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Background: Primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS) may reduce the risk of subsequent cardiovascular events but remains challenging. The study aim was to evaluate the clinical characteristics and long-term outcomes of patients undergoing primary PCI for STEMI with CS., Methods: We conducted an observational cohort study of patients with STEMI who underwent primary PCI between April 2004 and December 2017 at Juntendo University Shizuoka Hospital. The primary outcome was cardiovascular death (CVD) during the median 3-year follow-up. We performed a landmark analysis for the incidence of CVD from 0 day to 1 year and from 1 to 10 years., Results: Among the 1758 STEMI patients in the cohort, 212 (12.1 %) patients with CS showed significantly higher 30-day CVD rate on admission than those without (26.4 % vs 2.9 %). Landmark Kaplan-Meier analysis showed that CVD from day 0 to year 1 was significantly higher in the patients with CS (log-rank p < 0.0001). Multivariate Cox regression analysis showed that CS was significantly associated with higher cardiovascular mortality (adjusted hazard ratio, 11.8; 95%confidence intervals, 7.78-18.1; p < 0.0001), but the mortality rates from 1 to 10 years were comparable (log-rank p = 0.68)., Conclusion: The cardiovascular 1-year mortality rate for patients with STEMI was higher for those with CS on admission than without, but the mortality rates of >1 year were comparable. Surviving the early phase is essential for patients with STEMI and CS to improve long-term outcomes., Competing Interests: Disclosures None. Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Standard modifiable cardiovascular risk factors (SMuRFs; hypertension, diabetes mellitus, dyslipidemia, and smoking) are widely recognized as risk factors for coronary artery disease. However, the associations between absence of SMuRFs and long-term clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients are unclear., Methods: Consecutive STEMI patients who underwent primary percutaneous coronary intervention (PCI) between 1999 and 2015 were retrospectively analyzed. The primary endpoint was up to 5-year all-cause mortality. Clinical characteristics and outcomes were compared between patients with at least one of the SMuRFs and those without any SMuRFs., Results: Of 1963 STEMI patients, 126 (6.4 %) did not have any SMuRFs. Patients without SMuRFs were significantly older, had lower body mass index, and were more likely to be female. During a median follow-up period of 4.9 years, the cumulative incidence of death was significantly higher in patients without SMuRFs than in those with SMuRFs (log-rank p < 0.0001). Landmark analysis showed that patients without SMuRFs had higher mortality within 30 days of STEMI onset (log-rank p = 0.0045) and >30 days after STEMI onset (log-rank p = 0.0004). Multivariable Cox hazards analysis showed that absence of SMuRFs was associated with a higher risk of mortality (hazard ratio, 1.59; 95 % confidence interval, 1.14-2.21; p = 0.006)., Conclusions: Of STEMI patients undergoing primary PCI, patients without any SMuRFs had higher mortality than those with at least one of the SMuRFs. Patients without any SMuRFs have a poor prognosis and require more attention., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Recent clinical trials have shown that percutaneous coronary intervention (PCI) for non-culprit lesions (NCLs) reduces the risk of adverse events in patients with ST-segment elevation myocardial infarction (STEMI), but the effect on long-term outcomes remains unclear in acute coronary syndrome (ACS) patients and a real-world clinical setting., Methods: A retrospective observational cohort study of ACS patients who underwent primary PCI between April 2004 and December 2017 at Juntendo University Shizuoka Hospital, Japan, was performed. The primary endpoint was the composite of cardiovascular disease death (CVD death) and non-fatal myocardial infarction (MI) during the mean follow-up period of 2.7 years, and a landmark analysis for the incidence of the primary endpoint from 31 days to 5 years between the multivessel PCI group and the culprit only PCI group was performed. Multivessel PCI was defined as PCI including non-infarct-related coronary arteries within 30 days after the onset of ACS., Results: Of the 1109 ACS patients with multivessel coronary artery disease of the current cohort, multivessel PCI was performed in 364 (33.2 %) patients. The incidence of the primary endpoint from 31 days to 5 years was significantly lower in the multivessel PCI group (4.0 % vs. 9.6 %, log-rank p = 0.0008). Multivariate Cox regression analysis showed that multivessel PCI was significantly associated with fewer cardiovascular events (HR 0.37, 95 % CI 0.19-0.67, p = 0.0008)., Conclusion: In ACS patients with multivessel coronary artery disease, multivessel PCI may reduce the risk of CVD death and non-fatal MI compared to culprit-lesion-only PCI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The impact of shorter door-to-balloon (DTB time on long-term outcomes in ST-segment elevation myocardial infarction (STEMI treated with primary percutaneous coronary intervention (PPCI has not been fully elucidated., Methods: We investigated 3283 consecutive patients with acute myocardial infarction selected from a prospective, nationwide, multicenter registry (J-MINUET database comprising 28 institutions in Japan between July 2012 and March 2014. Among the study population, we analyzed 1639 STEMI patients who had PPCI within 12 h of onset. Patients were stratified into four groups (DTB time < 45 min, 45-60 min, 61-90 min, >90 min. The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. We performed landmark analysis for incidence of the primary endpoint from 31 days to 3 years among the four groups., Results: The primary endpoint rate from 31 days to 3 years increased significantly and time-dependently with DTB time (10.2 % vs. 15.3 % vs. 16.2 % vs. 19.3 %, respectively; log-rank p = 0.0129. Higher logarithm-transformed DTB time was associated with greater risk of a primary endpoint from 31 days to 3 years, and the increased number of adverse long-term clinical outcomes persisted even after adjusting for other independent variables., Conclusion: Shorter DTB time was associated with better long-term clinical outcomes in STEMI patients treated with PPCI in contemporary clinical practice. Further efforts to shorten DTB time are recommended to improve long-term clinical outcomes in STEMI patients., Trial Registration: UMIN Unique trial Number: UMIN000010037., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Yukio Ozaki has received several research grants from Bayer Yakuhin, Ltd., Research Institute for Production Development, Daiichi-Sankyo Co., Ltd., and Dainippon Sumitomo Co., Ltd. Kazuo Kimura has received honoraria from AstraZeneca, Toa Eiyo Ltd., MSD K.K., Bayer Yakuhin, Ltd., and Daiichi-Sankyo Co., Ltd., and has received several research grants from MSD K.K., Daiichi-Sankyo Co., Ltd., Ono Pharmaceutical Co., Pfizer Japan Inc., Bayer Yakuhin Ltd., Takeda Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan, Tanabe Mitsubishi, and Astellas Pharma Inc. Wataru Shimizu has received honoraria from Daiichi-Sankyo Co., Ltd., Boehringer Ingelheim Japan, Bayer Yakuhin Ltd., Bristol, and Ono Pharmaceutical Co., and has received several research grants from Daiichi-Sankyo Co., Ltd., Boehringer Ingelheim Japan, Ono Pharmaceutical Co., Otsuka Pharmaceutical Co., Eisai Co., Mitsubishi Tanabe Pharma Co., Asterllas Pharma Inc., and St Jude Medical. Yoshihiko Saito has received honoraria from Otsuka Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Novartis Pharma K.K., and has received several research grants from Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Eisai Co., Ltd., ZERIA Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Astellas Pharma Inc., Daiichi Sankyo Co., Ltd., and Boston Scientific Japan K.K. Toshiaki Mano has received a research grant from Abbot Vascular Japan. Kengo Tanabe has received honoraria from Abbot Vascular Japan, Mitsubishi Tanabe Pharma Co., and Daiichi Sankyo Co., Ltd. and has received several research grants from Kaneka and Terumo. Kenichi Tsujita has received honoraria from Amgen Astellas Bio Pharma K.K., Bayer Yakuhin, Ltd., Daiichi Sankyo Co., Ltd., MSD K.K., and Sanofi K.K., and has received several research grants from AstraZeneca K.K., Astellas Pharma Inc., Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan, Boston Scientific Japan K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Kowa Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., MSD K.K., Pfizer Japan Inc., Sanofi K.K., Shionogi & Co., Ltd., and Takeda Pharmaceutical Co., Ltd. Masaharu Ishihara has received honoraria from Bayer Yakuhin Ltd., MSD K.K., Astra Zeneca, and Astellas Pharma Inc. and has received several research grants from Abbott Vascular Japan, Boston Scientific Japan K.K., Sanofi K.K., MSD K.K., Astellas Pharma Inc., Bayer Yakuhin Ltd., Pfizer, Daiichi Sankyo Co., Ltd., MID, and Goodman. No funders played any role in this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Diabetes was reported to be associated with an impaired response to clopidogrel., Objectives: The aim of this study was to evaluate the safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) in patients with diabetes undergoing percutaneous coronary intervention (PCI)., Methods: A subgroup analysis was conducted on the basis of diabetes in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2) Total Cohort (N = 5,997) (STOPDAPT-2, n = 3,009; STOPDAPT-2 ACS [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 for the Patients With ACS], n = 2,988), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT with aspirin and clopidogrel after cobalt-chromium everolimus-eluting stent implantation. The primary endpoint was a composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (TIMI [Thrombolysis In Myocardial Infarction] major or minor) endpoints at 1 year., Results: There were 2,030 patients with diabetes (33.8%) and 3967 patients without diabetes (66.2%). Regardless of diabetes, the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (diabetes, 3.58% vs 4.12% [HR: 0.87; 95% CI: 0.56-1.37; P = 0.55]; nondiabetes, 2.46% vs 2.49% [HR: 0.99; 95% CI: 0.67-1.48; P = 0.97]; P interaction  = 0.67) and for the cardiovascular endpoint (diabetes, 3.28% vs 3.05% [HR: 1.10; 95% CI: 0.67-1.81; P = 0.70]; nondiabetes, 1.95% vs 1.43% [HR: 1.38; 95% CI: 0.85-2.25; P = 0.20]; P interaction  = 0.52), while it was lower for the bleeding endpoint (diabetes, 0.30% vs 1.50% [HR: 0.20; 95% CI: 0.06-0.68; P = 0.01]; nondiabetes, 0.61% vs 1.21% [HR: 0.51; 95% CI: 0.25-1.01; P = 0.054]; P interaction  = 0.19)., Conclusions: Clopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT reduced major bleeding events without an increase in cardiovascular events regardless of diabetes, although the findings should be considered as hypothesis generating, especially in patients with acute coronary syndrome, because of the inconclusive result in the STOPDAPT-2 ACS trial. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498)., Competing Interests: Funding Support and Author Disclosures This work (STOPDAPT-2 and STOPDAPT-2 ACS) was supported by Abbott Vascular Japan. The study sponsor is not involved in the implementation of the study, data collection, event fixation and statistical analysis. However, approval of the study sponsor should be obtained for presentation in scientific meetings and submission of papers. Dr H. Watanabe has received honoraria from Abbott Medical, Abiomed, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Kowa, Pfizer, and Otsuka; and has received support for attending meetings from Abbott Medical. Dr Morimoto has received lecture fees from Bristol Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; has received manuscript fees from Bristol Myers Squibb and Kowa; and has participated on an advisory board for Sanofi. Dr Natsuaki has received honoraria from Abbott Medical. Dr Ogita has received honoraria from Abbott Medical, Daiichi Sankyo, and Japan Lifeline. Dr Suwa has received honoraria from Abbott Medical and Daiichi Sankyo. Dr Kimura has received research grant support from Abbott Medical and Boston Scientific; has received honoraria from Abbott Medical, Boston Scientific, Daiichi Sankyo, Sanofi, and Terumo; and has participated on advisory boards for Abbott Medical, Boston Scientific, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate the impact of thrombotic risk on the occurrence of cardiovascular events in patients with coronary artery disease with deferred revascularization after fractional flow reserve (FFR) measurements., Background: Deferral of revascularization on the basis of FFR is generally considered to be safe, but after deferral, some patients have cardiovascular events over time., Methods: From J-CONFIRM registry (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry), 1,263 patients with deferral of revascularization on the basis of FFR were evaluated. The association between thrombotic risk as assessed by CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) thrombotic score and 5-year target vessel failure (TVF) and major adverse cardiac and cerebrovascular events (MACCE) was investigated., Results: FFR and high thrombotic risk (HTR) were associated with increased risk for 5-year TVF (FFR per 0.01-unit decrease: HR: 1.08; 95% CI: 1.05-1.11; P < 0.001; HTR: HR: 2.16; 95% CI: 1.37-3.39; P < 0.001) and MACCE (FFR per 0.01-unit decrease: HR: 1.05; 95% CI: 1.02-1.06; P < 0.001; HTR: HR: 2.11; 95% CI: 1.56-2.84; P = 0.001). Patients with HTR had higher risk for 5-year TVF (HR: 2.30; 95% CI: 1.45-3.66; P < 0.001) and MACCE (HR: 2.34; 95% CI: 1.75-3.13; P < 0.001) than those without HTR, even when they had negative FFR., Conclusions: Assessment of thrombotic risk provides additional prognostic value to FFR in predicting 5-year TVF and MACCE in patients with deferral of revascularization after FFR measurements. (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry; UMIN000014473)., Competing Interests: Funding Support and Author Disclosures This work was supported by Abbott Medical Japan, Phillips Japan, and Boston Scientific Japan. The funders of the study had no role in the study design, data collection, data analysis, interpretation of the data, writing of the report, or decision to submit the paper for publication. Dr Shiono has received lecture fees from Abbott Medical Japan and Phillips Japan. Dr Kuramitsu has received lecture fees from Abbott Medical Japan and Boston Scientific Japan. Dr Matsuo serves as an advisory board member for Zeon Medical; and has received lecture fees from Abbott Medical Japan, Phillips Japan, and Boston Scientific Japan. Dr Kikuta has received lecture fees from Abbott Medical Japan and Phillips Japan. Dr Asano has received lecture fees from Abbott Medical Japan and Phillips Japan. Dr Tanaka serves as advisory board member for Abbott Medical Japan and Boston Scientific Japan. Dr Yokoi has received lecture fees from Boston Scientific Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Because primary squamous cell carcinoma (SCC) of the breast is a rare disease, the standard therapy has not been established. We examined the clinical outcomes of postoperative adjuvant radiotherapy for breast SCC., Material and Methods: We conducted a multicenter retrospective cohort study. Patients diagnosed with primary breast SCC who received adjuvant radiotherapy as part of their primary