Intima-media thickness

Intima-media thickness (IMT), also called intimal medial thickness, is a measurement of the thickness of tunica intima and tunica media, the innermost two layers of the wall of an artery. The measurement is usually made by external ultrasound and occasionally by internal, invasive ultrasound catheters; see Intravascular ultrasound. Measurements of the wall thickness of blood vessels can also be done using other imaging modalities.

IMT is used to detect the presence of atherosclerotic disease in humans and, more contentiously, to track the regression, arrest or progression of atherosclerosis. Ultrasound IMT measurements have been first proposed and in vitro validated in Milan by Paolo Pignoli in 1984[1] and later publicized in a most cited article.[2] The use of IMT as a non-invasive tool to track changes in arterial walls has increased substantially since the mid-1990s.[3] Although IMT is predictive of future cardiovascular events,[4] the usefulness of measuring change in IMT over time is disputed, as meta-analyses have found that change in IMT is not predictive of cardiovascular events.[5][6] As such, the use of change in IMT as a surrogate endpoint measure of drug efficacy in clinical trials, or in clinical management of cardiovascular disease, is debated.[5]

IMT is occasionally used in clinical practice, but its role is not clear. After systematically reviewing the evidence base for IMT, the United States Preventive Services Task Force found no support for its routine use in stratification of risk for people at intermediate cardiovascular risk.[7] However, in 2003 the European Society of Hypertension–European Society of Cardiology guidelines for the management of arterial hypertension[8] recommended the use of IMT measurements in high-risk patients to help identify target organ damage and in 2010 the American Heart Association and the American College of Cardiology advocated the use of IMT on intermediate risk patients if usual risk classification was not satisfactory.[9]

IMT measurements in the carotid artery

Since the 1990s, both small clinical and several larger scale pharmaceutical trials have used carotid artery IMT as a surrogate endpoint for evaluating the regression and/or progression of atherosclerotic cardiovascular disease. Many studies have documented the relation between the carotid IMT and the presence and severity of atherosclerosis.

Although carotid intima-media thickness is strongly associated with atherosclerosis, thickening of the intima-media may not be due to atherosclerosis. Intimal thickening is a complex process, depending on a variety of factors, including local hemodynamics , shear stress and blood pressure. Changes in shear stress may adversely affect endothelial function and particle residence time, affecting the delivery and transport of potentially atherogenic particles into the arterial wall and consequent plaque formation. Blood pressure may affect IMT through blood vessel remodelling or wall hypertrophy in response to altered circumferential stress. Variations in IMT between different locations, such as the inflow side of branches, the inner curvature at bends and opposite the flow divider at bifurcations may reflect differences in local hemodynamic forces. However, an IMT greater than 0.9-1mm is almost certainly are indicative of atherosclerosis and increased risk of cardiovascular disease.[10]

Mechanisms such as these may explain, at least in part, why the carotid artery seems to be a preferential site for analyzing the relation between wall thickness and atherosclerosis. In general, wall thickening may be in the intimal layer or in the muscular, medial, layer. As the carotid artery is an elastic artery, the muscular media is relatively small. Hence, thickening of the carotid arterial wall is due essentially to intimal thickening. In muscular arteries wall thickening may imply instead (or also) a thickening of the medial wall. Whether or not wall thickening in the carotid artery and the femoral artery (or other muscular arteries) have the same meaning is as yet uncertain. Several studies seem to suggest that the mechanisms underlying their evolution may at least in part differ, with consequently possibly different clinical implications.

Another issue to consider, once the choice to examine the carotid artery has been defined, is on which segment of the carotid artery to perform the measurement. Often, the measurement of the IMT is measured in three tracts: in the common carotid, at one or two cms from the flow divider, at the bifurcation and in the internal carotid artery.

From an academic standpoint, the region to select for IMT measurement is still an object of study. IMT measurements of the deep wall, by ultrasound, are generally more reliable than measurements performed on the outer wall. This difference in the accuracy of near and far wall measurements may be a problem, as some studies have used both measurements to quantify the IMT.

A practical approach to tracking disease presence and progression on any given individual is to select and track those regions with the greatest thickness, i.e. greatest disease burden, as opposed to arbitrarily selecting a particular segment in which the individual may not have much pathology.

Ultrasound methods

By ultrasound, IMT can be measured from either outside the body, in larger arteries relatively close to the skin (e.g., carotids, brachial, radial and/or femoral arteries), and/or internally by IVUS using special catheters that use ultrasound to image blood vessels from inside out. The carotid artery is the usual site of measurement of IMT and the American Society of Echocardiography published a consensus statement on measurement of carotid IMT in 2007 [11]

Key advantages of external ultrasound methods are:

  1. lower cost compared with most other methods
  2. relative comfort and convenience for the patient being examined
  3. lack of need for any IV's of other body invasive methods (usually) and
  4. lack of any X-Ray radiation;

Ultrasound can be used repeatedly, over years, without compromising the patient's short or long term health status.

One 20 year National Institutes of Health ongoing study, called CARDIA, which began recruitment in 1985, is focusing on the efficacy of CIMT to identify subclinical cardiovascular disease at earlier, younger stages in over 5000 individuals.

