Published papers

Background: In initial analyses, we found significant differences between serum adiponectin in Japanese living in Japan and Hawaii. Objective: We investigated whether differences in dietary and other lifestyle factors explain higher serum adiponectin concentrations in Japanese in Japan compared with Japanese emigrants living a Western lifestyle in Hawaii. Design: Serum adiponectin and nutrient intakes were examined by standardized methods in men and women aged 40-59 y from 2 population samples, one Japanese American in Hawaii (99 men, 104 women), the other Japanese in central Japan (124 men, 125 women). Multiple linear regression models were used to assess the role of dietary and other lifestyle traits in accounting for serum adiponectin difference between Hawaii and Japan. Results: Mean adiponectin was significantly higher in Japan than in Hawaii (10.5 ± 5.5 μg/mL compared with 6.7 ± 3.2 μg/mL in men, P = 0.002; 12.9 ± 5.9 μg/mL compared with 9.4 ± 4.2 in women, P < 0.0001). In men, the difference in body mass index (BMI; in kg/m2) in the 2 populations explained ≈90% of the difference in serum adiponectin; in women, only 29%. In multiple linear regression analyses in women further adjustment for physical activity and 4 nutrients (nonvegetable protein, n-3 polyunsaturated fatty acid, arachidonic acid, dietary cholesterol) produced a further reduction in the coefficient for the difference (total 56%); P value for the difference became 0.074. Conclusions: The significantly higher mean serum adiponectin concentration in Japan than in Hawaii may be attributable largely to differences in BMI. Differences in nutrient intake in the 2 samples were associated with only modest relation to the adiponectin difference. © 2008 American Society for Nutrition.

Marital status is related to cardiovascular disease (CVD) risk factors in Western countries. However, few studies have addressed the relationship between marital status and CVD risk factors in other populations. We investigated lifestyle and CVD risk factors relative to marital status among middle-aged Japanese men. We analyzed baseline data of 40-59-yr-old male workers who participated in the high-risk and population strategy for occupational health promotion (HIPOP-OHP) study. We compared lifestyle and CVD risk factors between men who were married (Group M; n=1,419, mean age 47.9 ±5.1 yr) and those who had never married (Group N; n=163, mean age 46.7 ±4.3 yr). Men in Group N were more likely to skip breakfast, work more shifts and exercise less. Current smoking rates, as well as average values of diastolic blood pressure (DBP), serum total cholesterol and fasting plasma glucose were also higher in Group N than in Group M. The proportion of participants with three or more CVD risk factors, namely smoking, hypertension, hypercholesterolemia and hyperglycemia was higher in Group N, than in Group M (12.9% vs. 5.0%, p<0.01). The difference between Groups M and N was more evident in the subgroup of living with others, than in the subgroup of living alone. Since men who have never married might be at higher risk for CVD, effort should be made to educate this population about decreasing lifestyle-related risk factors.

As body composition in Asian populations is largely different from Western populations, a healthy BMI could also differ between the two populations. Thus, further study is needed to determine whether a healthy BMI in Asians should be lower than Western populations, as recommended by the World Health Organization (WHO). We investigated the relationship between BMI and mortality in a sample of 8,924 Japanese men and women without stroke or heart disease. During 19 years of follow-up, 1,718 deaths were observed. We found a U-shaped relationship between BMI and fatal events. Risk of total mortality was highest in participants with BMI <18.5 kg/m2 and lowest in participants with BMI 23.0-24.9 kg/m2. These findings persisted even after excluding the first 5 years of follow-up with a focus on healthy participants who never smoked, were aged <70 years, and had total cholesterol (TC) levels ≥4.1 mmol/l (N = 3712). For both the full sample and healthy participants, all-cause mortality risk did not differ between BMI ranges 21.0-22.9 and 23.0-24.9 kg/m2. Our findings do not support the recent WHO implications that BMIs <23.0 kg/m2 is healthy for Asians. Therefore, further studies are needed to identify an optimal BMI range for Asia. © 2008 The Obesity Society.

