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Background: Hypertension is a risk factor for bleeding events and is included in the HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/Alcohol concomitantly)score. However, the effects of blood pressure (BP) and changes in BP on bleeding events in patients undergoing percutaneous coronary intervention (PCI) remain poorly understood. This study is aimed to investigate the relationship between systolic BP (SBP) changes during hospitalisation and bleeding events in patients undergoing PCI., Methods: From the Clinical Deep Data Accumulation System database, a multicentre database encompassing seven tertiary medical hospitals in Japan that includes data for patient characteristics, medications, laboratory tests, physiological tests, cardiac catheterisation and PCI treatment, data for 6351 patients undergoing PCI between April 2013 and March 2019 were obtained. The study population was categorised into three groups based on the changes in SBP during hospitalisation: (1) elevated BP (≥20 mm Hg), (2) no change (≥-20 to <20 mm Hg) and (3) decreased BP (<-20 mm Hg) groups. The primary outcome was a 3-year major bleeding event defined as moderate or severe bleeding according to the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries bleeding criteria., Results: The elevated BP group exhibited significantly lower SBP at admission and higher SBP at discharge (p<0.001). Multivariable Cox hazard regression models showed that elevated BP was associated with a high risk of bleeding events (HR: 1.885; 95% CI, 1.294 to 2.748). The multivariable logistic regression model identified female sex, chronic coronary syndrome, peripheral artery disease and chronic kidney disease as independent factors associated with elevated BP., Conclusions: These findings suggest that BP management is essential to prevent bleeding events after PCI., Competing Interests: Competing interests: No., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Recent studies highlight artificial intelligence's ability to identify ventricular dysfunction via electrocardiograms (ECGs); however, specific indicative waveforms remain unclear. This study analysed ECG and echocardiography data from 17,422 cases in Japan and Germany. We developed 10-layer convolutional neural networks to detect left ventricular ejection fractions below 50%, using four-fold cross-validation. Model performance, evaluated among different ECG configurations (3 s strips, single-beat, and two-beat overlay) and segments (PQRST, QRST, P, QRS, and PQRS), showed two-beat ECGs performed best, followed by single-beat models, surpassing 3 s models in both internal and external validations. Single-beat models revealed limb leads, particularly I and aVR, as most indicative of dysfunction. An analysis indicated segments from QRS to T-wave were most revealing, with P segments enhancing model performance. This study confirmed that dual-beat ECGs enabled the most precise ventricular function classification, and segments from the P- to T-wave in ECGs were more effective for assessing ventricular dysfunction, with leads I and aVR offering higher diagnostic utility.

The Japanese Society of Hypertension have established a blood pressure (BP) target of 130/80 mmHg for patients with coronary artery disease (CAD). We evaluated the data of 8793 CAD patients in the Clinical Deep Data Accumulation System database who underwent cardiac catheterization at six university hospitals and the National Cerebral and Cardiovascular Center (average age 70 ± 11 years, 78% male, 43% with acute coronary syndrome [ACS]). Patients were divided into two groups based on whether or not they achieved the guideline-recommended BP of <130/80 mmHg. We analyzed the relationship between BP classification and major adverse cardiac and cerebral event (MACCE) separately in two groups: those with ACS and those with chronic coronary syndrome (CCS). During an average follow-up period of 33 months, 710 MACCEs occurred. A BP below 130/80 mmHg was associated with fewer MACCEs in both the overall (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.70-1.00, p = 0.048) and the ACS group (HR 0.67, 95%CI 0.51-0.88, p = 0.003). In particular, stroke events were also lower among those with a BP below 130/80 mmHg in both the overall (HR 0.69, 95%CI 0.53-0.90, p = 0.006) and ACS groups (HR 0.44, 95%CI 0.30-0.67, p < 0.001). In conclusion, the achievement of BP guidelines was associated with improved outcomes in CAD patients, particularly in reducing stroke risk among those with ACS., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Polypharmacy is associated with an increased risk of adverse events due to the higher number of drugs used. This is particularly notable in patients with chronic coronary syndrome (CCS), who are known to use a large number of drugs. Therefore, we investigated polypharmacy in patients with CCS, using CLIDAS, a multicenter database of patients who underwent percutaneous coronary intervention., Method and Results: Between 2017 and 2020, 1411 CCS patients (71.5 ± 10.5 years old; 77.3 % male) were enrolled. The relationship between cardiovascular events occurring during the median follow-up of 514 days and the number of drugs at the time of PCI was investigated. The median number of drugs prescribed was nine. Major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke, heart failure, transient ischemic attack, or unstable angina, occurred in 123 patients, and all-cause mortality occurred in 68 patients. For each additional drug, the adjusted hazard ratios for MACE and all-cause mortality increased by 2.069 (p = 0.003) and 1.102 (p = 0.010). The adjusted hazard ratios for MACE and all-cause mortality were significantly higher in the group using nine or more drugs compared to the group using eight or fewer drugs (1.646 and 2.253, both p < 0.001)., Conclusion: This study showed that an increase in the number of drugs used for CCS may be associated with MACE and all-cause mortality. In patients with CCS, it might be beneficial to minimize the number of medications as much as possible, while managing comorbidities and using guideline-recommended drugs., Competing Interests: 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., (© 2024 The Author(s).)

