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Peripheral artery disease (PAD) is a vascular pathology with high prevalence among the aging population. PAD is associated with decreased cognitive performance, but the underlying mechanisms remain obscure. Normal brain function critically depends on an adequate adjustment of cerebral blood supply to match the needs of active brain regions via neurovascular coupling (NVC). NVC responses depend on healthy microvascular endothelial function. PAD is associated with significant endothelial dysfunction in peripheral arteries, but its effect on NVC responses has not been investigated. This study was designed to test the hypothesis that NVC and peripheral microvascular endothelial function are impaired in PAD. We enrolled 11 symptomatic patients with PAD and 11 age- and sex-matched controls. Participants were evaluated for cognitive performance using the Cambridge Neuropsychological Test Automated Battery and functional near-infrared spectroscopy to assess NVC responses during the cognitive n-back task. Peripheral microvascular endothelial function was evaluated using laser speckle contrast imaging. We found that cognitive performance was compromised in patients with PAD, evidenced by reduced visual memory, short-term memory, and sustained attention. We found that NVC responses and peripheral microvascular endothelial function were significantly impaired in patients with PAD. A positive correlation was observed between microvascular endothelial function, NVC responses, and cognitive performance in the study participants. Our findings support the concept that microvascular endothelial dysfunction and neurovascular uncoupling contribute to the genesis of cognitive impairment in older PAD patients with claudication. Longitudinal studies are warranted to test whether the targeted improvement of NVC responses can prevent or delay the onset of PAD-associated cognitive decline. NEW & NOTEWORTHY Peripheral artery disease (PAD) was associated with significantly decreased cognitive performance, impaired neurovascular coupling (NVC) responses in the prefrontal cortex (PFC), left and right dorsolateral prefrontal cortices (LDLPFC and RDLPFC), and impaired peripheral microvascular endothelial function. A positive correlation between microvascular endothelial function, NVC responses, and cognitive performance may suggest that PAD-related cognitive decrement is mechanistically linked, at least in part, to generalized microvascular endothelial dysfunction and subsequent impairment of NVC responses.

Peripheral artery disease (PAD) is highly prevalent, affecting up to 20% of people over 70 years of age. To test the hypothesis that PAD promotes the pathogenesis of vascular cognitive impairment (VCI), we compared cognitive function in older adults with symptomatic PAD and in participants without PAD who had a burden of comorbid conditions. Furthermore, we compared the cognitive function of these groups after adjusting for demographic and clinical characteristics, comorbid conditions, and cardiovascular risk factors. Participants with PAD (age: 69 ± 8 years; n = 58) and those without PAD (age: 62 ± 8 years; n = 30) were assessed on a battery of eight neuropsychological tests. The tests assessed attention and working memory, verbal memory, non-verbal memory, perceptuo-motor speed, and executive function. Participants were further characterized on demographic and clinical characteristics, comorbid conditions, cardiovascular risk factors, and ankle-brachial index. The PAD group had significantly lower neuropsychological scores than the non-PAD control group on all eight tests (P

Preclinical studies demonstrate that generalized endothelial cell dysfunction and microvascular impairment are potentially reversible causes of age-related vascular cognitive impairment and dementia (VCID). The present study was designed to test the hypothesis that severity of age-related macro- and microvascular dysfunction measured in the peripheral circulation is an independent predictor of cognitive performance in older adults. In this study, we enrolled 63 healthy individuals into young ( 65 years old) groups. We used principal component analysis (PCA) to construct a comprehensive peripheral vascular health index (VHI) encompassing peripheral microvascular reactivity, arterial endothelial function, and vascular stiffness, as a marker of aging-induced generalized vascular dysfunction. Peripheral macrovascular and microvascular endothelial function were assessed using flow-mediated dilation (FMD) and laser speckle contrast imaging tests. Pulse waveform analysis was used to evaluate the augmentation index (AIx), a measure of arterial stiffness. Cognitive function was measured using a panel of CANTAB cognitive tests, and PCA was then applied to generate a cognitive impairment index (CII) for each participant. Aged subjects exhibited significantly impaired macrovascular endothelial function (FMD, 5.6 ± 0.7% vs. 8.3 ± 0.6% in young, p = 0.0061), increased arterial stiffness (AIx 29.3 ± 1.8% vs 4.5 ± 2.6% in young, p

