Heart failure after myocardial infarction (MI) continues to be the most prevalent cause of morbidity and mortality worldwide. Although pharmaceutical agents and interventional strategies have contributed greatly to therapy, new and superior treatment modalities are urgently needed given the overall disease burden. Stem cell-based therapy is potentially a promising strategy to lead to cardiac repair after MI. An array of cell types has been explored in this respect, including skeletal myoblasts, bone marrow (BM)-derived stem cells, embryonic stem cells, and more recently, cardiac progenitor cells (CPCs). Recently studies have obtained evidence that transplantation of CPCs or BM-derived very small embryonic-like stem cells can improve cardiac function and alleviate cardiac remodeling, supporting the potential therapeutic utility of these cells for cardiac repair. This report summarizes the current data from those studies and discusses the potential implication of these cells in developing clinically-relevant stem cell-based therapeutic strategies for cardiac regeneration. (Circ J 2010; 74: 390 - 404)

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Angiotensin-converting enzyme 2 (ACE2), a first homolog of ACE, regulates the renin-angiotensin system by counterbalancing ACE activity. Accumulating evidence in recent years has demonstrated a physiological and pathological role of ACE2 in the cardiovascular, renal and respiratory systems. For instance, in the acute respiratory distress syndrome (ARDS), ACE, AngII, and AT1R promote the disease pathogenesis, whereas ACE2 and the AT2R protect from ARDS. Importantly, ACE2 has been identified as a key SARS-coronavirus receptor and plays a protective role in SARS pathogenesis. Furthermore, the recent explosion of research into the ACE2 homolog, collectrin, has revealed a new physiological function of ACE2 as an amino acid transporter, which explains the pathogenic role of gene mutations in Hartnup disorder. This review summarizes and discusses the recently unveiled roles for ACE2 in disease pathogenesis. (Circ J 2010; 74: 405 - 410)

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Although the concept of vulnerable plaque has become common, it is still impossible to predict effectively the onset of acute coronary syndrome (ACS). Thin-cap fibroatheroma (TCFA) is regarded as vulnerable from pathological studies and various diagnostic tools have tried to detect TCFA clinically but failed to predict ACS. Because there are so many silent plaque ruptures detected, it is supposed that many vulnerable plaques might have ruptured but not caused ACS. Some factor(s) other than the rupture of vulnerable plaque is required for the onset of ACS. "Vulnerable blood" may be one of them. The thrombogenic potential of blood (ie, vulnerable blood) may play an important and determinant role in the onset of ACS, the process of which will be discussed from the angioscopic point of view. (Circ J 2010; 74: 411 - 417)

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Myocardial infarction (MI) is accompanied by an inflammatory response, leading to the recruitment of leukocytes and subsequent myocardial injury and healing. Chemokines are potent chemoattractant cytokines that regulate leukocyte trafficking in inflammatory processes. Recent evidence indicates that chemokines play a role not only in leukocyte trafficking but also in angiogenesis and cardioprotection. In particular, stromal cell-derived factor-1α (SDF-1α) has generated considerable interest for its role in the pathophysiology of MI. This review will focus on the role of SDF-1 and its receptor CXC chemokine receptor 4 (CXCR4; ie, the SDF-1/CXCR4 system) in the pathophysiology of MI and discuss their potential as therapeutic targets for MI. (Circ J 2010; 74: 418 - 423)

