Nitroglycerin-mediated Vasodilation Research Articles

Leptin Is Associated with Testosterone, Nutritional Markers, and Vascular Muscular Dysfunction in Chronic Kidney Disease.

Chronic kidney disease (CKD) causes specific hormonal disturbances, such as variations in leptin and testosterone levels and function. These disturbances can promote errors in signaling interaction and cellular information processing and can be implicated in the pathogenesis of atherosclerosis. This study investigates the factors that affect leptin in CKD patients and examines how leptin is related to markers of vascular disease. We conducted a cross-sectional study of 162 patients with CKD in pre-dialysis and dialysis stages. We recorded clinical and laboratory data, including leptin, testosterone, and subclinical atherosclerosis markers like brachial-ankle pulse wave velocity (ba PWV) in pre-dialysis CKD patients and flow-mediated vasodilation (FMD) and nitroglycerin-mediated vasodilation (NMD) in hemodialysis (HD) patients. Leptin was significantly correlated with testosterone in CKD pre-dialysis stages (p < 0.001) and also in HD (p = 0.026), with adipose tissue mass in pre-dialysis stages (p < 0.001), and also in HD (p < 0.001). In women HD patients, leptin correlated with NMD (p = 0.039; r = -0.379); in all HD patients, leptin correlated with C reactive protein (p = 0.007; r = 0.28) and parathormone (p = 0.039; r = -0.220). Our research emphasizes the connection between leptin, adipose tissue, and testosterone in all stages of CKD. Leptin was associated with NMD in HD women and correlated with inflammatory syndrome and parathyroid hormone in all HD patients.

Abstract 3139: Evidence Of Vascular Endothelial Dysfunction In Habitual Hookah (i.e., Waterpipe) Users: Insights For Cardiovascular Disease Risk

Introduction: Flavored hookah tobacco smoking among young adults continues to be a public health concern. While short-term exposure to flavored hookah tobacco smoking impairs vascular function, data on the long-term impact of habitual use are not clearly delineated. Research Question: Is habitual flavored hookah tobacco smoking associated with vascular endothelial dysfunction in young healthy adults? Goals: Investigate the impact of regular flavored hookah tobacco smoking on vascular endothelial function, as compared to regular cigarette smoking and never tobacco use, in young healthy adults. Methods: We assessed brachial artery flow-mediated dilation (FMD)—a well-established index of vascular endothelial function—in 22 exclusive chronic hookah smokers (25±1 years of age, 23% women; mean±SE), who reported smoking flavored hookah tobacco on average two times per week for 9±1 years, 22 exclusive cigarette smokers who reported 4±1 pack years, and 23 non-smokers. FMD and vascular endothelium-independent nitroglycerin-mediated vasodilation was assessed using high resolution ultrasound. Results: Whereas baseline brachial artery diameter was comparable between groups ( P =ns), brachial artery FMD was significantly lower in habitual hookah users and cigarette users as compared to never smokers (cigarette smokers: 5.22±0.42; hookah smokers: 6.43±0.50; non-smokers: 9.80±0.83; P &lt;0.05). Endothelium-independent dilation of the brachial artery in response to sublingual nitroglycerin did not significantly differ between groups. Conclusions: Despite claims of safety advertised by the growing hookah tobacco industry, our findings provide evidence that, as compared to non-tobacco users, young and apparently healthy adults who regularly smoke flavored hookah tobacco exhibit reduced vascular endothelial function. These results suggest that flavored hookah tobacco smoking is not without harm and has potential harmful vascular effects, associated with increased cardiovascular disease risk.

Laughter therapy cardiac rehabilitation in patients with stable coronary artery disease: a randomized clinical trial

