Published papers

© 2019 Aya Higashiyama et al. Background: Left atrial dimension (LAD) and other parameters of echocardiography have been reported to be associated with the risk of atrial fibrillation (AF). However, few studies have investigated the associations between echocardiographic parameters and the risk of AF in the Asian general population, which has a low AF incidence. Methods: A prospective cohort study was performed in 1,424 individuals in the Suita study with echocardiographic parameters, including LAD, and no history of AF. After echocardiography, the participants were followed using 12-lead electrocardiography and questionnaires to detect AF incidence. The multivariable-adjusted hazard ratios (HRs) of echocardiographic parameters for AF incidence were estimated after adjustment for the risk factors of the AF risk score. Results: During the median 6.0 years of follow-up, 31 AF cases occurred. The multivariable-adjusted HR of a 1-mm increase in LAD for AF was 1.18 (95% confidence interval [CI], 1.08-1.28). The multivariable-adjusted HR for AF of a 1-standard-deviation increase in LAD was higher than that of left ventricular internal dimensions in diastole, left ventricular mass, ejection fraction, and percent fractional shortening, and it was the only significant factor. In 667 participants with both LAD and LA volume (LAV) measurements, LAD and LAV were independently associated with the risk of AF incidence. Conclusions: LAD on echocardiography was an independent risk factor of incident AF in the Japanese population. LAD might be useful for identifying individuals with a high risk of AF in health check-ups of the general population.

Aims/Introduction: To examine the cross-sectional relationship between sleep duration and impaired glucose tolerance (IGT), including diabetes mellitus (DM), we analyzed a large-scale healthy workers database in Japan. Materials and Methods: We examined the baseline database of 4143 participants (3415 men and 728 women) aged 19-69years. Sleep duration of participants was categorized into four groups: <6, 6 to <7, 7 to <8 and ≥8h. The physical activity of each participant was classified according to the International Physical Activity Questionnaire (IPAQ). We defined IGT including DM (IGT/DM) in the present study according to previous studies as follows: fasting blood sugar level ≥110mg/dL, or if <8h after meals ≥140mg/dL, or on medication for diabetes mellitus, or those diagnosed as having DM. Logistic regression was applied to estimate the odds ratio (OR) to examine the relationship between IGT/DM, sleep duration and other related factors. Results: The number of participants with IGT/DM was 402 (9.7%). The factors that significantly associated with IGT/DM were age (OR 1.08, 95% confidence interval [CI] 1.07-1.10, P<0.001), high blood pressure (OR 1.94, CI 1.52-2.47, P<0.001), and <6h of sleep duration in comparison with 6 to <7h sleep (OR 2.32, CI 1.18-4.55, P=0.015). The associations of difficulty in sleep initiation, IPAQ classification, current smoking and alcohol intake with IGT/DM were not statistically significant. Conclusions: Our results showed that shorter sleep duration (<6h of sleep duration per night) was associated with a risk of IGT/DM independent of other lifestyle habits and metabolic risk factors. © 2011 Asian Association for the Study of Diabetes and Blackwell Publishing Asia Pty Ltd.

© 2018, The Japanese Society of Hypertension. Excessive salt intake is an established risk factor for hypertension. We conducted a cross-sectional study to examine the association between salty taste recognition and estimated salt intake and masked hypertension in a healthy Japanese normotensive population. The participants were 892 apparently healthy community residents (246 men and 646 women) aged between 40 and 74 years with blood pressure below 140/90 mm Hg. Salty taste recognition was assessed using a salt-impregnated taste strip. Daily salt intake was calculated as estimated 24 h urinary sodium excretion using spot urine tests. Each participant performed home blood pressure measurements for a minimum of 5 days per week. The participants were classified into three groups according to their salty taste recognition threshold evaluated by the salt concentrations of the taste strips (0.6%, 0.8%, and ≥ 1.0%). In women, the multivariate odds ratio (95% confidence interval) for masked hypertension (≥ 135/85 mm Hg) was 2.98 (1.16–7.64) in the ≥ 1.0% group compared with that in the 0.6% group. In men, the proportion of masked hypertension in the ≥ 1.0% group did not differ from that in the 0.6% group, and no correlation was identified between estimated daily salt intake and the salty taste recognition threshold. In conclusion, impairment of salty taste recognition was associated with masked hypertension in women even with normal blood pressure in the clinical setting.