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Background: Atrial tachyarrhythmias (ATA) frequently develop during catheter ablation of atrial fibrillation (AF), but the mechanism of ATA during combined pulmonary vein isolation (PVI) and complex fractionated electrogram-guided ablation (CFEA) has not been reported. Methods and Results: This study involved 105 patients with symptomatic, drug-refractory AF. After PVI, CFEA was performed in the left/right atrium if AF remained inducible in paroxysmal AF (PAF) or persisted in persistent AF (PeAF). For the 70 PAF patients, PVI alone rendered AF non-inducible in 29 patients (41.4%), and converted inducible AF into inducible atrial flutter (AFl) in 10 patients (14.3%). For the remaining 31 PAF patients, additional CFEA rendered AF non-inducible in 11 patients (15.7%), whereas only AFl was inducible in 11 patients (15.7%). For 35 PeAF patients, PVI and CFEA converted AF into sinus rhythm in 2 (5.7%) and into AFl in 21 (60.0%) patients, while AF persisted in 12 patients (34.3%). The mechanism of ATA was focal (20/114, 17.5%), roof-dependent (20/114, 17.5%), peri-mitral (33/114, 28.9%), cavotricuspid isthmus-dependent (34/114, 29.8%) AFl or unknown (7/114, 6.1%). Successful ablation was achieved in 93/114 (81.6%) tachycardias. Conclusions: The major mechanism of ATA during the combined approach of PVI and CFEA is macroreentry around large anatomic obstacles such as the pulmonary vein or the mitral or tricuspid annuli. (Circ J 2010; 74: 434 - 441)

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Background: Despite abciximab-coated stents having an inhibitory effect on coronary artery restenosis, the medium-term clinical outcome is unknown. Methods and Results: This prospective, randomized study compared the effects of the abciximab-coated stent, which was implanted in 95 patients, with those of control bare metal stents (BMS) implanted in 93 patients for de novo coronary lesions. Stent implantation was performed without any complications associated with the procedure. The 6-month intravascular ultrasound analysis showed that the area of neointimal hyperplasia was significantly smaller in the abciximab-coated stent group compared with the control stent group (+2.0±1.6 mm² vs +3.4±1.7 mm², P=0.001). However, at 2-year clinical follow up, there were no statistically significant differences in the incidences of total major adverse cardiac events (16% vs 24%, P=0.19) and cardiac death (0% vs 1.1%, P=0.3), target vessel revascularization (16% vs 21%, P=0.4) or non-fatal myocardial infarction (0% vs 2.3%, P=0.16) in the abciximab-coated stent group compared with the control stent group. Conclusions: Although abciximab-coated stents are safe and inhibit neointimal hyperplasia, they have no superiority over BMS in 2-year clinical outcome. (Circ J 2010; 74: 442 - 448)

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Background: The optimal revascularization strategy for unprotected left main coronary artery (ULMCA) disease in the era of drug-eluting stents (DES) has become more controversial between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). Methods and Results: Since April 2004, 89 patients underwent CABG, including 82 (92.1%) off-pump procedures and 63 patients underwent PCI with DES for ULMCA disease. Major adverse cardiac and cerebrovascular events (MACCE: death, acute myocardial infarction, stroke and repeat revascularization) and hospitalization costs were compared. Patients in the CABG group were likely to have multivessel disease and higher euroSCORE. The mean follow-up was 2.2±1.1 years in the CABG group and 1.6±0.8 years in the DES group (P<0.001). The overall survival rate did not differ (P=0.288) between the groups (CABG: 93.4% and DES: 91.9% at 2 years). The MACCE-free survival rate was better (P=0.033) in the CABG group (CABG: 82.2% and DES: 62.6% at 2 years). Total hospitalization costs were lower (P=0.013) in the CABG group (median: 3,225 thousand yen) than in the DES group (median: 4,192 thousand yen). Conclusions: CABG might be associated with cost-effectiveness and could be still the first revascularization strategy for ULMCA disease. (Circ J 2010; 74: 449 - 455)

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Background: Few prospective studies have explored blood pressure (BP) and other components of the metabolic syndrome (MetS) and their interaction in the development of cardiovascular diseases (CVD) in China. Methods and Results: A prospective study of the prevention of multiple metabolic disorders and MetS in Jiangsu province, China: 3,598 subjects were followed for a median of 6.3 years. The Asian criterion of the National Cholesterol Education Program Adult Treatment Panel III was used to define the MetS. Independent risk of the MetS and its components on developing CVD was analyzed, but only BP was associated with CVD. Incidence and risk of CVD increased with the number of MetS components. A linear association was found between the risk of CVD, BP and the number of other components (trend, P<0.01). The adjusted relative risk of developing CVD was increased when BP and other components coexisted. However, the interaction of BP and other components of MetS was not significant (P>0.05). Conclusions: In Chinese, among the components of MetS BP was an independent risk factor for CVD. No significant interaction was found between BP and the other MetS components. (Circ J 2010; 74: 456 - 461)

