Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 74 , Issue 8
Showing 1-45 articles out of 45 articles from the selected issue
Massage From the Editor-in-Chief
Reviews
  • – Insights Into the Neointimal Algorithm and Management Strategies –
    Akihito Muto, Lynn Model, Kenneth Ziegler, Sammy D.D. Eghbalieh, Alan ...
    2010 Volume 74 Issue 8 Pages 1501-1512
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: July 01, 2010
    JOURNALS FREE ACCESS
    For patients with coronary artery disease or limb ischemia, placement of a vein graft as a conduit for a bypass is an important and generally durable strategy among the options for arterial reconstructive surgery. Vein grafts adapt to the arterial environment, and the limited formation of intimal hyperplasia in the vein graft wall is thought to be an important component of successful vein graft adaptation. However, it is also known that abnormal, or uncontrolled, adaptation may lead to abnormal vessel wall remodeling with excessive neointimal hyperplasia, and ultimately vein graft failure and clinical complications. Therefore, understanding the venous-specific pathophysiological and molecular mechanisms of vein graft adaptation are important for clinical vein graft management. Of particular importance, it is currently unknown whether there exist several specific distinct molecular differences in the venous mechanisms of adaptation that are distinct from arterial post-injury responses; in particular, the participation of the venous determinant Eph-B4 and the vascular protective molecule Nogo-B may be involved in mechanisms of vessel remodeling specific to the vein. This review describes (1) venous biology from embryonic development to the mature quiescent state, (2) sequential pathologies of vein graft neointima formation, and (3) novel candidates for strategies of vein graft management. Scientific inquiry into venous-specific adaptation mechanisms will ultimately provide improvements in vein graft clinical outcomes.  (Circ J 2010; 74: 1501 - 1512)
    Download PDF (486K)
  • Hidehiko Hara, Robert S. Schwartz
    2010 Volume 74 Issue 8 Pages 1513-1517
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: July 17, 2010
    JOURNALS FREE ACCESS
    Although surgery is the gold standard for severe aortic stenosis (AS) treatment, it is considered high risk in elderly patients because of high complication rates, which leads to substantial hesitation in submitting such patients to surgery. With the growing need to treat elderly patients with severe AS, percutaneous transcatheter aortic valve implantation (TAVI) was pioneered in 2001, followed by implantation of a self-expanding percutaneous aortic valve in 2005. As of April 2010, these 2 methods of TAVI have been used in more than 15,000 patients throughout the world. The acute success rate of this procedure is now increasing up to 95.4% by the transfemoral approach and 92.7% by the transapical approach with regard to Edwards SAPIEN® valve implantation. In terms of the Corevalve ReValving® system, it is reported as 98.2% in an expert's hands. This article reviews the methods of TAVI and the devices, not yet been approved in Japan but are expected to be available in a few years.  (Circ J 2010; 74: 1513 - 1517)
    Download PDF (463K)
  • Ken-ichi Aihara
    2010 Volume 74 Issue 8 Pages 1518-1523
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: July 17, 2010
    JOURNALS FREE ACCESS
    Heparin cofactor II (HCII), a serine protease inhibitor (serpin), inactivates thrombin action in the subendothelial layer of the vascular wall. Because a congenitally HCII-deficient patient has been shown to have multiple atherosclerotic lesions, it is hypothesized that HCII plays a pivotal role in the development of vascular remodeling, including atherosclerosis. To clarify this issue, 3 clinical studies concerning plasma HCII activity and atherosclerosis were carried out, and results demonstrated that a higher incidence of in-stent restenosis after percutaneous coronary intervention, maximum carotid arterial plaque thickness, and prevalence of peripheral arterial disease occurred in subjects with low plasma HCII activity. Furthermore, HCII-deficient mice were generated by a gene targeting method to determine the mechanism of the vascular protective action of HCII. Because HCII-/- mice were embryonically lethal, we used HCII+/- mice and found that they manifested augmentation of intimal hyperplasia and increased thrombosis after cuff or wire injury to the femoral arteries. HCII+/- mice with vascular injury showed augmentation of inflammatory cytokines and chemokines and oxidative stress. These abnormal phenotypes of vascular remodeling observed in HCII+/- mice were almost restored by human HCII protein supplementation. HCII protects against vascular remodeling, including atherosclerosis, in both humans and mice, and plasma HCII activity might be a predictive biomarker and novel therapeutic target for the prevention of cardiovascular diseases.  (Circ J 2010; 74: 1518 - 1523)
    Download PDF (2403K)
Editorials
Original Articles
Arrhythmia/Electrophysiology
  • Miki Yokokawa, Hiroshi Tada, Keiko Koyama, Toshihiko Ino, Shigeto Nait ...
    2010 Volume 74 Issue 8 Pages 1538-1546
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 19, 2010
    JOURNALS FREE ACCESS
    Background: Inflammatory responses following atrial fibrillation (AF) ablation may aggravate arrhythmogenic activity and cause an early recurrence of AF (ERAF). Methods and Results: In 56 patients who underwent circumferential pulmonary vein ablation (CPVA) for paroxysmal AF, cardiovascular magnetic resonance imaging (CMRI) was evaluated in 5 subdivided left atrial (LA) regions before the CPVA and at 1 day and 1 month after. At a mean of 7±10 days after the CPVA, 23 patients (41%) developed 1 or more episodes of AF (ERAF group), while 33 patients (59%) remained free from AF during the first month of follow up (no-ERAF group). LA wall thickness increased 1 day after the CPVA in both groups, as demonstrated by high T2-weighted signal. The LA roof thickness and its increase, however, were greater in the ERAF group than in the no-ERAF group (P<0.05). Regions of delayed enhancement (DE) were also frequently detected in both groups, but the total number of DE regions did not differ between the 2 groups. The thickening of the LA wall associated with a high T2-weighted signal resolved within 1 month. No significant difference between the 2 groups was found in any of the CMRI parameters before or 1 month after CPVA. Conclusions: Thickening of the LA roof shortly after CPVA may predict an ERAF.  (Circ J 2010; 74: 1538 - 1546)
    Download PDF (1009K)
  • Yung-Kuo Lin, Feng-Zhi Lin, Yao-Chang Chen, Chen-Chuan Cheng, Cheng-I ...
