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Context: There have been insufficient data on the threshold of body mass index (BMI) for developing diabetes mellitus (DM) and the relationship between change in BMI and the subsequent risk of DM. Objective: We sought to clarify the association of BMI and its change with incident DM. Methods: We conducted a retrospective observational cohort study using the JMDC Claims Database between 2005 and 2021. We included 3 400 303 individuals without a prior history of DM or usage of glucose-lowering medications. The median age was 44 years, and 57.5% were men. We categorized the study participants into 4 groups: underweight (BMI < 18.5 kg/m²), normal weight (BMI 18.5-24.9 kg/m²), overweight (BMI 25.0-29.9 kg/m²), and obese (BMI ≥ 30 kg/m²). According to the change in BMI from the initial health check-up to the health check-up 1 year after that, we divided the study participants into 3 groups: ≤-5.0%, -5.0% to +5.0%, and ≥+5.0%. Results: The risk of developing DM increased steeply after BMI exceeded approximately 20 to 21 kg/m². Compared with participants with stable BMI (-5.0% to +5.0%), the relative risk for DM among those whose BMI had increased by 5.0% or more was 1.33 (95% CI 1.31-1.36). In contrast, the relative risk for DM among those whose BMI decreased by 5.0% or more was 0.82 (95% CI 0.80-0.84). Moreover, people classified as normal weight, overweight, and obese reduced the risk of developing DM when they reduced their BMI, whereas the risk of developing DM for people classified as underweight increased when they reduced their BMI. Conclusion: Our findings offer novel insights into improving an optimal bodyweight management strategy to prevent the development of DM. [ABSTRACT FROM AUTHOR]

Aims There have been scarce data on the relationship of normal-weight central obesity (NWCO) with the subsequent risk for heart failure (HF) and atrial fibrillation (AF). Using a nationwide health check-up and administrative claims database, we sought to clarify whether NWCO would be associated with the incidence of HF and AF. Methods and results Medical records of 1 697 903 participants without prior history of cardiovascular disease (CVD) and normal-weight (body mass index of 18.5-23.0 kg/m2) were extracted from the JMDC Claims Database, which is a health check-up and claims database. We defined NWCO as normal-weight and CO (waist circumference=90 cm for men or= 80 cm for women). The median age was 44.0 (37.0-52.0) years and 872 578 (51.4%) participants were men. Overall, 154 778 individuals (9.1%) had CO. The mean follow-up period was 3.3+2.6 years. Participants with NWCO were older and more likely to be women than those without. HF and AF occurred in 26 936 (1.6%) and 6554 (0.4%) participants, respectively. People having NWCO were associated with a greater risk for HF [hazard ratio (HR): 1.072, 95% confidence interval (CI) 1.026-1.119] and AF (HR: 1.202, 95% CI: 1.083-1.333) compared with those having normalweight without CO. Conclusion Our analysis of a nationwide health check-up and administrative claims database including 1.7 million participants without prevalent CVD history demonstrated the potential impact of NWCO on the risk for HF and AF, suggesting the importance of abdominal obesity in the developing HF and AF even in normal-weight individuals. [ABSTRACT FROM AUTHOR]

We present the autopsy procedure and findings of severe coronavirus disease 2019 (COVID-19) pneumonia in an 85-year-old man. The patient required intubation immediately after admission for severe COVID-19 pneumonia. He had severe hypoxia that did not improve despite treatment with remdesivir, corticosteroids, and appropriate mechanical ventilation. On day 13, the patient developed sudden hypercapnia. His renal dysfunction subsequently worsened and became associated with hyperkalemia, and he passed away on day 15. An autopsy was performed to clarify the cause of the hypercapnic hypoxia. None of the medical personnel involved in the autopsy developed symptoms of COVID-19. Histologic examination showed various stages of diffuse alveolar damage throughout the lungs, with intra-alveolar hemorrhage in the upper zones. Microscopic examination of the kidneys revealed acute tubular necrosis. There was no significant systemic thrombosis. The autopsy findings were consistent with those typical of COVID-19. [ABSTRACT FROM AUTHOR]

Objective: Patients with coronary artery disease (CAD) and atrial fibrillation (AF) can be treated with multiple antithrombotic therapies including antiplatelet and anticoagulant therapies; however, this has the potential to increase bleeding risk. Here, we aimed to evaluate the efficacy and safety of P2Y12 inhibitors and aspirin in patients also receiving anticoagulant therapy.Methods: We evaluated patients from the Atrial Fibrillation and Ischaemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial who received rivaroxaban plus an antiplatelet agent; the choice of antiplatelet agent was left to the physician's discretion. The primary efficacy and safety end points, consistent with those of the AFIRE trial, were compared between P2Y12 inhibitors and aspirin groups. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularisation or death from any cause. The primary safety end point was major bleeding according to the International Society on Thrombosis and Haemostasis criteria.Results: A total of 1075 patients were included (P2Y12 inhibitor group, n=297; aspirin group, n=778). Approximately 60% of patients were administered proton pump inhibitors (PPIs) and there was no significant difference in PPI use in the groups. There were no significant differences in the primary end points between the groups (efficacy: HR 1.31; 95% CI 0.88 to 1.94; p=0.178; safety: HR 0.79; 95% CI 0.43 to 1.47; p=0.456).Conclusions: There were no significant differences in cardiovascular and bleeding events in patients with AF and stable CAD taking rivaroxaban with P2Y12 inhibitors or aspirin in the chronic phase.Trial Registration Number: UMIN000016612; NCT02642419. [ABSTRACT FROM AUTHOR]

