Seven-plus hours of daily sedentary time and the subsequent risk of breast cancer: Japan Multi-Institutional Collaborative Cohort Study.

This study aimed to investigate the association between daily sedentary time and the risk of breast cancer (BC) in a large Japanese population. The participants were 36,023 women aged 35-69 years from the Japan Multi-Institutional Collaborative Cohort Study. Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for BC incidence in relation to time spent sedentarily (categorical variables: <7 and ≥7 hours/day [h/d]). Additionally, the associations of BC incidence to the joint effect of sedentary time with each component of physical activity, such as leisure-time metabolic equivalents (METs), frequency of leisure-time physical activity, and daily walking time, were examined. During 315,189 person-years of follow-up, 554 incident cases of BC were identified. When compared to participants who spent <7 h/d sedentary, those who spent ≥7 h/d sedentary have a significantly higher risk of BC (HR, 1.36; 95% CI, 1.07-1.71). The corresponding HRs among participants who spent ≥7 h/d sedentary with more physical activity, such as ≥1 h/d for leisure-time METs, ≥3 days/week of leisure-time physical activity, and ≥1 h/d of daily walking were 1.58 (95% CI, 1.11-2.25), 1.77 (95% CI, 1.20-2.61), and 1.42 (95% CI, 1.10-1.83), respectively, compared with those who spent <7 h/d sedentary. This study found that spending ≥7 h/d of sedentary time is associated with the risk of BC. Neither leisure-time physical activity nor walking had a BC-preventive effect in those with ≥7 h/d of sedentary time.

The gut microbiota and coronary artery calcification in Japanese men.

BACKGROUND: The gut microbiota differs between patients with coronary artery disease (CAD) and healthy controls; however, it currently remains unclear whether these differences exist prior to the onset of CAD. We herein investigated the gut microbiota associated with subclinical coronary artery calcification (CAC) in a Japanese population. METHODS: A total of 663 Japanese men were enrolled in this cross-sectional study. Computed tomography and gut microbiology tests were performed, and CAC scores were calculated using the Agatston method. Participants were categorized into 4 groups based on their CAC scores: CAC = 0, 0

Relationship Between Hemoglobin Concentration and Cardiovascular Disease Mortality in a 25-Year Follow-up Study of a Japanese General Population　- NIPPON DATA90.

BACKGROUND: Deviations of hemoglobin from normal levels may be a factor in cardiovascular disease (CVD) risk; however, conclusive evidence is lacking. In addition, preclinical conditions may influence hemoglobin concentrations, but studies focusing on reverse causation are limited. Thus, we examined the relationship between hemoglobin concentrations and CVD mortality risk, considering reverse causation.Methods and Results: In a prospective cohort representative of the general Japanese population (1990-2015), we studied 7,217 individuals (mean age 52.3 years; 4,219 women) without clinical CVD at baseline. Participants were categorized into sex-specific hemoglobin quintiles (Q1-Q5) and data were analyzed using the Cox proportional hazards model adjusted for possible confounders. During a 25-year follow-up, 272 men and 334 women died from CVD. Adjusted hazard ratios for CVD mortality across sex-specific quintiles, using Q3 as the reference, were significantly higher for Q1 (1.40; 95% confidence interval [CI] 1.08-1.82) and Q5 (1.49; 95% CI 1.14-1.96), and remained significant after excluding deaths within the first 5 years of follow-up to consider reverse causation (1.35 [95% CI 1.02-1.79] and 1.45 [95% CI 1.09-1.94], respectively). A similar U-shaped association was seen between transferrin saturation levels and CVD mortality, but after excluding deaths within the first 5 years the association was significant only for Q1. CONCLUSIONS: Low and high hemoglobin concentrations were associated with an increased risk of CVD mortality.

[Development of a new method for assessing the availability of low-sodium foods in Japan].

