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• W2088652309 abstract "Integrated backscatter intravascular ultrasound (IB-IVUS) capable of assessing plaque properties has recently become clinically applicable. We observed short-term atorvastatin-induced changes in coronary arterial plaque properties using IB-IVUS. The patient was a 57-year-old man who underwent coronary angiography when admitted to our hospital for cerebrovascular surgery, and lesions were observed in 2 branches: 99% and 90% stenoses in the proximal anterior descending branch (LAD) and middle region of the circumflex, respectively. Stenting was performed for the LAD on November 4, 2009 and for the circumflex on December 9. Oral atorvastatin administration at 10 mg/day was initiated on November 5 because the LDL-cholesterol level was high (160 mg/dl). A region about 5 mm in length proximal to the stent placed in the LAD was analyzed using IB-IVUS. Atorvastatin lowered the LDL cholesterol level from 160 to 79 mg/dl. On IB image analysis, although the period was as short as about 1 month, a marked decrease in the fatty component (44% → 26%) and an increase in the fibrous component (53% → 66%) were observed in the plaque. It was suggested that atorvastatin changes the tissue properties of coronary arterial plaques from a very early phase. It might be associated with the stabilization of coronary plaque. Integrated backscatter intravascular ultrasound (IB-IVUS) capable of assessing plaque properties has recently become clinically applicable. We observed short-term atorvastatin-induced changes in coronary arterial plaque properties using IB-IVUS. The patient was a 57-year-old man who underwent coronary angiography when admitted to our hospital for cerebrovascular surgery, and lesions were observed in 2 branches: 99% and 90% stenoses in the proximal anterior descending branch (LAD) and middle region of the circumflex, respectively. Stenting was performed for the LAD on November 4, 2009 and for the circumflex on December 9. Oral atorvastatin administration at 10 mg/day was initiated on November 5 because the LDL-cholesterol level was high (160 mg/dl). A region about 5 mm in length proximal to the stent placed in the LAD was analyzed using IB-IVUS. Atorvastatin lowered the LDL cholesterol level from 160 to 79 mg/dl. On IB image analysis, although the period was as short as about 1 month, a marked decrease in the fatty component (44% → 26%) and an increase in the fibrous component (53% → 66%) were observed in the plaque. It was suggested that atorvastatin changes the tissue properties of coronary arterial plaques from a very early phase. It might be associated with the stabilization of coronary plaque. As clinical outcomes of cholesterol-lowering therapy in Japanese have recently been accumulated, the importance of the vascular plaque-stabilizing as well as lipid level-lowering effects of statins has been attracting attention. Intravascular ultrasound (IVUS) is available for evaluating plaques in the coronary artery, but accurate qualitative evaluation of plaques in conventional gray-scale images has been difficult. Integrated backscatter (IB)-IVUS has recently become clinically applicable, in which the plaque properties can be diagnosed into 4 types by combining spectral parameters of posterior scattering signals of IVUS: lipid pool, dense fibrosis, fibrosis, or calcification. In this study, we observed short-term atorvastatin-induced changes in the properties of coronary arterial plaques using IB-IVUS in a patient. In September 2009, a 57-year-old man who was a past smoker with a history of borderline diabetes, hyperlipidemia, and hypertension was admitted to the neurosurgery department of our hospital for close examination and treatment for severe stenosis in the left middle cerebral artery. Since there were many risk factors, the patient was referred to our department and coronary angiography was performed. Lesions were observed in 2 branches: 99% and 90% stenoses in the proximal anterior descending branch (LAD) and middle region of the circumflex, respectively. On November 4, 2009, a DRIVER stent (3.0 mm × 20 mm, Medtronic Vascular Inc., Santa Rosa, CA, USA) was placed for the lesion in the LAD, and plaque of about 5 mm in length was evaluated at a site 5 mm from the proximal end of the placed stent using IB-IVUS. For IVUS, Atlantis (40 MHz) (Boston Scientific