Correspondence

Multiple Complex Coronary Plaques in Patients with Acute Myocardial Infarction

N Engl J Med 2001; 344:527-528February 15, 2001

Article

To the Editor:

In their report on multiple complex coronary plaques in patients with acute transmural myocardial infarction, Goldstein et al. (Sept. 28 issue)1 conclude that the subgroup of patients with angiographic evidence of multiple complex coronary plaques is at increased risk for adverse clinical outcomes. Although the authors assert that “angiography has a limited ability to delineate the severity and complexity of coronary disease,” they have stretched the numerical interpretation of their findings beyond the limits of angiography.

In their study, Goldstein et al. considered lesions to be complex if they were associated with angiographic evidence of at least 50 percent stenosis. Intravascular ultrasound studies and postmortem observations have shown that expansive remodeling of large and complex plaques frequently leads to stenosis of less than 50 percent.2,3 In an angiographic study, Ambrose et al.4 reported that myocardial infarction originated from culprit lesions that were severely stenotic (more than 70 percent stenosis) in only 22 percent of patients. In a recent postmortem study,5 we observed an association between histopathological determinants of plaque instability and expansive remodeling. In our study, the area of the lumen was not associated with histologic determinants of plaque instability. Thus, the data reported by Goldstein et al. represent a subgroup of atherosclerotic lesions selected according to angiographic criteria that are likely to miss a substantial fraction of unstable plaques.

Goldstein et al. restricted their analysis to angiographically complex lesions. It is conceivable that, irrespective of the complexity of the lesions, multiple angiographically significant lesions in general are associated with an increased risk of adverse events. The authors did not report on the outcome for patients with one or more noncomplex lesions. Therefore, their conclusion may not be limited to angiographically complex lesions.

Gerard Pasterkamp, M.D., Ph.D.
Aryan Vink, M.D.
Cornelius Borst, M.D., Ph.D.
University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands

5 References

1
Goldstein JA, Demetriou D, Grines CL, Pica M, Shoukfeh M, O'Neill WW. Multiple complex coronary plaques in patients with acute myocardial infarction. N Engl J Med 2000;343:915-922
Full Text | Web of Science | Medline

2
Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987;316:1371-1375
Full Text | Web of Science | Medline

3
Hermiller JB, Tenaglia AN, Kisslo KB, et al. In vivo validation of compensatory enlargement of atherosclerotic coronary arteries. Am J Cardiol 1993;71:665-668
CrossRef | Web of Science | Medline

4
Ambrose JA, Tannenbaum MA, Alexopoulos D, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol 1988;12:56-62
CrossRef | Web of Science | Medline

5
Pasterkamp G, Schoneveld AH, van der Wal AC, et al. Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox. J Am Coll Cardiol 1998;32:655-662
CrossRef | Web of Science | Medline

To the Editor:

Goldstein and coworkers highlight the prognostic importance of the presence of multiple complex coronary plaques with regard to subsequent clinical events, such as repeated coronary angioplasty and bypass grafting, in patients with acute myocardial infarction. The authors discuss intraplaque lipid components or systemic lipid disorders, as well as systemic inflammatory processes, as possible contributors to the “generalized” plaque instability observed in this group of patients. However, they provide no information on previous therapy with statins in patients who already had clinical manifestations of coronary artery disease or on the initiation of statin therapy on the occasion of the myocardial infarction.

Statins have been shown to be effective for the secondary prevention of coronary artery disease in subjects with elevated low-density lipoprotein (LDL) cholesterol levels,1 as well as in those with nearly normal levels,2 reducing cardiovascular risk by about 30 percent. The rapid reduction in risk achieved with statins in patients with coronary artery disease indicates that these drugs may act by increasing plaque stability rather than through effects on atherogenesis itself. Statins may influence plaque stability through lipid-lowering effects as well as through non–lipid-related, probably antiinflammatory, effects.3 To exclude the possibility of treatment-related bias in this study, it is therefore important to consider LDL cholesterol levels, as well as the proportion of patients who had already been treated with a statin and the proportion with newly initiated statin therapy. In the absence of such additional information, the increased risk of adverse outcomes among patients with multiple complex coronary plaques, as reported by the authors, may be significantly overestimated or underestimated.

Thomas C. Wascher, M.D.
Antonella deCampo, M.D.
Isabella Schmoelzer, M.D.
Karl-Franzens University of Graz, A-8036 Graz, Austria

3 References

1
Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-1389
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2
Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001-1009
Full Text | Web of Science | Medline

3
Koh KK. Effects of statins on vascular wall: vasomotor function, inflammation, and plaque stability. Cardiovasc Res 2000;47:648-657
CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Pasterkamp et al. point out that angiography has limitations in delineating plaques that may be biologically unstable but not sufficiently severe to have angiographic features of complexity and that such lesions may progress to clinical instability. We agree that the absence of angiographic evidence of complexity does not preclude the possibility that a less stenotic, noncomplex lesion will progress and cause adverse events, and our observations cannot be construed to mean that angiographically less complex plaques are necessarily benign. In our report, we emphasized the limitations of angiography in delineating the precise architecture and biologic behavior of any given lesion, whether angiographically complex or not. Nevertheless, observations from our study and others1-4 consistently demonstrate that complex plaques have a strong predilection to angiographic progression associated with adverse clinical events.

Wascher et al. emphasize the important relation of LDL cholesterol levels and statin therapy to the outcome of acute coronary syndromes. We used a retrospective analysis of a data base that included total cholesterol levels but did not include detailed data on the responses of cholesterol fractions (LDL and high-density lipoprotein) over time to therapy with cholesterol-lowering medications. Therefore, we cannot with certainty exclude the remote possibility that in our study the strong association between multiple complex plaques and clinical adverse events was influenced by LDL cholesterol levels and statin therapy.

James A. Goldstein, M.D.
Cindy Grines, M.D.
William W. O'Neill, M.D.
William Beaumont Hospital, Royal Oak, MI 48073-6769

4 References

1
Moise A, Theroux P, Taeymans Y, et al. Unstable angina and progression of coronary atherosclerosis. N Engl J Med 1983;309:685-689
Full Text | Web of Science | Medline

2
Chester MR, Chen L, Kaski JC. The natural history of unheralded complex coronary plaques. J Am Coll Cardiol 1996;28:604-608
CrossRef | Web of Science | Medline

3
Chen L, Chester MR, Crook R, Kaski JC. Differential progression of complex culprit stenoses in patients with stable and unstable angina pectoris. J Am Coll Cardiol 1996;28:597-603
CrossRef | Web of Science | Medline

4
Kaski JC, Chester MR, Chen L, Katritsis D. Rapid angiographic progression of coronary artery disease in patients with angina pectoris: the role of complex stenosis morphology. Circulation 1995;92:2058-2065
Web of Science | Medline

Citing Articles (1)

Citing Articles

1
Di Mario Carlo, Sansa Mara, Airoldi Flavio, Sheiban Imad, Manari Antonio, Petronio Anna, Piccaluga Emanuela, De Servi Stefano, Ramondo Angelo, Colusso Stefania, Formosa Anna, Cernigliaro Carmelo, Colombo Antonio, Nicoletta Monzini, Maria Antonietta Bonardi. (2004) Single vs multivessel treatment during primary angioplasty: results of the multicentre randomised HEpacoat™ for cuLPrit or multivessel stenting for Acute Myocardial Infarction (HELP AMI) Study. Acute Cardiac Care 6:3-4, 128-133
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