Abstract-Endothelial dysfunction is an early atherosclerotic event that precedes clinical symptoms and may also render established plaque vulnerable to rupture. Noninvasive assessment of endothelial function is commonly undertaken using the flow-mediated dilation (FMD) technique. Some studies indicate that FMD possesses independent prognostic value to predict future cardiovascular events that may exceed that associated with traditional risk factor assessment. It has been assumed that this association is related to the proposal that FMD provides an index of endothelium-derived nitric oxide (NO) function. Interestingly, placement of the occlusion cuff during the FMD procedure alters the shear stress stimulus and NO dependency of the resulting dilation: cuff placement distal to the imaged artery leads to a largely NO-mediated response, whereas proximal cuff placement leads to dilation which is less NO dependent. We used this physiological observation and the knowledge that prognostic studies have used both approaches to examine whether the prognostic capacity of FMD is related to its role as a putative index of NO function. In a meta-analysis of 14 studies (Ͼ8300 subjects), we found that FMD derived using a proximal cuff was at least as predictive as that derived using distal cuff placement, despite the latter being more NO dependent. This suggests that, whilst FMD is strongly predictive of future cardiovascular events, this may not solely be related to its assumed NO dependency. Although this finding should be confirmed with more and larger studies, we suggest that any direct measure of vascular (endothelial) function may provide independent prognostic information in humans. Cost-effective prevention of cardiovascular disease (CVD) is predicated on cardiovascular risk assessment, which aims to distinguish between individuals at high and low risk of future disease manifestation. An optimal screening method should be inexpensive, relatively noninvasive and reproducible. It should predict risk in patients with known disease and, ideally, the future risk of events in currently healthy asymptomatic populations. 1 Despite several decades of development and refinement, algorithms for the prediction of cardiovascular risk in humans that are based on "traditional" or "conventional" risk factors fail to predict a substantial proportion of cardiovascular events. 1 A recent review pertaining to identification of the "vulnerable patient" concluded that high Framingham risk scores fall short in accurately predicting events in individual patients and cannot provide a clear clinical route for identification or treatment of near future victims of acute coronary syndrome or sudden death. 1 A recent computed tomography angiographic study of 1650 subjects concluded that only 55% of patients with a high plaque burden had high National Cholesterol Education Program/Framingham risk scores. Of the patients identified as high risk by Framingham in this study, 10% had no evidence of plaque, 32% with no plaque were taking statins based on t...

E ndothelial cells synthesize paracrine hormones such as nitric oxide (NO), 1 which have important antiatherogenic properties.2 Early studies in humans that used intra-arterial infusion of endothelial stimulants and inhibitors established that endothelial function is impaired in individuals with cardiovascular diseases and risk factors [3][4][5][6] and that coronary 7,8 and peripheral 9-12 endothelial dysfunction can predict clinical events. In 1992, Celermajer et al 13 introduced an ultrasound technique involving temporary suprasystolic cuff inflation around the limbs and measurement of conduit artery dilation consequent to postischemic hyperemia and an arterial shear stress stimulus. Owing to its relative simplicity, its noninvasive nature, and prognostic research studies that have consistently suggested clinical utility, [14][15][16][17][18][19][20] this so-called flowmediated dilation (FMD) approach has become widely used by both scientists and clinicians.Despite the popularity of the FMD approach, important questions remained unanswered when it was introduced, and the uptake of the technique largely preceded detailed physiological description of underlying mechanisms. In the watershed article of Celermajer and Deanfield, it was reasonably assumed, on the basis of previous animal data, 21,22 that FMD was a flow-and NO-mediated response, despite no evidence being available about its NO dependency. Eventually, the assumption that FMD reflected NO-mediated vascular function was reinforced by physiological experiments that infused NO blockers upstream from an insonated conduit artery and reported that dilator responses to ischemia and shear stress were almost completely abolished. [23][24][25][26] Nonetheless, there have been some well-designed and controlled studies that have been unable to inhibit FMD using NO blockade. 27,28 This disparity in the literature may not only be related to differences in the methodology used to measure FMD, but also to the inclusion of different population groups.Therefore, the aim of this study was to systematically review and meta-analyze the literature relating to crossover studies that have compared FMD under local infusion of saline (FMD saline ) with FMD under local infusion of theto obtain an estimate of the contribution of NO to FMD in human conduit arteries. We used a staged approach and explored the contribution of NO in FMD studies that adopted the standardized approach (ie, using distal cuff placement and ≈5-minute cuff inflation in healthy individuals). Finally, the effect of automated, continuous method of analysis on NO dependency was explored. Abstract-Flow-mediated dilation (FMD) is a noninvasive index of endothelial function and vascular health in humans.Studies examining the role of nitric oxide (NO) are not conclusive. In this article, we quantified the contribution of NO in FMD of conduit arteries and explored the effect of the protocol (ie, distal cuff, ≈5-minute ischemia) and method of analysis (ie, automated and continuous edge detection) on the NO dependenc...

IPC improves 5-km time trial performance in healthy male individuals. Moreover, we found that IPC is associated with an attenuated rise in blood lactate concentration at submaximal level during an incremental running test. This could indicate that IPC allows for higher work rates and thus improves time trial performance.

Daily exposure to IPC for 7 days leads to local and remote improvements in brachial artery FMD and resting skin microcirculation that remain after cessation of the intervention and beyond the late phase of protection. These findings may have clinical relevance for micro- and macrovascular improvements.

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Colder water temperatures may be more effective in the treatment of exercise-induced muscle damage and injury rehabilitation because of greater reductions in muscle blood flow.

35Non-Alcoholic Fatty Liver Disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, 36 adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its 37 effect on insulin resistance in NAFLD is unknown. 38We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve 51With exercise, peripheral insulin sensitivity significant increased (following high-dose insulin) despite 52 no significant change in hepatic glucose production (following low-dose insulin); no changes were 53 observed in the control group. 54Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the 55 reduction in liver fat was insufficient to improve hepatic IR.

Background and aims: Simple clinical algorithms including the fatty liver index (FLI) and lipid accumulation product (LAP) have been developed as surrogate markers for non-alcoholic fatty liver disease (NAFLD), constructed using (semi-quantitative) ultrasonography. This study aimed to validate FLI and LAP as measures of hepatic steatosis, as determined quantitatively by proton magnetic resonance spectroscopy ( 1 H-MRS).