Emerging evidence is revealing the different roles of steady laminar flow (s-flow) and disturbed flow (d-flow) in the regulation of the vascular endothelium. s-flow is atheroprotective while d-flow creates an atheroprone environment. Most recently, we found unique atheroprone signals, which involve protein kinase C (PKC)ζ activation, elicited by d-flow. We and others have defined a novel role for PKCζ as a shared mediator for tumor necrosis factor alpha (TNF alpha) and d-flow, which cause pro-inflammatory and pro-apoptotic events in endothelial cells (ECs) in the atheroprone environment. Under such conditions, ONOO^- formation is increased in a d-flow-mediated PKCζ-dependent manner. Here, we propose a new signaling pathway involving d-flow-induced EC inflammation via PKCζ-ERK5 interaction-mediated downregulation of KLF2/eNOS stability, which leads to PKCζ-mediated p53-SUMOylation and EC apoptosis. In addition, we highlight several mechanisms contributing to endothelial dysfunction, focusing on the relations bet-ween flow patterns and activation of reactive oxygen species generating enzymes. (Circ J 2011; 75: 2722-2730)

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Untreated acute pulmonary thromboembolism (APTE) is associated with high mortality, which is reduced by prompt treatment. Anticoagulation is fundamental in the treatment of APTE and should be initiated from suspicion. The efficacy and safety of novel anticoagulant drugs, such as oral anti-Xa and anti-IIa inhibitors, are topics in the treatment of APTE and are now under investigation. Thrombolytic therapy is a widely accepted treatment strategy for massive APTE, but its use for submassive APTE is controversial. Catheter intervention, percutaneous cardiopulmonary support and surgical embolectomy are also necessary and effective for some patients with APTE. A retrievable inferior vena cava filter is preferred for transient protection against APTE. Some studies have demonstrated the feasibility of outpatient treatment in patients with APTE after risk stratification. (Circ J 2011; 75: 2731-2738)

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Chronic inflammation appears to underlie most, if not all, the chronic diseases of today, including cardiovascular disease, type 2 diabetes, chronic kidney disease, Alzheimer's disease and cancer. We have demonstrated that obesity induces chronic local inflammation in adipose tissue. We also found that chronic inflammation is crucially involved in the development of heart failure and chronic kidney disease. In this article, I review recent findings reported by my group and others regarding the mechanisms underlying the chronic inflammatory processes commonly observed in adipose tissue, heart and kidney. I then discuss the key features of the chronic inflammation seen in chronic diseases. (Circ J 2011; 75: 2739-2748)

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Background: Dyslipidemia, an important risk factor for cardiovascular disease, may be associated with atrial fibrillation (AF). Cross-sectional studies that have examined this association, however, have produced controversial results, and few longitudinal studies have been conducted. Methods and Results: Using annual health examinations in Japan, the association between lipid profile and the risk of new-onset AF was investigated in the general population. A total of 28,449 individuals who did not have AF at baseline were included in the study. During a follow-up of 4.5±2.7 years, 265 individuals (0.9%) developed AF. In multivariate models, low high-density lipoprotein (HDL) cholesterol was associated with the development of AF in women (hazard ratio [HR], 2.86; 95% confidence interval [CI]: 1.49-5.50) but not in men (HR, 1.35; 95%CI: 0.77-2.38). Women had a 28% higher risk of AF with each 10% decrease in HDL cholesterol. Neither triglycerides nor lipid ratios were associated with AF. After excluding individuals with risk factors for AF, including those who were taking anti-hypertensive drugs, had diabetes, and structural heart disease, the association between low HDL cholesterol and AF remained significant in women. Conclusions: Low HDL cholesterol was associated with an increased risk of new-onset AF in women, but not in men. (Circ J 2011; 75: 2767-2774)

