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Aims: Cardiovascular disease (CVD) is a common cause of death in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Therefore, CVD surveillance is important, but it is not well established. We evaluated the association between liver fibrosis, carotid artery atherosclerosis, and coronary artery stenosis in patients with MASLD., Methods: Overall, 153 patients with MASLD who underwent carotid artery ultrasound were enrolled. Maximum intima-media thickness including plaques (Max-IMT) was measured by ultrasound. To predict liver fibrosis, liver stiffness was measured by vibration-controlled transient elastography and the fibrosis 4 (FIB-4) index was calculated. Coronary computed tomography angiography was performed to detect coronary artery stenosis based on a Max-IMT of ≥ 1.1 mm., Results: The median Max-IMT was 1.3 mm, and 63 patients (41.2%) had a Max-IMT of ≥ 1.5 mm. FIB-4 index and liver stiffness was significantly correlated with Max-IMT, respectively (ρ=0.356, p＜0.001, ρ=0.25, p=0.002). Liver stiffness was significantly associated with a Max-IMT of ≥1.5 mm, independent of age. Individuals with higher FIB-4 index had moderate or severe coronary artery stenosis more frequently. Individuals with higher LSM level also had moderate or severe coronary artery stenosis more frequently, especially severe stenosis., Conclusions: Liver fibrosis parameters were associated with carotid artery atherosclerosis and coronary artery stenosis. Evaluation of liver fibrosis may be useful to identify significant atherosclerosis and coronary artery stenosis in patients with MASLD.

