Atherosclerosis in angiographically "normal" coronary artery reference segments: an intravascular ultrasound study with clinical correlations

Intravascular Ultrasound Imaging and Cardiac Catheterization Laboratories, Washington Hospital Center, Washington, DC 20010, USA.

OBJECTIVES: This study evaluated the magnitude, patterns and clinical correlates of atherosclerosis in angiographically "normal" reference segments in patients undergoing transcatheter therapy for symptomatic coronary artery disease. BACKGROUND. Pathologic studies indicate that the extent of coronary atherosclerosis is underestimated by visual analysis of angiographically normal coronary artery segments. Intravascular ultrasound allows detailed, high quality cross-sectional imaging of the coronary arteries in vivo. METHODS. Intravascular ultrasound was used to study angiographically normal coronary artery reference segments in 884 patients evaluated for transcatheter therapy for symptomatic native coronary artery disease. The reference segment was the most visually normal intravascular ultrasound cross section within 10 mm proximal to the target lesion but distal to any major side branch. Results are presented as mean value +/- 1 SD. RESULTS. Only 60 (6.8%) of 884 angiographically normal reference segments were normal by intravascular ultrasound. Reference segment percent cross-sectional narrowing measured 51 +/- 13% and correlated poorly with the target lesion percent cross-sectional narrowing (r = 0.166, p < 0.0001). Reference segments contained less calcific and dense fibrotic plaque and proportionately more soft plaque elements. Independent predictors of reference segment percent cross-sectional narrowing were male gender, patient age, diabetes mellitus, hypercholesterolemia and presence of multivessel disease. Independent predictors of reference segment calcification were patient age and serum creatinine levels. Reference segment percent cross-sectional narrowing in 723 patients undergoing transcatheter therapy was similar to that in patients studied for diagnostic purposes; however, reference segment arc of calcium was greater in treated patients (43 +/- 81 vs. 25 +/- 57, p = 0.015). Reference segment disease was not an independent predictor of subsequent angiographic restenosis or clinical events within 12 months of follow-up. CONCLUSIONS. Atherosclerosis is ubiquitous in angiographically normal coronary artery reference segments. Reference segment disease parallels the severity of target lesion disease and is associated with many of the conventional risk factors for coronary artery disease. Because of its sensitivity in detecting atherosclerosis in angiographically normal reference segments, intravascular ultrasound should enhance the study of risk factors for atherosclerosis and the results of therapies to control disease progression.

This article has been cited by other articles:

				M.-C. Parent and S. Rinfret The unresolved issues with risk stratification and management of patients with coronary artery disease undergoing major vascular surgery: [Questions non resolues concernant la stratification du risque et la prise en charge des patients atteints de maladie coronarienne subissant une chirurgie vasculaire majeure] Can J Anesth, August 1, 2008; 55(8): 542 - 556. [Abstract] [Full Text] [PDF]

				J. D. Schuijf, J. M. van Werkhoven, G. Pundziute, J. W. Jukema, I. Decramer, M. P. Stokkel, P. Dibbets-Schneider, M. J. Schalij, J. H.C. Reiber, E. E. van der Wall, et al. Invasive Versus Noninvasive Evaluation of Coronary Artery Disease J. Am. Coll. Cardiol. Img., March 1, 2008; 1(2): 190 - 199. [Abstract] [Full Text] [PDF]

				S. Lamon-Fava, D. M. Herrington, D. M. Reboussin, M. Sherman, K. V. Horvath, L. A. Cupples, C. White, S. Demissie, E. J. Schaefer, and B. F. Asztalos Plasma Levels of HDL Subpopulations and Remnant Lipoproteins Predict the Extent of Angiographically-Defined Coronary Artery Disease in Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): 575 - 579. [Abstract] [Full Text] [PDF]

				L. O. Jensen, P. Thayssen, L. Thuesen, H. S. Hansen, J. F. Lassen, H. Kelbaek, A. Junker, K. N. Hansen, H. E. Boetker, L. R. Krusell, et al. Influence of a Pressure Gradient Distal to Implanted Bare-Metal Stent on In-Stent Restenosis After Percutaneous Coronary Intervention Circulation, December 11, 2007; 116(24): 2802 - 2808. [Abstract] [Full Text] [PDF]

