Curriculum in cardiologyDetection of endothelial dysfunction with brachial artery ultrasound scanning
Section snippets
Normal endothelium
The vascular endothelium is a monolayer of highly specialized cells that regulates the complex vascular milieu, acting as both a barrier to and facilitator of interactions between the plasma and the vessel. The endothelium accomplishes this goal through the expression of diverse molecules in response to a variety of mechanical and chemical stimuli (Table I). Of these factors, nitric oxide (NO) is essential. NO is produced by the endothelium from L-arginine via a constitutive form of nitric
Endothelial dysfunction
Normal arterial function depends on the complex interplay between endothelium-derived molecules and the vascular milieu. Endothelial dysfunction refers to altered vasoactive, anticoagulant, and anti-inflammatory properties, and dysregulated vascular growth remodeling that results from a loss of NO bioactivity in the endothelium. A reduction in NO activity may be caused by 1) decreased eNOS expression (decreased transcription and/or message stability); 2) insufficient substrate (L-arginine) or
Clinical implications of endothelial dysfunction
Increased NO degradation by ROS and impaired EDV is associated with established cardiovascular risk factors, including hyperlipidemia, cigarette smoking, diabetes mellitus, and hypertension, and an increasing number of diseases (Table II). 11 Importantly, endothelial dysfunction in peripheral arteries correlates with the presence of coronary artery endothelial dysfunction12, 13 and angiographically proven coronary artery disease (CAD).12, 14 In addition, patients with coronary endothelial
Assessment of endothelial function
Endothelial function has been assessed in the literature with a variety of invasive and noninvasive surrogate assays (Table III). Elevation of serum markers (eg, adhesion molecules, selectins, C-reactive protein) has been associated with endothelial dysfunction and its risk factors, but distinguishing between endothelial stimulation and endothelial damage is difficult.6 In addition, assays measuring NO activity in plasma and urine exist, but are heavily affected by dietary habits.16 As a
Brachial artery flow-mediated vasodilation
The measurement of brachial artery flow-mediated vasodilation (FMD) was first described by Anderson and Mark in 198920 and began to see clinical research application in the early 1990s.2 Blood flow through the brachial artery is increased in response to transient hyperemia, which is provoked by inducing postischemic dilation of distal vascular beds. Ischemia is induced by the inflation of an arterial occlusion cuff, positioned on the proximal or mid-forearm. After cuff deflation, brachial
Clinical value of brachial artery flow-mediated vasodilation
Several lines of data suggest that brachial artery FMD may soon have a role beyond the research laboratory. First, brachial artery FMD appears to be a suitable surrogate for coronary arterial reactivity.26 Takase et al13 compared brachial artery FMD to coronary endothelial dysfunction measured angiographically after adenosine triphosphate infusion in 15 patients with suspected CAD. There was a strong correlation between abnormal coronary and brachial FMD (r = 0.78, P < .001), implying that
Limitations of brachial artery FMD
Although the measurement of brachial artery FMD is a noninvasive index of endothelial function with an established relationship to CAD (and its risk factors) and is associated with a panoply of clinical entities, technique- and patient-related limitations and the lack of a “gold-standard” test for endothelial function presently preclude its widespread use as a clinical screening tool.
Technically, measurement of brachial artery diameter can be difficult. Vessel sizes are generally in the 3 to 5
Ongoing studies
Several ongoing clinical trials may help define a clinical application for brachial artery ultrasound scanning. Brachial artery FMD is measured in the Cardiovascular Health Study (CHS), a National Heart, Lung, and Blood Institute study of cardiovascular risk involving >5000 subjects. The subjects in this study, which should be completed in 2005, are being prospectively observed for coronary events. The Multi-ethnic Studies of Atherosclerosis (MESA) trial, which started in 1999, is another
Conclusion
The endothelium is a complex organ that serves as the final common target for a variety of pathophysiologic mechanisms related to CVD. Endothelial dysfunction precedes overt clinical disease, making the endothelium an attractive target for early, preventative pharmacotherapy. Although improvement of endothelial dysfunction has not been shown to result in clinical benefit, prospective trials with firm clinical end points have yet to be performed, in part because of the lack of an accurate,
References (49)
- et al.
Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis
Lancet
(1992) Cholesterol lowering and endothelial function
Am J Med
(1999)- et al.
Endothelial dysfunctionfrom physiology to therapy
J Mol Cell Cardiol
(1999) - et al.
Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease
Am J Cardiol
(1998) - et al.
Noninvasive determination of endothelium-mediated vasodilation as a screening test for coronary artery diseasepilot study to assess the predictive value in comparison with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging
Am Heart J
(1999) Assessment and treatment of endothelial dysfunction in humans
J Am Coll Cardiol
(1999)- et al.
Acute effects of vasoactive drug treatment on brachial artery reactivity
J Am Coll Cardiol
(2002) - et al.
Close relation of endothelial function in the human coronary and peripheral circulations
J Am Coll Cardiol
(1995) - et al.
Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction
J Am Coll Cardiol
(1994) - et al.
Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease
J Am Coll Cardiol
(2001)
Abnormal brachial artery flow-mediated vasodilation in young adults with major depression
Am J Cardiol
Temporal response of brachial artery dilation after occlusion and nitroglycerin
Am J Cardiol
Vascular effects of estrogen in type II diabetic postmenopausal women
J Am Coll Cardiol
Effect of losartan in aging-related endothelial impairment
Am J Cardiol
Randomized trial of a medical food for the dietary management of chronic, stable angina
J Am Coll Cardiol
Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary artery disease (BANFF study)
J Am Coll Cardiol
The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes
J Am Coll Cardiol
The endotheliuma new target for therapy
Vasc Med
Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease
Circulation
Simvastatin, an HMG-CoA-coenzyme A reductase inhibitor, improves endothelial function within 1 month
Circulation
Testing for endothelial function
Ann Med
Regulation of tissue factor expression in human microvascular endothelial cells by nitric oxide
Circulation
The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine
Nature
Endothelial dysfunction in cardiovascular diseasesthe role of oxidant stress
Circ Res
Cited by (183)
The effect of vascular function on the musculoskeletal system
2023, Vascularization and its Role in Medicine and Tissue Engineering