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In recent years, transthyretin amyloid cardiomyopathy (ATTR-CM) has received increasing attention; however, the epidemiology of ATTR-CM in Japan is not yet understood. In the Kumamoto Cardiac Amyloid Survey, we evaluated the current incidence, clinical characteristics, diagnostic approaches, and treatment strategies for ATTR-CM and compared tafamidis-prescription hospitals with regional hospitals.We conducted a retrospective multicenter observational cohort study. The registry included patients with ATTR-CM diagnosed in two tafamidis-prescription hospital institutes [Japanese Circulation Society (JCS)-certified facilities] and 15 regional cardiovascular facilities in Kumamoto between January 2018 and December 2020.In total, 174 patients were diagnosed with ATTR-CM. The incidence of ATTR-CM was estimated to be approximately 1 per 10,000 person-years in the elderly population (65 years old) in Kumamoto. Compared with that in the JCS-certified facilities cohort (n=115), age at diagnosis was significantly older (84.5 ± 5.6 vs. 77.5 ± 6.3 years old; p0.01) in the regional hospitals cohort (n=59). Histological (25% vs. 81%; p0.01) and genetic diagnosis (7% vs. 82%) were also less frequently performed. Probable (as indicated by positive bone scintigraphy findings with confirmation of monoclonal protein absence) and possible (as indicated by positive bone scintigraphy findings without confirmation of monoclonal protein absence) ATTR-CM accounted for the majority of cases (75% vs. 19%; p0.01) in the regional hospitals cohort compared to the JCS-certified facilities cohort. There were no cases of hereditary ATTR-CM among the patients who underwent TTR genetic testing (n=98).We confirmed the incidence of ATTR-CM in Kumamoto and the diagnostic approach used in patients with ATTR-CM. Further prospective studies with a larger sample are needed to validate our results and to further shed light on the epidemiology of ATTR-CM in Japan.

Background The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. Methods The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. Results Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4–8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). Conclusions This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

Aim Matrix metalloproteinases (MMPs) play critical roles in acute myocardial infarction (AMI). This trial was conducted to determine the potential effects of higher-dose rosuvastatin on circulating MMP levels in patients with AMI. Methods This was a multicenter, open-label, 1:1 randomized, parallel-group study. Patients with AMI were randomly assigned to the appropriate-dose group (10 mg rosuvastatin once daily) or the low-dose group (2.5 mg rosuvastatin once daily) within 24 hours after percutaneous coronary intervention. MMP-2 and MMP-9 levels were measured on day 1 and at week 4, 12, and 24 after enrollment. The primary endpoint was the change in MMP levels at 24 weeks after enrollment. The secondary endpoints were change in MMP levels at day 1 and weeks 4 and 12 after enrollment. Results Between August 2017 and October 2018, 120 patients with AMI from 19 institutions were randomly assigned to either the appropriate-dose or the low-dose group. There were 109 patients who completed the 24-week follow-up. The primary endpoint for both MMP-2 and MMP-9 was not significantly different between the two groups. The change in the active/total ratio of MMP-9 at week 12 after baseline was significantly lower in the appropriate-dose group compared with the low-dose group (0.81 [-52.8-60.1]% vs. 70.1 [-14.5-214.2]%, P=0.004), while the changes in MMP-2 were not significantly different between the two groups during the study period. Conclusions This study could not demonstrate the superiority of appropriate-dose of rosuvastatin in inhibiting serum MMPs levels in patients with AMI.