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Background: The present study explored the relationship between metabolic syndrome (MetS) and chronic kidney disease (CKD) in patients with coronary artery disease (CAD) in China. Methods and Results: The prevalence of MetS and CKD were determined in 3,465 participants with CAD from the China Heart Survey, from June 1^st to August 31^st 2005. The relationship between MetS and CKD was analyzed. The prevalence of MetS and CKD was 53.0% and 21.1%, respectively. Patients with MetS had a higher prevalence of CKD than those without MetS. All traits of MetS except central obesity were statistically significantly associated with CKD. The multivariate-adjusted odds ratio (OR) of CKD in participants with and without MetS was 1.27 (95% confidence interval (CI) 1.07-1.51). In the multivariate-adjusted model, patients with 3 MetS components, excluding central obesity, had a higher OR for CKD (OR 2.17, 95%CI 1.21-3.88). Conclusions: MetS is a significantly higher risk factor for CKD in patients with CAD. Central obesity might attenuate the effect of MetS on CKD in patients with CKD, regardless of the number of MetS components. (Circ J 2010; 74: 462 - 467)

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Background: Increased oxidative stress might contribute to diabetic (DM) neuropathy, so the effects of long-term treatment with fluvastatin (FL) on myocardial oxidative stress and cardiac sympathetic neural function were investigated in diabetic rats. Methods and Results: FL (10 mg · kg^-1 · day^-1, DM-FL) or vehicle (DM-VE) was orally administered for 2 weeks to streptozotocin-induced DM rats. Cardiac oxidative stress was determined by myocardial 8-iso-prostaglandin F_2α (PGF_2α) and NADPH oxidase subunit p22^phox mRNA expression. Sympathetic neural function was quantified by autoradiography using ¹³¹I- and ¹²⁵I-metaiodobenzylguanidine (MIBG). FL did not affect plasma glucose levels but remarkably decreased PGF_2α levels compared with DM-VE rats (13.8±9.2 vs 175.0±93.9 ng/g tissue), although PGF_2α levels were below the detection limit in non-DM rats. FL significantly reduced myocardial p22^phox mRNA expression. Cardiac ¹³¹I-MIBG uptake was lower in DM-VE rats than in non-DM rats, but the decrease was attenuated in DM-FL rats (1.31±0.08, 1.88±0.22, and 1.58±0.18 %kg dose/g, respectively, P<0.01). Cardiac MIBG clearance was not affected by the induction of DM or by FL, indicating that the reduced MIBG uptake in DM rats might result from impaired neural function. Conclusions: FL ameliorates cardiac sympathetic neural dysfunction in DM rats in association with attenuation of increased myocardial oxidative stress. (Circ J 2010; 74: 468 - 475)

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Background: Delayed enhancement (DE) on cardiac magnetic resonance imaging (CMR) is a marker of myocardial fibrosis. The absence of DE in CMR is a predictor of left ventricular (LV) functional improvement in patients with non-ischemic cardiomyopathy (NICM), so in the present study it was investigated whether presence of DE has prognostic significance in patients with NICM at long-term follow-up. Methods and Results: The 79 patients (56.4±13.5 years, 48 males) with NICM (LV ejection fraction <35%, no significant coronary artery disease) were monitored for occurrence of cardiac events. CMR was performed to assess DE. Cardiac events were defined as rehospitalization (because of worsening of heart failure), cardiac transplantation or death. There were 37 patients without and 42 patients with DE. The mean follow-up duration was 19±10 months. There was 1 event (2.7%, 1 rehospitalization) in the DE (-) group, whereas 13 events (30.9%, 1 death, 1 transplantation, 11 rehospitalizations) occurred in the DE (+) group. The event-free survival was significantly longer in the DE (-) group than in the DE (+) group (38.9±1.0 vs 28.4±2.7 months, P<0.01). Multivariate regression analysis revealed that presence of DE was the most potent, independent predictor of cardiac events (hazard ratio 8.06, confidence interval 1.03±63.41, P<0.05). Conclusions: The presence of DE in CMR is a significant predictor of future cardiac events in patients with NICM. (Circ J 2010; 74: 476 - 483)