Detailed effect of sodium-glucose cotransporter 2 inhibitors on blood pressure (BP) in Japanese patients with type 2 diabetes (T2D) at a high risk of cardiovascular disease (CVD) is not fully understood. In this post-hoc sub-analysis of placebo-controlled randomized EMBLEM trial for Japanese patients with T2D and CVD, 105 participants (empagliflozin N = 52, placebo N = 53) were included, and office systolic/diastolic BPs and mean arterial pressure (MAP) over 24 weeks were estimated using mixed-effects models for repeated measures. Empagliflozin therapy, compared to placebo, reduced systolic/diastolic BPs (mean group difference in change from baseline to week 24; -5.9 [95% confidence interval (CI), -10.4 to -1.4] mmHg/-2.9 [95% CI, -6.2 to 0.4] mmHg) and MAP ( - 3.8 [95% CI, -7.0 to -0.7] mmHg). The systolic BP reduction was almost consistent across differing background clinical characteristics and usage status of anti-hypertensive medications., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background and Aims: The efficacy and safety of early sacubitril/valsartan (Sac/Val) initiation after acute heart failure (AHF) has not been demonstrated outside North America. The present study aimed to evaluate the effect of in-hospital Sac/Val therapy initiation after an AHF episode on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in Japanese patients., Methods: This was an investigator-initiated, multicentre, prospective, randomized, open-label, blinded-endpoint pragmatic trial. After haemodynamic stabilization within 7 days after hospitalization, eligible inpatients were allocated to switch from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to Sac/Val (Sac/Val group) or to continue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (control group). The primary efficacy endpoint was the 8-week proportional change in geometric means of NT-proBNP levels., Results: A total of 400 patients were equally randomized, and 376 (median age 75 years, 31.9% women, de novo heart failure rate 55.6%, and median left ventricular ejection fraction 37%) were analysed. The per cent changes in NT-proBNP level geometric means at Weeks 4/8 were -35%/-45% (Sac/Val group) and -18%/-32% (control group), and their group ratio (Sac/Val vs. control) was 0.80 (95% confidence interval 0.68-0.94; P = .008) at Week 4 and 0.81 (95% confidence interval 0.68-0.95; P = .012) at Week 8, respectively. In the pre-specified subgroup analyses, the effects of Sac/Val were confined to patients with a left ventricular ejection fraction < 40% and were more evident in those in sinus rhythm and taking mineralocorticoid receptor antagonists. No adverse safety signal was evident., Conclusions: In-hospital Sac/Val therapy initiation in addition to contemporary recommended therapy triggered a greater NT-proBNP level reduction in Japanese patients hospitalized for AHF. These findings may expand the evidence on Sac/Val therapy in this clinical situation outside North America., Clinical Trial Registration: ClinicalTrial.gov (NCT05164653) and Japan Registry of Clinical Trials (jRCTs021210046)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Patients with overweight and obesity are at increased risk of death from multiple causes, including cardiovascular (CV) death, with few therapies proven to reduce the risk., Objectives: This study sought to assess the effect of semaglutide 2.4 mg on all-cause death, CV death, and non-CV death, including subcategories of death and death from coronavirus disease-2019 (COVID-19)., Methods: The SELECT (Semaglutide Effects on Cardiovascular Outcomes in Patients With Overweight or Obesity) trial randomized 17,604 participants ≥45 years of age with a body mass index ≥27 kg/m 2 with established CV disease but without diabetes to once-weekly subcutaneous semaglutide 2.4 mg or placebo; the mean trial duration was 3.3 years. Adjudicated causes of all deaths, COVID-19 cases, and associated deaths were captured prospectively., Results: Of 833 deaths, 485 (58%) were CV deaths, and 348 (42%) were non-CV deaths. Participants assigned to semaglutide vs placebo had lower rates of all-cause death (HR: 0.81; 95% CI: 0.71-0.93), CV death (HR: 0.85; 95% CI: 0.71-1.01), and non-CV death (HR: 0.77; 95% CI: 0.62-0.95). The most common causes of CV death with semaglutide vs placebo were sudden cardiac death (98 vs 109; HR: 0.89; 95% CI: 0.68-1.17) and undetermined death (77 vs 90; HR: 0.85; 95% CI: 0.63-1.15). Infection was the most common cause of non-CV death and occurred at a lower rate in the semaglutide vs the placebo group (62 vs 87; HR: 0.71; 95% CI: 0.51-0.98). Semaglutide did not reduce incident COVID-19; however, among participants who developed COVID-19, fewer participants treated with semaglutide had COVID-19-related serious adverse events (232 vs 277; P = 0.04) or died of COVID-19 (43 vs 65; HR: 0.66; 95% CI: 0.44-0.96). High rates of infectious deaths occurred during the COVID-19 pandemic, with less infectious death in the semaglutide arm, and resulted in fewer participants in the placebo group being at risk for CV death., Conclusions: Compared to placebo, patients treated with semaglutide 2.4 mg had lower rates of all-cause death, driven similarly by CV and non-CV death. The lower rate of non-CV death with semaglutide was predominantly because of fewer infectious deaths. These findings highlight the effect of semaglutide on mortality across a broad population of patients with CV disease and obesity. (Semaglutide Effects on Cardiovascular Outcomes in Patients With Overweight or Obesity [SELECT]; NCT03574597)., Competing Interests: Funding Support and Author Disclosures Dr Scirica has received institutional research grants to Brigham and Women’s Hospital from Better Therapeutics, Merck, Novo Nordisk, and Pfizer; has received consulting fees from Allergan, Amgen, Boehringer Ingelheim, Better Therapeutics, Elsevier Practice Update Cardiology, Esperion, Hanmi, Lexicon, and Novo Nordisk; and holds equity in Health [at] Scale and Doximity. Dr Lincoff has received research grants from AbbVie Inc, AstraZeneca, CSL Behring, Eli Lilly and Company, Esperion Therapeutics, Inc, and Novartis paid to his institution; and has served as a consultant for Akebia Therapeutics Inc, Alnylam Pharmaceuticals Inc, Ardelyx, Eli Lilly and Company, FibroGen, GlaxoSmithKline, Intarcia, Medtronic Vascular Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk, Provention Bio, Entity, and ReCor Medical. Dr Lingvay has received research grants from Boehringer Ingelheim, Merck, Mylan Pharmaceuticals Inc, Novo Nordisk, Pfizer, and Sanofi US Services Inc; has served as a consultant for AstraZeneca, Bayer Healthcare Pharmaceuticals Inc, Biomea, Boehringer Ingelheim, Carmot, Eli Lilly and Company, Intarcia, Intercept Pharmaceuticals, Inc, Janssen Global Services, LLC, Johnson & Johnson Medical Devices & Diagnostics Group-Latin America, LLC, MannKind Corporation, Merck, Novo Nordisk, Pfizer Inc, Sanofi US Services Inc, Shionogi Inc, Structure Therapeutics, Target Pharma, Valeritas, Inc, and Zealand Pharma; and has received travel expenses from Boehringer Ingelheim, Eli Lilly and Company, Johnson & Johnson Medical Devices & Diagnostics Group-Latin America, LLC, Novo Nordisk, Sanofi US Services Inc, and Zealand Pharma A/S. Dr Buscemi has received advisory/consulting honoraria from Novo Nordisk, Eli Lilly, Pfizer, Boehringer Ingelheim, and Dompè. Dr Colhoun has served on advisory panels for Novo Nordisk and Bayer; has received research funding from Sanofi, Roche, and IQVIA; has received grants from Chief Scientist Office, Diabetes UK, European Commission, Juvenile Diabetes Research Foundation, and Medical Research Council; has served on the Speakers Bureau for Novo Nordisk; and holds equity in Roche Pharmaceuticals and Bayer. Dr Craciun has received advisory/consulting fees and/or other support from Novo Nordisk, Eli Lilly, Sanofi, Boehringer Ingelheim, Servier, Berlin Chemie, and Viatris. Dr Hardt-Lindberg is an employee of and stakeholder in Novo Nordisk. Dr Jeppesen is an employee of and stakeholder in Novo Nordisk. Dr Matos is an employee of and stakeholder in Novo Nordisk. Dr Node has received honoraria from AstraZeneca, Bayer Yakuhin, Boehringer Ingelheim Japan, Daiichi-Sankyo, Eli Lilly Japan, Mitsubishi Tanabe Pharma, Merck Sharp & Dohme, Novartis Pharma, and Otsuka; has received research grants from Astellas, Bayer Yakuhin, Boehringer Ingelheim Japan, Fujiyakuhin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, and Novartis Pharma; and has received scholarships from Abbott, Boehringer Ingelheim Japan, Daiichi-Sankyo, Mitsubishi Tanabe Pharma, and Teijin Pharma. Dr Toplak has received institutional research grants from Amgen, Daiichi-Sankyo, Novo Nordisk, and Novartis; and has received consulting/speaker honoraria from Amgen, Daiichi-Sankyo, Novartis, and Novo Nordisk. Dr van Beek has been contracted via the University of Groningen (no personal payment) to undertake consultancy for Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Dr Weeke is an employee of and stakeholder in Novo Nordisk. Dr Wiviott has received research grants from Amgen, AstraZeneca, Janssen, Merck, and Pfizer; has received consulting fees from Icon, Novo Nordisk, and Verian; has received speaking honoraria from Harvard Medical School; is a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc, Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc, Roche, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, The Medicines Company, and Zora Biosciences; and his spouse, Dr Caroline Fox, is a former employee of Merck, Flagship Labs, and current employee of Vertex. Dr Deanfield has received consulting honoraria from Amgen, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, and Bayer; and has received research grants from British Heart Foundation, MRC(UK), National Institute for Health and Care Research, PHE, Merck Sharp & Dohme, Pfizer, Aegerion, Colgate, and Roche. Dr Ryan has received consulting honoraria from Altimmune, Amgen, Biohaven, Boehringer Ingelheim, Calibrate, Carmot Therapeutics, CinRx, Eli Lilly, Epitomee, Gila Therapeutics, Ifa Celtic, Novo Nordisk, Pfizer, Rhythm, Scientific Intake, Wondr Health, and Zealand; and has received stock options from Calibrate, Epitomee, Scientific Intake, and Xeno Bioscience. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The left-digit bias (LDB), a numerical-related cognitive bias, not only potentially influences decision-making among the general public but also that of medical practitioners. Few studies have investigated its role in out-of-hospital cardiac arrest (OHCA)., Methods: We retrospectively included all consecutive patients with OHCA witnessed by family members registered in the All-Japan Utstein Registry of the Fire and Disaster Management Agency between January 1, 2005, and December 31, 2020. Target outcomes were the percentage of bystander cardiopulmonary resuscitation (BCPR) performed by family members or paramedics and the percentage of prehospital physician-staffed advanced cardiac life support (ACLS). Using a nonparametric regression discontinuity methodology, we examined whether a significant change occurred in the percentages of BCPR and ACLS at the age thresholds of 60, 70, 80, and 90 years, which would indicate the presence of LDB., Results: Of the 1,930,273 OHCA cases in the All-Japan Utstein Registry, 384,200 (19.9%) cases witnessed by family members were analyzed. The mean age was 75.8 years (±SD 13.7), with 38.0% (n = 146,137) female. We identified no discontinuities in the percentages of chest compressions, mouth-to-mouth ventilation, or automated external defibrillator (AED) usage by family members for the age thresholds of 60, 70, 80, and 90 years. Moreover, no discontinuities existed in the percentages of chest compressions, advanced airway management, and AED usage by paramedics or prehospital ACLS by physicians for any of the age thresholds., Conclusions: In conclusion, our study did not find any evidence that age-related LDB affects medical decision-making in patients with OHCA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Suzuki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: This prospective multicenter study assessed the prevalence of myocardial injury in patients with COVID-19 using cardiac magnetic resonance imaging (CMR)., Methods and Results: We prospectively screened 505 patients with moderate to severe COVID-19 disease from 7 hospitals in Japan. Of these patients, 31 (mean [±SD] age 63.5±10.4 years, 23 [74%] male) suspected of myocardial injury, based on elevated serum troponin or B-type natriuretic peptide concentrations either upon admission or 3 months after discharge, underwent CMR 3 months after discharge. The primary endpoint was the presence of myocardial injury, defined by any of the following: (1) contrast enhancement in the left or right ventricle myocardium on late gadolinium enhancement CMR; (2) left or right ventricular dysfunction (defined as <50% and <45%, respectively); and (3) pericardial thickening on contrast enhancement. The mean (±SD) duration between diagnosis and CMR was 117±16 days. The primary endpoint was observed in 13 of 31 individuals (42%), with 8 (26%) satisfying the modified Lake Louise Criteria for the diagnosis of acute myocarditis., Conclusions: This study revealed a high incidence of myocardial injury identified by CMR in patients with moderate to severe COVID-19 and abnormal findings for cardiac biomarkers.

