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Relationship between smaller calcifications and lipid-rich plaques on integrated backscatter-intravascular ultrasound
Letters to the Editor
347
Relationship between smaller calcifications and lipid-rich plaques on integrated backscatter-intravascular ultrasound Shinji Inaba a, Hideki Okayama a,⁎, Jun-ichi Funada b, Hidetoshi Hashida b, Go Hiasa c, Takumi Sumimoto c, Yasunori Takata d, Kazuhisa Nishimura a, Katsuji Inoue a, Akiyoshi Ogimoto a, Tomoaki Ohtsuka a, Jitsuo Higaki a a
Division of Cardiology, Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan Department of Cardiology, Ehime National Hospital, Toon, Ehime, Japan c Department of Cardiology, Kitaishikai Hospital, Ozu, Ehime, Japan d Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan b
a r t i c l e
i n f o
Article history: Received 30 November 2009 Accepted 4 December 2009 Available online 29 December 2009 Keywords: Coronary artery disease Spotty calcification Acute coronary syndrome Vulnerable plaque
Spotty calcification has been observed frequently in acute coronary syndromes [1]. However, there are no reports evaluating the relationship between coronary plaque characteristics and the calcification pattern. Integrated backscatter-IVUS (IB-IVUS) enables qualitative analysis of coronary plaques [2]. Accordingly, we investigated the association between plaque characteristics on IB-IVUS and calcification morphology, focusing specifically on a spotty pattern of calcification. Seventy-two culprit coronary plaques (72 patients; mean age 67 ± 8, male 52: unstable angina pectoris 49, stable angina pectoris 23) with spotty calcification were evaluated. The study was approved by the ethics committee at our hospital, and informed consent was obtained from all patients before participation in the study. IB values for each histological category were determined by previous IB-IVUS studies [2]. A 10-mm length of the culprit lesion was measured using 11 serial cross-sectional IB-IVUS images at the center of the slice with the minimum luminal cross-sectional area (CSA). In the conventional IVUS analyses, external elastic membrane (EEM) CSA was measured at each minimum luminal site. The eccentricity score was calculated as the ratio of (maximum–minimum thickness) to maximum thickness measured at the minimum luminal site. The remodeling index was defined as the ratio of the EEM CSA at the minimum luminal site to the mean EEM CSA of the reference segments. Positive remodeling was defined as a remodeling index N1.05. In the IB-IVUS analysis, the percentage of lipid volume (% LV) was calculated from 11 slices: % LV = (∑ lipid area / ∑ plaque CSA) × 100. Spotty calcification was defined as a lesion containing only small calcium deposits within an arc of less than 90° for all calcium deposits as reported previously [1]. The averaged arc, the average degree of all the spotty calcifications in one culprit lesion, was defined as follows:
⁎ Corresponding author. Division of Cardiology, Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. Tel.: + 81 89 960 5302; fax: + 81 89 960 5306. E-mail address: [email protected] (H. Okayama).
∑ arc / number of calcifications. Statistical analysis was carried out using SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, USA). A value of p b 0.05 was considered to indicate statistical significance. The averaged arc negatively correlated with EEM CSA and remodeling index on gray scale IVUS imaging (r2 = 0.31, p b 0.001; r2 = 0.11, p = 0.004, respectively). Moreover, the averaged arc negatively correlated with % LV (r2 = 0.39, p b 0.001) (Fig. 1). % LV positively correlated with the number of spotty calcifications (r2 = 0.24, p b 0.001), but not with the sum of arcs. A representative case is demonstrated in Fig. 2. Multivariate analysis after adjustment for confounding covariates (age, gender, body mass index, UAP, averaged arc, EEM CSA and positive remodeling) showed that EEM CSA (r = 0.39, p b 0.001), UAP (r = 0.29, p b 0.001), averaged arc (r = −0.29, p = 0.002) and positive remodeling (r = 0.17, p = 0.035) were independent predictors of % LV (R2 = 0.65, p b 0.001). The major findings of this study were: (1) coronary plaques with a smaller arc and a larger number of spotty calcifications were associated with lipid-rich characteristics on IB-IVUS; and (2) coronary plaques characterized by these features were an independent predictor of lipid-rich characteristics on IB-IVUS, in parallel with vulnerable plaque (large EEM, UAP, and positive remodeling), a finding which has been reported previously using conventional IVUS. Typical histological features of vulnerable plaque include a lipid-rich component with positive remodeling and thinner fibrous cap. In our study, multivariate analysis revealed plaques with increased lipid content were characterized by larger EEM, positive remodeling and the presence of UAP. In addition, a lower averaged arc was associated with a larger lipid component. A recent experimental study has highlighted the fact that inflammatory cells are associated with macrophage burden followed by formation of microscopic calcifications,
Fig. 1. Relationship between the % LV and averaged arc.
