Measurement of Arterial Wall Thickness as a Surrogate Marker for Atherosclerosis

Abstract

Abstract-Large observational studies and atherosclerosis regression trials of lipid-modifying pharmacotherapy have established that intima-media thickness of the carotid and femoral arteries, as measured noninvasively by B-mode ultrasound, is a valid surrogate marker for the progression of atherosclerotic disease. To exploit fully the potential of ultrasound imaging in atherosclerosis research, standardized and strictly implemented imaging protocols should be used in both observational studies and applied clinical research. This article describes such a protocol developed at the Academic Medical Center of the University of Amsterdam, the Netherlands. Results are presented from a study that estimated atherosclerosis progression from childhood into old age by measuring intima-media thickness in subjects with familial hypercholesterolemia compared with healthy controls. Key Words: B-mode ultrasound Ⅲ familial hypercholesterolemia Ⅲ intima-media thickness Ⅲ surrogate markers A therosclerosis is a generalized disease of the arterial wall, which may progress or regress depending on a plethora of factors. [1][2][3][4][5][6] This dynamic process is characterized by arterial wall remodeling that may go unnoticed for a lifetime, but may also present as acute vascular disease and become clinically manifest. 2 Because atherosclerosis progresses over decades, epidemiological studies and intervention trials with clinical end points require long-term follow-up, participation of large populations, or both. [3][4][5][6] These requirements have to be met to provide data from which valid conclusions about the determinants of disease or the efficacy of a therapeutic intervention can be drawn. 7 As a consequence, such studies consume precious time and financial resources. 8 To overcome these challenges, surrogate markers became the focus of intense attention. 8 Such markers might be used to investigate determinants of atherosclerosis at an early stage of the process and can, subsequently, assess modifiers of atherosclerotic disease progression, such as lifestyle and pharmacological interventions.Boissel and coworkers have proposed criteria for the validity of surrogate markers as a substitute for clinical end points. 9 These investigators stipulated 3 conditions for the determination of validity. First, a surrogate marker should be more sensitive and more readily available (sensitivity and availability) than the clinical end point. Also, the surrogate marker should be easy to evaluate (convenient), preferably by noninvasive means. Second, the causal relationship between the surrogate marker and the clinical end point (proximity) should be established on the basis of epidemiological, pathophysiological, and clinical studies. It is a prerequisite that patients with and without vascular disease exhibit differences in surrogate marker measurements (specificity). Third, in intervention studies, anticipated clinical benefits (assessment of benefit) should be deducible from the observed changes in the surrogate marker. The latter argument ...

Time-related arterial changes after allogeneic hematopoietic stem cell transplantation in children

“…Nowadays, echographic methods are commonly used to assess not only the flow-mediated vasodilation of the brachial artery but also vascular changes in the wall of the carotid artery (12,23). However, the ultrasonic method for the evaluation of the endothelial function is not yet clinical routine.…”

Depression symptoms and the progression of carotid intima-media thickness: a 5-year follow-up study

“…IMT for the common carotid artery was defined as the mean of the maximum wall thicknesses for the near and far walls on the right and left common carotid segments: (maximum near left wall + maximum far left wall + maximum near right wall + maximum far right wall)/4. For each segment, IMT was defined as the average of 3 measurements [ [17], [20]]. Inter-observer comparisons showed a mean measurement variation equal to 0.04 mm (SD = 0.07 mm; range −0.13 to 0.13 mm).…”

“…As a secondary additional analysis, we investigated whether depressed subjects had a higher likelihood of developing carotid wall thickening (defined as a IMT > 0.9 mm) during the follow-up [ [18], [20]]. We excluded the subjects who already had IMT > 0.9 mm at baseline, and compared the proportion of subjects developing carotid wall thickening according to the depression group using logistic regression.…”

Endarterectomy and Stenting for Asymptomatic Carotid Stenosis

“…Carotid intima-media thickness as measured by ultrasound is rapidly becoming a surrogate marker for systemic atherosclerosis and correlates well with the risk of stroke and other vascular events. 3 In the Cardiovascular Health Study, the 6-year risk of myocardial infarction and stroke increased more than 3-fold for individuals in the highest quintile of carotid intima-media thickness. 4 The triggers behind the transformation of a carotid atherosclerotic plaque from "asymptomatic" to "symptomatic" remain elusive despite significant advances.…”