definitive treatment were included. Overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free interval (RFi) were evaluated., Results: Between January 2002 and December 2017, 25 breast SCC patients received adjuvant radiotherapy as a primary treatment were included. Median follow-up time was 43.5 months. Three (12%), fifteen (60%) and seven (28%) patients had clinical stage I, II and III disease, respectively. Fourteen patients underwent breast-conserving surgery and subsequent adjuvant radiotherapy. Eleven patients underwent mastectomy and post-mastectomy radiotherapy. Ten patients received regional lymph node irradiation. Nine (36%) patients had disease recurrence. The first site of recurrence was locoregional in five, but distant metastasis arose in one. Concurrent local and distant metastasis were seen in two. Six cases of local recurrence occurred within the irradiated site. Seven patients died, and six of the deaths were due to breast cancer. Five-year OS, BCSS, and Rfi were 69%, 70%, and 63%, respectively. In multivariate analysis, age and lymphatic invasion were associated with increased risk of recurrence., Conclusion: Breast SCC has a high incidence of locoregional recurrence and poor prognosis. Age and lymphatic invasion are significant risk factors for recurrence., Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Serum levels of lipoprotein (a) [Lp(a)] have been reported as a residual risk marker for adverse events in patients with coronary artery disease (CAD). However, the prognostic impact of Lp(a) on long-term clinical outcomes among diabetic patients on statin therapy after percutaneous coronary intervention (PCI) remains unclear., Methods: The present investigation was a single-center, observational, retrospective cohort study. Among consecutive patients with CAD who underwent first PCI in our institution from 2000 to 2016, we enrolled diabetic patients on statin treatment. As a result, 927 patients (81% men; mean age, 67 years) were enrolled and divided into 2 groups according to a median Lp(a) level of 19.5 mg/dL. The incidence of major adverse cardiac events (MACE), including all-cause death, non-fatal myocardial infarction (MI), and non-fatal cerebral infarction (CI), was evaluated., Result: No significant differences were seen in age, sex, smoking habits, hypertension, chronic kidney disease, or body mass index between high and low Lp(a) groups. During follow-up (median, 5.0 years; interquartile range, 1.9-9.7 years), MACE occurred in 90 cases (17.6%), including 40 (7.9%) cardiac deaths, 18 (3.6%) non-fatal MI, and 37 (7.9%) non-fatal CI. Frequency of MACE was significantly higher in the high-Lp(a) group than in the low-Lp(a) group (log-rank test, p = 0.002). Higher Lp(a) level at the time of PCI was significantly associated with higher frequency of MACE, even after adjusting for other covariates, including other lipid profiles (hazard ratio, 1.91; 95% confidence interval, 1.20-3.09; p = 0.006)., Conclusion: Our results demonstrated that in diabetic patients with CAD on statin treatment, increased Lp(a) levels could offer a good residual lipid risk marker. Assessing Lp(a) levels may be useful for risk stratification of long-term clinical outcomes after PCI, especially in diabetic patients., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: Previous studies in older populations have shown a cardioprotective effect for obesity, an observation known as the obesity paradox. However, whether a decrease or increase in body weight over a certain period affects disability and mortality in older adults remains unknown. Hence, we examined whether the percent body weight change can predict the risk of mortality and disability in older Japanese adults., Design: We performed a longitudinal prospective cohort study., Setting and Participants: We investigated 1229 community-dwelling older adults (aged ≥65 years) living in Japan., Methods: Participants were divided into 3 groups (weight loss, stable weight, and weight gain) based on percentage body weight change (using 1 standard deviation from the mean as cutoff points) between 2011 and 2013. Death and disability incidences were monitored between April 2013 and March 2016. Disability was defined as the need for new long-term care insurance (LTCI)., Results: The rates of death and new LTCI requests over the 3-year follow-up were 2.4% and 4.7%, respectively. The weight loss group (reduction >4.8%) had a 5.0% death rate and an 11.1% new LTCI rate, which were significantly higher than those in the stable weight (1.6% and 3.8%, respectively) and weight gain (ie, gain >3.1%) groups (3.9% and 4.7%, respectively). Cox regression analysis confirmed a higher risk for death [hazard ratio (HR) = 3.10, 95% confidence interval (CI) = 1.31-7.31] and new LTCI requests (HR = 3.03, 95% CI = 1.69-5.43) only in the weight loss group. The body mass index did not significantly influence the risk of death or disability., Conclusions/implications: Weight loss over 2 years but not body mass index was associated with a higher death and disability risk during the subsequent 3-year follow-up period among older participants. Weight change surveillance can improve the quality of health care by early identifying frailty and death risk population., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Suvorexant, an orexin receptor antagonist, is known as a safe and effective sleep medication. Many patients with heart failure (HF) have sleep-disordered breathing (SDB) and are short sleepers, and it is unknown whether suvorexant is effective in HF patients and can improve insomnia safely. The aim of this study is to examine the effect of suvorexant on SDB in patients with HF., Methods: The Heart Failure with Insomnia and Suvorexant trial of Juntendo University Hospital and Juntendo Shizuoka Hospital (J-FLAVOR trial) is a multicenter trial with a randomized double crossover design. We will enroll a total of 30 HF patients treated in the Juntendo University Hospital and Juntendo Shizuoka Hospital. Eligible patients will undergo portable sleep monitoring twice with or without oral administration of suvorexant in a randomly assigned order. Before the study night, patients in the suvorexant first group will receive suvorexant for 4 consecutive days. There are at least 3 wash-out days between the study nights with and without suvorexant. Primary outcome measures of the non-inferiority trial of suvorexant include the apnea-hypopnea index and the severity of SDB, and the results will be compared between the study nights with and without suvorexant., Conclusion: The present study can determine whether suvorexant can be used in HF patients without affecting their SDB. This is a pilot study to primarily assess whether suvorexant affects the severity of SDB in patients with HF. Therefore, further study is warranted to investigate whether suvorexant alters short- and long-term clinical outcomes by providing longer and better sleep in patients with HF., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Introduction: C-reactive protein (CRP) is an established marker for vascular inflammation and predictor of adverse cardiovascular events, but the prognostic value of preprocedural CRP in coronary artery disease (CAD) patients who have undergone percutaneous coronary intervention (PCI) remains controversial. Furthermore, the impact of CRP levels during follow-up in CAD patients after PCI on long-term adverse clinical outcomes is uncertain. We evaluated the association between high-sensitivity (hs)-CRP values at follow-up angiography and long-term clinical outcomes in CAD patients after coronary intervention., Methods: We prospectively enrolled 3507 consecutive CAD patients who underwent first PCI between 1997 and 2011 at our institution. We identified 2509 patients (71.5%) who underwent