Objectives　Food environment improvement involving salt reduction requires improving access to and labeling low-sodium foods. Assessing the implementation status of these measures is also necessary. However, to date, no established methods exist for assessing the availability of low-sodium foods in communities. In this study, we aimed to devise a survey on the availability of low-sodium foods as a community food environment assessment method in order to establish common assessment methods, criteria, and practical measures, as well as standardization nationwide.Methods　A preliminary survey on the availability of low-sodium foods was conducted in Kitakyushu City in four stores with nationwide representation. Consent for providing information on handled product lists was obtained. The on-site lists collected through direct investigation by surveyors were compared with the handled product lists provided by the stores and analyzed to identify survey challenges and examine feasibility and the potential for accuracy. The definition of low-sodium foods, which emerged as a challenge in the preliminary survey, was confirmed. Preliminary survey data were carefully reviewed to establish classification criteria for low-sodium foods and create a low-sodium food list to serve as a reference for on-site surveys. Forms for recording the results of on-site surveys and a survey manual were developed. Registered dietitians conducted on-site surveys using the manual to confirm its applicability.Results　The preliminary survey results revealed that the on-site lists had fewer omissions and greater feasibility than store-provided lists. After clearly defining low-sodium foods, we established classification criteria (three major categories, seven subcategories, and 37 minor categories) considering the ease of on-site investigations and purchases. Three forms for recording survey results were developed, including a standard input form allowing detailed documentation of the availability of individual low-sodium foods, an aggregation form for a quantitative assessment of low-sodium foods availability, and a display form visualizing the availability of low-sodium foods by store. Furthermore, a survey manual was developed explaining the purpose and approach of the low-sodium foods availability survey, definition and classification criteria for low-sodium foods, and the three forms for recording survey results. Findings indicated that all registered dietitians could conduct on-site surveys using the manual and successfully collect and organize data.Conclusion　On-site surveys using the manual and documentation forms enabled easy and accurate assessments of low-sodium foods availability. Thus, this standardized method to assess the availability of low-sodium foods could be a food environment assessment method for regional salt reduction initiatives.

Risk Factors That Most Accurately Predict Coronary Artery Disease Based on the Duration of Follow-up　- NIPPON DATA80.

BACKGROUND: This study assessed sex-specific time-associated changes in the impact of risk factors on coronary artery disease (CAD) mortality in a general population over long-term follow-up.Methods and Results:A prospective longitudinal cohort study was conducted on representative Japanese populations followed up for 29 years. Data from 8,396 participants (3,745 men, 4,651 women) were analyzed. The sex-specific multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of 4 risk factors (smoking, diabetes, serum total cholesterol [TC], and systolic blood pressure [SBP]) for CAD mortality were calculated at baseline and at 10, 15, 20, 25, and 29 years of follow-up. In men, smoking (HR 3.23; 95% CI 1.16-9.02) and a 1-SD increase in TC (HR 1.82; 95% CI 1.29-2.57) were strongly associated with a higher risk of CAD in the first 10 years, but this association decreased over time. Diabetes (HR 2.30; 95% CI 1.37-3.85) and a 1-SD increase in SBP (HR 1.23; 95% CI 1.00-1.50) were strongly correlated with a higher risk of CAD after 29 years). In women, diabetes was correlated with CAD after 20 years (HR 2.53; 95% CI 1.19-5.36) and this correlation persisted until after 29 years (HR 2.47; 95% CI 1.40-4.35). CONCLUSIONS: The duration of follow-up needed for the accurate assessment of risk factors for CAD mortality varies according to risk factor and sex.

Time-Related Changes in Relationships Between the Keys Score, Dietary Lipids, and Serum Total Cholesterol in Japan　- NIPPON DATA80/90/2010.

BACKGROUND: In recent years, individuals with high serum total cholesterol (TC) have been more likely to modify their diet by reducing their intake of dietary lipids. The aim of this study was to investigate time-related changes in the relationships between the Keys score, dietary lipids, and TC between 1980 and 2010 in representative Japanese populations. Methods and Results: We used 3 cross-sectional cohort studies conducted among Japanese representative populations in 1980, 1990, and 2010 (NIPPON DATA80/90/2010) for the analyses. We analyzed data for 10,365, 7,714, and 2,657 participants, respectively, in each dataset. The relationships between TC and the Keys score (calculated by dietary lipids, cholesterol, and energy intake)/dietary lipids were examined. In men, a 1-unit higher Keys score correlated with 0.92 mg/dL and 0.64 mg/dL TC in 1980 and 1990, respectively, but not in 2010. In women, a 1-unit higher Keys score correlated with 0.70 mg/dL and 0.74 mg/dL TC in 1980 and 1990, respectively, but with 0.33 mg/dL in 2010. In men and women, dietary cholesterol, saturated fatty acid (SFA), and trans fatty acid (TFA) levels were positively associated with TC concentrations in 1980 and 1990, but not in 2010. CONCLUSIONS: In these representative Japanese populations, a higher Keys score as well as dietary cholesterol, SFA, and TFA levels correlated with higher TC concentrations in 1980/1990, but the relationships were weaker or not observed in 2010.