Aims Intestinal oedema is one of the manifestations associated with right-sided heart failure (HF), which is known to be associated with poorer patient outcomes. We attempted to reveal the association between intestinal oedema and diuretic resistance in hospitalized patients with acute HF. Methods and results Among 213 hospitalized patients with acute HF, abdominal ultrasonography was performed under clinically stable conditions after initial HF treatments. The association among abdominal ultrasonographic parameters, maintenance doses of loop diuretics, and responsiveness to initial loop diuretic treatment was evaluated. Higher mean colon wall thickness (CWT) independently correlated with a higher dose of loop diuretics at enrolment (adjusted β = 0.198, P = 0.0004). Increased mean CWT also correlated with poor response to oral loop diuretics as an initial treatment, whereas it did not correlate with the response to intravenous loop diuretics. Discrimination of non-responders to initial oral loop diuretics resulted in a sensitivity of 0.772 and a specificity of 0.733 using a mean CWT cut-off value of ≥3 mm. Conclusions In hospitalized patients with acute HF, a strong correlation was identified among the severity of intestinal oedema, required quantities as maintenance loop diuretic doses, and poor responsiveness to oral loop diuretics at admission. [ABSTRACT FROM AUTHOR]

Introduction The present study is the largest registry study ever conducted in Japan exploring the prevalence of familial hypercholesterolaemia (FH) among patients with acute coronary syndrome (ACS). Our study aims to (1) evaluate the status of lipid management and the subsequent risk of major cardiovascular events following hospitalisation of Japanese patients with ACS in real-world clinical practice; (2) determine the proportion of Japanese patients with ACS who achieve the lipid management goal and have a reduction of event risks with strict lipid management (low-density lipoprotein-cholesterol <1.81 mmol/L); (3) determine the prevalence of FH and (4) investigate the clinical significance of proprotein convertase subtilisin kexin 9 (PCSK9) level. Methods and analysis We will conduct a multicentre, prospective, observational study of approximately 2000 Japanese patients with ACS with/without FH hospitalised between April 2015 and August 2016. The primary end point is the incidence of major adverse cardiovascular events (MACEs) after initial hospitalisation. The secondary end points are (1) MACE developed from visit 1 to visit 2 (day 30); (2) MACE developed from visit 2 (day 30) to visit 5 (day 730); (3) treatment rate by lipid-lowering therapies (any statin or intensive, PCSK9 inhibitor, fibrates and ezetimibe); (4) incidence of events by the addition of the following outcomes to the primary end point: coronary revascularisation due to myocardial ischaemia, revascularisation other than coronary artery, inpatient treatment for occurrence or exacerbation of heart failure, transient ischaemic attack, acute arterial occlusion, central retinal artery occlusion and other adverse events prolonging or requiring hospitalisation and (5) proportion of subjects achieving target lipid levels. Ethics and dissemination The study protocol was submitted to the ethical review committee of each participating centre for approval. Participation in the study is voluntary and anonymous. The study findings will be disseminated in international peer-reviewed journals and presented at relevant conferences. [ABSTRACT FROM AUTHOR]

Background: Xanthine oxidase inhibitors are anti-hyperuricemic drugs that decrease serum uric acid levels by inhibiting its synthesis. Xanthine oxidase is also recognized as a pivotal enzyme in the production of oxidative stress. Excess oxidative stress induces endothelial dysfunction and inflammatory reactions in vascular systems, leading to atherosclerosis. Many experimental studies have suggested that xanthine oxidase inhibitors have anti-atherosclerotic effects by decreasing in vitro and in vivo oxidative stress. However, there is only limited evidence on the clinical implications of xanthine oxidase inhibitors on atherosclerotic cardiovascular disease in patients with hyperuricemia. We designed the PRIZE study to evaluate the effects of febuxostat on a surrogate marker of cardiovascular disease risk, ultrasonography-based intima-media thickness of the carotid artery in patients with hyperuricemia. Methods: The study is a multicenter, prospective, randomized, open-label and blinded-endpoint evaluation (PROBE) design. A total of 500 patients with asymptomatic hyperuricemia (uric acid >7.0 mg/dL) and carotid intima-media thickness ≥1.1 mm will be randomized centrally to receive either febuxostat (10-60 mg/day) or non-pharmacological treatment. Randomization is carried out using the dynamic allocation method stratified according to age (<65, ≥65 year), gender, presence or absence of diabetes mellitus, serum uric acid (<8.0, ≥8.0 mg/dL), and carotid intimamedia thickness (<1.3, ≥1.3 mm). In addition to administering the study drug, we will also direct lifestyle modification in all participants, including advice on control of body weight, sleep, exercise and healthy diet. Carotid intima-media thickness will be evaluated using ultrasonography performed by skilled technicians at a central laboratory. Follow-up will be continued for 24 months. The primary endpoint is percentage change in mean intima-media thickness of the common carotid artery 24 months after baseline, measured by carotid ultrasound imaging. Conclusions: PRIZE will be the first study to provide important data on the effects of febuxostat on atherosclerosis in patients with asymptomatic hyperuricemia. [ABSTRACT FROM AUTHOR]