Aim: Coronary plaque regression is weak in acute coronary syndrome (ACS) patients with diabetes mellitus (DM). We evaluated whether dual lipid-lowering therapy (DLLT) with ezetimibe and atorvastatin attenuates coronary plaques in ACS patients with DM. Methods: The prospective, randomized controlled, multicenter PRECISE-IVUS (Plaque Regression with Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound) trial assigned 246 patients undergoing percutaneous coronary intervention to DLLT or atorvastatin monotherapy and evaluated IVUS-derived changes in percent atheroma volume (ΔPAV), at baseline and 9–12-month follow-up, in 126 ACS cases, including 25 DM patients. The atorvastatin dose was up-titrated to achieve low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL. Results: In DM patients, the monotherapy group (n = 13) and the DLLT group (n = 12) showed a similar prevalence of coronary risks and baseline lipid profiles. During the study, the change in LDL-C level was similar between DM and non-DM patients. Compared with non-DM patients, DM patients showed weaker regression of ΔPAV by DLLT than those who underwent monotherapy (DM: −2.77 ± 3.47% vs. −0.77 ± 2.51%, P = 0.11; non-DM: −2.01 ± 3.36% vs. −0.08 ± 2.66%, P = 0.008). The change in LDL-C level was not correlated with ΔPAV in non-DM patients, but there was significant correlation between the change in LDL-C level and ΔPAV in DM patients (r = 0.52, P = 0.008). Conclusions: ACS patients with DM showed weaker coronary plaque regression than their counterparts. A significant correlation between the change in LDL-C level and ΔPAV in DM patients suggested that more intensive lipid-lowering therapy is required in ACS patients with DM.

Chronic kidney disease (CKD) deteriorates the prognosis of patients undergoing percutaneous coronary intervention (PCI). Because coronary artery disease (CAD) is the major cause of death in CKD patients, cardiovascular risk reduction has been clinically important in CKD. We hypothesized intensive lipid-lowering with statin/ezetimibe attenuated coronary atherosclerotic development even in patients with CKD.In the prospective, randomized, controlled, multicenter PRECISE-IVUS trial, 246 patients undergoing intravascular ultrasound (IVUS)-guided PCI were randomly assigned to receive atorvastatin/ezetimibe combination or atorvastatin alone (the dosage of atorvastatin was up-titrated to achieve the level of low-density lipoprotein cholesterol 70 mg/dL). Serial volumetric IVUS findings obtained at baseline and 9-12 month follow-up to quantify the coronary plaque response in 202 patients were compared stratified by the presence or absence of CKD.CKD was observed in 52 patients (26%) among 202 enrolled patients. Compared with the non-CKD group, the CKD group was significantly older (71.5 ± 8.6 years vs. 64.4 ± 9.6 years, P 0.001) with similar prevalence of comorbid coronary risk factors and lipid profiles. Similar to the non-CKD group (-1.4 [-2.8 to -0.1]% vs. -0.2 [-1.7 to 1.0]%, P = 0.002), the atorvastatin/ezetimibe combination significantly reduced ∆PAV compared with atorvastatin alone even in the CKD group (-2.6 [-5.6 to -0.4]% vs. -0.9 [-2.4 to 0.2]%, P = 0.04).As with non-CKD, intensive lipid-lowering therapy with atorvastatin/ezetimibe demonstrated stronger coronary plaque regression effect even in patients with CKD compared with atorvastatin monotherapy.NCT01043380 (ClinicalTrials.gov).

A 59-year-old man was referred to our hospital for chest pain he had been experiencing for several hours. The electrocardiogram showed ST-segment elevation in leads II, III, aVF, V4-V6. Emergent coronary angiography (CAG) showed a total occlusion of the proximal right coronary artery (RCA) with multiple calcified coronary artery aneurysms (CAAs) (Figure 1 A). There was no significant lesion of the left coronary artery.

Background and aims Although dual low-density lipoprotein cholesterol (LDL-C)-lowering therapy (DLLT) with statin-ezetimibe combination showed clinical benefit in patients with acute coronary syndrome (ACS) confirming "the lower, the better," the underlying mechanisms of DLLT are still unknown. Methods PRECISE-IVUS trial evaluated the effects of DLLT on IVUS-derived coronary atherosclerosis and lipid profile, compared with atorvastatin monotherapy, quantifying the coronary plaque response in 100 ACS patients. We explored the potential predictors of plaque regression. Results Lower total cholesterol, LDL-C, triglyceride, remnant-like particles cholesterol, and stronger reduction of small dense LDL-C and cholesterol absorption markers were observed in patients with plaque regression compared to those with progression. Multivariate analysis revealed that achieved LDL-C was the strongest predictor for coronary plaque regression (95% CI: 0.944–1.000, p = 0.05), followed by age (95% CI: 0.994–1.096, p = 0.09). Conclusions Incremental LDL-C lowering by DLLT was associated with stronger coronary plaque regression, reconfirming that lowering LDL-C to levels below previous targets provided additional clinical benefit.