Abstract Background Different non-pharmacological strategies have been studied in patients with stable coronary artery disease (CAD). However, the potential benefits of laughter therapy cardiac rehabilitation (LTRehab) for patients with stable CAD have not been fully investigated, especially through randomized clinical trials (RCT). Purpose This study aimed to evaluate the impact of LTRehab on functional capacity, endothelial function, and inflammatory biomarkers in CAD patients. Methods This is a randomized, parallel-design, examiner-blinded, controlled clinical trial conducted from August 2016 to December 2020. Peak oxygen uptake (VO2peak) and flow-mediated dilation (FMD) were measured using maximal cardiopulmonary exercise testing (CPET) and ultrasound, respectively. Inflammatory biomarkers, including interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, vascular cell adhesion molecule (VCAM), and intercellular adhesion molecule (ICAM), were measured. Thirteen patients were assigned to the LTRehab group, who watched two self-selected comedy sessions per week, and thirteen patients to the control group (CG), who watched two neutral documentaries (24 movies per group). Generalized Estimated Equations were used to identify the main factors of Group, Time, and the interaction between Group*Time. The Bonferroni correction was applied to identify differences. P &amp;lt; 0.05 was considered statistically significant. This study was approved by the Institutional Review Board (protocol No. 13-0124). Furthermore, it was conducted in accordance with Resolution no.466/12 of the National Health Council. Results A total of 26 CAD patients (69% male; mean age of 63.58 ± 9.97 years) were included in the study. There was a significant interaction between Group*Time (P&amp;lt;0.01) for VO2peak (LTRehab group: 19.09±0.85 to 21.06±1.00 vs. CG: 23.21±1.74 to 22.24±1.96 mL.kg-1.min-1). There was a mean difference of 1.98±0.45 between times for the LTRehab group with significant Bonferroni correction (P&amp;lt;0.01), but not for the control group (-0.96±0.75, P=0.20). Nitroglycerin-mediated vasodilation (endothelium-independent function) and VCAM showed significant differences in the Time factor (P = 0.02 and P = 0.05, respectively). All CPET tests reached maximal criteria (R&amp;gt;1.10). Conclusion This is the first RCT to evaluate the impact of LTRehab on CAD patients, showing an increase in VO2peak and improvements in endothelium-independent function and inflammatory biomarkers. LTRehab may constitute an effective form of cardiac rehabilitation in this patient population.

The effect of vitamin C on nitroglycerin-mediated vasodilation in individuals with and without the aldehyde dehydrogenase 2 polymorphism.

To mediate its pharmacodynamic effects, glyceryl trinitrate (GTN) requires bioactivation, by which it releases nitric oxide or a nitric oxide moiety. The exact mechanism of GTN bioactivation remains uncertain. Mitochondrial aldehyde dehydrogenase (ALDH-2) has been proposed as the primary enzyme responsible for this bioactivation process. Evidence for the importance of ALDH-2 in GTN bioactivation has been inconsistent, particularly in human models. An alternative hypothesis suggests that decreased ALDH-2 activity leads to accumulation of reactive cytotoxic aldehydes, which either inhibit the vasoactive product(s) of GTN or impair other enzymatic pathways involved in the bioactivation of GTN. We investigated the effect of supplemental vitamin C on vascular responses to GTN in healthy volunteers of East Asian descent, of whom 12 with and 12 without the ALDH-2 polymorphism participated. Subjects underwent 2 sequential brachial artery infusions of GTN at rates of 5, 11 and 22 nmol/min, separated by a 30-min washout period. The GTN infusions were carried out in the presence and absence of vitamin C using a randomized, crossover design. Venous occlusion plethysmography was used to measure forearm blood flow responses to GTN. Compared to subjects with functional ALDH-2, the variant group exhibited blunted hemodynamic responses to intra-arterial GTN infusions, although this reduction in response was not statically significant. Contrary to our hypothesis, vitamin C had an inhibitory effect on GTN mediated vasodilation as compared to GTN during saline in both groups. We conclude that vitamin C did not augment the acute vascular response to GTN in those with the ALDH-2 polymorphism.