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Background: The aim of the present study was to characterize the heart rate dynamics of sinus bradycardia (SB) from sinus node dysfunction (SND) using non-linear dynamical system analysis. No data are yet available on how the dynamics change in the presence of SND. Methods and Results: Conventional time and frequency domain analysis, the short- (DFAα₁) and intermediate-term fractal scaling exponent (DFAα₂), approximate entropy (ApEn) and sample entropy (SampEn) were calculated in 60-min sinus RR interval data of SB from 24-h ambulatory electrocardiograms of 110 patients: 44 SND patients, 44 age-matched controls, and 22 younger controls. All of the time and frequency domain parameters, ApEn and SampEn, were significantly reduced in the age-matched control group, compared with the young control group. DFAα₁ and DFAα₂ increased with aging. Both the DFAα₁ and DFAα₂ of SND patients were paradoxically reduced, which was not appropriate for their age. Only the percentage of consecutive RR intervals with absolute differences >50ms (pNN₅₀), low-frequency power, and DFAα₂ made a significant contribution to prediction of SND on logistic regression analysis. Among them, DFAα₂ was the most significant variable for prediction of SND (odds ratio, 0.927; 95% confidence interval: 0.888-0.969, P=0.001). DFAα₂ remained as a significant variable for prediction of SND, when compared with overall control patients, combining the 2 control groups. Conclusions: Inappropriate reduction of DFAα₂ is a robust measure and could be an adjunctive tool for improvement of diagnostic performance in detection of SND. (Circ J 2011; 75: 2775-2780)

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Background: Atrial structural remodeling is increasingly emphasized in initiation and perpetuation of atrial fibrillation (AF). Osteoprotegerin (OPG)/receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL) axis, a key regulatory system in bone homeostasis, was recently linked to some cardiovascular disorders for its regulatory functions to myocardial remodeling. It was hypothesized that OPG/RANK/RANKL axis is involved in the development and progression of AF by regulating atrial structural remodeling. Methods and Results: Clinical data, and biopsies of right atrial appendage were collected from sex- and age-matched subjects: 24 persistent AF patients, 24 paroxysmal AF patients, 24 sinus rhythm patients undergoing isolated mitral valve surgery and 24 healthy heart donors. AF groups had higher atrial gene expression of OPG/RANK/RANKL axis and RANKL/OPG ratio, particularly in paroxysmal AF. This upregulated expression and activity were positively correlated with higher regulatory indicators of atrial structural remodeling as reflected by higher transcripts of tumor necrosis factor (TNF)-related apoptosis-inducing ligand, matrix metalloproteinase (MMP)-2 and MMP-9, pro-inflammatory factors TNF-α and interleukin-6, and higher ratios of MMP-9/tissue inhibitor of metalloproteinase (TIMP)-1 and MMP-2/TIMP-2 in AF. Conclusions: The present findings suggest a potential role for known mediators of bone metabolism in the development and progression of AF and possibly represent new targets for therapeutic intervention in this disorder. (Circ J 2011; 75: 2781-2788)

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Background: A prospective observational study using optical coherence tomography (OCT) of patients with myocardial infarction (MI), late following drug-eluting (DES) or bare metal stent (BMS) implantation, when the stented segment was considered culprit. Methods and Results: Seventeen patients (58.9±8.3 years; 7 DES, 10 BMS) with MI at 50 (3-180) months post-stenting. Patients with BMS sustained a MI later than patients with DES (95 (3-180) vs. 8 (3-62) months, P=0.01]; 5 (71.4%) of the DES patients demonstrated binary angiographic restenosis, in contrast to 8 (80%) with BMS (P=1.0). DES had significantly less thickness of the neointimal hyperplasia compared with BMS (0.08±0.04 vs. 0.36±0.2mm, P=0.003). None of the DES was totally covered with neointimal tissue. The overall percentage of uncovered and malapposed struts (ANCOVA), was significantly higher in DES than BMS (1.96, 95% confidence interval (CI) 1.5-2.4 vs. 0.25, 95%CI 0.1-0.6, P<0.001, and 0.66, 95%CI 0.29-1.03 vs. 0.11, 95%CI 0.19-0.4, P=0.03, respectively). OCT features of atherosclerosis (lipid, neovascularization, or calcification) and possible neointimal rupture were found only in patients with BMS. Thrombus detection was not different between the 2 groups. Conclusions: Stent-related, non-fatal, late acute MI following stent implantation occurs later in patients with a BMS compared with those with a DES, and the mechanism includes delayed healing (mainly DES), and neointimal hyperplasia with atherosclerotic transformation and subsequent rupture (mainly BMS). (Circ J 2011; 75: 2789-2797)