    2010 Volume 74 Issue 8 Pages 1547-1556
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 16, 2010
    JOURNALS FREE ACCESS
    Background: Oxidative stress and pulmonary veins (PVs) play critical roles in the pathophysiology of atrial fibrillation. The purpose of the present study was to investigate whether oxidative stress and antioxidant agents can change the electrophysiological characteristics of the left atrium (LA) and PVs. Methods and Results: Conventional microelectrodes were used to record the action potentials (APs) in isolated rabbit PV and LA specimens before and after H2O2 administration with or without ascorbic acid or N-mercaptopropionyl-glycine (N-MPG, a free radical ·OH scavenger). H2O2 (0.02 and 0.2 mmol/L) decreased the PV spontaneous rates from 2.0±0.1 Hz to 1.6±0.1 Hz, and 1.7±0.1 Hz (n=10, P<0.05), but H2O2 (2 mmol/L) increased PV spontaneous rates from 2.0±0.1 Hz to 2.8±0.2 Hz. H2O2 easily induced PV burst firing and early afterdepolarizations, but not in the LA. H2O2 shortened the AP duration and increased the contractile force to a greater extent in the LA than in PVs. In addition, the H2O2-induced PV burst firing and increasing spontaneous rates were suppressed or attenuated by pretreatment with ascorbic acid (1 mmol/L) or N-MPG (10 mmol/L). Conclusions: H2O2 significantly changed the electrophysiological characteristics of PV and LA through activation of free radicals and may facilitate the occurrence of atrial fibrillation.  (Circ J 2010; 74: 1547 - 1556)
    Download PDF (6523K)
  • Jae Hyung Park, Sang Weon Park, Jong Youn Kim, Sook Kyoung Kim, Boyoun ...
    2010 Volume 74 Issue 8 Pages 1557-1563
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 16, 2010
    JOURNALS FREE ACCESS
    Background: Complex fractionated atrial electrogram (CFAE) guided ablation is effective in some patients with persistent atrial fibrillation (PeAF), but the pattern of CFAE may be different in the remodeled left atrium (LA). Methods and Results: In 100 AF patients (83 males, 55.0±10.6 years old) with AF (51 paroxysmal AF (PAF), 49 PeAF) who underwent catheter ablation, CFAE cycle length (CL) and distribution (NavX 3D map) were compared according to the LA volume (3D-CT) and endocardial voltage (during high right atrial pacing 500-ms (VolPACE) and AF (VolAF; NavX). The mean CFAE-CL was longer (P=0.003) and the % area CFAE was smaller (P=0.006) in patients with LA ≥125 ml than those with <125 ml. The mean CFAE-CL was longer in patients with VolPACE <1.7 mV than those with ≥1.7 mV (P=0.002) and in VolAF <0.7 mV than ≥0.7 mV (P<0.001). The % area CFAE was smaller in patients with VolPACE <1.7 mV than those with ≥1.7 mV (P=0.006). The incidence of septal CFAE was consistently high, regardless of the degree of LA remodeling. Conclusions: In the AF patients with an electroanatomically remodeled LA, the % area of CFAE was smaller and mean CFAE-CL was longer than in those with a less remodeled LA. However, the majority of CFAE are consistently positioned on the septum in the remodeled LA.  (Circ J 2010; 74: 1557 - 1563)
    Download PDF (1129K)
Cardiovascular Surgery
  • Hongseok Yang, Young-Nam Youn, Kyung Jong Yoo
    2010 Volume 74 Issue 8 Pages 1564-1569
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 29, 2010
    JOURNALS FREE ACCESS
    Background: The aim of the present study was to identify the clinical implications of newly developed akinesia in echocardiography after off-pump coronary artery bypass graft (CABG) surgery and its relationship with graft patency. Methods and Results: A total of 512 patients underwent off-pump CABG from January 2007 to November 2008. Two hundred and thirty-nine patients, whose echocardiography and multi-slice computed tomography data were available, were included in the study. Wall motion was subdivided into 16 segments and analyzed. Patients were separated into group A with newly developed akinesia (n=20), and group B without newly developed akinesia (n=219). Morbidity and early mortality, cardiac enzyme level, and graft patency were compared. The incidence of newly developed akinesia according to the anatomical territory was as follows: anterior, 5; lateral, 3; posterior, 7; and multiple territories, 5. Significant differences in preoperative ejection fraction were observed between the 2 groups (group A, 45.0±7%; group B, 58.0±12.2%, P<0.001). There was no statistical difference in the mean number of bypassed grafts and the complete revascularization rate. Complication and early mortality rates were insignificant between the 2 groups. There was little association between graft patency, cardiac enzyme level, and newly developed akinesia (P>0.05). Multivariate analysis showed that the preoperative ejection fraction was a risk factor for newly developed akinesia. Conclusions: The mechanism of development of akinesia after off-pump CABG might be attributable to intraoperative coronary malperfusion, which is probably due to cardiac manipulation rather than graft occlusion.  (Circ J 2010; 74: 1564 - 1569)
    Download PDF (253K)
Epidemiology
  • Minoru Hongo, Hiroya Hidaka, Shigeko Sakaguchi, Keisuke Nakanishi, Mot ...
    2010 Volume 74 Issue 8 Pages 1570-1577
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 09, 2010
    JOURNALS FREE ACCESS
    Background: The present study was designed to examine whether serum uric acid (SUA) levels were associated with cardiometabolic risk factors and to determine optimal cut-offs for SUA to identify multiple risk factors among Japanese junior high school students. Methods and Results: A total of 958 students (518 boys and 440 girls, aged 12.1-15.0 years) who were enrolled between April 2005 and June 2008 were divided into 4 groups according to SUA quartiles. Compared with the lowest quartile of SUA, prevalence of abdominal obesity, hypertension, and dyslipidemia was significantly increased in the highest quartile in boys and that of abdominal obesity was increased in the highest quartile in girls. The adjusted odds ratios (95% confidence interval) of the highest quartile of SUA for 2 or more cardiometabolic risk factors were 2.59 (1.16-5.79) for boys and 1.54 (0.43-5.56) for girls. Receiver operating characteristic curve analysis demonstrated that the most appropriate cut-offs for SUA to identify multiple cardiometabolic risk factors were 6.4 mg/dl for boys and 4.9 mg/dl for girls. Conclusions: SUA was strongly associated with the prevalence of cardiometabolic risk factors among male Japanese junior high school students. The present study may provide insights into the role of SUA in the school screening system for the development of educational programs on prevention of lifestyle-related diseases among school children.  (Circ J 2010; 74: 1570 - 1577)
    Download PDF (1073K)
Heart Failure
  • Hiroyuki Ito, Yuji Nagatomo, Takashi Kohno, Toshihisa Anzai, Tomomi Me ...