				K. M. Marques, P. Knaapen, R. Boellaard, N. Westerhof, A. A. Lammertsma, C. A. Visser, and F. C. Visser Hyperaemic microvascular resistance is not increased in viable myocardium after chronic myocardial infarction Eur. Heart J., October 1, 2007; 28(19): 2320 - 2325. [Abstract] [Full Text] [PDF]

				D. Bose, C. von Birgelen, and R. Erbel Intravascular Ultrasound for the Evaluation of Therapies Targeting Coronary Atherosclerosis J. Am. Coll. Cardiol., March 6, 2007; 49(9): 925 - 932. [Abstract] [Full Text] [PDF]

				J. Tobis, B. Azarbal, and L. Slavin Assessment of Intermediate Severity Coronary Lesions in the Catheterization Laboratory J. Am. Coll. Cardiol., February 27, 2007; 49(8): 839 - 848. [Abstract] [Full Text] [PDF]

				M. J. Budoff, S. Achenbach, R. S. Blumenthal, J. J. Carr, J. G. Goldin, P. Greenland, A. D. Guerci, J. A.C. Lima, D. J. Rader, G. D. Rubin, et al. Assessment of Coronary Artery Disease by Cardiac Computed Tomography: A Scientific Statement From the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology Circulation, October 17, 2006; 114(16): 1761 - 1791. [Full Text] [PDF]

				S. J. Nicholls, E. M. Tuzcu, I. Sipahi, P. Schoenhagen, and S. E. Nissen Intravascular Ultrasound in Cardiovascular Medicine Circulation, July 25, 2006; 114(4): e55 - e59. [Full Text] [PDF]

				K. Nasu, E. Tsuchikane, O. Katoh, D. G. Vince, R. Virmani, J.-F. Surmely, A. Murata, Y. Takeda, T. Ito, M. Ehara, et al. Accuracy of In Vivo Coronary Plaque Morphology Assessment: A Validation Study of In Vivo Virtual Histology Compared With In Vitro Histopathology J. Am. Coll. Cardiol., June 20, 2006; 47(12): 2405 - 2412. [Abstract] [Full Text] [PDF]

				P. Schoenhagen, E. M. Tuzcu, C. Apperson-Hansen, C. Wang, K. Wolski, S. Lin, I. Sipahi, S. J. Nicholls, W. A. Magyar, A. Loyd, et al. Determinants of Arterial Wall Remodeling During Lipid-Lowering Therapy: Serial Intravascular Ultrasound Observations From the Reversal of Atherosclerosis With Aggressive Lipid Lowering Therapy (REVERSAL) Trial Circulation, June 20, 2006; 113(24): 2826 - 2834. [Abstract] [Full Text] [PDF]

				M. Suzuki, M. Saito, T. Nagai, H. Saeki, and Y. Kazatani Prevention of Positive Coronary Artery Remodeling with Statin Therapy in Patients with Coronary Artery Diseases Angiology, May 1, 2006; 57(3): 259 - 265. [Abstract] [PDF]

				S. J. Nicholls, E. M. Tuzcu, I. Sipahi, P. Schoenhagen, T. Crowe, S. Kapadia, and S. E. Nissen Relationship Between Atheroma Regression and Change in Lumen Size After Infusion of Apolipoprotein A-I Milano J. Am. Coll. Cardiol., March 7, 2006; 47(5): 992 - 997. [Abstract] [Full Text] [PDF]

				P. Jimenez-Quevedo, M. Sabate, D. Angiolillo, F. Alfonso, R. Hernandez-Antolin, C. Banuelos, E. Bernardo, C. Ramirez, R. Moreno, C. Fernandez, et al. LDL-cholesterol predicts negative coronary artery remodelling in diabetic patients: an intravascular ultrasound study Eur. Heart J., November 1, 2005; 26(21): 2307 - 2312. [Abstract] [Full Text] [PDF]

