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| 1.
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Takashima, Hiroaki ; Ozaki, Yukio ; Morimoto, Takeshi ; Kimura, Takeshi ; Hiro, Takafumi ; Miyauchi, Katsumi ; Nakagawa, Yoshihisa ; Yamagishi, Masakazu ; Daida, Hiroyuki ; Mizuno, Tomofumi ; Asai, Kenji ; Kuroda, Yasuo ; Kosaka, Takashi ; Kuhara, Yasushi ; Kurita, Akiyoshi ; Maeda, Kazuyuki ; Amano, Tetsuya ; Matsuzaki, Masunori ; 山岸, 正和
概要:
金沢大学医薬保健研究域医学系<br />Background: The JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndr
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ome) trial showed that intensive statin therapy could induce significant coronary plaque regression in acute coronary syndrome (ACS). We evaluated the impact of metabolic syndrome (MetS) and its components on coronary plaque regression in the JAPAN-ACS patients. Methods and Results: Serial intravascular ultrasound measurements over 8-12 months were performed in 242 ACS patients receiving pitavastatin or atorvastatin. Patients were divided into groups according to the presence of MetS or the number of MetS components. Although the percent change in plaque volume (%PV) was not significantly different between the MetS (n=119) and non-MetS (n=123) groups (P=0.50), it was significantly associated with an increasing number of MetS components (component 0: -24.0%, n=7; components 1: -20.8%, n=31; components 2: -16.1%, n=69; components 3: -18.7%, n=83; components 4: -13.5%, n=52; P=0.037 for trend). The percent change in body mass index (%BMI) significantly correlated with %PV (r=0.15, P=0.021), especially in the MetS components 4 group (r=0.35, P=0.017). In addition, %BMI was an independent predictor of plaque regression after adjustment for the changes of low- and high-density lipoprotein cholesterol, triglycerides and HbA1c. Conclusions: The clustering of MetS components, but not the presence of MetS itself, could attenuate coronary plaque regression during intensive statin therapy in ACS patients. Therefore, to achieve a greater degree of plaque regression, it is necessary to treat to each MetS component and use lifestyle modification.<br />出版者照会後に全文公開
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| 2.
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Miyauchi, Katsumi ; Kimura, Takeshi ; Morimoto, Takeshi ; Nakagawa, Yoshihisa ; Yamagishi, Masakazu ; Ozaki, Yukio ; Hiro, Takafumi ; Daida, Hiroyuki ; Matsuzaki, Masunori ; 山岸, 正和
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金沢大学医薬保健研究域医学系<br />Background: Many trials have shown that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase i
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nhibitors reduce the incidence of cardiovascular events and mortality. One method of decreasing the incidence of cardiovascular events could be to reduce the progression of coronary atherosclerosis, and a recent study found that atorvastatin can cause coronary plaque to regress. To generalize this finding, using conventional HMG-CoA reductase inhibitors at many Japanese centers, randomized trials of pitavastatin and atorvastatin will be conducted with patients with acute coronary syndrome (ACS). Methods and Results: Patients with ACS who have undergone successful percutaneous coronary intervention under intravascular ultrasound guidance will be studied. They will be randomly allocated to pitavastatin or atorvastatin groups and followed up for 8-12 months. The primary endpoint will be the percent change in coronary plaque volume, and secondary endpoints will include absolute changes in coronary plaque volume, serum lipid levels and inflammatory markers. The safety profile will also be evaluated. Conclusions: This study will examine the ability of HMG-CoA reductase inhibitors to regress coronary plaque in Japanese patients with ACS and the findings should help to improve the prognosis of such patients and clarify the involved mechanisms.<br />出版者照会後に全文公開
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Fukushima, Yoshifumi ; Daida, Hiroyuki ; Morimoto, Takeshi ; Kasai, Takatoshi ; Miyauchi, Katsumi ; Yamagishi, Sho-ichi ; Takeuchi, Masayoshi ; Hiro, Takafumi ; Kimura, Takeshi ; Nakagawa, Yoshihisa ; Yamagishi, Masakazu ; Ozaki, Yukio ; Matsuzaki, Masunori ; JAPAN-ACS Investigators ; 山岸, 正和
概要:
金沢大学医薬保健研究域医学系<br />Background: The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-