    2010 Volume 74 Issue 8 Pages 1578-1583
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 16, 2010
    JOURNALS FREE ACCESS
    Supplementary material
    Background: The aim of the present study was to verify the effects of β-blockers on renal function in patients with heart failure (HF). Methods and Results: A total of 40 patients with HF (New York Heart Association class, II-III) were enrolled, who had β-blocker therapy initiated with carvedilol (n=23) or metoprolol (n=17). The changes in renal and cardiac function were retrospectively analyzed over 16 weeks. The study population was divided into 2 groups according to the median baseline (65.9 ml/min) of estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease formula. eGFR significantly decreased in the higher eGFR group (P=0.04), but did not in the lower eGFR group. Left ventricular ejection fraction significantly increased in both groups with lower eGFR (P=0.01) and higher eGFR (P<0.01). There was an interaction between plasma norepinephrine concentration and eGFR in terms of β-blocker treatment (P=0.02, ANOVA). eGFR significantly decreased in patients who received metoprolol (from 75.7±33.5 to 59.5±20.0 ml·min-1·1.73 m-2, P<0.01), but did not change in those who received carvedilol (from 67.1±27.7 ml·min-1·1.73 m-2 to 65.6±23.2 ml·min-1·1.73 m-2). Conclusions: β-Blockers preserved renal function in HF patients with lower baseline eGFR, but not in those with higher baseline eGFR. Carvedilol may be preferable to metoprolol to prevent the development of chronic kidney disease during β-blocker therapy for HF.  (Circ J 2010; 74: 1578 - 1583)
    Download PDF (294K)
  • Kensaku Higashi, Hideki Tanaka, Hiroto Shimokawahara, Norihito Nuruki, ...
    2010 Volume 74 Issue 8 Pages 1584-1590
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: July 01, 2010
    JOURNALS FREE ACCESS
    Background: Plasma B-type natriuretic peptide (BNP) level is reported to be a strong marker of congestive heart failure (CHF). Heterogeneity of the BNP levels among individuals with CHF, however, can cause confusion in interpreting the results. The influence of mitral mechanical prostheses on BNP levels in patients presenting with CHF is not well known. Methods and Results: In the present study 214 consecutive patients with CHF diagnosed using the Framingham criteria were enrolled and divided into 2 groups with and without mitral mechanical prostheses (prosthesis group, n=31; native group, n=183). The plasma BNP levels were measured, and clinical examinations including echocardiography were performed at the same time to assess cardiac performance. There was no difference in the left ventricular ejection fractions between the 2 groups. Despite having a lower body mass index, larger prevalence ratio of atrial fibrillation and larger size of the left atrium, the prosthesis group had a significantly lower logBNP level than the native group (prosthesis group vs native group: 5.12±1.01 vs 6.21±0.92, P<0.001; BNP level: 167±324 pg/ml vs 498±380 pg/ml). On multivariate analysis the presence of a mitral mechanical prosthesis was extracted as an independent predictor for decreased BNP level in patients with CHF. Conclusions: Plasma BNP level cannot correctly reflect the severity of CHF in patients with mechanical prostheses in the mitral position.  (Circ J 2010; 74: 1584 - 1590)
    Download PDF (1325K)
Imaging
  • – A Subanalysis of the J-ACCESS Study –
    Yasuhiro Usui, Taishiro Chikamori, Kenichi Nakajima, Satoshi Hida, Aki ...
    2010 Volume 74 Issue 8 Pages 1591-1599
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 19, 2010
    JOURNALS FREE ACCESS
    Background: To determine the prognostic value of post-ischemic stunning, the Japanese assessment of cardiac event and survival study by quantitative gated myocardial single-photon emission computed tomography (SPECT) (J-ACCESS) study was reevaluated. Methods and Results: Of the 4,031 patients of the J-ACCESS, the present study evaluated 1,089 who completed gated SPECT both after stress and at rest. To assess post-ischemic stunning, the following measurements (left ventricular volumes after stress minus volumes at rest) were made: Δend-systolic volume (ΔESV), Δenddiastolic volume (ΔEDV) and Δejection fraction (ΔEF). Myocardial stunning defined either as ΔESV ≥5 ml, ΔEDV ≥5 ml or ΔEF ≤5% was observed in 21%, 22%, or 26%, respectively. During a 3-year follow-up, 101 cardiac events occurred. Kaplan-Meier survival estimation indicated worse event-free survival rates in patients with dilated ESV, dilated EDV, LVEF ≤45%, ΔESV ≥5 ml or ΔEDV ≥5 ml than in those without, whereas ΔEF ≤5% did not predict events. Multivariate analysis demonstrated that LVEF ≤45% was the independent predictor for cardiac events. Nevertheless, ΔEDV ≥5 ml was also an independent parameter, in addition to LVEF ≤45%, to predict the combined endpoint of cardiac death, myocardial infarction, and revascularization, but excluding heart failure. Conclusions: These results indicate that post-ischemic stunning, as assessed by gated SPECT, is a marker for poor prognosis, particularly for ischemic cardiac events.  (Circ J 2010; 74: 1591 - 1599)
    Download PDF (1464K)
  • Motoko Hosaka, Atsushi Takagi, Tsutomu Takagi, Kyomi Ashihara, Nobuhis ...