Effect of menopause and age on vascular impairment

AimsThe prevalence of cardiovascular diseases increases in women after menopause. The aim of the study was to determine the impact of conventional cardiovascular risk factors such as age, blood pressure, smoking, cholesterol, obesity, and glucose balance, but also menopausal state and sleep-disordered breathing on vascular impairment during menopausal transition. Methods89 women initiated the study and 74 of them participated in the 10-year follow-up. Cardiovascular disease risk factor assessments, ultrasound measurements of brachial artery function, including nitroglycerin-mediated vasodilatation and flow-mediated endothelium-dependent vasodilation, and sleep studies were repeated at baseline and at 5-year and 10-year follow-ups. ResultsOver the study period, all the cardiovascular disease risk estimates increased. Both flow-mediated endothelium-dependent vasodilatation (decline 55 %) and nitroglycerin-mediated vasodilatation (decline 18 %) worsened over the 10 years (p < 0.001). Vascular function was not associated with menopausal state (determined with follicle stimulating hormone). Systolic blood pressure (p = 0.009) and smoking (p = 0.006) at baseline were negatively associated with nitroglycerin-mediated vasodilatation at 5-year follow-up and the use of hormonal therapy at 5-year follow-up was positively associated with concurrent nitroglycerin-mediated vasodilatation (p = 0.041). Intermittent nocturnal hypoxemia at baseline was associated with flow-mediated endothelium-dependent vasodilatation at 10-year follow-up (p = 0.043). High body mass index and impaired glucose balance at 5-year follow-up were associated with nitroglycerin-mediated vasodilatation decline at 10-year follow-up (p = 0.022 and p = 0.037, respectively). ConclusionsWe demonstrate how cardiovascular risk factors and vascular function evolve during menopausal transition. Although menopause was not associated with vascular impairment, short-term improvement in vascular function was observed in those using menopausal hormonal therapy. Intermittent nocturnal hypoxemia, obesity and impaired glucose control are early predictors of vascular decline during postmenopause.

Comprehensive Meta-Analysis of Functional and Structural Markers of Subclinical Atherosclerosis in Women with Polycystic Ovary Syndrome.

The relationship between polycystic ovary syndrome (PCOS) and subclinical atherosclerosis remains unclear. We performed a comprehensive systematic review and meta-analysis to evaluate the effect of PCOS on functional and structural markers of subclinical atherosclerosis as measured by carotid intima-media thickness (cIMT), flow-mediated vasodilation (FMD), nitroglycerin-mediated vasodilation (NMD), pulse wave velocity (PWV), and coronary artery calcium (CAC). Standard mean differences (SMDs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Ninety-six articles involving 5550 PCOS patients and 5974 controls were included. Compared with controls, PCOS patients showed significantly thicker cIMT (SMD (95% CI) = .587 (.398, .776), P < .001), lower FMD (SMD (95% CI) = -.649 (-.946, -.353), P < .001) and NMD (SMD (95% CI) = -.502 (-.686, -.317), P < .001), as well as higher PWV (SMD (95% CI) = .382 (.019, .746), P = .039), and increased CAC incidence (OR (95% CI) = 2.204 (1.687, 2.879), P < .001). When analyzing subgroups by age and body mass index (BMI), results were still significant (P < .05) except for PWV in the BMI subgroup. There was no significant result on sensitivity analysis, and Begg' test or Egger's test. PCOS contributes to subclinical atherosclerosis, resulting in functional and structural changes in cIMT, FMD and NMD, PWV, and CAC incidence.

Current status of flow-mediated vasodilation and nitroglycerin-mediated vasodilation

Current status of flow-mediated vasodilation and nitroglycerin-mediated vasodilation

The area under curve for time-course analysis parameters is associated with abdominal aortic aneurysms and the severity of peripheral artery disease in men

BackgroundAbdominal aortic aneurysm (AAA) and peripheral artery disease (PAD) are associated with vascular endothelial dysfunction. To date, flow-mediated vasodilatation (FMD) and nitroglycerin-mediated vasodilatation (NMD) have been used to evaluate vascular function. Recently, parameters of time-course analysis have been proposed as useful evaluations for arteriosclerotic diseases. In this study, the correlation between the parameters of time-course analysis, to the degree of vascular endothelial damage in AAA and PAD, together with their applicability as a vascular function test, was investigated. MethodsBrachial artery vasoreactivity was assessed in male patients with AAA (n = 150) and PAD (n = 50). The percentage change in peak diameters (ΔFMD and ΔNMD), the time to diameter change, the time to peak diameter from the diameter change, the blood flow decay time constant, the area under the curve (AUC), the maximum dilation rate and the extended time constant were measured. ResultsAmong the groups of aneurysm diameter in AAA, the FMD-AUC was highly different (p = .01), while the ΔFMD was not significantly different (p = .36). Among the Fontaine stages in PAD, the FMD-AUC was inversely associated with severity (p = .01) although the ΔFMD was not significantly different (p = .71). Among the Fontaine stages, the NMD-AUC was also inversely associated with severity (p = .03) although the ΔNMD was not significantly different (p = .11). ConclusionThis study suggests that FMD-AUC and NMD-AUC are useful for estimating vascular endothelial and vascular smooth muscle dysfunction, serving as supplementary markers for the diagnosis and evaluation of PAD and AAA.