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ACS) trial demonstrated that early aggressive statin therapy in patients with ACS significantly reduces plaque volume (PV). Advanced glycation end products (AGEs) and the receptors of AGEs (RAGE) may lead to angiopathy in diabetes mellitus (DM) and may affect on the development of coronary PV. The present sub-study of JAPAN-ACS investigates the association between AGEs and RAGE, and PV.Methods: Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment (either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin), in patients with ACS. In the 208 JAPAN-ACS subjects, PV using IVUS in non-culprit segment > 5 mm proximal or distal to the culprit lesion and, serum levels of AGEs and soluble RAGE (sRAGE) were measured at baseline and 8-12 months after PCI.Results: At baseline, no differences in the levels of either AGEs or sRAGE were found between patients with DM and those without DM. The levels of AGEs decreased significantly with statin therapy from 8.6 ± 2.2 to 8.0 ± 2.1 U/ml (p < 0.001), whereas the levels of sRAGE did not change. There were no significant correlations between changes in PV and the changes in levels of AGEs as well as sRAGE. However, high baseline AGEs levels were significantly associated with plaque progression (odds ratio, 1.21; 95% confidence interval, 1.01 - 1.48; p = 0.044) even after adjusting for DM in multivariate logistic regression models.Conclusions: High baseline AGEs levels were associated with plaque progression in the JAPAN-ACS trial. This relationship was independent of DM. These findings suggest AGEs may be related to long-term glucose control and other oxidative stresses in ACS.Trial registration: NCT00242944. © 2013 Fukushima et al.; licensee BioMed Central Ltd.
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Gamou, Tadatsugu ; Sakata, Kenji ; Tada, Hayato ; Konno, Tetsuo ; Hayashi, Kenshi ; Ino, Hidekazu ; Yamagishi, Masakazu ; Kawashiri, Masa-aki ; on behalf of the MILLION Study Group ; 坂田, 憲治 ; 多田, 隼人 ; 今野, 哲雄 ; 林, 研至 ; 井野, 秀一 ; 山岸, 正和 ; 川尻, 剛照
概要:
Background:The MILLION study, a prospective randomized multicenter study, revealed that lipid and blood pressure (BP)-lo
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wering therapy resulted in regression of coronary plaque as determined by intravascular ultrasound (IVUS). In the present study we performed additional analysis to investigate the associated factors with regression of coronary plaque. Methods and Results:We investigated serial 3D IVUS images from 68 patients in the MILLION study. Standard IVUS parameters were assessed at both baseline and follow-up (18–24 months). Volumetric data were standardized by length as normalized volume. In patients with plaque regression (n=52), plaque volumenormalizedsignificantly decreased from 64.8 to 55.8 mm3(P<0.0001) and vessel volumenormalizedsignificantly decreased from 135.0 to 127.5 mm3(P=0.0008). There was no difference in lumen volumenormalizedfrom 70.1 to 71.8 mm3(P=0.27). There were no correlations between % changes in vessel volume and cholesterol or BP. On the other hand, negative correlations between % change in vessel volume and vessel volumenormalizedat baseline (r=−0.352, P=0.009) or plaque volumenormalizedat baseline (r=−0.336, P=0.01) were observed. Conclusions:The current data demonstrated that in patients with plaque regression treated by aggressive lipid and BP-lowering therapy, the plaque regression was derived from reverse vessel remodeling determined by vessel volume and plaque burden at baseline irrespective of decreases in lipids and BP.<br />出版者照会後に全文公開
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| 5.
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Hiro, Takafumi ; Kimura, Takeshi ; Morimoto, Takeshi ; Miyauchi, Katsumi ; Nakagawa, Yoshihisa ; Yamagishi, Masakazu ; Ozaki, Yukio ; Kimura, Kazuo ; Saito, Satoshi ; Yamaguchi, Tetsu ; Daida, Hiroyuki ; Matsuzaki, Masunori ; The JAPAN-ACS Investigators ; 山岸, 正和
概要:
Background: The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS) trial has found
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that early aggressive statin therapy in patients with acute coronary syndrome (ACS) significantly reduces the plaque volume (PV) of non-culprit coronary lesions. The purpose of the present study was to evaluate clinical factors that have an impact on plaque regression using statin therapy. Methods and Results: Serial intravascular ultrasound observations over 8-12 months were performed in 252 ACS patients receiving pitavastatin or atorvastatin. Linear regression analysis identified the presence of diabetes mellitus (DM) and PV at baseline as inhibiting factors, and serum remnant-like particle-cholesterol level at baseline as a significant factor significantly affecting the degree of plaque regression. Significant correlation between % change of PV and low-density lipoprotein cholesterol (LDL-C) level was found in patients with DM (n=73, P<0.05, r=0.4), whereas there was no significant correlation between the 2 parameters in patients without DM (n=178). Conclusions: The regression of coronary plaque induced by statin therapy after ACS was weaker in diabetic patients than their counterparts. Moreover, vigorous reduction of the LDL-C levels might induce a greater degree of plaque regression in ACS patients with DM. (Circ J 2010; 74: 1165 - 1174)<br />出版者照会後に全文公開
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| 6.