Objective The purpose of this study was to examine the cardiovascular protective effects of candesartan in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). Background Candesartan has been reported to reduce cardiovascular events when therapy was started 6 months after PCI with bare-metal stents in patients who survived restenosis. Candesartan started immediately after PCI with DESs was also effective in preventing cardiovascular events. Methods The 4C trial was a multicenter, prospective, randomized, open-label study. A total of 1145 patients at 39 centers in Japan were randomly assigned to receive candesartan plus standard medical treatment or standard medical treatment alone. The primary endpoints were all-cause death, and a composite of non-fatal myocardial infarction (MI), unstable angina pectoris (uAP), congestive heart failure (CHF), and non-fatal cerebrovascular events. The follow-up period was up to 3 years after the index PCI (ClinicalTrials.gov NCT00139386 ). Results The incidence of total death, one of the primary endpoints, was comparable between the two treatment groups (3.8% each, p = 0.9702). Another primary endpoint, non-fatal major cardiovascular events, tended to occur more often in the control group than in the candesartan group (9.2% vs. 12.5%, p = 0.0985). In contrast, candesartan significantly reduced one of the pre-specified secondary endpoints: cardiovascular events that included non-fatal MI, uAP, and CHF (4.4% vs. 6.7%, p = 0.0136). Furthermore, candesartan significantly reduced another secondary endpoint that included cardiovascular events and cardiovascular death (5.0% vs. 7.7%, p = 0.0493). Conclusions The 4C trial showed that candesartan administered immediately after PCI with DESs did not improve the prognosis after the index procedure, but did reduce some cardiac-related events for 3 years.

Background Although the positive association between achieved low-density lipoprotein cholesterol (LDL-C) level and the risk of coronary artery disease (CAD) has been confirmed by randomized studies with statins, many patients remain at high residual risk of events suggesting the necessity of novel pharmacologic strategies. The combination of ezetimibe/statin produces greater reductions in LDL-C compared to statin monotherapy. Purpose The Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS) trial was aimed at evaluating the effects of ezetimibe addition to atorvastatin, compared with atorvastatin monotherapy, on coronary plaque regression and change in lipid profile in patients with CAD. Methods The study is a prospective, randomized, controlled, multicenter study. The eligible patients undergoing IVUS-guided percutaneous coronary intervention will be randomly assigned to receive either atorvastatin alone or atorvastatin plus ezetimibe (10 mg) daily using a web-based randomization software. The dosage of atorvastatin will be increased by titration within the usual dose range with a treatment goal of lowering LDL-C below 70 mg/dL based on consecutive measures of LDL-C at follow-up visits. IVUS will be performed at baseline and 9–12 months follow-up time point at participating cardiovascular centers. The primary endpoint will be the nominal change in percent coronary atheroma volume measured by volumetric IVUS analysis. Conclusion PRECISE-IVUS will assess whether the efficacy of combination of ezetimibe/atorvastatin is noninferior to atorvastatin monotherapy for coronary plaque reduction, and will translate into increased clinical benefit of dual lipid-lowering strategy in a Japanese population.

