Published papers

The relationship between serum osmolarity and cognitive function has not been fully characterized. This study aimed to examine the cross-sectional association between repeated high serum osmolarity and cognitive performance among elderly community residents. We performed a subanalysis of the Kobe Orthopedic and Biomedical Epidemiological Study, including residents aged ≥ 75 years who completed the Japanese Montreal Cognitive Assessment (MoCA-J) in 2016–2017 (n = 127), 2018–2019 (n = 71), and 2020 (n = 16). Serum osmolarity was obtained from the data in the 2012–2013 survey and in the 2016–2017 survey. MoCA-J scores were dichotomized at ≤ 22 versus > 22. Multivariate logistic regression adjusted for demographic, lifestyle including daily non-alcohol drink intake, seasonal, and clinical covariates to assess associations between osmolarity status and cognitive group. Among 214 participants (mean age 76.2 ± 1.3 years; 56% female), high osmolarity (≥ 300 mOsm/L) in 2012–2013 was associated with MoCA-J ≤ 22 (OR 2.67, 95% CI 1.29–5.53, p = 0.008). A similar association emerged for 2016–2017 measurements (OR 6.12, 95% CI 1.46–25.61, p = 0.013). Participants with high serum osmolarity at both time points showed a stronger cross-sectional association with lower MoCA-J scores (OR 17.64, 95% CI = 1.8–184.83, p = 0.017). No significant association was observed between daily non-alcoholic drink (NAD) intake and either MoCA-J scores or serum osmotic pressure. Repeated high serum osmolarity was cross-sectionally associated with lower cognitive performance in Japanese community-dwelling older adults. While NAD intake showed no significant association, further research is needed to explore the potential role of serum osmolarity in cognitive health. These findings warrant confirmation in larger prospective studies.

In the Japanese workplace, employers are required to provide annual health checkups for workers in accordance with the "Industrial Safety and Health Law," which also mandates that an occupational physician be assigned to companies employing at least 50 workers. The annual medical examination includes testing for the early detection of cardiovascular risk factors such as hypertension, dyslipidemia, diabetes, and the metabolic syndrome. This approach has successfully contributed to the extremely low incidence of coronary artery disease among Japanese workers. However, problems such as poor health and the low rate of participation in health checkups among small-scale companies still persist. Furthermore, although most wellness delivery systems in Japan employ strategies targeting high-risk individuals, instituting a strategy addressing the broader population irrespective of screening may be effective in reducing disease risk in the overall population. As a future direction, we should therefore develop practical methods for implementing a population strategy. © 2014 Elsevier Inc.

IMPORTANCE Previous studies have suggested an association between vegetarian diets and lower blood pressure (BP), but the relationship is not well established. OBJECTIVE To conduct a systematic review and meta-analysis of controlled clinical trials and observational studies that have examined the association between vegetarian diets and BP. DATA SOURCES MEDLINE andWeb of Science were searched for articles published in English from 1946 to October 2013 and from 1900 to November 2013, respectively. STUDY SELECTION All studiesmet the inclusion criteria of the use of (1) participants older than 20 years, (2) vegetarian diets as an exposure or intervention, (3) mean difference in BP as an outcome, and (4) a controlled trial or observational study design. In addition, none met the exclusion criteria of (1) use of twin participants, (2) use of multiple interventions, (3) reporting only categorical BP data, or (4) reliance on case series or case reports. DATA EXTRACTION AND SYNTHESIS Data collected included study design, baseline characteristics of the study population, dietary data, and outcomes. The data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES Net differences in systolic and diastolic BP associated with the consumption of vegetarian diets were assessed. RESULTS Of the 258 studies identified, 7 clinical trials and 32 observational studiesmet the inclusion criteria. In the 7 controlled trials (a total of 311 participants; mean age, 44.5 years), consumption of vegetarian diets was associated with a reduction in mean systolic BP (?4.8 mmHg; 95%CI, ?6.6 to ?3.1; P < .001; I2 = 0; P = .45 for heterogeneity) and diastolic BP (?2.2 mmHg; 95%CI, ?3.5 to ?1.0; P < .001; I2 = 0; P = .43 for heterogeneity) compared with the consumption of omnivorous diets. In the 32 observational studies (a total of 21 604 participants; mean age, 46.6 years), consumption of vegetarian diets was associated with lower mean systolic BP (?6.9mmHg; 95%CI, ?9.1 to ?4.7; P < .001; I2 = 91.4; P < .001 for heterogeneity) and diastolic BP (?4.7mmHg; 95%CI, ?6.3 to ?3.1; P < .001; I2 = 92.6; P < .001 for heterogeneity) compared with the consumption of omnivorous diets. CONCLUSIONS AND RELEVANCE Consumption of vegetarian diets is associated with lower BP. Such diets could be a useful nonpharmacologic means for reducing BP. Copyright © 2014 American Medical Association. All rights reserved.

