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Aim: This study examined the association between the metabolic score for insulin resistance (METS-IR), a novel surrogate indicator of insulin resistance, and brachial-ankle pulse wave velocity (baPWV) in Japanese health check participants. Methods: A cross-sectional research was conducted involving individuals in a program of medical health screening at the Medical Health Check-up Center in Japan. The study assessed the connection between METS-IR and baPWV in 912 participants who joined the program between 3/1/2004 and 12/31/2012. Serum laboratory tests and lifestyle surveys were the covariates. Multivariate linear regression analysis and subgroup analyses were performed. Results: 912 participants were involved in this cross-sectional study. Adjusted for age, sex, BMI, AST, UA, HDL, eGFR, ankle-brachial index (ABI), alcohol consumption, and smoking status, multivariate linear regression analysis showed that METS-IR and baPWV showed a significant positive association (adjusted β=15.3, 95% confidence interval (CI): 6.61-23.98) with METS-IR as a continuous variable. When converting METS-IR to quartile categorical variables, higher quartile METS-IR indices had longer baPWV (Q3 vs Q1, β=86.14, 95% CI: 23.45-148.83; Q4 vs Q1, β=125.41, 95% CI: 39.99-210.84). In subgroup analysis, METS-IR was associated with baPWV in people with eGFR > 60 ml/min (adjusted β= 14.44, 95% CI: 5.61-23.26, P=0.001), none or light alcohol consumption (adjusted β=16.92, 95% CI: 6.85-27, P=0.001), non-smokers (adjusted β=15.48, 95% CI: 5.86-25.1, P=0.002), non-regular exercisers(adjusted β=17.34, 95% CI: 8.03-26.65, P<0.001), non-fatty liver (adjusted β=17.65, 95% CI: 5.92-29.39, P=0.003), and non-hypertensive (adjusted β=16.13, 95% CI:8.45-23.8, P<0.001). Conclusion: METS-IR are remarkably associated with baPWV among health check-up participants in Gifu, Japan. As a simple, easily calculated predictor of arterial stiffness, METS-IR could be considered for primary care as a monitoring tool to identify people with high risk of cardiovascular disease in order to intervene early on risk factors. Future prospective, large-sample researches are still needed to confirm this. [ABSTRACT FROM AUTHOR]

Background and Objectives: Central aortic pressure (CAP) can be measured through noninvasive methods, and CAP wave analysis can provide information about arterial stiffness. The objective of this study was to compare CAP in women with preeclampsia and normotensive postpartum women from an urban region in western Mexico. Materials and Methods: We recruited 78 women in immediate puerperium, including 39 with preeclampsia and 39 with normotension, who received delivery care in our hospital between September 2017 and January 2018. Pulse wave analysis was used to assess central hemodynamics as well as arterial stiffness with an oscillometric device. For this purpose, the measurement of the wave of the left radial artery was obtained with a wrist applanation tonometer and the ascending aortic pressure wave was generated using the accompanying software (V 1.1, Omron, Japan). Additionally, the systolic CAP, diastolic pressure, pulse pressure, heart rate, and rise rate adjusted for a heart rate of 75 bpm were determined. The radial pulse wave was calibrated using the diastolic and mean arterial pressures obtained from the left brachial artery. For all the statistical analyses, we considered p < 0.05 to be significant. Results: The results were as follows: a systolic CAP of 125.40 (SD 15.46) vs. 112.10 (SD 10.12) with p < 0.0001 for women with and without preeclampsia, respectively. Systolic CAP was significantly elevated in women with preeclampsia and could indicate an elevated risk of cardiovascular disease. Conclusion: CAP is an important parameter that can be measured in this group of patients and is significantly elevated in women with postpartum preeclampsia, even when the brachial blood pressure is normal. [ABSTRACT FROM AUTHOR]

Purpose: Specialized pressure transducers for arterial pulse waveform analysis (S-APWA) devices are dedicated kits connected to an arterial pressure catheter that monitors hemodynamic parameters, such as cardiac output, pulse pressure variation, and stroke volume variation, less invasively. While the association between the use of S-APWA devices and clinical outcomes in perioperative patients has been previously evaluated, its assessment in patients with septic shock remains inadequate. Materials and Methods: This retrospective cohort study utilized a nationwide Diagnosis Procedure Combination database in Japan. Adult patients with septic shock admitted to the intensive care unit (ICU) with arterial pressure catheter placement on the admission day from August 2012 to February 2021 were included. Hospitalizations meeting the eligibility criteria were categorized into groups based on S-APWA device usage. The primary outcome, evaluated using Cox regression analysis, was 30-day all-cause mortality in the propensity score overlap-weighted population. Secondary outcomes included in-hospital mortality, ICU duration, and overall hospital stay. Results: Among 5130 eligible hospitalizations, 643 were in the S-APWA group and 4487 were in the conventional pressure transducer group. Cox regression analysis within the propensity score overlap-weighted population showed no significant difference in 30-day mortality (adjusted hazard ratio: 0.94; 95% confidence interval: 0.9-1.38; P  = .58). Logistic regression analysis indicated no significant differences in the in-hospital mortality. While the S-APWA group had prolonged ICU stays, no significant difference in the overall hospital stay was observed according to linear regression analyses. Conclusions: Our study found no significant association between S-APWA use and 30-day mortality in patients with septic shock. These findings offer insights into optimizing monitoring systems in ICUs.

Background: The association between the triglyceride-glucose (TyG) index and arterial stiffness in individuals with normoglycaemia remains unclear. We aimed to evaluate the relationship between the TyG index and arterial stiffness in Japanese individuals with normoglycaemia, providing additional evidence for predicting early arterial stiffness., Methods: This study included 15,453 adults who participated in the NAGALA Physical Examination Project of the Murakami Memorial Hospital in Gifu, Japan, from 2004 to 2015. Data on clinical demographic characteristics and serum biomarker levels were collected. The TyG index was calculated from the logarithmic transformation of fasting triglycerides multiplied by fasting glucose, and arterial stiffness was measured using the estimated pulse wave velocity calculated based on age and mean blood pressure. The association between the TyG index and arterial stiffness was analysed using a logistic regression model., Results: The prevalence of arterial stiffness was 3.2% (500/15,453). After adjusting for all covariates, the TyG index was positively associated with arterial stiffness as a continuous variable (adjusted odds ratio (OR) = 1.86; 95% Confidence Interval = 1.45-2.39; P<0.001). Using the quartile as the cutoff point, a regression analysis was performed for arterial stiffness when the TyG index was converted into a categorical variable. After adjusting for all covariates, the OR showed an upward trend; the trend test was P<0.001. Subgroup analysis revealed a positive association between the TyG index and arterial stiffness in Japanese individuals with normoglycaemia and different characteristics., Conclusion: The TyG index in Japanese individuals with normoglycaemia is significantly correlated with arterial stiffness, and the TyG index may be a predictor of early arterial stiffness., (© 2024. The Author(s).)

Aim: This study examined the association between the metabolic score for insulin resistance (METS-IR), a novel surrogate indicator of insulin resistance, and brachial-ankle pulse wave velocity (baPWV) in Japanese health check participants., Methods: A cross-sectional research was conducted involving individuals in a program of medical health screening at the Medical Health Check-up Center in Japan. The study assessed the connection between METS-IR and baPWV in 912 participants who joined the program between 3/1/2004 and 12/31/2012. Serum laboratory tests and lifestyle surveys were the covariates. Multivariate linear regression analysis and subgroup analyses were performed., Results: 912 participants were involved in this cross-sectional study. Adjusted for age, sex, BMI, AST, UA, HDL, eGFR, ankle-brachial index (ABI), alcohol consumption, and smoking status, multivariate linear regression analysis showed that METS-IR and baPWV showed a significant positive association (adjusted β=15.3, 95% confidence interval (CI): 6.61~23.98) with METS-IR as a continuous variable. When converting METS-IR to quartile categorical variables, higher quartile METS-IR indices had longer baPWV (Q3 vs Q1, β=86.14, 95% CI: 23.45~148.83; Q4 vs Q1, β=125.41, 95% CI: 39.99~210.84). In subgroup analysis, METS-IR was associated with baPWV in people with eGFR > 60 ml/min (adjusted β= 14.44, 95% CI: 5.61~23.26, P=0.001), none or light alcohol consumption (adjusted β=16.92, 95% CI: 6.85~27, P=0.001), non-smokers (adjusted β=15.48, 95% CI: 5.86~25.1, P=0.002), non-regular exercisers(adjusted β=17.34, 95% CI: 8.03~26.65, P<0.001), non-fatty liver (adjusted β=17.65, 95% CI: 5.92~29.39, P=0.003), and non-hypertensive (adjusted β=16.13, 95% CI:8.45~23.8, P<0.001)., Conclusion: METS-IR are remarkably associated with baPWV among health check-up participants in Gifu, Japan. As a simple, easily calculated predictor of arterial stiffness, METS-IR could be considered for primary care as a monitoring tool to identify people with high risk of cardiovascular disease in order to intervene early on risk factors. Future prospective, large-sample researches are still needed to confirm this., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu.)