Background Despite standard statin therapy, a majority of patients retain a high “residual risk” of cardiovascular events. Objectives The aim of this study was to evaluate the effects of ezetimibe plus atorvastatin versus atorvastatin monotherapy on the lipid profile and coronary atherosclerosis in Japanese patients who underwent percutaneous coronary intervention (PCI). Methods This trial was a prospective, randomized, controlled, multicenter study. Eligible patients who underwent PCI were randomly assigned to atorvastatin alone or atorvastatin plus ezetimibe (10 mg) daily. Atorvastatin was uptitrated with a treatment goal of low-density lipoprotein cholesterol (LDL-C) Results The combination of atorvastatin/ezetimibe resulted in lower levels of LDL-C than atorvastatin monotherapy (63.2 ± 16.3 mg/dl vs. 73.3 ± 20.3 mg/dl; p Conclusions Compared with standard statin monotherapy, the combination of statin plus ezetimibe showed greater coronary plaque regression, which might be attributed to cholesterol absorption inhibition–induced aggressive lipid lowering. (Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound [PRECISE-IVUS]; NCT01043380 )

Aim Few multicenter studies have assessed the effects of angiotensin receptor blockers on cardiovascular events after drug-eluting stent implantation in patients with ischemic heart disease. Methods An open-label multicenter randomized prospective study is in progress to evaluate the effects of candesartan on cardiovascular events in patients with ischemic heart disease after implantation of sirolimus- and/or paclitaxel-eluting stents. Results A total of 1,145 patients were enrolled at 39 institutes in the Candesartan for prevention of Cardiovascular events after CYPHER or TAXUS Coronary stenting (4C trial). Patients were randomized into a group treated with candesartan (n=602) and a group treated with standard medical therapy without candesartan (n=543). The primary endpoint of the 4C trial is a composite of all-cause death, successful resuscitation after cardiopulmonary arrest and cardiovascular events including non-fatal myocardial infarction, unstable angina requiring emergent hospitalization, congestive heart failure requiring emergent hospitalization and cerebrovascular attacks. All patients will be followed-up for 36 months. Conclusions The 4C trial will be the first multicenter study to elucidate the effects of candesartan after drug-eluting stent implantation and may provide new information to optimize medical therapy after percutaneous coronary interventions.

The IMPROVE-IT trial showed that the clinical benefit of statin/ezetimibe combination appeared to be pronounced in patients with prior statin therapy. We hypothesized that the antiatherosclerotic effect of atorvastatin/ezetimibe combination was pronounced in patients with statin pretreatment.In the prospective, randomized, controlled, multicenter PRECISE-IVUS trial, 246 patients undergoing intravascular ultrasound-guided percutaneous coronary intervention were randomized to atorvastatin/ezetimibe combination or atorvastatin alone. The dosage of atorvastatin was uptitrated with a treatment goal of lowering low-density lipoprotein cholesterol to below 70 mg/dl in both groups. Serial volumetric intravascular ultrasound was performed at baseline and 9-12 month follow-up to quantify the coronary plaque response in 202 patients. We compared the intravascular ultrasound endpoints in all subjects, stratified by the presence or absence of statin pretreatment.The baseline low-density lipoprotein cholesterol level (100.7 ± 23.1 mg/dl vs. 116.4 ± 25.9 mg/dl, p 0.001) and lathosterol (55 (38 to 87)) µg/100 mg total cholesterol vs. 97 (57 to 149) µg/100 mg total cholesterol, p 0.001) was significantly lower, and campesterol/lathosterol ratio (3.9 (2.4 to 7.4) vs. 2.6 (1.5 to 4.1), p 0.001) was significantly increased in patients with statin pretreatment. Contrary to the patients without statin pretreatment (-1.3 (-3.1 to -0.1)% vs. -0.9 (-2.3 to 0.9)%, p = 0.12), the atorvastatin/ezetimibe combination showed a significantly stronger reduction in delta percent atheroma volume, compared with atorvastatin alone, in patients with statin pretreatment (-1.8 (-3.6 to -0.3)% vs. -0.1 (-1.6 to 0.8)%, p = 0.002).Compensatory increase in cholesterol absorption observed in statin-treated patients might attenuate the inhibitory effects of statins on coronary plaque progression. A low-dose statin/ezetimibe combination might be a promising option in statin-hyporesponder.