    2010 Volume 74 Issue 8 Pages 1600-1608
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: July 01, 2010
    JOURNALS FREE ACCESS
    Background: In regional myocardial ischemia, contractile delay develops, which can be assessed by measuring time to peak strain (TPS) on tissue Doppler imaging. The aims of the present study were to clarify the usefulness of TPS measurements during adenosine triphosphate (ATP) stress in assessing myocardial ischemia and to evaluate whether prolongation of TPS disappears immediately after percutaneous coronary intervention (PCI) or not. Methods and Results: A total of 26 patients underwent strain measurements before and after PCI. Corrected TPS for heart rate (TPSc) in target regions and in control regions were measured both at baseline and during ATP infusion. TPSc ratio was calculated as a ratio of TPSc during ATP stress to TPSc at baseline. TPSc in the target region significantly increased during ATP infusion before PCI, which was significantly longer than hyperemic TPSc in control regions. Accordingly, TPSc ratio in the target regions before PCI was significantly greater than that in control regions (1.22±0.17 vs 0.96±0.09, respectively, P<0.0001). Following PCI, the TPSc ratio in the target regions significantly decreased to 0.98±0.05 (P<0.0001). Receiver operating characteristic curve analysis provided a cut-off of 1.04 in TPSc ratio for detecting myocardial ischemia with a sensitivity of 93% and specificity of 93%. Conclusions: TPS measurements during ATP stress differentiated target from control myocardium before PCI. The prolongation of TPSc disappeared immediately after PCI.  (Circ J 2010; 74: 1600 - 1608)
    Download PDF (2805K)
Ischemic Heart Disease
  • Yoshihiro Morino, Seiji Tamiya, Naoki Masuda, Yota Kawamura, Masakazu ...
    2010 Volume 74 Issue 8 Pages 1609-1616
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 09, 2010
    JOURNALS FREE ACCESS
    Background: Several studies have indicated that the clinical outcomes of sirolimus-eluting stents (SES) are significantly associated with longitudinal positioning of the stent relative to the underlying plaque distribution. Methods and Results: Optimal SES landing was determined using unique stepwise intravascular ultrasound (IVUS) criteria, mainly targeting the sites with plaque burden <50% (plaque area/external elastic membrane area ×100). To verify the criteria, (1) achievability and (2) actual impact on clinical and angiographic outcomes were assessed. A total of 162 consecutive patients with 180 lesions were enrolled and treated according to the IVUS criteria. Plaque burden at the proximal and distal margins was 41.4±13.6% (n=144) and 34.9±15.6% (n=170), respectively (within 3 mm of stent ends). The target was achieved in 72.3% of the proximal and 84.1% of the distal margin for the criteria. A strikingly low angiographic margin re-stenosis rate (2.7% of proximal and 1.4% of distal margin) and low target lesion revascularization rate (2.2%) were achieved. Receiver operator characteristic curve indicated that plaque burden was the strongest predictor of margin re-stenosis and its threshold (51.6%) was almost identical to that of the criteria. Conclusions: The proposed stepwise IVUS criteria mainly targeting plaque burden <50% are feasible and useful in the real-world practice of SES implantation.  (Circ J 2010; 74: 1609 - 1616)
    Download PDF (1501K)
  • – Insights From Randomized Clinical Trials –
    Lili Dong, Feng Zhang, Xianhong Shu
    2010 Volume 74 Issue 8 Pages 1617-1624
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 19, 2010
    JOURNALS FREE ACCESS
    Background: Recent data have demonstrated similar outcomes for patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI) and are treated with small-molecule glycoprotein IIb/IIIa inhibitors (smGPIs) compared with those treated with abciximab. In the present study, a meta-analysis was performed to evaluate the relative safety and efficacy of upstream vs deferred administration of smGPIs in STEMI patients. Methods and Results: A total of 10 randomized clinical trials comparing upstream vs deferred administration of smGPIs in 2,724 patients were located in the electronic databases of the published literature. Preprocedural Thrombolysis In Myocardial Infarction Study (TIMI) grade 2 or 3 flow was present in 45.0% of the upstream group compared with 36.9% in the deferred group (odds ratio (OR) 1.40, P<0.001). However, no difference in post-procedural TIMI 3 flow (OR 0.87, P=0.25) was found between the groups. The 30-day mortality rate in the upstream group did not differ from that of the deferred group (OR 1.04, P=0.85). No significant difference was noted with respect to major bleeding complications (OR 1.25, P=0.38). Conclusions: In STEMI patients scheduled for primary PCI, although early smGPIs treatment improved initial epicardial patency, no beneficial effect on post-procedural angiographic or 30-day clinical outcome was found. Thus, the current available data do not support the routine utilization of upstream smGPIs in STEMI patients treated with primary PCI.  (Circ J 2010; 74: 1617 - 1624)
    Download PDF (986K)
  • – Five-Year Results of the IMPORTANT Study –
    Tomonori Itoh, Ken'ichi Fukami, Tomomi Suzuki, Takumi Kimura, Yoshinor ...