Objective: The study aimed to investigate treatment options for older women with pelvic organ prolapse (POP) and postoperative outcomes based on their long-term care (LTC) status., Methods: We used the medical and LTC insurance claims databases of Tochigi Prefecture in Japan, covering 2014 to 2019. We included women 65 years and older with POP and evaluated their care status and treatment, excluding women with an observation period <6 months. Among women with a postsurgical interval ≥6 months, we compared care level changes and deaths within 6 months and complications within 1 month postoperatively between those with and without LTC using Fisher exact test., Results: We identified 3406 eligible women. Of the 447 women with LTC and 2959 women without LTC, 16 (3.6%) and 415 (14.0%), respectively, underwent surgery. Among 393 women with a postsurgical interval ≥6 months, 19 (4.8%) required LTC at surgery. Two of the 19 women with LTC (10.5%) and eight of 374 women without LTC (2.1%) experienced worsening care-needs level. No deaths were recorded. Urinary tract infection (UTI) was significantly more frequent in women with LTC than in women without LTC (36.8% vs 8.6%). Other complications were rare in both groups., Conclusion: The proportion of patients who underwent surgery for POP was lower in women with LTC than in women without LTC. Postoperative UTI was common and 11% had a worsening care-needs level postoperatively, whereas other complications were infrequent. Further detailed studies would contribute to providing optimal treatment to enhance patients' quality of life., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: Limited data exist on the prognostic value of changes in pulse pressure (PP, the difference between systolic and diastolic blood pressure) during hospitalization for patients with coronary artery disease who have undergone percutaneous coronary intervention (PCI)., Methods: In the Clinical Deep Data Accumulation System (CLIDAS), we studied 8,708 patients who underwent PCI. We aimed to examine the association between discharge PP and cardiovascular outcomes. PP was measured before PCI and at discharge. Patients were divided into five groups (quintiles) based on the change in PPQ1 (-18.0 ± 9.9 mmHg), Q2 (-3.8 ± 2.6), Q3 (reference; 3.7 ± 2.0), Q4 (11.3 ± 2.6), and Q5 (27.5 ± 11.2). We then analyzed the relationship between PP change and outcomes., Results: The mean patient age was 70 ± 11 years, with 6,851 (78 %) men and 3,786 (43 %) having acute coronary syndrome. U-shaped relationships were observed for the incidence rates of major adverse cardiac or cerebrovascular events (MACCE, a composite endpoint of cardiovascular death, myocardial infarction, and stroke), revascularization, and hospitalization for heart failure (HF). After adjusting for confounding factors, higher PP at discharge was associated with an increased risk of MACCE (adjusted hazard ratio 1.41; 95 %CI, 1.06-1.87 in Q5 [73.9 ± 9.3 mmHg]). Evaluating PP change revealed a U-shaped association with MACCE (1.50; 1.11-2.02 in Q1 and 1.47; 0.98-2.20 in Q5). Additionally, Q5 had a higher risk for hospitalization for HF (1.37; 1.00-1.88)., Conclusions: Our findings demonstrate a U-shaped association between changes in PP and cardiovascular outcomes. This data suggests the significance of blood pressure control during hospitalization for patients who have undergone PCI., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: TK has received scholarship funding from Abbott. KK has received a research grant from Otsuka Pharmaceutical, Sanwa Kagaku Kenkyusho, Daiichi Sankyo, MSD, Astellas Pharma, Eisai, Taisho Pharmaceutical, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, Teijin Pharma, Boehringer Ingelheim Japan, Bristol-Myers Squibb, Mochida Pharmaceutical; Consulting fees from Kyowa Kirin, Sanwa Kagaku Kenkyusho, Mochida Pharmaceutical; Honoraria from Otsuka Pharmaceuticals, Daiichi Sankyo, Novartis Pharma, Mylan EPD; Participation in Advisory Board of Daiichi Sankyo, Novartis Pharma. HF received scholarship funds from Abbott Vascular, speaking honoraria from Novartis and Otsuka Pharmaceutical Co., Ltd., and served as a consultant for Mehergen Group Holdings, Inc. KT has received personal fees from Abbott Medical Co., Ltd., personal fees from Amgen K.K., personal fees from AstraZeneca K.K., personal fees from Bayer Yakuhin, Ltd., personal fees from Daiichi Sankyo Co., Ltd., personal fees from Medtoronic Japan Co., Ltd., personal fees from Kowa Pharmaceutical Co. Ltd., personal fees from Novartis Pharma K.K., personal fees from Otsuka Pharmaceutical Co.,Ltd., personal fees from Pfizer Japan Inc., personal fees from Janssen Pharmaceutical K.K., grants from PPD-Shin Nippon Biomedical Laboratories K.K., grants from Alexion Pharmaceuticals, Inc., grants from Abbott Medical Co., Ltd., grants from Bayer Yakuhin, Ltd., grants from Boehringer Ingelheim Japan, grants from Daiichi Sankyo Co., Ltd., grants from ITI Co.,Ltd., grants from ONO PHARMACEUTICAL CO., LTD., grants from Otsuka Pharmaceutical Co.,Ltd., grants from Takeda Pharmaceutical Co., Ltd., other from Abbott Japan Co., Ltd., other from Boston Scientific Japan K.K., other from Fides-one, Inc., other from GM Medical Co., Ltd., other from ITI Co.,Ltd., other from Kaneka Medix Co., Ltd., other from NIPRO CORPORATION, other from TERUMO Co, Ltd., other from Abbott Medical Co., Ltd., other from Boston Scientific Japan K.K., other from Cardinal Health Japan, other from Fukuda Denshi Co., Ltd., other from Japan Lifeline Co.,Ltd., other from Medical Appliance Co., Ltd., other from Medtronic Japan Co., Ltd., outside the submitted work. TM has received lecture fees (Abbott, Bayer Yakuhin, and MSD) and research funding (Amgen, Bayer Yakuhin, and Kowa). YM received research funds from Kowa Company, Ltd., within the submitted work and from Tokyo Marine and Nichido Fire Insurance Co., Ltd., Fujitsu Co., Ltd., Softbank Co., Ltd., Saraya Co., Ltd., and Meiji Yasuda Life Insurance Company outside of the submitted work., (© 2024 The Author(s).)

Aim: There is little information on the relationships of serum small dense low-density lipoprotein cholesterol (sdLDL-C) levels and serum triglyceride (TG) levels with cardiovascular events in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who are receiving statins. The aim of this study was to evaluate the relationships of serum TG levels and sdLDL-C levels as residual risks for cardiovascular events in patients with CAD and type 2 DM who were being treated with statins., Methods: The subjects were divided into four groups based on TG levels and sdLDL-C levels: sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, and sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL. During a median follow-up period of 1419 days, cardiovascular events occurred in 34 patients., Results: The incidences of cardiovascular events were significantly higher in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL and in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL, but not in patients with sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, than in patients with sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL., Conclusions: Under the condition of treatment with statins, patients with CAD and type 2 DM who had sdLDL-C levels of ≥ 40.0 mg/dL had a high risk for cardiovascular events even though serum TG levels were controlled at ＜150 mg/dL.