Clinical outcomes of percutaneous coronary intervention (PCI) at hospital with or without onsite cardiac surgery backup Tomonori Akasaka , Seiji Hokimoto ⁎, Shuichi Oshima , Koichi Nakao , Kazuteru Fujimoto , Yuji Miyao , Hideki Shimomura , Ryusuke Tsunoda , Toyoki Hirose , Ichiro Kajiwara , Toshiyuki Matsumura , Natsuki Nakamura , Nobuyasu Yamamoto , Shunichi Koide , Hideki Oka , Yasuhiro Morikami , Naritsugu Sakaino , Koichi Kaikita , Sunao Nakamura , Kunihiko Matsui , Hisao Ogawa , on behalf of, Kumamoto Intervention Conference Study (KICS) Investigators

Previous studies have showed that the intensive lipid lowering therapy (ILLT) with statins could decrease coronary atheroma plaque, but the effect is weak in acute coronary syndrome (ACS) patients with diabetes mellitus (DM). We conducted to evaluate whether ILLT by ezetimibe combined with statin

Mannose-binding lectin (MBL), L-ficolin and H-ficolin are human serum lectins, all of which form complexes with MBL-associated serine proteases (MASP). The lectin-MASP complexes bind to the surface of microbes, leading to activation of the lectin pathway of complement. Enzyme-linked immunosorbent assays (ELISA) of the lectin pathway activity reported so far determined the activity via either MBL or L-ficolin, but an assay of activity via plural host defense lectins has not been established. To measure the lectin pathway activation mediated by plural lectins simultaneously, we developed an ELISA system in which N-acetylglucosamine-pentamer conjugated to dipalmitoylphosphatidylethanolamine (GN5-DPPE) was employed as a ligand for the lectins. In our ELISA system, both purified MBL and L-ficolin isolated from serum diluted in a buffer containing high ionic NaCl bound to GN5-DPPE and activated C4. Purified H-ficolin was not capable of binding to GN5-DPPE. MBL and L-ficolin in MBL-sufficient serum also bound to GN5-DPPE and activated C4. Mannose and N-acetylgalactosamine inhibited binding of MBL and L-ficolin to GN5-DPPE, respectively. MBL-deficient serum that had been depleted of L-ficolin did not exhibit C4 activation, but addition of both or either purified MBL and/or L-ficolin to the serum restored the activation in a dose-dependent manner. Thus, C4 cleaving activity could be evaluated with the co-existence of MBL and L-ficolin in vitro. In conclusion, we propose a novel method using GN5-DPPE for investigating the MBL- and L-ficolin-dependent lectin pathway and anticipate that this method will be useful in innate immunity and clinical research.

Background Based on the 2011 American College of Cardiology/American Heart Association percutaneous coronary intervention (PCI) guideline, it is recommended that PCI should be performed at hospital with onsite cardiac surgery. But, data suggest that there is no significant difference in clinical outcomes following primary or elective PCI between the two groups. We examined the impact of with or without onsite cardiac surgery on clinical outcomes following PCI for acute coronary syndrome (ACS). Methods and results From August 2008 to March 2011, subjects ( n = 3241) were enrolled from the Kumamoto Intervention Conference Study (KICS). Patients were assigned to two groups treated in hospitals with ( n = 2764) or without ( n = 477) onsite cardiac surgery. Clinical events were followed up for 12 months. Primary endpoint was in-hospital death, cardiovascular death, myocardial infarction, and stroke. And we monitored in-hospital events, non-cardiovascular deaths, bleeding complications, revascularizations, and emergent coronary artery bypass grafting (CABG). There was no overall significant difference in primary endpoint between hospitals with and without onsite cardiac surgery [ACS, 7.6% vs. 8.0%, p = 0.737; ST-segment elevation myocardial infarction (STEMI), 10.4% vs. 7.5%, p = 0.200]. There was also no significant difference when events in primary endpoint were considered separately. In other events, revascularization was more frequently seen in hospitals with onsite surgery (ACS, 20.0% vs. 13.0%, p p = 0.009). We performed propensity score matching analysis to correct for the disparate patient numbers between the two groups, and there was also no significant difference for primary endpoint (ACS, 8.6% vs. 7.5%, p = 0.547; STEMI, 11.2% vs. 7.5%, p = 0.210). Conclusions There is no significant difference in clinical outcomes following PCI for ACS between hospitals with and without onsite cardiac surgery backup in Japan.