				A. Repetto, B. D. Bello, M. Pasotti, M. Agozzino, M. Vigano, C. Klersy, L. Tavazzi, and E. Arbustini Coronary atherosclerosis in end-stage idiopathic dilated cardiomyopathy: an innocent bystander? Eur. Heart J., August 1, 2005; 26(15): 1519 - 1527. [Abstract] [Full Text] [PDF]

				N. H J Pijls Optimum guidance of complex PCI by coronary pressure measurement Heart, September 1, 2004; 90(9): 1085 - 1093. [Full Text] [PDF]

				L. O. Jensen, P. Thayssen, K. E. Pedersen, S. Stender, and T. Haghfelt Regression of Coronary Atherosclerosis by Simvastatin: A Serial Intravascular Ultrasound Study Circulation, July 20, 2004; 110(3): 265 - 270. [Abstract] [Full Text] [PDF]

				S. A. J. Chamuleau, M. Siebes, M. Meuwissen, K. T. Koch, J. A. E. Spaan, and J. J. Piek Association between coronary lesion severity and distal microvascular resistance in patients with coronary artery disease Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2194 - H2200. [Abstract] [Full Text] [PDF]

				M.-K. Hong, G. S. Mintz, C. W. Lee, Y.-H. Kim, J.-W. Lee, J.-M. Song, K.-H. Han, D.-H. Kang, J.-K. Song, J.-J. Kim, et al. Intravascular ultrasound assessment of patterns of arterial remodeling in the absence of significant reference segment plaque burden in patients with coronary artery disease J. Am. Coll. Cardiol., September 3, 2003; 42(5): 806 - 810. [Abstract] [Full Text] [PDF]

				C.F Madler, N Payne, U Wilkenshoff, A Cohen, G.A Derumeaux, L.A Pierard, J Engvall, L-A Brodin, G.R Sutherland, A.G Fraser, et al. Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography: optimal diagnostic models using off-line tissue Doppler in the MYDISE study Eur. Heart J., September 1, 2003; 24(17): 1584 - 1594. [Abstract] [Full Text] [PDF]

				D V. Anand, D. Lipkin, and A. Lahiri Finding the age of the patient's heart BMJ, May 15, 2003; 326(7398): 1045 - 1046. [Full Text] [PDF]

				M. Haude, T. F.M. Konorza, U. Kalnins, A. Erglis, K. Saunamaki, H. D. Glogar, E. Grube, R. Gil, A. Serra, H. G. Richardt, et al. Heparin-Coated Stent Placement for the Treatment of Stenoses in Small Coronary Arteries of Symptomatic Patients Circulation, March 11, 2003; 107(9): 1265 - 1270. [Abstract] [Full Text] [PDF]

				A. DeFranco Understanding the pathophysiology of the arterial wall: which method should we choose? Intra-vascular ultrasound Eur. Heart J. Suppl., September 1, 2002; 4(suppl_F): F29 - F40. [Abstract] [PDF]

				J. Larsen, M. Brekke, L. Sandvik, H. Arnesen, K. F. Hanssen, and K. Dahl-Jorgensen Silent Coronary Atheromatosis in Type 1 Diabetic Patients and Its Relation to Long-Term Glycemic Control Diabetes, August 1, 2002; 51(8): 2637 - 2641. [Abstract] [Full Text] [PDF]

				P. Schoenhagen and S. Nissen Understanding coronary artery disease: tomographic imaging with intravascular ultrasound Heart, July 1, 2002; 88(1): 91 - 96. [Full Text] [PDF]

				M. Hosoi, T. Sato, K. Yamagami, T. Hasegawa, T. Yamakita, M. Miyamoto, K. Yoshioka, T. Yamamoto, T. Ishii, S. Tanaka, et al. Impact of Diabetes on Coronary Stenosis and Coronary Artery Calcification Detected by Electron-Beam Computed Tomography in Symptomatic Patients Diabetes Care, April 1, 2002; 25(4): 696 - 701. [Abstract] [Full Text] [PDF]