Background: High-density lipoprotein-cholesterol (HDL-C) is a negative risk factor for cardiovascular events. Although several homogeneous HDL-C assays are available, their accuracy has not been validated, particularly in subjects with disease. We aimed to clarify whether HDL-C concentrations measured by homogeneous assays [HDL-C (H)] agree with those determined by the reference measurement procedures [HDL-C (RMP)] using ultracentrifugation and precipitation with heparin-manganese reagent in fresh clinical samples. Methods: HDL-C concentrations in samples from 48 healthy subjects and 119 subjects with disease were determined using 12 homogeneous assays and RMPs. Results: All reagents showed excellent intra- and inter-assay CVs (<2.23%) for two pooled sera. Furthermore, the mean bias was within ±1.0% in nine reagents using samples from healthy subjects and in eight reagents using samples from subjects with disease. In a single HDL-C (H) determination, the total error requirement of the National Cholesterol Education Program (95% of results<13%) was fulfilled in nine reagents using samples from healthy subjects and six reagents in those from subjects with disease. Error component analysis revealed that only one reagent exceeded ±10% total error in samples from healthy subjects, whereas four reagents exceeded this error in samples from subjects with disease. Correlations between HDL-C (H) and HDL-C (RMP) revealed that the slopes were within 1.00±0.06 in six reagents in healthy subjects, and eight reagents in subjects with disease. Conclusions: Except for three reagents, HDL-C (H) agrees well with HDL-C (RMP) in subjects with common disease, but not in those with extremely low HDL-C or abnormal HDL composition. © 2014 The Authors.

Background and aims The European Society of Cardiology developed prediction models (SCORE) for low- and high-risk populations in the European countries. However, whether or not these models are valid in different ethnicities is unknown. We aimed to evaluate the performance of the low-risk SCORE model in the general Japanese population. Methods Healthy middle-aged Japanese participating in the NIPPON DATA80 cohort had been observed. The predicted 10-year cardiovascular death risk was calculated using the low-risk SCORE model for the overall population as well as for each gender individually. The model performance of the low-risk SCORE model was evaluated with the Harrel's c-statistics for discrimination and the Grønnesby and Borgan goodness-of-fit test for calibration. Results A total of 4842 participants aged 40–64 years old and 47,606 person-years were evaluated in our study. 203 (4.19%) died within the ten-years of follow-up and 44 (0.91%) CV deaths were observed. The low-risk SCORE model in the overall population had reasonable discrimination (c statistics 0.72, 95% CI 0.71–0.73) but poor calibration (R2, 0.67, Chi-square value 6.15, p = 0.01). Discrimination was reasonable in both men (c statistics 0.71, 95% CI 0.69–0.73) and women (c statistics 0.71, 95% CI 0.70–0.73). However, calibration was poor in men (R2, 0.22, Chi-square value 0.749, p = 0.38) compared to women (R2, 0.96, Chi-square value 1.39, p = 0.24). Conclusions Although the low-risk SCORE model performs reasonably well in women, the SCORE models generally overestimated the risk of cardiovascular death risk in the Japanese general population.