Hypertension is a leading cause of death because of cardiovascular disease and predominantly affects total mortality. To reduce avoidable deaths from hypertension, we need to collect blood pressure data and assess their impact on total mortality. To examine this issue, a meta-analysis of 13 cohort studies was conducted in Japan. Poisson regression was used for estimating all-cause mortality rates and ratios. In the model, blood pressure data were treated as continuous (10-mm Hg increase) and categorical (every 10 mm Hg) according to recommendations of the Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of Hypertension. Potential confounders included body mass index, smoking, drinking, and cohort. The impact of hypertension was measured by the population-attributable fraction. After excluding participants with cardiovascular disease history, 176 389 participants were examined in the analysis. Adjusted mortality rates became larger as the blood pressure increased, and these were more distinct in younger men and women. Hazard ratios also showed the same trends, and these trends were more apparent in younger men (hazard ratio [unit: 10-mm Hg increase] aged 40 to 49 years: systolic blood pressure 1.37 (range: 1.15 to 1.62); diastolic blood pressure 1.46 [range: 1.05 to 2.03]) than older ones (hazard ratio: aged 80 to 89 years: systolic blood pressure 1.09 [range: 1.05 to 1.13]and diastolic blood pressure 1.12 [range: 1.03 to 1.22]). Population-attributable fraction of hypertension was ≈20% when the normal category was used as a reference level and was 10% when we included the prehypertension group in the reference level. In conclusion, high blood pressure raised the risk of total mortality, and this trend was higher in the younger Japanese population. © 2008 American Heart Association, Inc.

OBJECTIVE - We investigated the impact of active smoking and exposure to passive smoke on the risk of developing diabetes. RESEARCH DESIGN AND METHODS - Data were analyzed from a cohort of participants in the High-Risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP) conducted in Japan from 1999 to 2004. Active and passive smoking status in the workplace was evaluated at baseline. RESULTS - Of 6,498 participants (20.9% women), a total of 229 diabetes cases were reported over a median 3.4 years of follow-up. In the workplace, compared with zero-exposure subjects, the multivariable-adjusted hazard ratios of developing diabetes were 1.81 (95% CI 1.06-3.08, P = 0.028) for present passive subjects and 1.99 (1.29-3.04, P = 0.002) for present active smokers. CONCLUSIONS - In this cohort, exposure to passive smoke in the workplace was associated with an increased risk of diabetes after adjustment for a large number of possible confounders. © 2008 by the American Diabetes Association.

Individuals who are physically fit or engage in regular physical activity have a lower incidence of cardiovascular disease and risk of mortality. We conducted a large-scale controlled trial of interventions to decrease cardiovascular risk factors, during which we assessed the effect of a workplace-based intervention program, which was part of a population strategy for promoting long-term increases in physical activity, on the blood lipid profiles of participating employees. Data were collected from 2929 participants and this report presents the results of a survey conducted in five factories for the intervention group and five factories for the control group at baseline and year 5. The absolute/proportional changes in HDL-cholesterol were 2.7 mg/dL (4.8%) in the intervention group and -0.6 mg/dL (-1.0%) in the control group. The differences between the two groups in the change in serum levels of HDL-cholesterol were highly significant (p < 0.001) in each analysis of covariance, in which the number of cigarettes smoked was included or excluded. In the intervention group, the daily walking time increased significantly (p < 0.001) when compared between baseline and year 5, whereas no significant difference was observed in daily walking time in the control group over the identical period. Our results show that an intervention program promoting physical activity raises serum HDL-cholesterol levels of middle-aged employees. Increased awareness of the benefits of physical activity, using environmental rearrangement and health promotion campaigns, which especially target walking, may have contributed to a beneficial change in serum HDL-cholesterol levels in the participants. © 2007 Elsevier Ireland Ltd. All rights reserved.

