Korean Circ J.  2007 Jan;37(1):1-8. 10.4070/kcj.2007.37.1.1.

Imaging Markers of Subclinical Atherosclerosis

• Kim KS

• KMID: 2227086
• DOI: http://doi.org/10.4070/kcj.2007.37.1.1

Abstract

Atherosclerosis is a generalized disorder that progresses very slowly. Early detection of atherosclerosis is very important to prevent cardiovascular disease such as myocardial infarction, stroke and sudden cardiac death. Various surrogate markers have recently been proposed for the early detection of atherosclerosis in asymptomatic patients who have one or more risk factors. Among them, biomarkers such as CRP, Interleukin, myeloperoxidase, fibrinogen, homocystein and lipoprotein (a) are established as predictors of atherothrobotic events in apparently healthy individuals. Although these novel biomarkers provide important information into the pathophysiology of atherosclerosis, no clear evidence exist that lowering the plasma level of these markers reduces the vascular risk. Imaging markers such as the carotid intima-media thickness and brachial arterial flow mediated vasodilation as assessed by ultrasound, coronary calcification as assessed by CT, and the pulse wave velocity and augmentation index as assessed by tonometry can visualize the arterial wall and directly measure the arterial function. These imaging markers are very useful clinical tools for detecting the early changes of vascular structure and also for predicting cardiovascular events, in addition to being more precise biomarkers in asymptomatic subjects.

Keyword

Atherosclerosis; Intima-media thickness; Flow-mediated vasodilation; Arterial stiness; Surrogate markers

MeSH Terms

Atherosclerosis*
Biomarkers
Cardiovascular Diseases
Carotid Intima-Media Thickness
Death, Sudden, Cardiac
Fibrinogen
Humans
Interleukins
Lipoprotein(a)
Manometry
Myocardial Infarction
Peroxidase
Plasma
Pulse Wave Analysis
Risk Factors
Stroke
Ultrasonography
Vasodilation
Fibrinogen
Interleukins
Lipoprotein(a)
Peroxidase

Figure

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  Fig. 1 Carotid intima-media thickness and plague. A: automated computerized measure of carotid intima-media thickness. B: atherosclerotic plaque in right common carotid artery (arrow).

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  Fig. 2 Coronary calcium in left anterior descending artery (arrow).

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  Fig. 3 Multislice CT (right) and coronary angiographic view of LAD artery. Arrow indicate insignificant stenosis of mid LAD artery in angiography, but MSCT shows significant plaque burden of same site. CT: computed tomography, LAD: left anterior descending, MSCT: multislice CT.

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  Fig. 4 Mechanism of endothelial-dependant and endothelial-independent vasodilation. GTP: guanosine triphosphate, cGMP: cyclic guanosine monophosphate.

Reference

1. Kuulasmaa K, Tunstall-Pedoe H, Dobson A, et al. Estimation of contribution of changes in classic risk factors to trends in coronary. Lancet. 2000. 355:675–687.

2. Fletcher GF, Balady GJ, Vogel RA. Preventive cardiology: how can we do better? Proceedings of the 33rd Bethesda Conference; 2001 Dec 18; Bethesda, Maryland: USA. J Am Coll Cardiol. 2002. 40:580–651.

3. Smith SC Jr, Greenland P, Grundy SM. Prevention conference V: beyond secondary prevention: identifying the high-risk patient for primary prevention: executive summary. Circulation. 2000. 101:111–116.

4. Greenland P, Smith SC Jr, Grundy SM. Improving coronary heart disease risk assessment in asymptomatic people: role of traditional risk factors and noninvasive cardiovascular tests. Circulation. 2001. 104:1863–1867.

5. Popma JJ. Braunwald's Heart Disease. 2005. 7th ed. 423.

6. Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imagimg. Circulation. 1986. 74:1399–1406.

7. Salonen JT, Salonen R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb. 1991. 11:1245–1249.

8. Hollander M, Bots ML, Del Sol AI, et al. Carotid plaque increases the risk of stroke and subgroups of cerebral infarction in asymptomatic elderly: the Rotterdam Study. Circulation. 2002. 105:2872–2877.

9. Stork S, van den Beld AW, von Schacky C, et al. Carotid artery plaque burden, stiffness, and mortality risk in elderly men: a prospective, population-based cohort study. Circulation. 2004. 110:344–348.