L-NAME Releases Nitric Oxide and Potentiates Subsequent Nitroglycerin Mediated Vasodilation

L-NAME Releases Nitric Oxide and Potentiates Subsequent Nitroglycerin Mediated Vasodilation

L-NAME releases nitric oxide and potentiates subsequent nitroglycerin-mediated vasodilation

L-NG-Nitro arginine methyl ester (L-NAME) has been widely applied for several decades in both basic and clinical research as an antagonist of nitric oxide synthase (NOS). Herein, we show that L-NAME slowly releases NO from its guanidino nitro group. Daily pretreatment of rats with L-NAME potentiated mesenteric vasodilation induced by nitrodilators such as nitroglycerin, but not by NO. Release of NO also occurred with the NOS-inactive enantiomer D-NAME, but not with L-arginine or another NOS inhibitor L-NMMA, consistent with the presence or absence of a nitro group in their structure and their nitrodilator-potentiating effects. Metabolic conversion of the nitro group to NO-related breakdown products was confirmed using isotopically-labeled L-NAME. Consistent with Fenton chemistry, transition metals and reactive oxygen species accelerated the release of NO from L-NAME. Both NO production from L-NAME and its nitrodilator-potentiating effects were augmented under inflammation. NO release by L-NAME can confound its intended NOS-inhibiting effects, possibly by contributing to a putative intracellular NO store in the vasculature.

Role of Mitochondrial Aldehyde Dehydrogenase in Nitroglycerin-Mediated Vasodilation: Observations Concerning the Dose-Response Relationship.

The mechanism of the bioactivation of nitroglycerin has long been controversial, with a number of suggested enzymatic pathways. More recently, aldehyde dehydrogenase-2 (ALDH-2) has been reported as the important enzyme involved in the bioactivation of nitroglycerin at therapeutically relevant concentrations. Other previously described enzyme systems can also bioactivate nitroglycerin, but only at concentrations, which are significantly higher than achieved in clinical practice. This study investigated the vascular response to nitroglycerin given over a wide range of concentrations in subjects with and without the ALDH-2 Glu504Lys polymorphism, a common genetic variant that greatly reduces the activity of ALDH-2 (n = 10 in both groups). Forearm blood flow (FBF) responses to a brachial artery infusion of nitroglycerin were assessed using venous occlusion plethysmography. Intra-arterial infusion of nitroglycerin caused a significant increase in FBF beginning at 0.464 µg/min with increasing responses seen in both groups at all infusion rates. However, there were no differences in the FBF responses to nitroglycerin in those with and without the ALDH-2 polymorphism, suggesting that ALDH-2 is not solely responsible for the bioactivation of nitroglycerin at either low (therapeutically relevant) or high concentrations of nitroglycerin.

Association of Brachial Artery Measures with Estimated GFR&gt;60 mL/min/1.73 m2 in a Cross-Sectional Study of the Community-Based Women

Objective: The purpose of this study is to estimate whether early decline in kidney disease is correlated with brachial artery measures as surrogate markers of the endothelial function in community-based women. Methods: We studied 36 women with estimated glomerular filtration rate (eGFR)>60 mL/min/1.73 m2 in community-based population women were enrolled in this study. Brachial artery measures including Flow-Mediated Vasodilation (FMD), Nitroglycerin-Mediated Vasodilation (NMD), Brachial Artery Diameter (BAD), FMD/NMD ratio and Post-Nitroglycerin Brachial Artery Diameter (P-NTGD) examinations were measured in all subjects by using brachial artery ultrasonography. The eGFR was calculated using the Japanese GFR inference formula, which was developed by the Japanese Society of Nephrology. Results: There was significantly positive correlation between eGFR and FMD (r=0.348, p=0.041), positive correlation between eGFR and FMD/NMD ratio (r=0.471, p=0.004) and negative correlation between eGFR and P-NTGD (r=-0.405, p=0.016) were recognized. Negative correlation between Serum Uric Acid (SUA) and eGFR (r=-0.335, p=0.049) and negative correlation between FMD and SUA (r=-0.34, p=0.045) were also demonstrated. Conclusion: Mild renal dysfunction with eGFR>60 mL/min/1.73 m2 was associated with endothelial dysfunction in women. The cardio-renal interrelationship may be also suggested under mild renal dysfunction. It can be suggested that mild renal dysfunction might be a cardiovascular risk factor in women. Though it should not be distinctly stated just based on the results of the study. Keywords: Estimated glomerular filtration rate; Flow-mediated vasodilation; Endothelial dysfunction; Cardio-renal interrelationship; Mild renal dysfunction

