Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 76 , Issue 9
Showing 1-42 articles out of 42 articles from the selected issue
Message From the Editor-in-Chief
Cardiology Societies in the Asian/Pacific Region
Reviews
  • Jeffrey D. Lee, Mukta Srivastava, Johannes Bonatti
    2012 Volume 76 Issue 9 Pages 2058-2065
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: August 11, 2012
    JOURNALS FREE ACCESS
    Robotic totally endoscopic coronary artery bypass (TECAB) is a minimally invasive endoscopic surgical approach using the daVinci robotic telemanipulation system to perform coronary artery bypass grafting on the arrested or beating heart. It is a procedure that can be a useful alternative to the classic open procedure performed through sternotomy. After extensive modeling in cadavers, the first clinical case was performed in June 1998 placing a left internal thoracic artery graft (LITA) to the left anterior descending artery completely robotically on the arrested heart. During the early and late 2000s, international groups have adopted this evolving technology, which has included iterations such as beating-heart TECAB, use of bilateral ITA grafting and radial artery grafting, as well as 3- and 4-vessel TECAB. TECAB is combined with percutaneous coronary intervention in hybrid procedures. Despite increasing complexity of endoscopic coronary bypass surgery, conversion rates to open bypass surgery have dropped significantly and operative times have decreased. Published major morbidities and mortality rates in arrested-and beating-heart TECAB have been cumulatively in the 0–2% range and are considered well within the expected range for these highly complex surgical procedures. Long-term survival and freedom from major adverse events also meet the standards of open bypass surgery.  (Circ J 2012; 76: 2058–2065)
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  • – From Molecular Genetics to Clinical Features, Management, and Prognosis –
    Isao Shiraishi, Hajime Ichikawa
    2012 Volume 76 Issue 9 Pages 2066-2075
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: August 03, 2012
    JOURNALS FREE ACCESS
    Human heterotaxy syndrome is characterized by a wide variety of cardiac and extracardiac congenital malformations that are primarily induced by disorders of the left-right axis determination during early embryonic development. The cellular and molecular mechanisms of the left-right asymmetry have been extensively investigated in the past decade and the developmental mechanisms of the syndrome have been considerably elucidated. Medical and surgical management and treatment of heterotaxy syndrome have advanced as well. However, prognosis of the disease still remains unsatisfactory because the syndrome is often associated with a combination of complicated congenital heart diseases. Management of heterotaxy patients, particularly those who have undergone the Fontan procedure, is now one of the most important issues in pediatric and adult congenital heart disease clinics. In this review, we focus on the recent advances in knowledge of the genetic and molecular pathogenesis of heterotaxy syndrome, as well as its clinical features, management, and prognosis.  (Circ J 2012; 76: 2066–2075)
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  • Takashi Kubo, Atsushi Tanaka, Hironori Kitabata, Yasushi Ino, Takashi ...
    2012 Volume 76 Issue 9 Pages 2076-2083
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: July 31, 2012
    JOURNALS FREE ACCESS
    Optical coherence tomography (OCT) is a high resolution imaging technique that offers microscopic visualization of the coronary artery. The fast scanning speed and simple imaging procedure of new-generation frequency-domain OCT make this technology easy to use in the clinical setting. The OCT examination is useful for guidance and risk stratification of percutaneous coronary intervention (PCI). OCT-derived thin-cap fibroatheroma, which is characterized by large lipid-core and thin fibrous cap <65μm, is a predictor of peri-PCI complications, such as angiographic no-reflow, microvascular obstruction, and post-PCI cardiac troponin I elevation. Stent malapposition, tissue protrusion, and stent edge dissection are assessed in more detail by OCT than with conventional intravascular imaging modalities. Neointimal coverage at strut level assessed by OCT could be a surrogate endpoint for quickly scrutinizing safety after drug-eluting stent implantation. The OCT findings of in-stent neoatherosclerosis, such as lipid-rich neointima, microvascular proliferation, and neointimal plaque rupture, are associated with very late stent failure, including thrombosis and restenosis. With its excellent ability to assess coronary atherosclerosis and to guide PCI, OCT provides new insights into interventional cardiology.  (Circ J 2012; 76: 2076–2083)
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Editorials
Original Articles
Arrhythmia/Electrophysiology
  • Yoshihisa Naruse, Hiroshi Tada, Makoto Satoh, Mariko Yanagihara, Hidek ...
    2012 Volume 76 Issue 9 Pages 2096-2103
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 02, 2012
    JOURNALS FREE ACCESS
    Background: Obstructive sleep apnea (OSA) is often associated with atrial fibrillation (AF), but the impact of radiofrequency catheter ablation (RFCA) for AF on sleep apnea syndrome is unknown. Methods and Results: A total of 25 patients (3 women; 61±6 years) with sleep apnea syndrome who underwent RFCA for drug-refractory, persistent AF were studied. Polysomnography was also performed 1 day before and 1 week after RFCA in all patients. The total number of central or OSA or hypopnea events was analyzed and compared. Among the 25 patients who all predominantly had obstructive apnea, the apnea-hypopnea index (AHI; median, 21, interquartile range [IQR]: 11–38 to median 15, IQR: 7–23; P=0.002) and obstructive type of apnea (median 10, IQR: 6–19 to median 7, IQR: 2–14; P=0.003) decreased after RFCA. In patients in whom sinus rhythm was restored and maintained after RFCA, the AHI decreased after RFCA (median 22, IQR: 15–38 to median 15, IQR: 7–23; P<0.01), but it did not in those who had AF recurrence (median 10, IQR: 9–11 to median 11, IQR: 10–16; P<0.05). There was a significant correlation between the outcome of RFCA and % change in the AHI (rs=0.569, P=0.003). Conclusions: In patients with sleep apnea syndrome and AF, restoring sinus rhythm by RFCA was significantly associated with a decrease in AHI (Clinical Trial Registration: Trial number, UMIN000005538).  (Circ J 2012; 76: 2096–2103)
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  • – The J-ROCKET AF Study –
    Masatsugu Hori, Masayasu Matsumoto, Norio Tanahashi, Shin-ichi Momomur ...