				D. L. Packer, C. L. Stevens, M. G. Curley, C. J. Bruce, F. A. Miller, B. K. Khandheria, J. K. Oh, L. J. Sinak, and J. B. Seward Intracardiac phased-array imaging: methods and initial clinical experience with high resolution, under blood visualization: Initial experience with intracardiac phased-array ultrasound J. Am. Coll. Cardiol., February 6, 2002; 39(3): 509 - 516. [Abstract] [Full Text] [PDF]

				M. Haude and R. Erbel How big is small? Eur. Heart J., February 1, 2002; 23(3): 198 - 199. [Full Text] [PDF]

				C. Briguori, J. Tobis, T. Nishida, M. Vaghetti, R. Albiero, C. Di Mario, and A. Colombo Discrepancy between angiography and intravascular ultrasound when analysing small coronary arteries Eur. Heart J., February 1, 2002; 23(3): 247 - 254. [Abstract] [Full Text] [PDF]

				B. Johansson, H. Olsson, and B. Wennerblom Angiography-Guided Routine Coronary Stent Implantation Results in Suboptimal Dilatation Angiology, January 1, 2002; 53(1): 69 - 75. [Abstract] [PDF]

				B. De Bruyne, F. Hersbach, N. H.J. Pijls, J. Bartunek, J.-W. Bech, G. R. Heyndrickx, K. L. Gould, and W. Wijns Abnormal Epicardial Coronary Resistance in Patients With Diffuse Atherosclerosis but "Normal" Coronary Angiography Circulation, November 13, 2001; 104(20): 2401 - 2406. [Abstract] [Full Text] [PDF]

				S. Doucet, M. J. Schalij, M. C.M. Vrolix, D. Hilton, P. Chenu, B. de Bruyne, W. Udayachalerm, A. Seth, L. Bilodeau, J. H.C. Reiber, et al. Stent Placement to Prevent Restenosis After Angioplasty in Small Coronary Arteries Circulation, October 23, 2001; 104(17): 2029 - 2033. [Abstract] [Full Text] [PDF]

				P. Schoenhagen, K. M. Ziada, D. G. Vince, S. E. Nissen, and E. M. Tuzcu Arterial remodeling and coronary artery disease: the concept of "dilated" versus "obstructive" coronary atherosclerosis J. Am. Coll. Cardiol., August 1, 2001; 38(2): 297 - 306. [Abstract] [Full Text] [PDF]

				M Ishihara, H Sato, T Kawagoe, Y Shimatani, S Kurisu, K Nishioka, Y Kouno, T Umemura, and S Nakamura Impact of diabetes mellitus on long term survival after acute myocardial infarction in patients with single vessel disease Heart, August 1, 2001; 86(2): 133 - 138. [Abstract] [Full Text] [PDF]

				S. A. J. Chamuleau, M. Meuwissen, B. L. F. van Eck-Smit, K. T. Koch, A. de Jong, R. J. de Winter, C. E. Schotborgh, M. Bax, H. J. Verberne, J. G. P. Tijssen, et al. Fractional flow reserve, absolute and relative coronary blood flow velocity reserve in relation to the results of technetium-99m sestambi single-photon emission computed tomography in patients with two-vessel coronary artery disease J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1316 - 1322. [Abstract] [Full Text] [PDF]

				G. S. Mintz, S. E. Nissen, W. D. Anderson, S. R. Bailey, R. Erbel, P. J. Fitzgerald, F. J. Pinto, K. Rosenfield, R. J. Siegel, E. M. Tuzcu, et al. American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (ivus): A report of the american college of cardiology task force on clinical expert consensus documents developed in collaboration with the european society of cardiology endorsed by the society of cardiac angiography and interventions J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1478 - 1492. [Full Text] [PDF]

				S. E. Nissen and P. Yock Intravascular Ultrasound : Novel Pathophysiological Insights and Current Clinical Applications Circulation, January 30, 2001; 103(4): 604 - 616. [Abstract] [Full Text] [PDF]