follow-up angiography (6-8 months after PCI). Of those, 1605 patients (45.8%) who had data available for hs-CRP at follow-up angiography were stratified into three groups according to tertiles of hs-CRP level at the time of follow-up angiography. The primary endpoint was composite of all-cause death and non-fatal acute coronary syndrome (ACS)., Results: Median follow-up was 1716 days. The cumulative incidence of all-cause death and ACS differed significantly among groups (log-rank, p=0.0002). Multivariate Cox regression analysis showed that a higher hs-CRP level at follow-up angiography was associated with a greater risk of all-cause death and ACS [adjusted hazard ratio (HR) for all-cause death and ACS 2.14, 95% confidence interval (CI) 1.43-3.27, p=0.0002., Conclusion: Elevated hs-CRP levels during follow-up were significantly associated with higher frequencies of adverse long-term clinical outcomes in patients with CAD after PCI., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Although an elevated mean platelet volume (MPV) has been associated with poor clinical outcomes after acute coronary syndrome (ACS), the association between MPV and long-term outcomes in patients with stable coronary artery disease (CAD) remains uncertain. We aimed to investigate the impact of pre-procedural MPV levels in patients following elective percutaneous coronary intervention (PCI)., Methods: We studied 2872 stable CAD patients who underwent their first PCI and who had available data on pre-procedural MPV between 2002 and 2016. Patients were divided into quartiles based on their MPV. The incidences of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, were evaluated., Results: The median MPV was 10.4 fL (interquartile range: 9.8-11.0). During a median follow-up of 5.6 years, 498 (17.3%) MACE were identified, with a cumulative incidence significantly higher in the lowest MPV group than in other groups (p < 0.01). After adjustment for platelet count and the other cardiovascular risk factors, the lowest MPV group had a significantly higher risk of MACE compared with the highest MPV groups (hazard ratio: 1.43, 95% confidence interval 1.10-1.86, p = 0.009). Decreasing MPV as a continuous variable was associated with the incidence of MACE (hazard ratio: 1.16 per 1 fL decrease, 95% confidence interval 1.04-1.30, p = 0.007)., Conclusions: Contrary to previous studies on ACS patients, this study showed that a low MPV was associated with worse clinical outcomes among stable CAD patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The prognostic long-term impact of body mass index (BMI) on East Asian patients with coronary artery disease remains unclear., Methods: An observational retrospective cohort study was carried out involving 3571 patients who had undergone percutaneous coronary intervention (PCI) from 2000 to 2013. Patients were divided into the following five groups according to baseline BMI: Group 1 (underweight 1, BMI ≤20.0kg/m 2 ); Group 2 (underweight 2, BMI=20.1-22.5kg/m 2 ); Group 3 (normal weight, BMI=22.6-25.0kg/m 2 ); Group 4 (overweight 1, BMI=25.1-27.5kg/m 2 ); and Group 5 (overweight 2, BMI ≥27.6kg/m 2 ). We then evaluated the association between BMI and both all-cause and cardiac death after PCI., Results: The ratio of patients in the five groups was as follows: Group 1, 9.2%; Group 2, 21.6%; Group 3, 34.1%; Group 4, 21.1%; and Group 5, 14.5%. A decrease in age was observed from underweight to overweight, as was an increased prevalence of hypertension, diabetes mellitus, dyslipidemia, and smoking. The median follow-up period was 6.3 years (interquartile range, 3.2-9.6 years). In total, 473 deaths (frequency, 13.2%) were identified, including 183 (5.1%) cardiac deaths during follow-up. In unadjusted Cox proportional hazard analysis, using normal weight as the reference, underweight, but not overweight, was associated with a greater risk of both all-cause and cardiac death. In an adjusted model, Group 1 had the highest risk for all-cause death (hazard ratio, 1.58; 95% confidence interval, 1.19-2.10; p=0.0019); however, no significant differences were found for the risk of all-cause and cardiac death between normal weight and overweight patients., Conclusion: The results of the present long-term follow-up study do not support the so-called "obesity paradox," but rather, suggest that underweight Japanese patients are at greater risk for all-cause mortality following PCI., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Malnutrition has recently been reported to correlate with prognosis in patients with heart failure. However, the prognostic significance of nutritional status in patients with stable coronary artery disease (CAD) is unknown. The present study sought to examine the association between nutritional status assessed by the prognostic nutritional index (PNI) and cardiovascular outcomes in patients with stable CAD., Methods: A total of 1988 patients with stable CAD who underwent elective percutaneous coronary intervention (PCI) between 2000 and 2011 were examined. The PNI was calculated as 10×serum albumin (g/dL)+0.005×total lymphocyte count (per mm 3 ). Patients were assigned to tertiles based on their PNI. The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated., Results: The median PNI was 48.9 (interquartile range: 45.5-52.1). During the median follow-up of 7.5 years, Kaplan-Meier analysis showed that patients with lower PNI tertiles had higher rates of MACE (PNI <46.7: 35.5%; 46.7-50.8: 22.3%; >50.8: 16.0%; log-rank p<0.0001). After adjusting for other risk factors, the PNI was independently associated with MACE (hazard ratio 2.05 per 10 PNI decrease, 95% confidence interval: 1.66-2.54, p<0.0001). Adding the PNI to a baseline model with established risk factors improved the C-index (p=0.03), net reclassification improvement (p=0.03), and integrated discrimination improvement (p=0.0001)., Conclusions: The PNI was significantly associated with long-term cardiovascular outcomes in patients with stable CAD. Assessing PNI may be useful for risk stratification of CAD patients undergoing elective PCI., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: No nutritional index has been firmly established yet in patients with coronary artery disease (CAD). In this study, we propose a simple to calculate nutritional indicator in patients who underwent percutaneous coronary intervention (PCI) by using parameters routinely measured in CAD and evaluated its prognostic implication., Methods: This study is a retrospective observational analysis of a prospective database. The subjects were consecutive 3567 patients underwent their first PCI between 2000 and 2013 at Juntendo University Hospital in Tokyo. The median of the follow-up period was 6.3 years (range: 0-13.6 years). The novel nutritional index was calculated by the formula; Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI) = TG × TC × BW / 1000 (TG and TC: mg/dl, and BW: kg)., Results: The Spearman non-parametric correlation coefficient between TCBI and the most often used conventional nutritional index, Geriatric Nutritional Risk Index (GNRI), was 0.355, indicating modest correlation. Moreover, Unadjusted Kaplan-Meier analysis showed higher all-cause mortality, cardiovascular mortality, and cancer mortality in patients with low TCBI. Consistently, elevation of TCBI was associated with reduced all-cause (hazard ratio: 0.86, 95%CI: 0.77-0.96, p < 0.001), cardiovascular (0.78, 0.66-0.92, p = 0.003), and cancer mortality (0.76, 0.58-0.99, p = 0.041) in patients after PCI by multivariate Cox proportional hazard analyses., Conclusion: TCBI, a novel and easy to calculate nutrition index, is a useful prognostic indicator in patients with CAD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: Low serum albumin level is reportedly