348
Letters to the Editor
Fig. 2. A representative case with UAP showing left coronary angiography (A), conventional IVUS (B) and IB-IVUS (C). On conventional IVUS, the plaque contained calcifications with a smaller arc (white arrows), and had a large EEM CSA and positive remodeling. On IB-IVUS, the plaque had lipid-rich characteristics.
which are involved in plaque instability [3]. Our observations imply a possible link between smaller calcifications and plaque instability. This study has several limitations. First, a thrombus could not be detected by either conventional IVUS or IB-IVUS. We therefore performed the IVUS studies after careful thrombectomy in patients with UAP. Second, thin cap fibroatheroma, which is considered to be vulnerable plaque, cannot be detected correctly by IB-IVUS. To clarify the relationship between smaller calcification pattern and plaque vulnerability, other modalities (i.e., optical coherence tomography) or longitudinal observations are needed. In conclusion, our results suggest that among plaques with spotty calcification, plaques characterized by a larger calcification number and smaller arc calcium deposits are the most lipid-rich plaques. Taken together, our results provide new insights into understanding the relationship between smaller spotty calcifications and plaque instability in human culprit coronary artery plaques. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [4].
0167-5273/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2009.12.011
References [1] Ehara S, Kobayashi Y, Yoshiyama M, et al. Spotty calcification typifies the culprit plaque in patients with acute myocardial infarction: an intravascular ultrasound study. Circulation 2004;110:3424–9. [2] Kawasaki M, Sano K, Okubo M, et al. Volumetric quantitative analysis of tissue characteristics of coronary plaques after statin therapy using three-dimensional integrated backscatter intravascular ultrasound. J Am Coll Cardiol 2005;45:1946–53. [3] Aikawa E, Nahrendorf M, Figueiredo JL, et al. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation 2007;116:2841–50. [4] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.
347
Relationship between smaller calcifications and lipid-rich plaques on integrated backscatter-intravascular ultrasound Shinji Inaba a, Hideki Okayama a,⁎, Jun-ichi Funada b, Hidetoshi Hashida b, Go Hiasa c, Takumi Sumimoto c, Yasunori Takata d, Kazuhisa Nishimura a, Katsuji Inoue a, Akiyoshi Ogimoto a, Tomoaki Ohtsuka a, Jitsuo Higaki a a
Division of Cardiology, Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan Department of Cardiology, Ehime National Hospital, Toon, Ehime, Japan c Department of Cardiology, Kitaishikai Hospital, Ozu, Ehime, Japan d Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan b
a r t i c l e
i n f o
Article history: Received 30 November 2009 Accepted 4 December 2009 Available online 29 December 2009 Keywords: Coronary artery disease Spotty calcification Acute coronary syndrome Vulnerable plaque
Spotty calcification has been observed frequently in acute coronary syndromes [1]. However, there are no reports evaluating the relationship between coronary plaque characteristics and the calcification pattern. Integrated backscatter-IVUS (IB-IVUS) enables qualitative analysis of coronary plaques [2]. Accordingly, we investigated the association between plaque characteristics on IB-IVUS and calcification morphology, focusing specifically on a spotty pattern of calcification. Seventy-two culprit coronary plaques (72 patients; mean age 67 ± 8, male 52: unstable angina pectoris 49, stable angina pectoris 23) with spotty calcification were evaluated. The study was approved by the ethics committee at our hospital, and informed consent was obtained from all patients before participation in the study. IB values for each histological category were determined by previous IB-IVUS studies [2]. A 10-mm length of the culprit lesion was measured using 11 serial cross-sectional IB-IVUS images at the center of the slice with the minimum luminal cross-sectional area (CSA). In the conventional IVUS analyses, external elastic membrane (EEM) CSA was measured at each minimum luminal site. The eccentricity score was calculated as the ratio of (maximum–minimum thickness) to maximum thickness measured at the minimum luminal site. The remodeling index was defined as the ratio of the EEM CSA at the minimum luminal site to the mean EEM CSA of the reference segments. Positive remodeling was defined as a remodeling index N1.05. In the IB-IVUS analysis, the percentage of lipid volume (% LV) was calculated from 11 slices: % LV = (∑ lipid area / ∑ plaque CSA) × 100. Spotty calcification was defined as a lesion containing only small calcium deposits within an arc of less than 90° for all calcium deposits as reported previously [1]. The averaged arc, the average degree of all the spotty calcifications in one culprit lesion, was defined as follows:
⁎ Corresponding author. Division of Cardiology, Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. Tel.: + 81 89 960 5302; fax: + 81 89 960 5306. E-mail address: [email protected] (H. Okayama).