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Miyauchi, Katsumi ; Daida, Hiroyuki ; Morimoto, Takeshi ; Hiro, Takafumi ; Kimura, Takeshi ; Nakagawa, Yoshihisa ; Yamagishi, Masakazu ; Ozaki, Yukio ; Kadota, Kazushige ; Kimura, Kazuo ; Hirayama, Atsushi ; Kimura, Kazumi ; Hasegawa, Yasuhiro ; Uchiyama, Shinichiro ; Matsuzaki, Masunori ; for the JAPAN-ACS Investigators
概要:
Background: The JAPAN-ACS study demonstrated that statins significantly reduced coronary plaque volume in patients with
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acute coronary syndrome (ACS). The clinical implications of plaque regression for clinical outcomes in ACS patients has not been established. The Extended JAPAN-ACS study was conducted to evaluate the relationship between coronary plaque regression and long-term clinical outcome, and to explore the factors associated with cardiovascular events. Methods and Results: Patients with intravascular ultrasound (IVUS) data at both enrollment and follow-up in the JAPAN-ACS study were enrolled and observed for at least 3 years. Patients were divided into lesser and greater coronary plaque regression groups. The primary endpoint was defined as a composite of the following events: cardiovascular death, nonfatal myocardial infarction, nonfatal cerebral infarction, and unstable angina. The median value of the percent change in plaque volume, 18.0%, was used as a cutoff point. There were 4 primary events (3.4%) in the lesser regression group, and 2 events (1.7%) in the greater regression group (P=0.4). Cumulative secondary cardiovascular events did not differ between the 2 groups. Multivariate analysis identified the high-density lipoprotein cholesterol (HDL-C) at baseline and the % change of the external elastic membrane volume as independent risk factors of cardiovascular events. Conclusions: Coronary plaque regression induced by an intensive statin regimen did not predict future cardiovascular events in ACS patients. Rather, the baseline HDL-C level and reverse vessel remodeling might serve as predictors for cardiovascular events. (Circ J 2012; 76: 825-832)<br />出版者照会後に全文公開
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| 7.
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Miyauchi, Katsumi ; Kimura, Takeshi ; Morimoto, Takeshi ; Nakaagawa, Yoshihisa ; Yamagishi, Masakazu ; Ozaki, Yukio ; Hiro, Takafumi ; Daida, Hiroyuki ; Matsuzaki, Masunori
概要:
Background Many trials have shown that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce the
…
incidence of cardiovascular events and mortality. One method of decreasing the incidence of cardiovascular events could be to reduce the progression of coronary atherosclerosis, and a recent study found that atorvastatin can cause coronary plaque to regress. To generalize this finding, using conventional HMG-CoA reductase inhibitors at many Japanese centers, randomized trials of pitavastatin and atorvastatin will be conducted with patients with acute coronary syndrome (ACS). Methods and Results Patients with ACS who have undergone successful percutaneous coronary intervention under intravascular ultrasound guidance will be studied. They will be randomly allocated to pitavastatin or atorvastatin groups and followed up for 8-12 months. The primary endpoint will be the percent change in coronary plaque volume, and secondary endpoints will include absolute changes in coronary plaque volume, serum lipid levels and inflammatory markers. The safety profile will also be evaluated. Conclusions This study will examine the ability of HMG-CoA reductase inhibitors to regress coronary plaque in Japanese patients with ACS and the findings should help to improve the prognosis of such patients and clarify the involved mechanisms. (Circ J 2006; 70: 1624 - 1628)<br />出版者照会後に全文公開
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| 8.