© 2018 Japan Atherosclerosis Society. Aim: To investigate associations between socioeconomic status (SES) and the prevalence and treatment status of hypercholesterolemia in a general Japanese population. Methods: In 2010, we established a cohort study of 2417 adults (age 20-91 yr) from 300 randomly selected areas across Japan who participated in the National Health and Nutrition Survey of Japan. We cross-sectionally examined an association between SES and (1) prevalence of hypercholesterolemia in 2417 participants (999 men and 1418 women) and (2) not receiving medication for hypercholesterolemia in 654 participants (215 men and 439 women). SES included employment status, marital status, length of education, and household expenditures. Hypercholesterolemia was defined as a total serum cholesterol level of ≥ 6.21 mmol/L (240 mg/dL) or the use of lipid-lowering medications. Results: The overall prevalence of hypercholesterolemia was 21.5% in men and 31.0% in women. In men, the lowest quintile of household expenditures was associated with a higher prevalence of hypercholesterolemia (28.3%) compared with the upper 4 quintiles (19.9%) (multivariable-adjusted odds ratio 1.66; 95% confidence interval [CI] 1.16-2.38). Among participants with hypercholesterolemia, 55.4% of men and 55.1% of women were not receiving medication. Unmarried men were more likely to be untreated (75.0%) than married men (50.9%) (multivariable-adjusted odds ratio 2.53; 95%CI 1.05-6.08). SES had no significant effects in women. Conclusion: In a general population of Japanese men, low household expenditures were associated with a higher prevalence of hypercholesterolemia, and unmarried men with hypercholesterolemia were less likely to receive medication.

© 2018, Japanese Circulation Society. All rights reserved. Background: Recently, high-density lipoprotein particles (HDL-P) have been found to be more strongly inversely associated with coronary artery disease (CAD) risk than their counterpart, HDL cholesterol (HDL-C). Given that lifestyle is among the first targets in CAD prevention, we compared the associations of HDL-P and HDL-C with selected lifestyle factors. Methods and Results: We examined 789 Japanese participants of the INTERLIPID Study: men (n=386) and women (n=403) aged 40–59 years in 1996–1998. Participants treated for dyslipidemias were excluded. Lifestyle factors included alcohol intake, smoking amount, and body mass index (BMI). Multivariable linear regression was used for cross-sectional analyses of these factors with HDL-P, HDL-C, HDL-P size subclasses (small, medium and large) and mean HDL-P size. In men, higher alcohol intake was associated with higher HDL-P and higher HDL-C. The associations of alcohol, however, were strongest with HDL-P. A higher smoking amount tended to be associated with lower HDL-P and HDL-C. In contrast, BMI was not associated with HDL-P, but was strongly inversely associated with HDL-C. While alcohol intake favored larger mean HDL-P size, smoking and BMI favored a lipid profile with smaller HDL-P subclasses and overall smaller mean HDL-P size. Similar, but generally weaker results were observed in women. Conclusions: Although both HDL-P and HDL-C are parameters of HDL, they have different associations with alcohol, smoking and BMI.

