The impact of obstructive sleep apnea and heart rate on arterial stiffness: results from the Tokyo Sleep Heart Study.

We examined whether obstructive sleep apnea (OSA) and elevated heart rates (HR) independently increase the arterial stiffness and also the interaction between the two factors in increasing the arterial stiffness in a large Sleep Cohort. A total of 1611 subjects who underwent polysomnography and brachial-ankle pulse wave velocity (baPWV) measurement were included in the analysis. Apnea-hypopnea index (AHI) and heart rate were each categorized into three groups (non-mild: 0/h ≤ AHI < 15/h; moderate: 15/h ≤ AHI < 30/h; severe: ≥30/h; Low: HR < 70 bpm; Medium: 70 ≤ HR < 80 bpm; High: ≥80 bpm), followed by group comparisons.

A Simple Prognostic Index Based on Heart Rate, Age, and Systolic Blood Pressure for the Risk Stratification of Heart Failure With Preserved Ejection Fraction.

Aim: A rapid and effective risk stratification method is highly important for the emergency care of patients with acute heart failure with preserved ejection fraction (HFpEF). Previous studies (including our own), have suggested that heart rate, age, and systolic blood pressure contribute to the pathophysiology of HFpEF. This study aimed to examine the predictive utility of the thrombolysis in myocardial infarction risk index (TRI)-consisting of heart rate, age, and systolic blood pressure-for determining the in-hospital mortality in patients with acute HFpEF.

Circadian variation in patients with acute heart failure with preserved ejection fraction.

Background: The circadian system influences the pathophysiology of many cardiovascular diseases; however, circadian variations in patients with heart failure with preserved ejection fraction (HFpEF) are unknown. Thus, this study aimed to compare the clinical characteristics and risk factors for in-hospital mortality between patients with daytime- versus nighttime-onset HFpEF.

Methods: This multicenter retrospective study included 3875 consecutive patients with acute HFpEF.

Specific phenotypes of heart failure with preserved/reduced ejection fraction according to Body Mass Index.

Background: The relationship between Body Mass Index (BMI) and acute heart failure (HF) remains ill-defined. This study aimed to compare the influence of BMI on in-hospital mortality between patients with acute HF with preserved ejection fraction (HFpEF) and those with acute HF with reduced ejection fraction (HFrEF) and to examine the specific phenotypes of HFpEF/HFrEF according to BMI.

Methods: This multicenter retrospective study included 5313 and 6332 consecutive patients with acute HFpEF and HFrEF, respectively.

Hospital Variability in the Use of Vasoactive Agents in Patients Hospitalized for Acute Decompensated Heart Failure for Clinical Phenotypes.

Background: The absence of practice standards in vasoactive agent usage for acute decompensated heart failure has resulted in significant treatment variability across hospitals, potentially affecting patient outcomes. This study aimed to assess temporal trends and institutional differences in vasodilator and inotrope/vasopressor utilization among patients with acute decompensated heart failure, considering their clinical phenotypes.

Methods: Data were extracted from a government-funded multicenter registry covering the Tokyo metropolitan area, comprising consecutive patients hospitalized in intensive/cardiovascular care units with a primary diagnosis of acute decompensated heart failure between January 2013 and December 2021.

Effect of low-dose administration of carperitide for acute heart failure: the LASCAR-AHF trial.

Aims: The effects of low-dose carperitide on long-term clinical outcomes of patients with acute heart failure (AHF) have not yet been fully elucidated. This study aimed to evaluate the effects of low-dose intravenous carperitide on the long-term clinical outcomes of patients with AHF.

Methods And Results: In this multicentre, open-label, randomized controlled trial, 247 patients with AHF received low-dose carperitide intravenously with standard treatment or matching standard treatment for 72 h from November 2014 to March 2021 across nine sites in Japan.

Intermittent hypoxia by obstructive sleep apnea is significantly associated with electro-anatomical remodeling of the left atrium preceding structural remodeling in patients with atrial fibrillation.

Background: Obstructive sleep apnea (OSA) is one of the risk factors for atrial fibrillation (AF). However, the mechanism underlying the atrial structural and electro-anatomical remodeling by OSA has not yet been clearly elucidated.

Methods: This study was conducted in 83 patients who had undergone catheter ablation for AF (49 with OSA and 34 Controls without OSA).

The spin-Heisenberg antiferromagnet on the orthogonal-dimer lattice.

The spin-Heisenberg antiferromagnet on the orthogonal-dimer lattice is studied. In most of the investigations of the antiferromagnet on this lattice beginning with the study by Shastry and Sutherland, theS=1/2case has intensively been treated. In the present study, the cases of = 1 and 3/2 are particularly treated by the numerical-diagonalization method based on the Lanczos algorithm applied to finite-size clusters.

Structure-Activity Relationship Studies of SARS-CoV-2 Main Protease Inhibitors Containing 4-Fluorobenzothiazole-2-carbonyl Moieties.

The main protease (M) of SARS-CoV-2 is an attractive target for the development of drugs to treat COVID-19. Here, we report the design, synthesis, and structure-activity relationship (SAR) studies of highly potent SARS-CoV-2 M inhibitors including TKB245 ()/TKB248 (). Since we have previously developed M inhibitors () and (), several hybrid molecules of these previous compounds combined with nirmatrelvir () were designed and synthesized.

Central Systolic Blood Pressure as a Risk Factor for Accelerated Progression of Arterial Stiffness.

Aims: In the arterial tree, a pressure gradient of the systolic blood pressure (SBP) is observed from the center to the periphery, with the pressure being higher in the periphery because of pressure wave reflection. However, this gradient is attenuated, with elevation of the central SBP (cSBP), in cases with abnormal pressure wave reflection in the arterial tree. It remains unclear if increase of the cSBP might be an independent risk factor for accelerated progression of arterial stiffness.