    2012 Volume 76 Issue 9 Pages 2104-2111
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 05, 2012
    JOURNALS FREE ACCESS
    Supplementary material
    Background: The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. Methods and Results: J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87–1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050). Conclusions: J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice.  (Circ J 2012; 76: 2104–2111)
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  • Masateru Takigawa, Mihoko Kawamura, Takashi Noda, Yuko Yamada, Koji Mi ...
    2012 Volume 76 Issue 9 Pages 2112-2118
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 23, 2012
    JOURNALS FREE ACCESS
    Background: Although the incidence of ventricular tachyarrhythmias associated with structural heart disease is highest in winter and during the daytime, seasonal and circadian variations among cardiac events in patients with congenital long QT syndrome (LQTS) remain unknown. The present study aims to determine seasonal and circadian cardiac events in patients with a congenital LQTS genotype. Methods and Results: The medical records of 196 consecutive patients with symptomatic LQTS (age, 32±19 years; female, n=133; LQT1, n=86; LQT2, n=95; LQT3, n=15) who were genotyped between 1979 and 2006 at 2 major Japanese institutions were retrospectively analyzed. The patients with LQT1, LQT2, and LQT3 developed 223,550 and 59 cardiac events during a mean follow-up of 26, 33, and 25 years, respectively. The numbers of cardiac events significantly peaked during the summer among those with LQT1 (P<0.001) and from summer to fall in those with LQT2 (P<0.001), but reached the nadir in winter among those with LQT3 (P=0.003). Cardiac events significantly peaked in the afternoon (12:00–17:59) and morning (06:00–11:59) among those with LQT1 (P<0.001) and LQT2 (P<0.001). Conclusions: The frequency of cardiac events was specifically seasonal and circadian among patients with the 3 major genotypes of congenital LQTS.  (Circ J 2012; 76: 2112–2118)
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Cardiovascular Intervention
  • – Safe and Effective Guidance for Transcatheter Closure in Atrial Septal Defects –
    Nam Kyun Kim, Su-Jin Park, Jae Il Shin, Jae Young Choi
    2012 Volume 76 Issue 9 Pages 2119-2123
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 07, 2012
    JOURNALS FREE ACCESS
    Background: Intracardiac echocardiography (ICE) was introduced as a new guidance system for transcatheter closure of secundum atrial septal defect (ASD) with Amplatzer septal occluder® (ASO). The aim of this study was to investigate the clinical outcome of ICE-guided transcatheter closure of ASD compared with the trans-esophageal echocardiography (TEE)-guided method. Methods and Results: From May 2003 to April 2010, 560 patients who underwent transcatheter closure of ASD using ASO in a single institute were analyzed retrospectively. In the TEE-guided group (n=237), all the patients underwent general anesthesia. The median age was 24.2 years (range, 14 months–63 years) and the average weight was 42.3±21.6kg (range, 8.2–82kg). One patient underwent surgery due to migration of device. The remaining 236 patients underwent the procedure successfully without significant complication. In the ICE-guided group (n=323), the median age was 30.5 years (range, 7 months–75 years). One patient underwent surgery because of mitral valve encroachment by left atrial disk after device placement. Another patient also underwent surgery due to device embolization. The remaining 321 procedures were performed successfully without major complications. Procedure time was 104.2min and 87.7min, respectively (P<0.001). Conclusions: ICE-guided ASD occlusion with ASO is safe and effective and provides accurate anatomical information, sufficient to perform the procedure. In addition, there were benefits of avoidance of general anesthesia, and shorter procedure time.  (Circ J 2012; 76: 2119–2123)
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Heart Failure
  • Francisco J. Pastor-Pérez, Sergio Manzano-Fernández, Reb ...
    2012 Volume 76 Issue 9 Pages 2124-2129
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 06, 2012
    JOURNALS FREE ACCESS
    Background: Abnormalities in autonomic control are a feature of neuroendocrine activation in HF and are responsible for dysregulation of biological rhythms. The purpose was to investigate the presence and the prognostic significance of long-period heart rate (HR) rhythms in heart failure (HF) patients. Methods and Results: In the study, 92 HF patients were enrolled (age 53±14 years and left ventricular ejection fraction [LVEF] 37±10%). A rhythmometric analysis was used to assess the HR rhythms in 7-days (7D) Holter recordings. Rhythms properties were quantified by mesor and amplitude, in beats/min and by acrophase, in hours. Cardiac death or HF decompensation were registered. All patients had 24-h rhythm, 61 patients (77%) had 8-h rhythm, and 66 patients (83%) had 7D rhythm. Twelve patients (15%) experienced events. Among rhythm parameters only 7D median amplitude was different between patients with or without events: 1.1beats/min [0.5–1.5] vs. 2.0beats/min [0.0–3.9], P=0.049 respectively. After multivariate adjustment, LVEF (per 1%, hazard ratio 0.92, 95% confidence interval (CI) 0.87 to 0.98, P=0.01), N-terminal portion of pro-natriuretic hormone type B (per 100pg/ml, hazard ratio 1.036, 95% CI 1.005–1.069, P=0.022), and 7D amplitude of the HR ≤1.71beats/min (hazard ratio 5.4, 95% CI 1.2–34.4, P=0.047) were independent predictors of events. Conclusions: A 7D HR rhythm is present in most patients with HF, and has prognostic significance.  (Circ J 2012; 76: 2124–2129)
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  • Akihiro Nakagomi, Yoshihiko Seino, Keiichi Kohashi, Munenori Kosugi, Y ...