Little is known about the magnitude and nature of the combined effect of chronic kidney disease (CKD) and smoking on cardiovascular diseases. We studied this in a Japanese population using a pooled analysis of 15,468 men and 19,154 women aged 40-89 years enrolled in 8 cohort studies. The risk of mortality from all-causes and cardiovascular disease was compared in 6 gender-specific categories of baseline CKD status (non-CKD or CKD) and smoking habits (lifelong never smoked, former smokers, or currently smoking). CKD was defined as a decreased level of estimated glomerular filtration rate (under 60 ml/min per 1.73 m 2) and/or dipstick proteinuria. Hazard ratios were estimated for each category, relative to never smokers without CKD. During the follow-up period (mean 14.8 years), there were 6771 deaths, 1975 of which were due to cardiovascular diseases. In both men and women, current or former smokers with CKD had the first or second highest crude mortality rates from all-cause and cardiovascular diseases among the 6 categories. After adjustment for age and other major cardiovascular risk factors, the hazard ratios in male and female current smokers with CKD were 2.26 (95% confidence interval, 1.95-2.63) and 1.78 (1.36-2.32) for all-causes, and 2.66 (2.04-3.47) and 1.71 (1.10-2.67) for cardiovascular diseases, respectively. Thus, coexistence of CKD and smoking may markedly increase the risk of all-cause and cardiovascular mortality.

Because few studies have developed food frequency questionnaires (FFQ) and examined their reliability for Japanese urban populations, FFQ developed for urban Japanese populations may show reasonable reliability for estimating intakes of nutrients and food groups. Therefore, the objective of this study was to examine the reliability of an FFQ developed for a prospective cohort study in a Japanese urban area. A total of 29 men and 29 women aged 47 to 78 years were selected from participants in the Suita study from February 1997 to February 1998. Seven-consecutive-day dietary records (DR) was collected in each season (28-day DR). The FFQ were administered 3 times in total in each season, except in autumn. We calculated Spearman correlation coefficients to assess the validation of the first and third FFQ compared with 28-day DR and to assess the repeatability for 3-, 6-, and 9-month intervals. Reasonable validity of each FFQ compared with 28-day DR were observed for energy intake and for 27 nutrients, and 11 food groups were selected. Median (range) Spearman rank correlation coefficients for energy-adjusted nutrient and food group intakes of the first FFQ were 0.52 (0.14-0.88) and 0.53 (0.24-0.74), and those of the third FFQ were 0.51 (0.07-0.84) and 0.57 (0.16-0.75), respectively. The repeatability of each interval was relatively good; median (range) Spearman correlation coefficients of nutrients for 3-, 6-, and 9-month intervals were 0.67 (0.40-0.85), 0.63 (0.25-0.93), and 0.62 (0.31-0.87), respectively; those for food groups were 0.58 (0.42-0.76), 0.56 (0.24-0.80), and 0.65 (0.30-0.76), respectively. In conclusion, this FFQ is useful for evaluating the associations of nutrient and food intakes with cardiovascular diseases and their risk factors in Japanese urban populations.

© 2019 Wolters Kluwer Health, Inc. All rights reserved. Objective:We conducted a cross-sectional study to clarify whether home blood pressure (HBP) is more strongly associated with coronary artery calcification (CAC) than accurately measured office blood pressure (OBP) among the general population of Japanese men.Methods:We analyzed the data of 919 Japanese male participants who were randomly selected from general population (mean age 64.5 years). OBP was measured twice consecutively by a trained nurse using electrical device after 5 min of complete rest alone in a sitting position in a silent room. The participants were asked to measure HBP with an electrical device once in the morning during 7 consecutive days. CAC was assessed using computed tomography. Presence of CAC was defined as Agatston score at least 10. We calculated odds ratios for the presence of CAC per one SD higher OBP and HBP adjusted for age and other cardiovascular risk factors.Results:The mean systolic OBP (SD) and HBP (SD) were 136.8 (19.0) and 137.2 (18.5) mmHg, respectively, without statistical difference between the two (P = 0.595). OBP and HBP were highly correlated (r = 0.74 P < 0.001). CAC was found in 454 (49.4%) participants. Multivariable-adjusted odds ratios [95% confidence interval (CI)] for the presence of CAC were comparable between OBP (1.32, 95% CI: 1.12-1.56) and HBP (1.35, 95% CI: 1.14-1.60) (P heterogeneity = 0.813).Conclusion:The strength of association of accurately measured OBP with CAC was comparable with that of HBP among randomly selected male general population aged 40-79 years.