Introduction: Low estimated glomerular filtration rate (eGFR) is associated with an increased risk of arterial stiffness in participants with kidney damage. It is uncertain whether this association is due to eGFR itself or is mediated by the eGFR-associated increases in fasting blood glucose (FBG)., Method: The cross-sectional study included 865 Japanese participants with decreased kidney function, whose eGFR was less than 90 mL/min/1.73 m2, and recruited individuals who received medical healthcare. The mediating variable was FBG, with eGFR as the independent variable and brachial-ankle pulse wave velocity (baPWV) as the dependent variable. A mediation analysis was used to evaluate the mediating effect of FBG on the association between eGFR and arterial stiffness., Results: The mean age of the participants was 51.69 ± 9.25 years old, with 65.90% individuals being male. The mean values for FBG, eGFR, and baPWV were 5.46 ± 0.79 mmol/L, 68.83 ± 10.05 mL/min/1.73 m2, and 1,423.50 ± 247.78 cm/s, respectively. The mediation analysis revealed that eGFR had a significant direct effect on baPWV (β = -25.68 95% CI: -46.42, -7.45), and that FBG played a partial mediating role in the indirect effect of eGFR on baPWV (β = -3.54 95% CI: -11.88, -0.079). Mediation analysis showed that 12.10% of the effect of eGFR on risk of arterial stiffness was mediated through FBG., Conclusion: The study indicated that there is a mediating relationship between eGFR and FBG in people with decreased kidney function, which is associated with the risk of arterial stiffness. Therefore, the importance of FBG as a mediator should be acknowledged and taken into consideration., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Most comparisons of arterial stiffness between ethnic groups focus on pulse wave velocity. This study used the cardio-ankle vascular index (CAVI) in European compared to Japanese individuals to investigate how cardiovascular risk factors affect arterial aging across geographic regions., Methods: Four hundred and ninety-four European and 1044 Japanese individuals underwent measurements of CAVI, blood pressure and information on cardiovascular risk factors. Both datasets included individuals with 0-5 cardiovascular risk factors., Results: Average CAVI was higher in the Japanese than the European group in every age category, with significant differences up to 75 years for males and 85 for females. The correlation of CAVI with age, controlled for cardiovascular risk factors, was slightly higher in Japanese females (r = 0.594 vs. Europeans r = 0.542) but much higher in European males (r = 0.710 vs. Japanese r = 0.511). There was a significant correlation between CAVI and total cardiovascular risk factors in the Japanese (r = 0.141, P < 0.001) but not the European group. On linear regression, average CAVI was significantly dependent on age, sex, diabetes, BMI, SBP and geographic region. When divided into 'healthy' vs. 'high risk', the healthy group had a steeper correlation with age for Europeans (r = 0.644 vs. Japanese r = 0.472, Fisher's Z P < 0.001), whereas in the high-risk group, both geographic regions had similar correlations., Conclusion: Japanese patient groups had higher arterial stiffness than Europeans, as measured by CAVI, controlling for cardiovascular risk factors. Europeans had greater increases in arterial stiffness with age in healthy individuals, particularly for males. However, cardiovascular risk factors had a greater impact on the Japanese group., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

To evaluate whether continuous subcutaneous insulin infusion attenuates the progression of diabetic complications, we retrospectively extracted data from 35 individuals who had developed type 1 diabetes mellitus aged ≤20 years and whose treatment had been changed from multiple daily injections to continuous subcutaneous insulin infusion. The annual changes in estimated glomerular filtration rate, urinary albumin excretion rate, carotid intima-media thickness and brachial-ankle pulse wave velocity during each treatment period were calculated. Although mean glycated hemoglobin under the continuous subcutaneous insulin infusion treatment was lower than that under the multiple daily injection treatment, there were no significant differences in annual changes in diabetic nephropathy and atherosclerosis between the two treatment periods. This pilot study showed that, in Japanese patients with juvenile-onset type 1 diabetes mellitus, there was no significant difference in the progression of diabetic nephropathy and atherosclerosis, at least in the early stage, between the two treatments., (© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

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 1c 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. Increased brachial-ankle pulse wave velocity at the baseline was associated with a significant odds ratio (per 1 SD increase) for new onset of prehypertension/hypertension with (2.45/3.28; P <0.001) or without (2.49/2.76; P <0.001) coexisting prediabetes/diabetes, but not for new onset of prediabetes/diabetes without coexisting hypertension. Analyses using the latent growth curve model confirmed the bidirectional relationships between brachial-ankle pulse wave velocity and hypertension, but no such relationship was observed between brachial-ankle pulse wave velocity and abnormal glucose metabolism. Conclusions In middle-aged employees of a Japanese company, while bidirectional relationships were found to exist between increased arterial stiffness and hypertension, such a relationship was not found between increased arterial stiffness and diabetes. Therefore, it appears that increased arterial stiffness may be associated with the development of hypertension but not with that of diabetes.

Background: Few studies examined the relationship between triglyceride/glucose index (TyG index) and atherosclerosis in Japanese adults. Therefore, this study evaluated their relationship, as measured based on the brachial-ankle pulse wave velocity (baPWV) in Japanese adults., Methods: A total of 912 participants was selected from the NAGALA (NAFLD in Gifu Area, Longitudinal Analysis) study conducted from 2004 to 2012. The relationship between the TyG index and baPWV was estimated through a logistic model. Subgroup analyses by sex, age, body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol, estimated glomerular filtration rate (eGFR), and fatty liver was performed. The formula for TyG index was ln (½fasting triglyceride level [mg/dL] × fasting plasma glucose level [mg/dL])., Results: A linear relationship between TyG and baPWV was discovered after adjusting for underlying confounders. An increased risk of baPWV was observed after adjusting for sex, age, BMI, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, fatty liver, eGFR, and TyG as a continuous variable (adjusted odds ratio [adj OR], 1.57; 95% confidence interval [95% CI], 1.14-2.18). Compared with the TyG index in the first tertile, the probabilities of subjects in the third tertile that developed to baPWV were 1.78-fold higher (adj OR 1.78, 95% CI 1.08-2.95: P for trend 0.024). Moreover, stable associations were observed between the TyG index and baPWV in different variables through subgroup analyses., Conclusions: The highest tertile (above 8.57) of the TyG index was positively and linearly related to subclinical atherosclerosis in Japanese adults and may be valuable as a predicted marker., (© 2022. The Author(s).)

