CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Stephen J. Nicholls, MBBS, PhD, FACC*,
E. Murat Tuzcu, MD, FACC and
Steven E. Nissen, MD, FACC
* Department of Cardiovascular Medicine, Mail code JJ-65, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195 (Email: nichols1{at}ccf.org).
We read with interest the letter by Drs. von Birgelen and Hartmann with regard to our use of serial versus static assessments of atheroma burden using intravascular ultrasound (IVUS) (1
). Although static assessments do not adequately evaluate the dynamic process of arterial wall remodeling, the ability to apply a cross-sectional appraisal of a cohort of subjects provides a unique opportunity to investigate factors that correlate with the extent of atheroma throughout a coronary arterial segment. Serial assessments of atheroma burden have assumed a pivotal role in the elucidation of the factors, including pharmacological interventions, that influence the natural history of atherosclerosis. It is for this reason that the serial assessment of atheroma burden by IVUS has become a surrogate end point in clinical trials (2–7
).
The previous studies of the left main coronary artery cited by these investigators (8
) raise a number of important points with regard to the study of atherosclerosis. A major limitation of these studies includes their measurement of atheroma area at a single cross-sectional slice of the left main coronary artery in a small number of subjects (n = 60), which were deemed to have the smallest lumen area at baseline. As a result, these researchers used the single image that corresponded to the most severe angiographic stenosis in one specific segment of the coronary anatomy to make speculative assessments of atherosclerosis. Given that atherosclerosis is a systemic and not a focal process that would fit in a single ultrasound frame, in addition to the well-established discord between angiographic abnormalities and the extent of atheroma within the arterial wall, it is uncertain what conclusions can be made from investigating disease at one site.
The problem of using a single slice is further magnified in serial studies. Serial assessment of atheroma burden requires precise matching of that single slice, a task that is difficult to achieve in many cases. In contrast, our report describes the relationship between a broad range of clinical parameters and the volume of atheroma throughout a segment of coronary artery of at least 30 mm in length (1
). This was performed in a large cohort of subjects and includes sites that do not contain significant obstructive disease. Although one segment was studied in each subject, each epicardial coronary artery is reflected in the total cohort (i.e., this is not a study of disease limited to the left main segment). Further, the volumetric approach defines segments by the fixed anatomic presence of arterial side branches and provides a greater opportunity for precise matching and investigation of the factors that influence the natural history of atherosclerosis.
Studying atherosclerosis within the left main coronary artery, the investigators found no significant correlation between the level of low density lipoprotein (LDL) cholesterol and atheroma burden (8
), in support of our findings. Interestingly, they found a significant correlation between baseline LDL cholesterol and progression of atheroma at the region studied. The degree of correlation was much greater than what has been subsequently been reported for the relationship between the degree of change in LDL cholesterol and atheroma volume in patients treated with a statin (6
). Given that atherosclerosis is a complex pathological process that results from the influence of a large number of factors on the arterial wall and that there is a substantial overlap between levels of LDL cholesterol and incidence of cardiovascular disease, it would be surprising to expect anything greater than a mild correlation between these factors at most.
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Footnotes
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Please note: Neil Weissman, MD, acted as guest editor.
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References
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1. Nicholls SJ, Tuzcu EM, Crowe T, et al. Relationship between cardiovascular risk factors and atherosclerotic disease burden measured by intravascular ultrasound J Am Coll Cardiol 2006;47:1967-1975.[Abstract/Free Full Text]2. Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial JAMA 2006;295:1556-1565.[Abstract/Free Full Text] 3. Nissen SE, Tsunoda T, Tuzcu EM, et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial JAMA 2003;290:2292-2300.[Abstract/Free Full Text] 4. Nissen SE, Tuzcu EM, Brewer HB, et al. Effect of ACAT inhibition on the progression of coronary atherosclerosis N Engl J Med 2006;354:1253-1263.[Abstract/Free Full Text] 5. Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial JAMA 2004;292:2217-2225.[Abstract/Free Full Text] 6. Nissen SE, Tuzcu EM, Schoenhagen P, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial JAMA 2004;291:1071-1080.[Abstract/Free Full Text] 7. Tardif JC, Gregoire J, L’Allier PL, et al. Effects of the acyl coenzyme A:cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions Circulation 2004;110:3372-3377.[Abstract/Free Full Text] 8. von Birgelen C, Hartmann M, Mintz GS, Baumgart D, Schmermund A, Erbel R. Relation between progression and regression of atherosclerotic left main coronary artery disease and serum cholesterol levels as assessed with serial long-term ( 12 months) follow-up intravascular ultrasound Circulation 2003;108:2757-2762.[Abstract/Free Full Text]
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References