    2010 Volume 74 Issue 8 Pages 1625-1634
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 19, 2010
    JOURNALS FREE ACCESS
    Background: Acute efficacy and long-term prognostic differences between ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (primary PCI) and those treated with pre-intervention thrombolysis combined with back-up of facilitated PCI has not been evaluated in Japanese patients. The purpose of the present study was therefore to evaluate the differences between treatment with primary PCI (primary-PCI group) and pre-treatment with tissue-type plasminogen activator (t-PA) combined with back-up of facilitated PCI (prior-t-PA group). Methods and Results: One hundred and one patients with STEMI were randomly assigned to 2 groups. Patients in the prior-t-PA group were then divided into 2 further groups, the facilitated-PCI and prior-t-PA alone groups. The patency rate at initial angiography, left ventricular ejection fraction (LVEF) at 6 months, and the major adverse cardiac event (MACE)-free rate at 5 years were then compared between the groups. The patency rate and LVEF in the prior-t-PA group was significantly higher than in the primary-PCI group (69% vs 17% respectively, P<0.001; 61.6±9.5% vs 55.0±11.6%, respectively; P=0.01). The MACE-free rate in the prior-t-PA group, however, was lower than in the primary-PCI group (58.7% vs 80.9%; P=0.03). The MACE-free rate in the facilitated-PCI group was equal to that in the primary-PCI group (73.7% vs 80.9%; P=0.39), whereas the MACE-free rate in the prior-t-PA-alone group was significantly lower than in the primary-PCI group (48.1% vs 80.9%; P=0.01). Conclusions: Primary PCI is superior to pre-intervention thrombolysis for long-term prognosis. Moreover, facilitated PCI may be as effective as primary PCI in patients with STEMI.  (Circ J 2010; 74: 1625 - 1635)
    Download PDF (984K)
  • Hiromasa Horiguchi, Hideo Yasunaga, Hideki Hashimoto, Shinya Matsuda
    2010 Volume 74 Issue 8 Pages 1635-1643
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 16, 2010
    JOURNALS FREE ACCESS
    Background: In Japan, drug-eluting stents (DES) were introduced in September 2004. The aim of the present study was to clarify how DES affected the proportions of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) procedures performed in Japan. Methods and Results: Using the Japanese Diagnosis Procedure Combination (DPC) inpatient database, 19,248 patients with angina pectoris (AP) and 2,895 patients with acute myocardial infarction (AMI) were identified from 144 hospitals in July of each year between 2004 and 2007. Among AP patients, the proportion of conservative therapies decreased from 70% in 2004 to 61% in 2007, while the proportion of PCI procedures increased from 25% in 2004 to 32% in 2007. On-pump CABG cases decreased from 3.5% in 2004 to 2.7% in 2007, but the number of off-pump CABG cases continuously increased from 2.2% in 2004 to 4.0% in 2007. Overall in-hospital mortality in AP patients gradually decreased from 0.35% in 2004 to 0.18% in 2007. In 2007, DES was used in 23% of all AP patients and 26% of all AMI patients. Multi-nominal logistic regression analysis showed that the proportional use of DES was greater in non-teaching hospitals than in teaching hospitals. Conclusions: There has been marked expansion of PCI and a gradual increase in off-pump CABG after the introduction of DES. It is essential to establish guidelines in Japan for a consensus between cardiologists and cardiovascular surgeons on evidence-based best practice.  (Circ J 2010; 74: 1635 - 1643)
    Download PDF (1504K)
  • Keita Sano, Takamitsu Nakamura, Mitsumasa Hirano, Yoshinobu Kitta, Tsu ...
    2010 Volume 74 Issue 8 Pages 1644-1650
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 22, 2010
    JOURNALS FREE ACCESS
    Background: Remnant lipoproteinemia is a strong risk factor for cardiovascular (CV) diseases. This study examined which of 2 common lipid-lowering drugs (fibrates and statins) is more effective in patients with remnant lipoproteinemia and if lowering remnant lipoprotein levels can reduce CV risk. Methods and Results: Remnant lipoprotein levels were measured by an immunoseparation method (remnant-like lipoprotein particles cholesterol: RLP-C) in 274 patients with coronary artery disease and high RLP-C levels (≥5.0 mg/dl). They were randomly assigned to receive bezafibrate (200-400 mg/day) or pravastatin (10-20 mg/day), and were prospectively followed-up for 1 year or until the occurrence of CV events. Complete follow-up data were obtained in 180 patients. RLP-C levels at 1 year of treatment were reduced more by bezafibrate than pravastatin (37% and 25% from baseline, respectively). During follow-up, bezafibrate-treated patients had 3 CV events, compared with 12 events in pravastatin-treated patients (P<0.01). In multivariate logistic regression analysis, a decrease in RLP-C level was significantly associated with a reduction in CV events after adjustment for treatment group and changes in levels of other lipids. Conclusions: Bezafibrate therapy decreased RLP-C levels to a greater extent than pravastatin and a decrease in RLP-C level may be associated with a reduction in CV events in patients with high RLP-C levels.  (Circ J 2010; 74: 1644 - 1650)
    Download PDF (309K)
  • Tatsuya Maruhashi, Masaharu Ishihara, Ichirou Inoue, Takuji Kawagoe, Y ...
    2010 Volume 74 Issue 8 Pages 1651-1657
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 22, 2010
    JOURNALS FREE ACCESS
    Background: Prodromal angina pectoris (AP) has a cardioprotective effect by the mechanism of ischemic preconditioning, and the QRS score on the admission electrocardiogram (ECG) reflects myocardial damage at presentation. This study was undertaken to investigate the effect of prodromal AP on infarct progression after the onset of acute myocardial infarction (AMI). Methods and Results: The study group comprised 291 patients with a first ST-elevation AMI who underwent coronary angiography within 24 h of symptom onset. QRS score was calculated from the admission ECG. Patients were divided into 3 groups according to elapsed time from onset of AMI to angiography: early group (<2 h), intermediate group (2-6 h) and late group (6-24 h). Prodromal AP was defined as angina occurring 24 h before the onset of AMI. Patients with prodromal AP (n=101; 35%) had a significantly lower QRS score than those without (2.4±2.4 vs 3.2±3.0, P=0.02). In patients without prodromal AP, the QRS score linearly increased as elapsed time increased: 2.6±2.8, 3.0±3.0 and 5.5±2.9 in the early, intermediate and late groups, respectively. In patients with prodromal AP, the QRS score remained low until 6 h after onset and then increased: 2.0±1.8, 2.0±2.1, and 4.1±3.3, respectively. Conclusions: The findings suggested that prodromal AP might delay infarct progression during the early hours after the onset of AMI and extend the window of time for reperfusion therapy.  (Circ J 2010; 74: 1651 - 1657)
    Download PDF (323K)
  • Ryotaro Yamada, Hiroyuki Okura, Teruyoshi Kume, Yoji Neishi, Takahiro ...