Increased nitroglycerin-mediated vasodilation in migraineurs without aura in the interictal period

PurposeMigraine is associated with vascular disorders, but the underlying mechanism is unknown. Nitric oxide (NO) sensitivity is believed to play a major role in migraine pathophysiology. We investigated flow-mediated vasodilatation (FMD) and nitroglycerin-mediated vasodilatation (NMD) of the brachial artery by means of a key molecular mediator, NO, in patients with migraine without aura in the interictal period whether the abnormality is found.MethodsA total of 12 patients with migraine without aura and 12 matched healthy controls were enrolled in this study. FMD and NMD were measured in all patients and controls using brachial artery ultrasonography.ResultsThere was no significant difference in brachial artery diameter between migraineurs and nonmigraineurs (3.39 ± 0.68 vs 3.89 ± 0.67 mm, respectively; p = 0.083). A significant difference in FMD was not found between migraineurs and nonmigraineurs (6.94 ± 5.72 vs 6.08 ± 2.98%, respectively; p = 0.651). However, NMD in migraineurs was significant higher than that in nonmigraineurs (21.56 ± 7.36 vs 14.23 ± 7.41%, respectively; p = 0.024).ConclusionWe think that patients with migraine without aura in the interictal period have selective sensitivity in dilator response to nitroglycerin and may have systemic NO sensitivity.

Abstract 302: The PAT Ratio is Reduced by Beta-blockers

Background: Flow-mediated dilatation (FMD) of the brachial artery and Peripheral arterial tonometry (PAT) are both methods for assessing endothelial vascular function. FMD measures predominantly nitric oxide mediated vasodilation whereas PAT measures a more complex range of mechanisms. The recent study showed that the sympathetic nervous system plays a significant role in this response. Methods: The study involved 176 subjects (mean age66 ±12 years). Based on the medication of beta-blockers, they were divided into 2 groups: beta-blocker group (n=37) and control group (n=139). Flow mediated vasodilatation (FMD) and nitroglycerine-induced vasodilatation (NID) in the brachial artery was measured by using UNEXEF18G (UNEX CO, Japan), and nitroglycerin mediated vasodilatation (NMD) was used as a control test for FMD. At the same time, PAT ratio was measured by using Endo-PAT 2000 (Itamar Medical, Israel) Results: PAT ratio was significantly impaired in beta-blocker group compared to that in control group (1.5±0.4% vs. 1.9±0.6%, respectively; P&lt;0.05). However, FMD and NMD had no deference in both groups. Multivariable analysis revealed that blood sugar and medication of beta-blockers were independent variables for PAT ratio. Conclusion: These result show that beta-blockers is associated with a tendency towards reduced PAT ratio. PAT needs to be further studied, including the assessment of non-endothelial factor

Vasodilatory effect of nitroglycerin in Japanese subjects with different aldehyde dehydrogenase 2 (ALDH2) genotypes

The functional genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) influences the enzymatic activities of its wild type (Glu504 encoded by ALDH2*1) and mutant type (Lys504 encoded by ALDH2*2) proteins. The enzymatic activities of mutant-type ALDH2 are limited compared with those of the wild type. ALDH2 has been suggested as a critical factor for nitroglycerin-mediated vasodilation by some human studies and in vitro studies. Currently, there is no research on direct observations of the vasodilatory effect of nitroglycerin sublingual tablets, which is the generally used dosage form. In the present study, the contribution of ALDH2 to the vasodilatory effect of nitroglycerin sublingual tablets was investigated among three genotype groups (ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2) in Japanese. The results by direct assessments of in vivo nitroglycerin-mediated dilation showed no apparent difference in vasodilation among all genotypes of ALDH2. Furthermore, to analyze the effect of other factors (age and flow-mediated dilation), multiple regression analysis and Pearson's correlation coefficient analysis were carried out. These analyses also indicated that the genotypes of ALDH2 were not related to the degree of vasodilation. These results suggest the existence of other predominant pathway(s) for nitroglycerin biotransformation, at least with regard to clinical nitroglycerin (e.g., a sublingual tablet) in Japanese subjects.