Recent years have witnessed significant transformations in cardiovascular medicine, driven by the rapid evolution of artificial intelligence (AI). This scoping review was conducted to capture the breadth of AI applications within cardiovascular science. Employing a structured approach, we sourced relevant articles from PubMed, with an emphasis on journals encompassing general cardiology and digital medicine. We applied filters to highlight cardiovascular articles published in journals focusing on general internal medicine, cardiology and digital medicine, thereby identifying the prevailing trends in the field. Following a comprehensive full-text screening, a total of 140 studies were identified. Over the preceding 5 years, cardiovascular medicine's interplay with AI has seen an over tenfold augmentation. This expansive growth encompasses multiple cardiovascular subspecialties, including but not limited to, general cardiology, ischemic heart disease, heart failure, and arrhythmia. Deep learning emerged as the predominant methodology. The majority of AI endeavors in this domain have been channeled toward enhancing diagnostic and prognostic capabilities, utilizing resources such as hospital datasets, electrocardiograms, and echocardiography. A significant uptrend was observed in AI's application for omics data analysis. However, a clear gap persists in AI's full-scale integration into the clinical decision-making framework. AI, particularly deep learning, has demonstrated robust applications across cardiovascular subspecialties, indicating its transformative potential in this field. As we continue on this trajectory, ensuring the alignment of technological progress with medical ethics becomes crucial. The abundant digital health data today further accentuates the need for meticulous systematic reviews, tailoring them to each cardiovascular subspecialty., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: The somatopleure serves as the primordium of the amnion, an extraembryonic membrane surrounding the embryo. Recently, we have reported that amniogenic somatopleural cells (ASCs) not only form the amnion but also migrate into the embryo and differentiate into cardiomyocytes and vascular endothelial cells. However, detailed differentiation processes and final distributions of these intra-embryonic ASCs (hereafter referred to as iASCs) remain largely unknown., Results: By quail-chick chimera analysis, we here show that iASCs differentiate into various cell types including cardiomyocytes, smooth muscle cells, cardiac interstitial cells, and vascular endothelial cells. In the pharyngeal region, they distribute selectively into the thyroid gland and differentiate into vascular endothelial cells to form intra-thyroid vasculature. Explant culture experiments indicated sequential requirement of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) signaling for endothelial differentiation of iASCs. Single-cell transcriptome analysis further revealed heterogeneity and the presence of hemangioblast-like cell population within ASCs, with a switch from FGF to VEGF receptor gene expression., Conclusion: The present study demonstrates novel roles of ASCss especially in heart and thyroid development. It will provide a novel clue for understanding the cardiovascular development of amniotes from embryological and evolutionary perspectives., (© 2022 The Authors. Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Objective: This study aimed to investigate the association between heart failure (HF) severity measured based on brain natriuretic peptide (BNP) levels and future bleeding events after percutaneous coronary intervention (PCI)., Background: The Academic Research Consortium for High Bleeding Risk presents a bleeding risk assessment for antithrombotic therapy in patients after PCI. HF is a risk factor for bleeding in Japanese patients., Methods: Using an electronic medical record-based database with seven tertiary hospitals in Japan, this retrospective study included 7160 patients who underwent PCI between April 2014 and March 2020 and who completed a 3-year follow-up and were divided into three groups: no HF, HF with high BNP level and HF with low BNP level. The primary outcome was bleeding events according to the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries classification of moderate and severe bleeding. The secondary outcome was major adverse cardiovascular events (MACE). Furthermore, thrombogenicity was measured using the Total Thrombus-Formation Analysis System (T-TAS) in 536 consecutive patients undergoing PCI between August 2013 and March 2017 at Kumamoto University Hospital., Results: Multivariate Cox regression showed that HF with high BNP level was significantly associated with bleeding events, MACE and all-cause death. In the T-TAS measurement, the thrombogenicity was lower in patients with HF with high BNP levels than in those without HF and with HF with low BNP levels., Conclusions: HF with high BNP level is associated with future bleeding events, suggesting that bleeding risk might differ depending on HF severity., Competing Interests: Competing interests: TM received research grants from Amgen and honoraria from Abbott Medical and Bayer. TK received scholarship funds from Abbott Medical. YI received honoraria from Daiichi Sankyo and Toa Eiyo. KKario received research grants and honoraria from Sanwa Kagaku Kenkyusho. AK received honoraria from AstraZeneca, Eli Lilly and Sumitomo Pharma. YMizuno received research grants and consulting fees from Bayer. KT received research grants from PPD-Shin Nippon Biomedical Laboratories and Alexion Pharmaceuticals; and scholarship funds from Abbott Medical, Bayer, Boehringer Ingelheim, Daiichi Sankyo, ITI, Ono Pharmaceutical, Otsuka Pharmaceutical and Takeda Pharmaceutical; affiliation with the endowed department from Abbott Medical, Boston Scientific, Cardinal Health, Fides-ONE, Fukuda Denshi, GM Medical, ITI, Japan Lifeline, Kaneka Medix, Medical Appliance, Medtronic, Nipro and Terumo and honoraria from Abbott Medical, Amgen, AstraZeneca, Bayer, Daiichi Sankyo, Medtronic, Kowa, Novartis Pharma, Otsuka Pharmaceutical, Pfizer and Janssen Pharmaceutical. HS reports stock or stock options in Precision. HF received consulting fees from Mehergen Group Holdings; and honoraria from Novartis Pharma and Otsuka Pharmaceutical. RN received honoraria from Kowa, Takeda Pharmaceutical, Tanabe-Mitsubishi Pharmaceutical and Boehringer-Ingelheim. All other authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cancer cells inevitably interact with neighboring host tissue-resident cells during the process of metastatic colonization, establishing a metastatic niche to fuel their survival, growth, and invasion. However, the underlying mechanisms in the metastatic niche are yet to be fully elucidated owing to the lack of methodologies for comprehensively studying the mechanisms of cell-cell interactions in the niche. Here, we improve a split green fluorescent protein (GFP)-based genetically encoded system to develop secretory glycosylphosphatidylinositol-anchored reconstitution-activated proteins to highlight intercellular connections (sGRAPHIC) for efficient fluorescent labeling of tissue-resident cells that neighbor on and putatively interact with cancer cells in deep tissues. The sGRAPHIC system enables the isolation of metastatic niche-associated tissue-resident cells for their characterization using a single-cell RNA sequencing platform. We use this sGRAPHIC-leveraged transcriptomic platform to uncover gene expression patterns in metastatic niche-associated hepatocytes in a murine model of liver metastasis. Among the marker genes of metastatic niche-associated hepatocytes, we identify Lgals3, encoding galectin-3, as a potential pro-metastatic factor that accelerates metastatic growth and invasion., (© 2023. The Author(s).)

