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.

Association of step counts with cognitive function in apparently healthy middle-aged and older Japanese men.

Background: Increasing physical activity may prevent cognitive decline. Previous studies primarily focused on older adults and used self-reported questionnaires to assess physical activity. We examined the relationship between step count, an objective measure of physical activity, and cognitive function in community-based middle-aged and older Japanese men. Methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis randomly recruited community-dwelling healthy men aged 40-79 years from Shiga, Japan, and measured their step counts over 7 consecutive days using a pedometer at baseline (2006-2008). Among men who returned for follow-up (2009-2014), we assessed their cognitive function using the Cognitive Abilities Screening Instrument (CASI) score. We restricted our analyses to those with valid 7-day average step counts at baseline and those who remained free of stroke at follow-up (n = 676). Using analysis of covariance, we calculated the adjusted means of the CASI score according to the quartiles of the average step counts. Results: The mean (standard deviation) of age and unadjusted CASI score were 63.8 (9.1) years and 90.8 (5.8), respectively. The CASI score was elevated in higher quartiles of step counts (90.2, 90.4, 90.6, and 91.8 from the lowest to the highest quartile, respectively, [p for trend = 0.004]) in a model adjusted for age and education. Further adjustment for smoking, drinking, and other cardiovascular risk factors resulted in a similar pattern of association (p for trend = 0.005). Conclusion: In apparently healthy middle-aged and older Japanese men, a greater 7-day average step count at baseline was associated with significantly higher cognitive function score.

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.

Smoking is associated with impaired long-term quality of life in elderly people: a 22-year cohort study in NIPPON-DATA 90.

BACKGROUND: Whether smoking is associated with worse quality of life (QoL) or not is relatively controversial. Current study is to investigate relationship between smoking and subjective QoL in a long cohort study. METHODS: NIPPON DATA 90 project collected 8383 community residents in 300 randomly selected areas as baseline data in 1990, and 4 follow-up QOL surveys and mortality statistics were performed. We conducted multinomial logistic regression analysis to compare past smoker and current smoker to never smoker, of which impaired QOL and mortality as outcomes. RESULTS: In 4 follow-ups, QOL data was collected from 2035, 2252, 2522 and 3280 participants, in 1995, 2000, 2005, 2012, respectively. In 1995 follow-up, current smoking at baseline was not associated with worse QOL. In 2000 and 2005 follow-up, smoking is significantly associated with worse QOL, OR = 2.11[95%CI: 1.33, 3.36, P<0.01], OR = 2.29[95%CI:1.38, 3.80, P < 0.001], respectively. In 2012 follow-up, smoking is not associated with QOL. Sensitivity analysis didn't change the result significantly. CONCLUSIONS: In this study we found that baseline smoking is associated worse QOL in long-follow-up.

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.

Effect of omega-3 fatty acids on cardiovascular events in high-risk patients with hypertriglyceridemia in Japan: a 3-year post-marketing surveillance study (OCEAN3 survey).

BACKGROUND: Studies on the efficacy of prescription omega-3 polyunsaturated fatty acids to reduce cardiovascular events have produced conflicting results. RESEARCH DESIGN AND METHODS: This 3-year prospective post-marketing surveillance study evaluated the effect of omega-3-acid ethyl esters (O3AEE; usual dosage 2 g/day) on cardiovascular events in high-risk statin-treated Japanese patients with hypertriglyceridemia. Statin-treated patients not receiving O3AEE were included as a reference cohort. The composite primary endpoint was cardiovascular death, myocardial infarction, stroke, angina requiring coronary revascularization, or peripheral arterial disease requiring surgery or peripheral arterial intervention. RESULTS: At 3 years, Kaplan-Meier estimated cumulative incidence of the primary endpoint was 2.5% (95% confidence interval, 2.1%-2.9%) in O3AEE-treated patients (N = 6,580) and 2.7% (2.4%-3.1%) in non-O3AEE-treated patients (N = 7,784; hazard ratio, 0.99; 95% confidence interval, 0.79-1.23). Incidence of heart failure requiring hospitalization was 0.4% with O3AEE versus 0.8% in non-O3AEE-treated patients (hazard ratio, 0.47; 95% confidence interval, 0.28-0.78; P < 0.05). CONCLUSIONS: Among patients receiving statins, cardiovascular event incidence did not differ significantly between O3AEE-treated patients and non-O3AEE-treated patients. Further studies are required before definitive conclusions can be drawn on the effect of O3AEE on cardiovascular event incidence in high-risk patients with hypertriglyceridemia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02285166.

