the upper intensity threshold associated with best health outcome is difficult to determine. Water polo (WP) Olympic athletes present unique characteristics with very high intensity work, long training sessions and a combination of endurance and strength training. Purpose To examine how long term, intense mixed endurance and strength training affect peripheral and central hemodynamics and biomarkers of cardiovascular health. Methods The study population consisted of 20 WP Olympic team player's, 20 matched recreational active subjects (RA) and 20 sedentary control subjects (Cl). Reflected waves were assessed with the Augmentation index (AIx), central aortic stiffness with pulse wave velocity (PWV) and endothelial function with flow mediated dilation (FMD). Results From Cl subjects to RA active subjects and to WP players there was a stepwise decrease in aortic systolic pressure (116±16 mmHg vs. 107±14 mmHg vs. 106±6 mmHg, p=0.03) while there was no difference in branchial systolic pressure (p=0.52). There was also a stepwise improvement in AIx (−4.22±9.97% vs. −6.97±11.28% vs. −12.14±6.62%, p=0.03) and FMD (6.61±1.78% vs. 7.78±1.98% vs. 8.3±2.05%, p=0.04) according to the intensity of exercise and WP players had lower AIx and higher FMD compared to RA subjects and to Cl subjects. Conclusions In young WP Olympic team players intense mixed endurance and strength training has no adverse impact on arterial wall properties and endothelial function with a parallel improvement in central hemodynamics. These findings highlight that there are no definitive data to support on any adverse vascular related impact of ultra-endurance training while mixed endurance and strength training may be associated with a favorable vascular profile.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3983-3983
Author(s):  
Maya Koren-Michowitz ◽  
Batia Avni ◽  
Irma Zur ◽  
Yulia Volcheck ◽  
Naomi Rahimi-Levene ◽  
...  

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&lt;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


2013 ◽  
Vol 111 (4) ◽  
pp. 653-661 ◽  
Author(s):  
Sheila G. West ◽  
Molly D. McIntyre ◽  
Matthew J. Piotrowski ◽  
Nathalie Poupin ◽  
Debra L. Miller ◽  
...  

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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