The effects of low-dose radiation on undifferentiated cells carry important implications. However, the effects on developing retinal cells remain unclear. Here, we analyzed the gene expression characteristics of neuronal organoids containing immature human retinal cells under low-dose radiation and predicted their changes. Developing retinal cells generated from human induced pluripotent stem cells (iPSCs) were irradiated with either 30 or 180 mGy on days 4-5 of development for 24 h. Genome-wide gene expression was observed until day 35. A knowledge-based pathway analysis algorithm revealed fluctuations in Rho signaling and many other pathways. After a month, the levels of an essential transcription factor of eye development, the proportion of paired box 6 (PAX6)-positive cells, and the proportion of retinal ganglion cell (RGC)-specific transcription factor POU class 4 homeobox 2 (POU4F2)-positive cells increased with 30 mGy of irradiation. In contrast, they decreased after 180 mGy of irradiation. Activation of the "development of neurons" pathway after 180 mGy indicated the dedifferentiation and development of other neural cells. Fluctuating effects after low-dose radiation exposure suggest that developing retinal cells employ hormesis and dedifferentiation mechanisms in response to stress., (© 2023. Springer Nature Limited.)

Type 2 diabetes mellitus (T2DM) is a major cause of microvascular dysfunction. However, its effect on blood flow patterns during ischemic demand has not been adequately elucidated. In this study, we investigated the hypothesis that microvascular dysfunction in patients with T2DM manifests as brachial reactive hyperemia (BRH), defined as the ratio of peak blood flow velocities in a brachial artery before and after forearm cuff occlusion. The study enrolled 943 subjects (men, n = 152 [T2DM] and n = 371 [non-T2DM]; women, n = 107 [T2DM] and n = 313 [non-T2DM], respectively) with no history of cardiovascular disease. Semiautomatic measurements were obtained three times at 1.5-year intervals to confirm the reproducibility of factors involved in BRH for each sex. An age-adjusted mixed model demonstrated attenuated BRH in the presence of T2DM in both men (p = 0.022) and women (p = 0.031) throughout the study period. Post hoc analysis showed that the estimated BRH was significantly attenuated in patients with T2DM regardless of sex, except at baseline in women. In multivariate regression analysis, T2DM was a negative predictor of BRH at every measurement in men. For women, BRH was more strongly associated with alcohol consumption. Repeated measurements analysis revealed that T2DM was associated with attenuated postocclusion reactive hyperemia., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Heart failure (HF) is associated with a high bleeding risk after percutaneous coronary intervention (PCI). Additionally, major bleeding events increase the risk of subsequent major adverse cardiac events (MACE). However, whether brain natriuretic peptide (BNP) levels and major bleeding events following PCI are associated with MACE and all-cause death remains unknown. This study aimed to investigate the impact of HF severity or bleeding on subsequent MACE and all-cause death., Methods: The Clinical Deep Data Accumulation System (CLIDAS), a multicenter database involving seven hospitals in Japan, was developed to collect data from electronic medical records. This retrospective analysis included 7160 patients who underwent PCI between April 2014 and March 2020 and completed a three-year follow-up. Patients were divided according to the presence of HF with high BNP (HFhBNP) (>100 pg/ml) and major bleeding events within 30 days post-PCI (30-day bleeding): HFhBNP with bleeding (n = 14), HFhBNP without bleeding (n = 370), non-HFhBNP with bleeding (n = 74), and non-HFhBNP without bleeding (n = 6702)., Results: In patients without 30-day bleeding, HFhBNP was a risk factor for MACE (hazard ratio, 2.19; 95% confidence interval, 1.56-3.07) and all-cause death (hazard ratio, 1.60; 95% confidence interval, 1.60-2.23). Among HFhBNP patients, MACE incidence was higher in patients with 30-day bleeding than in those without bleeding, but the difference was not significant (p = 0.075). The incidence of all-cause death was higher in patients with bleeding (p = 0.001)., Conclusions: HF with high BNP and bleeding events in the early stage after PCI might be associated with subsequent MACE and all-cause death., (© 2023 The Authors. Published by Elsevier B.V.)

Background: Several studies have reported some sex differences in patients with coronary artery diseases. However, the results regarding long-term outcomes in patients with chronic coronary syndrome (CCS) are inconsistent. Therefore, the present study investigated sex differences in long-term outcomes in patients with CCS after percutaneous coronary intervention (PCI)., Methods and results: This was a retrospective, multicenter cohort study. We enrolled patients with CCS who underwent PCI between April 2013 and March 2019 using the Clinical Deep Data Accumulation System (CLIDAS) database. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, or hospitalization for heart failure. In all, 5,555 patients with CCS after PCI were included in the analysis (4,354 (78.4%) men, 1,201 (21.6%) women). The median follow-up duration was 917 days (interquartile range 312-1,508 days). The incidence of MACE was not significantly different between the 2 groups (hazard ratio [HR] 1.20; 95% confidential interval [CI] 0.97-1.47; log-rank P=0.087). After performing multivariable Cox regression analyses on 4 different models, there were still no differences in the incidence of MACE between women and men., Conclusions: There were no significant sex differences in MACE in patients with CCS who underwent PCI and underwent multidisciplinary treatments.

Background: The optimal heart rate (HR) and optimal dose of β-blockers (BBs) in patients with coronary artery disease (CAD) have been unclear. We sought to clarify the relationships among HR, BB dose, and prognosis in patients with CAD using a multimodal data acquisition system., Methods and results: We evaluated the data for 8,744 CAD patients who underwent cardiac catheterization from 6 university hospitals and the National Cerebral and Cardiovascular Center and who were registered using the Clinical Deep Data Accumulation System. Patients were divided into quartile groups based on their HR at discharge: Q1 (HR <60 beats/min), Q2 (HR 60-66 beats/min), Q3 (HR 67-74 beats/min), and Q4 (HR ≥75 beats/min). Among patients with acute coronary syndrome (ACS) and patients with chronic coronary syndrome (CCS), those in Q4 (HR ≥75 beats/min) had a significantly greater incidence of major adverse cardiac and cerebral events (MACCE) compared with those in Q1 (ACS patients: hazard ratio 1.65, P=0.001; CCS patients: hazard ratio 1.45, P=0.019). Regarding the use of BBs (n=4,964), low-dose administration was significantly associated with MACCE in the ACS group (hazard ratio 1.41, P=0.012), but not in patients with CCS after adjustment for covariates., Conclusions: HR ≥75 beats/min was associated with worse outcomes in patients with CCS or ACS.