PP.26.13

Objective: Endothelial function by flow-mediated (FMD) and nitroglycerin-mediated vasodilations (NMD) was scarcely investigated in resistant hypertension. We aimed to assess the independent correlates of FMD and NMD in resistant hypertensive patients, particularly their associations with ambulatory blood pressures (BP) and nocturnal BP fall patterns. Design and method: In a cross-sectional study, 280 resistant hypertensives performed 24-hour ambulatory BP monitoring, carotid-femoral pulse wave velocity, polysomnography, and brachial artery FMD and NMD by high-resolution ultrasonography. Independent correlates of FMD, NMD and brachial artery diameter were assessed by multiple linear and logistic regressions. Results: Median (interquartile range) FMD was 0.75% (-0.6 – 4.4%) and NMD was 11.8% (7.1 – 18.4%). Baseline brachial artery diameter and diabetes were independently associated with both FMD and NMD. Older age and prior cardiovascular diseases were associated with altered FMD, whereas higher nighttime systolic BP and lower nocturnal systolic BP fall were associated with impaired NMD. Moreover, there was a significant gradient of impaired NMD according to blunted nocturnal BP decline patterns (p for trend = 0.001). Brachial artery diameter was independently associated with age, gender, body mass index, albuminuria and nocturnal SBP fall. Further adjustments to blood flow velocity, aortic stiffness, plasma aldosterone concentration, and sleep apnea did not change these relationships. Conclusions: Nitroglycerin-mediated vasodilation, but not flow-mediated dilation, is independently associated with unfavorable nighttime BP levels and non-dipping patterns, and may be a better cardiovascular risk marker in patients with resistant hypertension. Brachial artery diameter also may provide additional prognostic information.

Differential Effects of Aliskiren/Amlodipine Combination and High-Dose Amlodipine Monotherapy on Endothelial Function in Elderly Hypertensive Patients

The aim of this study was to compare the effects of direct renin inhibitor, aliskiren, and amlodipine combination therapy with those of high-dose amlodipine monotherapy on endothelial function in elderly hypertensive patients. Participants included 105 patients (mean age 77 years) who had receive 5mg amlodipine for 4 weeks. Patients were allocated to the aliskiren/amlodipine group (AL/AM) or the high-dose amlodipine (AM) group. The AL/AM group received 150mg aliskiren in addition to 5mg amlodipine for 8 weeks; then the dose of aliskiren was doubled to 300mg for another 8 weeks. The AM group received 10mg amlodipine for 16 weeks. Of the 105 patients, 87 who underwent measurements of brachial flow-mediated vasodilation (FMD) and nitroglycerin-mediated vasodilation (NMD) before and after the study were included in the analysis. Blood pressure-lowering effects were similar in the 2 groups. Plasma renin activity significantly decreased in the AL/AM group (P < 0.001) but increased in the AM group (P < 0.001). Improvement of FMD was found in the AL/AM group (2.6% to 3.7%, P = 0.001) but not in the AM group, while NMD did not change in either group. The changes in 24-hour systolic blood pressure (r = -0.60, P < 0.001) and diastolic blood pressure (r = -0.46, P = 0.004) were significantly correlated with improvement of FMD in the AL/AM group but not in the AM group. Addition of aliskiren improved endothelial function in elderly hypertensive patients treated with amlodipine. UMIN000010163.

Pitavastatin subacutely improves endothelial function and reduces inflammatory cytokines and chemokines in patients with hypercholesterolaemia

BackgroundPitavastatin is a statin with strong pleiotropic effects, but the effects of pitavastatin on endothelial cell function (ECF) and both inflammatory cytokines and chemokines have not been fully investigated.Material and...