associated with worse clinical outcomes in patients with chronic kidney disease (CKD). However, associations between decreased serum albumin level and outcomes in non-CKD patients with coronary artery disease (CAD) remain unclear. Therefore, we aimed to evaluate the prognostic value of serum albumin concentrations in stable CAD patients with preserved renal function., Methods and Results: We studied 1316 patients with CAD and preserved renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m 2 ) who underwent their first PCI between 2000 and 2011 and had data available for pre-procedural serum albumin. Patients were assigned to quartiles based on pre-procedural albumin concentrations. The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated. Mean albumin concentration was 4.1 ± 0.4 g/dL. During the median follow-up of 7.5 years, 181 events occurred (13.8%). Kaplan-Meier curves revealed that patients with decreased serum albumin concentrations showed a higher event rate for MACE (log-rank, p < 0.0001). Using the highest tertiles (>4.3 g/dL) as reference, adjusted hazard ratios were 1.97 (95% CI, 1.12-3.55), 1.77 (95% CI, 0.99-3.25), and 1.19 (95% CI, 0.68-2.15) for serum albumin concentrations of <3.9, 3.9-4.0, and 4.1-4.3 g/dL, respectively. Decreased serum albumin concentration was associated with MACE even after adjusting for other independent variables (HR, 2.21 per 1-g/dL decrease; 95% CI, 1.37-3.56, p = 0.001)., Conclusion: Decreased serum albumin concentration independently predicted worse long-term prognosis in non-CKD patients after PCI. Pre-procedural serum albumin concentration could offer a useful predictor for patients with CAD and preserved renal function., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The association between patients with acute myocardial infarction (AMI) who present during off-hours and clinical outcomes has not been fully elucidated., Methods: We investigated 3283 consecutive patients with AMI who were selected from a prospective, nationwide, multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014 to determine the current impact of off-hours presentation on in-hospital mortality among Japanese patients with AMI., Results: Among the patients, 52% presented in off-hours. Baseline characteristics were comparable, although those who presented during off-hours were younger and had a higher incidence of ST-elevation myocardial infarction and advanced Killip Class. The time from symptom onset to presentation time was shorter in off-hour patients (120min, interquartile range 60 to 256 vs. 215min, interquartile range 90 to 610, p<0.0001). In contrast, 85% of patients underwent primary percutaneous coronary intervention (PCI) and door to balloon time was comparable between the groups (74min, interquartile range 52 to 113 vs. 75min, interquartile range 52 to 126, p=0.34). The rates of in-hospital mortality were comparable (6.2% vs 6.8%, p=0.39). Multivariate logistic regression analysis revealed that off-hours presentation was not significantly associated with in-hospital mortality [odds ratio (OR) 0.94; 95% CI, 0.68-1.30, p=0.70]., Conclusion: The clinical impact of presenting during off-hours or regular hours on AMI patients in Japan is comparable in contemporary practice., Trial Registration: UMIN Unique trial Number: UMIN000010037., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: An elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with worse clinical outcomes in patients with acute coronary syndrome. However, the long-term prognostic value of NLR in stable coronary artery disease (CAD) after percutaneous coronary intervention (PCI) has not been fully investigated. The aim of this study was to determine whether NLR is an independent predictor of long-term cardiac outcomes after PCI., Methods: A total of 2070 patients with CAD who underwent elective PCI were enrolled in the study. Patients were divided into three groups by NLR tertile (<1.7, 1.7-2.5, and 2.5<). Incidences of all-cause death and cardiac death were evaluated., Results: During follow-up (median, 7.4 years), 300 patients (14.5%) died. Kaplan-Meier curves revealed ongoing divergence in rates of all-cause death and cardiac death among tertiles (both log-rank p < 0.01). In multivariate analysis, using the lowest tertile as reference, the highest tertile remained significantly associated with greater incidences of all-cause death (hazard ratio (HR), 1.73; 95% confidence interval (CI), 1.29-2.34; p = 0.0002). Continuous NLR values were also an independent predictor of all-cause death (HR, 1.87 per log NLR 1 increase; 95% CI, 1.50-2.32; p < 0.0001) and cardiac death (HR, 2.11; 95% CI, 1.46-3.05; p < 0.0001). Adding NLR values to a baseline model with established risk factors improved the C-index (p = 0.002), net reclassification improvement (p = 0.008) and integrated discrimination improvement (p = 0.0001) for all-cause death., Conclusions: Elevated NLR was an independent predictor of long-term cardiovascular outcomes after elective PCI. Assessing pre-PCI NLR may be useful for risk stratification of stable CAD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Numerous studies have reported the relationship between elevated homocysteine (Hcy) levels and the risk of coronary artery disease. However, there is insufficient information about the effects of Hcy levels on long-term clinical outcomes in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI)., Methods: In the Juntendo-registry cohort from 2003 to 2004, pre-procedural Hcy levels and Hcy thiolactonase activity (HTlase) were measured in 315 consecutive all-comer patients who underwent PCI for stable coronary artery disease or acute coronary syndrome (ACS). Receiver-operating characteristic (ROC) curves were created to assess the optimal cut-off values of Hcy and HTlase. Multivariable Cox proportional hazard regression analysis was used to identify the predictors of clinical outcome. The primary endpoint was all-cause mortality., Results: The patients' mean age was 66±9 years, and 82.5% were males. The median follow-up period was 10.5 years, and overall mortality was 24.5% (73 deaths). On ROC analysis, the optimal cut-off values of Hcy and HTlase were 13.5μmol/L and 230IU/L, respectively. Kaplan-Meier survival analysis showed associations of both higher Hcy levels and lower HTlase activity with worse prognosis (both log-rank p<0.001). On multivariate Cox proportional hazard regression analysis, higher Hcy was strongly associated with the primary outcome, and the adjusted hazard ratio was 3.3 (95% confidence interval, 1.8-5.6; p<0.001)., Conclusions: Pre-procedural high Hcy levels and low HTlase activity were associated with worse long-term mortality in Japanese patients undergoing PCI. Moreover, Hcy levels are strongly predictive for mortality, independent of traditional risk factors. This may have implications for risk stratification and the therapeutic approach in this PCI era., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: It is clear that each trend of kyphosis with increased age and the ability to eat firm foods with the back teeth (chewing ability) has a strong influence on both the physical and mental condition of older people. Thus, this study aimed to examine whether the combination of kyphosis and chewing disorders was associated with mortality or the need for care under the new long-term care insurance (LTCI) service requirement, over 3 years in community-dwelling older Japanese adults., Design: A prospective cohort study., Setting and Participants: We analyzed the cohort data for older adults (65 years or older) from a prospective study in Kami town. The response rate was 94.3%, and we followed 5094 older individuals for 3 years. Thus, we analyzed 5083 older adults using multiple imputation to manage missing data., Outcome: The outcomes were mortality or new certifications for LTCI services in a 3-year period., Measurements: We developed 3 groups by asking 2 self-reported questions on both "no kyphosis" and "good chewing ability." The groups were no kyphosis and good chewing ability (GG), kyphosis and poor chewing ability (BB), and kyphosis and good chewing ability or no kyphosis and poor chewing ability (GB/BG)., Results: The prevalence of BB, BG/GB, and GG were 8.9%, 40.3%, and 50.8%, respectively, in our survey. During the 3-year follow-up period, 5.2% (n = 262) died and 13.9% (n = 708) individuals were newly certified as needing LTCI services. As determined by multivariate analyses, BG/GB older adults (adjusted hazard ratio: 1.3 [95% CI 1.1-1.6]) and BB older adults (adjusted hazard ratio: 2.0 [95% CI 1.5-2.4]) had a significantly higher risk of needing LTCI services than GG older adults. Similarly, BG/GB older adults (adjusted hazard ratio: 1.5 [95% CI 1.1-2.0]) and BB older adults (adjusted hazard ratio: 2.3 [95% CI 1.5-3.3]) had a significantly higher risk of mortality than GG older adults did., Conclusion: The presence of kyphosis or poor chewing ability was related to mortality and new certifications for LTCI services, and we found an additive effect of these 2 factors related to frailty., (Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Triple antithrombotic therapy increases the risk of bleeding events in patients undergoing percutaneous coronary intervention (PCI) compared with dual anti-platelet therapy (DAPT). However, whether warfarin control is associated with reduced cardiovascular events and major bleeding events in patients undergoing PCI with triple antithrombotic therapy is uncertain., Methods: We investigated 1207 consecutive patients who underwent PCI between 2004 and 2011. Major bleeding complications and major adverse cardiac and cerebrovascular events (MACCE) defined as all-cause death, acute coronary syndrome, target vessel revascularization, and stroke were compared between groups of patients who received either triple antithrombotic therapy or DAPT., Results: Triple antithrombotic therapy was administered to 95 (7.9%) patients. The mean international normalized ratio of prothrombin time (PT-INR) was 1.8. The target PT-INR level was set between 1.6 and 2.6 and the ratio (%) of time in the therapeutic range (TTR) was calculated. The median TTR was 78.4% (interquartile range, 67.4-87.6%). Kaplan-Meier survival curves showed that warfarin therapy was not associated with MACCE (p=0.89) and major bleeding (p=0.80). Multivariable Cox regression analysis revealed that triple antithrombotic therapy was not an independent predictor of MACCE and major bleeding., Conclusions: Triple antithrombotic therapy does not increase the occurrence of MACCE and major bleeding complications, if the warfarin dose is tightly controlled with a lower INR., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Female has been demonstrated to be at higher risk following percutaneous coronary intervention (PCI) compared with male in unadjusted analyses. However, conflicting results were observed after adjustment of confounding factors. Particularly, more recent studies reported that gender differences have diminished possibly by evolution of PCI-related devices and evidence-based medical therapy. We aimed to examine gender differences in long-term clinical outcomes following PCI during time period of 25 years., Methods: This was a single center retrospective study in which consecutive patients who received the first PCI in our institution between January 1984 and December 2008 were analyzed. A composite of all-cause death and acute coronary syndrome (ACS) at 5-year after the index PCI was compared between genders. The endpoint was also examined in plain-old balloon angioplasty (POBA)-, bare metal stent (BMS)- and drug-eluting stent (DES)-eras separately., Results: A total of 3531 patients (female; 605, male; 2926) were analyzed. The female patients had higher risk profiles than the male in terms of age, comorbid diseases, a prevalence of ACS, while male patients had a higher percentage of smoking, lower left ventricular ejection fraction (LVEF) and lower percentages of secondary prevention drugs. Gender difference was not observed in 5-year all-cause death and ACS in multivariable Cox regression analysis. After controlling variables, age, body mass index, hemoglobin value and LVEF were associated with the clinical outcomes in both genders., Conclusion: Gender difference was not observed in the long-term all-cause death and ACS in patients following PCI., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease. The predictive power of traditional risk factors for cardiovascular disease is diminished in patients with CKD. The serum level of lipoprotein(a) [Lp(a)] can be a risk factor for adverse events, but the clinical implications of Lp(a) in patients with CKD who have been treated by percutaneous coronary intervention (PCI) remain uncertain. We aimed to determine the role of Lp(a) on long-term outcomes in patients with CKD after PCI., Methods: We analyzed data from 904 patients with CKD among 3508 patients who underwent a first PCI between 1997 and 2011 at our institution. We divided patients into 2 groups [high (n=454) or low (n=450)] according to median levels of Lp(a). The primary outcome was a composite of all-cause death and acute coronary syndrome (ACS)., Results: The baseline characteristics of the groups were similar and the median follow-up period was 4.7 years. Cumulative event-free survival was significantly worse for the group with high, than low Lp(a) (P=0.01). Multivariable analysis indicated a high Lp(a) level as an independent predictor of primary outcomes (hazard ratio, 1.35; 95% CI, 1.01-1.82; P=0.04)., Conclusions: A high Lp(a) value is associated with a poor prognosis after PCI for patients with CKD., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Background: LR11, a member of LDL receptor family, is a novel marker of the proliferation of intimal smooth muscle cells (SMCs). LR11 is released in soluble form (sLR11) by proteolytic shedding and has biological activity toward SMC migration. We previously showed that circulating sLR11 positively correlates with carotid intima-medial thickness (IMT) independently of classical atherosclerotic risk factors and that it significantly associates with the severity of CAD. However, the association between sLR11 and long-term clinical outcomes remain uncertain., Methods and Results: This study included 438 consecutive patients (mean age, 65.8 ± 9.6 y; male, 82.4%) who underwent coronary intervention between March 2003 and December 2004 at our institution. The patients were assigned to quartiles according to pre-procedural sLR11 values. The primary endpoints were composite cardiovascular disease (CVD) endpoints including cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke. During median follow-up of 2876 days, composite CVD endpoints occurred 97 (22.1%) patients including 41 (9.4%) with cardiovascular disease (CVD)-related death, 36 (8.2%) non-fatal ACS and 20 (4.6%) non-fatal strokes. The hazard ratio (HR) for composite CVD endpoints significantly and dose-dependently increased with sLR11 levels (p for trend = 0.0077). A higher logarithm-transformed sLR11 value was associated with a greater risk of composite CVD endpoints, and the increased number of adverse long-term clinical outcomes persisted even after adjustment for other independent variables (HR 1.87 95%CI 1.02-3.31, p = 0.0435)., Conclusions: Elevated sLR11 levels were significantly associated with higher long-term adverse cardiac events in patients with CAD. Further extensive studies are expected to elucidate the mechanistic role of sLR11 and its clinical value as a prognostic marker in the development of atherosclerosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