We assessed the association of employee lifestyles (e.g., smoking, exercise, drinking, and sleep habits) with mental health-related absenteeism and turnover rates utilizing data from the annual Health and Productivity Management survey by Japan's Ministry of Economy, Trade and Industry. This analysis included data from 1,748 companies, encompassing 4,199,021 employees. The average proportions of mental health-related absenteeism and employee turnover rates were 1.1% (±1.0%) and 5.0% (±5.0%), respectively. In multivariable regression models that incorporated all lifestyle factors and confounders, a 1 percentage point increase in the proportion of employees who slept well was associated with reductions in their turnover rate (mean -0.020%; 95% CI, -0.038% to -0.002%) and in mental health-related absenteeism (mean -0.005%; 95% CI, -0.009% -0.001%). A similar increase in the proportion of employees engaging in regular physical activity corresponded with a 0.005% decrease in the prevalence of mental health-related absenteeism (95% CI, -0.010% to -0.001%). A 1 percentage point increase in the proportion of employees who smoked was associated with a 0.013% reduction in mental health-related absenteeism (95% CI, -0.017% to -0.008%). Nonetheless, the current study's observational and cross-sectional design restricted the ability to establish causality between employee lifestyle factors and mental health issues.

Background: The influence of a change to a default X summary posting strategy on article viewership has not been investigated., Methods and Results: We conducted a retrospective analysis of X-posting rates and journal viewership data for both the Circulation Journal and Circulation Reports from April 2022 to September 2023. Following protocol modifications in March 2023, there was a notable increase in the X-posting rate from 12.4% to 61.7%, along with an uptick in median access counts to article pages within 30 days, from 175 to 231.5., Conclusions: Trend analysis of journal viewership after a default X-posting strategy revealed an increase in viewer access., Competing Interests: No conflicts of interest exist in this study, but we declare that our co-authors, Shoji Sanada, Masataka Sata, Koichi Node, and Toshihisa Anzai are members of the Editorial Team of Circulation Report., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: 1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or 2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence., (© 2024. The Author(s).)

Hypertension and cancer are both increasing with age. Recently, the new concept of "Onco-Hypertension" has been proposed to address the mutual risks posed by hypertension and cancer and to provide comprehensive care for patients with these two conditions in an aging society. Hypertension and cancer share common risk factors and may be interrelated in pathogenesis: hypertension is involved in the development of certain cancers, and cancer survivors have a higher incidence of hypertension. With recent advances in cancer therapy, the number of cancer survivors has increased. Cancer survivors not only have a higher risk of incident hypertension but also an increased risk of future cardiovascular events, highlighting the growing importance of comprehensive care. In this review, we provide an overview of the current status and future perspective of the "Onco-Hypertension," including our research findings., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Aims: This study aimed to investigate the clinical impact of pre-procedural left atrial strain (LAS) in patients undergoing permanent pacemaker implantation (PPI)., Methods and Results: This single-centre retrospective study enrolled 434 patients who were admitted for transvenous PPI between 2010 and 2020. After excluding patients with persistent atrial fibrillation, PPI for complete atrioventricular block, severe valvular disease, history of open-heart surgery and those without LAS data, 172 patients were analysed. The LAS was measured using commercially available software to calculate the average strain value of the apical four- and two-chamber views before PPI. The primary composite endpoint was hospitalization due to heart failure or cardiovascular death. Cox proportional hazard models were used to evaluate risk factors for the primary composite endpoint. The mean patient age was 78 ± 8 years, and 42% of the patients were men. PPI was performed for sick sinus syndrome in 64% and second-degree atrioventricular block in 36% of the patients. The pre-procedure left atrial reservoir strain (LASr) was 28 ± 11%. The median follow-up period was 4.7 years, and the primary endpoint was observed in 23 (13%) patients. In multivariate Cox proportional risk analysis, LASr was independently associated with the primary composite endpoint (hazard ratio, 1.08 per 1% decrease; 95% confidence interval, 1.02-1.15; P = 0.007). The receiver operating characteristic curve of the LASr for the primary composite endpoint showed a cutoff value of 21% (area under the curve 0.657, P = 0.004). The prognostic impact of LASr was consistent with that of sick sinus syndrome and atrioventricular block., Conclusions: A decreased pre-procedure LASr was associated with long-term adverse outcomes after PPI use., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aim: To investigate the clinical significance of body weight changes on kidney outcomes among individuals with diabetes using sodium-glucose cotransporter-2 (SGLT2) inhibitors., Materials and Methods: This is a retrospective cohort study using a nationwide epidemiological database, and we conducted an analysis involving 11 569 individuals with diabetes who were newly prescribed SGLT2 inhibitors. The main outcome was the rate of decline in estimated glomerular filtration rate (eGFR), determined through a linear mixed-effects model with an unstructured covariance structure., Results: The median age of the patients was 52 (Q1-Q3: 47-58) years, and the median fasting plasma glucose and glycated haemoglobin (HbA1c) levels were 144 (Q1-Q3: 124-175) mg/dL and 7.4 (Q1-Q3: 6.8-8.3)%, respectively. The median estimated eGFR was 77.7 (Q1-Q3: 67.2-89.1) mL/min/1.73 m 2 . The median follow-up period was 1.7 (Q1-Q3: 1.0-2.6) years. Participants were stratified into three groups based on the body mass index change rate tertiles between baseline and 1 year after (tertile 1: <-4.55%, tertile 2: -4.55% to -1.43%, tertile 3: >-1.43%). The annual change in eGFR was -0.78 (-0.94 to -0.63) mL/min/1.73 m 2 in tertile 1, -0.95 (-1.09 to -0.81) mL/min/1.73 m 2 in tertile 2, and -1.65 mL/min/1.73 m 2 (-1.84 to -1.47) in tertile 3 (p interaction  < 0.001). A variety of sensitivity analyses confirmed the relationship between the 1-year body mass index decrease and favourable kidney outcomes after SGLT2 inhibitor administration., Conclusions: Our analysis of a nationwide epidemiological cohort revealed that kidney outcomes following the initiation of SGLT2 inhibitors would be more favourable, with greater body weight loss observed after the initiation of SGLT2 inhibitors., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: The association between stage 1 hypertension and the risk of cardiovascular disease (CVD) has not been established in older adults. Furthermore, little is known about whether lowering blood pressure (BP) is beneficial in older adults with stage 1 hypertension., Methods: This cohort study analyzed nationwide data collected from the Japanese DeSC database, including 476,654 individuals aged ≥60 years. Individuals were categorized into four groups according to the 2017 ACC/AHA BP guidelines: normal BP, elevated BP, stage 1 hypertension, and stage 2 hypertension. The primary outcome was a composite CVD event, including myocardial infarction, angina pectoris, stroke, and heart failure., Results: During a mean follow-up of 3.1 years, 53,946 composite CVD events were recorded. Hazard ratios of stage 1 hypertension for composite CVD events, myocardial infarction, angina pectoris, stroke, and heart failure were 1.10 (95 % CI, 1.07-1.13), 1.16 (95 % CI, 1.03-1.31), 1.06 (95 % CI, 1.01-1.10), 1.13 (95 % CI, 1.08-1.18), and 1.13 (95 % CI, 1.09-1.16), respectively. Individuals with a ≥5 mmHg decrease in systolic BP over one year had a lower risk of stroke among individuals with stage 1 hypertension. The positive association between stage 1 hypertension and composite CVD events was attenuated in individuals aged ≥75 years., Conclusions: Stage 1 hypertension is associated with a higher risk of developing CVD events among older adults. The 2017 ACC/AHA BP guidelines could be applied to older populations; however, the applicability of these guidelines to older adults aged ≥75 years requires further investigations., Competing Interests: Declaration of competing interest Research funding and scholarship funds (Hidehiro Kaneko and Katsuhito Fujiu) from Medtronic Japan Co., LTD, Abbott Medical Japan Co., LTD, Boston Scientific Japan Co., LTD, and Fukuda Denshi, Central Tokyo Co., Ltd. Speaker fees from AstraZeneca, Ono Pharmaceutical, Nippon Boehringer Ingelheim; Scholarship donation from Idorsia, Sanofi, Toa Eiyo; Affiliation with endowed chairs from Idorsia Pharmaceuticals Japan, Novo Nordisk Pharma, Toa Eyo Co, Takara Bio Inc., Nippon Boehringer Ingelheim Co., BioStream, Inc. (Issei Komuro). Other authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives　Food environment improvement involving salt reduction requires improving access to and labeling low-sodium foods. Assessing the implementation status of these measures is also necessary. However, to date, no established methods exist for assessing the availability of low-sodium foods in communities. In this study, we aimed to devise a survey on the availability of low-sodium foods as a community food environment assessment method in order to establish common assessment methods, criteria, and practical measures, as well as standardization nationwide.Methods　A preliminary survey on the availability of low-sodium foods was conducted in Kitakyushu City in four stores with nationwide representation. Consent for providing information on handled product lists was obtained. The on-site lists collected through direct investigation by surveyors were compared with the handled product lists provided by the stores and analyzed to identify survey challenges and examine feasibility and the potential for accuracy. The definition of low-sodium foods, which emerged as a challenge in the preliminary survey, was confirmed. Preliminary survey data were carefully reviewed to establish classification criteria for low-sodium foods and create a low-sodium food list to serve as a reference for on-site surveys. Forms for recording the results of on-site surveys and a survey manual were developed. Registered dietitians conducted on-site surveys using the manual to confirm its applicability.Results　The preliminary survey results revealed that the on-site lists had fewer omissions and greater feasibility than store-provided lists. After clearly defining low-sodium foods, we established classification criteria (three major categories, seven subcategories, and 37 minor categories) considering the ease of on-site investigations and purchases. Three forms for recording survey results were developed, including a standard input form allowing detailed documentation of the availability of individual low-sodium foods, an aggregation form for a quantitative assessment of low-sodium foods availability, and a display form visualizing the availability of low-sodium foods by store. Furthermore, a survey manual was developed explaining the purpose and approach of the low-sodium foods availability survey, definition and classification criteria for low-sodium foods, and the three forms for recording survey results. Findings indicated that all registered dietitians could conduct on-site surveys using the manual and successfully collect and organize data.Conclusion　On-site surveys using the manual and documentation forms enabled easy and accurate assessments of low-sodium foods availability. Thus, this standardized method to assess the availability of low-sodium foods could be a food environment assessment method for regional salt reduction initiatives.