Corporation/Cardiovascular System Inc., San Jose, CA, USA) was used. Data were collected at a 0.5-mm/s auto pullback and analyzed using IVUS console (Galaxy, Boston Scientific Corporation/Cardiovascular System Inc.). Since hyperlipidemia was detected on blood testing on admission [low-density lipoprotein cholesterol (LDL-C), 160 mg/dl; triglyceride (TG), 98 mg/dl; high-density lipoprotein cholesterol (HDL-C), 41 mg/dl], oral atorvastatin administration was initiated at 10 mg/day on the day following surgery (Fig. 1). The patient was readmitted in December 2009 for coronary intervention for the lesion in the circumflex. On blood testing, LDL-C, TG, and HDL-C were lowered to 79 mg/dl, 82 mg/dl, and 36 mg/dl, respectively (Table 1). The lesion proximal to the stent placed in the LAD was re-evaluated using IB-IVUS before stenting. The components in the central, middle, and peripheral regions assumed to be the same lesion based on the distance from the stent end were also evaluated, and a marked reduction of the blue area and an increase in the green area were visually observed (Fig. 2). The percent volume of each plaque component in the analytical region was also investigated. The percent volumes of the fatty (lipid pool) and fibrous (fibrosis) components changed from 44% to 26% and from 53% to 66% (Table 2), respectively, showing stabilization of the plaque. The total plaque volume was slightly decreased from 33.8 mm3 to 32.5 mm3 (Table 2).Table 1Changes in laboratory profiles.Baseline (4th November)Follow-up (9th December)HDL cholesterol (mg/dl)4136LDL cholesterol (mg/dl)16079Triglycerides (mg/dl)9882C-reactive protein (mg/dl)0.250.18Hemoglobin A1c (%)5.45.5HDL, high-density lipoprotein; LDL, low-density lipoprotein. Open table in a new tab Figure 2Typical changes in IB images. (A) Distal area at 5.5 mm from the proximal end of the stent. (B) Mid area at 7.0 mm from the proximal end of the stent. (C) Proximal area at 9.0 mm from the proximal end of the stent. IB, integrated backscatter.View Large Image Figure ViewerDownload (PPT)Table 2Changes in lesion characteristics and IB parameters.Baseline (4th November)Follow-up (9th December)Plaque volume (mm3)33.832.5Mean vessel area (mm2)14.3 ± 1.313.4 ± 1.0Mean lumen area (mm2)7.5 ± 1.56.9 ± 1.1Fibrosis volume (mm3)18 (53%)22 (66%)Lipid pool volume (mm3)15 (44%)8 (26%)Dense fibrosis volume (mm3)0.7 (2.6%)2.2 (6.7%)Calcification volume (mm3)0.1 (0.4%)0.4 (1.3%)Mean area: mean value ± standard deviation. IB, integrated backscatter. Open table in a new tab HDL, high-density lipoprotein; LDL, low-density lipoprotein. Mean area: mean value ± standard deviation. IB, integrated backscatter. Statins comprise a group of drugs lowering the blood cholesterol level by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity. Since the first statin was discovered by Japanese researchers in 1973, various types of statin have been developed and used as therapeutic drugs for hypercholesterolemia worldwide. It has been proposed that the reduction of coronary events by active lipid-lowering treatment using drugs, such as statins, is due to the qualitative or functional improvement of plaques [[1]Libby P. Molecular bases of the acute coronary syndromes.Circulation. 1995; 91: 2844-2850Crossref PubMed Scopus (1814) Google Scholar]. In the Reversal of Atherosclerosis with Lipitor (REVERSAL) study reported in 2004, the LDL-C level was moderately reduced by pravastatin or aggressively reduced by atorvastatin, and changes in the plaque volume on IVUS after 6 months were compared between the 2 groups. The LDL-C level was reduced by 25.2% from 150 to 110 mg/dl on average in the pravastatin group and by 46.3% from 150 to 79 mg/dl on average in the atorvastatin group. The plaque volume increased by 2.7% in the pravastatin group, but decreased by 0.4% in the atorvastatin group. These findings suggested that an increase in the plaque mass can be inhibited by lowering the LDL-C level to about 80 mg/dl [[2]Nissen S.E. Tuzcu E.M. Schoenhagen P. Brown B.G. Ganz P. Vogel R.A. Crowe T. Howard G. Cooper C.J. Brodie B. Grines C.L. DeMaria A.N. REVERSAL InvestigatorsEffect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial.JAMA. 2004; 29: 1071-1080Crossref Scopus (2077) Google Scholar]. The GAIN Study reported that the composition of plaques may change based on an increase in the echo brightness of plaques on IVUS, showing that statins may stabilize unstable plaques [[3]Schartl M. Bocksch W. Koschyk D.H. Voelker W. Karsch K.R. Kreuzer J. Hausmann D. Beckmann S. Gross M. Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease.Circulation. 2001; 104: 387-392Crossref PubMed Scopus (335) Google Scholar]. The stabilization of plaque was also observed in the IB-IVUS image in this patient, suggesting that the pleiotropic effect of statins centering on the anti-inflammatory effect plays an important role. IB-IVUS has recently become clinically applicable, in which plaque properties can be diagnosed by combining spectral parameters of posterior scattering signals of IVUS [[4]Kawasaki M. Radiofrequency signal analysis, IB-IVUS.Heart View. 2006; 10 (in Japanese): 68-73Google Scholar]. Kawasaki et al. divided 52 stable angina pectoris patients with hyperlipidemia into 3 groups: atorvastatin (20 mg/day) and pravastatin (20 mg/day) treatment groups, and a control group (dietary therapy), and the plaque properties were evaluated using IB-IVUS during percutaneous coronary arterioplasty and after 6 months. It was demonstrated within a short 6-month period that lipid-lowering therapy stabilized plaques by reducing the fatty component and increasing the fibrous component in fatty component-rich plaques [[5]Kawasaki M. Sano K. Okubo M. Yokoyama H. Ito Y. Murata I. Tsuchiya K. Minatoguchi S. Zhou X. Fujita H. Fujiwara H. 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: 1946-1953Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar]. Large-scale clinical studies reported that plaques shrank after statin administration for 6 months to 3 years [2Nissen S.E. Tuzcu E.M. Schoenhagen P. Brown B.G. Ganz P. Vogel R.A. Crowe T. Howard G. Cooper C.J. Brodie B. Grines C.L. DeMaria A.N. REVERSAL InvestigatorsEffect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial.JAMA. 2004; 29: 1071-1080Crossref Scopus (2077) Google Scholar, 3Schartl M. Bocksch W. Koschyk D.H. Voelker W. Karsch K.R. Kreuzer J. Hausmann D. Beckmann S. Gross M. Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease.Circulation. 2001; 104: 387-392Crossref PubMed Scopus (335) Google Scholar, 6Takagi T. Yoshida K. Akasaka T. Hozumi T. Morioka S. Yoshikawa J. Intravascular ultrasound analysis of reduction in progression of coronary narrowing by treatment with pravastatin.Am J Cardiol. 1997; 79: 1673-1676Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar, 7Jensen L.O. Thayssen P. Pedersen K.E. Stender S. Haghfelt T. Regression of coronary atherosclerosis by simvastatin.Circulation. 2004; 110: 265-270Crossref PubMed Scopus (174) Google Scholar, 8Okazaki S. Yokoyama T. Miyauchi K. Shimada K. Kurata T. Sato H. Daida H. Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event. The ESTABLISH study.Circulation. 2004; 110: 1061-1068Crossref PubMed Scopus (483) Google Scholar], but changes in the tissue properties may have occurred very early within about 1 month in this patient, showing that early statin administration is effective for stabilizing coronary arterial plaques. There are several limitations of the current study. First, acoustic shadowing by a guide wire may affect tissue characterization. The lesion which is masked by acoustic shadowing, might be misinterpreted as lipid pool. Second, thrombus has several IB values according to its formation. Fresh thrombus and lipid pool have similar IB values and organized thrombus and fibrosis also have similar IB values. It is possible that fresh thrombus at baseline was misclassified as lipid-pool (blue) and organized thrombus at follow-up as fibrosis (green). This is a limitation of analyses using IB-IVUS. Third, it is possible that other medications which had been initiated before, contributed to the change in plaque composition. However, atorvastatin was the only drug which had been added after the first IB-IVUS. Therefore, the atorvastatin might play the most important role in the changes. In conclusion, short-term atorvastatin-induced changes in the coronary arterial plaque properties were observed using IB-IVUS in a patient. It was suggested that IB-IVUS is useful for short-term course observation during lipid-lowering therapy, and atorvastatin changes the tissue properties of coronary arterial plaques from a very early phase. It might be associated with the stabilization of coronary plaque." @default.
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