Both the American Heart Association[12] and the National Cholesterol Education Program, Third Adult Treatment Panel report, i.e. ATP III have encouraged the clinical use of CIMT, but caution that the procedure be done with attention to accuracy and reliability.

As of 2007, while IMT has increasingly become easier to measure using higher grade equipment and careful attention to image quality, most clinical carotid ultrasound software in widespread use in the United States is not designed to easily facilitate measurement of IMT and most clinical ultrasound technicians remain unfamiliar with either performing or the importance of IMT measurements. Instead, most carotid ultrasound examinations remain focused on the older concept of measuring blood velocities within the lumen as an indication of the anatomic changes that occur after disease has progressed to advanced stages of severity.

Radiographic methods

By radiographic, i.e. X-Ray, methods, after arteries have developed advanced calcified atherosclerotic plaque, IMT can also be semi-estimated by the distance between the outer edges of calcification (actually this leaves out most of the media) and the outer edges of an angiographic dye column within the artery lumen. This is a far more complex technique; it is invasive to the body due to the use of X-Ray radiation, catheters and angiographic contrast agents.

The radiographic approach can sometimes be done during angiography, however usually only when an artery segment happens to be visualized on end so that the calcification within the outer edges of plaques can be sufficiently seen.

Radiographic IMT is more often approximated using advanced CAT scanners due to the ability to use software to more slowly and carefully process the images (after the patient's scan has been completed) and then examine artery segments from whatever angle appears most appropriate. In particular some papers have recently produced that indicated that CT and US have an excellent agreement in the analysis of the IMT (in CT analysis is known as CAWT : carotid artery wall thickness)

However, one of the concerns with all CT scanners, both EBT and perhaps more so with the spiral scanners (which are more commonly used because they are less expensive to purchase), is the dose of X-Ray delivered to the patient’s body and concerns about the safety of repeated doses of X-Ray to track disease status over time.

References

  1. ↑ Pignoli P. "Ultrasound B-mode imaging for arterial wall thickness measurement". Atherosclerosis Reviews (1984) 12:177-184
  2. ↑ Pignoli P, Tremoli E, Poli A, Oreste PL, Paoletti R (Dec 1986). "Intima plus media thickness of the arterial wall: a direct measurement with ultrasound imaging". Circulation 74:1399-1495
  3. ↑ de Groot E, van Leuven SI, Duivenvoorden R et al. (May 2008). "Measurement of carotid intima-media thickness to assess progression and regression of atherosclerosis". Nat Clin Pract Cardiovasc Med 5 (5): 280–8. doi:10.1038/ncpcardio1163. PMID 18332891.
  4. ↑ Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M (January 2007). "Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis". Circulation 115 (4): 459–67. doi:10.1161/CIRCULATIONAHA.106.628875. PMID 17242284.
  5. ↑ 5.0 5.1 Costanzo P, Perrone-Filardi P, Vassallo E, Paolillo S, Cesarano P, Brevetti G, Chiariello M. (7 Dec 2010). "Does carotid intima-media thickness regression predict reduction of cardiovascular events? A meta-analysis of 41 randomized trials". J Am Coll Cardiol 56 (24): 2006–20. doi:10.1016/j.jacc.2010.05.059. PMID 21126642.
  6. ↑ Lorenz MW, Polak JF, Kavousi M, Mathiesen EB, Völzke H, Tuomainen TP, Sander D, Plichart M, Catapano AL, Robertson CM, Kiechl S, Rundek T, Desvarieux M, Lind L, Schmid C, Dasmahapatra P, Gao L, Ziegelbauer K, Bots ML, Thompson SG; on behalf of the PROG-IMT Study Group. (26 Apr 2012 (epub ahead of print)). "Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data.". Lancet 379 (9831): 2053–62. doi:10.1016/S0140-6736(12)60441-3. PMID 22541275. Check date values in: |date= (help)
  7. ↑ Helfand M, Buckley DI, Freeman M, Fu R, Rogers K, Fleming C, Humphrey LL. (6 Oct 2009). "Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force.". Ann Intern Med 151 (7): 496–507. doi:10.7326/0003-4819-151-7-200910060-00010. PMID 19805772.
  8. ↑ "2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension". J. Hypertens. 21 (6): 1011–53. June 2003. doi:10.1097/01.hjh.0000059051.65882.32. PMID 12777938.
  9. ↑ LPhilip Greenland, MD, FACC, FAHA (15 November 2010). "2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults.". Journal of the American College of Cardiology.
  10. ↑ Filippo Molinari; Jasjit S. Suri; Chirinjeev Kathuria (2010). Atherosclerosis Disease Management. Berlin: Springer. ISBN 1-4419-7221-8.
  11. ↑ James H. Stein, MD, FASE (November 2007). "Use of Carotid Ultrasound to Identify SubclinicalVascular Disease and Evaluate Cardiovascular Disease Risk: A Consensus Statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force Endorsed by the Society for Vascular Medicine.". American Society of Echocardiography.
  12. ↑ Prevention Conference V : Beyond Secondary Prevention : Identifying the High-Risk Patient for Primary Prevention : Noninvasive Tests of Atherosclerotic Burden : Writing Group III - Greenland et al. 101 (1): e16 - Circulation