Abstract: Objective: This study examined the relationship between job stain and radial arterial wave reflection as expressed by the augmentation index (AI), a marker of cardiovascular risk, in middle-aged male workers. Methods: Radial AI was measured using automated applanation tonometry in 808 working men (mean age; 47±5 years) at a company in Kanagawa, Japan in 2007. An elevated AI represents the deterioration of arterial properties and increased cardiovascular risk. Job demand and job control (decision latitude) were evaluated by a self-administered, Brief Job Stress Questionnaire. High job strain was defined as the combination of high job demand and low job control. Results: In the entire study population, the mean±SD and the median of AI were 74±13% and 75%, respectively. High job strain was seen in 267 subjects. In a multiple logistic regression analysis with adjustment for multiple potential confounders, high job strain showed a significantly increased odds ratio (1.47, 95% CI; 1.04–2.09, P =0.029) for an elevated AI (≥75%). Conclusion: High job strain was significantly associated with an elevated radial AI. The measurement of AI may be useful when incorporated in workplace interventions to reduce the risk of cardiovascular disease, especially at sites where workers tend to perceive high job strain. [Copyright &y& Elsevier]

Telomere (TL) is a biomarker of biological aging, and its shortening is associated with major risk factors for cardiovascular diseases (CVD). This study aimed to identify whether TL is associated with arterial stiffness as reflected by brachial–ankle pulse wave velocity (baPWV). This population-based cross-sectional study involved 1065 individuals in the Iwaki area, Japan. Total TL length and TL G-tail length were measured by hybridization protection assay. The baPWV was measured on the right and left sides using a non-invasive vascular screening device. The associations between TL and baPWV were assessed by multivariate linear regression. Compared with the shortest total TL tertile, the longest total TL group showed a significant decrease in baPWV (lowest vs. highest tertile: adjusted beta: −41.24, 95% confidence interval (CI): −76.81, −5.68). The mean baPWV decreased with a longer TL (TL G-tail length: p trend < 0.001, total TL: p trend < 0.001). TL G-tail and total TL lengths were inversely associated with baPWV, implicating TL shortening in the development of CVD. This study provides evidence of the factors influencing CVD risks at a very early stage when individuals can still take necessary precautions before CVD gives rise to a symptomatic health outcome. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that periodontal disease may be an independent risk factor for the development of atherosclerosis. However, the relationship between periodontal disease and atherosclerosis has not been fully elucidated. This study aimed to assess the effects of periodontal disease on atherosclerosis. Methods: The study design was a cross-sectional study. Subjects were 291 healthy male workers in Japan. We used the Community Periodontal Index of Treatment Needs (CPITN) score, average probing depth and gingival bleeding index (rate of bleeding gums) to assess the severity of periodontal disease. We also used the Brachial-Ankle Pulse Wave Velocity (baPWV) as the index for the development of atherosclerosis. Results: The unadjusted odds ratio (OR) of atherosclerosis in relation to the CPITN score was 1.41 [95% CI: 1.16-1.73]. However, after adjustment for age, systolic blood pressure and smoking, the CPITN score had no relationship with atherosclerosis (adjusted OR: 0.91 [0.68-1.20]). Conclusion: Our results show no relationship between mild periodontal disease and atherosclerosis after appropriate adjustments. [ABSTRACT FROM AUTHOR]

Height is inversely associated with an increase in arterial stiffness after habitual resistance exercise (RE). Considering that RE is performed during exercise prescriptions, the association between height and the acute effects of RE on arterial stiffness should be clarified. We investigated the effects of height on arterial stiffness following transient RE. Thirty-nine young Japanese men were studied under parallel experimental conditions [sham control (seated rest) and RE (5 sets of 10 repetitions at 75% of one-repetition maximum)], which were randomly ordered on two separate days. The subjects were divided into tertiles of height (each group, n = 13). The β-stiffness index (index of arterial stiffness), assessed by carotid pulse pressure and distension, was measured in all subjects. A significant interaction between time, height, and RE was found for the β-stiffness index ( P = 0.01). RE significantly increased the β-stiffness index in the lower-height group ( P < 0.001), but not in the middle- and higher-height groups. Height was negatively associated with an increase in β-stiffness index following RE, even after controlling the confounders, including exercise volume and changes in heart rate and carotid pulse pressure ( P = 0.003). The mediation analysis demonstrated a mediating effect of carotid distension on the relationship between height and changes in the β-stiffness index. These results suggest that short height individuals have increased arterial stiffness following RE due to decreased mechanical distension, rather than through the widening of pulsatile pressure.

Aim: To examine whether improvement in flow-mediated endothelium-dependent dilatation (FMD) of the brachial artery and brachial-ankle pulse wave velocity (baPWV) has an additive effect on achieving optimal goals of traditional risk factors to reduce cardiovascular risk in patients with coronary artery disease (CAD)., Methods: We assessed 323 patients with CAD and impaired vascular function, defined as an impaired FMD of the brachial artery (＜5.5%) and increased baPWV (＞1,440 cm/sec). After FMD and baPWV measurements at 24 weeks of optimal medical treatment (OMT), the study patients were followed up for ＜60 months or until a composite of cardiac death, nonfatal myocardial infarction (MI), unstable angina, or ischemic stroke occurs., Results: During the median follow-up period of 35 months, cardiovascular events occurred in 72 patients. Multivariate Cox hazards analysis showed that patients with an improvement in FMD and baPWV had the lowest probability of future cardiovascular events. In addition, the improvement in FMD and baPWV had a significant incremental effect on the predictive value of the achievement of optimal goals for blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and hemoglobin A1c (HbA1c) using net reclassification improvement (NRI) and integrated discrimination improvement (IDI)., Conclusions: The improvement in FMD and baPWV had additive effects on risk reduction of the achievement of the optimal goals of traditional risk factors in patients with CAD. Thus, serial measurements of FMD and baPWV may be useful for identifying CAD patients at residual risk for adverse cardiovascular events following OMT.

Associations of arterial stiffness with glucose, insulin, and proinsulin dynamics during the oral glucose tolerance test (OGTT) remain under debate. The aim of this study was to investigate whether plasma glucose (PG), insulin, and proinsulin (Pro) contribute to arterial stiffness, measured by pulse wave velocity (PWV), in young Japanese persons. PG, immunoreactive insulin (IRI), and Pro levels were determined in 1193 young Japanese subjects (<40 years of age) with normal glucose tolerance or nondiabetic hyperglycemia before and at 30, 60, and 120 min during a 75-g OGTT. Participants were divided into two groups according to the median PWV. Background factors, PG, IRI, and Pro levels during the OGTT, and insulin sensitivity (SI) indices in each group were compared. Several multiple regression analysis models were used to evaluate factors contributing to PWV. All IRI and Pro levels before and after glucose loading and the area under the curve (AUC) values for IRI and Pro increased with higher PWV. 1/HOMA-IR and ISI-Matsuda as measures of SI decreased with higher PWV. The IRI AUC and Pro level before glucose loading (Pro0) were independently associated with PWV, in addition to male sex, heart rate, and mean blood pressure. The IRI AUC had a stronger relationship with PWV than Pro0. The IRI AUC had an independent relationship with PWV, whereas both SI indices did not. Postloading insulinemia, but not reduced SI, was independently associated with arterial stiffness in young Japanese persons., (© 2021. The Author(s).)

Background We assessed cases of incidental unruptured intracranial aneurysm (UIA) discovered on screening magnetic resonance angiography to identify hemodynamic and atherosclerotic risk factors. Methods and Results The data of 1376 healthy older subjects (age range, 31-91 years) without cerebro- or cardiovascular diseases who underwent brain magnetic resonance angiography as part of a medical checkup program at a health screening center were examined retrospectively. We looked for an increase in classical risk factors for UIAs (age, sex, hypertension, and smoking) and laboratory data related to lifestyle diseases among subjects with UIAs. Brachial-ankle pulse wave velocity, central systolic blood pressure, radial augmentation index, and carotid flow pulsatility index were also compared between those with and without UIAs. We found UIAs in 79 (5.7%) of the subjects. Mean age was 67.1±9.0 years, and 55 (70%) were women. Of the 79 aneurysms, 75 (95%) were in the anterior circulation, with a mean diameter of 3.1 mm (range, 2.0-8.0 mm). Subjects with UIAs were significantly older and had more severe hypertension. The carotid flow pulsatility index was significantly lower in subjects with UIAs and negatively and independently correlated with UIAs. Tertile analysis stratified by carotid flow pulsatility index revealed that subjects with lower indices had higher levels of low-density lipoprotein cholesterol. Conclusions The presence of UIAs correlated with lower carotid flow pulsatility index and elevated low-density lipoprotein cholesterol in the data from a population of healthy older volunteers. A reduced carotid flow pulsatility index may affect low-density lipoprotein cholesterol elevation by some molecular pathways and influence the development of cerebral aneurysms. This may guide aneurysm screening indications for institutions where magnetic resonance angiography is not routine.