Although patients with hyperuricemia and gout often have dyslipidemia, the effects of febuxostat, a xanthine oxidase inhibitor, on their lipid profiles are unclear. Thus, we performed a sub-analysis of the randomized PRIZE study in which the effects of febuxostat on carotid atherosclerosis were investigated in patients with hyperuricemia. The participants were randomized to the febuxostat or control group. The primary endpoint of this sub-analysis was changes in the patients' non-high-density lipoprotein cholesterol (HDL-C) levels from baseline to 6-month follow-up. Correlations between the changes in lipid profiles and cardiometabolic parameters were also evaluated. In total, 456 patients were included. From baseline to 6 months, non-HDL-C levels were significantly reduced in the febuxostat group (-5.9 mg/dL, 95% confidence interval [CI]: -9.1 to -2.8 mg/dL, p < 0.001), but not in the control group (-1.3 mg/dL, 95% CI: -4.4 to 1.8, p = 0.348). The reduction in non-HDL-C levels was more pronounced in women and correlated with changes in serum uric acid and estimated glomerular filtration rate levels only in the febuxostat group. In patients with hyperuricemia, febuxostat treatment was associated with reduced non-HDL-C levels from baseline to the 6-month follow-up compared to the control treatment, suggesting that the lipid-lowering effect of febuxostat should be considered when targeting dyslipidemia.

Background and Hypothesis: While the kidney protective effects of sodium glucose co-transporter-2 (SGLT2) inhibitors have attracted much attention, there are limited real-world clinical data examining the effects of SGLT2 inhibitors on kidney function in older individuals. We aimed to compare the kidney outcomes between SGLT2 inhibitor and dipeptidyl peptidase 4 (DPP4) inhibitor use in older adults with diabetes., Methods: Using a nationwide claims database, we studied 6 354 older adults (≥ 60 years of age) who had diabetes and newly initiated on SGLT2 inhibitors or DPP4 inhibitors. A 1:4 propensity score matching algorithm was used to compare changes in eGFR between SGLT2 inhibitor and DPP4 inhibitor users. The primary outcome was a decline in the rate of estimated glomerular filtration rate (eGFR), which was obtained using a linear mixed-effects model with an unstructured covariance., Results: Following propensity score matching, 6 354 individuals including 1 271 SGLT2 inhibitor users and 5 083 DPP4 inhibitor users (median age: 68 [65-70] years); men, 60.4%; median eGFR:69.0 [59.1-79.0] ml/min/1.73 m2, median hemoglobin A1c [HbA1c]:6.9 [6.5-7.4]%) were analyzed. SGLT2 inhibitor users had a slower eGFR decline than did DPP4 inhibitor users (-0.97 [95% CI, -1.24 to -0.70] ml/min/1.73m2 vs. -1.83 [95% CI, -1.97 to -1.69] ml/min/1.73m2 per year; p for interaction < 0.001). This finding remained consistent across subgroups based on age, sex, body mass index, HbA1c level, renin-angiotensin system inhibitor use, and baseline eGFR. Additionally, the risk of a ≥ 20%, ≥ 30%, and ≥ 40% decrease in eGFR from baseline was significantly lower in SGLT2 inhibitor users than that in DPP4 inhibitor users., Conclusions: Our analysis, utilizing a nationwide epidemiological dataset, demonstrated that the decline in eGFR was slower in individuals aged ≥ 60 years with diabetes who were prescribed SGLT2 inhibitors compared to those prescribed DPP4 inhibitors, suggesting a potential advantage of SGLT2 inhibitors for kidney outcomes even in older individuals with diabetes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Although living alone versus with others is a key social element for cardiovascular prevention in diabetes, evidence is lacking about whether the benefit of intensive glycemic and blood pressure (BP) control differs by living arrangements. We thus aim to investigate heterogeneity in the joint effect of intensive glycemic and BP control on cardiovascular events by living arrangements among participants with diabetes., Methods and Results: This study included 4731 participants with diabetes in the ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes-Blood Pressure) trial. They were randomized into 4 study arms, each with glycated hemoglobin target (intensive, <6.0% versus standard, 7.0-7.9%) and systolic BP target (intensive, <120 mm Hg versus standard <140 mm Hg). Cox proportional hazard models were used to estimate the joint effect of intensive glycemic and BP control on the composite cardiovascular outcome according to living arrangements. At a mean follow-up of 4.7 years, the cardiovascular outcome was observed in 445 (9.4%) participants. Among participants living with others, intensive treatment for both glycemia and BP showed decreased risk of cardiovascular events compared with standard treatment (hazard ratio [HR], 0.68 [95% CI, 0.51-0.92]). However, this association was not found among participants living alone (HR, 0.96 [95% CI, 0.58-1.59]). P for interaction between intensive glycemic and BP control was 0.53 among participants living with others and 0.009 among those living alone ( P value for 3-way interaction including living arrangements was 0.049)., Conclusions: We found benefits of combining intensive glycemic and BP control for cardiovascular outcomes among participants living with others but not among those living alone. Our study highlights the critical role of living arrangements in intensive care among patients with diabetes.