High blood pressure and colorectal cancer mortality in a 29-year follow-up of the Japanese general population: NIPPON DATA80.

Onco-hypertension has been proposed, although associations of high blood pressure (BP) with cancer risk remain inconsistent. We examined associations of high BP with risk of mortality from stomach, lung, colorectal, liver, and pancreatic cancers independent of possible confounders in an analysis that excluded deaths within the first 5 years of follow-up to consider the reverse causality. In a prospective cohort representative of the general Japanese population (1980-2009), we studied 8088 participants (mean age, 48.2 years; 56.0% women) without clinical cardiovascular disease or antihypertensive medication at baseline. Fine-Gray competing risks regression was used to estimate hazard ratios for 10 mmHg higher BP adjusted for confounders including smoking, alcohol-drinking, obesity, and diabetes mellitus. During 29-year follow-up, 159 (2.0%), 159 (2.0%), 89 (1.1%), 86 (1.1%), and 68 (0.8%) participants died from stomach, lung, colorectal, liver, and pancreatic cancers, respectively. We observed a positive association of high BP with risk of colorectal cancer mortality but not with mortality risks from any other cancers. The association with colorectal cancer mortality for systolic and diastolic BP was evident in those aged 30-49 years (hazard ratios 1.43 [95% confidence interval, 1.22-1.67] and 1.86 [1.32-2.62], respectively) but not in those aged 50-59 years and ≥60 years (P for age interaction <0.01 for systolic and diastolic BP). The associations with colorectal cancer mortality were similar in the analyses stratified by smoking, alcohol-drinking, obesity, and diabetic status. In conclusion, high BP among young to middle-aged adults was independently associated with risk of colorectal cancer mortality later in life.

Association of Pro-Inflammatory Diet with Long-Term Risk of All-Cause and Cardiovascular Disease Mortality: NIPPON DATA80.

AIM: A pro-inflammatory diet may increase the risk of cardiovascular disease (CVD) and all-cause mortality. However, this remains inconclusive as there is yet no study using a dietary record method that has been conducted in a large general population. Furthermore, an underestimation of the pro-inflammatory diet may exist due to the unmeasured effect of salt intake. Thus, in this study, we aimed to examine how pro-inflammatory diet is associated with the long-term risk of all-cause and CVD mortality in a representative Japanese population. METHODS: A national nutrition survey was conducted throughout Japan in 1980. After considering the exclusion criteria, 9284 individuals (56% women aged 30-92 years) were included in this study. In total, 20 dietary parameters derived from 3-day weighed dietary records were used to calculate the dietary inflammatory index (DII). The causes of death were monitored until 2009. The Cox proportional hazards model was used to determine multivariable-adjusted hazard ratios (HRs). Stratified analysis according to salt intake level was also performed. RESULTS: Compared with the lowest quartile of DII, multivariable-adjusted HRs (95% confidence intervals) in the highest quartile were 1.28 (1.15, 1.41), 1.35 (1.14, 1.60), 1.48 (1.15, 1.92), 1.62 (1.11, 2.38), and 1.34 (1.03, 1.75) for all-cause mortality, CVD mortality, atherosclerotic CVD mortality, coronary heart disease mortality, and stroke mortality, respectively. Stratified analysis revealed stronger associations among individuals with higher salt intake. CONCLUSIONS: As per our findings, a pro-inflammatory diet was determined to be positively associated with the long-term risk of all-cause and CVD mortality in a representative Japanese population. Thus, considering both salt intake and pro-inflammatory diet is deemed crucial for a comprehensive assessment of CVD risk.

Mortality from major causes and lifestyles by proportions of public assistance recipients among 47 prefectures in Japan: Ecological panel data analysis from 1999 to 2016.

