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Introduction To investigate whether nocturnal intermittent hypoxia (NIH), a surrogate marker for sleep apnoea, is associated with cardiovascular risk factors, we conducted epidemiological studies. Methods The CIRCS is a prospective cohort study across Japan since 1963 to examine risk factors for cardiovascular disease. Subjects aged 40–69 years were recruited to the sleep study in three communities. NIH was estimated by hourly occurrences of oxygen desaturation of ≥3% (3% oxygen desaturation index [3% ODI]) by a pulse-oximeter during a night9s sleep in the participant9s own home. We defined no, mild and moderate-to-severe NIH by 3% ODI as Results Compared with no NIH, the multivariable OR of hypertension was 1.63 (95% CI 1.1 to 2.5) for moderate-to-severe NIH. The prevalence of a high CRP (≥1.0 mg/l) was 1.4 to 1.7-fold higher for mild to severe NIH in both sexes. The multivariable ORs of metabolic syndrome was 3.2 (2.2 to 4.7) for moderate-to-severe NIH among men and 5.8 (3.4 to 9.8) among women, respectively. The multivariable-adjusted HRs of developing type 2 diabetes was 1.3 (0.9 to 1.8) among those with mild NIH and 1.7 (1.0 to 2.8) among those with moderate-to-severe NIH. Conclusion NIH was associated with hypertension, elevated serum CRP levels, the accumulation of metabolic risk factors, and increased risk of developing type 2 diabetes among middle-aged Japanese.

Neurotrophins such as brain-derived neurotrophic factor (BDNF) are thought to be transferred from post- to presynaptic neurons and to be involved in the formation and plasticity of neural circuits. However, direct evidence for a transneuronal transfer of BDNF and its relation to neuronal activity remains elusive. We simultaneously injected complementary DNAs of green fluorescent protein (GFP)–tagged BDNF and red fluorescence protein into the nucleus of single neurons and visualized expression, localization, and transport of BDNF in living neurons. Fluorescent puncta representing BDNF moved in axons in the anterograde direction, though some moved retrogradely, and transferred to postsynaptic neurons in an activity-dependent manner.

There is little information on the relation of plasma fibrinogen concentration to the risk of coronary heart disease in Asians, including Japanese, whose plasma fibrinogen concentration has been reported to be low by Western standards. The authors conducted a prospective study with 4.8 years of follow-up of 11,977 men and women aged 21-89 years (mean value of fibrinogen = 267 mg/dl) living or working in Osaka, Japan, in 1990-1996 to examine the relation of plasma fibrinogen with the incidence of coronary heart disease (myocardial infarction and angina pectoris). Mean fibrinogen concentration was 293.6 mg/dl for men who developed coronary heart disease (n = 35) compared with 261.6 mg/dl for men free of coronary heart disease (n = 8,094; difference, p < 0.01), and 355.2 mg/dl for women who developed coronary heart disease (n = 6) compared with 276.8 mg/dl for women free of coronary heart disease (n = 3,842; difference, p < 0.01). With a Cox proportional hazards model to adjust for cardiovascular risk factors, the relative risk for the highest fibrinogen quartile (≥295 mg/dl) compared with the lowest (

Background and Purpose —Although randomized clinical trials have demonstrated the benefit of antihypertensive treatment in preventing stroke, the effectiveness of community-based programs is largely unknown. We investigated long-term community-based prevention activities. Methods —In rural northeastern Japan, people aged ≥30 years numbered 3219 in the full intervention community and 1468 in the minimal intervention community in 1965. Systematic blood pressure screening and health education began in 1963. Stroke was registered through 1987. Results —More than 80% of people aged 40 to 69 years were screened in both communities in the 1960s. One community charged for screening services after 1968, whereas the other community intensified intervention; subsequently, screening rates and the follow-up of hypertensive individuals declined in the minimal intervention community, especially in men. In men, stroke incidence declined more ( P Conclusions —Delivery of hypertension control services through intensive, free, community-wide screening and health education was effective in prevention of stroke for men in a community.