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Background: Patients with chronic kidney disease have had conflicting results between drug-eluting stents (DES) and bare-metal stents (BMS). The aim of the present study was to determine whether DES is preferable for the treatment of acute myocardial infarction (AMI) with renal insufficiency, and to elucidate the impact of diabetes mellitus (DM) on outcomes of each stent. Methods and Results: As a part of the Korea Acute Myocardial Infarction Registry (KAMIR), 2,175 AMI patients with renal insufficiency (glomerular filtration rate <60ml/min) comprising 208 patients with BMS and 1,967 DES implantation were selected. Primary outcome was major adverse cardiac event (MACE), defined as a composite of mortality, nonfatal myocardial infarction, and target lesion revascularization. In the overall population, the MACE rate at 1 year was significantly higher in the BMS group than that of DES (44% vs. 26%, P<0.05), which was mainly due to death rather than repeat intervention (44% vs. 26%, P<0.05). In the diabetic group with DES implantation, the MACE rate was higher compared with the DES group without DM, mainly due to repeat intervention (5% vs. 8%, P<0.05). Conclusions: In AMI patients with renal insufficiency, DES implantation exhibits a favorable 1-year clinical outcome than BMS implantation, and subgroup analysis for diabetic subjects showed worse outcomes in the DM group with implanted DES. (Circ J 2011; 75: 2798-2804)

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Background: The optimal time delay between last clopidogrel dose and surgery is controversial. The aim of the present study was to analyze the impact of preoperative clopidogrel on the need for blood transfusions with reference to the proper timing of discontinuation. Methods and Results: Between January 2005 and December 2010, 1,947 consecutive patients undergoing coronary surgery were enrolled. Of these, 255 patients receiving preoperative clopidogrel were matched to a control group by propensity score analysis. Clopidogrel discontinuation interval before surgery was examined in 1-day increments from 0 to 5 days and >5 days. Patients who discontinued clopidogrel within 5 days of surgery accounted for 91% (211/255). Clopidogrel stop within 5 days before surgery was independently associated with transfusion requirement (P=0.001). Preoperative clopidogrel was not associated with an increased risk of hemorrhagic complications (P=0.696). No differences were observed between patients taking clopidogrel and those not taking clopidogrel with regard to hospital resource utilization and mortality. Patients receiving clopidogrel in association with aspirin did not have an additive risk for transfusion or hemorrhagic complications compared with those on clopidogrel alone (odds ratio [OR], 1.25; 95% confidence interval [CI]: 0.77-2.03; OR, 1.02; 95%CI: 0.38-2.79, respectively). Conclusions: Clopidogrel administration in the 5 days preceding coronary surgery was an independent predictor for increased transfusion requirements, supporting the discontinuation of clopidogrel >5 days before surgery. (Circ J 2011; 75: 2805-2812)

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Background: The aim of the present study was to evaluate the diagnostic accuracy of high-sensitivity troponin T (hsTnT) in patients with suspected acute coronary syndrome (ACS) in comparison to heart fatty acid-binding protein (H-FABP), high-sensitivity C-reactive protein, myeloperoxidase (MPO), and pentraxin 3 (PTX3). Methods and Results: Patients (n=432) with chest pain were recruited for the analysis. ACS was diagnosed in 298 patients (69%). The diagnostic accuracy of measurements obtained at presentation, as quantified by the area under the receiver operating curve (AUC), was highest for hsTnT (AUC=0.82; 95% confidence interval [CI]: 0.78-0.87) and H-FABP (AUC=0.83; 95%CI: 0.78-0.87). Sensitivity (87.9%) and negative likelihood (LH; 0.2) for hsTnT were the highest and lowest, respectively, but H-FABP had the highest specificity (78.5%) and positive LH (3.6). Among patients who presented within 2h after the onset of chest pain, MPO had the highest AUC (0.82; 95%CI: 0.69-0.94). Combined use of H-FABP and MPO measurements yielded a sensitivity of 69.2%, specificity of 84.2%, positive LH of 4.4, and negative LH of 0.4. Conclusions: The hsTnT assay offers excellent diagnostic performance to rule out ACS, but it is prone to false-positive results. H-FABP offers similar overall diagnostic performance, while the combination of H-FABP and MPO assays may improve the diagnosis of ACS, particularly in patients with recent onset of chest pain. (Circ J 2011; 75: 2813-2820)