Background: The causal relationship between hyperuricemia and cardiovascular diseases is still unknown. We hypothesized that hyperuricemic patients after percutaneous coronary intervention (PCI) had a higher risk of major adverse cardiovascular events (MACE)., Methods: This was a large-scale multicenter cohort study. We enrolled patients with chronic coronary syndrome (CCS) after PCI between April 2013 and March 2019 using the database from the Clinical Deep Data Accumulation System (CLIDAS), and compared the incidence of MACE, defined as a composite of cardiovascular death, myocardial infarction, and hospitalization for heart failure, between hyperuricemia and non-hyperuricemia groups., Results: In total, 9,936 patients underwent PCI during the study period. Of these, 5,138 patients with CCS after PCI were divided into two group (1,724 and 3,414 in the hyperuricemia and non-hyperuricemia groups, respectively). The hyperuricemia group had a higher prevalence of hypertension, atrial fibrillation, history of previous hospitalization for heart failure, and baseline creatinine, and a lower prevalence of diabetes than the non-hyperuricemia group, but the proportion of men and age were similar between the two groups. The incidence of MACE in the hyperuricemia group was significantly higher than that in the non-hyperuricemia group (13.1 vs. 6.4%, log-rank P < 0.001). Multivariable Cox regression analyses revealed that hyperuricemia was significantly associated with increased MACE [hazard ratio (HR), 1.52; 95% confidential interval (CI), 1.23-1.86] after multiple adjustments for age, sex, body mass index, estimated glomerular filtration rate, left main disease or three-vessel disease, hypertension, diabetes mellitus, dyslipidemia, history of myocardial infarction, and history of hospitalization for heart failure. Moreover, hyperuricemia was independently associated with increased hospitalization for heart failure (HR, 2.19; 95% CI, 1.69-2.83), but not cardiovascular death or myocardial infarction after multiple adjustments. Sensitive analyses by sex and diuretic use, B-type natriuretic peptide level, and left ventricular ejection fraction showed similar results., Conclusion: CLIDAS revealed that hyperuricemia was associated with increased MACE in patients with CCS after PCI. Further clinical trials are needed whether treating hyperuricemia could reduce cardiovascular events or not., Competing Interests: HS was employed by Precision, Inc. TM has received research grants from Amgen; and honoraria from Abbott Medical and Bayer. TKa has received scholarship funds from Abbott Medical. YIm has received honoraria from Daiichi Sankyo and Toa Eiyo. KK has received research grants and honoraria from Sanwa Kagaku Kenkyusho. AK has received honoraria from AstraZeneca, Eli Lilly, and Sumitomo Pharma. YN has received research grants and consulting fees from Bayer. KT has received research grants from PPD-Shin Nippon Biomedical Laboratories and Alexion Pharmaceuticals; and scholarship funds from Abbott Medical, Bayer, Boehringer Ingelheim, Daiichi Sankyo, ITI, Ono Pharmaceutical, Otsuka Pharmaceutical, and Takeda Pharmaceutical; affiliation with endowed department from Abbott Medical, Boston Scientific, Cardinal Health, Fides-ONE, Fukuda Denshi, GM Medical, ITI, Japan Lifeline, Kaneka Medix, Medical Appliance, Medtronic, Nipro, and Terumo; and honoraria from Abbott Medical, Amgen, AstraZeneca, Bayer, Daiichi Sankyo, Medtronic, Kowa, Novartis Pharma, Otsuka Pharmaceutical, Pfizer, and Janssen Pharmaceutical. HS reports stock or stock options in Precision. HF has received consulting fees from Mehergen Group Holdings; and honoraria from Novartis Pharma and Otsuka Pharmaceutical. RN has received from honoraria from Kowa, Takeda Pharmaceutical, Tanabe-Mitsubishi Pharmaceutical, Boehringer-Ingelheim. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Akashi, Kuwabara, Matoba, Kohro, Oba, Kabutoya, Imai, Kario, Kiyosue, Mizuno, Nochioka, Nakayama, Iwai, Nakao, Iwanaga, Miyamoto, Ishii, Nakamura, Tsujita, Sato, Fujita and Nagai.)

Background: Several studies have demonstrated the efficacy of prednisolone and cyclosporine as initial combination treatments for the prevention of coronary artery abnormalities (CAA) in patients with Kawasaki disease. However, whether prednisolone or cyclosporine results in superior clinical outcomes is unknown. Thus, this study aimed to compare the outcomes of these two treatments., Methods: Using the Japanese Diagnosis Procedure Combination database, we identified patients with Kawasaki disease who had received prednisolone or cyclosporine in addition to initial intravenous immunoglobulin treatment between April 2014 and March 2021. The primary outcome was the proportion of CAA; secondary outcomes included intravenous immunoglobulin resistance, medical costs, and length of hospital stay. Propensity score matching was conducted to compare outcomes between the two groups., Results: We identified 6288 patients with Kawasaki disease who had received prednisolone (n = 6147) or cyclosporine (n = 141) as an initial treatment in combination with intravenous immunoglobulin. Four-to-one propensity score-matched analysis demonstrated no significant difference in the proportion of CAA (0.7% vs. 2.8%; p = 0.098), intravenous immunoglobulin resistance, or medical costs between the treatment groups. The length of hospital stay was significantly longer in the prednisolone group (14 vs. 11 days, p < 0.001)., Conclusions: Prednisolone and cyclosporine used in the initial combination treatment for Kawasaki disease showed similar clinical outcomes regarding the risk of CAA, intravenous immunoglobulin resistance, and medical costs, whereas the length of hospital stay was longer in the prednisolone group than in the cyclosporine group., (© 2023 Japan Pediatric Society.)