    2012 Volume 76 Issue 9 Pages 2130-2138
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 13, 2012
    JOURNALS FREE ACCESS
    Background: The effects of statin therapy on the production of monocyte pro-inflammatory cytokines, cardiac function and the long-term prognosis in chronic heart failure (CHF) patients with dyslipidemia remain unclear. Methods and Results: A total of 146 CHF patients with a mean left ventricular ejection fraction (LVEF) of 26.9±6.6% were divided into 2 groups based on whether or not statins were included in their treatment: a statin group (n=63) and a no statin group (n=83). Only patients with dyslipidemia were treated with statins. Peripheral blood mononuclear cells (PBMCs) were isolated, and the production of monocyte tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured at baseline and after 6 months of treatment, and the data expressed as mean±SD (pg·ml–1·10–6 PBMCs). The LVEF in the statin group improved, and the monocyte TNF-α and IL-6 production decreased (respectively, P<0.001), but the LVEF and cytokine production remained unchanged in the no statin group. Multivariate Cox hazard analysis showed that statin therapy (hazard ratio, 0.14; 95% confidence interval: 0.02–0.97, P=0.046) was an independent predictor of cardiac events. Conclusions: Statin therapy attenuates the production of monocyte pro-inflammatory cytokines, and ameliorates the cardiac function and may improve long-term prognosis in CHF patients with dyslipidemia.  (Circ J 2012; 76: 2130–2138)
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  • Wei-Hsian Yin, Jeng Wei, Wen-Pin Huang, Jaw-Wen Chen, Mason Shing Youn ...
    2012 Volume 76 Issue 9 Pages 2139-2147
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 15, 2012
    JOURNALS FREE ACCESS
    Background: The aim of this study was to ascertain whether expressions of adipokines in the myocardium or their circulating levels can provide prognostic information concerning patients with chronic heart failure (HF). Methods and Results: Circulating levels of 3 adipokines (leptin, adiponectin, and resistin), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein were measured in 96 patients with chronic HF. Major adverse cardiac events (MACE) involving death, heart transplantation, and hospitalization with deteriorating HF during a median follow-up period of 288 days were recorded. From that group, immunohistochemistry and Western blotting studies of the myocardial tissues were conducted on 7 patients with end-stage HF undergoing heart transplantation. The levels of the 3 adipokines significantly correlated with that of NT-proBNP; however, only adiponectin concentration increased with the severity of HF, after correction for body mass index. Cox proportional hazards analyses revealed that high levels of corrected adiponectin were predictive of the development of MACE (hazard ratio, 2.947, P=0.037). Moreover, adiponectin was significantly expressed in the myocardium, and its tissue expression positively correlated with the severity of HF. Conclusions: This study showed that adiponectin is associated with clinical outcomes and severity of HF. Further research into the precise mechanisms of these adipokine derangements in HF is important to help clarify the exact role of adipokines in the pathophysiology of HF.  (Circ J 2012; 76: 2139–2147)
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  • Nelson Chavarria, Tomoko S. Kato, Raffay Khan, Aalap Chokshi, Elias Co ...
    2012 Volume 76 Issue 9 Pages 2148-2152
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 12, 2012
    JOURNALS FREE ACCESS
    Background: Chronic heart failure is associated with higher risk for developing diabetes mellitus. Secretory products from adipocytes may contribute to the deterioration in glycemic control and increased insulin resistance (IR). Retinol binding protein 4 (RBP4) is an adipose tissue-derived protein with pro-diabetogenic effects. The aim of the present study was to investigate the relationship of RBP4 in patients with heart failure. Methods and Results: Serum levels of RBP4, insulin, and fasting glucose were assessed in 58 patients with severe heart failure at the time of left ventricular assist device (LVAD) implantation and in 44 patients at the time of explantation, as well as in 10 normal control subjects. Serum RBP4 levels were measured by specific enzyme-linked immunosorbent assay, and IR was assessed using the homeostatic model of IR (HOMA-IR). Fasting glucose, insulin and HOMA-IR were significantly higher in patients at the time of LVAD implantation compared to controls (all P<0.01). RBP-4 and HOMA-IR significantly decreased after LVAD implantation (21.7±8.8mg/dl to 16.0±3.8mg/dl, P<0.05; 4.2±2.7 to 2.5±2.0, P<0.01). Conclusions: Patients with advanced heart failure have increased levels of RBP4, and LVAD implantation reduces RBP4. These findings implicate RBP4 in the cascade of reversible metabolic derangements in advanced heart failure.  (Circ J 2012; 76: 2148–2152)
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  • Akiomi Yoshihisa, Satoshi Suzuki, Makiko Miyata, Takayoshi Yamaki, Koi ...
