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Nowadays, the mHealth market is flooded with smartphone applications (apps) lacking validation for blood pressure (BP)-lowering effects and BP measurement accuracy. This systematic review for Guidelines for BP control using digital technologies of the Japanese Society of Hypertension aimed to assess the validation studies of apps. We searched eligible studies in Ovid MEDLINE, Cochrane Library, and Ichushi, focusing on randomized controlled trials and observational studies comparing the effects of smartphone app-based interventions with non-digital healthcare. Random effects models of meta-analysis were employed to estimate the pooled effects of mean BP change and 95% confidence intervals (CIs). Out of 7385 studies screened, 76 studies with 46,459 participants were included. The interventions were significantly associated with a reduction in office systolic and diastolic BP at six months (systolic BP, -2.76 mmHg, 95% CI: -3.94 to -1.58; diastolic BP, -1.23 mmHg, -1.80 to -0.67). Normotensives saw a significant reduction in office systolic BP at three-month (-4.44 mmHg, -6.96 to -1.92), diminishing afterward (six-month, 0.86 mmHg, -2.81 to 4.52; twelve-month, 0.86 mmHg, -2.81 to 4.52). Conversely, hypertensive participants experienced a significant reduction in office systolic BP at both three- and six-month (three-month, -7.71 mmHg, -10.63 to -4.79; six-month, -1.88 mmHg, -3.41 to -0.35), albeit with limited evidence thereafter. A larger BP reduction was observed among participants using apps with wireless transmission of BP measurements (P = 0.047 for interaction), while there was no clear difference in BP reduction according to the presence of other functions. Smartphone app-based interventions may hold the potential to improve BP levels., Competing Interests: Compliance with ethical standards Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Objective While an association between a reduced kidney function and hyperuricemia has been reported, its association with hypouricemia is not well understood. The present study therefore investigated this association. Methods Using a large Japanese health examination dataset, we performed a multivariable logistic regression analysis to assess the association between serum uric acid (SUA) levels and a reduced kidney function. The covariates included the age, body mass index, alcohol intake, and the presence of hypertension, dyslipidemia, or diabetes. Patients This study included 227,672 patients (104,854 men; 46.1%), and the analyses were performed separately for men and women. The patients were classified into 5 groups: hypouricemia (SUA ≤2.0 mg/dL) (1st) and four other (2nd-5th) groups with SUA levels of ≤2.0, 2.1-5.1, 5.2-5.9, 6.0-6.8, ≥6.9 mg/dL in men and ≤2.0, 2.1-3.7, 3.8-4.4, 4.5-5.1, ≥5.2 mg/dL in women, respectively. Results The characteristics of the study population were as follows: men, age 55.9±14.9 years old, SUA 5.9±1.3 mg/dL, estimated glomerular filtration rate (eGFR) 80.0±17.2 mL/min/1.73 m 2 , and a reduced kidney function (eGFR <60.0 mL/min/1.73 m 2 ) 9.4%; women, age 57.3±15.0 years old, SUA 4.5±1.1 mg/dL, eGFR 81.2±18.0 mL/min/1.73 m 2 , and a reduced kidney function 9.4%. Compared with the 2nd group, the other 4 groups groups had a significantly higher prevalence of a reduced kidney function [odds ratio (OR), 2.58; 95% confidence interval (CI), 1.64-4.06 in men; OR, 1.66; 95% CI, 1.16-2.39 in women]. Conclusion The prevalence of a reduced kidney function was high in both men and women in the hypouricemia and high-SUA groups. SUA levels and the prevalence of a reduced kidney function showed a J-shaped association.

The association between uric acid (UA) and hyperuricemia with 5-year hypertension incidence using different blood pressure (BP) diagnostic references in men and women without cardiometabolic diseases is unknown. We used the checkup data from Kagoshima Kouseiren Hospital. All participants with hypertension or on BP medication, diabetes, dyslipidemia, obesity, estimated glomerular filtration rate<60 ml/min/1.73m 2 , metabolic syndrome, history of gout, and UA-lowering medication were excluded. UA was categorized into sex-specific quartiles and hyperuricemia was defined as UA > 7 mg/dl in men and UA > 6 mg/dl in women. We performed multivariate logistic regression to assess the effects of UA on hypertension development. The 5-year hypertension incidence was defined as subsets of BP ≥ 140/90 mmHg in cohort 1 and BP ≥ 130/80 mmHg in cohort 2. The study enrolled 21,443 participants (39.8%, men) in cohort 1 and 15,245 participants (36.5%, men) in cohort 2. The incidence of hypertension in cohorts 1 and 2 over 5 years was 16.3% and 29.7% in men and 10.9% and 21.4% in women, respectively. When comparing the fourth to the first UA quartile, there was an association with hypertension in men in cohort 1, with odds ratio (OR): 1.36 (95% confidence interval [CI], 1.13-1.63, p < 0.01) and cohort 2, OR: 1.31 (95%CI, 1.09-1.57, p < 0.01), respectively, but not in women. Additionally, an association between hyperuricemia and hypertension was observed in men only in cohort 1, with OR: 1.23 (95%CI, 1.07-1.42, p = 0.02), and in women in cohort 2, OR: 1.57 (95%CI, 1.14-2.16, p < 0.01). The effect of UA on the development of hypertension is influenced by sex and incidence differs with the BP reference used. Uric acid effect on the development of hypertension is affected by sex and incidence differs with the BP reference used., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Although quitting smoking lowers the risk of developing chronic conditions, it usually leads to weight gain. Literature on the association between weight gain after quitting smoking and the future development of hypertension is scarce. Among 234 596 individuals who visited our health center, 856 who had quit smoking for whom data were available at least 6 years after smoking cessation were included. We evaluated changes in blood pressure and antihypertensive drug prescription rate at 1 and 6 years after smoking cessation. We also compared weight and blood pressure between the smoking cessation and continued smoking groups after 6 years. Multiple regression analyses were performed to identify predictors of changes in systolic and diastolic blood pressures using covariates affecting blood pressure. Since a median weight gain of 1.8 kg was observed at 1 year after smoking cessation, we divided the participants into high and low-weight gain groups. No significant intergroup difference in the antihypertensive drug prescription rate was observed after 6 years. The high weight gain group showed significant increases in systolic and diastolic blood pressures after 6 years. Multiple regression analyses revealed that systolic blood pressure was affected by age and high weight gain, while diastolic blood pressure was affected by high weight gain. Our findings suggest that weight gain following smoking cessation leads to blood pressure elevation: the smoking cessation group gained more weight and had higher blood pressure than the continued smoking group. Therefore, weight loss guidance may be useful for individuals who want to quit smoking. Participants in the high weight gain group showed significant increases in systolic and diastolic blood pressures at 6 years after smoking cessation that were significantly different from those observed in participants in the low weight gain group and the continued smoking group., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Atrial fibrillation (AF) is an arrhythmic disease. Prediction of AF development in healthy individuals is important before serious complications occur. We aimed to develop a risk prediction score for future AF using participants' data, including electrocardiogram (ECG) measurements and information such as age and sex. We included 88,907 Japanese participants, aged 30-69 years, who were randomly assigned to derivation and validation cohorts in a ratio of 1:1. We performed multivariate logistic regression analysis and obtained the standardised beta coefficient of relevant factors and assigned scores to them. We created a score based on prognostic factors for AF to predict its occurrence after five years and applied it to validation cohorts to assess its reproducibility. The risk score ranged from 0 to 17, consisting of age, sex, PR prolongation, QT corrected for heart rate prolongation, left ventricular hypertrophy, premature atrial contraction, and left axis deviation. The area under the curve was 0.75 for the derivation cohort and 0.73 for the validation cohort. The incidence of new-onset AF reached over 2% at 10 points of the risk score in both cohorts. Thus, in this study, we showed the possibility of predicting new-onset AF using ECG findings and simple information., (© 2024. The Author(s).)

