Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: A report of the International Brachial Artery Reactivity Task Force

The Multi-Ethnic Study of Atherosclerosis was initiated in July 2000 to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease (CVD) in a population-based sample of 6,500 men and women aged 45-84 years. The cohort will be selected from six US field centers. Approximately 38% of the cohort will be White, 28% African-American, 23% Hispanic, and 11% Asian (of Chinese descent). Baseline measurements will include measurement of coronary calcium using computed tomography; measurement of ventricular mass and function using cardiac magnetic resonance imaging; measurement of flow-mediated brachial artery endothelial vasodilation, carotid intimal-medial wall thickness, and distensibility of the carotid arteries using ultrasonography; measurement of peripheral vascular disease using ankle and brachial blood pressures; electrocardiography; and assessments of microalbuminuria, standard CVD risk factors, sociodemographic factors, life habits, and psychosocial factors. Blood samples will be assayed for putative biochemical risk factors and stored for use in nested case-control studies. DNA will be extracted and lymphocytes will be immortalized for genetic studies. Measurement of selected subclinical disease indicators and risk factors will be repeated for the study of progression over 7 years. Participants will be followed through 2008 for identification and characterization of CVD events, including acute myocardial infarction and other coronary heart disease, stroke, peripheral vascular disease, and congestive heart failure; therapeutic interventions for CVD; and mortality.

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Multi-Ethnic Study of Atherosclerosis: Objectives and Design

Atherosclerosis begins in childhood, progresses silently through a long preclinical stage, and eventually manifests clinically, usually from middle age. Over the last 30 years, it has become clear that the initiation and progression of disease, and its later activation to increase the risk of morbid events, depends on profound dynamic changes in vascular biology.1 The endothelium has emerged as the key regulator of vascular homeostasis, in that it has not merely a barrier function but also acts as an active signal transducer for circulating influences that modify the vessel wall phenotype.2 Alteration in endothelial function precedes the development of morphological atherosclerotic changes and can also contribute to lesion development and later clinical complications.3

Appreciation of the central role of the endothelium throughout the atherosclerotic disease process has led to the development of a range of methods to test different aspects of its function, which include measures of both endothelial injury and repair. These have provided not only novel insights into pathophysiology, but also a clinical opportunity to detect early disease, quantify risk, judge response to interventions designed to prevent progression of early disease, and reduce later adverse events in patients.

The present review summarizes current understanding of endothelial biology in health and disease, the strengths and weaknesses of current testing strategies, and their potential applications in clinical research and patient care.

Although only a simple monolayer, the healthy endothelium is optimally placed and is able to respond to physical and chemical signals by production of a wide range of factors that regulate vascular tone, cellular adhesion, thromboresistance, smooth muscle cell proliferation, and vessel wall inflammation. The importance of the endothelium was first recognized by its effect on vascular tone. This is achieved by production and release of several vasoactive molecules that relax or constrict the vessel, as …

Endothelial Function and Dysfunction Testing and Clinical Relevance

The clinical implications of endothelial dysfunction.

Endothelial dysfunction is now considered an important early event in the development of atherosclerosis, which precedes gross morphological signs and clinical symptoms. The assessment of flow-mediated dilation (FMD) was introduced almost 20 years ago as a noninvasive approach to examine vasodilator function in vivo. FMD is widely believed to reflect endothelium-dependent and largely nitric oxide-mediated arterial function and has been used as a surrogate marker of vascular health. This noninvasive technique has been used to compare groups of subjects and to evaluate the impact of interventions within individuals. Despite its widespread adoption, there is considerable variability between studies with respect to the protocols applied, methods of analysis, and interpretation of results. Moreover, differences in methodological approaches have important impacts on the response magnitude, can result in spurious data interpretation, and limit the comparability of outcomes between studies. This review results from a collegial discussion between physiologists with the purpose of developing considered guidelines. The contributors represent several distinct research groups that have independently worked to advance the evidence base for improvement of the technical approaches to FMD measurement and analysis. The outcome is a series of recommendations on the basis of review and critical appraisal of recent physiological studies, pertaining to the most appropriate methods to assess FMD in humans.

https://www.physiology.org/doi/pdf/10.1152/ajpheart.00471.2010

Assessment of flow-mediated dilation in humans: a methodological and physiological guideline

Background Experimental evidence suggests that flow-dependent dilatation of conduit arteries is mediated by nitric oxide (NO) and/or prostacyclin. The present study was designed to assess whether NO or prostacyclin also contributes to flow-dependent dilatation of conduit arteries in humans. Methods and Results Radial artery internal diameter (ID) was measured continuously in 16 healthy volunteers (age, 24±1 years) with a transcutaneous A-mode echo-tracking system coupled to a Doppler device for the measurement of radial blood flow. In 8 subjects, a catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of the NO synthase inhibitor NG-monomethyl-l-arginine (L-NMMA; 8 μmol/min for 7 minutes; infusion rate, 0.8 mL/min). Flow-dependent dilatation was evaluated before and after L-NMMA or aspirin as the response of the radial artery to an acute increase in flow (reactive hyperemia after a 3-minute cuff wrist occlusion). Under control conditions, release of the occlusion...

El Hassan Bakkali

Papers

Nitric Oxide Is Responsible for Flow-Dependent Dilatation of Human Peripheral Conduit Arteries In Vivo