Cardiovascular disease (CVD) remains the leading cause of death, but the risk factors for CVD differ between men and women. Although carotid intima-media thickness (IMT), carotid plaque, and pulse wave velocity (PWV) are useful atherosclerotic parameters, patient backgrounds have differed in previous reports. Therefore, this study aimed to investigate gender differences in associations between these three parameters and traditional risk factors in the same population. We enrolled 3888 participants (women: 743) who underwent routine health checkups. High IMT, high carotid plaque score (PS), or high brachial-ankle PWV (baPWV) were defined by the median values for each gender. We analyzed the association between each parameter and atherosclerotic risk factors, such as obesity, smoking, blood pressure (BP) elevation, impaired fasting glucose (IFG), and dyslipidemia (DL). In both sexes, BP elevation was the only common risk factor for high IMT, high PS, and high baPWV in the multivariate logistic regression analysis adjusted for age. In men, IFG and DL were common risk factors for the three parameters. Furthermore, obesity was an additional risk factor for high IMT and smoking was an additional risk factor for high IMT and high PS. In contrast, in women, obesity, DL, or IFG was an additional risk factor for high IMT, high PS, or high baPWV, respectively. The risk factors for IMT, PS, and baPWV differ in in men and women. The management for atherosclerotic risk factors on early stage should be considered in terms of gender-specific risk factors.

Aim: Fatty liver and the liver fibrosis are known risk factors for cardiovascular disease (CVD). The severity of fatty liver can be assessed by determining the fatty liver index (FLI), and the severity of liver fibrosis can be assessed by determining the fibrosis-4 (FIB-4) score. We examined the differences in the associations of these two liver scoring systems with the pathophysiological abnormalities associated with the risk of development of CVD., Methods: The FLI and FIB-4 score were calculated in 2,437 Japanese men without any history of CVD. The serum NT-pro-BNP levels and brachial-ankle pulse wave velocity (baPWV) were also measured at the start of the study and the end of three years' follow-up., Results: The FLI was significantly correlated with the baPWV (p＜0.01) and the FIB-4 score was significantly correlated with the serum NT-pro-BNP level (p＜0.01). Furthermore, the delta change of the FLI was significantly correlated with the delta change of the baPWV during the study period (p=0.01), and the delta change of the FIB-4 score was significantly correlated with the delta change of the serum NT-pro-BNP level during the study period (p＜0.01)., Conclusions: While the FIB-4 score may serve as a marker of the risk of development of heart failure, the FLI may be a marker of arterial stiffness in Japanese men without any history of CVD.

Past reports indicated that total-body irradiation at low to moderate doses could be responsible for cardiovascular disease risks, but the mechanism remains unclear. The purpose of this study was to investigate the association between radiation exposure and atherosclerosis, an underlying pathology of cardiovascular diseases, in the Japanese atomic bomb survivors. We performed a cross-sectional study measuring 14 clinical-physiological atherosclerosis indicators during clinical exams from 2010 to 2014 in 3274 participants of the Adult Health Study cohort. Multivariable analyses were performed by using a structural equation model with latent factors representing underlying atherosclerotic pathologies: (1) arterial stiffness, (2) calcification, and (3) plaque　as measured with indicators chosen a priori on the basis of clinical-physiological knowledge. Radiation was linearly associated with calcification (standardized coefficient per Gy 0.15, 95 % confidence interval: CI [0.070, 0.23]) and plaque (0.11, 95 % CI [0.029, 0.20]), small associations that were comparable to about 2 years of aging per Gy of radiation exposure, but not with arterial stiffness (0.036, 95 % CI [- 0.025, 0.095]). The model fitted better and had narrower confidence intervals than separate ordinary regression models explaining individual indicators independently. The associations were less evident when the dose range was restricted to a maximum of 2 or 1 Gy. By combining individual clinical-physiological indicators that are correlated because of common, underlying atherosclerotic pathologies, we found a small, but significant association of radiation with atherosclerosis.

Background: Previous studies have suggested that high mean glucose levels and glycemic abnormalities such as glucose fluctuation and hypoglycemia accelerate the progression of atherosclerosis in patients with type 2 diabetes. Although continuous glucose monitoring (CGM) that could evaluate such glycemic abnormalities has been rapidly adopted, the associations between CGM-derived metrics and arterial stiffness are not entirely clear., Methods: This exploratory cross-sectional study used baseline data from an ongoing prospective, multicenter, observational study with 5 years of follow-up. Study participants included 445 outpatients with type 2 diabetes and no history of apparent cardiovascular disease who underwent CGM and brachial-ankle pulse wave velocity (baPWV) measurement at baseline. Associations between CGM-derived metrics and baPWV were analyzed using multivariate regression models., Results: In a linear regression model, all CGM-derived metrics were significantly associated with baPWV, but HbA1c was not. Some CGM-derived metrics related to intra-day glucose variability, hyperglycemia, and hypoglycemia remained significantly associated with baPWV after adjusting for possible atherosclerotic risk factors, including HbA1c. Based on baPWV ≥ 1800 cm/s as indicative of high arterial stiffness, multivariate logistic regression found that some CGM-derived metrics related to intra-day glucose variability and hyperglycemia are significantly associated with high arterial stiffness even after adjusting for possible atherosclerotic risk factors, including HbA1c., Conclusions: Multiple CGM-derived metrics are significantly associated with baPWV and high arterial stiffness in patients with type 2 diabetes who have no history of apparent cardiovascular disease. These metrics might be useful for identifying patients at high risk of developing cardiovascular disease.

Background: Tofogliflozin, an SGLT2 inhibitor, is associated with favorable metabolic effects, including improved glycemic control and serum lipid profile and decreased body weight, visceral adipose tissue, and blood pressure (BP). This study evaluated the effects of tofogliflozin on the brachial-ankle pulse wave velocity (baPWV) in patients with type 2 diabetes (T2DM) without a history of apparent cardiovascular disease., Methods: The using tofogliflozin for possible better intervention against atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. As one of the prespecified secondary outcomes, changes in baPWV over 104 weeks were evaluated in 154 individuals (80 in the tofogliflozin group and 74 in the conventional treatment group) who completed baPWV measurement at baseline., Results: In a mixed-effects model, the progression in the right, left, and mean baPWV over 104 weeks was significantly attenuated with tofogliflozin compared to that with conventional treatment (- 109.3 [- 184.3, - 34.3] (mean change [95% CI] cm/s, p = 0.005; - 98.3 [- 172.6, - 24.1] cm/s, p = 0.010; - 104.7 [- 177.0, - 32.4] cm/s, p = 0.005, respectively). Similar findings were obtained even after adjusting the mixed-effects models for traditional cardiovascular risk factors, including body mass index (BMI), glycated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, systolic blood pressure (SBP), hypertension, smoking, and/or administration of drugs, including hypoglycemic agents, antihypertensive agents, statins, and anti-platelets, at baseline. The findings of the analysis of covariance (ANCOVA) models, which included the treatment group, baseline baPWV, and traditional cardiovascular risk factors, resembled those generated by the mixed-effects models., Conclusions: Tofogliflozin significantly inhibited the increased baPWV in patients with T2DM without a history of apparent cardiovascular disease, suggesting that tofogliflozin suppressed the progression of arterial stiffness. Trial Registration UMIN000017607. Registered 18 May 2015. ( https://www.umin.ac.jp/icdr/index.html ).

The present prospective observational study was conducted to examine the differences in longitudinal associations of the conventional risk factors for cardiovascular disease (CVD) with arterial stiffness and with abnormal pressure wave reflection using repeated measurement data. In 4016 healthy middle-aged (43 ± 9 years) Japanese men without CVD at baseline, the conventional risk factors for CVD, brachial-ankle pulse wave velocity (brachial-ankle PWV) and radial augmentation index (rAI) were measured annually over a 9-year period. Mixed-model linear regression analysis demonstrated a significant independent positive longitudinal association of the mean blood pressure with both the brachial-ankle PWV (estimate = 5.51, standard error = 0.30, P < 0.01) and the rAI (estimate = 0.19, standard error = 0.02, P < 0.01). On the other hand, the serum levels of glycohemoglobin, low-density lipoprotein cholesterol and triglycerides showed longitudinal associations only with the brachial-ankle PWV and not the rAI. In addition, while the radial AI was found to show a significant longitudinal association with the brachial-ankle PWV, the inverse association was not significant. In conclusion, the conventional risk factors for CVD showed heterogeneous longitudinal associations with arterial stiffness and/or abnormal pressure wave reflection. Elevated blood pressure showed independent longitudinal associations with both arterial stiffness (macrovascular damage) and abnormal pressure wave reflection, suggesting that BP is also longitudinally associated, at least in part, with microvascular damage. On the other hand, abnormal glucose metabolism and dyslipidemia showed independent longitudinal associations with only arterial stiffness (macrovascular damage).