Introduction: Ezetimibe (EZE) is a cholesterol absorption inhibitor and its clinical benefit, as combined with statin for pts with coronary artery disease (CAD), was shown by IMPROVE-IT trial. Campesterol (camp) is the cholesterol absorption marker and the benefit of EZE/statin combination therapy for pts with low camp (LC) value, in whom EZE appears to ineffective, is not clearly understood. The PRECISE-IVUS (Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound) trial was a prospective, randomized, controlled, multicenter study evaluating the effects of EZE addition to atorvastatin (atorva), compared with atorva monotherapy, on coronary atherosclerosis evaluated by IVUS and lipid profile. Hypothesis: In this study, we investigated the effect of EZE for pts with the LC value. Methods: 246 pts undergoing IVUS-guided percutaneous coronary intervention were randomized to EZE/atorva combination (EA) group or atorva alone (A) group. The dosage of atorva was uptitrated with a treatment goal of lowering low-density lipoprotein cholesterol (LDL-C) below 70mg/dL. Serial volumetric IVUS was performed at baseline and 9–12 months follow-up to quantify the coronary plaque response in 202 patients. Results: There were significantly positive correlation between baseline LDL-C level and baseline camp value (R=0.399, p Conclusions: Even in pts with CAD and LC value, statin-EZE combined therapy showed significantly decreased LDL-C and regressed coronary plaque burden. Even if the cholesterol absorption ability is declined, EZE-statin combined therapy might be the promising option for pts with CAD.

The aim of this study was to examine the effects of different statins on the clinical outcomes of Japanese patients with coronary stent implants.This study included 5,801 consecutive patients (males, 4,160; age, 69.7±11.1 years, mean±SD) who underwent stent implantation between April 2008 and March 2011. They were treated with a strong statin (n=3,042, 52%, atorvastatin, pitavastatin, or rosuvastatin), a regular statin (n=1,082, 19%, pravastatin, simvastatin, or fluvastatin) or no statin (n=1,677, 29%). The patients with chronic kidney disease (CKD) were divided into mild-to-moderate CKD (30≤eGFR60, n=1,956) and severe CKD (eGFR30, n=559). Primary endpoints included cardiovascular death and nonfatal myocardial infarction, including stent thrombosis and ischemic stroke. The clinical outcome for the primary endpoint in mild-to-moderate CKD patients treated with a strong statin (hazard ratio 0.50, 95% confidence interval 0.31-0.81; P=0.005) was significantly lower than in those on no statins, but that in the patients treated with a regular statin was not (P=0.160). The clinical outcome for the primary endpoint in severe CKD patients treated with a strong or regular statin was no different than not being on statin therapy (P=0.446, P=0.194, respectively).In patients with mild-to-moderate CKD, only strong statins were associated with lower risk compared with no statin, but regular statins were not. It is possible that taking a strong statin from the early stage of CKD is useful for suppression of cardiovascular events.

Stent thrombosis (ST) has emerged as a severe complication of percutaneous coronary intervention (PCI). Since the occurrence of ST is lower in Japan than Western countries, there are few data to predict ST after drug-eluting stent (DES) implantation in Japan. We examined the independent predictors of ST incidence after DES implantation in Japanese patients, including the use of calcium channel blockers (CCBs).We used data from the Kumamoto Intervention Conference Study registry. There were 6286 consecutive patients enrolled from June 2008 to March 2011. Among them, we analyzed 3493 patients who underwent DES implantation. The incidence of definite/probable ST throughout a median follow-up period of 364 days was 0.57% (20 patients). There were 8 patients with early ST (within 30 days), 8 patients with late ST (between 31 and 365 days), and 4 patients with very late ST (after 1 year). The frequency of CCB use was significantly lower in ST than non-ST patients (25.0% versus 51.4%, respectively, p=0.016). Multiple regression analysis showed that longer stent length (p=0.034), acute coronary syndrome (p=0.039), and the absence of CCB use (p=0.046) were significant and independent predictors of ST within 1 year.These results suggest that CCB use may be associated with a decreased risk of ST after DES implantation within 1 year in Japanese patients.