To examine contribution of plasma fibrinogen concentrations to coronary atherosclerosis in Japanese, a cross-sectional study was conducted from 1991 to 1993 for 169 myocardial infarction cases and 1 : 1 matched references. All cases had one to three coronary vessels with 50 percent or more stenosis. References were chosen out of Osaka residents who had no cardiac event by matching sex and age ((+)-3 years) with cases. Mean (SD) values of plasma fibrinogen concentration were 322 (81) mg/dl in men and 377 (77) mg/dl in women for cases, and were 282 (56) mg/dl in men and 277 (48) mg/dl in women for references; mean plasma fibrinogen was significantly higher in cases than in references for both men and women. Furthermore, mean plasma fibrinogen was progressively higher as the number of stenotic vessels increased for men, and similar trend was seen for women. The case-reference difference remained significant even after adjusting smoking status, hypertension, serum total cholesterol, serum HDL cholesterol. Although plasma fibrinogen concentration was reported lower in Japanese than in American Caucasians, plasma fibrinogen is suggested to be a risk factor for myocardial infarction among Japanese as so among Caucasians.

Background. The intention of the study was to examine determinants of plasma fibrinogen concentrations in Japanese men. Method. A cross-sectional study was conducted in 1991 among 995 male employees aged 40-59 years in two urban companies. Results. The overall mean value (standard deviation) of plasma fibrinogen concentration was 257 (57) mg/dl. There was a strong dose-response relationship between cigarette smoking and plasma fibrinogen concentration. Plasma fibrinogen was positively associated with age and serum total cholesterol, and inversely associated with ethanol intake, dietary intake of sea foods such as squid, octopus or shrimp. Intake of other major protein and lipid resources such as meat, eggs and milk, or intake of vegetables was not related to plasma fibrinogen. An effect of dietary intake of sea foods on plasma fibrinogen was small but significant after controlling for the other covariates ; an 80 g/week larger intake of sea foods was associated with a 3.9 mg/dl (95% confidence interval : 0.5, 7.3) lower fibrinogen concentration. Conclusions. This study confirms the relation of known coronary risk factors to plasma fibrinogen in Japanese men, and suggests that dietary intake of sea foods affects plasma fibrinogen concentrations.

Objective There is little evidence whether sudden cardiac death (SCD) is increasing in Asia, although the incidence of coronary heart disease among urban middle-aged Japanese men has increased recently. We examined trends in the incidence of SCD and its risk factors in the Circulatory Risk in Communities Study. Design and setting This was a population-based longitudinal study. Surveillance of men and women for SCD incidence and risk factors was conducted from 1981 to 2005. Subjects The surveyed population was all men and women aged 30–84 years who lived in three rural communities and one urban community in Japan. Main outcome measures Trends in SCD incidence and its risk factors. Results Age-adjusted and sex-adjusted incidence of SCD decreased from 1981–1985 to 1991–1995, and plateaued thereafter. The annual incidence per 100 000 person-years was 76.0 in 1981–1985, 57.9 in 1986–1990, 39.3 in 1991–1995, 31.6 in 1996–2000 and 36.8 in 2001–2005. The prevalence of hypertension decreased from 1981–1985 to 1991–1995, and plateaued thereafter for men and women. The age-adjusted prevalence of current smoking for men decreased while that of diabetes mellitus increased for both sexes from 1981–1985 to 2001–2005. Conclusions The incidence of SCD decreased from 1981 to 1995 but was unchanged from 1996 to 2005. Continuous surveillance is necessary to clarify future trends in SCD in Japan because of an increasing incidence of diabetes mellitus., Article summary Article focus The incidence of coronary heart disease among urban middle-aged Japanese men increased from the 1990s to the 2000s, therefore the incidence of sudden cardiac death (SCD) may have increased in recent decades. This is the first study to examine recent trends in SCD in Japan. Key messages The age-adjusted and sex-adjusted incidence of SCD among men and women aged 30–84 years in four Japanese communities decreased from 1981–1985 to 1991–1995 and plateaued after 1996. Continuous surveillance is necessary to clarify future trends in SCD in Japan because of an increasing incidence of diabetes mellitus. Strengths and limitations of this study Trends in SCD were analysed using population-based data from a large number of participants in a long-term observational study and annual cardiovascular risk factor surveys ascertained the trends in predisposing risk factors of SCD. The incidence of SCD was only examined for people aged 30–84 years; other age ranges were not included. Clinical features and neuroimaging reports were used to exclude death due to stroke; some cases may have been misclassified, especially out-of-hospital deaths.