Objective: Comprehensive investigations of correlations between subnational socioeconomic factors and trends in mortality and lifestyle are important for addressing public health problems. Methods: Forty-seven prefectures in Japan were divided into quartiles based on the proportion of public assistance recipients (PPAR). Age-standardized mortality from all causes, cancer, heart disease, and stroke in each prefecture were averaged for these quartiles in 2000, 2005, 2010, and 2015. Data from the National Health and Nutrition Survey were obtained for the following periods: 1999-2001, 2003-2005, 2007-2009, 2012, and 2016. Body mass index (BMI), intake of total energy, vegetable and salt, step count, and prevalence of current smoking and drinking for individuals aged 40-69 years age range were standardized for each prefecture and averaged by quartile. A two-way analysis of variance was used to assess differences in mortality and lifestyle across different years or periods, and quartiles. Results: Mortality rates decreased, with the first (lowest) quartile showing the lowest rates, across all causes, cancer and heart diseases in both sexes. BMI exhibited an increase in men, whereas, BMI in women and other lifestyle factors in both sexes, excluding smoking and drinking in women, exhibited a decrease. BMI, vegetable and salt intake, total energy intake in men, and smoking in women varied across quartiles. Lower quartiles exhibited lower BMI and smoking prevalence but higher energy, vegetables, and salt intake. Conclusions: PPAR exhibited favorable trends and significant differences in mortality related to all causes, cancer and heart disease across both sexes, along with BMI among women.

Association of gut microbiome with COPD in Japanese male residents: the SESSA study.

Background: Altered gut microbiota may contribute to COPD development or progression. Herein, we investigated the association of gut microorganisms with COPD, taking into account the impact of smoking status. Methods: This cross-sectional observational study was a part of the Shiga Epidemiological Study of Subclinical Atherosclerosis, a population-based cohort study of Japanese men aged 46-76 years, conducted from 2010 to 2016. The gut microbiome, determined using 16S rRNA gene sequencing, was compared among 99 never-smokers, 306 non-COPD ever-smokers and 76 patients with COPD while adjusting for age, body mass index, ethanol consumption and treatment for type 2 diabetes mellitus. Results: The abundance of phylum Firmicutes was comparable between patients with COPD and non-COPD ever-smokers but tended to be higher in never-smokers. Similarly, the α- and ß-diversity analysis showed similarity between patients with COPD and non-COPD ever-smokers, which tended to differ from never-smokers. Discriminant analysis identified the genus [Prevotella] to be more prevalent in patients with COPD than in never-smokers or non-COPD ever-smokers. Post hoc analysis confirmed similarity of gut microbiome between COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and non-COPD ever-smokers, which was different from GOLD II. Conclusion: Smoking may alter the overall gut microbial composition, but gut microbial composition itself may not play a role in the development of COPD. Rather, specific gut bacteria, such as [Prevotella], could be a risk factor for the development of COPD; this may be a potential therapeutic target.

Small High-Density Lipoprotein and Omega-3 Fatty Acid Intake Differentiates Japanese and Japanese-Americans: The INTERLIPID Study.

AIM: To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii, in the absence of possible genetic confounders, and cross-sectionally examine the associated modifiable lifestyle factors. METHODS: Overall, 1,241 (aged 40-59 years) Japanese living in Japan and Japanese-Americans in Hawaii were included. We quantified 130 serum lipid profiles (VLDL 1-5, IDL, LDL 1-6, high-density lipoprotein [HDL] 1-4, and their subfractions) using Bruker's 1H-nuclear magnetic resonance spectrometer for the primary outcome. Modifiable lifestyle factors included body mass index (BMI), physical activity, alcohol and smoking habits, and 70 nutrient parameters. We evaluated the different lipids between the groups using partial least squares-discriminant analysis and association between extracted lipids and lifestyle factors using multivariable linear regression analysis. RESULTS: Concentrations of HDL4, HDL with the smallest particle size, were lower in Japanese than in Japanese-Americans of both sexes. Higher fish-derived omega-3 fatty acid intake and lower alcohol intake were associated with lower HDL4 concentrations. A 1% higher kcal intake of total omega-3 fatty acids was associated with a 9.8-mg/dL lower HDL4. Fish-derived docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid intake were inversely associated with HDL4 concentration. There was no relationship between country, sex, age, or BMI. CONCLUSIONS: Japanese and Japanese-Americans can be differentiated based on HDL4 concentration. High fish intake among the Japanese may contribute to their lower HDL4 concentration. Thus, HDL particle size may be an important clinical marker for coronary artery diseases or a fish consumption biomarker.