Series of pyrimidine and pyridine analogous compounds have been developed in order to interpret the relationship between stability of antiferroelectricity and the conjugation along the long axis of the molecule. On the appearance of antiferroelectricity, the longitudinal polarization of whole molecules promotes to stabilize the antiferroelectricity.

A series of polymer alignment layers consisting of fluoro and non-fluoro polyimide, polyamide-imide and polyamide were developed for antiferroelectric liquid crystal display devices. These polymer alignment layers were evaluated for their electrooptical properties. The alignment characteristics such as double hysteresis behavior and driving margin strongly depend upon the polymer alignment structure. Alignment layers with less hindered or linear diamine unit in the polymer backbone showed superiority, in comparison with sterically hindered diamine, in aligning and electrooptical properties of antiferroelectric liquid crystal devices.

Smooth muscle cells play an important role in human vascular diseases. Several lines of evidence demonstrate that circulating smooth muscle precursor cells contribute to intimal hyperplasia in animal models. We obtained large spindle cells expressing alpha-smooth muscle actin (α-SMA), denoted here as “smooth muscle-like cells” (SMLC), from human peripheral blood mononuclear cells (PBMC). SMLC derived from human PBMC proliferated readily and expressed pro-inflammatory genes during early culture. After long-term culture, SMLC could contract and express characteristic smooth muscle cell markers. We found peripheral blood mononuclear cell expressing α-smooth muscle actin in the circulating blood that bore CD14 and CD105. Sorted CD14/CD105 double-positive PBMC could differentiate into SMLC. The number of CD14–CD105-bearing PBMC increased significantly in patients with coronary artery disease compared to patients without coronary artery disease. These results support the novel concept that smooth muscle precursor cells exist in circulating human blood and may contribute to the pathogenesis of vascular diseases.

Experimental investigations were previously conducted with a direct-injection diesel engine with the aim of reducing exhaust emissions, especially nitrogen oxides (NOx) and particulate matter (PM). As a result of that work, a combustion concept, called Modulated Kinetics (MK) combustion, was developed that reduces NOx and smoke simultaneously through low-temperature combustion and premixed combustion to achieve a cleaner diesel engine. In subsequent work, it was found that applying a low compression ratio was effective in expanding the MK combustion region on the high-load side. The MK concept was then combined with an exhaust after-treatment system and applied to a test vehicle. The results indicated the attainment of ULEV emission levels, albeit in laboratory evaluations. In the present work, the combination of the MK combustion concept and certain fuel properties has been experimentally investigated with the aim of reducing exhaust emissions further. The results indicated that the use of a high cetane number gas-to-liquid (GTL) fuel with a lower compression ratio provides a sufficiently long ignition delay to accomplish MK combustion. The effect on a simultaneous reduction of NOx and smoke was confirmed. The results also indicated that the use of GTL fuel can reduce the total hydrocarbon level substantially under a cold condition because of its good ignition characteristics, with a high cetane number and high levels of paraffin compounds. As a result, one possible approach to the attainment of SULEV emission levels was found.

Objectives This study prospectively examined whether the levels of high remnant-like lipoprotein particles (RLP) cholesterol have a significant risk and influence prognosis in patients with coronary artery disease (CAD) and type II diabetes mellitus (DM). Background Several studies have shown that triglyceride-rich lipoproteins contribute to atherosclerotic complications in type II DM. However, it remains to be established which triglyceride-rich lipoproteins contribute to this risk. Methods Levels of RLP cholesterol in fasting serum were measured by an immunoseparation method in 240 type II DM patients with (n = 120) or without (n = 120) CAD. The patients with CAD were followed up for a period of ≤24 months until the occurrence of one of the following clinical coronary events: re-admission or coronary revascularization due to recurrent or refractory angina pectoris, nonfatal myocardial infarction, or cardiac death. Results Patients with CAD had higher RLP levels than patients without CAD. Multivariate logistic regression analysis showed that high RLP cholesterol levels (>4.7 mg cholesterol/dl, representing the 75th percentile of the distribution of RLP cholesterol levels in control subjects) were a significant risk factor for the presence of CAD, independent of traditional risk factors. Kaplan-Meier analysis demonstrated that higher RLP cholesterol levels in patients with CAD resulted in a significantly higher probability for the development of coronary events. Multivariate Cox hazards analysis showed that high RLP cholesterol levels in patients with CAD were a significant predictor of future coronary events, independent of other risk factors. Conclusions Increased levels of RLP cholesterol are a significant and independent risk factor of CAD and predict future coronary events in patients with CAD and type II DM.