Purpose: Koreans are recently at higher risk for coronary heart disease than are the Japanese. We aimed to evaluate levels of carotid intima-media thickness (IMT) and coronary risk factors in Korean and Japanese men in the post-World War II birth cohort. Methods: We conducted a population-based study of 352 randomly selected healthy men 40 to 49 years of age: 102 Koreans in Ansan City, Gyeonggi-do, Korea and 250 Japanese in Kusatsu City, Shiga, Japan. Imaging carotid IMT by ultrasonography and other procedures were standardized. Analyzing blood samples and reading carotid IMT were performed at the University of Pittsburgh. Results: Despite more favorable or similar features in coronary risk factors as compared to Japanese men, the Korean men had a higher crude IMT level than the Japanese men (mean ± standard error, 0.655 ± 0.008 mm vs 0.616 ± 0.005 mm, respectively, p < 0.0001). The difference in the levels of carotid IMT significantly remained after adjusting for metabolic and conventional risk factors (0.654 ± 0.008 mm vs. 0.616 ± 0.005 mm, respectively; p < 0.0001). Conclusions: Among men 40 to 49 years of age, Koreans had significantly higher levels of carotid IMT than the Japanese. Factors that underlie the different susceptibility to subclinical atherosclerosis need to be explored. © 2008 Elsevier Inc. All rights reserved.

Aims/hypothesis: High fasting blood glucose is one of the well-known risk factors for CHD. However, in certain settings, patients cannot always be expected to fast. For example, community screenings for cardiovascular disease (CVD) risk factors in Japan are performed under non-fasting conditions to achieve high participation rates. Thus, we examined a representative cohort of the Japanese population (n=9,444, follow-up period 17.3 years) to clarify whether high casual blood glucose (CBG) can predict CVD mortality. Methods: We defined CBG groups as follows: high CBG≥11.1 mmol/l or participants with a history of diabetes mellitus; borderline high, 7.77≤CBG<11.1 mmol/l; higher normal, 5.22≤CBG<7.77 mmol/l); and lower normal, CBG<5.22 mmol/l. The multivariate-adjusted hazard ratios (HRs) for CHD, CVD and all-cause mortality were calculated. Results: The crude CHD mortality rate was 0.84 per 1,000 person-years. Age- and sex-adjusted HRs for CHD mortality were high among participants with CBG levels ≥7.77 mmol/l, regardless of time since last meal. Multivariate-adjusted HRs (95% CI) of CHD mortality in high and borderline high CBG groups were 2.62 (1.46-4.67) and 2.43 (1.29-4.58), respectively. Similar results were observed for both CVD and all-cause mortality. Even within the normal blood glucose range, each 1 mmol/l increase in CBG was associated with a statistically significant increase in the HR for CVD mortality (1.12, 95% CI 1.02-1.22). Population-attributable fractions of the combined groups of high and borderline high CBG for CHD, CVD and all-cause mortality were 12.0, 4.9 and 3.5%, respectively. Conclusions/interpretation: Increases in CBG, even within the normal range, predict CVD mortality. © 2007 Springer-Verlag.

OBJECTIVES: To examine the association between levels of serum albumin and total cholesterol (TC) and risk of subsequent mortality and future decline in activities of daily living (ADLs) in elderly people. DESIGN: Population-based cohort study. SETTING: National Integrated Project for Prospective Observation of Non-Communicable Disease and Its Trends in the Aged, 1980. PARTICIPANTS: One thousand eight hundred forty-four Japanese individuals aged 60 to 74 randomly selected throughout Japan and followed for 12.4 years. MEASUREMENTS: Decline in ADLs and mortality. RESULTS: After adjusting for other covariates, the multivariable odds ratios (ORs) of impaired ADLs were highest in the lowest albumin quartile (≤40 g/L) for women. The multivariable OR of having a composite outcome of death or impaired ADL for the lowest albumin quartile compared with the highest was 1.56 (95% confidence interval (CI)=1.94-2.57) for men and 3.06 (95% CI=1.89-4.95) for women. Serum albumin was significantly and inversely associated with a composite outcome of death or impaired ADLs in the group below the median of TC in both sexes (multivariable OR for 1-g/L increase in serum albumin=0.88 for men (95% CI=0.79-0.97) and 0.79 for women (95% CI=0.72-0.87)), which was not significantly associated in the group with TC at or above the median. CONCLUSION: In the Japanese general population, low-normal serum albumin and TC levels are associated with loss of activity during old age, especially for women. © 2007, Copyright the Authors.