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Background: There is little data about the additive effects of ischemia-modified albumin (IMA) on the exercise stress test (EST) used for the screening of ischemic heart disease. The relationship between myocardial ischemic burden and the change in IMA (ΔIMA) during EST was investigated. Methods and Results: EST was performed using the Bruce protocol to evaluate chest pain or exertional dyspnea in 155 patients (men 89, 53±13 years). Blood samples for IMA were obtained before and immediately after EST. According to the EST results and the pattern of ΔIMA, patients were categorized into 3 groups (none was classified as EST(-)/ΔIMA(+)): (1) (EST(-); (2) EST(+)/ΔIMA(-); and (3) EST(+)/ΔIMA(+). After EST, 60 of 155 (38.7%) patients were EST(+) and 14/60 (23.3%) were EST(+)/ΔIMA(+). Duke treadmill score was significantly lower in the EST(+)/ΔIMA(+) group compared with the other groups (-9.0±7.9, -1.7±4.2, 6.7±4.4, respectively, P<0.001); 43/60 (72%) patients with EST(+) underwent coronary angiography and the proportion of patients with a large ischemic burden was higher in the EST(+)/ΔIMA(+)group compared with the EST(+)/ΔIMA(-) group (72.7% vs 15.6%, P=0.001). Conclusions: Increased IMA after EST suggests a large ischemic burden in coronary artery disease, so the ΔIMA during EST may be useful for predicting the severity of myocardial ischemia. (Circ J 2010; 74: 484 - 489)

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Background: The aim of the present study was to explore the association of 3 coronary scores with major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). Methods and Results: The 958 consecutive patients with ACS were followed up until either MACE or 31^st December 2008 occurred; 257 patients reached clinical endpoints. Cox regression analysis demonstrated that the Gensini score was associated with 90-day MACE (relative risk (RR) 1.021, P=0.004), 6-month MACE (RR 1.021, P<0.001), 1-year MACE (RR 1.017, P=0.002), and MACE during follow-up (RR 1.010, P=0.040). Leaman score was associated with 90-day MACE (RR 1.094, P=0.014), 6-month MACE (RR 1.098, P=0.002), and 1-year MACE (RR 1.074, P=0.009). The logistic regression analysis demonstrated that the Gensini score (odds ratio (OR) 1.037, P=0.001), Leaman score (OR 1.165, P=0.007) and American College of Cardiology/American Heart Association (ACC/AHA) score (OR 1.235, P=0.025) were all associated with cardiogenic death. Conclusions: The Gensini score provides more valuable prognostic information on cardiovascular risk than either the Leaman or ACC/AHA score in patients with ACS. (Circ J 2010; 74: 490 - 495)

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Background: According to recent reports, reduced weekend staffing in hospitals may lead to a lower intensity of management of patients with acute conditions such as acute myocardial infarction (AMI). The present study evaluated differences in the case fatality rate of Korean patients admitted with AMI on weekdays vs those admitted on weekends. Methods and Results: The dataset was constructed from the Korea National Health Insurance Claims Database. The study population was 97,466 patients who were admitted to a hospital in Korea from 2003 to 2007 with AMI. Patients admitted on weekends had a higher 30-day fatality rate (20.1% vs 17.3%) than did those admitted on weekdays. Differences in the 30-day fatality rate were significant after adjusting for baseline characteristics and the severity of disease (odds ratio (OR), 1.21; 95% confidence interval (CI), 1.16-1.26). However, the 30-day fatality rate was insignificantly different after additional adjustment for medical or invasive management (OR 1.05; 95%CI 0.99-1.11). Conclusions: Differences in the case fatality rate of AMI patients admitted on weekdays and on weekends in Korea are caused by differences in the rate of performance of medical or invasive procedures. (Circ J 2010; 74: 496 - 502)