Background —Triglyceride-rich lipoproteins (TGLs) are atherogenic. However, their cellular mechanisms remain largely unexplained. This study examined the effects of isolated remnant-like lipoprotein particles (RLPs) on the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and tissue factor (TF), proatherothrombogenic molecules, in cultured human endothelial cells. Methods and Results —RLPs were isolated from plasma of hypertriglyceridemic patients by use of the immunoaffinity gel mixture of anti–apoA-1 and anti–apoB-100 monoclonal antibodies. The incubation of cells with RLPs significantly upregulated mRNA and protein expression of these molecules. Total TGLs ( d N -acetylcysteine, both antioxidants, suppressed RLP-induced increase in expression of these molecules. In patients with higher plasma levels of RLPs, plasma levels of soluble forms of ICAM-1 and VCAM-1 were significantly higher than in patients with lower RLP levels. Treatment with α-tocopherol for 1 month decreased levels of the soluble adhesion molecules concomitantly with an increase in resistance of RLPs to oxidative modification in patients with high RLP levels. Conclusions —RLPs upregulated endothelial expression of ICAM-1, VCAM-1, and TF, proatherothrombogenic molecules, partly through a redox-sensitive mechanism. RLPs may have an important role in atherothrombotic complications in hypertriglyceridemic patients.

A73-year-old man was admitted to the hospital because of severe back pain. CT and MRI (Figure 1⇓) revealed aortic dissection. Transesophageal echocardiography (Figure 2⇓) showed a thickened intimal tear of the thoracic aorta. The patient was treated with calcium blockers (cilnidipine and diltiazem) and a β-blocker (metoprolol). One month …

ObjectivesThe purpose of this study was to examine whether echolucent carotid plaques predict future coronary events in patients with clinically stable coronary artery disease (CAD).BackgroundAlthough rupture of coronary plaques is considered a major cause of acute coronary syndromes (ACS), the clinical estimation of coronary vulnerability still remains inconclusive. Ultrasound evaluation of carotid plaques with integrated backscatter (IBS) analysis can indicate the consistency/structure of the plaques. Lipid-rich lesions known as “unstable plaques” appear as echolucent plaques with low IBS values using this technique.MethodsWe investigated the echogenicity of carotid plaques using ultrasound with IBS in 286 consecutive CAD patients (71 with ACS and 215 with stable CAD). Coronary plaque complexity was also determined angiographically in stable CAD patients followed up for 30 months or until the occurrence of coronary events.ResultsThe calibrated IBS values of carotid plaques in ACS patients were significantly lower than those in stable CAD patients (p < 0.01). Echolucent carotid plaques accurately predicted the existence of complex coronary plaques (predictive power of 83%). Kaplan-Meier analysis demonstrated a significantly higher probability of coronary events developing in patients with echolucent carotid plaques than in patients without this type of plaque (p < 0.001). The presence of echolucent carotid plaques in stable CAD patients predicted future coronary events independent of other risk factors (odds ratio 7.0, 95% confidence interval 2.3 to 21.4; p < 0.001).ConclusionsEcholucent carotid plaques with low IBS values predicted coronary plaque complexity and the development of future coronary complications in patients with stable CAD. Qualitative evaluation of carotid plaques using ultrasound with IBS is a clinically useful procedure for risk assessment of CAD patients.