∑ arc / number of calcifications. Statistical analysis was carried out using SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, USA). A value of p b 0.05 was considered to indicate statistical significance. The averaged arc negatively correlated with EEM CSA and remodeling index on gray scale IVUS imaging (r2 = 0.31, p b 0.001; r2 = 0.11, p = 0.004, respectively). Moreover, the averaged arc negatively correlated with % LV (r2 = 0.39, p b 0.001) (Fig. 1). % LV positively correlated with the number of spotty calcifications (r2 = 0.24, p b 0.001), but not with the sum of arcs. A representative case is demonstrated in Fig. 2. Multivariate analysis after adjustment for confounding covariates (age, gender, body mass index, UAP, averaged arc, EEM CSA and positive remodeling) showed that EEM CSA (r = 0.39, p b 0.001), UAP (r = 0.29, p b 0.001), averaged arc (r = −0.29, p = 0.002) and positive remodeling (r = 0.17, p = 0.035) were independent predictors of % LV (R2 = 0.65, p b 0.001). The major findings of this study were: (1) coronary plaques with a smaller arc and a larger number of spotty calcifications were associated with lipid-rich characteristics on IB-IVUS; and (2) coronary plaques characterized by these features were an independent predictor of lipid-rich characteristics on IB-IVUS, in parallel with vulnerable plaque (large EEM, UAP, and positive remodeling), a finding which has been reported previously using conventional IVUS. Typical histological features of vulnerable plaque include a lipid-rich component with positive remodeling and thinner fibrous cap. In our study, multivariate analysis revealed plaques with increased lipid content were characterized by larger EEM, positive remodeling and the presence of UAP. In addition, a lower averaged arc was associated with a larger lipid component. A recent experimental study has highlighted the fact that inflammatory cells are associated with macrophage burden followed by formation of microscopic calcifications,
Fig. 1. Relationship between the % LV and averaged arc.
348
Letters to the Editor
Fig. 2. A representative case with UAP showing left coronary angiography (A), conventional IVUS (B) and IB-IVUS (C). On conventional IVUS, the plaque contained calcifications with a smaller arc (white arrows), and had a large EEM CSA and positive remodeling. On IB-IVUS, the plaque had lipid-rich characteristics.
which are involved in plaque instability [3]. Our observations imply a possible link between smaller calcifications and plaque instability. This study has several limitations. First, a thrombus could not be detected by either conventional IVUS or IB-IVUS. We therefore performed the IVUS studies after careful thrombectomy in patients with UAP. Second, thin cap fibroatheroma, which is considered to be vulnerable plaque, cannot be detected correctly by IB-IVUS. To clarify the relationship between smaller calcification pattern and plaque vulnerability, other modalities (i.e., optical coherence tomography) or longitudinal observations are needed. In conclusion, our results suggest that among plaques with spotty calcification, plaques characterized by a larger calcification number and smaller arc calcium deposits are the most lipid-rich plaques. Taken together, our results provide new insights into understanding the relationship between smaller spotty calcifications and plaque instability in human culprit coronary artery plaques. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [4].
0167-5273/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2009.12.011
References [1] Ehara S, Kobayashi Y, Yoshiyama M, et al. Spotty calcification typifies the culprit plaque in patients with acute myocardial infarction: an intravascular ultrasound study. Circulation 2004;110:3424–9. [2] Kawasaki M, Sano K, Okubo M, et al. Volumetric quantitative analysis of tissue characteristics of coronary plaques after statin therapy using three-dimensional integrated backscatter intravascular ultrasound. J Am Coll Cardiol 2005;45:1946–53. [3] Aikawa E, Nahrendorf M, Figueiredo JL, et al. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation 2007;116:2841–50. [4] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.