No existing reports demonstrate the association between anthropometric indices (body mass index, waist circumference, body roundness index, a body shape index) and hypertension according to sex and age in the general Japanese population. This retrospective analysis involved individuals aged 30-69 years who underwent annual medical checkups at Kagoshima Koseiren Hospital in 2005-2019, and who did not meet hypertension criteria at baseline. The outcome was hypertension incidence after 5 years, and its association with baseline anthropometric indices was evaluated using multivariable logistic regression analysis by sex and age. In 41,902 participants (age 52.3 ± 10.2 years, 47.7% men), 7622 individuals (18.2%) developed hypertension after 5 years. Body mass index, waist circumference, and body roundness index were significantly associated with the development of hypertension in both men and women across all age categories from 30 s to 60 s. In the population with a body mass index <25 kg/m 2 , waist circumference and body roundness index were significantly associated with hypertension after 5 years. A body shape index was significantly associated with the development of hypertension in men in their 40 s and 50 s but not in women of any age group. The area under the curve values were lower for a body shape index than for body mass index, waist circumference, and body roundness index in both men and women of all age groups. A body shape index was not a stronger indicator for 5-year hypertension incidence than body mass index, waist circumference, or body roundness index in both men and women across age groups from their 30s-60 s. The results of this study will help to more efficiently identify populations at high risk of developing hypertension and provide preventive interventions. A total of 41,902 participants from health checkup programs were stratified by gender and age to investigate the association between baseline anthropometric indices and hypertension incidence over a 5-year period. BMI, WC, and BRI were almost equally effective and showed a better association with risk of developing hypertension in women and young adults compared to men and old adults. Conversely, ABSI showed no greater association than BMI or WC in any age group in both men and women. ABSI, a body shape index; AUC, area under the curve from receiver operating characteristic curve analysis; BMI, body mass index; BRI, body roundness index; WC, waist circumference., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Hypertension and insulin resistance are established risk factors for chronic kidney disease. However, the association between chronic kidney disease and insulin resistance in detailed hypertension pattern groups such as isolated diastolic hypertension remains unclear. Triglyceride-glucose index has been noted as an indicator of insulin resistance. This study investigated the association between the triglyceride-glucose index and chronic kidney disease in four blood pressure groups: isolated diastolic hypertension, isolated systolic hypertension, systolic diastolic hypertension, and normotension. Using a database of 41,811 middle-aged men who had two or more annual health checkups from 2007 to 2019, those with chronic kidney disease at the first visit, antihypertensive/diabetes/dyslipidemia medication users, and incomplete data were excluded. Four groups were categorized using the 140/90 mmHg threshold. A COX proportional hazards model was used to assess the triglyceride-glucose index with incident chronic kidney disease. Participants were divided: isolated diastolic hypertension: 2207 (6.72%), isolated systolic hypertension: 2316 (7.06%), systolic-diastolic hypertension: 3299 (10.05%), normal: 24,996 (76.17%). The follow-up period was 6.78 years. Adjusted hazard ratios (HRs) and 95% CIs per unit increase in triglyceride-glucose index: isolated diastolic hypertension (HR = 1.31, 95% CI (1.06-1.62)), isolated systolic hypertension (HR = 1.36, 95% CI (1.12-1.64)), systolic-diastolic hypertension (HR = 1.40, 95% CI (1.19-1.64)), normal (HR = 1.18, 95% CI (1.09-1.28)). Triglyceride-glucose index is relevant for predicting chronic kidney disease development in all subtypes of hypertension. The results may lead to early prediction and prevention of the development of chronic kidney disease., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Blood pressure variability is an independent predictor of cardiovascular disease. Defecation status has also been associated with the risk of developing cardiovascular disease. This study aimed to investigate the association between blood pressure variability and defecation status. A total of 184 participants who could measure their home blood pressure for at least 8 days monthly, both at baseline and 1 year later, were included in this study. All participants had their home blood pressure measured using HEM-9700T (OMRON Healthcare). Day-to-day variability of systolic blood pressure was assessed using the coefficient of variation of home systolic blood pressure during 1 month. Data on defecation status was obtained using a questionnaire survey. Eighty-nine patients had an elevated coefficient of variation at 1 year. The proportion of participants with elevated coefficient of variation at 1 year was significantly higher in the no daily bowel movement group than in the daily bowel movement group (72% vs. 42%, P = 0.001). In multivariable logistic regression analysis with the elevated coefficient of variation at 1 year as the objective variable and age, sex, no daily bowel movement, taking medications, including antihypertensive drugs, laxatives, and intestinal preparations, and coefficient of variation at baseline as independent variables, no daily bowel movement was independently associated with the elevated coefficient of variation at 1 year (odds ratio: 3.81, 95% confidence interval: 1.64-8.87, P = 0.0019). In conclusion, no daily bowel movement was independently associated with elevated day-to-day blood pressure variability at 1 year. Relationship between defecation status and blood pressure level or blood pressure variability., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Carotid plaque is a well-known prognostic factor for cardiovascular diseases. It is unclear which risk factors are associated with the transformation of carotid plaque over time. In this longitudinal study, we examined the risk factors related to carotid plaque progression., Methods: We enrolled 738 men without medication (mean age: 55 ± 10 years) who underwent the first and second health examinations. We measured carotid plaque thickness (PT) at three points of the right and left carotid artery. Plaque score (PS) was calculated by summing all the PTs. We divided the PS into three groups: None-group (PS <1.1), Early-group (1.1 ≤ PS <5.1), and Advanced-group (PS ≥5.1). We analyzed the relationship between PS progression and parameters such as age, body mass index, systolic blood pressure (SBP), fasting blood sugar, low-density lipoprotein cholesterol (LDL-C), and smoking and exercise habits., Results: In multivariable logistic regression analysis, age and SBP were independent factors for PS progression from none to early stages (age, OR 1.07, p = 0.002; SBP, 10 mmHg, OR 1.27, p = 0.041). Age, follow-up period and LDL-C were independently associated factors for PS progression from early to advanced stages (age, OR 1.08,p < 0.001; follow-up period OR1.19, p = 0.041; LDL-C, 10 mg/dL, OR 1.10, p = 0.049)., Conclusions: SBP was independently associated with the progress of early atherosclerosis, while LDL-C was independently associated with the progression of advanced atherosclerosis in the general population. Further studies are needed to assess whether early control of SBP and LDL-C levels can reduce the occurrence of future cardiovascular events., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest regarding this manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Aim: In this study, we aim to analyze the correlation between brachial-ankle pulse wave velocity (baPWV) and Suita score or Framingham risk score and obtain the cutoff value of baPWV by sex and age for cardiovascular risk, as assessed by these scores in the large Japanese annual health checkup data., Methods: In total, 25,602 participants (14,539 men and 11,063 women), who had their annual health checkups, were included in this study. Cutoff values of baPWV for the moderate- and high-risk groups stratified by sex and age were obtained using a receiver operating characteristic (ROC) curve analysis., Results: As per our findings, the Suita score demonstrated better correlations with baPWV than the Framingham risk score in both sexes (men, Suita score R 2 =0.41 and Framingham risk score R 2 =0.37; women, Suita score R 2 =0.54 and Framingham risk score R 2 =0.33). The ROC curve analysis demonstrated the cutoff values of baPWV for moderate- and high-risk groups estimated using the Suita score, and they are as follows: in men, the baPWV cutoff values were 1,350 cm/s in the 40s, 1,430 cm/s in the 50s, 1,520 cm/s in the 60s, and 1,880 cm/s in the 70s. In women, the baPWV cutoff values were 1,350 cm/s in the 40s, 1,430 cm/s in the 50s, 1,570 cm/s in the 60s, and 1,800 cm/s in the 70s., Conclusions: We demonstrated that baPWV significantly correlated with the Suita score or Framingham risk score in both men and women, with the former presenting a stronger correlation than the latter. We propose the cutoff values of baPWV for moderate- and high-risk groups estimated using the Suita score.

