BackgroundPatients with peripheral artery disease (PAD) experience significant morbidity and mortality. The OMEGA-PAD I Trial, a randomized, double-blinded, placebo-controlled trial, addressed the hypothesis that short-duration, high-dose n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation improves endothelial function and inflammation in PAD.Methods and ResultsEighty patients with stable claudication received 4.4 g of fish oil or placebo for 1 month. The primary end point was endothelial function as measured by brachial artery flow-mediated vasodilation. Secondary end points included biomarkers of inflammation, n-3 polyunsaturated fatty acids metabolome changes, lipid profile, and walking impairment questionnaires. Although there was a significant increase in FMD in the fish oil group following treatment (0.7±1.8% increase from baseline, P=0.04), this response was not different then the placebo group (0.6±2.5% increase from baseline, P=0.18; between-group P=0.86) leading to a negative finding for the primary endpoint. There was, however, a significant reduction in triglycerides (fish oil: −34±46 mg/dL, P<0.001; placebo −10±43 mg/dL, P=0.20; between-group differential P-value: 0.02), and an increase in the omega-3 index of 4±1% (P<0.001) in the fish oil group (placebo 0.1±0.9%, P=0.49; between-group P<0.0001). We observed a significant increase in the production of pathway markers of specialized pro-resolving mediators generated from n-3 polyunsaturated fatty acids in the fish oil group.ConclusionsHigh-dose, short-duration fish oil supplementation did not lead to a different response in the primary end point of endothelial function between the treatment and placebo group, but improved serum triglycerides and increased the production of downstream n-3 polyunsaturated fatty acids–derived products and mediators in patients with PAD.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov/. Unique identifier: NCT01310270.

Introduction Sedentarism, also termed physical inactivity, is an independent risk factor for cardiovascular diseases. Mechanisms thought to be involved include insulin resistance, dyslipidemia, hypertension, and increased inflammation. It is unknown whether changes in vascular and endothelial function also contribute to this excess risk. We hypothesized that short-term exposure to inactivity would lead to endothelial dysfunction, arterial stiffening and increased vascular inflammation. Methods Five healthy subjects (4 males and 1 female) underwent 5 days of bed rest (BR) to simulate inactivity. Measurements of vascular function [flow-mediated vasodilation (FMD) to evaluate endothelial function; applanation tonometry to assess arterial resistance], inflammation and metabolism were made before BR, daily during BR and after 2 recovery days. Subjects maintained an isocaloric diet throughout. Results Bed rest led to significant decreases in brachial artery and femoral artery FMD [Brachial: 11 ± 3% pre-BR vs. 9 ± 2% end-BR, P=0.04; Femoral: 4 ± 1% vs. 2 ± 1%, P=0.04]. The central augmentation index increased with BR [−4 ± 9% vs. 5 ± 11%, P=0.03]. Diastolic blood pressure (DBP) increased [58 ± 7 mmHg vs. 62 ± 7 mmHg, P=0.02], while neither systolic blood pressure nor heart rate changed. 15-HETE, an arachidonic acid metabolite, increased but the other inflammatory and metabolic biomarkers were unchanged. Conclusions Our findings show that acute exposure to sedentarism results in decreased endothelial function, arterial stiffening, increased DBP, and an increase in 15-HETE. We speculate that inactivity promotes a vascular “deconditioning” state characterized by impaired endothelial function, leading to arterial stiffness and increased arterial tone. Although physiologically significant, the underlying mechanisms and clinical relevance of these findings need to be further explored.

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Hemodynamic parameters play an important role in regulating vascular remodeling in arterio-venous fistula (AVF) maturation. Investigating the changes in hemodynamic parameters during AVF maturation is expected to improve our understanding of fistula failure, but very little data on actual temporal changes in human AVFs is available. The present study aimed to assess the feasibility of using a noncontrast-enhanced MRI protocol combined with CFD modeling to relate hemodynamic changes to vascular remodeling following native AVF placement. MR angiography (MRA) and MR velocimetry (MRV) data was acquired peri-operatively, 1 month, and 3 months later in three patients. Vascular geometries were obtained by segmentation of the MRA images. Pulsatile flow simulations were performed in the patient specific vascular geometries with time-dependent boundary conditions prescribed from MRV measurements. A principal result of the study is the description of WSS changes over time in the same patients. The disturbed flow observed in the venous segments resulted in a variability of the WSS distribution and could be responsible for the non-uniform remodeling of the vessel. The artery did not show regions of disturbed flow upstream from the anastomosis, which would be consistent with the uniform remodeling. MRI use demonstrated the ability to provide a comprehensive evaluation of clinically relevant information for the investigation of upper extremity AVFs. 3D geometry from MRA in combination with MRV provides the opportunity to perform detailed CFD analysis of local hemodynamics in order to determine flow descriptors affecting fistula maturation.