© 2018 Yosuke Shibata et al. Background: The trend of association between overweight and high serum total cholesterol (TC) among the elderly is unclear. In addition, there is little evidence of risk of underweight for high TC. Therefore, we examined the trend of association of overweight or underweight with high TC among Japanese elderly people using nationwide population-based data. Methods: Data of the National Survey on Circulatory Disorders and National Health and Nutrition Survey for 1980, 1990, 2000, and 2010 were used in the analysis. High TC was defined as 220mg=dL and above. For participants aged =50 years, sex-specific odds ratios (ORs) of overweight or underweight compared with normal body mass index participants for high TC were calculated using a logistic regression model adjusted for age, smoking, drinking, exercise, food, and treatment of hyperlipidemia. Results: A total of 5,734, 4,673, 5,059, and 2,105 participants enrolled in these surveys in 1980, 1990, 2000, and 2010, respectively. Although overweight was positively and significantly associated with high TC in 1980, the association has gradually weakened since (ORs in 1980 and 2010 were 2.44; 95% confidence interval [CI], 1.83-3.24 and 0.92; 95% CI, 0.66-1.27 among men and 1.43; 95% CI, 1.18-1.72 and 1.08; 95% CI, 0.81-1.44 among women, respectively). While underweight was inversely and significantly associated with high TC in 1980, the association also gradually weakened among women (ORs in 1980 and 2010 were 0.28; 95% CI, 0.12-0.60 and 0.37; 95% CI, 0.10-1.28 among men and 0.39; 95% CI, 0.26-0.57 and 0.96; 95% CI, 0.58-1.57 among women, respectively). Conclusions: These findings provide evidence that high TC prevention efforts must expand the target to not only overweight but also to normal and underweight people.

© 2018 Atsushi Hozawa et al. Background: We sought to investigate the optimal values of BMI for the lowest risk of all-cause death and whether the optimal BMI differs according to smoking status in large-scale pooled analysis of 13 Japanese cohorts. Methods: Data from 179,987 participants of 13 well-qualified cohort studies conducted throughout Japan were used for our analysis. A cohort-stratified Cox proportional hazard model was used. P values for interactions were calculated based on the cross product of BMI and age, sex, or smoking status. Results: In the entire study population, all-cause mortality risk was lowest when the BMI was 22.0–24.9 kg=m2. This was also the case for selected healthy participants (never smoked, baseline total cholesterol level ≥4.1 mmol=L; the first 5 years of follow-up data were excluded). No effect modification of age, sex, or smoking status was observed. Regardless of their BMI, never smokers always had a lower all-cause mortality risk than did current smokers even with an ideal BMI in terms of mortality risk. Conclusion: A BMI of 22–24.9 kg=m2 correlated with the lowest risk of mortality, regardless of whether all participants or selected healthy participants were analyzed. The fact that smoking was more strongly associated with mortality than obesity emphasizes the urgency for effective anti-smoking programs.

The consumption of red meat has been recommended for individuals with reduced kidney function. However, red meat intake was recently suspected to increase cardiovascular disease (CVD) risk. We evaluated the association of red meat intake with CVD mortality risk in Japanese with/without reduced kidney function. Overall, 9112 participants of a Japanese national survey in 1980, aged ≥30 years, were followed for 29 years. Red meat intake was assessed using weighed dietary record. Cox proportional hazards models were used to estimate the hazard ratio (HR) of CVD mortality according to sex-specific tertiles of red meat intake. We also performed stratified analyses with/without reduced kidney function defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m . Red meat intake was not associated with CVD mortality risk in men and women. In stratified analyses, the HR of the highest compared with the lowest tertile of red meat intake was lower only in women with reduced kidney function (0.67, 95% confidence interval 0.46–0.98). In conclusion, there were no clear associations between red meat intake and CVD mortality risk in Japanese population; however, a higher intake of red meat was associated with lower risk of future CVD mortality in women with reduced kidney function. 2

© 2018 Asian Pacific Organization for Cancer Prevention. Objective: We employed a large-scale pooled analysis to investigate the association of liver cancer-related mortality with being overweight/obese and total cholesterol (TC) levels, since limited and inconsistent data on these associations exist in Japan. Methods: A total of 59,332 participants (23,853 men and 35,479 women) from 12 cohorts without a history of cancer who were followed for a median of 14.3 years were analyzed. A sex-specific stratified Cox proportional hazards model adjusted for age and other potential confounders was used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for liver cancer-related mortality. Results: A total of 447 participants (266 men and 181 women) died of liver cancer within the follow-up period. Individuals classified as having a high BMI (≥25.0 kg/m2) and low TC levels (< 160 mg/dL) had a significantly increased risk for liver cancer-related mortality (HR 7.05, 95% CI 4.41-11.26 in men; HR 8.07, 95% CI 4.76-13.67 in women) when compared with those in the intermediate BMI (18.5-24.9 kg/m2) and TC (160-219 mg/dL) categories. These associations remained after limiting the follow-up duration to > 5 years. Conclusion: Being overweight/obese, combined with low TC levels, was strongly associated with liver cancer-related mortality in the EPOCH-JAPAN.