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Takayama, Tadateru ; Hiro, Takafumi ; Yamagishi, Masakazu ; Daida, Hiroyuki ; Saito, Satoshi ; Yamaguchi, Tetsu ; Matsuzaki, Masunori
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http://www.j-circ.or.jp/english/<br />Background There have been few multicenter studies using intravascular ultrasound
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(IVUS) to assess the process of atherosclerosis in a Japanese population with hypercholesterolemia that is being treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for control of low-density lipoprotein-cholesterol. Methods and Results An open-label multicenter study is planned to evaluate with IVUS whether treatment with rosuvastatin for 76 weeks results in regression of coronary artery atheroma volume in patients who have coronary heart disease (CHD) and hypercholesterolemia. Sample size is 200 subjects with CHD who are to undergo percutaneous coronary intervention. The planned duration is between October 2005 and October 2008. Conclusions The COSMOS study will be the first multicenter cardiovascular study in a Japanese population and may provide new evidence on the effects of rosuvastatin on the progression of coronary atherosclerotic lesions. (Circ J 2007; 71: 271 -275)<br />出版者照会後に全文公開
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Daida, Hiroyuki ; Takayama, Tadateru ; Hiro, Takafumi ; Yamagishi, Masakazu ; Hirayama, Atsushi ; Saito, Satoshi ; Yamaguchi, Tetsu
概要:
Background: The incidence of cardiac events is higher in patients with diabetes than in people without diabetes. The Cor
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onary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS) demonstrated significant plaque regression in Japanese patients with chronic coronary disease after 76 weeks of rosuvastatin (2.5 mg once daily, up-titrated to a maximum of 20 mg/day to achieve LDL cholesterol <80 mg/dl).Methods: In this subanalysis of COSMOS, we examined the association between HbA1c and plaque regression in 40 patients with HbA1c ≥6.5% (high group) and 86 patients with HbA1c <6.5% (low group).Results: In multivariate analyses, HbA1c and plaque volume at baseline were major determinants of plaque regression. LDL cholesterol decreased by 37% and 39% in the high and low groups, respectively, while HDL cholesterol increased by 16% and 22%, respectively. The reduction in plaque volume was significantly (p = 0.04) greater in the low group (from 71.0 ± 39.9 to 64.7 ± 34.7 mm3) than in the high group (from 74.3 ± 34.2 to 71.4 ± 32.3 mm3). Vessel volume increased in the high group but not in the low group (change from baseline: +4.2% vs -0.8%, p = 0.02). Change in plaque volume was significantly correlated with baseline HbA1c.Conclusions: Despite similar improvements in lipid levels, plaque regression was less pronounced in patients with high HbA1c levels compared with those with low levels. Tight glucose control during statin therapy may enhance plaque regression in patients with stable coronary disease.Trial registration: ClinicalTrials.gov, Identifier NCT00329160. © 2012 Daida et al.; licensee BioMed Central Ltd.
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| 10.
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Fukushima, Yoshifumi ; Daida, Hiroyuki ; Morimoto, Takeshi ; Kasai, Takatoshi ; Miyauchi, Katsumi ; Yamagishi, Sho-ichi ; Takeuchi, Masayoshi ; Hiro, Takafumi ; Kimura, Takeshi ; Nakagawa, Yoshihisa ; Yamagishi, Masakazu ; Ozaki, Yukio ; Matsuzaki, Masunori
概要:
Background: The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS) trial demonstra
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ted that early aggressive statin therapy in patients with ACS significantly reduces plaque volume (PV). Advanced glycation end products (AGEs) and the receptors of AGEs (RAGE) may lead to angiopathy in diabetes mellitus (DM) and may affect on the development of coronary PV. The present sub-study of JAPAN-ACS investigates the association between AGEs and RAGE, and PV.Methods: Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment (either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin), in patients with ACS. In the 208 JAPAN-ACS subjects, PV using IVUS in non-culprit segment > 5 mm proximal or distal to the culprit lesion and, serum levels of AGEs and soluble RAGE (sRAGE) were measured at baseline and 8-12 months after PCI.Results: At baseline, no differences in the levels of either AGEs or sRAGE were found between patients with DM and those without DM. The levels of AGEs decreased significantly with statin therapy from 8.6 ± 2.2 to 8.0 ± 2.1 U/ml (p < 0.001), whereas the levels of sRAGE did not change. There were no significant correlations between changes in PV and the changes in levels of AGEs as well as sRAGE. However, high baseline AGEs levels were significantly associated with plaque progression (odds ratio, 1.21; 95% confidence interval, 1.01 - 1.48; p = 0.044) even after adjusting for DM in multivariate logistic regression models.Conclusions: High baseline AGEs levels were associated with plaque progression in the JAPAN-ACS trial. This relationship was independent of DM. These findings suggest AGEs may be related to long-term glucose control and other oxidative stresses in ACS.Trial registration: NCT00242944. © 2013 Fukushima et al.; licensee BioMed Central Ltd.