Although the relation between serum total cholesterol and coronary heart disease is well established, the relation with mortality from non-coronary disease is controversial. Inverse relations of serum cholesterol with hemorrhagic stroke and cancer have stimulated the examination of cholesterol-non-coronary mortality associations. The population surveyed is 12,187 men and women aged 40-69 years living in Yao City, a suburb of Osaka, who undertook baseline examinations between 1975 and 1984 and had no history of stroke and coronary heart disease at baseline. The subjects were followed on average 8.9 years until the end of 1988 using systematic mortality surveillance. During the follow-up, there were 343 deaths, comprising 170 cancer deaths (International Classification of Death 9th edition: ICD-9, 140-239), 21 coronary heart disease deaths (ICD-9, 410-414), 67 other cardiovascular deaths (ICD-9, 390-458 excluding 410-414), and 85 non-cardiovascular, non-cancer deaths. There was a significant inverse association of serum cholesterol with total and cancer mortality for men, and no significant association for women. The cholesterol-disease association, although not significant, was positive for coronary heart disease and other cardiovascular disease deaths, and inverse for non-cardiovascular, non-cancer deaths in both sexes. The inverse association of serum cholesterol with total and cancer mortality for men remained significant after controlling for age, job classification, hypertension category, usual alcohol intake, cigarette smoking, and relative weight index.(ABSTRACT TRUNCATED AT 250 WORDS)

To examine whether blood pressure (BP), a major risk factor of cardiovascular disease, can be controlled in the elderly as well as in middle-aged persons, we analyzed the data of observational studies on trends for BP and cardiovascular disease incidence in a northeast rural community of Japan. This community was the subject of an ongoing hypertension control program that was initiated in 1963. A significant decline in BP levels was noted in each sex-age group between 1963 and 1966 and 1987 and 1991. The decline was greater in older persons compared with younger individuals. The BP decline was attributable to an increase in antihypertensive medication use, beginning in the 1970s. We compared BP levels of untreated offspring and parents when both were 40 to 49 years old. Blood pressure levels were significantly lower in the offspring than in parents. This result and the large downward shift of BP distribution in the second decade of follow-up suggested that the improvements in diets and other environmental factors contributed to the BP decline. Between 1964 and 1968 and 1989 and 1992, stroke incidence declined 70% to 79% for all sex and age groups (40-69 and greater than 70 years). The number of totally dependent stroke patients decreased in both the middle-aged and the elderly between 1976 and 1991. The decline in stroke mortality tended to be larger in the surveyed community than in adjacent communities. These results indicated that hypertension control is effective in preventing stroke in the elderly as well as in the middle-aged.

Introduction To examine whether the accumulation of obesity-related eating behaviours such as eating quickly, eating until full, eating right before bedtime and breakfast skipping are associated with incidence of type 2 diabetes mellitus (T2DM) among middle-aged Japanese men and women. Methods The 2840 subjects (890 men and 1950 women) who were aged 40–69 year and free of T2DM were enrolled at baseline survey from 2003 to 2006 in a community-based longitudinal study, the CIRCS. The subjects were asked following four eating behaviours by questionnaire at baseline: “speed of eating”, “eating until full”, “eating right before bedtime” and “breakfast skipping”. T2DM was defined as fasting serum glucose ≥7.0 mmol/l, non-fasting serum glucose ≥11.1 mmol/l or medication for T2DM. We followed up to March 2010, and calculated HR and 95% coefficient interval (95% CI) of T2DM by using Cox proportional hazard model after adjustment for potential risk factors. Results During 7-year follow-up period, 155 cases (70 men and 85 women) had an onset of T2DM. We calculated multivariate HR (95% CI) of T2DM for each number of eating behaviours among both men and women. Compared with persons without any eating behaviours, the multivariable HR (95% CI) of persons with 1, 2 and ≥3 of eating behaviours were 2.35 (1.06 to 5.19), 1.54 (0.65 to 3.63) and 3.24 (1.29 to 8.13), p for trend=0.09 in men and 0.92 (0.52 to 1.62), 0.67 (0.35 to 1.30) and 1.97 (0.92 to 4.22), p for trend=0.67 in women. Conclusion Our finding suggests that the accumulation of obesity-related eating behaviours raise the risk of T2DM for middle-aged Japanese men.

Introduction The purpose of this study was to examine trends in the prevalence of diabetes (DM) and diabetic retinopathy (DR) between 2001 and 2009 years among Japanese population in Osaka, urban area in Japan. Methods This study was a population-based study including 10 companies9 employees and 1 community residents in Osaka, aged in 30–79 years, who underwent cardiovascular routine health examination at 2001–2003 (7186 participants), 2004–2006 (6908 participants) and 2007–2009 (7530 participants). We compared the prevalence of DM and DR among these three periods. DM was defined as HbA1c≥6.5% (Japan Diabetes Society9s unit) or patients taking medication, and pre-DM was defined as HbA1c≥5.6% and HbA1c Results Age-adjusted prevalence of DM was also significantly increased from 2001 to 2003 (2.6%) to 2007–2009 (3.9%) in men and women (p for trend Conclusion A significant increase in the prevalence of DM and pre-DM implies the importance of prevention and early detection for DM and DR in urban Japanese populations.