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Background: Nicorandil has cardioprotective effects in the ischemic myocardium, mimicking ischemic preconditioning, and is thus expected to improve the prognosis of ischemic heart disease (IHD). As part of the Japanese Coronary Artery Disease (JCAD) Study, a multicenter collaborative prospective observational study of a large cohort of coronary artery disease patients, the effect of nicorandil on outcome was examined. Methods and Results: In total, 2,558 patients with nicorandil treatment and controls subjected to propensity score matching were eligible among 13,812 patients registered in the JCAD study. The mean follow-up interval was 2.7 years. The primary endpoint, death from all causes, was significantly lower, by 35% (hazard ratio 0.65, P=0.0008), in the nicorandil group than in the control group. There were also significant reductions in secondary endpoints, including cardiac death (56%), fatal myocardial infarction (56%), cerebral or vascular death (71%), and congestive heart failure (33%) in the nicorandil group, with no excess of deaths from other non-cardiovascular causes. Treatment with nicorandil reduced the number of deaths from all causes to a similar extent with or without treatment with sulfonylureas. Conclusions: The reduction in cardiovascular death with nicorandil was large in patients with IHD, which has important implications for treatment. (Circ J 2010; 74: 503 - 509)

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Background: Despite the risk of critical heart disease, poor adherence to treatment is common in patients with lifestyle-related diseases such as hypercholesterolemia. The association between adherence to treatment and clinical outcome was examined in JELIS (Japan EPA Lipid Intervention Study) and strategies for avoiding poor adherence were explored. Methods and Results: Patients taking 80% or more of the study medications were considered to exhibit good adherence. The primary endpoint was either sudden cardiac death or myocardial infarction. Adherence was lower in the eicosapentaenoic acid (EPA) + statin group (66.5%) than in the statin alone group (72.5%). In good adherers with previous coronary artery disease, EPA substantially reduced the risk compared with statin alone (hazard ratio 0.55, 95% confidence intervals 0.34-0.88, P<0.014). Furthermore, the clinical benefit of EPA + statin was significantly larger in patients with good adherence than in those with poor adherence (P=0.041). Finally, a 5-year risk prediction model constructed from the data indicated that complete adherence would lead to 51% reduction of risk compared with non-adherence. Conclusions: Good adherence to medication was associated with a lower cardiovascular risk than with poor adherence, and the assistance of a pharmacist is of great importance in achieving persistent adherence during treatment. (Circ J 2010; 74: 510 - 517)

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Background: The association between single nucleotide polymorphisms (SNPs) at 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and low-density lipoprotein-cholesterol (LDL-C) levels has been well replicated in genome-wide association studies (GWAS) of white populations. Recently, the common intronic SNP of HMGCR (rs3846662) has been reported to be a functional variant, influencing the alternative splicing of exon 13. The aim of this study was to examine the association between rs3846662 of HMGCR and the level of LDL-C in Japanese. Methods and Results: Significant differences in LDL-C levels were observed among the genotypes of rs3846662 (P=0.0002 (n=2,686) and P=0.004 (n=2,110)) for the Suita and Ehime samples, respectively. The G allele of rs3846662 was associated with higher LDL-C levels (β, 3.56; P=4.91×10^-5). Consistent with this observation, the risk G allele at rs3846662 was more prevalent in subjects with myocardial infarction (MI) (n=701) than in subjects without MI (n=3,118); 0.559 and 0.511 in MI cases and controls, respectively (nominal P=0.0038). The odds ratio adjusted for age, sex, diabetes, hypertension, and drinking and smoking habits was 1.15 (95% confidence interval 1.04-1.28; P=0.0075). Conclusions: The previously reported association of rs3846662 with LDL-C levels was replicated in the present Suita and Ehime samples. The LDL-associated SNP, rs3846662, appears to confer susceptibility to MI in Japanese. (Circ J 2010; 74: 518 - 522)

