The integrity of endothelial function in major arteries (EFMA) is a powerful independent predictor of heart attack and stroke. Existing ultrasound-based non-invasive assessment methods are technically challenging and suitable only for laboratory settings. EFMA, like blood pressure (BP), is both acutely and chronically affected by factors such as lifestyle and medication. Consequently, laboratory-based measurements cannot fully gauge the effects of medical interventions on EFMA. EFMA and BP have, arguably, comparable (but complementary) value in the assessment of cardiovascular health. Widespread deployment of EFMA assessment is thus a desirable clinical goal. To this end, we propose a device based on modifying the measurement protocol of a standard electronic sphygmomanometer. The protocol involves inflating the cuff to sub-diastolic levels to enable recording of the pulse waveform before and after vasodilatory stimulus. The mechanical unloading of the arterial wall provided by the cuff amplifies the distension that occurs with each pulse, which is measured as a pressure variation in the cuff. We show that the height of the rising edge of each pulse is proportional to the change in lumen area between diastole and systole. This allows the effect of vasodilatory stimuli on the artery to be measured with high sensitivity. We compare the proposed cuff flow-mediated dilation (cFMD) method to ultrasound flow-mediated dilation (uFMD). We find significant correlation (r = 0.55, p = 0.003, N = 27) between cFMD- and uFMD-based metrics obtained when the release of a 5 min cuff occlusion is employed to induce endothelial stimulus via reactive hyperemia. cFMD is approximately proportional to the square of uFMD, representing a typical increase in sensitivity to vasodilation of 300-600%. This study illustrates the potential for an individual to conveniently measure his/her EFMA by using a low-cost reprogrammed home sphygmomanometer.
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. Methods and Results A total of 214 outpatients treated at the San Francisco Veterans Affairs Medical Center underwent tests of endothelial function and evaluation for PTSD . Flow‐mediated vasodilation of the brachial artery was performed to assess endothelial function, and current PTSD status was defined by the PTSD Checklist, based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), with a score ≥40. Multivariable linear regression models were used to estimate the association between PTSD status and endothelial function. Patients with PTSD (n=67) were more likely to be male (99% versus 91%, P =0.04) and to have depression (58% versus 8%, P <0.0001) and were less likely to be on an angiotensin‐converting enzyme inhibitor (17% versus 36%, P =0.007) or β‐blocker treatment (25% versus 41%, P =0.03). Univariate analysis demonstrated that patients with PTSD had significantly lower flow‐mediated vasodilation (5.8±3.4% versus 7.5±3.7%; P =0.003); furthermore, lower flow‐mediated vasodilation was associated with increasing age ( P =0.008), decreasing estimated glomerular filtration rate ( P =0.003), hypertension ( P =0.002), aspirin ( P =0.03), and β‐blocker treatments ( P =0.01). In multivariable analysis, PTSD remained independently associated with lower flow‐mediated vasodilation ( P =0.0005). Conclusions After adjusting for demographic, comorbidity, and treatment characteristics, PTSD remained associated with worse endothelial function in an outpatient population. Whether poor endothelial function contributes to the higher risk of cardiovascular disease in patients with PTSD deserves further study.
The vascular endothelium is a monolayer of cells that cover the interior of blood vessels and provide both structural and functional roles. The endothelium acts as a barrier, preventing leukocyte adhesion and aggregation, as well as controlling permeability to plasma components. Functionally, the endothelium affects vessel tone. Endothelial dysfunction is an imbalance between the chemical species which regulate vessel tone, thombroresistance, cellular proliferation and mitosis. It is the first step in atherosclerosis and is associated with coronary artery disease, peripheral artery disease, heart failure, hypertension, and hyperlipidemia. The first demonstration of endothelial dysfunction involved direct infusion of acetylcholine and quantitative coronary angiography. Acetylcholine binds to muscarinic receptors on the endothelial cell surface, leading to an increase of intracellular calcium and increased nitric oxide (NO) production. In subjects with an intact endothelium, vasodilation was observed while subjects with endothelial damage experienced paradoxical vasoconstriction. There exists a non-invasive, in vivo method for measuring endothelial function in peripheral arteries using high-resolution B-mode ultrasound. The endothelial function of peripheral arteries is closely related to coronary artery function. This technique measures the percent diameter change in the brachial artery during a period of reactive hyperemia following limb ischemia. This technique, known as endothelium-dependent, flow-mediated vasodilation (FMD) has value in clinical research settings. However, a number of physiological and technical issues can affect the accuracy of the results and appropriate guidelines for the technique have been published. Despite the guidelines, FMD remains heavily operator dependent and presents a steep learning curve. This article presents a standardized method for measuring FMD in the brachial artery on the upper arm and offers suggestions to reduce intra-operator variability.
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.The study was institutional review board approved and was in compliance with HIPAA regulations. All participants provided written informed consent. TOF and first-pass 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 five-point 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.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±0.1 [standard error of the mean]; vs 3.0±0.3 for arterial inflow, 4.1±0.3 vs 1.9±0.3 for arterial outflow, 3.7±0.3 vs 1.8±0.2 for anastomosis, and 4.5±0.2 vs 2.1±0.2 for venous outflow; P<.001), intraluminal signal homogeneity (0.3±0.02 vs 0.4±0.06, P=.005), and CNR efficiency in the venous outflow (5.1±0.6 vs 2.5±0.4, P=.01).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.
Introduction: Current guidelines recommend a diet rich in fish or n-3 polyunsaturated fatty acid (PUFA) supplementation in patients with cardiovascular disease including PAD. The omega-3 index represents the red blood cell (RBC) content of the two major long-chain n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with less within-patient variation compared to plasma levels of n-3 PUFA. We aimed to quantify the change in the omega-3 index with high-dose n-3 PUFA supplementation in a PAD cohort. Methods: This study was a secondary analysis of the OMEGA-PAD I Trial (NCT01310270), a randomized, double-blinded, placebo-controlled trial addressing the hypothesis that short-duration, high-dose n-3 PUFA oral supplementation improves endothelial function and inflammation in subjects with PAD. Eighty patients with stable claudication received 4.4g of fish oil (2.6g of EPA + 1.8g of DHA) daily (n=40) or placebo capsules (n=40) for 1 month. The RBC fatty acids (FA) content was measured by gas chromatography (OmegaQuant Analytics, Sioux Falls, SD) and expressed as a percent of total FA. Results: There was no difference in baseline PUFA content between the two groups. There was a shift in the n-6:n-3 ratio in RBC from 5 ± 1 to 3 ± 1 (p<0.0001) and the omega-3 index increased from 5 ± 1 to 9 ± 2 (p<0.0001) in the fish but not in the placebo group (Table). There was a significant increase in EPA, DHA, and n-3 docosapentaenoic acid and a significant decrease in all n-6 PUFA content of RBC in the fish oil but not in the placebo group. Following treatment, there was also a significant reduction in plasma triglycerides (-34 ± 46, p<0.001) in the fish oil group. The change in triglycerides was significantly correlated with the change in omega-3 index (p=0.03). Conclusions: High-dose fish oil supplementation increases the omega-3 index and reduces n-6 PUFA levels. The implications of these changes for patients with PAD will continue to be investigated in a follow-up trial (OMEGA-PAD II).