Background Information on the impact of fatty acid composition on dementia has not yet been elucidated. Methods We performed a nested case-control study based on a cohort of approximately 12 000 Japanese people from two communities in the CIRCS, aged 45–85 at baseline (1984–1994). Fatty acid compositions were measured for 350 dementia cases and 700 controls (age, sex, community and baseline-year matched). The subjects were followed-up from 1999 through 2008, and incident disabling dementia was defined as dependent individuals who had moderate to severe dementia-related behavioural disturbance and/or cognitive impairment. This criterion was previously validated with 5-cog test (specificity 90%, positive predictive value 71%). The conditional OR and 95% CI for disabling dementia was calculated according to one SD increment of each fatty acid with adjustment for body mass index, smoking status, alcohol consumption, systolic blood pressure, antihypertensive medication use, serum total cholesterol and diabetes. Results Serum α-linolenic acids were inversely associated with disabling dementia (OR=0.82 [0.70–0.95] for 1-SD increment). No associations were observed for other fatty acids: OR=1.07 [0.91–1.26] for saturated fatty acids, 0.99 [0.84–1.17] for monounsaturated fatty acids, 0.98 [0.83–1.15] for n−6 polyunsaturated fatty acids, 1.00 [0.87–1.16] for eicosapentaenoic acid, and 1.03 [0.87–1.22] for docosahexaenoic acid. Conclusions We found a significant inverse association between serum α-linolenic acid and incident disabling dementia.

Introduction To examine whether dietary folate, vitamin B 6 and B 12 intakes are associated with the risk of sudden cardiac death (SCD) among Japanese men and women. Method We conducted a nested case-control study. For each case of SCD entered between 1973 and 2001 in the CIRCS, two controls were randomly selected for each case and matched for age (±3 years), sex and community from among participants without history of SCD. The 77 cases and 154 controls aged 30–84 years were enrolled. Dietary folate, vitamin B 6 and B 12 intakes were assessed by 1 day 24 h dietary recall. We calculated conditional OR and 95% CI of each nutrients for risk of SCD adjusted for potential confounding factors. Result Higher intake of folate was associated with lower risk of SCD. The multivariable adjusted OR (95% CI) of highest quartile was 0.32 (95% CI 0.12 to 0.82), p for trend=0.06 compared with lowest quartile. However, vitamin B 6 and B 12 intakes were not associated with risk of SCD. The multivariable adjusted OR (95% CI) of highest quartile of vitamin B 6 and B 12 intakes were 1.25 (95% CI 0.49 to 3.21), p for trend=0.64 and 0.83 (95% CI 0.34 to 1.98), p for trend=0.86 compared with lowest quartiles, respectively. Conclusion Our findings suggest that higher dietary folate intake is associated with lower risk of SCD among Japanese men and women.

Objective In Japan, there is growing concern that employees' health condition has been worsening under the severe labor conditions of the continuing recent deep recession. To determine trends in the prevalence of cardiovascular risk factors among employees, we analyzed 32 yr of systematic surveillance of urban Japanese employed men. Subjects and methods The surveyed population included male employees aged 40 to 59 yr who worked for four companies, a trading company, two banks and a company maintaining expressways in Osaka. Surveillance of cardiovascular risk factors was conducted from 1977 to 2008. We examined the annual mean values of systolic blood pressure, diastolic blood pressure, body mass index, and total serum cholesterol, and the prevalence of hypertension, obesity, hypercholesterolemia, smoking, alcohol drinkers, and high risk individuals who had two or more risk factors: (high blood pressure, high glucose and dyslipidemia). Results The total number of employees aged 40-59 yr increased from 822 in 1977 to 2,651 in 1992, but then declined gradually to 1,455 in 2008. Among men aged 40-49 and 50-59, the prevalence of hypertension decreased from 25% and 39% in 1977 to 14% and 23% in 1992, respectively. However, the respective prevalence of hypertension started to rise thereafter to 29% and 47% in 2008, accompanied by an increase in blood pressure levels and the prevalence of antihypertensive medication use. Mean body mass index and the prevalence of obesity showed significant upward linear trends from the mid-1980's to 2008. Therefore, we speculate that the increase in blood pressure levels seen after the early 1990's associated with an increase in obesity. However the proportion of hypertension among non-overweight men also increased between the early 1990's and 2008, suggesting other factors are also involved in the increase of hypertension. The prevalence of hypercholesterolemia and high-risk individuals with obesity also increased in recent years. Mean total cholesterol level showed a linear increase from 195 mg/dl for men aged 40-49 and 196 mg/dl for men aged 50-59 in 1977 to 204 mg/dl and 207 mg/dl in 2008, respectively. The prevalence of high-risk individuals with obesity was 13% for men aged 40-49 and 15% for men aged 50-59 in 2008. Among men aged 50-59, the prevalence of non-overweight high-risk individuals became higher than that of high-risk individuals with obesity over time. Conclusions Although these findings were limited to the study companies, our data support evidence that Japanese employees have become increasingly at risk of cardiovascular diseases under the severe working conditions experienced since the 1990's. It is important to improve working conditions as well as personally control risk factors from the point of public health.