Subclinical vascular disease in patients with erectile dysfunction: correlation with high sensitivity C-reactive protein levels

Background: Erectile Dysfunction (ED) may be the early clinical manifestation of a generalized vascular disease (VD) & carries an independent risk for Cardiovascular (CVS) events. Low-grade subclinical inflammation affects endothelial function & is involved in all stages of atherosclerotic process. Objectives: To test the hypothesis that,ED in men without CVS disease or its Major Risk Factors (MRF) may be the earliest sign of generalized (VD) & correlate this with high sensitivity C-reactive protein (hs-CRP) levels. Patients and methods: The current study enrolled 115 men with ED without CVS disease or its (MRF) & 40 age matched healthy men as a control group. For all participants, assessment of LV function, aortic strain (AS), distensibility (AD) & aortic wall systolic velocity(AWSV) was done using conventional echocardiography & Doppler tissue imaging. B-mode ultrasonography of common carotid & brachial arteries was performed for measurement of carotid intima-media thickness(CIMT), brachial artery flow-mediated(FMD) & nitroglycerine-mediated vasodilatation(NTGMD). Ultrasensitive immunoassay used to measure hs-CRP. Results: CIMT & hs-CRP were significantly higher in patients than controls (0.82±0.22 mm vs. 0.53±0.31 mm & 6.72±1.5 mg/L vs. 2.1±0.78 mg/L respectively, p<0.001 for all),whereas AWSV,AS & AD were significantly lower in patients compared to controls (6.1±2.1 cm/sec vs. 9.1±1.6 cm/sec, 10.6±6% vs. 17.9±7% & 7±3 cm2/dyn/103 vs. 12±5 cm2/dyn/103 respectively, p<0.001 for all). ΔFMD & FMD% that reflect endothelial function status were significantly impaired in patients when compared to controls (0.67±0.33 mm vs. 2.1±0.29 mm & 21% vs. 50% respectively, P<0.001 for each);while ΔNTGMD and NTGMD% did not differ significantly between the two groups (2.1±0.73 mm vs. 2.3±0.59 mm & 49% vs. 51% respectively, P>0.05 for each). A strong positive correlation was found between ED severity & CIMT (r=0.55), hs-CRP (r=0.6)while the correlation was negative between ED & AWSV (r= -0.83), AS (r= -0.63), AD (r= -0.65)), FMD (r= -0.85), p<0.001 for all correlations. Conclusion: Aortic, carotid & brachial artery functional parameters are all impaired in addition to elevated hs-CRP levels in patients with ED without CVS disease or its (MRF), suggesting that, ED would represent an early clinical manifestation of a diffuse systemic subclinical VD. It is, therefore, crucial to identify asymptomatic patients with ED who may be at risk of occult CVS diseases. Their early recognition may lead to treatment of risk factors & conditions associated with endothelial dysfunction, hopefully reducing the rate of major CVS events.

Influence of Erythropoietin on Arterial Stiffness and Endothelial Function in Renal Transplant Recipients

Background/Aims: Recent retrospective studies suggest an association of therapy with erythropoiesis-stimulating agents (ESAs) and increased mortality in renal transplant recipients (RTR). Large artery structure and function are significantly impaired in RTR which contributes to their high cardiovascular morbidity and could be altered by erythropoietin. We aimed to examine the influence of ESA therapy on large artery stiffness and endothelial function in RTR. Methods: 63 RTR with chronic allograft dysfunction and renal anemia were randomized to a group receiving darbepoetin alfa (Dar) and a control group (Co). At baseline and after 8 months of treatment (cumulative Dar dose 11.1 µg/kg b.w.) brachial and common carotid artery distensibility coefficients, aortic pulse wave velocity, brachial artery flow-mediated and nitroglycerin-mediated vasodilation were measured as well as the following biomarkers of vascular function: vWF, sVCAM, sICAM, E-selectin, t-PA and PAI-1. Results: 23 patients in the Dar group and 17 patients in the Co group were available for per-protocol analysis. Hemoglobin increased significantly from 10.9 to 12.6 g/dl after 8 months in the Dar group, whereas it remained stable at 11.3 g/dl in the Co group. Effects on large artery stiffness, endothelial function and biomarkers of vascular function did not differ significantly between the two groups. Conclusion: Therapy with Dar during 8 months did not significantly impact parameters of large artery stiffness and endothelial function in RTR. These data suggest that therapy with erythropoietin does not deteriorate arterial stiffness and endothelial function in RTR.