In men in the post-World War II birth cohort, that is, men aged 40 to 49 years, whites in the United States had significantly higher levels of intima-media thickness of the carotid arteries (IMT) than the Japanese in Japan (Electron-Beam Tomography and Risk Assessment Among Japanese and US Men in the Post World War II Birth Cohort [ERA JUMP] study). The difference remained after adjusting for traditional risk factors. Primary genetic effects are unlikely, given the degree to which IMT is increased in the Japanese who migrated to the United States. We investigated whether the differences in the distributions of lipoprotein subclasses explain the difference in IMT between the 2 populations. We examined population-based samples of 466 randomly selected men aged 40 to 49 years (215 whites from Allegheny County, Pennsylvania, and 241 Japanese from Kusatsu, Shiga, Japan). Lipoprotein subclasses were determined by nuclear magnetic resonance (NMR) spectroscopy. The whites had significantly higher levels of large very low-density lipoprotein particles and significantly lower levels of large high-density lipoprotein particles than the Japanese, whereas the 2 populations had similar levels of small low-density lipoprotein particles. The 2 populations had similar associations of IMT with NMR lipoproteins. Adjusting for NMR lipoproteins did not attenuate the significant difference in IMT between the 2 populations (0.671 ± 0.006 mm for the whites and 0.618 ± 0.006 mm for the Japanese, P = .01, mean ± SE). Differences in the distributions of NMR lipoproteins between the 2 populations did not explain the higher IMT in the whites. © 2008 Elsevier Inc. All rights reserved.

Background: The association of obesity measures (ie, body mass index (BMI), waist circumference (WC) and waist-to hip ratio (WHR)) with metabolic risk factors in community-based populations has not been well studied. Methods and Results: In the present study 759 men and 1,255 women aged between 30 and 79 years, without histories of stroke or coronary heart diseases, were dichotomized at the medians of BMI-WHR, WC-WHR and BMI-WC. The accumulation of 4 metabolic risk factors (risk _ sum) were examined: high blood pressure (≥130/85 mmHg or on antihypertensive therapy); high triglycerides (≥170 mg/dl); low high-density lipoprotein-cholesterol (<40 mg/dl); and impaired glucose tolerance (hemoglobin A1c ≥5.6% or on antidiabetic therapy). BMI and WC correlated well in both men (r=0.871) and women (r=0.874). All 3 obesity measures related with the metabolic risk factors. The area under the receiver-operating characteristic curve for BMI, WC and WHR to predict the risk sum ≥2 for men was 0.683, 0.709, and 0.700, respectively, and 0.715, 0.739, and 0.746, respectively, for women. Conclusions: BMI may be used instead of WC if the latter is not available. When WC is measured, hip circumference also should be measured because the WHR may be the most valuable measure of obesity.

Background. The effect of sleep on the risk of developing diabetes has not been explored in an Asian population. The objective of this study is to investigate the effect of self-reported sleep duration and sleep quality on the risk of developing diabetes in a prospective cohort in Japan. Methods. Data were analyzed from the cohort of participants in a High-risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP), conducted in Japan from the year 1999 until 2004. A Cox proportional hazard model was used to evaluate the association between sleep duration or sleep quality and the risk of diabetes. Results. Of 6509 participants (26.1% of women, 19-69 years of age), a total of 230 type 2 diabetes cases were reported over a median 4.2 years of follow-up. For participants who often experienced difficulty in initiating sleep, the multivariate-adjusted hazard ratios for diabetes were 1.42 (95%CI, 1.05-1.91) in participants with a medium frequency of difficulty initiating sleep, and 1.61 (95%CI, 1.00-2.58) for those with a high frequency, with a statistically significant linear trend. Significant association was not observed in the association between difficulty of maintaining sleep or duration of sleep, and risk of diabetes. Conclusion. Medium and high frequencies of difficulty initiating sleep, but not difficulty in maintaining sleep or in sleep duration, are associated with higher risks of diabetes in relatively healthy Asian workers, even after adjusting for a large number of possible further factors. © 2007 Hayashino et al; licensee BioMed Central Ltd.