    2012 Volume 76 Issue 9 Pages 2153-2158
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 13, 2012
    JOURNALS FREE ACCESS
    Background: Sleep-disordered breathing (SDB), including Cheyne-Stokes respiration with central sleep apnea (CSR-CSA), causes a deterioration in the prognosis of patients with chronic heart failure (CHF). Adaptive servo-ventilation (ASV) and oxygen therapy (O2) are useful for improving the CSR-CSA of CHF. The purpose of the present study was to examine the short-term effects of ASV and O2 on suppressing SDB (CSR-CSA dominant) in CHF, and the accompanying neurohumoral abnormalities (cardiac overload, sympathetic nervous activation, and myocardial damage). Methods and Results: Forty-two patients with CHF and SDB (mean LVEF 34.6%, apnea hypopnea index (AHI) 39.0/h, central apnea index (CAI) 17.6/h, obstructive apnea index (OAI) 2.6/h) were enrolled. We performed polysomnography (baseline, O2, and ASV) for 3 consecutive days, and we measured levels of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), noradrenalin, urinary catecholamines, and high-sensitivity troponin T. Both O2 and ASV reduced the AHI, CAI, arousal index, mean heart rate during sleep, and the levels of noradrenalin, urinary catecholamines, and high-sensitivity troponin T. However, only ASV, not O2, decreased the levels of ANP and BNP. Conclusions: ASV reduces cardiac overload, attenuates sympathetic nervous activity and ongoing myocardial damage effectively in CHF patients with SDB, and for patients who cannot use ASV, O2 is an alternative therapy.  (Circ J 2012; 76: 2153–2158)
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Hypertension and Circulatory Control
  • Katsumi Miyauchi, Tsutomu Yamazaki, Hirotaka Watada, Yasushi Tanaka, R ...
    2012 Volume 76 Issue 9 Pages 2159-2166
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 09, 2012
    JOURNALS FREE ACCESS
    Background: Angiotensin II receptor blocker (ARB) as a first-line drug for hypertension in diabetes often fails to control blood pressure adequately. The objective of the study was to evaluate the effect of amlodipine combined therapy on home blood pressure (HBP) useful for management of hypertension. Methods and Results: A total of 263 type 2 diabetes with hypertension refractory to standard dose of ARB were randomized to increased ARB regimen (n=132) or amlodipine combination regimen (n=131). The primary endpoint was change in morning HBP at 1 year. The combination regimen significantly lowered morning HBP than the increased ARB regimen (158.2/82.5mmHg in the combination regimen, 157.3/84.4mmHg in the increased ARB regimen, at baseline; 142.7/76.3 vs. 155.0/83.1mmHg, respectively, P<0.001 for both, at 8 weeks; 139.6/74.6 vs. 149.1/78.1mmHg, respectively, P<0.001 for systolic and P=0.010 for diastolic, at 1year). The combination regimen showed significantly higher rates of achieving target morning HBP at 8 weeks (11.3% vs. 2.7%, P=0.015). In the combination regimen, estimated glomerular filtration rate declined slower, and carotid intima-media thickness decreased in contrast to the increased ARB regimen. Conclusions: In type 2 diabetes patients with hypertension refractory to standard dose of ARB, the amlodipine combination regimen provides superior antihypertensive effect on HBP to the increased ARB regimen, and beneficial effects on reducing risks of cardiovascular events.  (Circ J 2012; 76: 2159–2166)
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Ischemic Heart Disease
  • Jifu Li, Yuan Guo, Xiaorong Luan, Tianjun Qi, Daqing Li, Yuguo Chen, X ...
    2012 Volume 76 Issue 9 Pages 2167-2173
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 05, 2012
    JOURNALS FREE ACCESS
    Background: Monocyte chemotactic factors contribute to the formation of atherosclerotic plaques. The present study aimed to elucidate the roles of monocyte chemoattractant protein-1 (MCP-1), Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) and fractalkine on the vulnerability of atherosclerotic plaques in patients with acute myocardial infarction (AMI) or unstable angina pectoris (UAP). Methods and Results: Sixty patients with AMI, 60 patients with UAP, 60 patients with stable angina pectoris (SAP) and 40 patients without coronary heart disease comprised the study group. Quantitative coronary angiography and intravascular ultrasound (IVUS) were performed. Concentrations and mRNA expression levels of high-sensitivity C-reactive protein, MCP-1, RANTES and fractalkine were measured by ELISA and RT-PCR, respectively. IVUS found that 51.3% of the AMI patients and 47.7% of the UAP patients had soft lipid plaques. Among the SAP patients, 52.4% had fibrous plaques and only 17.1% had soft plaques. AMI and UAP patients had larger plaque burden and vascular remodeling index than did the SAP patients (P<0.01). The averaged number of migrated monocytes was higher in AMI and UAP patients. Concentrations and mRNA expression levels of MCP-1, RANTES and fractalkine were significantly higher in AMI and UAP patients than in SAP patients (P<0.05–0.01). The plaque burden in UAP patients as measured with IVUS correlated well with monocytes chemotaxis (r=0.56, P<0.01). Conclusions: MCP-1, RANTES and fractalkine independently participate in the pathogenesis of plaque vulnerability and subsequent plaque rupture.  (Circ J 2012; 76: 2167–2173)
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  • Luigi Marzio Biasucci, Italo Porto, Luca Di Vito, Giovanni Luigi De Ma ...
    2012 Volume 76 Issue 9 Pages 2174-2182
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 05, 2012
    JOURNALS FREE ACCESS
    Background: Microparticles (MP) are vesicles released from activated or apoptotic cells. Endothelial MP (EMP) are derived from injured endothelium, platelet MP (PMP) from activated platelets, and Annexin V positive MP (AMP) from apoptotic endothelial cells. The aim was to assess the release of MP and its association with inflammation and atherosclerotic burden. Methods and Results: AMP, EMP and PMP were measured on admission (Day 0) in 33 patients with stable angina (SA) and 43 patients with acute coronary syndrome (ACS) undergoing percutaneous coronary interventions (PCI). In SA, peripheral artery disease (PAD) was assessed by ultrasound examination. In 30 of the 76 patients (20 ACS and 10 SA), MP, high-sensitivity-C-reactive protein (hs-CRP), and troponin T (TnT) levels were also assessed 24h (Day 1) and 48h (Day 2) after PCI. AMP, EMP, and PMP were higher in ACS than in SA (all P<0.01). In the SA group, AMP, PMP, and EMP were similar in patients with or without PAD. In the ACS group, AMP increased until Day 2 (P=0.001), while EMP and PMP peaked on Day 1 (P<0.01) then decreased to baseline values. Day 2 AMP correlated with Day 2 TnT levels (r=0.43, P=0.01) while Day 1 EMP and PMP correlated with Day 1 hs-CRP (r=0.37, P=0.04 and r=0.33, P=0.05; respectively). Conclusions: Higher MP levels were observed in ACS than in SA. Atherosclerotic burden did not affect MP levels in stable patients.  (Circ J 2012; 76: 2174–2182)
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  • Dimitrios Alexopoulos, Ioanna Xanthopoulou, Grigorios Tsigkas, Anastas ...