    2010 Volume 74 Issue 8 Pages 1658-1662
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 29, 2010
    JOURNALS FREE ACCESS
    Background: Several reports suggest that virtual histology intravascular ultrasound (VH-IVUS) assessment could predict microvascular damage during percutaneous coronary intervention (PCI). A novel index of microcirculatory resistance (IMR) has been developed as a reproducible and less hemodynamic-dependent index. The purpose of this study was to investigate the relationship between thin-cap fibroatheroma (TCFA) defined by VH-IVUS and a change in the IMR during PCI in patients with angina pectoris (AP). Methods and Results: The study investigated 30 lesions from 28 AP patients. VH-IVUS imaging was performed before PCI. TCFA was defined as the presence of confluent necrotic core (>10%) without detectable overlying fibrous cap segment. Patients were divided into 2 groups according to the presence of TCFA. Using a pressure guidewire, IMR were measured before and after PCI. After successful PCI, patients were prospectively followed up clinically. TCFA was detected in 9 lesions (30%). IMR tended to improve after PCI in the non-TCFA group, but tended to worsen in the TCFA group. ΔIMR (=IMR after PCI-IMR before PCI) was significantly higher in the TCFA group compared with the non-TCFA group (13.2±29.9 vs -4.4±16.0, P=0.04). During follow-up (mean 20 months), survival free of major adverse cardiac events was significantly less in the TCFA group than in the non-TCFA group. Conclusions: Target lesion TCFA may be related to both microvascular injury and the long-term clinical outcome after successful PCI in patients with AP.  (Circ J 2010; 74: 1658 - 1662)
    Download PDF (333K)
Pediatric Cardiology and Adult Congenital Heart Disease
  • Daisuke Hazeki, Masao Yoshinaga, Hideto Takahashi, Yuji Tanaka, Yasue ...
    2010 Volume 74 Issue 8 Pages 1663-1669
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 09, 2010
    JOURNALS FREE ACCESS
    Background: The corrected QT interval (QTc) according to Bazett's formula (QTc = QT/RR1/2) has been used in clinical practice. Bazett's formula, however, overcorrects the QT interval at fast heart rates and undercorrects it at low heart rates. Guidelines and some investigators have recommended using Fridericia's formula (QTc = QT/RR1/3) in these cases, especially in tachycardic subjects. The aim of the present study was to determine cut-offs for QTc suitable for screening pediatric subjects with prolonged QT intervals, based on manually measured values corrected by Fridericia's formula in a large number of subjects. Methods and Results: Three consecutive QT and RR intervals were measured in 4,655, 4,655, and 5,273 1st, 7th, and 10th graders, aged 6, 12, and 15 years, respectively. Each QT interval was corrected by Fridericia's formula, and mean values were calculated. Determination of the cut-offs for screening was based on the prevalence of abnormal electrocardiographic phenotypes of 1:1,164 and on the upper 0.025 percentile in the QTc distribution derived from previous studies. The tentative cut-offs suitable for screening subjects with prolonged QT intervals were 430 ms for 1st graders, 445 ms for 7th graders, and 440 and 455 ms for 10th grade boys and girls, respectively. Conclusions: These tentative cut-offs can be used to screen subjects with prolonged QT intervals in the clinical setting. Further studies are needed to confirm their validity.  (Circ J 2010; 74: 1663 - 1669)
    Download PDF (1411K)
  • Koichi Sakata, Kenji Hamaoka, Seiichiro Ozawa, Ayumi Niboshi, Tomoyo Y ...
    2010 Volume 74 Issue 8 Pages 1670-1675
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 09, 2010
    JOURNALS FREE ACCESS
    Background: Matrix metalloproteinases (MMPs) contribute to extracellular remodeling in Kawasaki disease (KD). MMP-9 is an essential vasculature-remodeling factor but its role in the vascular lesions of KD is not understood. This study focused on MMP-9 regulation via cytokines in endothelial cells (ECs). Methods and Results: Plasma and peripheral blood mononuclear cells were obtained from 30 KD patients, and 15 non-febrile and 25 febrile children. Plasma MMP-1, -2, -9, and tissue inhibitor of MMP (TIMP)-1 and -2 were measured by 2-step sandwich ELISA. Immunohistology was performed on coronary arterial lesions (CAL) from a patient who died of KD in the acute phase. MMP-9 mRNA expression in human umbilical ECs (HUVECs) treated with plasma or cytokines, and in mononuclear cells was measured by semi-quantitative reverse transcription-polymerase chain reaction. Plasma MMP-1, -2 and TIMP-2 levels were normal for KD. Plasma MMP-9 and TIMP-1 levels increased during the acute phase of the disease (P<0.001 vs each control). MMP-9 stained diffusely in CAL. MMP-9 mRNA levels were higher in HUVECs treated with plasma in the acute and convalescent phases. Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α stimulated MMP-9 expression, whereas interferon (IFN)-γ suppressed it. There was no MMP-9 mRNA elevation in mononuclear cells. Conclusions: ECs are a source of MMP-9 in the vascular lesions of KD. MMP-9 is regulated by cytokines IL-1β, IL-6, TNF-α and IFN-γ.  (Circ J 2010; 74: 1670 - 1675)
    Download PDF (519K)
  • – Medium- and Long-Term Outcomes From the JPIC Stent Survey –
    Hideshi Tomita, Toshio Nakanishi, Kenji Hamaoka, Toshiki Kobayashi, Ya ...
    2010 Volume 74 Issue 8 Pages 1676-1683
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 29, 2010
    JOURNALS FREE ACCESS
    Background: Medium- and long-term efficacy of intravascular stenting for congenital heart disease (CHD) has not been determined in Japan. Methods and Results: The study comprised a retrospective survey of Palmaz or Palmaz Genesis stent implantation for pulmonary artery stenosis (PA), aortic coarctation, and superior and inferior vena cava lesions (SIVC) from May 1995 to February 2009, occurring in association with pre- or postoperative CHD at 14 leading hospitals. Stents were implanted in 255 patients with 312 lesions (PA, 253 lesions in 199 patients; aorta, 38 lesions in 35 patients; SIVC, 21 lesions in 21 patients). Age at the initial stenting was median 10 years, and the follow-up interval ranged from 6 to 144 months. The minimum lumen diameter (MLD) of the PA, aorta, and SIVC was increased from 4.7±2.1, 6.6±2.3, and 4.4±2.2 mm to 8.8±2.7, 12.0±3.8, and 9.2±2.6 mm, respectively (P<0.01). Cumulative freedom from redilation was 84% at 72 months, 95% at 54 months, and 81% at 50 months, for the PA, aorta, and SIVC, respectively. In 187 redilations, the MLD of the PA, aorta, and SIVC increased from 6.1±2.5, 7.9±2.9, and 5.3±2.4 mm, to 8.3±2.7, 9.8±3.5, and 7.3±1.9 mm, respectively (P<0.01). There were no deaths associated with stent implantation. Conclusions: Percutaneous stenting using Palmaz or Palmaz Genesis stents and redilation are now common procedures in Japan with little morbidity during the medium- and long-term follow-up period.  (Circ J 2010; 74: 1676 - 1683)
    Download PDF (440K)
Peripheral Artery Disease
  • – Relationship Between Corkscrew Type and Prevalence of Ischemic Ulcers –
    Yuichi Fujii, Junko Soga, Shuji Nakamura, Takayuki Hidaka, Takaki Hata ...