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Background: Detailed characteristics of those who experience an out-of-hospital cardiac arrest (OHCA) with public-access defibrillation (PAD) are unknown. Methods and Results: A prospective, population-based observational study involving consecutive OHCA patients with emergency responder resuscitation attempts was conducted from July 1, 2004 through December 31, 2008 in Osaka City. We extracted data for OHCA patients shocked by a public-access automated external defibrillator (AED) and evaluated the patients' and rescuers' characteristics. The main outcome measure was neurologically favorable 1-month survival. During the study period, 10,375 OHCA patients were registered and of 908 patients suffering ventricular fibrillation arrest, 53 (6%) received public-access AED shocks by lay-rescuers, with the proportion increasing from 0% in 2004 to 11% in 2008 (P for trend<0.001). Railway stations (34%) were the places where PAD shocks were most frequently delivered, followed by nursing homes (11%), medical facilities (9%), and fitness facilities (7%). In 57% of cases, the subject received public-access AED shocks delivered by non-medical persons, including employees of railway companies (13%), school teachers (6%), employees of fitness facilities (6%), and security guards (6%). The proportion of neurologically favorable 1-month survival tended to increase from 0% in 2005 to 58% in 2008 (P for trend=0.081). Conclusions: Railway stations are the most common places where shocks by public-access AEDs were delivered in large urban communities of Japan, and among lay-rescuers railway station workers use AEDs more frequently. (Circ J 2011; 75: 2821-2826)

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Background: It has been reported that elevated levels of serum uric acid are related to hypertension and cardiovascular disease. Recent studies, however, have found little association between hyperuricemia and hypertension. Methods and Results: The association of serum uric acid with blood pressure was examined in 3,960 Japanese male workers (18-64 years of age; mean age, 42.3±0.2 years). Systolic blood pressure was significantly correlated with serum uric acid. Multiple regression analysis also showed that both systolic and diastolic blood pressures were independently associated with serum uric acid. When subjects were divided into 6 groups according to blood pressure on the basis of the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009), serum uric acid was elevated in a linear fashion as blood pressure increased. A similar relationship was found even in 3,608 subjects who were not taking anti-hypertensive or uric acid-lowering agents. In contrast, no relation was found between serum uric acid and blood pressure in 352 subjects taking anti-hypertensive medicine. Conclusions: Blood pressure is closely associated with serum uric acid. Serum uric acid might be associated with the increase in blood pressure, because there is no relation between serum uric acid and blood pressure in the subjects treated with anti-hypertensive medications. (Circ J 2011; 75: 2827-2832)

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Background: Diabetes mellitus (DM) is a risk factor of poor prognosis in patients with heart failure (HF). The prevalence and prognostic impact of the pre-diabetic state, however, are not well understood. Methods and Results: One hundred and thirty-six consecutive patients admitted due to HF were included in this prospective study. The 75-g oral glucose tolerance test (OGTT) was performed in all patients without known DM, and patients were classified into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and DM groups. Forty-two of the 136 patients had previously been diagnosed with diabetes. Of the remaining 94 patients without known diabetes, 35 (37.2%) patients were classified as NGT, 9 (9.6%) as having IFG, 37 (39.4%) were classified as having IGT, and 13 (13.8%) were newly diagnosed with DM. During follow-up, patients with DM or IGT had significantly lower major adverse cardiac and cerebrovascular event (MACCE)-free rates than NGT patients (P=0.006, P=0.036, respectively). IFG, however, was not significantly related to increased MACCE risk. The presence of IGT (hazard ratio [HR], 4.51; P=0.011) and DM (HR, 4.74; P=0.005) were independent predictors of MACCE even after multivariate analysis. Conclusions: IGT and DM contribute to adverse prognosis in patients with HF. It is feasible to perform diabetes screening using OGTT in patients with HF for risk stratification. (Circ J 2011; 75: 2833-2839)