Aim: To examine whether subclinical atherosclerosis of the carotid arteries is concordant with the categories in the 2012 atherosclerosis prevention guidelines proposed by the Japan Atherosclerosis Society (JAS guidelines 2012), which adopted the estimated 10-year absolute risk of coronary artery disease (CAD) death in the NIPPON DATA80 Risk Assessment Chart. Methods: Between 2006 and 2008, 868 Japanese men 40 to 74 years of age without a history of cardiovascular disease were randomly selected from Kusatsu City, Japan. The intima media thickness (IMT) and plaque number from the common to internal carotid arteries were investigated using ultrasonography. The absolute risk of CAD death was estimated based on the individual risk factor data, and the mean IMT and plaque number in Categories I, II and III of the guidelines were examined. Results: The estimated 10-year absolute risk of CAD was directly related to the IMT (mean IMT (mean±SD) (mm) for a 10-year absolute risk of ≥2.0% and ≥5.0%: 0.88±0.18 and 0.95±0.19, respectively) and the plaque number. These results are compatible with the categories described by the guidelines (mean IMT (mean±SD) (mm) for Categories I, II, and III: 0.70±0.11, 0.81±0.16 and 0.88±0.18, respectively; mean plaque number: 0.9, 2.1 and 3, respectively). These findings were similar for Category III participants with or without DM and CKD. Conclusions: Subclinical atherosclerosis of the carotid arteries is concordant with the 10-year absolute risk of CAD and the categories in the JAS guidelines 2012.

© 2020 Japan Atherosclerosis Society. Aim: To construct a risk prediction model for cardiovascular disease (CVD) based on the Suita study, an urban Japanese cohort study, and compare its accuracy against the Framingham CVD risk score (FRS) model. Methods: After excluding participants with missing data or those who lost to follow-up, this study consisted of 3,080 men and 3,470 women participants aged 30–79 years without CVD at baseline in 1989–1999. The main outcome of this study was incidence of CVD, defined as the incidence of stroke or coronary heart disease. Multi-variable Cox proportional hazards models with stepwise selection were used to develop the prediction model. To assess model performance, concordance statistics (C-statistics) and their 95% confidence intervals (CIs) were cal-culated using a bootstrap procedure. A calibration test was also conducted. Results: During a median follow-up period of 16.9 years, 351 men and 241 women developed CVD. We for-mulated risk models with and without electrocardiogram (ECG) data that included age, sex, systolic blood pres-sure, diastolic blood pressure, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, diabetes mellitus, smoking, and urinary protein as risk factors. The C-statistics of the Suita CVD risk models with ECG data (0.782; 95% CI, 0.766–0.799) and without ECG data (0.781; 95% CI, 0.765–0.797) were significantly higher than that of the FRS model (0.768; 95% CI, 0.750–0.785). Conclusions: The Suita CVD risk model is feasible to use and improves predictability of the incidence of CVD relative to the FRS model in Japan.

© 2018 National Kidney Foundation, Inc. Rationale & Objective: Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework. Study Design: Cross-sectional individual participant-level analyses in a global consortium. Setting & Study Populations: 17 CKD and 38 general population and high-risk cohorts. Selection Criteria for Studies: Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension. Data Extraction: Data were obtained and analyzed between July 2015 and January 2018. Analytical Approach: We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses. Results: The CKD cohorts (n = 254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n = 1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59 mL/min/1.73 m 2 ), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30 mg/g). Limitations: Variations in study era, health care delivery system, typical diet, and laboratory assays. Conclusions: Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.