© 2019 Elsevier Inc. Aims: To test a hypothesis that women with diabetes mellitus (DM)versus those without DM had a significantly higher risk of heart disease (HD), stroke and all-cause mortality than their male counterparts in the U.S. as well as in Japan. Methods: We analyzed two nationally representative datasets, one from the U.S. NHANES III cohort (n = 13,169), and the other from the Japan NIPPON DATA90 cohort (n = 7445). Hazard ratios (HRs)of DM for risk of mortality and sex-DM interaction effect on mortality were analyzed prospectively using Cox's proportional hazards regression models. Results: Patients with DM had significantly higher mortality from HD, stroke and all-cause mortality in the U.S. and in Japan. However, the HRs of DM versus non-DM for HD and all-cause mortality were significantly higher in women compared to men in the U.S. (sex-DM interaction: HR = 1.59, p = 0.01, and 1.24, p = 0.045 for HD and all-cause mortality), but the sex-DM interaction effect was not statistically significant in the Japanese cohort. Discussion: Patients with DM had a significantly higher risk of mortality than those without DM in the U.S. and Japan. However, women with DM versus those without DM had a higher relative risk of HD and all-cause mortality than their counterparts in men in the U.S, but this sex difference by DM status was not observed in the Japanese cohort. Whether the sex-difference effect of DM on HD and all-cause mortality is due to a difference in metabolic disorders between the two populations warrants consideration and further studies.

© 2019 The Authors Aims: To calculate process quality measures of diabetes care in Japan using nationwide exclusive claims database. Methods: Using the National Database of health insurance claims during 2015–2016, the proportions of outpatients who received recommended examinations at least annually among those with regular antidiabetic medication were calculated as quality indicators, reported altogether and by prefecture and institutional certification (from the Japan Diabetes Society). Distributions of institutional-level quality indicators were also reported. Results: Among 4,154,452 outpatients, 96.7% underwent HbA1c or glycated albumin examination. Retinopathy examination was conducted among 46.5% of patients [prefecture (range): 37.5%–51.0%, institutional certification: 44.8% (without) vs. 59.8% (with)]. Urinary qualitative examination was conducted among 67.3% of patients at institutions with <200 beds (prefecture: 54.1%–81.9%, institutional certification: 66.8% vs. 92.8%), whereas urinary quantitative albumin or protein examination was conducted among 19.4% of patients (prefecture: 10.8%–31.6%, institutional certification: 18.7% vs. 54.8%). Distributions of institutional-level quality indicators showed that most institutions without institutional certification seldomly order urinary quantitative examination. Conclusions: Although the quality indicator for glycaemic control examination was favourable, some aspects of diabetes care were suboptimal and varied greatly by prefecture and institution; individual and organisational efforts to improve quality of diabetes care would be needed in Japan.

© 2020 Elsevier B.V. Background and aims: Dysfunctional high-density lipoprotein (HDL) is a risk factor for cardiovascular disease (CVD) beyond HDL concentrations. Recently, a novel method has been introduced to measure LOX-1 ligand containing apolipoprotein AI (LAA), which is an indicator of various types of modified HDL with binding capacity to LOX-1 and related to impaired anti-atherogenic functions of HDL. This study aimed to examine the relationship between LAA as a novel marker of dysfunctional HDL and coronary artery calcification (CAC). Methods: We selected 910 community-dwelling Japanese men aged 40–79 years without a history of CVD. The odds ratios per 1SD of LAA for the presence of CAC (Agatston score >10) were estimated using logistic regression model adjusted for confounders, including HDL-C or HDL particle (HDL-P) concentration. In addition, we performed further analysis stratified by age (<65 and ≥ 65 years). Results: The mean age of the participants was 63.6 years, and the median LAA was 187.0 ng/mL. The prevalent CAC was 46.2%. The multivariable adjusted odds ratio (95% confidence interval) per 1SD of LAA for CAC was 1.14 (0.96–1.36) for all participants. After stratification by age, multivariable adjusted odds ratios per 1SD of LAA were 1.34 (1.02–1.76) and 0.97 (0.77–1.23) in men aged <65 and ≥ 65 years, respectively. Conclusions: The present study showed that LAA was associated with CAC independent of HDL-C or HDL-P in middle-aged Japanese men. This finding suggests that LAA might be an early marker for CVD events. Future longitudinal studies are warranted.