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Background: The purpose of the present study was to investigate gender differences in age-related changes of left ventricular (LV) and right ventricular (RV) geometries and functions throughout the entire adult age range using the Japanese Normal Values for Echocardiographic Measurements Project (JAMP) study database. Methods and Results: Seven hundred healthy volunteers (aged 20-79 years) underwent 2-dimensional and Doppler echocardiography. The subjects were stratified into 6 different age groups and then stratified by gender in each age group. LV diastolic function was assessed from pulsed wave Doppler measurements of mitral early (E) and late (A) inflow velocities and tissue Doppler measurements of mitral early (e') and late (a') annular velocities. LV volume decreased and LV mass increased with age to a similar extent in both men and women. Furthermore, for subjects <50 years, women had significantly greater E, E/A ratio and e' than men, but these parameters were similar between genders in subjects >50 years. In addition, there was a significant interaction between age and gender that affected the differences in E, e' and E/e' among the groups (P<0.03, P<0.01, and P<0.03, respectively; ANOVA). There were no gender differences in age-related changes in RV parameters. Conclusions: Gender differences were found in age-related changes in LV diastolic function in a healthy population. Gender differences should be considered for optimal diagnosis and management of cardiovascular disease. (Circ J 2011; 75: 2840-2846)

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Background: The serum lipoprotein (a) [Lp(a)] level is genetically determined and remains consistent during a person's life. Previous cohort studies have reported that subjects with a high Lp(a) level are at high risk of cardiac events. Methods and Results: This study consisted of 410 patients who underwent primary percutaneous coronary intervention within 24h of the onset of acute myocardial infarction (AMI). Lp(a) was measured 1 week after AMI and patients were divided into 2 groups based: high Lp(a) group (>40mg/dl, n=95) and low Lp(a) group (≤40mg/dl, n=315). A major adverse cardiac event (MACE) was defined as cardiac death, myocardial infarction and/or revascularization for new lesions. The incidence of MACE during 5 years was significantly higher in the high Lp(a) group than in the low Lp(a) group (34.7% vs. 16.5%, P<0.001). This difference was primarily driven by a higher incidence of new lesions requiring revascularization in the high Lp(a) group (31.6% vs. 15.2%, P<0.001). Multivariate analysis showed that Lp(a) was an independent predictor for MACE (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.31-2.06, P<0.001) and revascularization of a new lesion (OR 1.61, 95%CI 1.32-2.13, P<0.001). Conclusions: Lp(a) levels could predict the progression of the non-culprit coronary lesions after AMI. (Circ J 2011; 75: 2847-2852)

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Background: Matrix metalloproteinase-9 (MMP-9) is regarded as a biomarker of plaque rupture or vulnerability and is elevated in patients with acute coronary syndrome (ACS). The aim of the present study was to evaluate the diagnostic value of MMP-9 for early ACS (≤4h of onset) and late ACS (>4h after onset), compared with high-sensitivity troponin T (hs-TnT). Methods and Results: MMP-9 and hs-TnT were measured in 200 patients with ST elevation ACS (STEACS; 115 early STEACS and 85 late STEACS patients), and 66 patients with non-ST elevation ACS (NSTEACS; 25 early NSTEACS and 41 late NSTEACS patients). Forty patients with stable angina pectoris (SAP) were enrolled as a control group. MMP-9 levels were significantly higher in patients with early STEACS (P<0.001), early NSTEACS (P<0.001), late STEACS (P<0.001) and late NSTEACS (P=0.025) than SAP. MMP-9 levels were significantly higher in patients with early STEACS (P=0.017) and early NSTEACS (P=0.034) than late STEACS and late NSTEACS, respectively. Levels of hs-TnT were significantly lower in patients with early STEACS (P<0.001) and early NSTEACS (P=0.007) than late STEACS and late NSTEACS, respectively. On receiver operating characteristic curve analysis, area under the curve of early STEACS, early NSTEACS, late STEACS and late NSTEACS was 0.880, 0.782, 0.790 and 0.648 for MMP-9, and 0.707, 0.725, 0.993 and 0.920 for hs-TnT, respectively. Conclusions: MMP-9 levels were elevated earlier than hs-TnT and had a higher diagnostic value for early ACS, but not for late ACS, reflecting plaque rupture or vulnerability. (Circ J 2011; 75: 2853-2861)