Background: Predicting metabolic syndrome (MetS) is important for identifying high-risk cardiovascular disease individuals and providing preventive interventions. We aimed to develop and validate an equation and a simple MetS score according to the Japanese MetS criteria., Methods: In total, 54,198 participants (age, 54.5±10.1 years; men, 46.0%), with baseline and 5-year follow-up data were randomly assigned to 'Derivation' and 'Validation' cohorts (ratio: 2:1). Multivariate logistic regression analysis was performed in derivation cohort and scores were assigned to factors corresponding to β-coefficients. We evaluated predictive ability of the scores using area under the curve (AUC), then applied them to validation cohort to assess reproducibility., Results: The primary model ranged 0-27 points had an AUC of 0.81 (sensitivity: 0.81, specificity: 0.81, cut-off score: 14), and consisted of age, sex, blood pressure (BP), body mass index (BMI), serum lipids, glucose measurements, tobacco smoking, and alcohol consumption. The simplified model (excluding blood tests) ranged 0-17 points with an AUC of 0.78 (sensitivity: 0.83, specificity: 0.77, cut-off score: 15) and included: age, sex, systolic BP, diastolic BP, BMI, tobacco smoking, and alcohol consumption. We classified individuals with a score <15 and ≥15 points as low- and high-risk MetS, respectively. Furthermore, the equation model generated an AUC of 0.85 (sensitivity: 0.86, specificity: 0.55). Analysis of the validation and derivation cohorts yielded similar results., Conclusion: We developed a primary score, an equation model, and a simple score. The simple score is convenient, well-validated with acceptable discrimination, and could be used for early detection of MetS in high-risk individuals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Salim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chronic kidney disease (CKD) is a risk factor for end-stage renal disease and contributes to increased risk of cardiovascular disease morbidity and mortality. We aimed to develop a risk prediction score and equation for future CKD using health checkup data. This study included 58,423 Japanese participants aged 30-69 years, who were randomly assigned to derivation and validation cohorts at a ratio of 2:1. The predictors were anthropometric indices, life style, and blood sampling data. In derivation cohort, we performed multivariable logistic regression analysis and obtained the standardized beta coefficient of each factor that was significantly associated with new-onset CKD and assigned scores to each factor. We created a score and an equation to predict CKD after 5 years and applied them to validation cohort to assess their reproducibility. The risk score ranged 0-16, consisting of age, sex, hypertension, dyslipidemia, diabetes, hyperuricemia, and estimated glomerular filtration rate (eGFR), with area under the curve (AUC) of 0.78 for the derivation cohort and 0.79 for the validation cohort. The CKD incidence gradually and constantly increased as the score increased from ≤ 6 to ≥ 14. The equation consisted of the seven indices described above, with AUC of 0.88 for the derivation cohort and 0.89 for the validation cohort. We developed a risk score and equation to predict CKD incidence after 5 years in Japanese population under 70 years of age. These models had reasonably high predictivity, and their reproducibility was confirmed through internal validation., (© 2023. The Author(s).)