© 2018 Masaki Sumi et al. Background: Excessive alcohol intake has been shown to be associated with cardiovascular disease via metabolic pathways. However, the relationship between alcohol intake and obesity has not been fully elucidated. We aimed to examine the association of alcohol consumption with fat deposition and anthropometric measures. Methods: From 2006–2008, we conducted a cross-sectional study in a population-based sample of Japanese men aged 40 through 79 years. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography imaging. Based on a questionnaire, we classified participants into five groups according to weekly alcohol consumption, excluding former drinkers: Non-drinkers (0 g=week), 0.1–160.9, 161–321.9, 322–482.9, and ≥483 g=week. Multivariable linear regression was used to estimate adjusted means of obesity indices for each group. Results: We analyzed 998 men (mean age and body mass index [BMI], 63.8 years and 23.6 kg=m2, respectively). Higher weekly alcohol consumption was strongly and significantly associated with higher abdominal VAT area, percentage of VAT, and VATto- SAT ratio (all P for trend <0.001), and also with waist circumferences and waist-to-hip ratio (P for trend = 0.042 and 0.007, respectively). These associations remained significant after further adjustment for BMI, whereas alcohol consumption had no significant association with abdominal SAT area. Conclusions: Higher alcohol consumption was associated with higher VAT area, VAT%, and VAT-to-SAT ratio, independent of confounders, including BMI, in general Japanese men. These results suggest that alcohol consumption may have a potential adverse effect on visceral fat deposition.

AimsConflicting evidence exists regarding whether obesity is independently associated with coronary artery calcium (CAC), a measure of coronary atherosclerosis. We examined an independent association of obesity with prevalent CAC among samples of multi-ethnic groups whose background populations have varying levels of obesity and coronary heart disease (CHD).Methods and resultsWe analysed a population-based sample of 1212 men, aged 40-49 years free of clinical cardiovascular disease recruited in 2002-06; 310 Japanese in Japan (JJ), 294 Koreans in South Korea (KN), 300 Japanese Americans (JA), and 308 Whites in the USA (UW). We defined prevalent CAC as an Agatston score of ≥10. Prevalent CAC was calculated by tertile of the body mass index (BMI) in each ethnic group and was plotted against the corresponding median of tertile BMI. Additionally, logistic regression was conducted to examine whether an association of the BMI was independent of conventional risk factors. The median BMI and crude prevalence of CAC for JJ, KN, JA, and UW were 23.4, 24.4, 27.4, and 27.1 (kg/m2); 12, 11, 32, and 26 (%), respectively. Despite the absolute difference in levels of BMI and CAC across groups, higher BMI was generally associated with higher prevalent CAC in each group. After adjusting for age, smoking, alcohol, hypertension, lipids, and diabetes mellitus, the BMI was positively and independently associated with prevalent CAC in JJ, KN, UW, but not in JA.ConclusionIn this multi-ethnic study, obesity was independently associated with subclinical stage of coronary atherosclerosis among men aged 40-49 years regardless of the BMI level. © 2013 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013.

© 2020 Elsevier B.V. Aim: To assess the current situation and neurologically favourable outcomes after out-of-hospital cardiac arrest (OHCA) with respect to the type of witness. Methods: This retrospective observational study used data from the All-Japan Utstein Registry of the Fire and Disaster Management Agency collected between January 1, 2016, and December 31, 2016. Patients with cardiogenic OHCA aged ≥18 years who were witnessed by bystanders were included. The primary outcome measure was a neurologically favourable outcome 1 month after the OHCA. Results: Among the 123,554 patients with OHCA registered between January 1, 2016, and December 31, 2016, 24,856 patients were included. Of them, 15,139 were witnessed by family, and 9717 were witnessed by non-family (friends, 1306; colleagues, 951; passers-by, 997; others, 6463). When witnessed by family, the rate of neurologically favourable outcomes was significantly lower than that when witnessed by non-family (odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.41–0.49, P < 0.001). After adjusting for potential confounders, the rate of neurologically favourable outcomes remained lower when OHCA was witnessed by family (OR = 0.88, 95% CI = 0.79–0.99, P = 0.03). However, in subgroup analysis, adjusted ORs for neurologically favourable outcomes were slightly greater for 65–84-year-old women and ≥85-year-old women with family witnesses than for those with non-family witnesses. For all other groups, non-family witnesses outperformed family witnesses. Conclusion: Family-witnessed OHCA events had fewer neurologically favourable outcomes before and after adjusting for confounders. BLS education for family members may lead to improved prognosis of witnessed cardiogenic OHCAs.