The SELECT trial previously reported a 20% reduction in major adverse cardiovascular events with semaglutide (n = 8,803) versus placebo (n = 8,801) in patients with overweight/obesity and established cardiovascular disease, without diabetes. In the present study, we examined the effect of once-weekly semaglutide 2.4 mg on kidney outcomes in the SELECT trial. The incidence of the pre-specified main composite kidney endpoint (death from kidney disease, initiation of chronic kidney replacement therapy, onset of persistent estimated glomerular filtration rate (eGFR) < 15 ml min -1  1.73 m - 2 , persistent ≥50% reduction in eGFR or onset of persistent macroalbuminuria) was lower with semaglutide (1.8%) versus placebo (2.2%): hazard ratio (HR) = 0.78; 95% confidence interval (CI) 0.63, 0.96; P = 0.02. The treatment benefit at 104 weeks for eGFR was 0.75 ml min -1  1.73 m - 2 (95% CI 0.43, 1.06; P < 0.001) overall and 2.19 ml min -1  1.73 m - 2 (95% CI 1.00, 3.38; P < 0.001) in patients with baseline eGFR <60 ml min -1  1.73 m - 2 . These results suggest a benefit of semaglutide on kidney outcomes in individuals with overweight/obesity, without diabetes.ClinicalTrials.gov identifier: NCT03574597 ., (© 2024. The Author(s).)

Hypertension is the leading risk factor for cardiovascular disease (CVD). Although cancer has recently been increasingly recognized as a novel risk factor for CVD events, little is known about whether co-morbid cancer in individuals with hypertension could further increase the risk of CVD events. We sought to determine the association between the cancer history and the risk of CVD in individuals with hypertension. We retrospectively analyzed a large cohort of 747,620 individuals diagnosed with hypertension from January 2005 through May 2022 using the JMDC Claims Database. Composite CVD events, including myocardial infarction (MI), angina pectoris (AP), stroke, heart failure (HF), and atrial fibrillation (AF), were recorded, and a Cox proportional hazard regression was done to estimate hazard ratios (HR) based on the history of cancer and chemotherapy. 26,531 individuals had a history of cancer. During the mean follow-up period of 1269 ± 962 days, 67,154 composite CVD events were recorded. Compared with individuals without a cancer history, cancer survivors had a higher risk of developing composite CVD events (HR: 1.21, 95% confidence interval [CI]: 1.17-1.26). The HRs (95% CIs) associated with cancer history for MI, AP, stroke, HF, and AF were 1.07 (0.90-1.27), 1.13 (1.06-1.20), 1.14 (1.06-1.24), 1.31 (1.25-1.38), and 1.22 (1.10-1.35), respectively. Lastly, individuals who had received chemotherapy for cancer had a particularly higher risk of developing CVD compared to those who did not undergo chemotherapy. A history of cancer was associated with a greater risk of developing CVD among individuals with hypertension., (© 2024. The Author(s).)

Aims: Individuals with diabetes have a high risk of developing cardiovascular disease (CVD). Little was known whether the association between modifiable risk factors and incident CVD would change according to the presence of diabetes., Methods: In this study, we analyzed 4,132,006 individuals including 173,262 individuals (4.2%) with diabetes registered in the JMDC Claims Database, and compared the association between modifiable risk factors and risk of CVD between individuals with and without diabetes., Results: The median age was 44 years, and 57.5% were men. Multivariable Cox regression analyses showed that the relationship of obesity, hypertension, and dyslipidemia with incident CVD was attenuated in individuals with diabetes, whereas that of non-ideal eating habits, smoking, and physical inactivity with incident CVD was pronounced in those with diabetes. The hazard ratio per 1-point increase in non-ideal lifestyle-related factors was 1.03 [95% confidence interval (CI) 1.03-1.04] in individuals with non-diabetes, whereas 1.09 [95% CI 1.07-1.11] in individuals with diabetes (p-value for interaction < 0.001). Further, hazard ratios for developing CVD were 1.02 [95% 1.01-1.04] in individuals not having diabetes, whereas 1.09 [95% CI 1.04-1.13] in individuals having diabetes for the increase of lifestyle-related factor after 1-year follow-up (p-value for interaction 0.007)., Conclusion: Our analysis utilizing a nationwide epidemiological dataset presented that the relationship of lifestyle-related factors with incident CVD would be pronounced in people having diabetes, suggesting that the maintenance of a healthy lifestyle would play a more important role in the development of CVD in individuals having diabetes. (244 words)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Despite advances in multidisciplinary acute care for myocardial infarction (MI), the clinical need to manage heart failure and elevated mortality risks in the remote phase of MI remains unmet. Various prognostic models have been established using clinical indicators obtained during the acute phase of MI; however, most of these indicators also show chronic changes in the post-MI phase. Although relevant guidelines recommend follow-up assessments of some clinical indicators in the chronic phase, systematic reassessment has not yet been fully established and implemented in a real-world clinical setting. Therefore, clinical evidence of the impact of such chronic transitions on the post-MI prognosis is lacking. We speculate that post-MI reassessment of key clinical indicators and the impact of their chronic transition patterns on long-term prognoses can improve the quality of post-MI risk stratification and help identify residual risk factors. Several recent studies have investigated the impact of the chronic transition of some clinical indicators, such as serum albumin level, mitral regurgitation, and left-ventricular dysfunction, on post-MI prognosis. Interestingly, even in MI survivors with these indicators within their respective normal ranges in the acute phase of MI, chronic transition to an abnormal range was associated with worsening cardiovascular outcomes. On the basis of these recent insights, we discuss the clinical significance of post-MI reassessment to identify the trajectories of several clinical indicators and elucidate the potential residual risk factors affecting adverse outcomes in MI survivors., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Although several randomized clinical trials have reported the potential benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in reducing blood pressure (BP), whether SGLT2i can reduce incident hypertension is unknown. We analyzed individuals with diabetes who were newly prescribed SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i) in a large-scale epidemiological database. The primary outcome was the incidence of hypertension. A propensity score matching algorithm was employed to compare the subsequent development of hypertension between the SGLT2i and DPP4i groups. After propensity score matching, 5708 well-balanced pairs of SGLT2i and DPP4i users were identified. SGLT2i administration was associated with a reduced risk of hypertension (HR 0.91, 95% CI: 0.84-0.97). The advantage of SGLT2i use over DPP4i use for incident hypertension was generally consistent in several sensitivity analyses, and subgroup analyses showed that SGLT2i use was significantly associated with a lower risk of hypertension in men, patients with baseline HbA1c of <7.5%, and baseline systolic blood pressure ≥127 mmHg. Our investigation using nationwide real-world data demonstrated the potential advantage of SGLT2i over DPP4i in reducing the development of hypertension in individuals with diabetes., (© 2024. The Author(s).)

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes., Methods: A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values., Results: In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was - 1.07 (95% confidence interval [CI] - 1.29 to - 0.86; P < 0.001). The change in the number of appropriate device discharges during and before treatment was 0.06 in the empagliflozin group and 0.27 in the placebo group, with no significant difference between the groups (P = 0.204). Empagliflozin was associated with an increase in blood ketones and hematocrit and a decrease in blood brain natriuretic peptide and body weight., Conclusions: In patients with type 2 diabetes treated with ICD/CRT-D, empagliflozin reduces the number of ventricular arrhythmias compared with placebo. Trial registration jRCTs031180120., (© 2024. The Author(s).)