Background and Aims: We examined the cross-sectional and longitudinal association of arterial stiffness and pressure wave reflection with the ankle-brachial pressure index (ABI) in middle-aged Japanese subjects free of peripheral artery disease (PAD)., Methods: ABI, brachial-ankle pulse wave velocity (baPWV) and radial augmentation index (rAI) were measured annually during the 9-year observation period in 3066 men (42 ± 9 years old) with ABI ≥1.00 at baseline of the study period, and not taking any antihypertensive medication., Results: In the cross-sectional assessments, mediation analysis demonstrated that baPWV showed both direct and indirect (via the rAI) associations with ABI, and rAI showed both direct and indirect (via the heart-arm difference of systolic blood pressure) associations with the ankle-arm difference of systolic blood pressure, both at study baseline and end of study period. Mixed model linear regression analysis of the repeated-measurement data obtained over the 9-year observation period demonstrated that annual increase of baPWV (estimate = 0.73 × 10 -4 , p < 0.01) and rAI (estimate = 0.33 × 10 -3 , <0.01) was associated with ABI. When baPWV and rAI were entered into the same model, only baPWV showed a significant longitudinal association with ABI., Conclusion: In middle-aged Japanese men free of PAD, arterial stiffness may contribute to ABI directly and via pressure wave reflection. Pressure wave reflection may contribute to ABI directly and, at least in part, via attenuation of peripheral pulse pressure amplification., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Previous researches demonstrate that mean arterial pressure (MAP) is associated with major cardiovascular events, but there are few research on the correlation between MAP and brachial-ankle pulse wave velocity (BaPWV). Thus, the present study is designated to examine the association between MAP and BaPWV. Our study is a cross-sectional study in Japanese. They participated in a medical check-up program which included BaPWV and standardized questionnaires. The main measurements include systolic blood pressure, diastolic blood pressure, BaPWV, ankle-brachial index (ABI), fatty liver diagnosed by ultrasonography, etc. It needs to be emphasized that Fukuda et al. finished the study and their data are used for secondary analysis. MAP is positively related with BaPWV [effect size = 10.4; 95% confidence interval (CI), 9.2-11.6] after adjusting age, sex, BMI, smoking status, alcohol consumption, exercise, glutamyltranspeptidase, alanine aminotransferase, aspartate transaminase, total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein cholesterol (HDL), fatty liver, fasting-blood glucose, uric acid, estimated glomerular filtration rate, and ABI. The nonlinear association is identified between MAP and BaPWV whose inflection point is 94 mmHg. The effect size and 95% CI on the bilateral sides of the inflection point are 8.0 (4.4-11.6) and 14.8 (12.5-17.1), respectively. Subgroup analysis indicates that MAP has a more significantly positive association with BaPWV in ex-smokers, old people (age ≥60), and participants with lower HDL (<40 mg/dL). Consequently, it is practicable for us to roughly predict BaPWV with simple MAP measurement instead of the BaPWV examination.

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

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

Aims: To investigate the longitudinal association of microalbuminuria with overactive bladder (OAB)., Methods: This longitudinal study investigated 561 participants of the Iwaki Health Promotion Project in both 2015 and 2019 in Japan. Microalbuminuria and OAB symptoms were assessed using the urine albuminuria creatinine ratio (ACR) and the overactive bladder symptom score (OABSS), respectively. Urine ACR was defined as high if ≥9.3 mg/gCr. Differences in OABSS between 2015 and 2019 were evaluated as ∆OABSS. Participants were divided into two groups according to ΔOABSS: high (ΔOABSS > 1) and control (≤1). We used baseline data acquired in 2015, such as urine ACR, the Pittsburgh Sleep Quality Index (PSQI), and arterial stiffness expressed by brachial-ankle pulse wave velocity (baPWV). Predictive factors of a ΔOABSS > 1 were assessed by multivariable logistic regression analysis., Results: This study included 332 women and 229 men. Of those, 86 (34 males and 52 females) were classified into the ΔOABSS > 1 group. There were significant group differences in age, renal function, and hemoglobin A1c. Participants in the ΔOABSS > 1 had a higher prevalence of PSQI > 5, baPWV ≥ 1400 seconds/cm, and urine ACR ≥ 9.3 mg/gCr (49% vs 20%, P = .001) than those in the control group. Multivariable analysis revealed that PSQI > 5 (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.15-4.60; P = .002) and urine ACR ≥ 9.3 mg/gCr (OR, 1.93; 95% CI, 1.15-3.23; P = .013) were independent risk factors for ΔOABSS > 1., Conclusions: Microalbuminuria may be an independent risk indicator for OAB symptom exacerbation., (© 2020 Wiley Periodicals LLC.)

Background: Orthostatic hypotension, blood pressure (BP) variability, and arterial stiffness are three markers of cardiovascular risk beyond the average BP. However, the relationships between these three parameters are not well known., Aim: To examine the relationships between orthostatic hypotension, BP variability, and arterial stiffness., Methods and Results: In the Three-City study, a sample of 1151 elderly participants (mean age = 80 ± 3 years) was screened for orthostatic hypotension, undertook home BP and pulse wave velocity (PWV) measurements. We performed logistic regression analyses to look at the associations between orthostatic hypotension and both day-to-day (D-to-D) BP variability quartiles and PWV quartiles. Orthostatic hypotension was detected in 210 participants who were more likely to be hypertensive, exhibit higher BP variability and have increased arterial stiffness. In the multivariate logistic regression analysis, the frequency of orthostatic hypotension increased by 20% with every quartile of D-to-D SBP variability and by 20% with every quartile of PWV. PWV and D-to-D BP variability were not associated. In stratified analysis, the use of beta-blocker changes these relationships: orthostatic hypotension was not associated to PWV anymore but its association with D-to-D SBP variability was apparently stronger., Conclusion: In this large sample of elderly individuals, orthostatic hypotension was independently associated with both BP variability and PWV. BP variability being more indicative of a baroreflex dysfunction and PWV being a marker of vascular ageing, these two components would participate to the orthostatic hypotension mechanisms.

Increased blood pressure (BP) variability, an index of hemodynamic stress, leads to cardiac overload and worse cardiovascular prognosis. The association between day-by-day home BP variability and NT-proBNP (N-terminal pro-B-type natriuretic peptide) as an index of cardiac overload may be amplified by increased arterial stiffness as assessed by brachial-ankle pulse wave velocity (baPWV). J-HOP (Japan Morning Surge-Home Blood Pressure) Study participants who were selected from a practitioner-based population with at least one cardiovascular risk factor underwent home BP monitoring, and their BP levels and SD, coefficient of variation, and average real variability as indexes of systolic BP variability were assessed. We analyzed 2115 individuals without prevalent heart failure and divided them into lower (<1800 cm/s, n=1464) and higher (≥1800 cm/s, n=651) baPWV groups. The higher baPWV group had significantly higher SD SBP , CV SBP , ARV SBP values, and NT-proBNP levels than the lower baPWV group (all P <0.001). In the higher baPWV group, a multiple linear regression analysis revealed that the SD SBP was associated with the NT-proBNP level after adjustment for traditional cardiovascular risk factors including the average home systolic BP (coefficient per 1 SD increase, 0.049 [95% CI, 0.018-0.081]; P =0.002). Similar trends were found for CV SBP ( P =0.003) and ARV SBP ( P =0.004). However, these associations were not found in the lower baPWV group. There was an interaction between all indexes of systolic BP variability and the NT-proBNP level according to lower or higher baPWV group (all P <0.05). Arterial stiffness amplified the association between home BP variability and cardiac overload.

