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ACUTE MYOCARDIAL ISCHEMIA/INFARCTION

Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease

Briain D. MacNeill, MB, MSC^*,, Ik-Kyung Jang, MD, PHD^*, Brett E. Bouma, PHD, Nicusor Iftimia, PHD, Masamichi Takano, MD, PHD^*,, Hiroshi Yabushita, MD, PHD^*,,||, Milen Shishkov, PHD, Christopher R. Kauffman, BS, Stuart L. Houser, MD^,, H.Thomas Aretz, MD, Denise DeJoseph, ACNP^*, Elkan F. Halpern, PHD and Guillermo J. Tearney, MD, PHD^,,*

^* Cardiology Division
Wellman Center for Photomedicine
Department of Pathology
Department of Radiology, Harvard Medical School, Boston, MassachusettsUSA
^|| Department of Cardiology, Kinki University School of Medicine, Kinki, Japan

Manuscript received October 23, 2003; accepted May 31, 2004.

^* Reprint requests and correspondence: Dr. Guillermo J. Tearney, Wellman Center for Photomedicine, Massachusetts General Hospital, BAR 703, Boston, Massachusetts 02114 (Email: gtearney{at}partners.org).

OBJECTIVES: This study was designed to utilize optical coherence tomography (OCT) images of coronary atherosclerotic plaque macrophages to investigate the relationship between macrophage distributions and clinical syndrome.

BACKGROUND: The relative significance of focal macrophage infiltration and generalized coronary inflammation for predicting acute coronary events is a currently a source of considerable controversy in cardiology. Lack of a high-resolution cross-sectional imaging modality has limited macrophage evaluation in vivo.

METHODS: Intracoronary OCT imaging was performed at culprit and non-culprit plaques in patients presenting with stable angina pectoris, unstable angina pectoris,and ST-segment elevation myocardial infarction. Macrophage densities were quantified from these images and analyzed with respect to the clinical presentations of the patients under investigation.

RESULTS: A significantly greater macrophage density was found in unstable patients, both for fibrous and lipid-rich plaques (p = 0.025 and p = 0.002, respectively). Within each patient, the macrophage densities at culprit and non-culprit lesions correlated significantly (r = 0.66, y = 0.88x + 0.43, p = 0.01). Sites of plaque rupture demonstrated a greater macrophage density than non-ruptured sites (6.95 ± 1.60%, 5.29 ± 1.17%; p = 0.002). Surface macrophage infiltration was a stronger predictor of unstable clinical presentation than subsurface infiltration for culprit lesions (p = 0.035) but not for remote lesions (p = 0.80).

CONCLUSIONS: Our results demonstrate that increases in both multi-focal and focal macrophage densities are highly correlated with symptom severity. By providing a means of detecting increases in plaque macrophage content before an acute event, this technique may aid in determining prognosis and guiding preventive therapy.

Abbreviations and Acronyms   ACS = acute coronary syndrome   AUC = area under the curve   NSD = normalized standard deviation   OCT = optical coherence tomography   ROC = receiver operator characteristic   SAP = stable angina pectoris   STEMI = ST-segment elevation myocardial infarction

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