Trends in mortality from major causes and lifestyle factors by per capita prefectural income: Ecological panel data analysis from 1995 to 2016 in Japan.

In Japan, trends in mortality and lifestyle have not been fully investigated according to subnational socioeconomic factors. Forty-seven prefectures (subnational units) were divided into quartiles by annual per capita prefectural income. Age-standardized mortality from all causes, cancer, heart disease, and stroke was averaged by quartile in 1995, 2000, 2005, 2010, and 2015. Data from the National Health and Nutrition Survey were obtained for periods 1 (1995-1997), 2 (1999-2001), 3 (2003-2005), 4 (2007-2009), 5 (2012), and 6 (2016). Body mass index (BMI), the intake of vegetables and salt, the number of steps, and the prevalence of current smoking and drinking for the 40-69-year age range were standardized by 10-year age groups in the 2010 Japanese population and were averaged by quartile. Differences in mortality and lifestyle by year and period, and quartile were tested using a two-way analysis of variance. Mortality decreased in both sexes and mortality in men from all causes, cancer, and stroke differed by quartile, with mortality highest in the first (lowest) quartile. BMI in men and smoking prevalence in women increased, whereas remaining lifestyle factors except for the prevalence of drinking decreased in women. BMI and the number of steps in both sexes and current smoking prevalence in women differed by quartile, with lower quartiles showing a higher BMI and fewer step counts. In conclusion, favorable trends and significant differences in mortality from all causes, cancer, and stroke in men and BMI in women were observed by per capita prefectural income level.

Circulating plasma phospholipid fatty acid levels as a biomarker of habitual dietary fat intake: The INTERMAP/INTERLIPID Study.

BACKGROUND: Accurate assessment of fat intake is essential to examine relationships between diet and disease risk. However, estimating individual intakes of fat quantity by dietary assessment is difficult. OBJECTIVE: We assessed the association of plasma phospholipid fatty acid levels with dietary intake of fatty acids in the INTERMAP/INTERLIPID study, conducted with a standardized protocol. METHODS: The study participants were 1339 men and women ages 40-59 years from five Japanese populations one from Hawaii; four from Japan. Fatty acid intake was estimated from four standardized 24-hour dietary recalls. Plasma phospholipid fatty acid composition was analyzed by gas chromatography. We illustrated the relationship between intake and circulating fatty acid levels using Spearman's rank-correlation coefficients, mean, and median values. RESULTS: Spearman's rank-correlation coefficients between intake (g/d) and circulating fatty acid levels (µg/ml) were -0.03 to 0.21 for saturated fatty acids and monounsaturated fatty acids and -0.04 to 0.32 for trans fatty acids. The coefficients for essential n-3 and n-6 fatty acids were moderate to high, especially for eicosapentaenoic acid (EPA), 0.60; docosahexaenoic acid (DHA), 0.41; and EPA+DHA, 0.51. The circulating levels and intake of marine-derived n-3 fatty acids showed a linear association, at least for the intake of EPA+DHA up to 2.1 g/d. CONCLUSION: We observed high correlation between intake and circulating levels of marine-derived n-3 fatty acids in participants from Japanese and Japanese-American populations with high and low fish intake. Plasma phospholipid marine-derived n-3 fatty acid measurements are a simple and reliable biomarker for assessing dietary intake.

Efficacy of a meal sequence in patients with type 2 diabetes: a systematic review and meta-analysis.