We examined whether the number of teeth could be a surrogate marker for metabolic syndrome (MetS) risk in cross-section. A total of 3771 individuals from the general urban Japanese population (1690 men, 2081 women; mean age 67.1 ± 11.0 years) participated in this study. Participants were diagnosed with MetS with three or more components hypertension, hyperglycemia, lipid metabolism abnormality, and abnormal abdominal girth. Questionnaires were administered to determine the number of teeth, smoking status, drinking status, and past illnesses. To clarify the relationships between the number of teeth and the presence of MetS components, we divided subjects into two groups: those with less than 20 residual teeth and those with 20 or more, then statistical analyses (Mantel-Haenszel tests and logistic regression analysis) were performed. MetS were higher for those with ≤19 teeth than those with ≥20 teeth when examining all participants and women-only groups. Hyperglycemia, low HDL cholesterol, high triglycerides, and diagnosis with MetS were all significantly higher in the ≤19 teeth group for both sexes combined and for women. These results suggest that less than 20 teeth may be a surrogate marker for MetS risk, but further studies on gender differences and pathological background are needed.

Purpose: This study aimed to examine the association between sleep duration and quality and sarcopenia, assessed by factors such as low muscle mass (LMM), low muscle strength (LMS), and low physical performance (LPP) among older community-dwellers in Japan. Methods: In this cross-sectional study, a total of 2,069 (men, 902; women, 1,167) participants aged 65 to 80 years were included. Sarcopenia and each low physical function were defined using the definitions of the Asian Working Groups of Sarcopenia 2019. Sleep duration was stratified into three categories: short sleep (<6 h), normal sleep (6-8 h), and long sleep (>8 h). Sleep quality was classified into two groups based on 8-item Athens Insomnia Scale score: insomnia (≥6), and non-insomnia (<6). We analyzed the association between sleep parameters and sarcopenia, including low physical functions, by logistic regression analysis. Results: Compared to normal sleepers, long sleepers had a positive association with sarcopenia (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.25-3.58). In particular, long sleep was strongly associated with LMS (OR 1.77, 95%CI 1.07-2.94) and LPP (OR 1.90, 95%CI 1.25-2.88). On the other hand, poor sleep quality was not associated with sarcopenia in long sleepers, but in normal sleepers. Conclusions: Long sleep was associated with sarcopenia, including LMS and LPP. However, in long sleepers, insomnia was not associated with sarcopenia or any of its components.

The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35–74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study uses an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants, and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability and functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women’s health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.

Background: Because few have reported the prognostic significance of cardiac magnetic resonance imaging (CMR) for idiopathic pulmonary arterial hypertension (IPAH), in this study we evaluated the value of CMR measurements as a prognostic predictor of IPAH before starting intravenous prostacyclin therapy. Methods and Results: A total of 121 consecutive CMR studies for evaluating right ventricular (RV) function were reviewed. Forty-one patients were diagnosed with IPAH and served as the study group. Factors, such as age, sex, New York Heart Association functional class (NYHAFC), 6-min walk test, plasma brain natriuretic peptide level, serum uric acid level and CMR measurements were analyzed as predictors of first hospitalization and death. The mean follow- up period was 1,350±769 days. Nine patients were hospitalized because of heart failure, and 4 patients died from cardiopulmonary causes. The univariate analyses suggested that the left ventricular (LV) mass index, the left and right ventricular end-diastolic volume indices (LVEDVI, RVEDVI), the LV and RV end-systolic volume indices (LVESVI, RVESVI) and NYHAFC predicted the risk for hospitalization and that RVEDVI, RVESVI and NYHAFC predicted mortality. The multivariate analyses suggested that RVEDVI and NYHAFC are independent predictors of both hospitalization and mortality. The effects of RVEDVI and NYHAFC on hospitalization were not substantially affected by the concomitant medication. Conclusions: In IPAH patients, the RVEDVI predicts both hospitalization for right heart failure and mortality before initiating intravenous prostacyclin therapy.