Relationship of Higher-level Functional Capacity With Long-term Mortality in Japanese Older People: NIPPON DATA90.

BACKGROUND: Basic and instrumental activities of daily living (BADL and IADL, respectively) are known predictors of mortality. However, the relationship between higher-level functional capacity (HLFC) and mortality and related sex differences have rarely been investigated. METHODS: A prospective population-based cohort study was conducted in 1,824 older residents (≥65 years) with independent BADL from 300 randomly selected areas in Japan from 1995, and the participants were followed up until 2010. Using the Cox proportional hazards model, the relationship between HLFC and mortality risk was investigated, with adjustment for possible confounders. HLFC was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Baseline data were collected using a questionnaire or by home-visit interviews. RESULTS: During an average 12.2-year follow-up, all-cause death was observed in 836 (45.8%) participants. Impaired HLFC was significantly associated with mortality (hazard ratio [HR] 1.37; 95% confidence interval [CI], 1.13-1.65). Lower social role was significantly associated with higher mortality risk in men (HR 1.38; 95% CI, 1.13-1.68). Lower IADL and intellectual activity were significantly associated with higher mortality risk in women (HR 1.50; 95% CI, 1.15-1.95 and HR 1.46; 95% CI, 1.19-1.79, respectively). The relationship between HLFC and mortality risk showed a similar tendency among cardiovascular diseases, stroke, cancer, and pneumonia. CONCLUSION: Impaired HLFC was associated with a high risk of all-cause mortality among community-dwelling older people with independent BADL. In particular, social role in men and IADL and intellectual activity in women were associated with long-term mortality risk.

Effect of Chronic Kidney Disease or Anemia or Both on Cardiovascular Mortality in a 25-Year Follow-Up Study of Japanese General Population (From NIPPON DATA90).

The relation between chronic kidney disease (CKD) and cardiovascular disease (CVD) in the general population is well elucidated. In patients with CKD, anemia is associated with adverse outcomes. However, the effects of CKD and anemia on CVD in the general population remains poorly explored, especially in Asian populations. This study aimed to investigate the effect of CKD and/or anemia on CVD mortality in a long-term cohort study involving Japanese community dwellers. We assessed 7,339 participants (aged ≥30 years) with no CVD history. These participants were divided into 4 categories according to their CKD (estimated glomerular filtration rate <60 or urine protein >1+ by dipstick qualitative test) and/or anemia (hemoglobin: <13 g/100 ml [men], <12 g/100 ml [women]) statuses. For each category, we calculated the hazard ratios (HRs) of CVD mortality by using the Cox proportional hazards model after adjusting for age, body mass index, hypertension, diabetes, dyslipidemia, smoking, and alcohol drinking. Within 25 years of follow-up, 637 participants died because of CVD. The HRs of CVD in patients with CKD only, anemia only, and both were 1.27, 1.59, and 2.60 (95% confidence intervals [CI] 1.06 to 1.53, 1.34 to 1.90, and 1.80 to 3.76) in men and 1.42, 1.08, and 2.00 (95% CI 1.19 to 1.69, 0.99 to 1.18, and 1.54 to 2.60) in women, respectively. In conclusion, CKD with anemia is associated with an increased risk for CVD mortality in a general population in Japan.

Association of ambulatory blood pressure with aortic valve and coronary artery calcification.