Hypertension is a risk factor for atherosclerosis. Achieving the therapeutic target value of blood pressure (BP) prevents the onset of cardiovascular events; however, it is not clear how antihypertensive drug use and BP control status relate to arterial stiffness. The purpose of this study is to investigate the relationship between BP control status with or without antihypertensive drugs and arterial stiffness. Nine hundred eighty individuals (mean age: 68 ± 11 years) who participated in a community-based cohort study were enrolled. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). Higher BP was defined as a systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. Participants were divided into four groups: normal, non higher BP without antihypertensive drugs (n = 421); untreated, higher BP without antihypertensive drugs (n = 174); good control, non higher BP with antihypertensive drugs (n = 209); and poor control, higher BP with antihypertensive drugs (n = 176). In multivariable logistic analysis adjusted for age, sex, dyslipidemia and diabetes mellitus medication use, obesity, smoking, alcohol drinking, and heart rate at the CAVI measurement for a high CAVI-using a borderline cutoff value of 8.0-the other three groups were significantly associated with a high CAVI when compared with the normal group. By contrast, multivariable logistic analysis of a high CAVI using an abnormal cutoff value of 9.0 demonstrated that the poor control and untreated groups were significantly associated with a high CAVI, whereas the good control group was not. In conclusion, even with antihypertensive drugs, poor BP control is independently associated with a high CAVI., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Aim: This study aims to investigate the association of the Cardio-Ankle Vascular Index (CAVI) with self-reported sleep duration and sleep quality in community-dwelling older adults aged ≥ 65 years., Methods: The Tarumizu Study was a cohort of community-based health checkups conducted in the Tarumizu City, Japan, in 2018 and 2019. In total, 997 participants aged ≥ 65 years (median age, 74 years) were examined. We obtained the average sleep duration and sleep quality using self-reported questionnaires and classified them into three separate groups according to sleep duration (＜6 h, 6-8 h, and ≥ 8 h) and sleep quality (good, medium, and poor). The arterial stiffness was measured using the CAVI., Results: As per our findings, the CAVI was significantly higher in the ≥ 8 h sleep group (CAVI=9.6±1.3) than in the ＜6 h (CAVI=9.1±1.1) or 6-8 h (CAVI=9.1±1.2) groups (p＜0.001). After adjustment for age, sex, systolic blood pressure, current smoking status, body mass index, frequency of exercise, educational background, frailty, sleep medication, sleep quality, and nap duration, multivariable regression analysis demonstrated that the CAVI was significantly higher in the ≥ 8 h group than in the 6-8 h group (p=0.016). In contrast, multivariable regression analysis showed that there was no significant association between sleep quality and CAVI., Conclusions: A significant association was noted between long sleep duration (≥ 8 h) and elevated CAVI in community-dwelling older adults aged ≥ 65 years. We, therefore, suggest that long sleep duration, not sleep quality, is correlated with arterial stiffness in older adults.