INTRODUCTION: This systematic review investigated the efficacy of a meal sequence, the carbohydrate-later meal pattern (CL), on type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov until April 2020 to perform meta-analyses using random-effects models. Primary outcomes were hemoglobin A1c (HbA1c) and quality of life. Secondary outcomes were plasma concentrations of glucose, insulin and incretin 120 min after a meal, and any adverse outcomes. The revised Cochrane risk-of-bias tool and Grading of Recommendations, Assessment, Development, and Evaluation approach were used to assess the quality of individual studies and the body of evidence, respectively. The present study was registered in the UMIN Clinical Trials Registry. RESULTS: We included 230 participants in eight trials, including both trials that examined long-term changes (more than 2 months and less than 2 years) and short-term changes (in 2-hour postprandial values). CL resulted in a slight to no difference in HbA1c (mean difference (MD), -0.21% in the intervention group; 95% CI -0.44% to+0.03%), plasma glucose (MD,+4.94 mg/dL; 95% CI -8.34 mg/dL to +18.22 mg/dL), plasma insulin (MD, -3.63 µIU/mL; 95% CI -11.88 µIU/mL to +4.61 µIU/mL), plasma GLP-1 (MD, +0.43 pmol/L; 95% CI -0.69 pmol/L to +1.56 pmol/L), and plasma GIP (MD, -2.02 pmol/L; 95% CI -12.34 pmol/L to +8.31 pmol/L). All of these outcomes were of low-certainty evidence or very low-certainty evidence. None of the trials evaluated quality of life or adverse events. CONCLUSIONS: There was no evidence for the potential efficacy of recommending CL beyond standard dietary advice on T2DM. TRIAL REGISTRATION NUMBER: UMIN000039979.

Effectiveness of angiotensin converting enzyme inhibitors in preventing pneumonia: A systematic review and meta-analysis.

We performed a systematic review and meta-analysis to re-evaluate the effectiveness of angiotensin-converting enzyme inhibitors (ACE-I) in the reduction of pneumonia risk. We searched relevant publications in five databases. All studies included patients older than 18 years, who had used ACE-I as an intervention, and had assessed pneumonia. Seven RCTs (n = 8704) and 38 observational studies (n = 1,705,030) were included. The overall risk of bias was high. ACE-I-treated patients were associated with a slightly lower risk of pneumonia, both from pooled estimates of RCTs [pooled odds ratio (OR), 0.75; 95% confidence interval (CI), 0.62-0.90; low certainty of evidence] and observational studies (pooled OR, 0.85; 95% CI, 0.78-0.92; very low certainty of evidence). Considering the small effect size of ACE-I in preventing pneumonia and the low quality of the evidence, routine use of ACE-I for pneumonia prevention is not recommended.

Trends in Prevalence, Treatment, and Control of Hypertension According to 40-Year-Old Life Expectancy at Prefectures in Japan from the National Health and Nutrition Surveys.

The prevalence of hypertension has been decreasing in Japan due to improved medical treatment and a decrease in dietary salt intake. However, disparities in the prevalence, treatment, and control of hypertension are expected to occur in different regions. This study aimed to investigate the trends in the prevalence, treatment, and control of hypertension at the prefectural level of life expectancy among Japanese population. We used data from the National Health and Nutrition Survey and analysed the individual survey information of individuals aged 40-69 years by dividing it into six terms, i.e., 1995-1997, 1999-2001, 2003-2005, 2007-2009, 2012, and 2016. Prefectures were classified into four groups according to their 40-year-old life expectancy in 2000. Outcome values were standardised to the population by 10-year age groups in 2010, and they were tested by two-way analysis of variance according to six terms and life expectancies. The prevalence of hypertension tended to decrease, especially among women, whereas the treatment and control tended to improve from the first to the sixth period in both men and women. The prevalence and treatment of hypertension in men with longer life expectancy tended to be lower than that in other groups, and there was no obvious difference in the control. In women, there were no obvious differences in the prevalence, treatment, or control. Reducing the prevalence of hypertension by improving lifestyle factors, such as high salt intake in each prefecture with a relatively short life expectancy, may be important to resolve the disparity in life expectancy among prefectures.

Investigation of the urinary sodium-to-potassium ratio target level based on the recommended dietary intake goals for the Japanese population: The INTERMAP Japan.