    2010 Volume 74 Issue 8 Pages 1684-1688
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 09, 2010
    JOURNALS FREE ACCESS
    Background: A corkscrew collateral appearance on angiography is one of the diagnostic criteria for Buerger's disease. The purpose of the present study was to classify the angiographic findings of corkscrew collaterals and to evaluate the relationship between corkscrew collateral type and the severity of Buerger's disease. Methods and Results: Corkscrew collaterals were assessed on digital subtraction angiography in lower extremities of 28 patients with Buerger's disease (55 limbs). The corkscrew sign was classified into 4 types by size and pattern as follows: type I, artery diameter >2 mm, large helical sign; type II, diameter >1.5 mm and ≤2 mm, medium helical sign; type III, diameter ≥1 mm and ≤1.5 mm, small helical sign; and type IV, diameter <1 mm, tiny helical sign. The prevalence of ischemic ulcers was significantly higher in patients with types III and IV corkscrew collaterals than in patients with types I and II corkscrew collaterals either below or above the knee. Multiple regression analysis indicated that types III and IV below the knee are independent predictors of risk of ischemic ulcers. Conclusions: The prevalence of ischemic ulcers is significantly higher in patients who have small corkscrew patterns in distal segments of limb collaterals than in patients who have large corkscrew collaterals.  (Circ J 2010; 74: 1684 - 1688)
    Download PDF (404K)
  • Yoshimitsu Soga, Hiroyoshi Yokoi, Tomoko Urakawa, Atsushi Tosaka, Masa ...
    2010 Volume 74 Issue 8 Pages 1689-1695
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 22, 2010
    JOURNALS FREE ACCESS
    Background: The natural history of patients with intermittent claudication (IC) has been reported, but little is known about that of claudicant patients after endovascular therapy (EVT). Methods and Results: A total of 271 consecutive patients (mean age, 68±6 years, 82% men) with IC were treated with EVT for a de novo iliofemoral lesion. Primary patency was defined as treated vessel without re-stenosis and repeat revascularization. Major adverse cardiovascular event (MACE) included death, myocardial infarction and stroke. Median follow-up interval was 11.7±2.9 years. During the follow-up period, 132 patients died (cardiovascular death; 66%). Major amputation was performed in 4 patients. Primary patency rate was 82%, 79%, and 78% at 5, 10 and 15 years, respectively. Freedom from all-cause death (MACE) was 73% (69%), 58% (49%), and 43% (34%) at 5, 10 and 15 years. On multivariate Cox regression, Trans-Atlantic Inter-society Consensus grade C/D, and involvement of femoropopliteal lesion were independent predictors of primary patency. Independent predictors for overall survival were age, left ventricular dysfunction (ejection fraction <40%), coronary artery disease, diabetes, chronic kidney disease and below-the-knee disease. Conclusions: Regardless of good clinical patency of treated vessel in patients with IC, survival was poor. Independent predictors were different between long-term patency and late mortality.  (Circ J 2010; 74: 1689 - 1695)
    Download PDF (1543K)
Pulmonary Circulation
  • Erquan Zhang, Baohua Jiang, Ayumu Yokochi, Junko Maruyama, Yoshihide M ...
    2010 Volume 74 Issue 8 Pages 1696-1703
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: July 01, 2010
    JOURNALS FREE ACCESS
    Background: An earlier study showed that all-trans-retinoic acid (ATRA) prevents the development of monocrotalin-induced pulmonary hypertension (PH). The purpose of the present study was to determine the effect of ATRA on another model of chronic hypoxia-induced PH. Methods and Results: Male Sprague - Dawley rats were given 30 mg/kg ATRA or vehicle only by gavage once daily for 14 days during hypobaric hypoxic exposure. Chronic hypoxic exposure induced PH, right ventricular hypertrophy (RVH), and hypertensive pulmonary vascular changes. Quantitative morphometry of the pulmonary arteries showed that ATRA treatment significantly reduced the percentage of muscularized arteries in peripheral pulmonary arteries only with an external diameter between 15 and 50 μm. ATRA treatment also significantly reduced the medial wall thickness in small muscular arteries only with an external diameter between 50 and 100 μm. Unfortunately, these reductions did not accompany the lowering of pulmonary artery pressure nor decrease in RVH. Chronic hypoxia-induced PH rats with ATRA had a loss in body weight. Chronic hypoxia increased the expression of endothelial nitric oxide synthase in the lung on western blotting and immunohistochemistry, in which ATRA treatment had no effect. Conclusions: The administration of ATRA might not have a therapeutic role in preventing the development of chronic hypoxia-induced PH, because of body weight loss and the subtle preventable effects of vascular changes.  (Circ J 2010; 74: 1696 - 1703)
    Download PDF (2016K)
Vascular Medicine
  • Naozumi Kubota, Katsumi Miyauchi, Takatoshi Kasai, Takafumi Iesaki, Ka ...