Chronic kidney disease is a progressive disease that may lead to end-stage renal disease. Interstitial fibrosis develops as the disease progresses. Therapies that focus on fibrosis to delay or reverse progressive renal failure are limited. We and others showed that sphingosine kinase 2-deficient mice ( Sphk2 -/- ) develop less fibrosis in mouse models of kidney fibrosis. Sphingosine kinase2 (SphK2), one of two sphingosine kinases that produce sphingosine 1-phosphate (S1P), is primarily located in the nucleus. S1P produced by SphK2 inhibits histone deacetylase (HDAC) and changes histone acetylation status, which can lead to altered target gene expression. We hypothesized that Sphk2 epigenetically regulates downstream genes to induce fibrosis, and we performed a comprehensive analysis using the combination of RNA-seq and ChIP-seq. Bst1/CD157 was identified as a gene that is regulated by SphK2 through a change in histone acetylation level, and Bst1 -/- mice were found to develop less renal fibrosis after unilateral ischemia-reperfusion injury, a mouse model of kidney fibrosis. Although Bst1 is a cell-surface molecule that has a wide variety of functions through its varied enzymatic activities and downstream intracellular signaling pathways, no studies on the role of Bst1 in kidney diseases have been reported previously. In the current study, we demonstrated that Bst1 is a gene that is regulated by SphK2 through epigenetic change and is critical in kidney fibrosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Inoue, Nakamura, Tanaka, Kohro, Li, Huang, Yao, Kawamura, Inoue, Nishi, Fukaya, Uni, Hasegawa, Inagi, Umene, Wu, Ye, Bajwa, Rosin, Ishihara, Nangaku, Wada and Okusa.)

Background: Elevated levels of triglyceride (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) are regarded as a residual lipid risk in low-density lipoprotein cholesterol (LDL-C)-lowering therapy. This study investigated the association between lipid risk stratified by TG and non-HDL-C and the prognosis of patients with coronary artery disease (CAD), and the association between stratified lipid risk and flow-mediated dilatation (FMD) index., Methods and results: The 624 CAD patients enrolled in flow-mediated dilation (FMD)-J study A were divided into 4 groups: low-risk group (n=413) with TG <150 mg/dL and non-HDL-C <170 mg/dL; hyper-TG group (n=180) with TG ≥150 mg/dL and non-HDL-C <170 mg/dL; hyper-non-HDL group (n=12) with TG <150 mg/dL and non-HDL-C ≥170 mg/dL; and high-risk group (n=19) with TG ≥150 mg/dL and non-HDL-C ≥170 mg/dL. Comparison of the groups showed the cumulative incidence of a 3-point major adverse cardiovascular event (MACE) was different and highest in the high-risk group in all the patients (P=0.009), and in patients with a FMD index ≥7.0% (P=0.021), but not in those with a FMD index <7.0%. Multivariable regression analysis showed that high lipid risk (P=0.019) and FMD <7.0% (P=0.040) were independently correlated with the incidence of a 3-point MACE., Conclusions: Novel stratification of lipid risk, simply using TG and non-HDL-C levels, combined with FMD measurement, is useful for predicting cardiovascular outcomes in patients with CAD.

The Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study and its pooled analysis showed that intensive blood pressure (BP) lowering reduced recurrent stroke risk by 22% in patients with a history of stroke. Here, we report the effect of intensive BP lowering on the risk of recurrent stroke subtypes in patients with a history of ischemic stroke. RESPECT was a randomized clinical trial among 1280 people with a history of cerebral infarction or intracerebral hemorrhage. Participants were assigned to the intensive blood pressure control group (blood pressure < 120/80 mmHg) or standard blood pressure control group (blood pressure < 140/90 mmHg). In this post hoc analysis, we analyzed 1074 patients with a history of cerebral infarction. The mean BP at baseline was 140.7/81.4 mmHg. Throughout the follow-up period, the mean BP was 133.4/77.5 (95% CI, 132.7-134.1/76.9-78.2) mmHg in the standard group and 126.7/74.1 (95% CI, 126.0-127.4/73.5-74.8) mmHg in the intensive group. During a mean follow-up of 3.9 years, 78 first recurrent strokes occurred. Intensive treatment tended to reduce overall annual stroke recurrence (1.74% in intensive vs. 2.17% in standard; P = 0.351 by log-rank test) and did not change the risk of ischemic stroke (1.74% vs. 1.75%, P = 0.999) but markedly reduced the risk of hemorrhagic stroke (0.00% vs. 0.39%, P = 0.005). Beneficial effects of intensive BP control were observed for the risk of hemorrhagic stroke in patients with a history of ischemic stroke. The findings of this study indicate the benefit of intensive BP control for patients with a history of ischemic stroke at high risk of hemorrhagic stroke., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Cardiovascular and cerebrovascular diseases are frequently interconnected due to underlying pathology involving atherosclerosis and thromboembolism. The aim of this study was to investigate the impact of clinical interactions among cardiovascular and cerebrovascular diseases on patient outcomes using a large-scale nationwide claims-based dataset. Cardiovascular diseases were defined as myocardial infarction, heart failure, atrial fibrillation, and aortic dissection. Cerebrovascular diseases were defined as cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage. This retrospective study included 2,736,986 inpatient records (1,800,255 patients) at 911 hospitals from 2015 to 2016 from Japanese registry of all cardiac and vascular disease-diagnostic procedure combination dataset. Interactions among comorbidities and complications, rehospitalization, and clinical outcomes including in-hospital mortality were investigated. Among hospitalization records that involved cardiovascular disease, 5.9% (32,686 records) had cerebrovascular disease as a comorbidity and 2.1% (11,362 records) included an incident cerebrovascular complication after hospitalization. Cerebrovascular disease as a comorbidity or complication was associated with higher in-hospital mortality than no cerebrovascular disease (adjusted odds ratio (OR) [95% confidence interval]: 1.10 [1.06-1.14], 2.02 [1.91-2.13], respectively). Among 367,904 hospitalization records that involved cerebrovascular disease, 17.7% (63,647 records) had cardiovascular disease listed as comorbidity and 3.3% (11,834 records) as a complication. Only cardiovascular disease as a complication was associated with higher in-hospital mortality (adjusted OR [95% confidence interval]: 1.29 [1.22-1.37]). In addition, in-hospital mortality during rehospitalization due to the other disease was significantly higher than mortality during the hospitalization due to the first disease. In conclusion, substantial associations were observed between cardiovascular and cerebrovascular disease in a large-scale nationwide claims-based dataset; these associations had a significant impact on clinical outcomes. More intensive prevention and management of cardiovascular and cerebrovascular disease might be crucial., Competing Interests: Dr. Iihara reports personal fees and other funding from Megwell, personal fees from Daiichi Sankyo. Co. Ltd., personal fees from Otsuka Pharmaceutical, and grants from Idorsia Pharmaceuticals Japan outside of the submitted work. Dr. Komuro reports grants and personal fees from Daiichi Sankyo Company, Ltd., grants from Sumitomo Dainippon Pharma Co., Ltd., grants and personal fees from Takeda Pharmaceutical Company Ltd., grants from Mitsubishi Tanabe Pharma Corporation, grants from Teijin Pharma Ltd., grants from Idorsia Pharmaceuticals Ltd., grants from Otsuka Pharmaceutical Co., Ltd., grants and personal fees from Bayer Yakuhin, Ltd., grants and personal fees from Ono Pharmaceutical Co., Ltd., grants from Toa Eiyo Ltd., and personal fees from AstraZeneca, and personal fees from Pfizer Japan Inc. outside of the submitted work. Dr. Matoba reports grants and personal fees from Bayer Yakuhin, Ltd., grants from Amgen, personal fees from Merck & Co., Inc., and personal fees from Abbott Vascular outside of the submitted work. Dr. Nishimura reports personal fees from Philips Japan, Ltd., personal fees from Tokyo Electric Power Company, personal fees from Terumo Company, and personal fees from H.U. group holdings outside of the submitted work. Dr. Nakayama reports personal fees from Pfizer Japan Inc, AstraZeneca K.K., Astellas Pharma Inc., Toppan Forms Co., InterSystems Corporation, Fujitsu Research Institute, Nikkei Business Publications, Inc., NIHON KOHDEN Co., FUKUDA DENSHI, Deloitte Tohmatsu Consulting LLC, and PwC Consulting LLC, outside of the submitted work. Dr. Toyoda reports personal fees from Daiichi-Sankyo, personal fees from Bayer Yakuhin, personal fees from Bristol-Myers-Squibb, personal fees from Outsuka Pharmaceutical Company Ltd., personal fees from Novartis Pharma Japan., and personal fees from Abbott Medical Japan Co., Ltd.,outside of the submitted work. Dr. Tsujita reports personal fees from Amgen K.K., grants and personal fees from Bayer Yakuhin, Ltd., grants and personal fees from Daiichi Sankyo Co., Ltd., personal fees from Kowa Pharmaceutical Co. Ltd., personal fees from Novartis Pharma K.K., grants and personal fees from Otsuka Pharmaceutical Co., Ltd., personal fees from Pfizer Japan Inc., grants from AMI Co., Ltd., grants from Bristol-Myers K.K., grants from EA Pharma Co. Ltd., grants from Mochida Pharmaceutical Co., Ltd., grants from Nippon Boehringer Ingelheim, grants from Chugai Pharmaceutical Co., Ltd., grants from Edwards Lifesciences Corporation., grants from Johnson & Johnson K.K., grants from Ono Pharmaceutical Co., Ltd., grants from Takeda Pharmaceutical Co., Ltd., other funding from Abbott Japan Co., Ltd., other funding from Boston Scientific Japan K.K., other funding from Fides-one, Inc., other funding from ITI Co., Ltd., other funding from Kaneka Medix Co., Ltd., other funding from Nipro Corporation, other funding from Terumo Co., Ltd., other funding from Abbott Medical Co., Ltd., other funding from Cardinal Health Japan, other funding from Fides-one, Inc., other funding from Fukuda Denshi Co., Ltd., other funding from Japan Lifeline Co., Ltd., other funding from Medical Appliance Co., Ltd., and other funding from Medtronic Japan Co., Ltd. outside of the submitted work. Dr. Yasuda reports personal fees from Bristol-Meyers, grants and personal fees from Bayer, personal fees from Daiichi-Sankyo, grants and other funding from Takeda Pharmaceutical Company Ltd., grants from NEC, grants from Daiichi-Sankyo, grants and other funding from Abbott, other funding from Terumo Co., Ltd., other funding from Nihon Kohden, other funding from Medtronic, other funding from Japan Lifeline, other funding from Otsuka, other funding from Ono, other funding from Nippon Boehringer Ingelheim, other funding from Kowa, other funding from Zeon, other funding from Shionogi, other funding from Nippon-Shinyaku, other funding from Mochida, and other funding from Tesco outside of the submitted work. Dr. Miyamoto reports personal fees from Tokyo Marine, personal fees from Nichido Fire Insurance Co., Ltd., personal fees from Fujitsu Co., Ltd., personal fees from Softbank Co., Ltd., personal fees from Meiji Yasuda Life Insurance Company., and personal fees from Saraya Co., Ltd. outside of the submitted work. Dr. Ogawa reports personal fees from Towa Pharmaceutical Co., Ltd., personal fees from Bristol-Meyers Squibb Co., Ltd., personal fees from Pfizer Co., Ltd., personal fees from Toa Eiyo Co., Ltd., personal fees from Bayer Yakuhin Co., Ltd., and personal fees from Novartis Pharma Co., Ltd., personal fees from Takeda Pharmaceutical Co., LTD, personal fees from Daiichisankyo Co., Ltd., personal fees from Eisai Co., Ltd., personal fees from Teijin Co., Ltd. personal fees from Behringer Ingelheim Co., Ltd., Abbott Medical Japan Co., Ltd. outside of the submitted work. No other potential conflict of interest relevant to this article was reported. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The sympathetic nervous system regulates immune cell dynamics. However, the detailed role of sympathetic signaling in inflammatory diseases is still unclear because it varies according to the disease situation and responsible cell types. This study focused on identifying the functions of sympathetic signaling in macrophages in LPS-induced sepsis and renal ischemia-reperfusion injury (IRI)., Methods: We performed RNA sequencing of mouse macrophage cell lines to identify the critical gene that mediates the anti-inflammatory effect of β 2-adrenergic receptor (Adrb2) signaling. We also examined the effects of salbutamol (a selective Adrb2 agonist) in LPS-induced systemic inflammation and renal IRI. Macrophage-specific Adrb2 conditional knockout (cKO) mice and the adoptive transfer of salbutamol-treated macrophages were used to assess the involvement of macrophage Adrb2 signaling., Results: In vitro , activation of Adrb2 signaling in macrophages induced the expression of T cell Ig and mucin domain 3 ( Tim3 ), which contributes to anti-inflammatory phenotypic alterations. In vivo , salbutamol administration blocked LPS-induced systemic inflammation and protected against renal IRI; this protection was mitigated in macrophage-specific Adrb2 cKO mice. The adoptive transfer of salbutamol-treated macrophages also protected against renal IRI. Single-cell RNA sequencing revealed that this protection was associated with the accumulation of Tim3 -expressing macrophages in the renal tissue., Conclusions: The activation of Adrb2 signaling in macrophages induces anti-inflammatory phenotypic alterations partially via the induction of Tim3 expression, which blocks LPS-induced systemic inflammation and protects against renal IRI., (Copyright © 2021 by the American Society of Nephrology.)