Background: Pulmonary vein (PV) stenosis (PVS) is a serious complication of atrial fibrillation (AF) ablation. The objective of this study was to describe interventional treatments for PVS after AF ablation and long-term outcomes in Japanese patients., Methods and results: This multicenter retrospective observational study enrolled 30 patients (26 [87%] male; median age 55 years) with 56 severe PVS lesions from 43 PV interventional procedures. Twenty-seven (90%) patients had symptomatic PVS and 19 (63%) had a history of a single AF ablation. Of the 56 lesions, 41 (73%) were de novo lesions and 15 (27%) were retreated. Thirty-three (59%) lesions were treated with bare metal stents, 14 (25%) were treated with plain balloons, and 9 (16%) were treated with drug-coated balloons. All lesions were successfully treated without any systemic embolic event. Over a median follow-up of 584 days (interquartile range 265-1,165 days), restenosis rates at 1 and 2 years were 35% and 47%, respectively. Multivariate Cox regression analysis revealed devices <7 mm in diameter (hazard ratio [HR] 2.52; 95% confidence interval [CI] 1.04-6.0; P=0.040) and totally occluded lesions (HR 3.33; 95% CI 1.21-9.15; P=0.020) were independent risk factors for restenosis., Conclusions: All PVS lesions were successfully enlarged by the PV intervention; however, restenosis developed in approximately half the lesions within 2 years.

Background: There have been limited studies examining age-dependent associations between physical inactivity and cardiovascular disease (CVD). We aimed to clarify the age-dependent relationship of physical inactivity with incident CVD., Methods: We analyzed 1,097,424 participants, aged 18 to 105 years, without histories of CVD, enrolled in the DeSC database (median age, 63 years; 46.4% men). We categorized participants into the following 4 groups based on age: ≤ 44 years (n = 203,835); 45 to 64 years (n = 403,619); 65 to 79 years (n = 437,236); and ≥ 80 years (n = 52,734). We used 3 physical inactivity components gained from the self-reported questionnaire during a health checkup. The outcomes were composite CVD events including myocardial infarction, stroke, heart failure, and each CVD event., Results: During a mean follow-up of 3.2 ± 1.9 years, 81,649 CVD events were observed. The hazard ratios of 3 physical inactivity components for CVD events increased with age category (P for interaction < 0.001). For example, the hazard ratio (95% confidence interval) of physical inactivity defined as not doing light sweaty exercise for 30 minutes at least twice a week for incident CVD in the groups aged ≤ 44 years, 45 to 64 years, 65 to 79 years, and ≥ 80 years were 0.97 (0.88-1.05), 1.08 (1.05-1.12), 1.12 (1.10-1.15), and 1.17 (1.12-1.21), respectively (P for interaction < 0.001). This association was consistent across subtypes of CVD including heart failure, myocardial infarction, and stroke., Conclusions: The association of physical inactivity with a higher risk of developing CVD increased with age. Preventive efforts for physical activity optimization may be more valuable in older people., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There are limited data on how advancing age influences prediction of CVD risk based on the estimated glomerular filtration rate (eGFR) and proteinuria, especially in older adults, including those aged ≥ 85 years. This study aimed to clarify the association of eGFR and proteinuria with CVD outcomes and the impact of age on this association., Methods: The distribution of eGFR and urine protein in Japan was assessed retrospectively using real-world administrative claims and health checkup data collected between April 2014 and November 2022. We investigated the associations of these two parameters with the incidence of CVD, with an emphasis on the impact of aging., Results: We assessed 1 829 020 individuals for distribution of eGFR and proteinuria; after excluding those with known CVD, their association with CVD risk was examined in 1 040 101 individuals aged ≥ 40 years. The prevalence of impaired kidney function (eGFR <60 mL/min/1.73 m2) increased with age, being 0.7%, 9.2%, 21.9%, 40.2%, and 60.2% at the ages of 18-39, 40-64, 65-74, 75-84, and ≥ 85 years (P for trend < 0.001); similarly, the proportion with positive proteinuria increased with age, being 2.7%, 4.3%, 5.6%, 9.2%, and 15.8%, respectively (P for trend < 0.001). Both eGFR and urine protein were identified to be independent risk factors for CVD. Hazard ratios for CVD increased significantly when eGFR was <45 mL/min/1.73 m2 at the ages of 40-64, 65-74, and 75-84 and <30 mL/min/1.73 m2 at ≥ 85 years, while proteinuria remained significantly associated with a high CVD risk regardless of age. These findings were consistent even when analyzed separately by sex., Conclusions: This study identified eGFR and urine dipstick proteinuria to be independent risk factors for CVD, even among individuals aged ≥ 85 years. However, the contribution of eGFR to the CVD risk was attenuated by aging, whereas proteinuria remained less affected by advancing age., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

The efficacy of renal denervation (RDN) has been controversial, but recent randomized sham-controlled trials demonstrated significant blood pressure reductions after RDN in patients with hypertension. We conducted a systematic review and updated meta-analysis to evaluate the effects of RDN on ambulatory and office blood pressures in patients with hypertension. Databases were searched up to 15 November 2023 to identify randomized, sham-controlled trials of RDN. The primary endpoint was change in 24 h ambulatory systolic blood pressure (SBP) with RDN versus sham control. The secondary endpoints were changes in 24 h ambulatory diastolic blood pressure, daytime and nighttime blood pressure (BP), office BP, and home BP. A sub-analysis determined outcomes by medication, procedure, and device. From twelve trials, 2222 patients with hypertension were randomized to undergo RDN (n = 1295) or a sham procedure (n = 927). At 2-6 months after treatment, RDN significantly reduced 24 h ambulatory SBP by 2.81 mmHg (95% confidence interval: -4.09, -1.53; p < 0.001) compared with the sham procedure. RDN also reduced daytime SBP by 3.17 mmHg (- 4.75, - 1.58; p < 0.001), nighttime SBP by 3.41 mmHg (- 4.69, - 2.13; p < 0.001), office SBP by 4.95 mmHg (- 6.37, - 3.54; p < 0.001), and home SBP by 4.64 mmHg (- 7.44, - 1.84; p = 0.001) versus the sham control group. There were no significant differences in the magnitude of BP reduction between first- and second-generation trials, between devices, or between with or without medication. These data from randomized sham-controlled trials showed that RDN significantly reduced all blood pressure metrics in medicated or unmedicated patients with hypertension, including resistant/uncontrolled hypertension., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Aim: To compare the risk of developing kidney outcomes with use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus use of sodium-glucose cotransporter-2 (SGLT2) inhibitors among individuals with diabetes., Materials and Methods: In this retrospective observational study, we analysed 12 338 individuals with diabetes who newly initiated SGLT2 inhibitors or GLP-1RAs using data from the JMDC claims database. The primary outcome was change in the estimated glomerular filtration rate (eGFR), estimated using a linear mixed-effects model. A 1:4 propensity-score-matching algorithm was used to compare the changes in eGFR between GLP-1RA and SGLT2 inhibitor users., Results: After propensity-score matching, 2549 individuals (median [range] age 52 [46-58] years, 80.6% men) were analysed (510 GLP-1RA new users and 2039 SGLT2 inhibitor new users). SGLT2 inhibitor use was associated with a slower eGFR decline when compared with GLP-1RA use (-1.41 [95% confidence interval -1.63 to -1.19] mL/min/1.73 m 2 vs. -2.62 [95% confidence interval -3.15 to -2.10] mL/min/1.73 m 2 )., Conclusions: Our analysis demonstrates the potential advantages of SGLT2 inhibitors over GLP-1RAs in terms of kidney outcomes in individuals with diabetes., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: The anti-inflammatory effects of the xanthine oxidase inhibitor, febuxostat, a urate-lowering agent, have been reported in animal studies. However, the anti-inflammatory effects of urate-lowering therapy and its associated cardiovascular protective effects have not been fully determined in actual clinical practice. This study aimed to investigate the effect of febuxostat on white blood cell (WBC) count in patients with asymptomatic hyperuricemia and to assess for potential correlations between changes in WBC count and inflammatory biomarkers and atherosclerosis in this patient population., Methods: This was a post hoc subanalysis of the PRIZE study, a multicenter, prospective, randomized, open-label clinical trial. In the PRIZE study, asymptomatic hyperuricemia patients were randomized to febuxostat group or control group with non-pharmacological therapy and evaluated the effect on vascular. The primary endpoints of this study were the assessment of the time course of WBC count over 24 months and its changes from baseline. Correlations of WBC count with high-sensitivity C-reactive protein (hs-CRP) and mean common carotid artery (CCA)-IMT were also exploratorily examined in the febuxostat group., Results: A total of 444 patients (febuxostat group, n=223; control group, n=221) with WBC measurements available at baseline and at least one of the follow-up time points of 12 or 24 months, were enrolled. Febuxostat modestly, but significantly, reduced WBC counts at 12 and 24 months compared with the baseline levels (P=0.002 and P=0.026, respectively). Notably, the WBC count in the febuxostat group at 12 and 24 months was significantly lower than that in the control group (P=0.007 and P=0.023, respectively). The changes in WBC count were associated with those of hs-CRP (P=0.038), but not with CCA-IMT (P=0.727)., Conclusions: Febuxostat therapy for 24 months modestly, but significantly, decreased WBC count in patients with asymptomatic hyperuricemia. This might potentially reflect a modest anti-inflammatory action of febuxostat in clinical settings.