Hypertension is a risk factor for cardiovascular disease. We developed a simple scoring method for predicting future hypertension using health checkup data. A total of 41,902 participants aged 30-69 years without baseline hypertension who underwent annual health checkups (mean age, 52.3 ± 10.2 years; male, 47.7%) were included. They were randomly assigned to derivation (n = 27,935) and validation cohorts (n = 13,967) at a ratio of 2:1. In the derivation cohort, we performed multivariable logistic regression analysis and assigned scores to each factor significantly associated with 5-year hypertension. We evaluated the predictive ability of the scores using area under the curve (AUC) analysis and then applied them to the validation cohort to assess their validity. The score including items requiring blood sampling ranged from 0 to 14 and included seven indicators (age, body mass index, blood pressure, current smoking, family history of hypertension, diabetes, and hyperuricemia). The score not including items requiring blood sampling ranged from 0 to 12 and included five indicators (the above indicators, except diabetes and hyperuricemia). The score not including items requiring blood sampling was better; blood sampling did not improve diagnostic ability. The AUC of the score not including items requiring blood sampling was 0.76, with a sensitivity and specificity of 0.82 and 0.60, respectively, for scores ≥6 points. The incidence of hypertension gradually and constantly increased (from 0.9 to 49.6%) as the score increased from 0 to ≥10. Analysis in the validation cohort yielded similar results. We developed a simple and useful clinical prediction model to predict the 5-year incidence of hypertension among a general Japanese population. The model had reasonably high predictive ability and reproducibility., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Blood pressure variability (BPV) is associated with the prognosis of cardiovascular diseases. However, it is unclear how BPV is related to various organs. The aim of this study is to investigate the association between BPV and multiple organ functions. A total of three hundred fifteen participants (114 males; mean age: 70 ± 9 years) participated in a community health checkup held in Tarumizu City. Home blood pressure (BP) was measured using a HEM-9700T (OMRON Healthcare, Kyoto, Japan). Day-to-day BPV was evaluated by the coefficient of variation (CV) of home BP measured in the morning for one month. N-terminal pro B-type natriuretic peptide (NT-pro BNP) and high-sensitivity (hs-)troponin T were measured as cardiac biomarkers. Liver stiffness and renal function were evaluated using the Fibrous-4 (Fib4) index and estimated glomerular filtration rate (eGFR), respectively. NT-pro BNP and hs-troponin T were divided by the median value. Fib4 index greater than 2.67 and eGFR less than 60 mL/min/1.73 m 2 were defined as high Fib4 index and low eGFR, respectively. In a multivariable logistic regression analysis, the CV of systolic BP was significantly associated with high NT-pro BNP, high Fib 4 index, and low eGFR, but not with high hs-troponin T. In contrast, the CV of diastolic BP was not associated with low eGFR, and the other three biomarkers had the same results as systolic BP. In conclusion, day-to-day BPV of systolic BP is independently associated with NT-pro BNP, eGFR, and Fib4 index, but not with hs-troponin T. In contrast, diastolic BPV was not found to be associated with eGFR., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The incidence of atrial fibrillation (AF) is expected to increase with increasing obesity and number of geriatric patients in Japan. Although higher body mass index and abdominal obesity are associated with an increased risk of AF, the sex-specific relationship between abdominal obesity and new-onset AF is unclear. This study aimed to investigate the sex-specific relationship between abdominal obesity and new-onset AF. This retrospective study evaluated the annual health checkup data of 67,379 adults (33,562 males; age, 54 ± 10 years) without baseline AF from April 2008 to March 2016. Participants were grouped according to waist circumference (WC): large-WC group (males, ≥ 85 cm; females, ≥ 90 cm) and normal-WC group. Logistic regression analyses were performed to determine the strength of the association between abdominal obesity and new-onset AF, overall and separately for males and females. During a median follow-up of 5 years, 280 (0.4%) new cases of AF were recorded. Univariate analysis revealed a significant increase in new-onset AF in males (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.49-2.60; p < 0.001) but not in females (OR, 1.69; 95% CI, 0.96-2.97; p = 0.068) in the large-WC group. After adjusting for clinical variables, multivariate analysis revealed that a large WC was significantly associated with new-onset AF in males (OR, 1.76; 95% CI, 1.31-2.36; p < 0.001) but not in females (OR, 1.22; 95% CI, 0.68-2.18; p = 0.514). Abdominal obesity is associated with an increased risk of new-onset AF in men., (© 2021. Springer Japan KK, part of Springer Nature.)

Background: Body mass index (BMI) and the waist-to-height ratio (WHtR) are widely used anthropometric indices of obesity to predict cardiovascular risks. However, the usefulness of combining WHtR and BMI values to predict hypertension risk by sex has not been well elucidated. Methods and Results: This cohort study enrolled 45,921 participants (mean [±SD] age 53.8±10.5 years; 47.0% men) without hypertension from among those undergoing annual health checkups. Participants were divided into 4 categories based on median BMI and WHtR values, and the 5-year incidence of hypertension was assessed for both sexes using logistic regression analysis. Mean (±SD) BMI and WHtR values were 23.5±3.1 kg/m 2 and 0.50±0.05, respectively, in men and 22.4±3.3 kg/m 2 and 0.53±0.06, respectively, in women. Among the women, those with high BMI and low WHtR had an increased risk of hypertension compared with those with low BMI and low WHtR (odds ratio [OR] 1.37, P<0.001); however, the same result was not found in men (OR 1.14, P=0.080). In both sexes, the incidence of hypertension was higher among participants with low BMI and high WHtR than among those with low BMI and low WHtR (men: OR 1.26, P<0.001; women: OR 1.15, P=0.048). Conclusions: Using WHtR and BMI together provides a better hypertension risk assessment. Among men, those with a high BMI had no increased hypertension risk when WHtR was low., Competing Interests: M.O. is a member of Circulation Reports’ Editorial Team. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022, THE JAPANESE CIRCULATION SOCIETY.)

Low and high serum uric acid levels are associated with an increased risk of cardiovascular diseases. However, whether there is a similar association between serum uric acid levels and blood pressure abnormalities has not yet been elucidated. Data from 236,221 individuals (age, 56.0 ± 15.0 years; 107,146 men) who underwent routine health checkups were analyzed. Participants with a serum uric acid level ≤2.0 mg/dL were separated, and the remaining participants were divided into quartiles according to their serum uric acid levels. Among each group, the proportions of participants with high blood pressure (≥130/80 mmHg, and/or medication) and hypertension (≥140/90 mmHg, and/or medication), were calculated. The adjusted odds ratio of each group compared to the group with the lowest proportion of blood pressure abnormalities was calculated. The participants were divided into five groups according to their serum uric acid levels, ≤2.0, 2.1-4.0, 4.1-5.0, 5.1-6.0, and ≥6.1 mg/dL, and the prevalence of high blood pressure was 49.0, 44.6, 52.3, 58.6, and 65.3% and that of hypertension was 31.0, 27.4, 33.5, 38.7, and 43.8%, respectively. Compared to the second-lowest serum uric acid group (2.1-4.0 mg/dL), groups with higher serum uric acid levels (4.1-5.0, 5.1-6.0, and ≥6.1 mg/dL), as well as the group with the lowest serum uric acid level (≤2.0 mg/dL), showed significantly higher odds ratios for high blood pressure and hypertension. High and low serum uric acid levels were significantly associated with an increased prevalence of high blood pressure and followed a J-shaped curve., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

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.