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Background: Although highly sensitive assays for troponin T (hs-TnT) have been developed, the sensitivity and specificity of hs-TnT for diagnosing acute coronary syndrome (ACS) remains imperfect. We evaluated the diagnostic value of a new biomarker of plaque vulnerability (soluble lectin-like oxidized low-density lipoprotein receptor-1, sLOX-1) as compared with hs-TnT in the emergency room (ER). Methods and Results: Plasma sLOX-1 and serum hs-TnT levels were measured in 200 consecutive patients presenting with chest symptoms and ECG abnormalities in the ER (116 ST elevation ACS [STEACS], 44 non-ST elevation ACS [NSTEACS], 40 non-ACS). The non-ACS group consisted of patients with cardiovascular diseases such as coronary spastic angina pectoris, pulmonary thromboembolism, perimyocarditis and takotsubo cardiomyopathy. Levels of sLOX-1 and hs-TnT were significantly higher in STEACS and NSTEACS than in non-ACS patients. The receiver-operating characteristic (ROC) curves of sLOX-1 and hs-TnT for detecting ACS, using the non-ACS patients as negative references, showed that the area under the curve (AUC) values of sLOX-1 and hs-TnT were 0.769 and 0.739, respectively. In the lower hs-TnT (<0.0205ng/ml) subgroup, the AUC value of the ROC curve of sLOX-1 for detecting ACS was 0.869. Conclusions: The diagnostic value for ACS was comparable between sLOX-1 and hs-TnT, and the accuracy of ACS diagnosis appeared to improve when sLOX-1 and hs-TnT were measured in combination. (Circ J 2011; 75: 2862-2871)

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Background: Several cases of horseshoe kidney with anomalous inferior vena cava (IVC) have been described, but there have been no reports of the incidence and variation of anomalous IVC in patients with horseshoe kidneys detected using multidetector row computed tomography (MDCT). Methods and Results: 105 patients with horseshoe kidneys were evaluated with MDCT and a variety of venous anomalies were identified in 30 patients (28.6%). Anatomical variations of the renal vein were identified in 24 patients (22.9%), which was no higher than the reported incidence in the general population. However, variations of the IVC were identified in 6 patients (5.7%), which was a higher incidence than expected to be found in the general population: 1 pre-isthmic IVC with retrocaval ureter, 2 double IVCs posterior to the horseshoe kidney, 2 left IVCs posterior to the horseshoe kidney, and 1 azygos continuation of the IVC. Conclusions: Horseshoe kidneys are frequently found in patients with other venous, and particularly IVC, anomalies, which should be evaluated using MDCT as part of treatment planning. (Circ J 2011; 75: 2872-2877)

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Background: The purpose of this study was to investigate the association between depression symptoms 1 year after onset and subsequent cardiovascular events among survivors of myocardial infarction (MI). Methods and Results: The participants were recruited from respondents to a district-based survey known as the Osaka Acute Coronary Insufficiency Study. Of 4,271 eligible MI patients, 1,951 completed the Zung Self-Rating Depression Scale (SDS) at their 1-year follow-up examination. After excluding patients who experienced cardiovascular events within 1 year, the data for the remaining 1,307 male patients and 280 female patients were analyzed. Among male patients, depression status at 1 year after onset of MI was significantly related to risk of subsequent cardiovascular events throughout the follow-up period (median 2.9 years). The male patients in the top vs. bottom tertiles of SDS scores (top tertile being ≥42) had a multivariable-adjusted hazard ratio (HR) of 1.67 (95% confidence interval (CI) 1.01-2.77, P=0.04), and a 1-SD increment in SDS score was significantly related to a heightened risk of cardiovascular events, with a multivariable-adjusted HR of 1.30 (95%CI 1.07-1.58, P=0.01). There were no significant associations between SDS scores and cardiovascular events among female patients. Conclusions: Depression symptoms 1 year after onset of MI are a significant predictor of subsequent cardiovascular events for male patients. (Circ J 2011; 75: 2878-2884)