Background: The risk of subsequent cardiovascular disease (CVD) is high in cancer survivors. Although metabolic syndrome is an established risk factor for CVD, its association with cancer survivors has not yet been established. This study aimed to clarify whether metabolic syndrome is associated with subsequent CVD risk in patients with cancer using a nationwide epidemiological dataset., Methods: We retrospectively analysed 53 510 patients with a history of breast, colorectal, or stomach cancer, which is reportedly a major site for developing cancer in Japan. Study participants were categorized into two groups based on the presence of metabolic syndrome, defined using the Japanese criteria (high waist circumference and ≥2 metabolic parameters including elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, or elevated fasting plasma glucose). The clinical outcomes were collected between 2005 and 2021. The primary endpoint was defined as the composite CVD outcome, including myocardial infarction, angina pectoris, stroke, and heart failure., Results: The median patient age was 54 years, and 37.5% of the patients were men. Metabolic syndrome was observed in 5558 (10.4%) patients. Over a mean follow-up period of 973 ± 791 days, 3085 composite CVD outcomes were recorded. Multivariable Cox regression analyses showed that metabolic syndrome was associated with a greater risk of developing CVD events (HR = 1.29, 95% CI = 1.15-1.45). Metabolic syndrome was also associated with an increased risk of CVD in patients with a follow-up period ≥1 year (HR = 1.33, 95% CI = 1.15-1.53). This relationship was also observed when metabolic syndrome was defined according to the International Diabetes Federation criteria (HR = 1.34, 95% CI = 1.21-1.49) and the National Cholesterol Education Program Adult Treatment Panel III criteria (HR = 1.32, 95% CI = 1.19-1.46). Subgroup analyses showed that the relationship between metabolic syndrome and incident CVD was more pronounced in the non-obese participants than in the obese participants., Conclusions: Metabolic syndrome is associated with a greater risk of developing CVD, even among cancer survivors., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Objective: To investigate the association between body mass index (BMI) changes and the risk of cardiovascular disease (CVD) in patients with cancer., Patients and Methods: This retrospective observational study used data from the JMDC Claims Database obtained between January 2005, and April 2021. We included 52,344 individuals (median [IQR] age, 53 years [46 to 60 years]; 23,584 [45.1%] men) with cancer and no prior CVD. Patients were classified into 3 groups based on the percentage change in BMI from the initial health checkup to the checkup 1 year later: -5.0% or less (BMI loss), -5.0% to 5.0% (stable BMI), and 5.0% or more (BMI gain). The primary end point was composite CVD events including heart failure, atrial fibrillation, ischemic heart disease, and stroke., Results: During a median follow-up period of 763 days (IQR, 369 to 1274 days), 3124 composite CVD events were observed. Compared with stable BMI, the hazard ratios (HRs) of BMI loss and gain for CVD events were 1.16 (95% CI, 1.00 to 1.34) and 1.10 (95% CI, 0.96 to 1.25), respectively. A U-shaped association was observed between the BMI changes and CVD events, particularly for nonatherosclerotic CVD outcomes including heart failure and atrial fibrillation. Compared with stable BMI, both BMI loss and gain increased the risk of heart failure (HR, 1.30; 95% CI, 1.08 to 1.57 and HR, 1.22; 95% CI, 1.02 to 1.47, respectively) and atrial fibrillation (HR, 1.70; 95% CI, 1.18 to 2.45 and HR, 1.55; 95% CI, 1.07 to 2.24, respectively)., Conclusion: Cancer survivors with BMI loss and gain were at greater risk of CVD. Body mass index loss is associated with a higher risk of CVD., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