Blood pressure (BP) is influenced by various factors, and it is known that temperature and BP have a negative relationship. However, few reports have examined the relationship between BP and temperature throughout the day in the same participant over time. Therefore, this study aimed to investigate the relationship between BP and temperature in the morning and evening in the same participants during a time period of ~1 year. In total, 401 participants, who participated in a community-based health checkup survey in Tarumizu, Japan, were enrolled. Five participants were excluded due to missing data. All participants measured their BP and the room temperature at home using a blood pressure monitor (HEM-9700T, OMRON Healthcare, Kyoto, Japan). The mean systolic BP (SBP) and diastolic BP (DBP) in the morning were significantly higher than the mean of the measurements taken in the evening (SBP: morning vs. evening 128 ± 15 mmHg vs. 122 ± 14 mmHg, P < 0.0001; DBP: morning vs. evening 77 ± 10 mmHg vs. 72 ± 8 mmHg, P < 0.0001). Using a linear mixed model with participants as a random effect, SBP and DBP were significantly associated with temperature in both the morning and evening. In the morning, in almost every month except July, a significant association between SBP and temperature was observed. However, there was a significant relationship between evening BP and temperature in all months. In conclusion, BP was significantly related to temperature in both the morning and evening during the year-long study. Furthermore, BP and temperature were significantly associated in all months except morning measurements in July.

Background: The effectiveness of weight loss (WL) in preventing blood pressure (BP) elevation is common knowledge; however, the effect of sex differences is not known. Methods and Results: Health checkup data from Kagoshima Kouseiren Medical Healthcare Center for middle-aged participants (40-49 years old) with mild obesity (body mass index [BMI] 25.0-29.9 kg/m 2 ) who had examination data for 2 follow-up time-points (after 3 and 10 years) were analyzed. Propensity score (PS) matching using data from the first examination was used to match participants with a decrease in BMI ≥1.0 kg/m 2 at 3 years (WL group) with those with a BMI decrease <1.0 kg/m 2 or weight gain (non-WL group). BP values were compared after 3 and 10 years between the 2 groups, as was the prevalence of hypertension after 10 years. PS matching resulted in 232 men and 160 women in each group. Among women, systolic BP (SBP) and hypertension prevalence after 10 years were significantly lower in the WL than non-WL group (P<0.01 and P<0.05, respectively). There were no significant differences in SBP and hypertension prevalence after 10 years in men in the 2 groups. Conclusions: There were sex differences in the effectiveness of WL in preventing future BP elevation in mildly obese middle-aged participants: WL prevented future BP elevation and hypertension onset in women, but not in men., Competing Interests: M.O. is a member of Circulation Reports ’ Editorial Team. The other authors declare that they have no conflicts of interest., (Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.)

Intima-media thickness (IMT), plaque score (PS), and brachial-ankle pulse wave velocity (baPWV) are noninvasive parameters used for the evaluation of atherosclerosis. There have been no reports investigating the associations between IMT, PS, or baPWV and known risk factors for atherosclerosis in the same participants. This study aimed to compare the contributing risk factors among IMT, PS, and baPWV. We enrolled 3128 male participants who underwent health checkups. Carotid ultrasonography was used to measure IMT and PS, and baPWV was measured using an automatic device. We analyzed the association between these parameters and risk factors for atherosclerosis including obesity, smoking, alcohol, high blood pressure (BP), impaired fasting glucose (IFG), dyslipidemia (DL), and high-sensitivity C-reactive protein (hs-CRP). Multivariate logistic regression analysis revealed high IMT (>0.9 mm) to be independently associated with high BP. The presence of atherosclerosis (PS ≥ 1.1 mm) was independently associated with high BP, IFG, and DL. In addition, advanced atherosclerosis (PS ≥ 5.1 mm) showed a significant association with high BP, IFG, DL, log hs-CRP, and smoking. High baPWV (≥1600 cm/s) was significantly correlated with high BP, IFG, and log hs-CRP. IMT, PS, and baPWV were all associated with different risk factors among male Japanese participants. Only high BP was a common risk factor for all three parameters. Furthermore, hs-CRP was associated with advanced atherosclerosis but not with the presence of atherosclerosis.

Background: Pulmonary hypertension (PH) is an important cause of morbidity in patients with connective tissue disease (CTD), and an early stage of PH could present as exercise-induced PH (EIPH). This study investigated the significant clinical indexes of EIPH in patients with CTD. Methods and Results: We enrolled 63 patients with CTD who did not have PH at rest. All patients underwent the 6-min walk test (6MWT), and systolic pulmonary artery pressure (SPAP) was evaluated on echocardiography before and after 6MWT. EIPH was defined as SPAP ≥40 mmHg after 6 WMT. Thirty-five patients had EIPH. On univariate logistic analysis, SPAP at rest, log brain natriuretic peptide (BNP), vital capacity (VC), and forced expiratory volume in 1 s (FEV1.0) were significantly correlated with EIPH. On multiple logistic analysis, SPAP at rest and VC were independent predictors of EIPH, whereas FEV1.0 and log BNP were not significantly associated with EIPH. The area under the receiver operating characteristics curve between EIPH and BNP, SPAP at rest, VC or FEV1.0 was 0.67, 0.76, 0.74, and 0.75, respectively. Conclusions: SPAP at rest and respiratory function, especially VC, could be independent predictors of EIPH in patients with CTD., Competing Interests: The authors declare no conflicts of interest. M.O. is a member of Circulation Reports’ Editorial Team., (Copyright © 2019, THE JAPANESE CIRCULATION SOCIETY.)