Brachial-ankle pulse wave velocity (baPWV) has been used as a simple and convenient method of evaluating arterial stiffness and is considered useful for screening subclinical vascular damage in primary care settings and in large populations. The aim of this study was to determine the reference values of baPWV in adolescents based on age and sex to evaluate and classify vascular abnormalities in this age population. Noninvasive baPWV measurements using an oscillometric device were carried out in 5936 participants aged 12-18 years who had no history of syndromic obesity, hypertension, dyslipidemia, diabetes mellitus, or renal disease. Of these, we extracted data from 4524 healthy adolescents free from atherosclerotic risk factors and constructed sex-specific reference percentiles normalized to age using the LMS method. The baPWV increased with age and was significantly higher in males than in females. Multivariate regression analysis demonstrated that age, body mass index, and blood pressure were the major determinants of baPWV for both males and females. Among a sample of 3825 adolescents, including individuals with risk factors, the prevalence of central obesity, raised blood pressure, raised triglycerides, reduced high-density lipoprotein cholesterol, and impaired fasting glycemia significantly increased along with the standardized baPWV z-score level. In addition, there was a graded nature regarding the association between the baPWV z-score and the clustering number of the metabolic syndrome components. These results suggest that the proposed reference values of baPWV could help classify vascular abnormalities of adolescents caused by the presence of risk factors and thereby contribute to determining individuals with cardiovascular risk in this age population.

Isolated systolic hypertension (ISH), defined as systolic blood pressure (SBP) ≥140 mmHg and diastolic BP (DBP) <90 mmHg, is a common type of hypertension among young men. This study aimed to investigate the clinical characteristics, central blood pressure, and arterial stiffness of young and middle-aged Japanese individuals with ISH. A total of 432 male participants, aged 18-49 years, were classified into six subgroups: optimal BP (SBP <120 mmHg and DBP <80 mmHg), high-normal BP (SBP 120-129 mmHg and DBP <80 mmHg), high-BP (SBP 130-139 mmHg and/or DBP 80-89 mmHg), ISH (SBP ≥140 mmHg and DBP <90 mmHg), isolated diastolic hypertension (IDH) (SBP <140 mmHg and DBP ≥90 mmHg), and systolic and diastolic hypertension (SDH) (SBP ≥140 mmHg and DBP ≥90 mmHg). Participants with ISH had a greater body mass index (BMI) and waist circumference than the optimal BP participants but were more likely to be physically active than the IDH and SDH participants. The central SBP of the ISH subgroup was higher than that of the optimal/high-normal/high-BP subgroups and lower than that of the SDH subgroup. The carotid-femoral pulse wave velocity (cfPWV) of the ISH subgroup was higher than that of the optimal and high-normal BP subgroups and lower than that of the SDH subgroup after adjusting for age, heart rate, BMI, and physical activity. These differences disappeared after further adjustment for central mean arterial pressure. In conclusion, the central SBP of Japanese men with ISH was greater than that of Japanese men with optimal/high-normal/high-BP, but the progression of arterial stiffness was unclear.

Background: Recently, coefficients in the equation of cardio-ankle vascular index (CAVI) used in VaSera ® device were disclosed. This study aimed to simulate the influence of adjusting the coefficients in the equation of CAVI and also aimed to validate the equation., Methods: The CAVI displayed by VaSera (CAVIvs) and the CAVI estimated (CAVIes) with fixing the coefficients of the middle range of the heart-ankle stiffness parameter β (haβ) in the equation were compared. Moreover, the heart-ankle pulse wave velocity (haPWV) which corresponds to the low cutoff haβ of 7.348 was estimated in various blood pressure patterns to validate the formula., Results: The CAVIvs was clearly lower than CAVIes in the low and the high range of CAVIvs. Moreover, it was virtually impossible to obtain the low cutoff haβ of 7.348 by using typical values of haPWV., Conclusion: The CAVIvs in the high-range of VaSera underestimates the original property of stiffness parameter β. Moreover, there will be also a missing information in the equations introduced in the corresponding article, especially in the calculation formula of CAVIvs from haβ. Therefore, in order to make the best use of the nature of the stiffness parameter β to be used in VaSera, fixing the coefficients or termination of its use should be considered., Competing Interests: Dai Ato is a former employee of Fukuda Colin (formerly Omron Colin, Nippon Colin) Co., Ltd., a distributor of Vascular Profiler® (form PWV/ABI, BP-203RPE series). Dai Ato is an independent researcher and wrote this article as an academic activity based on the guaranteed right of freedom in academia for the Japanese (Article 23) and on the supreme law provided in Article 98 of the Constitution of Japan. Dai Ato reports no other conflicts of interest in this work., (© 2019 Ato.)

Background: The precise mechanisms underlying the high prevalence of pulmonary hypertension (PH) with increased pulmonary vascular resistance (PVR) in heart failure with preserved ejection fraction (HFpEF) remain largely unknown. Measurements of brachial-ankle pulse wave velocity (baPWV) have been shown to be useful for risk assessment in HF patients. Thus, this study sought to define the association of PVR with baPWV and clinical outcomes in HFpEF., Methods and Results: Patients with HFpEF (n = 198) had measurements of baPWV and PVR by right heart catheterization, and were prospectively followed-up for <96 months or until the occurrence of a composite of all-cause death, hospitalization with worsening HF, and nonfatal acute coronary syndrome., Results: Multivariate logistic analysis showed that baPWV was independently associated with PH with increased PVR (P < .001). During the follow-up period, 46 clinical events occurred. Multivariate Cox proportional hazards analysis showed that PH with increased PVR was a significant predictor of adverse outcomes after adjustment for conventional risk factors (HR 1.96, 95% CI 1.03-3.76, P = .04)., Conclusions: PH with increased PVR was associated with increased baPWV and adverse clinical outcomes in HFpEF. Thus, increased arterial stiffness may contribute to increased risk predictability of PVR for patients with HFpEF., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: This study investigated the association between circadian hemodynamic characteristics and asymptomatic hypertensive organ damage., Methods: Circadian hemodynamics, including 24-hour brachial and aortic systolic blood pressure (SBP), pulse wave velocity (PWV), augmentation index (AIx@75), cardiac index, and total vascular resistance (TVR), were evaluated using an oscillometric device, Mobil-O-Graph, in 284 essential hypertensive patients (67.8 ± 16.0 years, 54% female). Hypertensive target organ damage (TOD), namely carotid wall thickening, left ventricular hypertrophy, and albuminuria, was assessed in all patients., Results: Office SBP and 24-hour brachial and aortic SBP all increased with increasing number of organs involved (all P < 0.01 for trend). After multivariate logistic regression analysis, 24-hour brachial SBP (odds ratio [OR] = 1.04 for 1 mm Hg increase, P < 0.001) as well as aortic SBP (OR = 1.03 for 1 mm Hg increase, P < 0.05) maintained significance. Percent decrease during nighttime in brachial SBP, PWV, and TVR, but not cardiac index, showed a significant graded relationship with the number of organs involved. In a multivariate stepwise regression model, the nighttime values of brachial SBP, PWV, and TVR emerged as independent predictors of the presence of TOD., Conclusion: In essential hypertension, 24-hour aortic SBP could be a marker of subclinical TOD, and further, the blunted nocturnal BP reduction in TOD patients might be mediated by disturbed circadian hemodynamic variations in aortic SBP, vascular resistance, and arterial stiffness., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Although pulse wave velocity (PWV) is recognized to be a risk predictor for various cardiovascular diseases, the association of brachial-ankle PWV (baPWV) with cardiovascular outcomes in heart failure (HF) with reduced ejection fraction (HFrEF) patients remains uncertain., Methods: We measured ankle-brachial pressure index (ABI) and baPWV values at stable condition after optimal therapy for HF in 201 consecutive HFrEF patients admitted to Kumamoto University Hospital from 2007 to 2015 who were enrolled and followed until the occurrence of cardiovascular events. We defined peripheral artery disease (PAD) as ABI value ≤ 0.9., Results: Kaplan-Meier analysis revealed that HFrEF patients with peripheral artery disease PAD had a significant higher risk of total cardiovascular and HF-related events than those without PAD (P = 0.03 and P = 0.01, respectively). Next, we divided HFrEF patients without PAD into 3 groups according to baPWV values. In the Kaplan-Meier analysis, total cardiovascular and HF-related events in the highest baPWV group (1,800 cm/second ≤ baPWV) had a significantly higher frequency than those in the mid-level baPWV group (1,400 cm/second ≤ baPWV < 1,800 cm/second) (P = 0.007 and P = 0.004, respectively). The hazard ratio between HFrEF patients in the mid-level baPWV group and those with other baPWV groups was compared after adjustment for other cofounders. The probabilities of HF-related events were significantly higher in the lowest and highest baPWV group., Conclusion: Identifying complications of PAD and measuring baPWV values in HFrEF patients were useful for predicting their prognosis.Trial Registration: UMIN000034358., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Male sexual function is regulated by vascular function and impaired vascular function is closely related with erectile dysfunction (ED). Vascular functions are positively influenced by physical fitness (i.e., aerobic capacity, muscle strength, and flexibility). The detailed associations between physical fitness and male sexual function remain poorly understood. The present study aimed to clarify the influence of physical fitness on male sexual function. In 177 adult men, peak oxygen consumption (VO 2 peak ), handgrip strength (HGS), and sit and reach were measured as indices of physical fitness. Arterial stiffness and erectile function were assessed by carotid-femoral pulse wave velocity (cfPWV) and the International Index of Erectile Function 5 (IIEF5) questionnaire, respectively. IIEF5 score was significantly correlated with VO 2 peak ( r s = 0.52), HGS ( r s = 0.37), and cfPWV ( r s = -0.44); and multivariate linear regression analyses showed that VO 2 peak , HGS, and cfPWV were significantly associated with IIEF5 score after considering confounders. The receiver operator characteristic curve analysis suggested that the cutoff values for predicting ED were 29.0 ml/min/kg for VO 2 peak and 39.3 kg for HGS. The IIEF5 score was the highest in the subjects with the values of both VO 2 peak and HGS were higher than their respective cutoff values, while the IIEF5 score was the lowest in the subjects with the values of both VO 2 peak and HGS were lower than their respective cutoff values. These results suggest that the maintenance of high aerobic capacity and muscular strength may offset deterioration of male sexual function.