    2012 Volume 76 Issue 9 Pages 2183-2187
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: May 31, 2012
    JOURNALS FREE ACCESS
    Background: Given that platelet inhibition is crucial when ST-elevation myocardial infarction (STEMI) patients undergo primary PCI (PPCI), the identification of factors associated with early high on-treatment platelet reactivity may be important. Methods and Results: Consecutive STEMI patients admitted for PPCI were considered for platelet reactivity assessment 2h after loading with 600mg clopidogrel using the VerifyNow point-of-care P2Y12 assay. A cut-off of ≥235 P2Y12 reaction units indicated high on-treatment platelet reactivity. Out of 92 STEMI patients, 63 (68.5%) were found to have high on-treatment platelet reactivity. Patients with high on-treatment platelet reactivity had received upstream clopidogrel loading and pantoprazol more frequently, had lower admission hemoglobin and tended to have an impaired renal function compared to those with an adequate response to clopidogrel. On multivariate analysis, upstream clopidogrel loading and creatinine clearance <60ml/min were independently associated with higher risk for high on-treatment platelet reactivity (relative risk [RR]=1.55, 95% confidence interval [CI]: 1.11–2.17, P=0.01; RR=1.31, 95% CI: 1.008–1.71, P=0.04, respectively). Conclusions: In patients with STEMI undergoing PPCI, use of upstream clopidogrel and impaired renal function independently predict high on-treatment platelet reactivity assessed as early as 2h following 600mg of clopidogrel loading dose on point-of-care P2Y12 function assay.  (Circ J 2012; 76: 2183–2187)
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  • – Subanalysis of the TRUTH Study –
    Tsuyoshi Nozue, Shingo Yamamoto, Shinichi Tohyama, Kazuki Fukui, Shige ...
    2012 Volume 76 Issue 9 Pages 2188-2196
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 12, 2012
    JOURNALS FREE ACCESS
    Background: Patients with diabetes mellitus (DM) have a markedly increased incidence of adverse cardiovascular events, but the mechanisms have not been well-characterized. Methods and Results: The TRUTH study evaluated the effects of 8-month statin therapy on coronary artery plaque composition using virtual histology intravascular ultrasound (IVUS). Analyzable IVUS data were obtained from 119 patients, including 50 DM patients. The pattern of arterial remodeling, extent of coronary atherosclerosis, and plaque composition were compared in subjects with and without DM. Significant decreases in atheroma volume (–2.3%, P=0.02) and external elastic membrane volume (–1.7%, P=0.02) were observed only in the non-DM group. Although statin therapy significantly decreased the fibro-fatty component in both groups, this component at follow-up was significantly greater in the DM group (0.99mm3/mm vs. 0.70mm3/mm, P=0.03). Multivariate regression analysis showed that the presence of DM was associated with greater atheroma volume (β=0.203, P=0.02), particularly fibro-fatty plaque volume at follow-up (β=0.215, P=0.01). Conclusions: DM attenuated the degree of regression of coronary atherosclerosis under statin therapy. A large amount of fibro-fatty plaque volume under statin therapy may affect the development of coronary events in patients with DM.  (Circ J 2012; 76: 2188–2196)
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  • Makoto Nishinari, Naoyoshi Aoyama, Zensuke Ogawa, Shogo Yukino, Shusak ...
    2012 Volume 76 Issue 9 Pages 2197-2203
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 08, 2012
    JOURNALS FREE ACCESS
    Background: Phosphoglucomutase (PGM), a key enzyme in cellular glucose utilization and energy homeostasis, has been reported to show a relationship with oxidative stress. However, the clinical importance of PGM activity has not been investigated in patients with ischemic heart disease (IHD). The aim of the present pilot study was to clarify whether PGM activity has potential as a cardiovascular risk predictor in patients with IHD. Methods and Results: The levels of serum PGM activity in 237 patients with IHD (63 patients with acute myocardial infarction (AMI) and 174 patients with stable effort angina pectoris (EAP)) were evaluated. PGM activity was compared with levels of various myocardial, thrombosis, and inflammatory biomarkers on admission. PGM activity in the AMI group was significantly increased relative to that in the EAP group on admission (AMI, 55.5μmol·min–1·L–1 (U/L); EAP, 14.4U/L (P<0.001)), and was observed to increase in parallel with well-established myocardial markers (P<0.001). Moreover, PGM activity and the lipid, thrombosis, and inflammatory biomarkers in the AMI group were higher than those in the EAP group. Conclusions: PGM activity increased with levels of myocardial, thrombosis, and inflammatory biomarkers in patients with AMI, and might be useful in diagnostic applications during the acute phase in patients with AMI.  (Circ J 2012; 76: 2197–2203)
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  • Mamoru Sakakibara, Shiro Yamada, Kiwamu Kamiya, Takashi Yokota, Koji O ...