We theoretically know that metabolic disorders, including overweight/obesity, insulin resistance, diabetes, dyslipidemia, and relevant tissue/organ damage, play a critical role in elevating blood pressure and developing hypertension. However, staying abreast of the ever-evolving and current research on the various metabolic disorder topics is difficult. At the same time, as hypertension in childhood and adolescence is attracting significant attention globally, it is becoming increasingly evident that metabolic disorders exert an important role in its pathogenesis. In order to effectively prevent hypertension, it is essential to appropriately approach metabolic disorders, and importantly, this approach must be practiced continuously throughout all generations. Thus, focusing on metabolic disorders is the first and essential step in effectively managing and preventing hypertension. In this Mini-Review, we introduce cutting-edge research findings on "Metabolism," published in 2023 by Hypertension Research, and discuss relevant topics and therapeutic and future perspectives., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background and Aims: Although the importance of hypertension in patients with cancer is widely recognized, little is known about the risk of developing hypertension in patients with a history of cancer., Methods and Results: This retrospective observational cohort study analysed data from the JMDC Claims Database between 2005 and 2022, including 78 162 patients with a history of cancer and 3692 654 individuals without cancer. The primary endpoint was the incidence of hypertension.During a mean follow-up period of 1208 ± 966 days, 311 197 participants developed hypertension. The incidence of hypertension was 364.6 [95% confidence interval (CI) 357.0-372.2] per 10 000 person-years among those with a history of cancer, and 247.2 (95% CI 246.3-248.1) per 10 000 person-years in those without cancer. Individuals with a history of cancer had an elevated risk of developing hypertension, according to multivariable Cox regression analyses [hazard ratio (HR) 1.17, 95% CI 1.15-1.20]. Both cancer patients requiring active antineoplastic therapy (HR 2.01, 95% CI 1.85-2.20), and those who did not require active antineoplastic therapy (HR 1.14, 95% CI 1.12-1.17) had an increased risk of hypertension. A multitude of sensitivity analyses confirmed the robustness of the relationship between cancer and incident hypertension. Patients with certain types of cancer were found to have a higher risk of developing hypertension than those without cancer, with varying risks dependent on the type of cancer., Conclusion: Our analysis of a nationwide epidemiological database revealed that individuals with a history of cancer have a higher risk of developing hypertension, and this finding applies to both cancer patients who require active antineoplastic therapy and those who do not., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The discipline of cardiology stands at a transformative juncture, primarily influenced by the surge in digital health technologies. These innovations hold the promise to redefine the realms of cardiovascular research and patient care, ushering in an era of individualized and data-driven treatments. This review delves into the heart of this evolution, introducing a comprehensive design for the future of cardiology. Emphasizing the emerging domains of "digitalomics" and "digital intervention", it explores how the integration of patient data, artificial intelligence-enabled diagnostics, and telehealth can lead to more streamlined and personalized cardiovascular health. The "digital-twin" model, a highlight of this approach, encapsulates individual patient characteristics, allowing for targeted treatments. The role of interdisciplinary collaboration in cardiovascular medicine is also underlined, emphasizing the importance of merging traditional cardiology with technological advancements. The convergence of traditional cardiology methods and digital health technologies, facilitated by a transdisciplinary approach, is set to chart a new course in cardiovascular health, emphasizing individualized care and improved clinical outcomes., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: To analyse the changes in erythropoietic and estimated fluid volume parameters after the initiation of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD)., Methods: This was a post-hoc analysis of the PROCEED trial, which evaluated the effect of 24-week ipragliflozin treatment on endothelial dysfunction in patients with T2DM and CKD. We evaluated the changes in erythropoietic and estimated fluid volume parameters from baseline to 24 weeks post-treatment in 53 patients who received ipragliflozin (ipragliflozin group) and 55 patients with T2DM and CKD without sodium-glucose co-transporter 2 inhibitors (control group), a full analysis set of the PROCEED trial., Results: The increases in haemoglobin [estimated group difference, 0.5 g/dl; 95% confidence interval (CI), 0.3-0.8; p < .001], haematocrit (estimated group difference, 2.2%; 95% CI, 1.3-3.1; p < .001) and erythropoietin (estimated log-transformed group difference, 0.1; 95% CI, 0.01-0.3; p = .036) were significantly greater in the ipragliflozin group than those in the control group. Ipragliflozin treatment was significantly associated with an increase in erythropoietin, independent of the corresponding change in haemoglobin (β = 0.253, p < .001) or haematocrit (β = 0.278, p < .001). Reductions in estimated plasma volume (estimated group difference, -7.94%; 95% CI, -11.6 to -4.26%; p < .001) and estimated extracellular volume (estimated group difference, -181.6 ml; 95% CI, -275.7 to -87.48 ml; p < .001) were significantly greater in the ipragliflozin group than those in the control group., Conclusions: Erythropoiesis was enhanced and estimated fluid volumes were reduced by ipragliflozin in patients with T2DM and CKD., Clinical Trial: PROCEED trial (registration number: jRCTs071190054)., (© 2024 John Wiley & Sons Ltd.)

Background: Hypertension is a major cause of cardiovascular disease (CVD). In patients with hypertension, unawareness of the disease often results in poor blood pressure control and increases the risk of CVD. However, data in nationwide surveys regarding the proportion of unaware individuals and the implications of such on their clinical outcomes are lacking. We aimed to clarify the association between unawareness of being prescribed antihypertensive medications among individuals taking antihypertensive medications and the subsequent risk of developing CVD.Methods and Results: This retrospective cohort study analyzed data from the JMDC Claims Database, including 313,715 individuals with hypertension treated with antihypertensive medications (median age 56 years). The primary endpoint was a composite of myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Overall, 19,607 (6.2%) individuals were unaware of being prescribed antihypertensive medications. During the follow-up period, 33,976 composite CVD endpoints were documented. Despite their youth, minimal comorbidities, and the achievement of better BP control with a reduced number of antihypertensive prescriptions, unawareness of being prescribed antihypertensive medications was associated with a greater risk of developing composite CVD. Hazard ratios of unawareness of being prescribed antihypertensive medications were 1.16 for myocardial infarction, 1.25 for angina pectoris, 1.15 for stroke, 1.36 for heart failure, and 1.28 for atrial fibrillation. The results were similar in several sensitivity analyses, including the analysis after excluding individuals with dementia., Conclusions: Among individuals taking antihypertensive medications, assessing the awareness of being prescribed antihypertensive medications may help identify those at high risk for CVD-related events.

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.

Background: Depression is a known risk factor for cardiovascular disease (CVD), but the potential sex differences in this association remain unclear., Objectives: The aim of this study was to investigate the association between depression and subsequent CVD events, and to explore potential sex differences., Methods: The authors conducted a retrospective analysis using the JMDC Claims Database between 2005 and 2022. The study population included 4,125,720 individuals aged 18 to 75 years without a history of cardiovascular disease or renal failure and missing data at baseline. Participants were followed up for a mean of 1,288 days to assess the association between depression and subsequent CVD events, such as myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation., Results: Our analysis revealed a significant association between depression and subsequent composite CVD events in both men and women, with a stronger association observed in women. The HR for the composite endpoint was 1.64 (95% CI: 1.59-1.70) in women and 1.39 (95% CI: 1.35-1.42) in men after multivariable adjustment ( P for interaction <0.001). Furthermore, the individual components of the composite endpoint were also associated with depression in both men and women, each of which was also observed to be more strongly associated in women., Conclusions: Our study provides evidence of a significant association between depression and subsequent CVD events in both men and women, with a more pronounced association observed in women. These findings highlight the importance of addressing depression and tailoring prevention and management strategies according to sex-specific factors., Competing Interests: This work was supported by grants from the Ministry of Health, Labour and Welfare, Japan (21AA2007), and the Ministry of Education, Culture, Sports, Science and Technology, Japan (20H03907, 21H03159, and 21K08123). The funding sources played no role in the current study. Drs Kaneko and Fujiu have received research funding and scholarship funds from Medtronic Japan Co, Ltd, Boston Scientific Japan Co, Ltd, Biotronik Japan, Simplex Quantum Co, Ltd, and Fukuda Denshi, Central Tokyo Co, Ltd. All other authors have reported that they have no relationships relevant to the contents of this study to disclose., (© 2024 The Authors.)

Background: There are few data on sex differences in the association between schizophrenia and the development of cardiovascular disease (CVD). We sought to clarify the relationship of schizophrenia with the risk of developing CVDs and to explore the potential modification effect of sex differences., Methods and Results: We conducted a retrospective analysis using the JMDC Claims Database between 2005 and 2022. The study population included 4 124 508 individuals aged 18 to 75 years without a history of CVD or renal replacement therapy. The primary end point is defined as a composite end point that includes myocardial infarction, angina pectoris, stroke, heart failure, atrial fibrillation, and pulmonary thromboembolism. During a mean follow-up of 1288±1001 days, we observed 182 158 composite end points. We found a significant relationship of schizophrenia with a greater risk of developing composite CVD events in both men and women, with a stronger association observed in women. The hazard ratio for the composite end point was 1.63 (95% CI, 1.52-1.74) in women and 1.42 (95% CI, 1.33-1.52) in men after multivariable adjustment ( P for interaction=0.0049). This sex-specific difference in the association between schizophrenia and incident CVD was consistent for angina pectoris, heart failure, and atrial fibrillation., Conclusions: Our analysis using a large-scale epidemiologic cohort demonstrated that the association between schizophrenia and subsequent CVD events was more pronounced in women than in men, suggesting the clinical importance of addressing schizophrenia and tailoring the CVD prevention strategy based on sex-specific factors.