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Background: Lipocalin-2/neutrophil gelatinase-B associated lipocalin (Lcn2/NGAL) is involved in the transport of iron and seems to play an important role in inflammation. A recent study has reported that it is also expressed in the failing heart and may be a biomarker not only for renal failure but also for heart failure. Because Lcn2/NGAL is thought to be induced by interleukin-1, it might be strongly induced in the presence of myocarditis. Methods and Results: This study investigated the expression of Lcn2/NGAL in rat experimental autoimmune myocarditis (EAM) and in human myocarditis. In EAM hearts, the expression of Lcn2/NGAL was markedly increased (>100-fold at an early stage), and in human myocarditis it was also highly expressed compared with non-inflammatory failing hearts. Lcn2/NGAL expressing cells in hearts with EAM and human myocarditis were identified as cardiomyocytes, vascular wall cells, fibroblasts and neutrophils. Lcn2/NGAL in EAM rats was also expressed in the liver. Plasma Lcn2/NGAL levels abruptly increased at an early stage of EAM, and high levels were initially sustained during the inflammatory stage, then decreased with recovery. In contrast, levels of B-type natriuretic peptide increased only slowly as the disease progressed. Conclusions: Cardiomyocytes, vascular wall cells and fibroblasts in myocarditis strongly express Lcn2/NGAL via proinflammatory cytokines. (Circ J 2010; 74: 523 - 530)

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Background: Increased maximal left ventricular wall thickness (LVWT; >30 mm) is a marker of risk for sudden cardiac death in hypertrophic cardiomyopathy (HCM). Patients with mild left ventricular hypertrophy (LVH) are not free of events. Regional heterogeneity of LVH may contribute to arrhythmic vulnerability. Methods and Results: 157 HCM patients underwent assessment of maximal and regional LVWT by 2-dimensional echocardiography, and arrhythmic burden in a follow-up of a median 3.7 years. 45 patients with ventricular arrhythmic events (VAEs+ group) had larger maximal LVWT and regional LVWTs (basal anterior-B12 and equatorial inferior-EQ6 segments, P=0.05). Maximal LVWT and B12 above a cut-off value of 15 mm were associated with a significant 4.5-fold (95% confidence interval (CI) 1.1-18.8, P=0.04), 3.2-fold (95%CI 1.5-6.7, P<0.002), and EQ6 above 19 mm with 5.9-fold (95%CI 2.0-16.9, P<0.001) increased the relative risk of VAEs. Multivariate analysis identified the 2 regional measures as the only predictors, independently associated with arrhythmic risk. Conclusions: Non-invasive imaging measures, such as LVWT, do have a role in identifying the patients at risk of VAEs. In addition to maximal LVWT, the key regional LVWTs provide complementary information of incremental value to the conventional risk stratification model. (Circ J 2010; 74: 531 - 537)

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Background: Myocardial bridge (MB) is regarded as a common benign lesion on coronary angiography (CAG). It is known to be harmless but may cause several cardiac events and recurrent hospitalization, so in the present study the long-term clinical course of patients with isolated MB and predictors of readmission were investigated. Methods and Results: Total 684 patients (343 males, 60.5±11.2 years) with persistent chest pain without critical stenosis on CAG were enrolled. The patients were divided into 2 groups according to the presence of MB. Clinical follow-up was performed with respect to readmission after baseline CAG. At a mean follow-up of 37 months, 92 patients (13.3%) were re-admitted because of 79 recurrent chest pain refractory to medication (11.5%), 8 myocardial infarctions (1.2%), 1 life-threatening arrhythmia (0.1%) and 4 deaths (0.6%). There was a significant higher incidence of readmission in the MB group (P=0.038). In multivariate analysis, long MB (hazard ratio (HR) 2.780; 95% confidence interval (CI) 1.070-7.218, P=0.036) and spontaneous vasospasm in CAG (HR 2.335; 95%CI 1.055-5.171, P=0.037) were the predictors of readmission. Moreover, additional use of aspirin or statin decreased the readmission rate. Conclusions: This study suggests that MB on non-occlusive CAG is not benign and may cause recurrent chest pain, myocardial infarction or life-threatening arrhythmia. Especially, patients with a long MB and vasospasm on CAG need intensive medical therapy, including antiplatelet treatment. (Circ J 2010; 74: 538 - 543)