We compared the prevalence of participants with and without symptomatic peripheral artery disease (PAD) who met the goals of attaining7000 and 10 000 steps/d, and we determined whether PAD status was significantly associated with meeting the daily step count goals before and after adjusting for demographic variables, comorbid conditions, and cardiovascular risk factors.Participants with PAD (n = 396) and without PAD (n = 396) were assessed on their walking for 7 consecutive days with a step activity monitor.The PAD group took significantly fewer steps/d than the non-PAD control group (6722 ± 3393 vs. 9475 ± 4110 steps/d; P.001). Only 37.6% and 15.7% of the PAD group attained the goals of walking7000 and 10 000 steps/d, respectively, whereas 67.9% and 37.4% of the control group attained these goals (P.001 for each goal). Having PAD was associated with a 62% lower chance of attaining 7000 steps/d than compared with the control group (OR = 0.383; 95% CI, 0.259-0.565; P.001), and a 55% lower chance of attaining 10 000 steps/d (OR = 0.449; 95% CI, 0.282-0.709; P.001). Significant covariates (P.01) included age, current smoking, diabetes, and body mass index.Participants with symptomatic PAD had a 29% lower daily step count compared with age- and sex-matched controls, and were less likely to attain the 7000 and 10 000 steps/d goals. Additionally, participants who were least likely to meet the 7000 and 10 000 daily step count recommendations included those who were older, currently smoked, had diabetes, and had higher body mass index.

Background Autonomic dysregulation in heart failure with reduced ejection fraction plays a major role in endothelial dysfunction. Low-level tragus stimulation (LLTS) is a novel, noninvasive method of autonomic modulation. Methods and Results We enrolled 50 patients with heart failure with reduced ejection fraction (left ventricular ejection fraction of ≤40%) in a randomized, double-blinded, crossover study. On day 1, patients underwent 60 minutes of LLTS with a transcutaneous stimulator (20 Hz, 200 μs pulse width) or sham (ear lobule) stimulation. Macrovascular function was assessed using flow-mediated dilatation in the brachial artery and cutaneous microcirculation with laser speckle contrast imaging in the hand and nail bed. On day 2, patients were crossed over to the other study arm and underwent sham or LLTS; vascular tests were repeated before and after stimulation. Compared with the sham, LLTS improved flow-mediated dilatation by increasing the percent change in the brachial artery diameter (from 5.0 to 7.5, LLTS on day 1, P = .02; and from 4.9 to 7.1, LLTS on day 2, P = .003), compared with no significant change in the sham group (from 4.6 to 4.7, P = .84 on day 1; and from 5.6 to 5.9 on day 2, P = .65). Cutaneous microcirculation in the hand showed no improvement and perfusion of the nail bed showed a trend toward improvement. Conclusions Our study demonstrated the beneficial effects of acute neuromodulation on macrovascular function. Larger studies to validate these findings and understand mechanistic links are warranted.

The primary aim of the study was to assess whether both the amount and pace of daily walking were associated with circulating antioxidant capacity in symptomatic patients with peripheral artery disease (PAD).Community-based walking was measured in 244 men and women who were limited by symptomatic PAD during a 1-week period in which they wore an ankle-mounted step activity monitor. Patients were further characterized by circulating antioxidant capacity with the OxiSelect (Cell Biolabs Inc, San Diego, Calif) hydroxyl radical antioxidant capacity (HORAC) activity assay.To assess the amount of walking, patients were grouped into low (≤2440 strides/d), middle (2441-3835 strides/d), and high (3835 strides/d) stride tertiles. HORAC was higher in the middle (P = .03) and high (P = .01) stride tertiles than in the low tertile, but there was no difference between middle and high tertiles (P = .44). To assess the pace of walking, patients were grouped into slow (25.0 strides/min), middle (25.0-31.6 strides/min), and fast (31.6 strides/min) cadence tertiles. HORAC was higher in the high cadence tertile than in the low (P .01) and middle (P .01) tertiles, but there was no difference between low and middle tertiles (P = .48). Similar findings were obtained on group differences in HORAC after adjusting for age, sex, race, and ankle-brachial index for both the amount and pace of daily walking.Walking2440 strides each day and walking at a cadence faster than 31.6 strides/min for 30 minutes each day are both associated with greater circulating antioxidant capacity in symptomatic patients with PAD. The clinical significance is that a home-based walking program may be one approach to increase endogenous antioxidant capacity.