Predicting clinical outcomes can be difficult, particularly for life-threatening events with a low incidence that require numerous clinical cases. Our aim was to develop and validate novel algorithms to identify major adverse cardiovascular events (MACEs) from claims databases. We developed algorithms based on the data available in the claims database International Classification of Diseases, Tenth Revision (ICD-10), drug prescriptions, and medical procedures. We also employed data from the claims database of Jichi Medical University Hospital, Japan, for the period between October 2012 and September 2014. In total, we randomly extracted 100 potential acute myocardial infarction cases and 200 potential stroke cases (ischemic and hemorrhagic stroke were analyzed separately) based on ICD-10 diagnosis. An independent committee reviewed the corresponding clinical data to provide definitive diagnoses for the extracted cases. We then assessed the algorithms' accuracy using positive predictive values (PPVs) and apparent sensitivities. The PPVs of acute myocardial infarction, ischemic stroke, and hemorrhagic stroke were low only by diagnosis (81.6% [95% CI 72.5-88.7]; 31.0% [95% CI 22.8-40.3]; and 45.5% [95% CI 34.1-57.2], respectively); however, the PPVs were elevated after adding the prescription and procedure data (87.0% [95% CI 78.3-93.1]; 44.4% [95% CI 32.7-56.6]; and 46.1% [95% CI 34.5-57.9], respectively). When we added event-specific prescription and procedure data to the algorithms, the PPVs for each event increased to 70%-98%, with apparent sensitivities exceeding 50%. Algorithms that rely on ICD-10 diagnosis in combination with data on specific drugs and medical procedures appear to be valid for identifying MACEs in Japanese claims databases., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

The score based on the office systolic blood pressure, age, fasting blood glucose level, and estimated glomerular filtration rate (SAGE score) has been proposed as a useful marker to identify elevated values of carotid-femoral pulse wave velocity (PWV). The present cross-sectional study was conducted to examine whether the SAGE score is also a useful marker to identify subjects with elevated brachial-ankle PWV values in Japanese subjects with hypertension. We measured the brachial-ankle PWV and calculated the SAGE score in a total of 1019 employees of a Japanese company with hypertension and 817 subjects with hypertension derived from a multicenter study cohort. The analyses in this study were based on data from these two study groups as well as on a composite population of the two (n = 1836). The receiver operating characteristic curve analysis showed that the area under the curve to identify subjects with brachial-ankle PWV values of ≥1800 cm/s was over 0.70 in each of the three study groups. Even after adjustments, a SAGE score ≥7 had a significant odds ratio for identifying subjects with brachial-ankle PWV values ≥1800 cm/s in the 1836 study subjects from the composite occupational and multicenter study cohort (odds ratio = 2.1, 95% confidence interval = 1.4-3.0, P < 0.01). Thus, in Japanese subjects with hypertension, the SAGE score may be a useful marker for identifying subjects with elevated brachial-ankle PWV values.

Background: In the era of big data, the utilization and analysis of large amounts of clinical data are imperative. The standardized structured medical information exchange version 2 (SS-MIX2) is a standard data storage format used in Japan to share clinical data from various vendor-derived hospital information systems. This storage format is divided into 2 categories: standardized and extension storage. Although the standardized storage includes clinical data such as basic patient data, prescriptions, and laboratory results, all other data are stored in the extension storage, because their formats are not standardized. Methods and Results: In 2015, the Japanese Circulation Society developed the standard export data format (SEAMAT) for electrocardiography (ECG), ultrasound cardiography (UCG), and catheterization (CATH) data for the SS-MIX2 extension storage. Using physical examination and catheter report systems in accordance with the SEAMAT, specific cardiological data such as ECG, UCG, and CATH can be transferred to the SS-MIX2 extension storage, resulting in efficient secondary use of these data for research purposes. Conclusions: SEAMAT can aid in the effective establishment of a nationwide clinical database, and reduce tedious manual data input by clinicians and clinical research coordinators. Moreover, a program that enables the conversion of comma-separated data from information systems into SEAMAT can provide a useful and economical tool for transferring huge clinical data to the SS-MIX2., Competing Interests: T.M. is a member of Circulation Reports’ Editorial Team., (Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.)

The usefulness of brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, is not fully known for the management of treated hypertensive patients with a history of coronary artery disease (CAD) who have blood pressure less than 130/80 mmHg, a recommended blood pressure target in the updated major hypertension guidelines. We analyzed data for 447 treated hypertensive patients with CAD enrolled in FMD-J Study A for assessment of the predictive value of baPWV for future cardiovascular events. The primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 47.6 months, the primary outcome occurred in 64 patients. Blood pressure less than 130/80 mmHg was significantly associated with a lower risk of the composite outcome independent of other cardiovascular risk factors in treated hypertensive patients with CAD (hazard ratio, 0.59; 95% confidence interval (CI), 0.35-0.99; P = 0.04). In treated hypertensive patients with CAD who had blood pressure less than 130/80 mmHg, baPWV above the cutoff value of 1731 cm/s, derived from receiver-operator characteristic curve analysis for the composite outcome was significantly associated with a higher risk of the composite outcome independent of conventional risk factors (hazard ratio, 2.83; 95% CI, 1.02-7.91; P = 0.04). baPWV was an independent predictor of cardiovascular events in treated hypertensive patients with CAD who had blood pressure less than 130/80 mmHg, for whom measurement of baPWV is recommended for cardiovascular risk assessment.