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Background: Approximately 8-38% of children with Kawasaki disease (KD) will have persistent or recrudescent fever after initial intravenous immunoglobulin (IVIG) treatment and are at increased risk for development of coronary artery abnormalities. Using genetic markers may be helpful to identify the high-risk group of IVIG-resistant patients for aggressive treatment. The aim of this study was to evaluate the associations between 4 potential polymorphisms in the interleukin (IL)-1 family of genes and initial IVIG treatment failure in KD children. Methods and Results: A total of 156 KD children (136 with and 20 without a response to IVIG treatment) who were treated with high-dose IVIG (2 g/kg) within 10 days of fever onset were recruited. Polymerase chain reaction and Taqman assays were used for genotyping. A significant increase in IVIG resistance risk was observed for IL-1B -511 TT and IL-1B -31 CC genotypes (adjusted odds ratio (AOR) 5.27, 95% confidence interval (CI) 1.69-16.38, P=0.004; AOR 3.95, 95%CI 1.26-12.41, P=0.019, separately). The diplotype TC/TC (at IL-1B -511 and -31) also showed a significantly increased risk of IVIG resistance (AOR 4.32, 95%CI 1.36-13.71, P=0.013). Conclusions: The IL-1B -511 TT and IL-1B -31 CC genotypes or the TC/TC diplotype may be associated with initial IVIG treatment failure in Taiwanese children with KD. (Circ J 2010; 74: 544 - 551)

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Background: Although adiponectin has been implicated as an antiinflammatory factor in atherosclerotic lesion development, little is known about its role in advanced atherosclerotic plaque. This study assessed the effect and mechanism of adiponectin on the expression of prolyl 4-hydroxylase (P4H) α1 and its role in the stability of preexisting plaque. Methods and Results: Atherosclerotic lesions in the carotid arteries of apolipoprotein E-deficient mice were induced by the placement of a perivascular collar. Six weeks after surgery, 120 mice were divided into phosphate-buffered saline (PBS) (n=40), empty adenovirus (Ad.Empty) (n=40) and adiponectin adenovirus (Ad.Adipo) groups (n=40). The number of vulnerable lesions were lower with Ad.Adipo than with Ad.Empty transfection. Mean cap thickness, cap area, cap-to-core ratio and intimal collagen content were all greater with Ad.Adipo than with Ad.Empty transfection; however, the groups did not differ in plaque area or intima-media thickness. Plasma adiponectin level positively correlated with intimal collagen content. Adiponectin transfection conferred enhanced expression of P4H, with no changes in the PBS and Ad.Empty groups. Conclusions: Adiponectin increases collagen production by inducing the expression of P4H, which may play a major role in the development of the thick fibrous cap of advanced atherosclerotic plaque. (Circ J 2010; 74: 552 - 559)

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Background: Few studies have reported on the relationship between metabolic syndrome (MetS) and carotid artery structure. The objective of this study was to examine the relationship between MetS and carotid artery parameters such as the common carotid artery intima-media thickness (CCA-IMT), plaques, and the diameter of the common carotid artery (CCAd). Methods and Results: The study population consisted of 1.730 community-dwelling Koreans aged 50 years and older without hypertension, diabetes mellitus or dyslipidemia. MetS was defined according to the modified National Cholesterol Education Program's Adult Treatment Panel III criteria. The risk for abnormal CCA-IMT (≥1.00 mm) was significant in women with MetS (odds ratio (OR) 2.22; 95% confidence interval (CI) 1.14-4.31), but not in men with MetS (OR 1.06; 95%CI 0.39-2.91). No significant relationship between MetS and carotid plaques was observed in either sex. The relationship between MetS and high CCAd (highest quintile) was significant in both men (OR 2.19; 95%CI 1.38-3.49) and women (OR 2.02; 95%CI 1.39-2.94). Conclusions: MetS independently correlates with carotid atherosclerosis and carotid enlargement. The effect of MetS on carotid atherosclerosis is more pronounced in women than in men. (Circ J 2010; 74: 560 - 566)