Background Cohort studies with metabolomics data are becoming more widespread, however, large-scale studies involving 10,000s of participants are still limited, especially in Asian populations. Therefore, we started the Tsuruoka Metabolomics Cohort Study enrolling 11,002 community-dwelling adults in Japan, and using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography–mass spectrometry. The CE-MS method is highly amenable to absolute quantification of polar metabolites, however, its reliability for large-scale measurement is unclear. The aim of this study is to examine reproducibility and validity of large-scale CE-MS measurements. In addition, the study presents absolute concentrations of polar metabolites in human plasma, which can be used in future as reference ranges in a Japanese population. Methods Metabolomic profiling of 8,413 fasting plasma samples were completed using CE-MS, and 94 polar metabolites were structurally identified and quantified. Quality control (QC) samples were injected every ten samples and assessed throughout the analysis. Inter- and intra-batch coefficients of variation of QC and participant samples, and technical intraclass correlation coefficients were estimated. Passing-Bablok regression of plasma concentrations by CE-MS on serum concentrations by standard clinical chemistry assays was conducted for creatinine and uric acid. Results and conclusions In QC samples, coefficient of variation was less than 20% for 64 metabolites, and less than 30% for 80 metabolites out of the 94 metabolites. Inter-batch coefficient of variation was less than 20% for 81 metabolites. Estimated technical intraclass correlation coefficient was above 0.75 for 67 metabolites. The slope of Passing-Bablok regression was estimated as 0.97 (95% confidence interval: 0.95, 0.98) for creatinine and 0.95 (0.92, 0.96) for uric acid. Compared to published data from other large cohort measurement platforms, reproducibility of metabolites common to the platforms was similar to or better than in the other studies. These results show that our CE-MS platform is suitable for conducting large-scale epidemiological studies.

Abstract: Background/objective: Egg intake was associated with serum total cholesterol adjusted for age (aTCH) and total mortality in women, but not in men, using data from NIPPON DATA (ND) 80 which followed up for 14 years. Re-evaluation of these associations in a different cohort is needed. Abstract: Subject/methods: We analyzed the associations of egg intake with aTCH and cause-specific and total mortality using the ND90 data set with a 15-year follow-up. A nutritional examination was done at the baseline in 1990 using the food-frequency method and by weighed food records. We followed 4686 female participants (ages ≥30 years), with no history of stroke or myocardial infarction (mean age 52.8 years) for 15 years. Abstract: Results: The participants were divided into 5 egg intake groups (<1/w, 1–2/w, 1/2d, 1/d, and ≥2/d). There were 203, 1462, 1594, 1387, and 40 women in each group, respectively. Egg intake was not associated with aTCH (P = 0.886). There were 183 cardiovascular disease (CVD), 210 cancer, and 599 total mortality cases during follow-up. Cox analysis, adjusted for background factors, found egg intake was directly associated with total and cancer mortality (HR in the ≥2/d vs. the 1 egg/d group: total, 2.05 (95% CI: 1.20–3.52); cancer, 3.20 (1.51–6.76)), and that cancer mortality in the 1–2/w group was significantly less than that in the 1 egg/d group (0.68 (0.47–0.97)). Egg intake was not associated with CVD mortality. Abstract: Conclusions: Egg intake was associated with cancer and total mortality. Reducing egg intake may have some definitive health benefits in women in Japan, at least.

Equol, a metabolite of the dietary isoflavone daidzein, is produced by the action of gut bacteria in some individuals who are termed as equol-producers. It is proposed to have stronger atheroprotective properties than dietary isoflavones. We examined a cross-sectional association of dietary isoflavones and equol-producer status with coronary artery calcification (CAC), a biomarker of coronary atherosclerosis, among men in Japan. A population-based sample of 272 Japanese men aged 40-49 years recruited from 2004 to 2007 was examined for serum isoflavones, serum equol, CAC and other factors. Equol-producers were classified as individuals having a serum level of equol >83 nm. The presence of CAC was defined as a coronary Ca score ≥10 Agatston units. The associations of dietary isoflavones and equol-producers with CAC were analysed using multiple logistic regression. The median of dietary isoflavones, equol and CAC were 512·7 (interquartile range (IQR) 194·1, 1170·0), 9·1 (IQR 0·10, 33·1) and 0·0 (IQR 0·0, 1·0) nm, respectively. Prevalence of CAC and equol-producers was 9·6 and 16·0 %, respectively. Dietary isoflavones were not significantly associated with CAC. After multivariable adjustment, the OR for the presence of CAC in equol-producers compared with equol non-producers was 0·10 (95 % CI 0·01, 0·90, P<0·04). Equol-producers had significantly lower CAC than equol non-producers, but there was no significant association between dietary isoflavones and CAC, suggesting that equol may be a key factor for atheroprotective properties of isoflavones in Japanese men. This finding must be confirmed in larger studies or clinical trials of equol that is now available as a dietary supplement.