OBJECTIVE: We aimed to investigate the effect of ambulatory blood pressure (BP) on aortic valve calcification (AVC) and coronary artery calcification (CAC), which are subclinical atherosclerotic diseases. METHODS: In this population-based, cross-sectional study, we assessed office BP, mean ambulatory BP (24-h, awake, and asleep), and variability of ambulatory BP, as determined by the coefficient of variation (awake and asleep). AVC and CAC were quantified using an Agatston score (>0) based on computed tomography scanning. We calculated relative risks (RRs) and 95% confidence intervals (CIs) with a 1-standard deviation increment in each BP index for the presence of AVC and CAC using a multivariate-adjusted Poisson regression with robust error variance. RESULTS: Of 483 participants (mean age: 66.8 years), 154 (31.9%) and 310 (64.2%) had AVC and CAC, respectively. The presence of AVC was associated with office systolic BP (SBP; RR, 1.15; 95% CI, 1.03-1.28), awake diastolic BP (DBP) variability (RR, 1.12; 95% CI, 1.01-1.25), and asleep SBP variability (RR, 1.14; 95% CI, 1.03-1.27). The presence of CAC was associated with office SBP (RR, 1.08; 95% CI, 1.01-1.15), mean 24-h SBP (RR, 1.10; 95% CI, 1.04-1.16), mean awake SBP (RR, 1.11; 95% CI, 1.04-1.17), mean asleep SBP (RR, 1.07; 95% CI, 1.01-1.13), and asleep SBP variability (RR, 1.07; 95% CI, 1.01-1.13). CONCLUSION: These findings highlight the association of ambulatory BP indices with both AVC and CAC, but with different effects on their presences.

Effect of diabetes and prediabetes on the development of disability and mortality among middle-aged Japanese adults: A 22-year follow up of NIPPON DATA90.

AIMS/INTRODUCTION: To examine the association between diabetes and prediabetes at baseline, and disability, mortality over a 22-year period among middle-aged Japanese adults. MATERIALS AND METHODS: Participants consisted of 1,788 adults aged 45-64 years at baseline from the cohort study National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged 1990 (NIPPON DATA90). Disability, defined as having a decline in activities of daily living (ADL), was assessed by a modified Katz questionnaire at four time points. Disability and death without disability for 22-year follow up were used as outcomes to test the association with a diagnosis of diabetes or prediabetes at baseline, using multinomial logistic regression. Adjusted odds ratios (ORs) were obtained from four models that contained appropriate adjustment factors, such as age, sex, smoking status, drinking status, body mass index and cardiovascular risk factors (hypertension, hypercholesterolemia, triglycerides, low serum high-density lipoprotein), at baseline. RESULTS: In the present study, 334 participants (18.7%) reported at least one disability, and 350 (19.6%) were reported dead without observation of disability during follow up. Adjusting sex and other risk factors, participants with diabetes and prediabetes had a higher risk for disability (OR 1.43, 95% confidence interval [CI] 1.07-1.91 and OR 1.66, 95% CI 1.10-2.50, respectively) and for mortality (OR 1.56, 95% CI 1.16-2.08 and OR 1.77, 95% CI 1.18-2.65, respectively) than individuals with normal glucose tolerance. CONCLUSIONS: In middle-aged Japanese adults, individuals with diabetes and prediabetes were more likely to be associated with disability and mortality. Our findings suggest that prediabetes and diabetes in middle-aged adults should be paid more attention, and requires more intervention to prevent disability and mortality in later life.

Premature Atrial Contractions and Their Determinants in a General Population of Japanese Men.

BACKGROUND: Premature atrial contractions (PACs) are predictors of atrial fibrillation, stroke, and cardiovascular mortality. The present study aimed to assess relevant factors for PACs among a general population of Japanese men.Methods and Results: This study conducted a population-based, cross-sectional study among 517 men, aged 40-79 years, with neither apparent myocardial infarction nor atrial fibrillation. 24-h Holter electrocardiography to assess PAC frequency was used. Age, body mass index, height, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, mean heart rate, diabetes mellitus, hypertension, physical activity, smoking, alcohol consumption, and lipid-lowering therapy were included in multivariable negative binomial regression analyses to assess correlation for the number of PACs per hour. Almost all participants (99%) had at least 1 PAC in 1 h (median number 2.84 PACs per h). In multivariable negative binomial regression after adjusting for all covariates simultaneously, age (relative risk [95% confidence interval], 1.30 [1.08-1.57] per 1-standard deviation [SD] increment), height (1.19 [1.02-1.39] per 1-SD increment), triglycerides (0.79 [0.65-0.97] per 1-SD increment), mean heart rate (0.69 [0.59-0.80] per 1-SD increment), physical activity (0.63 [0.43-0.93]), current smoking (1.69 [1.06-2.69]), current moderate (1.97 [1.23-3.16]) and heavy (1.84 [1.12-3.01]) alcohol consumption were independently associated with PAC frequency. CONCLUSIONS: PAC frequency was independently associated with age, height, smoking, alcohol consumption, heart rate, physical activity, and triglycerides.