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Background: Calcium channel blockers (CCB) are known to modulate immune reactions, so the present study was performed to examine the effects of various CCBs that have shown different effects on transcription factors and on the production of pro-inflammatory cytokines by human peripheral blood mononuclear cells (PBMC). Methods and Results: PBMC from healthy volunteers were isolated by Ficoll-paque density centrifugation. To study the effect of CCBs, the PBMC were stimulated with lipopolysaccharide or concanavalin A. After 24 h of incubation, the supernatants were harvested and the interleukin (IL)-1α, -1β, and -6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ levels were determined by specific enzyme-linked immunosorbent assay. The production of IL-1α and -1β stimulated with lipopolysaccharide was significantly increased in the presence of amlodipine. In contrast, nifedipine and verapamil suppressed the production of IL-1β, TNF-α, and IFN-γ. Amlodipine and diltiazem significantly increased production of IL-1α stimulated with concanavalin A. Nifedipine inhibited production of IL-1α, IL-6, and IFN-γ. Verapamil suppressed production of IFN-γ. Conclusions: Differential modulation of cytokine production was seen with various CCBs, and the suppressive effect of nifedipine was most prominent. (Circ J 2010; 74: 567 - 571)

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Background: The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors closely linked to inflammation and insulin resistance (IR). Tissue factor (TF) is an initiator of the extrinsic coagulation cascade and is expressed on peripheral blood monocytes and macrophages in atherosclerotic plaques. Monocytes are the principle cells capable of TF synthesis. Therefore, TF plays an important role in both thrombosis and atherosclerosis. Elevated levels of lipopolysaccharide (LPS), a strong stimulator of TF, have been observed in patients with MetS. No study has investigated the relationship between monocyte TF activity and inflammation, and IR in MetS. Methods and Results: Peripheral blood mononuclear cells (PBMCs) were collected from 40 normal subjects and 77 patients with MetS. Mononuclear cell TF procoagulant activity (MPCA) was measured with and without 100 pg/ml LPS stimulation using a 1-stage clotting assay and expressed as the mean ± SD (mU TF/10⁶ PBMCs). MPCA in MetS was significantly greater than in normal subjects (without LPS: 88.0±74.8 vs 52.6±9.8 mU TF/10⁶ PBMCs, P<0.001; with LPS: 269.6±165.6 vs 158.6±42.8 mU TF/10⁶ PBMCs, P<0.001). The LPS-stimulated log MPCA in MetS patients was significantly associated with homeostasis model assessment of IR (r=0.256, P=0.024) and log high-sensitivity C-reactive protein (r=0.332, P=0.003). Conclusions: Upregulation of monocyte TF is significantly associated with low-grade inflammation and IR in MetS. (Circ J 2010; 74: 572 - 577)

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Background: Because green tea reduces cardiovascular and cerebrovascular risk, the purpose of this study aimed to elucidate the effect of green tea catechins (GTC) on endothelial dysfunction in smokers. Methods and Results: The 30 healthy male smokers were divided into 3 groups and given green tea beverages containing 0 mg (control group), 80 mg (medium-dose group) or 580 mg (high-dose group) of GTC daily for 2 weeks. Endothelial-dependent and- independent vasodilatation was investigated by measuring the forearm blood flow (FBF) responses to acetylcholine and sodium nitroprusside using venous occlusion strain-gauge plethysmography. The FBF response to acetylcholine significantly increased at 2 h and 1 and 2 weeks after GTC intake in the high-dose group, but no increase was observed in the other groups. FBF responses to sodium nitroprusside did not alter in any group at any time point. A significant increase in plasma nitric oxide and a decrease in asymmetrical dimethylarginine, malondealdehyde and 4-hydroxynonenal, C-reactive protein, monocyte chemotactic protein-1, and soluble CD40 ligand levels were detected after chronic consumption of high-dose GTC. Conclusions: GTC have antiatherosclerotic effects on dysfunctional vessels in smokers through increasing the level of nitric oxide and reducing oxidative stress. (Circ J 2010; 74: 578 - 588)

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Background: Low-energy shock wave (SW) therapy has improved myocardial ischemia in both a porcine model and in patients with severe angina pectoris. Methods and Results: To further confirm the effectiveness and safety of SW therapy, 8 patients with severe angina pectoris were treated with SW therapy in a double-blind, placebo-controlled and cross-over manner. SW therapy, but not placebo, significantly improved chest pain symptoms and cardiac function without any complications or adverse effects. Conclusions: Extracorporeal cardiac SW therapy is an effective, safe and non-invasive therapeutic option for severe angina pectoris. (Circ J 2010; 74: 589 - 591)

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