				M. Nakamura, H. Nishikawa, S. Mukai, M. Setsuda, K. Nakajima, H. Tamada, H. Suzuki, T. Ohnishi, Y. Kakuta, T. Nakano, et al. Impact of coronary artery remodeling on clinical presentation of coronary artery disease: an intravascular ultrasound study J. Am. Coll. Cardiol., January 1, 2001; 37(1): 63 - 69. [Abstract] [Full Text] [PDF]

				A. Endo, H. Hirayama, O. Yoshida, T. Arakawa, T. Akima, T. Yamada, and M. Nanasato Arterial remodeling influences the development of intimal hyperplasia after stent implantation J. Am. Coll. Cardiol., January 1, 2001; 37(1): 70 - 75. [Abstract] [Full Text] [PDF]

				N. H.J. Pijls, B. De Bruyne, G. J. W. Bech, F. Liistro, G. R. Heyndrickx, H. J.R.M. Bonnier, and J. J. Koolen Coronary Pressure Measurement to Assess the Hemodynamic Significance of Serial Stenoses Within One Coronary Artery : Validation in Humans Circulation, November 7, 2000; 102(19): 2371 - 2377. [Abstract] [Full Text] [PDF]

				A Jeremias, C Spies, N A Herity, E Pomerantsev, P G Yock, P J Fitzgerald, and A C Yeung Coronary artery compliance and adaptive vessel remodelling in patients with stable and unstable coronary artery disease Heart, September 1, 2000; 84(3): 314 - 319. [Abstract] [Full Text] [PDF]

				Y. Miyao, K. Kugiyama, H. Kawano, T. Motoyama, H. Ogawa, M. Yoshimura, T. Sakamoto, and H. Yasue Diffuse intimal thickening of coronary arteries in patients with coronary spastic angina J. Am. Coll. Cardiol., August 1, 2000; 36(2): 432 - 437. [Abstract] [Full Text] [PDF]

				D Waters Is a mechanical or a metabolic approach superior in the treatment of coronary disease? Results of the atorvastatin versus revascularization (AVERT) trial. Eur. Heart J., July 1, 2000; 21(13): 1029 - 1031. [PDF]

				K. L. Gould, Y. Nakagawa, K. Nakagawa, S. Sdringola, M. J. Hess, M. Haynie, N. Parker, N. Mullani, and R. Kirkeeide Frequency and Clinical Implications of Fluid Dynamically Significant Diffuse Coronary Artery Disease Manifest as Graded, Longitudinal, Base-to-Apex Myocardial Perfusion Abnormalities by Noninvasive Positron Emission Tomography Circulation, April 25, 2000; 101(16): 1931 - 1939. [Abstract] [Full Text] [PDF]

				M. J. Kern, S. Puri, R. G. Bach, T. J. Donohue, P. Dupouy, E. A. Caracciolo, W. R. Craig, F. Aguirre, E. Aptecar, T. L. Wolford, et al. Abnormal Coronary Flow Velocity Reserve After Coronary Artery Stenting in Patients : Role of Relative Coronary Reserve to Assess Potential Mechanisms Circulation, December 21, 1999; 100(25): 2491 - 2498. [Abstract] [Full Text] [PDF]

				R. A. M. van Liebergen, J. J. Piek, K. T. Koch, R. J. G. Peters, R. J. de Winter, C. E. Schotborgh, and K. I. Lie Hyperemic coronary flow after optimized intravascular ultrasound-guided balloon angioplasty and stent implantation J. Am. Coll. Cardiol., December 1, 1999; 34(7): 1899 - 1906. [Abstract] [Full Text] [PDF]

				L. Gruberg, G. S. Mintz, L. F. Satler, K. M. Kent, A. D. Pichard, and M. B. Leon Intravascular imaging and physiologic lesion assessment to define critical coronary stenoses Ann. Thorac. Surg., October 1, 1999; 68(4): 1547 - 1551. [Abstract] [Full Text] [PDF]

				Y. Kobayashi, J. De Gregorio, N. Kobayashi, T. Akiyama, B. Reimers, L. Finci, C. Di Mario, and A. Colombo Stented segment length as an independent predictor of restenosis J. Am. Coll. Cardiol., September 1, 1999; 34(3): 651 - 659. [Abstract] [Full Text] [PDF]