Lifelong Heterogeneous Contribution of Cardiovascular Risk Factors to Slow and Fast Progression of Arterial Stiffness.

Background: Although some cardiovascular risk factors (CVRFs) are known to be associated with increased arterial stiffness, increased arterial stiffness does not mediate the cardiovascular risk associated with all CVRFs. Here, based on long-term repeated-measurement data, we examined the association of the lifelong status of each CVRF with the rate of progression of arterial stiffness.

Methods: We utilized the data from annual health checkups with the brachial-ankle pulse wave velocity measurements over a 16-year period in middle-aged Japanese occupational cohort.

Potent and biostable inhibitors of the main protease of SARS-CoV-2.

Potent and biostable inhibitors of the main protease (M) of SARS-CoV-2 were designed and synthesized based on an active hit compound 5h (). Our strategy was based not only on the introduction of fluorine atoms into the inhibitor molecule for an increase of binding affinity for the pocket of M and cell membrane permeability but also on the replacement of the digestible amide bond by a surrogate structure to increase the biostability of the compounds. Compound is highly potent and blocks SARS-CoV-2 infection without a viral breakthrough.

Association of the severity of vascular damage with discordance between the fractional flow reserve and non-hyperemic pressure ratios.

Background: While there is a discordance between fractional flow reserve (FFR) and non-hyperemic pressure ratios (NHPRs) in some cases, the mechanisms underlying these discordances have not yet been fully clarified. We examined whether vascular damage as assessed by measurement of the brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, or ankle brachial pressure index (ABI), a marker of atherosclerotic arterial stenosis, might be associated with their discordances.

Methods: FFR and NHPRs were measured in 283 consecutive patients (69 ± 10 years old).

Bidirectional Longitudinal Relationships Between Arterial Stiffness and Hypertension Are Independent of Those Between Arterial Stiffness and Diabetes: A Large-Scale Prospective Observational Study in Employees of a Japanese Company.

Background Hypertension and diabetes frequently coexist; however, it has not yet been clarified if the bidirectional longitudinal relationships between arterial stiffness and hypertension are independent of those between arterial stiffness and diabetes. Methods and Results In this 16-year prospective observational study, 3960 middle-aged employees of a Japanese company without hypertension/diabetes at the study baseline underwent annual repeated measurements of blood pressure, serum glycosylated hemoglobin A levels, and brachial-ankle pulse wave velocity. By the end of the study period, 664, 779, 154, and 406 subjects developed hypertension, prehypertension, diabetes, and prediabetes, respectively.

Longitudinal Associations between Alcohol Intake and Arterial Stiffness, Pressure Wave Reflection, and Inflammation.

Aims: This prospective observational study, which utilized repeated annual measurements performed over a 9-year period, applied mixed model analyses to examine age-related differences in longitudinal associations between alcohol intake and arterial stiffness, pressure wave reflection, and inflammation.

Methods: In 4016 middle-aged (43±9 years) healthy Japanese male employees, alcohol intake, brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), and serum C-reactive protein (CRP) levels were measured annually during a 9-year study period.

Results: The estimated marginal mean baPWV (non-drinkers=1306 cm/s, mild-moderate drinkers=1311 cm/s, and heavy drinkers=1337 cm/s, P＜0.

Longitudinal Association of Arterial Stiffness and Pressure Wave Reflection with Decline of the Cardiac Systolic Performance in Healthy Men.

Aims: This prospective observational study aimed to examine the individual longitudinal associations of the increases in the arterial stiffness and pressure wave reflection with the decline in the cardiac systolic performance during the study period in healthy middle-aged Japanese men.

Methods: In 4016 middle-aged Japanese healthy men (43±9 years), the brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), and pre-ejection period/ejection time (pre-ejection period (PEP)/ET) were measured annually during a 9-year study period.

Results: The baPWV, rAI, and PEP/ET showed steady annual increases during the study period.

Deep convolutional neural network-based algorithm for muscle biopsy diagnosis.

Histopathologic evaluation of muscle biopsy samples is essential for classifying and diagnosing muscle diseases. However, the numbers of experienced specialists and pathologists are limited. Although new technologies such as artificial intelligence are expected to improve medical reach, their use with rare diseases, such as muscle diseases, is challenging because of the limited availability of training datasets.

Moderate to severe obstructive sleep apnea is independently associated with inter-arm systolic blood pressure difference: Tokyo Sleep Heart Study.

Objective: Obstructive sleep apnea (OSA) is recognized as an independent risk factor for cardiovascular disease. On the other hand, inter-arm systolic blood pressure difference (IAD), inter-ankle systolic blood pressure difference (IAND), and ankle-brachial index (ABI) are all known predictors of cardiovascular events. The aim of the present study was to investigate the association between OSA and four-limb blood pressure differences.

Heart rate modulates the relationship of augmented systolic blood pressure with the blood natriuretic peptide levels.

Aims: Augmented central systolic blood pressure (cSBP), which is known to affect the cardiac afterload, is an independent risk factor for cardiovascular disease. While an inverse relationship is known to exist between the heart rate (HR) and the cSBP, it has not yet been clarified if the HR also modulates the association between the cSBP and the cardiac afterload. The present study was conducted to clarify whether the association of the cSBP with the serum levels of the N-terminal fragment B-type natriuretic peptide (NT-proBNP) differs between subjects with high and low HRs, using data obtained from the same subjects on two occasions (2009 and 2012) so as to confirm their consistency.