More than 4.2 billion inhabitants populate the Asia-Pacific region. Acute coronary syndrome (ACS) is now a major cause of death and disability in this region with in-hospital mortality typically exceeding 5%. Yet, the region still lacks consensus on the best approach to overcoming its specific challenges in reducing mortality from ACS. The Asia-Pacific Real world evIdenCe on Outcome and Treatment of ACS (APRICOT) project reviewed current published and unpublished registry data, unmet needs in ACS management and possible approaches towards improving ACS-related mortality in the region. There was striking heterogeneity in the use of invasive procedures, pharmacologic practice (hospitalization/post-discharge), and in short- and long-term clinical outcomes across healthcare systems; this heterogeneity was perceived to be far greater than in Western Europe or the United States. 'Benchmark' short-term clinical outcomes are preferred over long-term outcomes due to difficulties in follow-up, recording and maintenance of medication adherence in a geographically large and culturally diverse region. Key 'barriers' towards improving outcomes include patient education (pain awareness, consequences of missing medication and secondary prevention), geographical landscape (urban vs. metropolitan), limited long-term adherence to guideline-based management and widespread adoption of cost-based rather than value-based healthcare systems. Initiatives to overcome these barriers should include implementation of pre-hospital management strategies, toolkits to aid in-hospital treatment, greater community outreach with online patient/physician education and telemedicine, sustainable economic models to improve accessibility to effective pharmacotherapies and the acquisition of high-quality 'real-world' regional data to tailor secondary prevention initiatives that meet the unique needs of countries in this region., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background: To evaluate the prognostic impact of preprocedural high-sensitivity C-reactive protein (hsCRP) levels on the long-term clinical outcomes after first-generation drug-eluting stent (DES) implantation in chronic kidney disease (CKD) patients with stable coronary artery disease (CAD)., Methods and Results: We found significant interaction between CKD and hsCRP levels (p=0.0138) in 1176 consecutive patients with stable CAD who were treated with first-generation DES implantation between 2004 and 2009 at our institution. Therefore, we separately analyzed data from patients with and without CKD who were assigned to tertiles based on preprocedural hsCRP levels. We evaluated the incidence of major adverse cardiovascular events (MACE) comprising all-cause death, nonfatal myocardial infarction, and target vessel revascularization after percutaneous coronary intervention during a median follow-up period of 1266 days. The rate of MACE significantly differed among the tertiles (log-rank p=0.0074) in the group with CKD. Multivariate Cox regression analysis significantly associated a higher hsCRP tertile with MACE in the CKD group (hazard ratio 2.39, 95% confidence interval 1.27-4.75, p=0.0062)., Conclusion: Elevated preprocedural serum hsCRP levels might be associated with the long-term clinical outcomes of patients with stable CAD and CKD who were implanted with first-generation DES., (Copyright © 2015. Published by Elsevier Ltd.)

Objective: Restenosis after vascular intervention remains a major clinical problem. Circulating LR11 has been shown a novel marker of intimal smooth muscle cell (SMC) proliferation in human and animal studies. The present study was performed to clarify the clinical significance of circulating LR11 in patients with stable angina pectoris after coronary stenting., Methods and Results: We firstly investigated the circulating sLR11 levels for 28 days after arterial injury in mice, and then assessed time-dependent change in circulating sLR11 level after coronary stenting in a clinical study. Mouse sLR11 levels rapidly increased to 4.0-fold of the control value without cuff placement at postoperative day (POD) 14, and the levels gradually declined to 3.1-fold of the control value until POD 28 in mice. The circulating soluble LR11 levels were measured (before and at 14, 60 and 240 days after coronary stenting in a clinical study of 102 consecutive patients with stable angina pectoris who were treated with percutaneous coronary intervention. Circulating sLR11 levels were significantly increased on days 14 and 60 after the procedure and positively associated with the angiographic late loss index., Conclusions: Our study suggested that circulating sLR11 levels may be a potential marker for angiographic late loss in patients after coronary stenting. Further mechanistic studies are expected to know the clinical significance of sLR11 as a novel marker for intimal SMC., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Background: Limited data exist regarding the long-term prognosis of percutaneous coronary intervention (PCI) in young adults. The aim of this study was to retrospectively assess the long-term clinical outcomes in young patients who underwent PCI., Methods and Results: Between 1985 and 2011, 7649 consecutive patients underwent PCI, and data from 69 young adults (age ≤40 years) and 4255 old adults (age ≧65 years) were analyzed. A Cox proportional hazards regression analysis was used to determine the independent predictors of a composite endpoint that included all-cause death and acute coronary syndrome (ACS) during the follow-up period. The mean age of the 69 young patients was 36.1±4.9 years, and 96% of them were men. Approximately 30% were current smokers, and their body mass index (BMI) was 26.7±5.0kg/m(2). The prevalence of diabetes and hypertension was 33% and 48%, respectively. All patients had ≥1 conventional cardiovascular risk factor. At a median follow-up of 9.8 years, the overall death rate was 5.8%, and new-onset ACS occurred in 8.7%. Current smoking was an independent predictor of the composite endpoint (hazard ratio 4.46, confidence interval 1.08-19.1, p=0.04) for young adults., Conclusion: Current smoking and obesity (high BMI) are the important clinical characteristics in young Japanese coronary heart disease patients who undergo PCI. The long-term prognosis in young patients is acceptable, but current smoking is a significant independent predictor of death and the recurrence of ACS in young Japanese coronary heart disease patients who are obese., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Admission glucose levels have proven to be a predictor in patients with acute myocardial infarction and elevated glycosylated hemoglobin A1c (HbA1c) is associated with an increased risk of cardiovascular disease, even in patients without diabetes. However, the effect of both admission glucose and HbA1c levels on clinical outcomes in non-diabetic patients with acute coronary syndrome (ACS) has not been fully elucidated. We evaluated the combined effect of admission glucose and HbA1c values on long-term clinical outcomes in non-diabetic patients with ACS treated with percutaneous coronary intervention (PCI)., Methods and Results: This was an observational study of 452 consecutive non-diabetic patients with ACS who underwent PCI between January 1997 and December 2006. The patients were assigned to four groups according to the median values of admission glucose and HbA1c. The primary endpoint comprising a composite of all-cause death and non-fatal MI was compared among the four groups. The primary endpoint occurred in 13.3% of the participants during a median follow-up period of 4.7 years. The cumulative incidence rate of primary endpoint significantly