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Background: Smoking is still a major health problem among males in Japan. The effects of smoking and quitting on mortality and cardiovascular disease (CVD) need updating. Methods and Results: This was a prospective cohort study with a median follow-up of 7.5 years of a total of 25,464 healthy male Japanese workers aged 20-61 years who were not on any medication. The adjusted hazard ratios (HR; 95% confidence interval) for all-cause death were 1.51 (0.73, 2.94), 1.68 (1.07, 2.70), 1.30 (0.70, 2.34), and those for total CVD events 1.91 (0.72, 4.67), 2.94 (1.65, 5.63), and 3.25 (1.69, 6.54) for light smokers (1-10cigarettes/day), moderate smokers (11-20/day), and heavy smokers (≥21/day) compared to never-smokers, respectively. Total CVD events increased dose-dependently as the number of cigarettes/day increased. Acute myocardial infarction was increased at any level of smoking. Stroke was increased at a moderate level of smoking. Quitting for ≥4 years, compared with continuing smokers, reduced the HR for all-cause death to 0.64 (0.38, 1.01), and total CVD events to 0.34 (0.17, 0.62). Conclusions: In healthy young- and middle-aged Japanese males, a significant increase in HR for total CVD events was confirmed for a smoking level of 11-20 cigarettes/day. Quitting reduced the HR for total CVD events, with quitting for ≥4 years being statistically significant. A similar trend was observed for all-cause mortality. (Circ J 2011; 75: 2885-2892)

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Background: The purpose of the present study was to use virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relationship between microalbuminuria and plaque components in 920 patients. Methods and Results: Patients with albumin levels <30mg/g creatinine were defined as having normoalbuminuria (n=824), and those with albumin levels 30-300mg/g as having microalbuminuria (n=96). The microalbuminuria group contained more patients with acute coronary syndrome (ACS; 72% vs. 61%, P=0.018) and more patients with diabetes (53% vs. 26%, P<0.001). In ACS patients, %necrotic core (NC) volume was significantly greater in the microalbuminuria group compared with the normoalbuminuria group (19±10% vs. 15±9%, P=0.019), but not in patients with stable angina. In ACS patients, thin-cap fibroatheroma (TCFA) was observed more frequently in the microalbuminuria group (36% vs. 18%, P=0.008), and microalbuminuria was the independent predictor of TCFA (odds ratio [OR], 1.106; 95% confidence interval [CI]: 1.025-1.144, P=0.018). In diabetic patients, %NC volume was significantly greater in the microalbuminuria group compared with the normoalbuminuria group (20±9% vs. 16±10%, P=0.017), but not in non-diabetic patients. In diabetic patients, TCFA was observed more frequently in the microalbuminuria group (38% vs. 17%, P=0.002) and microalbuminuria was the independent predictor of TCFA (OR, 1.120; 95%CI: 1.038-1.204, P=0.012). Conclusions: Microalbuminuria was associated with a higher number of vulnerable plaque components in ACS and diabetic patients. More intensive medical therapy is needed to stabilize the vulnerable plaque if microalbuminuria is observed in diabetic ACS patients. (Circ J 2011; 75: 2893-2901)

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Background: Severe tricuspid regurgitation (TR) sometimes develops late after left-sided valve surgery without left heart failure, pulmonary hypertension or rheumatic tricuspid valve. The purpose of the present study was to investigate clinical characteristics and mechanisms of severe isolated TR late after left-sided valve surgery. Methods and Results: A total of 372 consecutive patients who underwent left-sided valve surgery between 1990 and 2003 and who were followed up with echocardiography for at least 5 years, were retrospectively investigated. The mean follow-up period was 9.4 years. Clinical background, preoperative and postoperative echocardiographic parameters were evaluated. Among the 372 patients, severe isolated TR was detected in 23 patients, which developed at a mean of 8.6 years after surgery. Twenty-two of 23 patients had undergone mitral valve surgery. Multivariate logistic regression analysis identified the presence of preoperative atrial fibrillation and preoperative ejection fraction as independent determinants for the development of severe isolated TR. In patients with severe isolated TR, the tricuspid annular diameter and the right atrial area were already enlarged early after surgery and both of these increased prior to TR progression. Conclusions: Severe isolated TR developing late after mitral valve surgery is not uncommon, thus it is important to recognize this disease entity. Annular dilatation was the main cause of isolated TR and serial echocardiographic data are important to detect progression of isolated TR and to assess its mechanisms. (Circ J 2011; 75: 2902-2907)

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