				A. S. Abizaid, G. S. Mintz, A. Abizaid, R. Mehran, A. J. Lansky, A. D. Pichard, L. F. Satler, H. Wu, K. M. Kent, and M. B. Leon One-year follow-up after intravascular ultrasound assessment of moderate left main coronary artery disease in patients with ambiguous angiograms J. Am. Coll. Cardiol., September 1, 1999; 34(3): 707 - 715. [Abstract] [Full Text] [PDF]

				A. J. Taylor, A. P. Burke, A. Farb, P. Yousefi, G. T. Malcom, J. Smialek, and R. Virmani Arterial remodeling in the left coronary system: The role of high-density lipoprotein cholesterol J. Am. Coll. Cardiol., September 1, 1999; 34(3): 760 - 767. [Abstract] [Full Text] [PDF]

				A. Takagi, Y. Tsurumi, Y. Ishii, K. Suzuki, M. Kawana, and H. Kasanuki Clinical Potential of Intravascular Ultrasound for Physiological Assessment of Coronary Stenosis : Relationship Between Quantitative Ultrasound Tomography and Pressure-Derived Fractional Flow Reserve Circulation, July 20, 1999; 100(3): 250 - 255. [Abstract] [Full Text] [PDF]

				A. S. Abizaid, G. S. Mintz, R. Mehran, A. Abizaid, A. J. Lansky, A. D. Pichard, L. F. Satler, H. Wu, C. Pappas, K. M. Kent, et al. Long-Term Follow-Up After Percutaneous Transluminal Coronary Angioplasty Was Not Performed Based on Intravascular Ultrasound Findings : Importance of Lumen Dimensions Circulation, July 20, 1999; 100(3): 256 - 261. [Abstract] [Full Text] [PDF]

				R. E. Kuntz Importance of Considering Atherosclerosis Progression When Choosing a Coronary Revascularization Strategy : The Diabetes–Percutaneous Transluminal Coronary Angioplasty Dilemma Circulation, February 23, 1999; 99(7): 847 - 851. [Full Text] [PDF]

				A. Oshima, D. Itchhaporia, and P. Fitzgerald New developments in intravascular ultrasound Vascular Medicine, November 1, 1998; 3(4): 281 - 290. [Abstract] [PDF]

				A. J. Lansky, G. S. Mintz, J. J. Popma, A. D. Pichard, K. M. Kent, L. F. Satler, D. S. Baim, R. E. Kuntz, C. Simonton, R. M. Bersin, et al. Remodeling after directional coronary atherectomy (with and without adjunct percutaneous transluminal coronary angioplasty): a serial angiographic and intravascular ultrasound analysis from the optimal atherectomy restenosis study J. Am. Coll. Cardiol., August 1, 1998; 32(2): 329 - 337. [Abstract] [Full Text] [PDF]

				M P Moore, T Spencer, D M Salter, P P Kearney, T R D Shaw, I R Starkey, P J Fitzgerald, R Erbel, A Lange, N W McDicken, et al. Characterisation of coronary atherosclerotic morphology by spectral analysis of radiofrequency signal: in vitro intravascular ultrasound study with histological and radiological validation Heart, May 1, 1998; 79(5): 459 - 467. [Abstract] [Full Text]

				E. R. Edelman Vessel Size, Antioxidants, and Restenosis : Never Too Small, Not Too Little, but Often Too Late Circulation, February 10, 1998; 97(5): 416 - 420. [Full Text] [PDF]

				I. Yokoyama, T. Ohtake, S.-i. Momomura, K. Yonekura, N. Kobayakawa, T. Aoyagi, S. Sugiura, Y. Sasaki, and M. Omata Altered Myocardial Vasodilatation in Patients With Hypertriglyceridemia in Anatomically Normal Coronary Arteries Arterioscler. Thromb. Vasc. Biol., February 1, 1998; 18(2): 294 - 299. [Abstract] [Full Text] [PDF]