    2010 Volume 74 Issue 8 Pages 1704-1710
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 29, 2010
    JOURNALS FREE ACCESS
    Background: The rate of stent thrombosis is increased in association with drug-eluting stents (DES) due to delayed endothelialization and prolonged inflammation. Clinical studies have shown that either an angiotensin-receptor blocker (ARB) or a calcium-channel blocker (CCB) can improve endothelial dysfunction and inhibit inflammatory reactions in patients with hypertension. The effects of co-administered CCB and ARB on vascular protection after DES implantation, however, remain unknown. Methods and Results: Pigs (n=24) were implanted with coronary stents and randomly assigned to control, CCB, ARB or CCB + ARB groups. Endothelium-mediated vasodilation at the distal edge was significantly impaired compared to the intact site in the control group (P<0.05), but the difference between two sites in the CCB + ARB group was not significant. The combination produced a synergistic effect at the distal edge compared to the ARB, CCB and control groups (P<0.05). The expression of tumor necrosis factor-α and inflammatory cell adhesion were significantly inhibited in the CCB or ARB monotherapy groups compared with the control (P<0.05). The combination of CCB + ARB also improved inflammation. Conclusions: Implanted DES exert adverse effects such as endothelial dysfunction and inflammatory reactions. The administration of either a CCB or an ARB reversed this adverse effect. Furthermore, recovery was synergistically enhanced by a CCB combined with an ARB.  (Circ J 2010; 74: 1704 - 1710)
    Download PDF (999K)
  • Atsushi Nakahira, Yukiko Minamiyama, Shigekazu Takemura, Hidekazu Hira ...
    2010 Volume 74 Issue 8 Pages 1711-1717
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: June 22, 2010
    JOURNALS FREE ACCESS
    Background: Long-term administration of nitroglycerin (NTG) causes tolerance secondary to increased vascular formation of reactive oxygen species. Carvedilol, which has potent antioxidant activity in addition to functioning as an adrenergic blocker, prevents nitrate tolerance by a still to be elucidated mechanism. The present study investigated how carvedilol attenuates nitrate tolerance, particularly with reference to cytochrome P450 (CYP), an enzyme involved in the development of tolerance. Methods and Results: Male Wistar rats were subjected to 48-h continuous infusion of NTG alone (0.5 mg/h) or NTG with concomitant carvedilol (20 or 100 μg/h), and then compared with vehicle-treated rats (4 groups; n=6 in each group). Following the continuous administration, nitrate tolerance, assessed by bolus NTG injections, was hemodynamically prevented by coadministration of carvedilol. Levels of CYP1A1/1A2, superoxide production, and phosphorylated vasodilator-stimulated phosphoprotein at serine 239 (P-VASP) were examined in the aortic wall and heart tissue. When NTG alone was continuously administered, vascular superoxide was produced, there was a decrease in the cardiac CYP1A1/1A2 level, and depletion of P-VASP. However, each of these changes induced by continuous NTG administration was significantly attenuated by coadministration of carvedilol and the extent of attenuation was more pronounced at the higher dose (100 μg/h). Conclusions: Coadministration of carvedilol attenuates nitrate tolerance through maintenance of NO/cGMP pathway activity by preventing free radical generation and CYP depletion.  (Circ J 2010; 74: 1711 - 1717)
    Download PDF (790K)
Controversies in Cardiovascular Medicine
  • – LDL-Cholesterol: The Lower, the Better; Is It True for Asians? (Pro) –
    Katsumi Miyauchi, Hiroyuki Daida
    2010 Volume 74 Issue 8 Pages 1718-1730
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: July 17, 2010
    JOURNALS FREE ACCESS
    Large clinical trials have elucidated that lipid-lowering therapy using statins reduces cardiovascular events in patients with coronary artery disease (CAD). The benefit of statin therapy is proportional to the achieved low-density lipoprotein cholesterol level (LDL-C) up to 70 mg/dl. On the basis of this evidence, the American Heart Association and American College of Cardiology offer an optimal LDL-C goal of <70 mg/dl for patients with a very high risk of CAD. In addition, with regard to acute coronary syndrome (ACS), which has a high risk for future cardiac events because of the presence of vulnerable plaque, intensive lipid-lowering therapy from the early stage is the standard treatment. On the other hand, the mechanism of inhibition of cardiac events by statins is thought to be predominantly based on stabilization of plaque, but research on the role of plaque regression is also advancing. The clinical significance of intensive lipid-lowering therapy using statins will be discussed from the following standpoints: (1) large-scale clinical trials around the world; (2) the relationship with plaque regression and stabilization; (3) the relationship with the diverse effects of statins; and (4) evidence generated from Japanese patients.  (Circ J 2010; 74: 1718 - 1730)
    Download PDF (6213K)
  • – LDL-Cholesterol: The Lower, the Better; Is It True for Asians? (Con) –
    Tomohiro Sakamoto, Hisao Ogawa
    2010 Volume 74 Issue 8 Pages 1731-1741
    Published: 2010
    Released: July 23, 2010
    [Advance publication] Released: July 17, 2010
    JOURNALS FREE ACCESS
    It is well known that statins improve the prognosis of cardiovascular diseases (CVD). Recent randomized control trials (RCTs) of statins conducted in Western countries revealed greater avoidance of cardiovascular events if low-density-lipoprotein cholesterol (LDL-C) reached lower levels. However, it is obvious that this evidence cannot be unconditionally extrapolated to Asians because there are great differences between Japanese and Caucasians in the absolute onset rate of CVD. Results of RCTs with Japanese for primary or secondary prevention of cardiovascular events indicate that we could benefit from statins with a relatively higher target LDL-C as compared with Western populations. In this situation, not only strong but also standard statins are still advantageous and the so-called pleiotropic effects of the drugs come to the fore. In this review, we first discuss differences in the absolute event rate in different populations, and then the lack of evidence for recommended LDL-C treatment targets, particularly in Japanese, although there is reliable evidence for reductions in plaque volume in coronary arteries from RCTs recently conducted in Japan with aggressive lipid-lowering therapy with strong statins. Finally, based on recent data, we propose a new concept regarding the secondary prevention of CVD for current Japanese populations.  (Circ J 2010; 74: 1731 - 1741)
    Download PDF (1769K)
Images in Cardiovascular Medicine
JCS Guidelines
Letters to the Editor
Author's Reply
feedback
Top