Ventricular Premature Complexes and Their Associated Factors in a General Population of Japanese Men.

Increased ventricular premature complexes (VPCs) are associated with a higher risk of cardiac morbidities. However, little information is available on the risk factors of Western general populations. Therefore, we aimed to assess the frequency and associated factors of VPCs in healthy general Japanese men. We conducted a population-based cross-sectional study in 517 men, aged 40 to 79 years, using 24-hour Holter electrocardiography. Age, body mass index, height, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, resting heart rate, diabetes mellitus, hypertension, physical activity, smoking, alcohol consumption, lipid-lowering therapy were included in multivariable negative binomial regression to assess independent correlates for the number of VPCs per hour. We observed at least 1 VPC in 1 hour in 429 men (83%). In multivariable negative binomial regression adjusted for all covariates simultaneously, age (risk ratio [95% confidence interval] 1.91 [1.56 to 2.33] per 1-SD increment), height (1.17 [1.04 to 1.49] per 1-SD increment), resting heart rate(1.34 [1.02 to 1.77] per 1-SD increment), diabetes mellitus (2.36 [1.17 to 4.76] ), hypertension (1.90 [1.03 to 3.50]), physical activity (0.67 [0.47 to 0.97] ), current smoking (4.23 [1.86 to 9.60] ), past smoking (2.08 [1.03 to 4.19] ), current light alcohol consumption (0.16 [0.04 to 0.64] ), and lipid-lowering therapy (0.47 [0.23 to 0.96] ) were independently associated with VPCs frequency. In conclusion, VPCs frequency was independently associated with age, height, resting heart rate, diabetes mellitus, hypertension, physical activity, smoking, alcohol consumption, and lipid-lowering therapy.

Prediction of Lifetime Risk of Cardiovascular Disease Deaths Stratified by Sex in the Japanese Population.

Background Lifetime risk is an informative estimate for driving lifestyle and behavioral changes especially for young adults. The impact of composite risk factors for cardiovascular disease on lifetime risk stratified by sex has not been investigated in the Japanese population, which has a much lower mortality of coronary heart disease compared with the Western population. We aimed to estimate lifetime risk of death from cardiovascular disease attributable to traditional risk factors. Methods and Results We analyzed pooled individual data from the Evidence for Cardiovascular Prevention from Observational Cohorts in a Japanese cohort study. A modified Kaplan-Meier approach was used to estimate the remaining lifetime risk of cardiovascular death. In total, 41 002 Japanese men and women with 537 126 person-years of follow-up were included. The lifetime risk at the index-age of 45 years for those with optimal risk factors (total cholesterol <4.65 mmol/L, systolic blood pressure <120 mm Hg, diastolic blood pressure <80 mm Hg, absence of diabetes, and absence of smoking habit) was lower compared with the highest risk profile of ≥2 risk factors (6.8% [95% CI, 0%-11.9%] versus 19.4% [16.7%-21.4%] for men and 6.9% [1.2%-11.5%] versus 15.4% [12.6%-18.1%] for women). Conclusions The magnitude and the number of risk factors were progressively associated with increased lifetime risk even in individuals in early adulthood who tend to have low short-term risk. The degree of established cardiovascular risk factors can be converted into lifetime risk. Our findings may be useful for risk communication in the early detection of future cardiovascular disease risk.

Lipoprotein Particle Profiles Compared With Standard Lipids in the Association With Subclinical Aortic Valve Calcification in Apparently Healthy Japanese Men.