10. Zanchetti A, Rosei EA, Dal Palu C, Leonetti G, Magnani B, Pessina A. The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness. J Hypertens. 1998. 16:1667–1676.

11. Zanchetti A, Bond MG, Hennig M, et al. Calcium antagonist lacidipine slows down progression of asymptomatic carotid atherosclerosis: principal results of the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double-blind, long-term trial. Circulation. 2002. 106:2422–2427.

12. Hyun DW, Kim KS, Hur SH. Correlation between the carotid intima-media thickness and the plaque burden of the left main coronary artery using ultrasonography. Korean Circ J. 2005. 35:795–800.

13. Simon A, Gariepy J, Chironi G, Megnien JL, Levenson J. Intima-media thickness: a new tool for diagnosis and treatment of cardiovascular risk. J Hypertens. 2002. 20:159–169.

14. Simon A, Gariepy J, Moyse D, Levenson J. Differential effects of nifedipine and co-amilozide on the progression of early carotid wall changes. Circulation. 2001. 103:2949–2954.

15. Hyun DW, Bae JH, Kim KY, Hwang IK, Kim WS. Measurement of the carotid intima, media and intima-media thickness with ultrasound and new software. Korean Circ J. 2005. 35:625–632.

16. Choi YS, Youn HJ, Hong EJ, et al. The prediction of high echogenicity of intimal area in carotid artery for the plaque burden of culprit lesion in coronary artery disease. Korean Circ J. 2006. 36:458–464.

17. Chambless LE, Heiss G, Folsom AR, et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993. Am J Epidemiol. 1997. 146:483–494.

18. Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation. 1997. 96:1432–1437.

19. O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med. 1999. 340:14–22.

20. Hodis HN, Mack WJ, LaBree L, et al. The role of intima-media thickness in predicting clinical coronary events. Ann Intern Med. 1998. 128:262–269.

21. O'Rourke RA, Brundage BH, Froelicher VF, et al. American College of Cardiology/American Heart Association Expert Consensus document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. Circulation. 2000. 102:126–140.

22. Arad Y, Spaduro LA, Goodman K, et al. Predictive value of electron beam computed tomography of the coronary arteries: 19-month follow-up of 1173 asymptomatic subjects. Circulation. 1996. 93:1951–1953.

23. Kondos GT, Hoff JA, Sevrukov A, et al. Electron-beam tomography coronary artery calcium and cardiac events: a 37-month follow-up of 5635 initially asymptomatic low- to intermediate-risk adults. Circulation. 2003. 107:2571–2576.

24. Detrano RC, Wong ND, Doherty TM, et al. Coronary calcium does not accurately predict near-tern future coronary events in high-risk adults. Circulation. 1999. 99:2633–2638.

25. Schoepf UJ, Becker CR, Ohnesorge BM, Yucel EK. CT of coronary artery disease. Radiology. 2004. 232:18–37.

26. de Feyter PJ, Nieman K. Noninvasive multi-slice computed tomography coronary angiography: an emerging clinical modality. J Am Coll Cardiol. 2004. 44:1238–1240.

27. Schoenhagen P, Hallibruton SS, Stillman AE, et al. Noninvasive imaging of coronary arteries: current and future role of multidetector row CT. Radiology. 2004. 232:7–17.

28. Corretti MC, Anderson TJ, Benjamin EJ, et al. 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. J Am Coll Cardiol. 2002. 39:257–265.

29. Levenson J, Pessana F, Gariepy J, Armentano R, Simon A. Gender differences in wall shear-mediated brachial artery vasoconstriction and vasodilation. J Am Coll Cardiol. 2001. 38:1668–1674.

30. Celemajor DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992. 340:1111–1115.

31. Gordon JB, Ganz P, Nabel EG, et al. Atherosclerosis influences the vasomotion responses of epicardial coronary artery to exercise. J Clin Invest. 1989. 83:1946–1952.

32. Zeiher AM, Drexler H, Wollschlaeger H, Saurbier B, Just H. Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium. J Am Coll Cardiol. 1989. 14:1181–1190.

33. Berry KL, Skyrme-Jones RA, Meredith IT. Occlusion cuff position is an important determinant of the time and magnitude humanbrachial artery flow-mediated dilation. Clin Sci. 2000. 99:261–267.