Background: The association of white blood cell (WBC) count with all-cause and cardiovascular disease (CVD) mortality were examined in the National Integrated Project for Prospective Observation of Non-communicable Disease and Its Trends in the Aged (NIPPON DATA) 90. Methods and Results: A total of 6,756 Japanese residents (2,773 men and 3,983 women) throughout Japan without a history of CVD were followed for 9.6 years. A Cox proportional hazards regression model was used to estimate the relative risk (RR) and 95% confidence interval (CI). We documented 576 deaths with 161 deaths from CVD. Overall, after adjusting for several confounders including age, sex, body mass index at baseline, smoking status, alcohol consumption, regular exercise, diastlic blood pressure, total cholesterol, high-density lipoprotein-cholesterol and hemoglobin A1c, a graded association between WBC count and higher risk of allcause mortality was observed (WBC of 9,000-10,000 cells/mm3 vs WBC of 4,000-4,900: RR =1.61, 95% CI: 1.07-2.40, p for trend=0.02). Elevated WBC count was almost significantly associated with high risk of CVD mortality (WBC of 9,000-10,000 vs WBC of 4,000-4,900: RR=1.79, 95% CI: 0.97-3.71). These associations strengthened among women. Stratified by smoking status, never-smokers with WBC counts of 9,000-10,000 had a 3.2 fold elevated risk for CVD death compared with those with WBC counts of 4,000-4,900. Conclusions: The WBC count may have potential as a predictor for all-cause mortality, particularly CVD mortality.

Background: Although obesity is required for some criteria defining metabolic syndrome, clustering of other risk factors also indicates an increased risk of cardiovascular disease. Whether the relationship between cardiovascular risk factor clustering and medical expenditures differs with body mass index (BMI) requires investigation, especially in a population with a low prevalence of obesity such as that in Japan. Methods and Results: A 10-year cohort study of 4,478 Japanese National Health Insurance beneficiaries aged 40-69 years in a community between 1990 and 2001 was carried out in the present study. The clustering of cardiovascular risk factors showed a positive and graded relationship to personal medical expenditures in participants who are overweight (BMI ≥25.0) and normal weight (BMI <25.0). The individual medical expenditures per month were 1.7-fold higher for participants with 2 or 3 risk factors and overweight than for those without these factors (26,782 vs 15,377 Japanese yen). Differences in the geometric means were similarly significant after adjustment for other confounding factors. However, the excess medical expenditures by risk clustering of normal weight categories within the total medical expenditures were higher than those of overweight categories because more participants were of normal weight. Conclusions: Cardiovascular risk factor clustering and being overweight can be a useful predictor of medical expenditures in a Japanese population.

Background: The extent to which atrial fibrillation (AF) contributes to mortality in the Japanese general population has not been clarified. Methods and Results: A randomly sampled general population from all over Japan (4,154 men, 5,329 women; age ≥30 years) was enrolled. Single electrocardiogram recordings were taken in the baseline survey. Stroke death, cardiovascular deaths and all-cause deaths during the subsequent 19 years were analyzed by the presence of AF at baseline. Cox's regression analysis was carried out to estimate the hazard ratios (HRs) of each cause of death attributable to AF after adjusting for other risk factors. Prevalence of AF was 0.64% in the study. The observed person-years were 162,980 among persons without AF and 699 among persons with AF. There were 1,919 deaths. Multivariate adjusted HRs for stroke death, cardiovascular death and all-cause death were 2.69, 2.76 and 1.88, respectively (p<0.05). These HRs were 14.7, 9.63 and 4.00 among persons aged 64 years or younger (p<0.05). Conclusion: AF affects stroke mortality, cardiovascular mortality and all-cause mortality in the Japanese general population. Careful attention should be paid to persons with AF in order to prevent future cardiovascular events.