    2012 Volume 76 Issue 9 Pages 2204-2210
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 02, 2012
    JOURNALS FREE ACCESS
    Background: Sleep-disordered breathing (SDB) is often associated with sudden cardiac arrest (SCA) during sleep. Coronary artery spasm (CS) also occurs during sleep and is rarely associated with SCA, but the role of SDB in the risk of SCA is unknown in CS patients. This study evaluated the breathing patterns during sleep in CS patients with a prior history of aborted SCA. Methods and Results: This study enrolled 24 patients (age 61.6±11.0 years, male/female 19/5) with CS proven by an acetylcholine provocation test. They were divided into 2 groups: prior history of aborted SCA due to fatal arrhythmia (SCA group; n=9) and no such history (no-SCA group; n=15). Patients underwent overnight polysomnography with ambulatory electrocardiography. The overall prevalence of SDB (apnea hypopnea index ≥15) was 45.8% in this cohort. SDB was more frequent in the SCA group than in the no-SCA group (88.9% vs. 20.0% P=0.001) and identified as a pivotal risk factor of aborted SCA (odds ratio: 38.9, 95% CI: 2.80–1,498.2, P=0.01). Very-low-frequency was significantly correlated with the apnea hypopnea index in patients with SCA (P=0.01, r=0.78) during sleep. Conclusions: SDB is a significant risk factor for SCA in CS patients and autonomic instability during sleep might be involved in this association.  (Circ J 2012; 76: 2204–2210)
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  • Kenichiro Tajika, Kentaro Okamatsu, Masamichi Takano, Shigenobu Inami, ...
    2012 Volume 76 Issue 9 Pages 2211-2217
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 19, 2012
    JOURNALS FREE ACCESS
    Background: The association between elevated malondialdehyde-modified low-density lipoprotein (MDA-LDL) and plaque instability in patients with coronary artery disease (CAD) is suspected but not established. The aim of the present study was therefore to investigate the association between serum MDA-LDL and plaque characteristics on angioscopy. Methods and Results: A total of 37 consecutive patients with CAD and single-vessel disease who underwent pre-interventional angioscopy, were studied. Using angioscopy at the target lesions, the presence of yellow plaque and complex plaque was examined. Moreover, we evaluated the yellow intensity, which has been shown to have an inverse correlation with the fibrous-cap thickness of the plaques, with quantitative colorimetry to identify a thin-cap atheroma. Serum MDA-LDL in patients with thin-cap atheroma diagnosed on quantitative colorimetry was significantly higher than in patients without thin-cap atheroma (P<0.0009). Univariate logistic regression indicated that serum MDA-LDL was a predictor for thin-cap atheroma (odds ratio [OR], 1.48; 95% confidence interval [CI]: 1.10–1.97; P=0.003) and for complex plaque (OR, 1.22; 95% CI: 1.00–1.48; P=0.046). On multivariate logistic regression serum MDA-LDL was the only independent predictor for thin-cap atheroma (OR, 1.48; 95% CI: 1.10–1.97; P=0.011). Conclusions: Using angioscopy and quantitative colorimetry, elevated MDA-LDL was confirmed to be associated with thin-cap atheroma in CAD patients.  (Circ J 2012; 76: 2211–2217)
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  • Yasutsugu Shiono, Hironori Kitabata, Takashi Kubo, Tomizou Masuno, Shi ...
    2012 Volume 76 Issue 9 Pages 2218-2225
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 21, 2012
    JOURNALS FREE ACCESS
    Background: For the identification of functionally significant coronary artery disease, there have not been any dedicated optical coherence tomography (OCT) studies reported previously, although OCT can clearly detect coronary vessel lumina at higher resolution than intravascular ultrasound (IVUS). Methods and Results: OCT and fractional flow reserve (FFR) measurements were performed in 62 intermediate coronary lesions in 59 patients. FFR was calculated as the ratio of distal coronary pressure divided by proximal coronary pressure during maximal hyperemia. FFR <0.75 was used as the threshold for diagnosing functionally significant stenosis. Minimal lumen area (MLA), minimal lumen diameter (MLD) and percent lumen area stenosis were measured by OCT. FFR values correlated significantly with OCT-derived MLA (r=0.75, P<0.01), MLD (r=0.76, P<0.01) and percent lumen area stenosis (r=−0.77, P<0.01). Receiver-operating characteristic curve suggested an OCT-derived MLA <1.91mm2 (sensitivity 93.5%, specificity 77.4%), MLD <1.35mm (sensitivity 90.3%, specificity 80.6%) and percent lumen area stenosis >70.0% (sensitivity 96.8%, specificity 83.9%) as the best cutoff values for a FFR <0.75. Conclusions: Anatomical measurements of coronary stenosis obtained by OCT show significant correlation with FFR. OCT has the potential to predict functionally significant stenosis, although the present OCT-derived parameters were smaller than those reported in previous IVUS studies.  (Circ J 2012; 76: 2218–2225)
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  • Te-Fa Chiu, Chih-Huang Li, Chun-Chuan Chen, Chien-Hsiun Chen, Chien-Ju ...