The correlations between organ damage and hourly ambulatory blood pressure (BP) have not been established. The patients were 1464 participants of the Japan Morning Surge-Home Blood Pressure (J-HOP) study participants who underwent ambulatory BP monitoring. The hourly systolic BP (SBP) at x o'clock was defined as the average of SBP values measured at times x - 30 minutes, x, and x + 30 minutes. The mean age was 64.8 ± 11.6 years. The percentage of male participants was 47.8%. The left ventricular mass index (LVMI) was significantly associated with SBP at 6 o'clock (r = 0.166, P < 0.001). The carotid intima-media thickness was significantly associated with SBP at 5 o'clock (r = 0.196, P < 0.001). After adjustment for age, sex, smoking, hyperlipidemia, diabetes mellitus, antihypertensive drug use, clinic SBP, and 24-hour ambulatory SBP, the correlations of the LVMI and hourly SBP at 6 o'clock remained significant (beta coefficient = 0.125, P < 0.01). In conclusion, morning ambulatory systolic BP especially at 5 and 6 o'clock was independently associated with organ damage., (©2019 Wiley Periodicals, Inc.)

Background: Evidence regarding the relationship between estimated glomerular filtration rate (eGFR) and arterial stiffness is limited, and the data analysis is not sufficient to clarify the true relationship between the two. We aimed to investigate the relationship between eGFR and brachial-ankle pulse wave velocity (baPWV) in Japanese., Methods: The present study was a cross-sectional study. Nine hundred twelve Japanese men and women, aging 24-84 years old, received a health medical check-up program including the results from baPWV inspection and various standardized questionnaires in a health examination center in Japan. The main outcome measures included eGFR, baPWV, fatty liver and postmenopausal status. Abdominal ultrasonography was used to diagnose fatty liver. Postmenopausal state was defined as beginning 1 year after the cessation of menses., Results: The average age of the 912 selected participants was 51.5 ± 9.6 years old, and about 57.6% of them were male. The participants' eGFR distribution was median 69.29 (min 39, max 122.28). The results of multivariate linear regression showed eGFR was not independently associated with baPWV after adjusting potential confounders (β = - 1.11, 95%CI -2.25 to 0.03), this is inconsistent with the result of eGFR (quartile) as a categorical variable (p for trend was 0.038). A non-linear relationship was detected between eGFR and baPWV, whose point was 77.05. The effect sizes and the confidence intervals of the left and right sides of inflection point were - 2.80 (- 4.41 to - 1.19) and 1.84 (- 0.50, 4.17), respectively. Subgroup analysis showed, the change in the elderly population is more pronounced (P for interaction = 0.018; - 2.83 with ≤60 year vs - 6.12 with > 60 year). The same trend was also seen in hypertensive people (P for interaction = 0.018; - 4.55 with hypertension vs - 0.82 with non-hypertension)., Conclusion: The relationship between eGFR and baPWV is non-linear. eGFR was negatively related to baPWV when eGFR is less than 77.05.

Arterial pulse waveform analysis (APWA) is used for cardiac output monitoring. However, data on the frequency of and patient characteristics for specialized pressure transducer for APWA (S-APWA) use are lacking. We retrospectively identified 175,201 patients aged 18 years or older, who underwent non-cardiac surgery under general anesthesia with an arterial catheter from January 1, 2014, to December 31, 2016. We extracted data on patient demographics, comorbidities, surgical and anesthesia characteristics, and hospital characteristics. Among the full study cohort, 24,605 (14.0%) patients were monitored using S-APWA. Further, the use of S-APWA was higher in patients undergoing high-risk surgery than in those undergoing low-risk surgery [high vs low: adjusted odds ratio (aOR) 1.95; 95% confidence interval (CI) 1.76-2.15, moderate vs low: aOR 1.11; 95% CI 1.01-1.22] and those with more comorbidities than in those with less comorbidities (high vs low: aOR 1.49; 95% CI 1.42-1.56, moderate vs low: aOR 1.25; 95% CI 1.20-1.31). S-APWA use was significantly associated with both surgery risk and patients' comorbidities. In conclusion, our study may provide a benchmark for future studies related to the appropriate use of S-APWA.

Objective: Only a few longitudinal studies have assessed the relationship between bone mineral density (BMD) and arteriosclerosis. This study aimed to determine whether low BMD at baseline is associated with the development of increased arterial stiffness, as evaluated by brachial-ankle pulse wave velocity (baPWV), in Japanese women., Methods: A baPWV value of ≥1800 cm/s was adopted as the criterion for increased arterial stiffness, i.e., the outcome of the study. Of the 725 women aged ≥50 years who completed the baseline survey, we excluded the 166 who already met this criterion. Of the remaining women, we analyzed data from the 446 who completed at least one of the follow-up surveys conducted 5 or 10 years after baseline. BMD at the lumbar spine (LS) and total hip (TH) was measured by dual-energy X-ray absorptiometry in the baseline survey. baPWV was measured both at baseline and at follow-up. Multivariate logistic regression was used to evaluate the independent effect of BMD at baseline on developing the outcome during 10-year follow-up., Results: We identified 166 women who newly developed increased arterial stiffness. The odds ratios (OR) for a 1 SD decrease in BMD at LS and TH for developing the outcome were 1.20 (95% confidence interval [CI]: 0.91-1.50), and 1.44 (95% CI: 1.14-1.81), respectively, after adjusting for age and systolic blood pressure. After additionally adjusting for baPWV at baseline, the OR for a 1 SD decrease in BMD at TH remained significant (1.33, 95% CI: 1.02-1.72)., Conclusion: Low BMD at TH was significantly associated with the development of increased arterial stiffness during a 10-year follow-up of Japanese women., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Both small and large artery disease might precede the development of hypertension. However, no prospective trial has yet determined the role of small and large artery disease on the rate of new-onset hypertension in a normotensive general population. This study investigated associations between both arterial stiffness and small artery retinopathy and the development of hypertension in adults from Japan. Normotensive individuals who underwent a baseline health checkup from 2005 to 2015 and at least 1 annual follow-up were eligible. The cardio-ankle vascular index (CAVI) was measured, and retinal fundus photography was performed at baseline. Follow-up visits included measurement of clinic blood pressure. The primary end point was new-onset hypertension (blood pressure ≥140/90 mm Hg or initiation of antihypertensive medication with self-reported hypertension). The analysis included 34 649 subjects (mean age, 44.2 years; 46.4% male). Mean follow-up duration was 3.18±2.50 years. The cumulative incidence of new-onset hypertension during the 10-year follow-up period was 40% of patients overall, with rates increasing in parallel with baseline CAVI (quartile [Q]1, 23%; Q2, 33%; Q3, 42%; Q4, 58%; P<0.001), and as the severity of retinopathy increased ( P<0.001). CAVI showed good discriminative ability for detecting new-onset hypertension. In multivariate analysis, both CAVI and small artery retinopathy were independent predictors of hypertension development. There was no interaction between CAVI and small artery retinopathy with respect to incident hypertension. In conclusion, we showed that both large and small artery disease predict future hypertension independently of each other and confounding risk factors in a general normotensive population.