Erythropoietin (EPO), originally identified for its critical hormonal role in regulating production and survival of erythrocytes, is a member of the type 1 cytokine superfamily. Recent studies have shown that EPO has cytoprotective effects in a wide variety of tissues, including the heart, by preventing apoptosis. However, EPO also has undesirable effects, such as thrombogenesis. In the present study, we investigated whether a helix B-surface peptide (HBSP), a nonerythropoietic, tissue-protective peptide mimicking the 3D structure of erythropoietin, protects cardiomyocytes from apoptosis in vitro and in vivo. In cultured neonatal rat cardiomyocytes, HBSP clearly inhibited apoptosis (≈80%) induced by TNF-α, which was comparable with the effect of EPO, and activated critical signaling pathways of cell survival, including Akt, ERK1/2, and STAT3. Among these pathways, Akt was shown to play an essential role in HBSP-induced prevention of apoptosis, as assessed by using a small interfering RNA approach. In the dilated cardiomyopathic hamster (J2N-k), whose cardiac tissues diffusely expressed TNF-a, HBSP also inhibited apoptosis (≈70%) and activated Akt in cardiomyocytes. Furthermore, the levels of serum creatine kinase activity and of cardiac expression of atrial natriuretic peptide, a marker of chronic heart failure, were down-regulated in animals treated with HBSP. These data demonstrate that HBSP protects cardiomyocytes from apoptosis and leads to a favorable outcome in failing hearts through an Akt-dependent pathway. Because HBSP does not have the undesirable effects of EPO, it could be a promising alternative for EPO to treat cardiovascular diseases, such as myocardial infarction and heart failure. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the relation between gender and plaque characteristics assessed by virtual histology intravascular ultrasound (VH-IVUS) in patients with stable angina pectoris. Preinterventional VH-IVUS image was available for analysis in 88 men and 60 women patients. Women had significantly smaller vessel volume (12.7 ± 3.9 versus 14.5 ± 4.2mm3/mm, P = .01) and smaller plaque volume (8.4 ± 3.5 versus 9.7 ± 3.5 mm3/mm, P = .04). However, these differences were no longer significant when corrected for body surface area (BSA). In VH-IVUS analysis, women had significantly higher dense calcium when corrected for BSA in the culprit lesion (volume: 0.32 ± 0.26 versus 0.44 ± 0.40 mm3/mm/BSA, P = .03; proportion: 8.2 ± 6.1 versus 11.2 ± 7.6%, P = .009). VH-IVUS analysis of plaque components in elderly patients with stable angina showed that women had higher calcium contents compared with men. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the relationship between the occurrence of the angiographic no-reflow phenomenon in patients with acute myocardial infarction (AMI) and the preintervention plaque composition as assessed by virtual histology intravascular ultrasound (VH-IVUS). Background: The angiographic no-reflow phenomenon is an adverse prognostic factor in patients with AMI. Method: We enrolled consecutive 50 patients with ST-elevation AMI was treated by primary stent implantation. All culprit lesions were imaged by VH-IVUS before stent implantation. The angiographic no-reflow phenomenon was defined as a decrease in final TIMI flow grade compared with TIMI flow grade before stent implantation. Results: Eight of 50 patients developed angiographic no-reflow after stent implantation. Gray-scale intravascular ultrasound (IVUS) showed significantly larger external elastic membrane volume and plaque burden in the no-reflow group. VH-IVUS showed a trend toward larger percentage of fibro-fatty plaque volume in the no-reflow group than in the reflow group (23.1 ± 3.5 vs. 17.0 ± 1.1%, P = 0.05). The presence of “ marble”-like image, mainly consisting of fibro-fatty and fibrous plaque (plaque volume of fibro-fatty + fibrous >80% and containing fibro-fatty plaque volume >10%) was associated with angiographic no-reflow (P = 0.02). Corrected TIMI frame counts of the cases with “marble”-like image were significantly larger than the cases without it (46.8 ± 5.6 vs. 27.4 ± 2.3, P = 0.01). Conclusion: The culprit lesions with large plaque burden, or with “marble”-like image by VH-IVUS, are associated with the angiographic no-reflow phenomenon in patients with AMI. [ABSTRACT FROM AUTHOR]