34. Lee SJ, Lee DW, Kim KS, Lee IK. Comparison of the lag time to initiation of flow-mediated vasodilation to endothelium-dependent vasodilation in the early diagnosis of endothelial dysfunction. Korean Circ J. 2001. 31:867–876.

35. Neunteufl T, Heher S, Katzenschlager R, et al. Late prognostic value of flow-mediated vasodilation in the brachial artery of patients with chest pain. Am J Cardiol. 2000. 86:207–210.

36. Gokce N, Keaney JF Jr, Hunter LM, et al. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol. 2003. 41:1769–1775.

37. Mitchell GF, Parise H, Vita JA, et al. Local shear stress and brachial artery flow-mediated dilation. Hypertension. 2004. 44:134–139.

38. Brevetti G, Silvestro A, Schiano V, Chiariello M. Endothelial dysfunction and cardiovascular risk prediction in peripheral arterial disease: additive value of flow mediated-dilation to ankle-brachial pressure index. Circulation. 2003. 108:2093–2098.

39. Chan SY, Mancini GB, Kuramoto L, Schulzer M, Frohlich J, Ignaszewski A. The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease. J Am Coll Cardiol. 2003. 42:1037–1043.

40. Wattanakit K, Folsom AR, Selvin E, et al. Risk factors for peripheral arterial disease incidence in persons with diabetes. Atherosclerosis. 2005. 180:389–397.

41. Asmar RG. Arterial Stiffness and Pulse Wave Velocity: clinical applications. 1999. Paris: Elsevier.

42. van der Heijden-Spek JJ, Staessens JA, Fagard RH, Hoeks P, Boudier HA, van Bortel LM. Effect of age on brachial artery wall properties differs from the aorta and is gender dependent: a population study. Hypertension. 2000. 35:637–642.

43. Simon A, Levenson J. Effect of hypertension on viscoelasticity of large arteries in humans. Curr Hypertens Rep. 2001. 3:74–79.

44. Graf S, Gariepy J, Massonneau M, et al. Experimental and clinical validation of arterial diameter waveform and intimal media thickness obtained from B-mode ultrasound image processing. Ultrasound Med Biol. 1999. 25:1353–1363.

45. Vlachopoulos C, Hirata K, O'Rourke MF. Pressure-altering agents affect central aortic pressures more than is apparent from upper limb measurements. In hypertensive patients: the role of arterial wave reflections. Hypertension. 2001. 38:1456–1460.

46. European Society of Hypertension-European Society of Cardiology Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens. 2003. 21:1011–1053.

47. Lee YS, Kim KS, Nam CW, et al. Clinical implication of carotid-radial pulse wave velocity for patients with coronary artery disease. Korean Circ J. 2006. 36:565–572.

48. Lee YS, Kim KS, Nam CW, Kim YN. Increased arterial stiffness in patients with cardiac syndrome X: pulse wave velocity in cardiac syndrome X. Korean Circ J. 2005. 35:424–428.

49. Rhee MY, Han SK, Lyu S, Lee MY, Kim YK, Yu SM. Short-term treatment with angiotensin II antagonist in essential hypertension: effects of losartan on left ventricular diastolic function, left ventricular mass, and aortic stiffness. Korean Circ J. 2000. 30:1341–1349.

50. Meaume S, Benetos A, Henry OF, Rudnichi A, Safar ME. Aortic pulse wave velocity predicts cardiovascular mortality in subjects >70 years of age. Arterioscler Thromb Vasc Biol. 2001. 21:2046–2050.

51. Blacher J, Pannier B, Guerin AP, Marchais SJ, Safar ME, London GM. Carotid arterial stiffness as a predictor of cardiovascular and all-cause mortality in end-stage renal disease. Hypertension. 1998. 32:570–574.

52. Williams B, Lacy PS, Thom SM, et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006. 113:1213–1225.

53. De Buyzere LM, Segers P. Peripheral or central augmentation index: an esoteric question or a non-invasive clue to central haemodynamics? J Hypertens. 2007. 25:289–293.

54. Asmar RG, London GM, O'Rourke ME, Safar ME. Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol. Hypertension. 2001. 38:922–926.