Background--Current research in behavioral cardiology reveals a significant association between posttraumatic stress disorder (PTSD) and increased risk for cardiovascular disease and mortality; however, the underlying mechanisms remain poorly understood. We hypothesized that patients with PTSD would exhibit endothelial dysfunction, a potential mechanism involved in the development and progression of cardiovascular disease.

Purpose:To determine the feasibility of using ferumoxytol-enhanced magnetic resonance (MR) angiography to depict the vasculature of hemodialysis fistulas and improve image quality compared with nonenhanced time-of-flight (TOF) MR angiography. Materials and Methods:The study was institutional review board approved and was in compliance with HIPAA regulations. All participants provided written informed consent. TOF and firstpass ferumoxytol-enhanced MR angiography were performed in 10 patients with upper extremity autogenous fistulas. Ferumoxytol was administered as a bolus solution containing 430 µmol of elemental iron. A qualitative comparison was performed on maximum intensity projection images. Lumen depiction was evaluated by using a fivepoint scale. The uniformity of intraluminal signal intensity was measured as the ratio between the mean signal intensity of the entirety of the imaged fistula and its standard deviation. The contrast-to-noise ratio (CNR) between intraluminal signal and adjacent tissue was evaluated as a function of image acquisition time. Lumen depiction scores, luminal signal heterogeneity, and CNR efficiency were compared between TOF and ferumoxytol-enhanced MR angiography by using a Wilcoxon-Mann-Whitney test. Results:Flow artifacts were greatly reduced by the use of ferumoxytol-enhanced MR angiography. Ferumoxytol-enhanced MR angiography had significantly better performance than TOF MR angiography as measured with the following: lumen depiction scores in all segments (mean, 4.7 6 0.1 [standard error of the mean]; vs 3.0 6 0.3 for arterial inflow, 4.1 6 0.3 vs 1.9 6 0.3 for arterial outflow, 3.7 6 0.3 vs 1.8 6 0.2 for anastomosis, and 4.5 6 0.2 vs 2.1 6 0.2 for venous outflow; P , .001), intraluminal signal homogeneity (0.3 6 0.02 vs 0.4 6 0.06, P = .005), and CNR efficiency in the venous outflow (5.1 6 0.6 vs 2.5 6 0.4, P = .01). Conclusion:This study demonstrates the feasibility of using ferumoxytol-enhanced MR angiography in imaging hemodialysis fistulas with consistently superior image quality compared with nonenhanced TOF MR angiography.q RSNA, 2012

Objective Patients with peripheral artery disease (PAD) have varying degrees of walking disability that does not completely correlate with ankle brachial index (ABI) or angiographic anatomy. We hypothesized that endothelial function (EF) is an independent predictor of symptom severity in PAD patients. Methods This was a cross-sectional study of PAD (N=100) patients presenting to a vascular surgery clinic. All patients received ABI testing and brachial artery flow-mediated, endothelium-dependent, vasodilation (FMD) to assess arterial EF. Symptom severity and walking disability reported by Rutherford category was based on the patient’s self-report during clinic visit, recorded by the investigator-vascular surgeons. Demographic, biochemical and physiologic parameters were entered into regression equations to determine association with symptom severity. Results Mean age was 66 ± 8 and 43% had diabetes. Mean FMD was 7.4% indicating impaired EF. EF progressively declined as Rutherford category increased (p=0.01). Brachial artery FMD, ABI, systolic blood pressure, C-reactive protein, LDL, HDL, beta-blocker use and a history of diabetes or coronary artery disease (CAD) were all associated with Rutherford category (all p<0.05). After multivariable regression, EF (p<0.02) and ABI (p<0.0001) were independently associated with walking disability. When the cohort was restricted to claudicants (n=73), EF remained associated with walking disability after adjustment for other covariates (p=0.0001). Conclusion Symptom severity in PAD is multifactorial, reflecting both impaired hemodynamics and vascular dysfunction. This is the first report demonstrating that walking disability in PAD is associated with arterial EF. The mechanistic link underlying these observations remains to be defined.

Despite current consensus guidelines recommending intensive cardiovascular risk factor management for peripheral artery disease (PAD), patients suffering from PAD continue to experience significant morbidity and mortality. This excess morbid burden is at least partially related to impaired vascular function and systemic inflammation. Interventions bridging this gap are critical. Dietary supplementation of n-3 polyunsaturated fatty acids (n-3 PUFA) has been shown to improve endothelial function and reduce inflammation in different cohorts, as well as to decrease cardiovascular events in secondary prevention trials in patients with coronary artery disease, Their effects in the PAD population are, however, less well understood. The OMEGA-PAD trial is a double-blinded, randomized, placebo-controlled trial that examines the impact of a high-dose, short-duration dietary oral supplementation of n-3 PUFA on vascular function and inflammation in patients with established PAD. The purpose of this article is to provide a detailed description of the design and methods of the OMEGA-PAD trial, and a summary of baseline characteristics of the cohort.