    2012 Volume 76 Issue 9 Pages 2226-2233
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 20, 2012
    JOURNALS FREE ACCESS
    Supplementary material
    Background: Heat shock proteins (HSPs) act as chaperones and have a protective function in cardiovascular diseases. The clinical association of a novel small HSPB7 with cardiovascular disease, however, has not been reported. The aim of this study was to investigate the potential biological functions of HSPB7 and its relationship with acute coronary syndrome (ACS). Methods and Results: A mouse myocardial infarction (MI) model and samples from clinical human subjects were used to determine plasma HSPB7 concentration after acute MI. The associations of plasma HSPB7 concentration with ACS and other risk factors of coronary artery disease were analyzed. Plasma HSPB7 concentration was found to be rapidly elevated in mice after coronary artery ligation. In addition, plasma HSPB7 concentration was significantly higher in patients with ACS than in control patients with non-cardiac chest pain (5.1ng/ml vs. 2.9ng/ml, P<0.001). Plasma HSPB7 was detected as early as 1–3h after the onset of symptoms and remained detectable up to 24h. Furthermore, in patients presenting to the emergency department with acute chest pain, HSPB7 level was an independent risk factor of ACS (adjusted odds ratio, 7.44; 95% confidence interval: 1.91–28.93, P<0.01). Conclusions: HSPB7 is a potential early biomarker after MI and serves as an independent risk factor of ACS in patients with acute chest pain.  (Circ J 2012; 76: 2226–2233)
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Metabolic Disorder
  • Shiro Nakamori, Katsuya Onishi, Hiroshi Nakajima, Yeonyee Elizabeth Yo ...
    2012 Volume 76 Issue 9 Pages 2234-2240
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 02, 2012
    JOURNALS FREE ACCESS
    Background: The purpose of this study was to determine whether the presence of fatty liver is associated with an alteration in myocardial perfusion reserve (MPR). Methods and Results: A retrospective analysis of 65 asymptomatic subjects who underwent both plain abdominal computed tomography and cardiac magnetic resonance imaging (MRI), and who had normal left ventricular wall motion, no regional myocardial ischemia and no myocardial scar on MRI was performed. Stress and rest myocardial perfusion MRI were analyzed by Patlak plot method to quantify myocardial blood flow (MBF) and MPR in 16 myocardial segments. Fatty liver was detected in 18 (28%) of the 65 subjects. No significant difference was found in rest-MBF between subjects with and without fatty liver (1.2±0.75 vs. 1.1±0.67ml·min–1·g−1, P=0.59). However, MPR was significantly lower in subjects with fatty liver than the non-fatty liver subjects (2.3±0.74 vs. 3.3±1.4, P<0.001). Subjects with fatty liver had a higher prevalence of MPR <2.5 (78% vs. 38%, P<0.005) and higher triglyceride levels (206±61 vs. 92±37mg/dl, P<0.001). Multivariate analysis revealed the presence of fatty liver as a significant predictor of reduced MPR with an odds ratio of 8.2 (P<0.01). Conclusions: Nonalcoholic fatty liver disease is related to reduced MPR, suggesting impaired coronary microcirculation.  (Circ J 2012; 76: 2234–2240)
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  • Bo Zhang, Emi Kawachi, Akira Matsunaga, Satoshi Imaizumi, Keita Noda, ...
    2012 Volume 76 Issue 9 Pages 2241-2248
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 26, 2012
    JOURNALS FREE ACCESS
    Background: The aim of the present study was to compare 2 direct measurements for low-density lipoprotein cholesterol (LDL-C) with the Friedewald calculation (LDL-C [F]) in serum and their relationship with size-and charge-based LDL subfractions in serum ultracentrifugation fractions in patients with hypercholesterolemia (HC). Methods and Results: Serum samples from 283 HC patients who participated in a statin trial (the PATROL trial) were analyzed. Homogeneous assays for LDL-C were performed using reagents from Sekisui Medical (LDL-C [Se]) and Kyowa Medex (LDL-C [Ky]). Charge-based LDL subfractions were analyzed by capillary isotachophoresis (cITP). In whole serum in HC patients at baseline, LDL-C (Se) and LDL-C (Ky) negatively and positively deviated, respectively, from LDL-C (F). The negative deviation of LDL-C (Se) from LDL-C (F) increased with increasing LDL-C, while the positive deviation of LDL-C (Ky) from LDL-C (F) was positively correlated with charge-modified LDL (cmLDL) as analyzed by cITP. In serum d>1.006g/ml and >1.040g/ml fractions (LDL and small, dense LDL fractions, respectively), the deviation of LDL-C (Ky) from LDL-C (Se) was positively correlated with LDL-apoB (the number of LDL particles) and cmLDL. Conclusions: The 2 homogenous assays for LDL-C differed with regard to reactivity toward LDL particles and cmLDL in patients with HC. Direct measurement of LDL-C that reflects modified LDL, could be a better marker for the risk of coronary heart disease.  (Circ J 2012; 76: 2241–2248)
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Pulmonary Circulation
  • Shinji Katsuragi, Kaoru Yamanaka, Reiko Neki, Chizuko Kamiya, Yoshihit ...
    2012 Volume 76 Issue 9 Pages 2249-2254
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 13, 2012
    JOURNALS FREE ACCESS
    Background: Pulmonary arterial hypertension (PAH), including Eisenmenger syndrome, has a risk of mortality in pregnancy of 10–40%. The aim of this study was to investigate whether pulmonary artery blood pressure (PABP) is a prognostic factor for pregnancy outcome in patients with PAH. Methods and Results: The subjects were 42 patients with PAH during pregnancy. Severe and mild cases were defined by PABP before and during the first 14 weeks of pregnancy, with severe cases having mean PABP >40mmHg by catheterization or systolic PABP >50mmHg on echocardiography. Eighteen women chose termination of pregnancy before 14 weeks, leaving 24 women (10 mild, 14 severe) for analysis. The women with severe PAH delivered earlier (35.4 vs. 31.5 weeks, P<0.05) and had higher rates of small-for-gestational-age infants (0/10 vs. 7/14, P<0.01). Among the women with severe PAH, the New York Heart Association class dropped by 1 in 9 cases, by 2 in 3 cases, and remained the same in 2 cases as pregnancy progressed, whereas among the women with mild PAH, the class dropped by 1 in 1 case and 9 women remained in the same class. Among the severe cases, 1 woman died and there was 1 fetal death; PABP markedly increased in later pregnancy from 54 to 74mmHg (catheter measurement) and from 78 to 93mmHg (echocardiography) (P<0.05). Conclusions: The level of PABP before or in the early stage of pregnancy is an important predictor of pregnancy outcome.  (Circ J 2012; 76: 2249–2254)
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Renal Disease
  • – A Systematic Review and Meta-Analysis –
    Jae-Sik Jang, Han-Young Jin, Jeong-Sook Seo, Tae-Hyun Yang, Dae-Kyeong ...