Deep vein thrombosis (DVT) is a prevalent disease. About 20 to 30% of patients with DVT will develop postthrombotic syndrome (PTS) within months after the initial diagnosis of DVT. There is no gold standard for diagnosis of PTS, but clinical signs include pitting edema, hyperpigmentation, phlebectatic crown, venous eczema, and varicose veins. Several scoring systems have been developed for diagnostic evaluation. Conservative treatment includes compression therapy, medications, lifestyle modification, and exercise. Compression therapy, the mainstay and most proven noninvasive therapy for patients with PTS, can be prescribed as compression stockings, bandaging, adjustable compression wrap devices, and intermittent pneumatic compression. Medications may be used to both prevent and treat PTS and include anticoagulation, anti-inflammatories, vasoactive drugs, antibiotics, and diuretics. Exercise, weight loss, smoking cessation, and leg elevation are also recommended. Areas of further research include the duration, compliance, and strength of compression stockings in the prevention of PTS after DVT; the use of intermittent compression devices; the optimal medical anticoagulant regimen after endovascular therapy; and the role of newer anticoagulants as anti-inflammatory agents.

Objective Time spent in sedentary behavior has been associated with worse inflammation and cardiometabolic biomarkers in various populations. However, the association between time spent in sedentary behavior and biomarkers remains unknown in patients with intermittent claudication. The aim of the current study was to analyze the relationship between sedentary behavior and inflammatory and cardiometabolic biomarkers in patients with symptomatic peripheral arterial disease (PAD). Methods The sample included 297 patients with intermittent claudication. Sedentary behavior was assessed using a step activity monitor. Biomarkers of inflammation, oxidative stress, lipid profile, insulin resistance, and endogenous fibrinolysis were assessed. Demographic data, body mass index, physical activity status, and measures of severity of PAD (ankle-brachial index, peak walking time, and ischemic window) also were obtained. Results Time spent in sedentary behavior was related with high-sensitivity C-reactive protein ( b = 0.187; P = .005), glucose ( b = 0.238; P b = 0.167; P = .017), plasminogen activator inhibitor 1 activity ( b = 0.143; P = .036), and high-density lipoprotein cholesterol ( b = −0.133; P = .029). After adjustment for sex, age, physical activity status, body mass index, and severity of PAD, sedentary behavior remained related with high-sensitivity C-reactive protein ( b = 0.170; P = .015), glucose ( b = 0.178; P = .004), fibrinogen ( b = 0.189; P = .010), and high-density lipoprotein cholesterol ( b = −0.128; P = .032). Conclusions Time spent in sedentary activities was associated with worse inflammatory and cardiometabolic profile in patients with intermittent claudication.

Background Peripheral artery disease (PAD) is a highly prevalent disease that impairs walking ability. Walking tests, such as the 6-minute walk test (6MWT) and 4-meter walk test, are commonly used to assess exercise endurance and ambulatory function over a short distance, respectively. The 6MWT performance is predictive of PAD severity and disease outcomes, but it is not feasible in many clinical settings because it requires a long walkway to serve as the test route and lengthens clinic visits. As an alternative, the 4-meter walk test is convenient, inexpensive, and repeatable, but whether it accurately predicts endurance performance in the long-distance 6MWT is not known. The goal of this study was to develop a statistical model to predict 6MWT gait speed from 4-meter walk test results and clinical characteristics among patients with PAD. Methods Measures of 6MWT gait speed were derived from 183 patients with symptomatic PAD who were evaluated at the University of Oklahoma Health Sciences Center (2004-2012). The testing procedures and research personnel remained constant throughout the duration of the study. Independent variables included demographic and clinical information and 4-meter walk test gait speed. Fivefold cross validation and manual backward selection were used for model selection. Adjusted R 2 and corrected Akaike information criterion were applied to quantify the predictive performance of the regression models. Results A total of 183 people (54% male; mean age, 65 [standard deviation (SD), 10] years) with moderate PAD severity (ankle-brachial index [ABI]; mean, 0.72 [SD, 0.24]) performed the walking tests. Participants covered an average distance of 335 (SD, 97) m distance in the 6MWT. The 4-meter walk gait speed, ABI, and dyspnea were independent predictors of 6MWT speed in the multivariate model (adjusted R 2 = 0.55). The model resulted in 95% prediction interval widths of 30 m for mean and 260 m for individual predicted 6MWT distance measures. Conclusions Slower 4-meter walking speed, lower ABI, and presence of dyspnea all predict slower 6MWT gait speed, which corresponds to shorter 6MWT distance. Prediction of group means is reasonably precise; however, prediction of individual patient 6MWT performance is imprecise relative to between-group differences that are clinically important.