BACKGROUND: Risk factors for atherosclerotic disease including dyslipidemia have been shown to be associated with aortic valve calcification (AVC). Nuclear magnetic resonance (NMR)-measured lipoprotein particles, low-density and high-density lipoprotein particles (LDL-p, HDL-p) in particular, have emerged as novel markers of atherosclerotic disease; however, whether NMR-measured particles are associated with AVC remains to be determined. This study aimed to examine the association between NMR-based lipoprotein particle measurements and standard lipids with AVC. The primary variables of interest were LDL-p (nmol/L), HDL-p (µmol/L), LDL-cholesterol, and HDL-cholesterol (both in mg/dL).Methods and Results:A community-based random sample of Japanese men aged 40-79 years examined in 2006-2008, in Shiga, Japan was studied. Presence of AVC was defined as an Agatston score >0. Lipoprotein particles were measured using NMR spectroscopy. In the main analysis, multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for the prevalence of AVC across the higher quartiles of lipids in reference to the lowest ones were obtained. Of 874 participants analyzed, 153 men had AVC. Multivariable-adjusted ORs of prevalent AVC for the highest vs. the lowest quartile were significantly elevated for LDL-p (OR, 2.20; 95% CI: 1.23-3.93) and LDL-cholesterol (OR, 2.16; 95% CI: 1.23-3.78). In contrast, neither HDL-p nor HDL-cholesterol was associated with AVC. CONCLUSIONS: The association of prevalent AVC with NMR-based LDL-p was comparable to that with LDL-cholesterol.

Estimation of 10-Year Risk of Death from Coronary Heart Disease, Stroke, and Cardiovascular Disease in a Pooled Analysis of Japanese Cohorts: EPOCH-JAPAN.

AIMS: We aimed to develop and validate risk prediction models to estimate the absolute 10-year risk of death from coronary heart disease (CHD), stroke, and cardiovascular disease (CVD). METHODS: We evaluated a total of 44,869 individuals aged 40-79 years from eight Japanese prospective cohorts to derive coefficients of risk equations using cohort-stratified Cox proportional hazard regression models. Discrimination (C-index) of the equation was examined in each cohort and summarised using random-effect meta-analyses. Calibration of the equation was assessed using Hosmer-Lemeshow chi-squared statistic. RESULTS: Within a median follow-up of 12.7 years, we observed 765 deaths due to CVD (276 CHDs and 489 strokes). After backward selection, age, sex, current smoking, systolic blood pressure (SBP), proteinuria, prevalent diabetes mellitus, the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDLC), interaction terms of age by SBP, and age by current smoking were retained as predictors for CHD. Sex was excluded in the stroke equation. We did not consider TC/HDLC as a risk factor for the stroke and CVD equations. The pooled C-indices for CHD, stroke, and CVD were 0.83, 0.80, and 0.81, respectively, and the corresponding p-values of the Hosmer-Lemeshow tests were 0.18, 0.003, and 0.25, respectively. CONCLUSIONS: Risk equations in the present study can adequately estimate the absolute 10-year risk of death from CHD, stroke, and CVD. Future work will evaluate the system as an education and risk communication tool for primary prevention of CHD and stroke.

Differences between home blood pressure and strictly measured office blood pressure and their determinants in Japanese men.

Conventional office blood pressure (OBP) and home blood pressure (HBP) measurements are often inconsistent. The purpose of this research was (1) to test whether strictly measured OBP values with sufficient rest time before measurement (st-OBP) is comparable to HBP at the population level and (2) to ascertain whether there are particular determinants for the difference between HBP and st-OBP at the individual level. Data from a population-based group of 1056 men aged 40-79 years were analyzed. After a five-min rest, st-OBP was measured twice. HBP was measured after a 2-min rest every morning for seven consecutive days. To determine factors related to ΔSBP (HBP minus st-OBP measurements), multiple linear regression analyses and analyses of covariance were performed. While st-OBP and HBP were comparable (136.5 vs. 137.2 mmHg) at the population level, ΔSBP varied with a standard deviation of 13.5 mmHg. Smoking was associated with a larger ΔSBP regardless of antihypertensive usage, and BMI was associated with a larger ΔSBP in participants using antihypertensive drugs. The adjusted mean ΔSBP in the highest BMI tertile category was 4.6 mmHg in participants taking antihypertensive drugs. st-OBP and HBP measurements were comparable at the population level, although the distribution of ΔSBP was considerably broad. Smokers and obese men taking antihypertensive drugs had higher HBP than st-OBP, indicating that their blood pressure levels are at risk of being underestimated. Therefore, this group would benefit from the addition of HBP measurements.