Screening and early detection of pulmonary arterial hypertension (PAH) in connective tissue disease (CTD) are currently recommended for early treatment. Exercise-induced pulmonary hypertension (EIPH) is thought to be a potential risk of developing resting pulmonary hypertension. However, accurate diagnosis of EIPH is needed hemodynamics by right heart catheterization during exercise. Therefore, we compared various parameters of EIPH group with non-EIPH group in patients with CTD. This study aimed to investigate noninvasive predictors of EIPH. A total of 162 consecutive patients with CTD who received screening of PAH was studied. Thirty-four patients with suspected PAH received right heart catheterization (RHC) at rest. Twenty-four patients without PAH underwent RHC during exercise, and they were divided into the EIPH group (n = 7) and the non-EIPH group (n = 17). Exercise tolerance such as 6-min walk distance and peak VO 2 /kg in the EIPH group was lower than that in the non-EIPH group. For hemodynamics, pulmonary artery pressure, right atrial pressure, and vascular resistance in the EIPH group were significantly higher than those in the non-EIPH group. In echocardiography, RV Tei index in the EIPH group was significantly higher than that in the non-EIPH group (EIPH vs non-EIPH = 0.42 [0.41, 0.47] vs 0.25 [0.20, 0.32], P = 0.007). The receiver operating characteristics curve showed a cutoff value of RV Tei index (0.41) with a sensitivity of 0.857 and specificity of 0.882. In conclusion, RV Tei index might be a feasible predictor of EIPH in patients with CTD.

Background and objectives: There is insufficient epidemiological knowledge of hypouricemia. In this study, we aimed to describe the distribution and characteristics of Japanese subjects with hypouricemia. Materials and Methods: Data from subjects who underwent routine health checkups from January 2001 to December 2015 were analyzed in this cross-sectional study. A total of 246,923 individuals, which included 111,117 men and 135,806 women, met the study criteria. The participants were divided into quartiles according to their serum uric acid (SUA) levels. We subdivided the subjects with hypouricemia, which was defined as SUA level ≤ 2.0 mg/dL, into two groups and compared their characteristics, including their cardiovascular risks. Results: The hypouricemia rates were 0.46% overall, 0.21% for the men and 0.66% for the women ( P < 0.001). The number of the subjects with hypouricemia showed two distributions at SUA levels of 0.4⁻1.1 mg/dL (lower hypouricemia group), which included a peak at 0.7⁻0.8 mg/dL, and at SUA levels of 1.4⁻2.0 mg/dL (higher hypouricemia group). The men in the higher hypouricemia group had lower body mass indexes (BMI) and triglyceride (TG) levels and had higher fasting blood glucose levels than those in the lower hypouricemia group. The women in the higher hypouricemia group were younger; had lower BMI, total protein, TG, total cholesterol and low-density lipoprotein cholesterol levels; and had higher estimated glomerular filtration rates levels compared to those in the lower hypouricemia group. Conclusions: The characteristics of the individuals in the lower and higher hypouricemia groups differed significantly, indicating different pathophysiologies within each group.

Background: The independent role of uric acid (UA) as a risk factor for atrial fibrillation (AF) has not been fully elucidated. Methods and Results: We studied 111,566 subjects (53,416 men; 58,150 women) who underwent annual health check-ups. We divided them by sex into tertile of baseline UA. To investigate the predictive power of UA for new-onset AF, we performed Cox proportional hazard analysis including UA tertiles, body mass index, creatinine, smoking and drinking status, and presence of hypertension, diabetes, and dyslipidemia. During 4.1 years, 467 men (0.87%) and 180 women (0.31%) had AF (P<0.001). Cut-off points for tertiles of UA were as follows: women, ≤3.9, 4.0-4.8, and ≥4.9 mg/dL; men, ≤5.4, 5.5-6.4, and ≥6.5 mg/dL. Hazard ratio (HR) for third to first tertile was 1.74 (95% CI: 1.15-2.70; P=0.008), whereas there were no differences between tertiles in men. Rate of new-onset AF was significantly higher in the group with initially increased UA (ΔUA ≥0.3 mg/dL) than that with unchanged UA (ΔUA, -0.2 or +0.2 mg/dL) in the third tertile of baseline UA in both sexes., Conclusions: Higher baseline UA was significantly associated with higher AF incidence in women. Initial increase in UA was significantly associated with AF incidence when baseline UA was ≥6.5 mg/dL in men, and ≥4.9 mg/dL in women.

Background: The independent role of serum triglyceride (TG) levels as a cardiovascular risk factor is still not elucidated. We aimed to investigate if the effect of TG on arterial stiffness is influenced by the serum level of low-density lipoprotein cholesterol (LDL-C). Methods and Results: We studied 11,640 subjects who underwent health checkups. They were stratified into 4 groups according to LDL-C level (≤79, 80-119, 120-159, and ≥160 mg/dL). Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). In each group, univariate and multivariete logistic regression analyses were performed to investigate the association between high TG (≥150 mg/dL) and high baPWV (>1,400 cm/s). In the univarite analysis, high TG was significantly associated with high baPWV in LDL-C <79 mg/dL (OR, 3.611, 95% CI, 2.475-5.337; P<0.0001) and 80-119 mg/dL (OR, 1.881; 95% CI, 1.602-2.210; P<0.0001), but not in LDL-C 120-159 mg/dL and ≥160 mg/dL. In the multivariate analysis, high TG was significantly associated with high baPWV in LDL-C ≤79 mg/dL (OR, 2.558; 95% CI, 1.348-4.914; P=0.0040) and LDL-C 80-119 mg/dL (OR, 1.677; 95% CI, 1.315-2.140; P<0.0001), but not in LDL-C 120-159 mg/dL and ≥160 mg/dL., Conclusions: High TG and increased arterial stiffness showed an independent relationship in a Japanese general population with LDL-C ≤119 mg/dL. TG-lowering therapy might be an additional therapeutic consideration in these subjects.