Introduction Heart Failure with reduced ejection fraction (HFrEF) is a major cause of morbidity and mortality. Endothelial dysfunction is common in HFrEF. We propose a novel non-invasive stimulation of vagus nerve via direct low-level tragus stimulation (LLTS) as a potential to improve endothelial function in HFrEF. Effects of LLTS mimic direct vagal stimulation, which is proven to reduce sympathetic drive and nitric oxide synthesis. We conducted a first in human pilot clinical study to investigate the effects of LLTS on endothelial function. Methods We enrolled 20 patients with HFrEF in a randomized, double-blinded crossover study. The cohort characteristics were: 75%-male, 65%-Caucasians, Ischemic etiology-80%, HTN-65%, Diabetes-20%, ICD- 60%. All patients had LVEF Results Experimental LLTS for 60 minutes resulted in the improved microcirculation/endothelial function when measured using LSCI in nail beds Figure 1C, 1.78±0.17 vs. 2.47±0.27, p Conclusion Our first human pilot study demonstrated the beneficial effects of neuromodulation/LLTS on microcirculation/endothelial function in patients with HFrEF. Larger studies are underway to further validate these findings.

The aim of the study was to determine whether gait characteristics were associated with endothelial cell inflammation, oxidative stress, and apoptosis and with circulating biomarkers of inflammation and antioxidant capacity in older patients with symptomatic peripheral artery disease (PAD). Gait measurements of 231 symptomatic men and women with PAD were assessed during a 4-m walk test. Patients were further characterized on endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells and on circulating inflammatory and vascular biomarkers. In a multivariate regression model for gait speed, the significant independent variables were age (p

A 69-year-old woman presented to an outside hospital with chest pressure radiating to the back and dyspnea. Computed tomography (CT) of the chest with pulmonary embolism protocol for elevated D-dimer was negative (Figure 1). She had mild Troponin elevation that resolved along with the symptoms, and the patient underwent a stress test to rule out acute coronary syndrome. She developed dyspnea during the test, prompting a chest x-ray, which showed left-sided pleural effusion and mediastinal shift to the right that was not seen on the admission chest x-ray (Figure 2). A thoracentesis demonstrated hemorrhagic fluid. A CT of the chest without contrast showed an intimal flap in the aorta with a centrally displaced calcified atherosclerotic plaque characteristic of aortic dissection that could not be seen in the previous CT with pulmonary embolism protocol (Figure 3). After this, she was transferred to our hospital, where a transthoracic echocardiogram almost 6 hours later showed a type I aortic …