    2012 Volume 76 Issue 9 Pages 2255-2265
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 07, 2012
    JOURNALS FREE ACCESS
    Background: Sodium bicarbonate has been postulated to prevent contrast-induced acute kidney injury (CI-AKI) by various mechanisms, although the reports are conflicting. Methods and Results: We searched MEDLINE, EMBASE, and the Cochrane databases for randomized controlled trials that compared a sodium chloride with a sodium bicarbonate hydration regimen with regard to CI-AKI. Data across 19 clinical trials consisting of 3,609 patients were combined. Preprocedural hydration with sodium bicarbonate was associated with a significant decrease in the rate of CI-AKI (odds ratio [OR] 0.56; 95% confidence interval [CI] 0.36–0.86; P=0.008). Stratified analyses by the type of contrast medium suggested lower odds of CI-AKI with sodium bicarbonate in studies using low-osmolar contrast media (OR 0.40; 95% CI 0.23–0.71, P=0.002) compared with those using the iso-osmolar agents (OR 0.76; 95% CI 0.41–1.43; P=0.40). No significant difference in the rates of postprocedural death (OR 0.49; 95% CI 0.23–1.04; P=0.06) and the requirement for renal replacement therapy (OR 0.94; 95% CI 0.46–1.91; P=0.86) was observed. However, we found significant changes in serum bicarbonate and potassium levels after sodium bicarbonate infusion. Conclusions: This updated meta-analysis demonstrates that sodium bicarbonate-based hydration is superior to sodium chloride in preventing CI-AKI of patients undergoing exposure to iodinated contrast media.  (Circ J 2012; 76: 2255–2265)
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  • Kazuhiro Dan, Toru Miyoshi, Masayuki Ueeda, Hiroaki Ohtsuka, Satoko Ug ...
    2012 Volume 76 Issue 9 Pages 2266-2272
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 09, 2012
    JOURNALS FREE ACCESS
    Supplementary material
    Background: Renal insufficiency plays a critical role in the pathogenesis of ischemic heart disease. The aim of the present study was to investigate the prevalence of renal dysfunction and its impact on prognosis in patients with left main coronary artery disease (LMCAD) and stable angina pectoris. Methods and Results: A total of 626 consecutive patients with significant coronary artery stenosis were enrolled. Renal insufficiency was graded using estimated glomerular filtration rate (eGFR) before coronary angiography. Chronic kidney disease (CKD) was defined as eGFR <60ml·min–1·1.73m–2 and/or proteinuria. Patients with LMCAD (n=95) had a significantly higher prevalence of CKD than those without LMCAD (P=0.02). Multiple logistic regression analysis showed that CKD was independently associated with LMCAD (adjusted odds ratio, 1.74; 95% confidence interval [CI]: 1.09–2.76, P=0.01). A 1-year follow-up of patients with LMCAD showed that the cumulative incidence of major adverse cardiovascular events among patients with eGFR <30ml·min–1·1.73m–2 was higher than that among patients with eGFR ≥60ml·min–1·1.73m–2 (P=0.03). The hazard ratio for a cardiovascular event was 9.54 (95% CI: 3.15–28.89, P<0.01) when comparing patients with LMCAD and eGFR <30ml·min–1·1.73m–2 vs. patients without LMCAD and eGFR ≥60ml·min–1·1.73m–2. Conclusions: Renal insufficiency is a risk factor for LMCAD and predicts poor prognosis in Japanese patients.  (Circ J 2012; 76: 2266–2272)
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Vascular Biology and Vascular Medicine
  • Jae Hoon Moon, Min Kyung Chae, Kwang Joon Kim, Hyun Min Kim, Bong Soo ...
    2012 Volume 76 Issue 9 Pages 2273-2279
    Published: 2012
    Released: August 24, 2012
    [Advance publication] Released: June 01, 2012
    JOURNALS FREE ACCESS
    Background: The aim of the present study was to investigate the serum levels of endothelial progenitor cells (EPCs) in type 2 diabetic patients without documented ischemic disease and the association between EPCs and atherosclerotic plaque formation in the carotid artery. Methods and Results: A clinic-based, prospective study of type 2 diabetic patients was conducted. A total of 73 subjects were enrolled in this study after cardiac magnetic resonance imaging and ankle-brachial index measurements to exclude patients with ischemic disease. Plaque formation in the carotid artery was measured on ultrasonography. Circulating EPCs (CD34+/CD133+/CD309+ cells) were counted on flow cytometry. Compared to subjects without carotid artery plaques, patients with plaques were significantly older (P=0.006) and had decreased EPC count (P=0.027). Serum glycated albumin (GA) level and the GA/glycated hemoglobin ratio tended to decrease in patients with plaques (P=0.091 and 0.067, respectively). Other cardiovascular disease risk factors were not significantly different between the 2 groups. On binary logistic regression analysis old age, low EPC count, and high serum GA level were independently correlated with carotid artery plaque formation. Conclusions: EPC count and serum GA level appear to be a protective and an aggravating factor for endothelial damage, respectively, and therefore, a reduced EPC count or an increased GA level results in atherosclerotic plaque formation in type 2 diabetic patients.  (Circ J 2012; 76: 2273–2279)
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