Objective An increased red cell distribution width (RDW) has been reported to be associated with adverse outcomes in patients with heart failure (HF). This study aimed to evaluate the prognostic power of the combined measurement of RDW and B-type natriuretic peptide (BNP) concentrations in patients with HF. Methods and Results We retrospectively studied 116 patients (mean age, 63.7±14.3 years) who were admitted for the treatment of HF. Data including demographic information, vital signs, and laboratory and echocardiographic measurements at admission were collected from medical records. The observational period was defined as the number of days from hospitalization, and the study endpoint was defined as cardiovascular death. The mean RDW and BNP concentration at admission were 14.5±2.0% and 626±593 pg/mL, respectively. During a median observation period of 1,046 days, 22 patients died of cardiovascular disease. A univariate Cox proportional hazard analysis revealed that both RDW [hazard ratio (HR) 1.252, p = 0.0391] and BNP (HR 1.001, p = 0.0445) were significant prognostic indices for cardiovascular death. A receiver operating characteristic curve analysis revealed that the optimal cut-off RDW and BNP values for cardiovascular death were 14.9% and 686 pg/mL, respectively. The Kaplan-Meier survival curve revealed that the survival rate of patients with both RDW ≥ 14.9% and BNP ≥ 686 pg/mL showed the poorest prognosis in comparison to the patients in the other groups. Conclusion The combined assessment of the RDW and BNP concentrations may be useful for predicting mortality in patients with HF.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are reported to have BP-lowering effect in addition to blood glucose-lowering effect, however, its mechanism is still unknown. This study aimed to investigate the mechanism of blood pressure (BP) lowering effects of SGLT2 inhibitors using 24-h urinary collection in obese type 2 diabetes patients., Methods: Twenty patients with type 2 diabetes (age 48.2 ± 10.7 years, BMI 33.0 ± 4.9 kg/m 2 ) were enrolled. Urine volume, 24-h urinary glucose and sodium excretion, and BP at baseline and 2 weeks and 6 months after administration were measured. Body weight, glycosylated hemoglobin, and BP were evaluated before and 1, 3, and 6 months after SGLT2 inhibitor administration. We evaluated the changes in urine volume and urinary excretion of glucose and sodium as well as correlations among urine volume and urinary sodium glucose excretion at 2 weeks and 6 months after administration of the SGLT2 inhibitors. Furthermore, we investigated the correlations between changes in BP and urinary excretion of sodium and glucose at the same time., Results: Two weeks after administration, systolic BP (SBP) significantly decreased (128.5 ± 11.0 to 123.2 ± 9.8 mmHg, P = 0.0314), but diastolic BP (DBP) did not (74.4 ± 10.4 to 73.4 ± 8.5 mmHg, P = 0.5821). The decreased SBP significantly correlated with increased urinary glucose excretion (R = -0.62, P = 0.0073), but not increased urinary sodium excretion. At 6 months, SBP (118.6 ± 11.0 mmHg, P = 0.0041) and DBP (68.4 mmHg, P = 0.0363) significantly decreased. The decreased SBP significantly correlated with increased urinary sodium excretion (R = -0.60, P = 0.0014), but not increased urinary glucose excretion., Conclusions: SGLT2 inhibitors significantly decreased SBP after 1 month and DBP after 6 months in obese patients with type 2 diabetes. The main mechanism of the BP-lowering effect may be plasma volume reduction by osmotic diuresis at 2 weeks and by natriuresis at 6 months after SGLT2 inhibitor administration.

Background: Although there have been several reports on the risk factors associated with intima-media thickness (IMT), many questions remain. The purpose of this study was to investigate the association between IMT and cardiovascular risk factors in a Japanese general population.Methods and Results:The study group consisted of 1,583 male subjects undergoing routine health checkups. IMT of the common carotid artery was measured by high-resolution ultrasonography. Brachial-ankle pulse wave velocity (baPWV) was measured using an automated device. Univariate analysis demonstrated that carotid IMT significantly associated with age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), baPWV, fasting glucose, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C). Multiple logistic regression analysis for carotid atherosclerosis (carotid IMT ≥1.0 mm) was performed using obesity (BMI ≥25.0 kg/m 2 ), high BP (SBP ≥130 mmHg or DBP ≥85 mmHg), dyslipidemia (LDL-C ≥140 mg/dL, TG ≥150 mg/dL, or HDL-C <40 mg/dL), impaired fasting glucose (IFG) (fasting glucose ≥110 g/dL), and high baPWV (≥1,400 cm/s). Carotid atherosclerosis was significantly associated with only high baPWV (OR: 2.22, 95% CI: 1.24-4.17, P<0.01)., Conclusions: High baPWV was a stronger predictor of early carotid atherosclerosis than high BP, dyslipidemia, or IFG in a Japanese general male population.

Background: The association between serum uric acid (UA) levels and atrial fibrillation (AF) in the general population in Japan is not well known.Methods and Results:In total, 285,882 consecutive subjects (men, 130,897; women, 154,985; age, 58±15 years) not receiving treatment for hyperuricemia who underwent health checkups were enrolled. Subjects were stratified into deciles according to age, body mass index, estimated glomerular filtration rate, systolic blood pressure, and UA level. AF prevalence was calculated for each decile. The odds ratio that defined the decile with the lowest AF prevalence as reference was calculated in each sex. In men, the mean UA was 6.0±1.4 mg/dl; AF prevalence was 1.8% and was lowest in the decile with UA 4.4-4.9 mg/dl. Deciles with both high and low UA (5.4-5.6 mg/dl to >7.8 mg/dl and <4.3 mg/dl) were associated with significantly higher AF prevalence. In women, the mean UA was 4.5±1.1 mg/dl; AF prevalence was 0.7% and was lowest in the decile with UA 3.6-3.8 mg/dl. Deciles with highest UA (5.0-5.2 mg/dl to >5.9 mg/dl) were associated with significantly higher AF prevalence. The analysis adjusted for other clinical covariates demonstrated an independent association between UA and AF in both sexes., Conclusions: In a representative Japanese general population, UA level was significantly associated with AF, independently of other cardiovascular risk factors. (Circ J 2016; 80: 2453-2459).

A novel N3S1 typed tripodal ligand bearing an SH group, N-(mercaptoethyl)-di(2-pyridylmethyl)amine, DPASH, was prepared and its zinc(II) complex, [ZnII(DPAS)Cl], was structurally characterized by X-ray crystallography. [ZnII(DPAS)Cl] promoted hydrolysis of sodium bis(p-nitrophenyl)hydrogenphosphate), BNP-.