Study Profile of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study.

BACKGROUND: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene-environment interactions in lifestyle-related diseases, including cancers, among the Japanese. This report describes the study design and baseline profile of the study participants. METHODS: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history and collected peripheral blood samples. RESULTS: The baseline survey included 92,610 adults (mean age: 55.2 [standard deviation, 9.4] years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65-69 years for men and 60-64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women. CONCLUSIONS: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.

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.

Exercise Habits Are Associated with Improved Long-Term Mortality Risks in the Nationwide General Japanese Population: A 20-Year Follow-Up of the NIPPON DATA90 Study.

Exercise habits are known as a protective factor for a variety of diseases and thus recommended worldwide; however, few studies have examined long-term effects of exercise habits on mortality. We continuously monitored death status in a nationwide population sample of 7,709 eligible persons from the National Integrated Project for Prospective Observation of Noncommunicable Disease and its Trends in the Aged in 1990 (NIPPON DATA90), for which baseline data were obtained in 1990. To investigate the long-term impact of baseline exercise habits, we calculated the relative risk of non-exercisers (participants without regular voluntary exercise habits) in reference to exercisers (those with these habits) for all-cause or cause-specific mortality using a Cox proportional hazard model, in which the following confounding factors were appropriately adjusted: sex, age, body mass index, total energy intake, smoking, drinking, and history of cardiovascular disease. During a median 20 years of follow-up, 1,747 participants died, 99 of heart failure. The risk for all-cause mortality was 12% higher in non-exercisers than in exercisers (95% confidence interval, 1%-24%), which was also observed for mortality from heart failure, as 68% higher in non-exercisers than in exercises (95% confidence interval, 3%-173%). These associations were similarly observed when the participants were divided to subgroups by sex, age, and the light, moderate, or vigorous intensity of physical activity, without any significant heterogeneities (P > 0.1). The present study has revealed significant impact of exercise habits on long-term mortality risks, supporting worldwide recommendations for improvement of exercise habits.

Relationship Between Step Counts and Cerebral Small Vessel Disease in Japanese Men.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is a common subclinical feature of the aging brain. Steps per day may contribute to its prevention. We herein investigated the association between step counts and CSVD in a healthy Japanese male population. METHODS: We analyzed data from 680 men who were free of stroke and participated in this observational study. Seven-day step counts were assessed at baseline (2006-2008) using a pedometer. CSVD was assessed at follow-ups (2012-2015) based on deep and subcortical white matter hyperintensities (WMHs), periventricular hyperintensities, lacunar infarcts, and cerebral microbleeds on magnetic resonance imaging. Using a logistic regression analysis, we computed the adjusted odds ratios, with 95% CIs, of prevalent CSVD according to quartiles of step counts (reference: Q1). We also investigated the association between step counts and WMH volumes using a quantile regression. RESULTS: Steps per day were significantly associated with lower odds ratios, with the lowest at Q3 (8175-10 614 steps/day), of higher (versus low or no burden) deep and subcortical WMHs (odds ratio, 0.52 [95% CI, 0.30-0.89]), periventricular hyperintensities (0.50 [95% CI, 0.29-0.86]), and lacunar infarcts (0.52 [95% CI, 0.30-0.91]) compared with Q1 (≤6060 steps/day) but not cerebral microbleeds. An inverse linear association was observed between step counts and WMH volumes. These associations were independent of age and smoking and drinking status and remained consistent when adjusted for vascular risk factors. CONCLUSIONS: We found a J-shaped relationship between step counts and prevalent CSVD in healthy Japanese men, with the lowest risk being observed among participants with ≈8000 to 10 000 steps/day. Higher steps were also associated with lower WMH volumes.