Background: Aspirin is beneficial for reducing the incidence of myocardial infarctions and ischemic strokes and has been recommended by United States Preventive Services Task Force (USPSTF) as a primary prevention strategy for men above the age of 45 years and women above the age of 55 years until the age of 80. This study was intended to evaluate the use of aspirin as a discharge medication for primary prevention in patients who have been assessed for cardiovascular risk in hospital. Methods: Data was collected prospectively over a period of six successive months from 250 consecutive patients who were admitted with chest pain without a history of coronary artery disease and had their cardiovascular risk assessed in hospital by means of patient history, physical exam, laboratory work and a stress test. Inclusion criteria included age within the USPSTF recommendations, not taking aspirin at the time of admission, a 10 year coronary heart disease risk and 10 year stroke risk greater than the risk of bleeding from the use of aspirin. Exclusion criteria included existing indication for aspirin use, contraindication to its use including documented allergy and already on other antiplatelet agents or anticoagulants. Predictors of discharge on aspirin where assessed with Logistic Regression. Statistical significance was determined at p ≤ 0.05. Data analysis was performed using SPSS 18.0 ® (SPSS, Inc., Chicago, IL). Results: Of the 250 patients, 120 patients fulfilled the existing recommendations for the use of aspirin for primary prevention as per USPSTF guidelines. Amongst the study population, 57.9% (33 of 57) men and only 42.9% (27 of 63) of the women were discharged home on aspirin. Having diabetes (OR 3.87; CI 1.39 - 10.77; p=0.01) and being older (OR 0.93; CI 0.87 - 0.89; p=0.003) played a significant role in being discharged on aspirin when using multivariate analysis. However a specific cut off age was not discernible. Amongst women, apart from diabetes (OR 7.85; CI 1.26 - 49.1; p=0.028) and age (OR 0.83; CI 0.74 - 0.93; p=0.002) with elderly patients more likely to be discharged on aspirin, hypertension (OR 4.16; CI 1.04 - 16.7; p=0.044) also played a significant role under multivariate analysis. Other factors including dyslipidemia, family history of cardiovascular disease, tobacco use and racial differences did not play a significant role.There were no such clinical predictors for men that was statistically significant. Conclusion: Aspirin is being under-utilized as part of primary prevention strategy. The presence of diabetes and an elderly patient often prompts a recommendation for aspirin use. A conscious effort should be made by hospital based care providers to ensure that the appropriate preventive strategies are part of their discharge medication list.

[Figure][1] [![Graphic][3] ][3][![Graphic][4] ][4][![Graphic][5] ][5] A 65-year-old gentleman presented with epigastric discomfort and dyspnea on exertion for 2 weeks. Electrocardiogram was consistent with atrial flutter with 2:1 conduction and persistent ST-segment

With the rampant spread of obesity in the United States (21) and throughout the world (1,9,38), coupled with the recognized impact of obesity on health-related outcomes, the assessment of body fat is becoming an increasingly important clinical measure. Significant technological advances have been made that allow for the estimation of total body fat and fat distribution non-invasively and with relatively good precision in humans (10). The application of many of these techniques in field settings is limited because of the expense associated with purchase and maintenance of equipment and specially trained and licensed operators required for use of some instruments (28). A pressing need remains for inexpensive and convenient measurement methods that are suitable for application in clinical, research, and field settings or in gyms where the latest equipment is not readily available. For more than three decades, prediction equations published by Durnin and Womersley (DW) in 1974 (5) have been widely used to estimate percent body fat from caliper-measured skinfold thicknesses. The authors’ thorough approach to equation development and provision of easy-to-use tables for estimation of percent body fat with any combination of four commonly used skinfolds (biceps, triceps, subscapular, and suprailiac) made this a seminal contribution to the field of body composition assessment. The equations were developed in a Caucasian population and were based on the linear relationship between the log of skinfolds and the hydrodensitometry-measured body density (5). Since then, several studies have reported that body density, and more specifically the density of fat-free mass, is not constant but varies according to age, sex, and race/ethnicity (3,36). Racial differences in body density (13) and subcutaneous fat patterning (33,40) may partially explain why the DW equations have shown modest differences in their ability to predict percent body fat in some African American (15) and Asian (6) subjects. Thus, a reevaluation of the DW equations is warranted within these and other race/ethnicity groups that have been shown to differ in body composition from Caucasians. The emergence and now widespread use of dual-energy x-ray absorptiometry (DXA) has added a new dimension to clinical body composition assessment since the development of the DW equations. Having added a third component, bone mineral density, to the two-compartment model used by hydrodensitometry, DXA has expanded clinical use (in addition to its original purpose in osteoporosis screening and bone mineral density assessment) and is increasingly used as a criterion measurement for body composition assessment in clinics and research facilities (24). The DW equations have recently been shown to underestimate percent body fat in a Caucasian sample using a four-compartment model (23), but as yet, no study has systematically evaluated whether these equations apply across race or ethnic groups to predict DXA-measured percent body fat. The primary aim of this study was to apply the 1974 DW equations, using the sum of four skinfolds to predict percentage body fat using DXA as the criterion method in a large multiracial adult sample. A secondary aim of this study was to develop sex- and race/ethnicity-specific equations for the prediction of DXA-measured percent fat using standard clinical anthropometric measures and any combination of the set of four skinfolds originally proposed by DW.