Objective To examine whether eating until full or eating quickly or combinations of these eating behaviours are associated with being overweight. Design and participants Cross sectional survey. Setting Two communities in Japan. Participants 3287 adults (1122 men, 2165 women) aged 30-69 who participated in surveys on cardiovascular risk from 2003 to 2006. Main outcome measures Body mass index (overweight ≥25.0) and the dietary habits of eating until full (lifestyle questionnaire) and speed of eating (validated brief self administered questionnaire). Results 571 (50.9%) men and 1265 (58.4%) women self reported eating until full, and 523 (45.6%) men and 785 (36.3%) women self reported eating quickly. For both sexes the highest age adjusted mean values for height, weight, body mass index, and total energy intake were in the eating until full and eating quickly group compared with the not eating until full and not eating quickly group. The multivariable adjusted odds ratio of being overweight for eating until full was 2.00 (95% confidence interval 1.53 to 2.62) for men and 1.92 (1.53 to 2.40) for women and for eating quickly was 1.84 (1.42 to 2.38) for men and 2.09 (1.69 to 2.59) for women. The multivariable odds ratio of being overweight with both eating behaviours compared with neither was 3.13 (2.20 to 4.45) for men and 3.21 (2.41 to 4.29) for women. Conclusion Eating until full and eating quickly are associated with being overweight in Japanese men and women, and these eating behaviours combined may have a substantial impact on being overweight.

Changes in the incidence of coronary heart disease (CHD) in the past 20 years have been observed in workers in the city and residents in rural areas and the risk factors of CHD studied. Findings show that the incidence of CHD in the residents in rural areas has hardly changed, and remains still low. However, the incidence of CHD in workers in the city has recently shown a tendency to increase. Furthermore, a study of CHD risk factors shows that in the rural areas residents hypertension has a strong influence on the incidence of CHD, while the role of serum total cholesterol is weak. In the city workers a high serum total cholesterol has become a risk factor. Therefore, it appears that the incidence of CHD caused by hypertension and by hypercholesterolemia are mixed in Japan. At present it appears that the influence of hypertension is becoming weaker, while the influence of hypercholesterolemia is becoming stronger. The resulting balance between them may be expressed as a rise and fall of CHD in Japan at present.

To examine the relation between alcohol intake and the incidence of coronary heart disease among Japanese, the authors analyzed data from a prospective study of 8,476 Japanese male employees, who were 40-59 years old at baseline (between 1975 and 1984) and worked for 13 urban companies in Osaka, Japan. These men were followed until the end of 1993, on average, an 8.8-year follow-up. Eighty-three coronary heart disease events (54 myocardial infarction, 32 angina pectoris) occurred during the employment period under study. Compared with the risk of coronary heart disease for never drinkers, the age-adjusted relative risk for those with an increased ethanol intake was lower, but the risk did not appear to be reduced further with the intake of > or = 69 g of ethanol per day. The multivariate relative risk adjusted for age, serum total cholesterol, cigarette smoking, body mass index, left ventricular hypertrophy, and a history of diabetes mellitus was 0.83 (95% confidence interval (CI) 0.24-2.86) in exdrinkers, 0.69 (95% CI 0.37-1.29) in drinkers of 1-22 g/day of ethanol, 0.55 (95% CI 0.29-1.05) in drinkers of 23-45 g/day, 0.41 (95% CI 0.19-0.88) in drinkers of 46-68 g/day, and 0.59 (95% CI 0.23-1.51) in drinkers of > or = 69 g/day. The inverse association with alcohol intake was similar between myocardial infarction and angina pectoris. Alcohol intake seemed to prevent the premature incidence of coronary heart disease among urban Japanese middle-aged men.