Background and Objective: Seasonal variation of blood pressure (BP) is well known, and a relationship between increases in BP and the incidence of cardiovascular accidents (CVAs) in the winter has been reported. Parameters of arterial stiffness may exhibit seasonal variation; however, available data are currently limited. Novel arterial stiffness indexes, namely the arterial velocity pulse index (AVI) and arterial pressure-volume index (API), can be determined through usual maneuver for BP measurement during the regular examination in the outpatient clinic.The present study assessed the seasonal variation of AVI and API in 59 hypertensive patients undergoing stable treatment and regularly visiting our outpatient clinic over a period of 30 months. Methods: BP, pulse rate (PR), AVI, and API were measured using the AVE-1500 (Pasesa) in the sitting position. Six time frames of assessment were established. All measurements (average: 17.9 measurements per person) were sorted using these six time frames, and their averages were used for analysis. Results: Significant seasonal variations in PR ( P  < 0.001) and AVI ( P  < 0.001), along with weak variation in systolic BP (SBP) ( P  = 0.047) and marginal variation in API ( P  = 0.055), were confirmed by repeated analysis of variance. SBP, API, and PR were decreased, whereas AVI was increased in the summer. Coefficient variations were SBP 5.1%, PR 4.9%, AVI 12.6%, and API 10.6%. Conclusion: AVI was associated with reflected wave like as augmentation index. Thus, a high AVI may suggest increased central wave reflection. Although the significance of seasonal variation of AVI remains unknown, AVI may influence seasonal variations in the incidence of CVA.

Arterial stiffness increases with advancing age and is an important risk factor for cardiovascular disease. As the number of research studies investigating arterial stiffness has increased dramatically over the recent years, their scope has broadened from physiological investigations to clinical domains focused on risk predictions. A number of key research studies were conducted in Japan in the formative years; however, some of these studies are unknown to most and largely forgotten. In this mini-review, some of these key formative research studies conducted in Japan by Japanese investigators are re-introduced and highlighted to provide appreciation for their pioneering work conducted in the land of the rising sun.

This article is a comprehensive review of recent studies of the authors on the indication of mental health from biological information contained in pulse waves. A series of studies discovered that the largest Lyapunov exponent (LLE) of the attractor, which is constructed for the time series data from pulse waves, can provide as an effective indicator of mental health. A low level of LLE indicates insufficiency of external adaptability, which is characteristic of dementia and depression sufferers. On the contrary, a continuous high level of LLE indicates excessive external adaptability, and people in this condition tend to resort to violence. With this discovery, real-time display of the LLE, combined with other physiological indexes such as the autonomic nerve balance (ANB), sample entropy, and vascular age, as a reference, can enable people to conduct self-check of mental status. To this end, software development was performed in order to enable users to conduct pulse wave measurement anywhere at any time and display the analytical results in real time during the measurement.

Background: The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known., Methods and Results: We measured flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver-operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06-0.74; P =0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09-0.79; P =0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01-3.44; P =0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23-3.90; P =0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed., Conclusions: In patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification., Clinical Trial Registration: URL: www.umin.ac.jp. Unique identifier: UMIN000012950., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Favorable effects of sauna bathing on cardiovascular disease have been demonstrated. Hot water bathing is an alternative, and could also have similar effects. Information pertaining to hot water bathing frequency and water temperature was obtained from 873 subjects. Carotid mean and max intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were measured as indices of atherosclerosis. Central haemodynamics were evaluated using radial pulse waveform analyses. Plasma levels of B-type natriuretic peptide (BNP) were measured as an index for cardiac loading. The mean duration of a single hot bath was 12.4 ± 9.9 min. Subject bathing in hot water ≥5 times per week had significantly lower baPWV, central pulse pressure (PP), and BNP after correcting for possible confounding parameters. Stepwise regression analyses revealed that hot water temperature was negatively associated with baPWV, while bathing frequency was negatively related to central PP and BNP. A longitudinal follow-up in 164 subjects showed that hot water bathing ≥5 times per week was associated with significantly lower increase in BNP over time, while the temperature of the water tended to be related to lower increases in carotid max IMT and baPWV. Hot water bathing showed a favorable effect on atherosclerotic and central haemodynamic parameters.

Background: We conducted analyses of repeated-measures data to examine whether pressure wave reflection acts additively or synergistically with arterial stiffness in the pathogenesis of hypertension., Methods and Results: In 3172 middle-aged (42±9 years) healthy Japanese men without hypertension at the study baseline, systolic and diastolic blood pressures, brachial-ankle pulse wave velocity, and radial augmentation index were measured annually during a 9-year study period. Of these, 474 participants (15%) developed hypertension by the end of the study period. Binary logistic regression analysis demonstrated significant individual odds ratios for both baseline brachial-ankle pulse wave velocity and radial augmentation index for the development of hypertension. The rate of onset of hypertension during the study period was highest in the participant group with high values for both brachial-ankle pulse wave velocity and radial augmentation index at study baseline (262 of 965 participants: 27%). The generalized estimating equation analysis revealed that both radial augmentation index (estimate=0.06, SE=0.03, P =0.05) and brachial-ankle pulse wave velocity (estimate=0.07×10 -1 , SE=0.02×10 -1 , P <0.01) showed significant longitudinal association with new onset of hypertension, with no significant interaction., Conclusions: In Japanese men, abnormal wave reflection and increased arterial stiffness may be additively associated with the risk of new onset of hypertension. Abnormal wave reflection and elevated central blood pressure may be longitudinally associated with increase in arterial stiffness, and this longitudinal association may be a mechanism underlying the additive effect of these 2 variables on the risk of new onset of hypertension., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Aims: Improvement in sleep quality is considered to be a viable target for prevention and treatment of cardiovascular diseases. To gain insight into its underlying mechanisms, we evaluated the significance of objectively measured sleep quality in patients with regard to progression of arterial stiffness over a 3-year follow-up period., Methods: This prospective cohort study included 306 serial patients registered in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA) study. In addition to classical cardiovascular risk factors (body mass index, current smoking, past history of cardiovascular disease, dyslipidemia, diabetes mellitus), the participants were examined for ambulatory blood pressure (BP), apnea-hypopnea index (AHI), standard deviation of the NN (RR) interval (SDNN) for heart rate variability (HRV), and objective sleep quality using actigraphy findings. Brachial-ankle pulse wave velocity (baPWV) was measured at both baseline and follow-up (36.6 ± 6.8 months) as a parameter of arterial stiffness., Results: Increases in PWV (%) were greater (p = 0.03) in the low sleep quality (LSQ) group (5.75 ± 1.15%) as compared to the normal sleep quality group (2.69 ± 0.85%). Patients with the greatest increase (≥20%) from baseline exhibited a significantly (p < 0.05) larger percentage of LSQ (75% vs. 49.6%) as compared to those without PWV progression (<0%), with the association still significant (odds ratio 3.62, 95% confidence interval 1.04-12.55, p = 0.04) even after adjustment for other clinical risk factors. For all subjects, univariate logistic regression analyses showed that diabetes and LSQ were significantly associated with the greatest increase of PWV. Comparisons of characteristics among specific subgroups showed more prominent associations of LSQ with the greatest increase of PWV in patients with greater age, dyslipidemia, and higher AHI., Conclusions: LSQ was associated with progression of arterial stiffness over a 3-year period, independent of cardiovascular risk factors such as BP, AHI, and HRV., (Copyright © 2018 Elsevier B.V. All rights reserved.)