differed among the groups (p=0.048). Multivariable Cox regression analysis showed that the combination of elevated admission glucose and HbA1c was independently associated with long-term clinical outcomes., Conclusions: Combined admission glucose and HbA1c values were independently associated with clinical outcomes in non-diabetic patients with ACS treated with PCI., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Lysophosphatidic acid (LPA) is a platelet activator and highly thrombogenic lipid constituent of atherosclerotic plaque. However, whether or not LPA locally released from culprit lesions is associated with acute coronary syndrome (ACS) remains unclear., Methods: We studied 52 patients with ACS who were treated by emergency percutaneous coronary intervention and thrombectomy. Levels of LPA and other established biomarkers were enzymatically assayed in samples of culprit coronary arterial and systemic peripheral arterial blood. Levels of LPA and lysophosphatidylcholine (LPC) were measured in plasma, and those of autotaxin, soluble CD40 ligand (sCD40L), hs-CRP and Lp-PLA2 were measured in serum., Results: Median LPA levels were significantly higher in coronary (CB) than in peripheral (PB) arterial blood (p = 0.009). Levels of sCD40L were higher in CB than in PB, but the difference did not reach statistical significance (p = 0.177). In contrast, autotaxin and Lp-PLA2 levels were significantly higher in PB than in CB (p = 0.005 and p = 0.038, respectively). Levels of LPC and hs-CRP were also higher in PB than in CB (p = 0.129 and p = 0.121, respectively). Levels of LPA in both CB and PB were positively and significantly associated with those of LPC (r = 0.632, p < 0.01 and r = 0.465, p < 0.001)., Conclusions: Culprit coronary arteries of ACS contained significantly more LPA than the systemic arterial circulation. Higher LPA concentrations might be associated with the pathophysiology of ACS., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: LR11 (also so called SorLA or SORL1) is a novel marker of intimal smooth muscle cell (SMC) proliferation. Vascular SMCs play important roles in the development of atherosclerosis interacting with macrophages in a vulnerable plaque of patients with acute coronary syndrome (ACS).The present study determines whether soluble LR11 (sLR11) is associated with ACS., Methods: We studied 100 patients with coronary artery disease (CAD) comprising 50 consecutive patients with acute coronary syndrome (ACS; mean age 62.3±13.0 years; male 78.0%) who were successfully treated with percutaneous coronary intervention and 50 age- and sex-matched stable angina pectoris (SAP) patients as control. Concentration of sLR11 was measured by sandwich enzyme-linked immunosorbent assay method., Results: Circulating sLR11 was significantly increased in patients with ACS compared with SAP (9.88±2.78 vs. 8.18±1.11 ng/ml, p<0.01). Multivariate logistic regression analysis indicated that sLR11 was independently associated with ACS (odds ratio (OR), sLR11 quartile increment, 2.18, 95% confidence interval (CI) 1.21-4.19, p<0.01). Among various biomarkers of acute coronary syndrome, hsCRP were significantly correlated with LR11 (r=0.480, p<0.01)., Conclusions: There is a statistical significant association between LR11 and ACS and may be a useful biomarker for the development of acute coronary syndrome., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Matrix metalloproteinases (MMPs) have been implicated in development of atherosclerosis. MMPs are activated in patients with acute coronary syndrome (ACS). However, little data exist regarding the correlation between circulating levels of MMPs and plaque volume (PV) in patients with ACS. We therefore evaluated the impact of MMPs on coronary PV as a post hoc analysis from the JAPAN-ACS study., Methods: The multicenter JAPAN-ACS trial revealed that aggressive statin therapy for patients with ACS significantly reduces coronary PV determined by intravascular ultrasound (IVUS). We studied 248 ACS patients who had serial IVUS examinations over 8-12 months in the trial. For each patient, MMP-1, 2, and 3 were measured both at baseline and at study end to evaluate the correlation between the percent change of PV and MMP levels., Results: MMP-3 levels were significantly decreased during the follow-up period (100 ng/mL to 73 ng/mL, p < 0.001), in contrast, MMP-1, -2 levels were significantly increased. MMP-3 levels at follow-up correlated with coronary plaque regression (p for trend = 0.016). A multivariable linear regression model showed both MMP-2 and MMP-3 levels at follow-up were independent variables for change of coronary PV (p = 0.038 and p = 0.016, respectively)., Conclusion: Circulating MMPs levels are associated with changes in coronary plaque volume determined by serial IVUS in patients with ACS., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vascular-specific inflammatory enzyme, of which increases are associated with cardiovascular events. However, the relationship between circulating Lp-PLA2 levels and coronary plaque volume has not been clarified in patients with acute coronary syndrome (ACS)., Methods: We studied 40 patients with ACS (age, 61.4 ± 8.0 years; male, 87.5%; statin use, 45.0%) who had undergone successful percutaneous coronary intervention (PCI). Plaque volume (PV) in non-culprit sites of PCI lesions was precisely determined using grayscale intravascular ultrasound (IVUS) at onset and at six months later. We then analyzed associations among PV, lipid profiles and Lp-PLA2 levels., Results: Circulating Lp-PLA2 levels and PV significantly decreased between baseline and six months of follow-up (458.6 ± 166.7 IU/L vs. 378.4 ± 158.5 IU/L, p < 0.001 and 82.2 ± 34.8mm(3) vs. 77.3 ± 33.1mm(3), p < 0.001, respectively). The % change in PV positively and significantly correlated with % change in LDL-C and in the LDL-C/HDL-C ratio (r = 0.444, p = 0.004 and r = 0.462, p = 0.003, respectively). Furthermore, % changes in Lp-PLA2 and in PV correlated even more closely (r = 0.496, p = 0.001). The absolute change in PV also significantly correlated with the change in Lp-PLA2 levels (r = 0.404, p = 0.009)., Conclusions: Circulating Lp-PLA2 levels are associated with changes in coronary plaque determined by IVUS in patients with ACS., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: The aim of this study was to characterize coronary plaque composition of non-target lesions in diabetic patients using virtual histology intravascular ultrasound (VH-IVUS)., Methods and Results: In 134 stable angina pectoris patients, plaque components of non-culprit (< 50% in diameter stenosis) lesions in de novo target vessels were analyzed by VH-IVUS. Plaque characterization was compared between diabetic (n=65) and non-diabetic groups (n=69). Diabetic patients were further divided into four groups according to estimated glomerular filtration rate (eGFR, ml/min): eGFR > or = 70 (n=20), 50 < or = eGFR < 70 (n=19), GFR < 50 (n=18), and end stage renal disease (ESRD) on hemodialysis (HD) (n=11). There was no significant difference in plaque composition between the diabetic and the non-diabetic patients except for the percentage of dense calcium (8.9% vs. 6.2%; p<0.05). In the diabetic patients, the percent volume of necrotic core was 9.6%, 11.4%, 14.8%, and 20.8% in the eGFR > or = 70, 50 < or = eGFR < 70, eGFR < 50, and the ESRD on HD groups, respectively, showing significantly higher percentage in eGFR < 50 (p<0.05 vs. eGFR > or = 70) and ESRD on HD group (p<0.001)., Conclusions: Diabetic patients have significantly larger amount of dense calcium than non-diabetic patients in non-culprit coronary artery segments, and the plaque components of non-culprit lesions in diabetes are significantly different according to the decline in renal function.