Growing epidemiological evidence has shown an association of the urinary sodium (Na) to potassium (K) ratio (Na/K ratio) with blood pressure and cardiovascular diseases. However, no clear cutoff level has been defined. We investigated the cutoff level of the urinary Na/K ratio under different dietary guidelines for Japanese individuals, especially that endorsed by the 2020 revised Japanese Dietary Reference Intakes (DRIs). A population of 1145 Japanese men and women aged 40 to 59 years from the INTERMAP study was examined. Using high-quality standardized data, the averages of two 24 h urinary collections and four 24 h dietary recalls were used to calculate the 24 h urinary and dietary Na/K ratios, respectively. Associations between the urinary and dietary Na/K ratios were tested by sex- and age-adjusted partial correlation. The optimal urinary Na/K ratio cutoff level was determined by receiver operating characteristic (ROC) curves and sex-specific cross tables for recommended dietary K and salt. Overall, the average molar ratio of 24 h urinary Na/K was 4.3. We found moderate correlations (P < 0.001) of the 24 h urinary Na/K ratio with 24 h urinary Na and K excretion (r = 0.52, r = -0.49, respectively) and the dietary Na/K ratio (r = 0.53). ROC curves showed that a 24 h urinary Na/K ratio of approximately 2 predicted Na and K intake that meets the dietary goals of the Japanese DRIs. The range of urinary Na/K ratios meeting the dietary goals of the Japanese DRIs for both Na and K was 1.6‒2.2 for men and 1.7‒1.9 for women. Accomplishing a urinary Na/K ratio of 2 would be desirable to achieve the DRIs dietary goals for both Na and K simultaneously in middle-aged Japanese men and women accustomed to Japanese dietary habits. This observational study is registered at www.clinicaltrials.gov as NCT00005271.

Cross-sectional association of equol producing status with aortic calcification in Japanese men aged 40-79 years.

Equol is an isoflavone (ISF)-derived metabolite by the gut microbiome in certain individuals termed equol-producers (EP). Equol might be the critical anti-atherogenic component of ISFs. In a population-based study of 979 Japanese men aged 40-79 without cardiovascular (CVD) or chronic kidney disease, we measured the urinary levels of equol and ISFs. Aortic calcification (AC) in the entire aorta was assessed by electron-beam or multi-detector-row computed tomography. Subjects with log10 (urinary equol to daidzein concentration) > - 1.5 were classified as EP. EP was further classified as person with low- and high-equol. We analyzed the association between equol-producing status and AC presence, defined as AC score > 0, by the logistic regressions. We found that EP (50% of the sample) had significantly lower odds of AC presence (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.39, 0.98) compared to non-EP. This association was independent of CVD risk factors. For the dose-response association, compared to non-EP, subjects with low and high levels of equol had ORs of 0.51 (95% CI 0.30, 0.84) and 0.67 (95% CI 0.39, 1.14) after adjusting for major CVD risk factors (p for trend = 0.06). ISFs concentrations were not significantly associated with AC presence (OR: 1.18, 95% CI: 0.82, 1.69). In conclusion, EP had a significantly lower burden of AC than non-EP, while ISFs were not associated with AC presence in Japanese men aged 40-79 years.

Relationships of Alcohol Consumption with Coronary Risk Factors and Macro- and Micro-Nutrient Intake in Japanese People: The INTERLIPID Study.

Several studies have reported a J-shaped relationship between alcohol consumption and coronary heart disease (CHD) risk. However, the mechanisms of this relationship remain unclear. This study aimed to evaluate the relationships of alcohol consumption with established CHD risk factors and with macro-/micro-nutrient intake among Japanese people. Participants were 1,090 Japanese men and women aged 40-59 y enrolled in the INTERLIPID study, excluding former drinkers. Based on two 7-d alcohol records, participants were classified as non-drinkers (0 g/wk), light-drinkers (<100 g/wk), moderate-drinkers (100-299 g/wk), or heavy-drinkers (≥300 g/wk). Detailed macro-/micro-nutrient intake was evaluated using four in-depth 24-h dietary recalls and adjusted for total energy intake excluding alcohol. We analyzed the associations of CHD risk factors and nutrient intake with alcohol consumption. Serum high-density lipoprotein cholesterol and blood pressure were higher and low-density lipoprotein cholesterol was lower among those with higher alcohol consumption. J-shaped relationships with alcohol consumption were observed for the proportion of current smokers, number of cigarettes smoked, and prevalence of hypertension; these risk factors were lowest among light-drinkers. Carbohydrate and total fiber intakes were lower and protein and dietary cholesterol intakes were higher among those with higher alcohol consumption. These associations were similar for men and women. Alcohol consumption was related to nutrient intake as well as established CHD risk factors. Non-drinkers were higher on some CHD risk factors than were light-drinkers. These findings may influence the J-shaped relationship between alcohol consumption and CHD risk.