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Naito, Ryo ; Miyauchi, Katsumi ; Daida, Hiroyuki ; Morimoto, Takeshi ; Hiro, Takafumi ; Kimura, Takeshi ; Nakagawa, Yoshihisa ; Yamagishi, Masakazu ; Ozaki, Yukio ; Matsuzaki, Masunori ; for the aJAPAN-ACS Investigators ; 山岸, 正和
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Aim: Diabetic patients with coronary artery disease have a high incidence of cardiovascular events, which was associated
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with increased coronary plaque volume. Low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) play pivotal roles in the progression of coronary plaque. Several trials have shown that intervention for a single risk factor reduced the development of coronary plaque progression. However, it remained uncertain whether total risk management for LDL-C, BP, and glycosylated Hb (HbA1c) has a beneficial effect on coronary plaque volume in diabetic patients. Methods: This study was a sub-study of the JAPAN-ACS that was a prospective, randomized, open-label trial that evaluated the impact of intensive lipid-lowering therapy on coronary plaque volume in patients with acute coronary syndrome (ACS). Among a total of 252 patients, 73 diabetic patients were analyzed. We examined the impact of total risk management (LDL-C ＜80 mg/dL, systolic BP ＜130 mmHg, and HbA1c ＜6.5%) on changes in coronary plaque volume. The patients were divided into four groups according to the number of risk factors that achieved the target value. Results: Baseline characteristics were similar among the groups. The degree of coronary plaque regression was greater in patients who achieved total risk management. The number of risk factors that achieved the target level was associated with the extent of the coronary plaque volume reduction in a dose-dependent manner. Conclusion: Total risk management that focused on LDL-C, BP, and HbA1c had a beneficial impact on the coronary plaque regression in diabetic patients with ACS.<br />出版者照会後に全文公開
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Arai, Hidenori ; Hiro, Takafumi ; Kimura, Takeshi ; Morimoto, Takeshi ; Miyauchi, Katsumi ; Nakagawa, Yoshihisa ; Yamagishi, Masakazu ; Ozaki, Yukio ; Kimura, Kazuo ; Saito, Satoshi ; Yamaguchi, Tetsu ; Daida, Hiroyuki ; Matsuzaki, Masunori ; 山岸, 正和
概要:
Aim: We have shown that aggressive lipid lowering by pitavastatin and atorvastatin results in marked regression of ather
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osclerotic coronary lesions after acute coronary syndrome (ACS). The purpose of this study was to address the association of lipid levels after statin therapy with regression of atherosclerotic coronary lesions and major cardiovascular events in patients after ACS. Methods: JAPAN-ACS is a prospective, randomized open-label study performed at 33 centers in Japan. Patients with ACS undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) were randomly assigned to receive either 4 mg/day pitavastatin or 20 mg/day atorvastatin within 72 hours after PCI. IVUS image was obtained in 251 patients, including 73 diabetic patients. Lipid profiles at the end of the study were divided into quartiles and the association with the percent change in non-culprit coronary plaque volume (PV) was assessed in total and diabetic patients. We also studied whether baseline and follow-up levels of HDL-cholesterol are associated with restenosis after PCI. Results: Decreasing LDL-cholesterol, non-HDL-cholesterol, LDL-C/HDL-C ratio, apolipoprotein B quartiles were associated with a progressively smaller plaque burden in total and diabetic patients. In diabetic patients, further reduction of these parameters was associated with a significantly greater reduction in PV. We also found that patients with lower HDL-cholesterol had a significantly higher incidence of target lesion revascularization. Conclusions: Early intensive statin therapy in patients after ACS results in remarkable regression of coronary PV. Diabetic patients can have a benefit with more intensive therapy to achieve a lower target level in Japanese.<br />出版者照会後に全文公開
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