Longitudinal trajectories of smoking status using 25 year annually-updated data and all-cause mortality followed over 30 years: A community-based prospective cohort study.

We aimed to evaluate the long-term risk of smoking for all-cause mortality according to smoking status trajectories using 25-year annually-repeated input, traced by group-based trajectory modeling with an extension to account for non-random participant attrition or truncation due to death. We examined 2682 men and 4317 women aged 40 to 59 years who participated in annual health checks for the community-based prospective cohort study, 1975-1984 enrollment in Japan. The main outcome measure was all-cause mortality (follow-up period: median 30.2 years in men and 32.2 years in women). We traced annual smoking trajectories, stratified by sex and smoking status at baseline. For smokers at baseline, we identified five trajectories in both sexes, with different patterns of smoking cessation (e.g., early quitters and lifelong smokers). We calculated HRs and 95% CI of all-cause mortality using Cox proportional hazards regression modeling adjusted for age, body mass index, alcohol intake, blood pressure category, dyslipidemia and glucose category. Compared with one-time-point-based smokers, trajectory-based lifelong smokers had an increased risk of all-cause mortality; HRs were 1.31 (95% CI, 1.18-1.46) in men and 1.26 (95% CI, 0.91-1.73) in women. Among community residents aged 40 to 59 years, 25-year-trajectory-based lifelong smokers had an approximately 30% increased risk for all-cause mortality compared to one-time-point-based smokers. Risk of all-cause mortality among smokers with earlier cessation varied materially. It is necessary to consider the trajectories of smoking status to clarify the long-term excess risk of smoking.

Predictors of herpes zoster severity and immune responses according to pain trajectories: A community-based prospective cohort study.

The authors aimed to identify determinants of the clinical course of herpes zoster and immunological responses, focusing on pain trajectories. This prospective community-based cohort study involved the analysis of responses to a valid pain survey provided by 375 patients diagnosed with herpes zoster based on clinical symptoms and virus identification by polymerase chain reaction. The authors analyzed most patients for humoral/cell-mediated immune response against varicella-zoster virus at the onset and 3 months post-onset. Six months post-initial visit, patients self-reported pain on a scale of 0 (no pain) to 5 (extremely strong pain) at up to 18 time points. Moreover, the pain trajectories were traced using group-based trajectory modeling. Subsequently, the authors used analysis of covariance to explore predictors and the humoral/cell-mediated immune response according to the pain trajectories. In addition, humoral/cell-mediated immune responses were assessed among each trajectory using paired t tests. Amon the five identified trajectories, two were isolated that particularly developed postherpetic neuralgia, with or without severe acute pain. Cancer therapy and corticosteroid use before herpes zoster onset specifically predicted postherpetic neuralgia without severe acute pain. In contrast, prescription of nonsteroidal anti-inflammatory drugs was uniquely associated with postherpetic neuralgia accompanied by severe acute pain. The aforementioned trajectories with postherpetic neuralgia showed increased antibodies and decreased cell-mediated immunity compared with those without postherpetic neuralgia. The authors could successfully distinguish between postherpetic neuralgia trajectories with and without severe acute pain. The identified key predictors and immunological responses against varicella-herpes zoster contribute further evidence to our understanding of the clinical features of herpes zoster and postherpetic neuralgia.

Nocturnal Intermittent Hypoxia and the Risk of Cardiovascular Disease among Japanese Populations: The Circulatory Risk in Communities Study (CIRCS).

AIMS: Information is limited about the influence of obstructive sleep apnea (OSA) on developing cardiovascular disease (CVD) among Asian community-dwelling populations. We examined the association between nocturnal intermittent hypoxia as a surrogate marker of OSA and the risk of CVD in a Japanese community-based cohort study. METHODS: We used baseline surveys from 2000 to 2008 to study the cohort data of 5,313 residents from three Japanese communities who were between the ages of 40 and 74 years and initially free from ischemic heart disease and stroke. We assessed the number of 3% oxygen desaturation index (ODI) as the indicator of nocturnal intermittent hypoxia. We divided individuals into two groups depending on 3% ODI (3% ODI ≥ 5 or 3% ODI ＜5). Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD according to 3% ODI. Age, sex, body mass index, alcohol, and smoking were adjusted in the multivariable models. RESULTS: During 12.8 years of the median follow-up with 66,796 person-years, 185 cases with CVD (115 stroke and 70 coronary heart disease [CHD]) were recorded. The multivariable HRs (95% CIs) were 1.49 (1.09-2.03), 2.13 (1.08-4.22), and 1.93 (1.16-3.19) for the 3% ODI ≥ 5 group versus the 3% ODI ＜5 group of developing CVD, lacunar infarction, and CHD, respectively. CONCLUSIONS: Nocturnal intermittent hypoxia may increase the risk of developing lacunar infarction and CHD among community-dwelling Japanese populations. However, we could not find a significant risk of developing total stroke or stroke subtypes such as intraparenchymal hemorrhage, subarachnoid hemorrhage, and total ischemic stroke.

Serum High-Sensitivity C-Reactive Protein Levels and the Risk of Atrial Fibrillation in Japanese Population: the Circulatory Risk in Communities Study.

AIM: This study aimed to investigate the association between the serum high-sensitivity C-reactive protein (hs-CRP) levels and incident atrial fibrillation risk in the general Japanese population, who have lower hs-CRP levels than the Western population, and assess whether the association is modified by sex, overweight, hypertension, and smoking status. METHODS: We conducted a prospective study in 6517 Japanese men and women aged 40-79 years without atrial fibrillation at baseline and enrolled in the Circulatory Risk in Communities Study (2002-2008). The hs-CRP levels were measured using the latex particle-enhanced immunonephelometric assay. Atrial fibrillation was identified using standard 12-lead electrocardiograms and information on physician-diagnosed atrial fibrillation history from the follow-up surveys. We used a Cox proportional hazard regression stratified by community. RESULTS: During a median follow-up of 11 years, 127 new cases of atrial fibrillation (74 and 53 cases among men and women, respectively) were found. Compared to the lowest quintile of hs-CRP levels, the multivariable hazard ratios (95% confidence intervals) were 2.54 (1.17-5.50), 2.28 (1.06-4.93), 2.92 (1.37-6.23), and 2.77 (1.30-5.91) for the second, third, fourth, and fifth (highest) quintiles, respectively. There was no significant effect modification by sex, overweight, hypertension, and smoking status (P for interaction ＞0.05). CONCLUSIONS: Elevated hs-CRP levels were significantly associated with increased risk of atrial fibrillation in the Japanese population. The association of hs-CRP levels with incident atrial fibrillation did not vary according to sex, overweight, hypertension status, or smoking status.

Weight Change and Mortality from Cardiovascular Diseases: The Japan Collaborative Cohort Study.

AIM: The aim of this study was to assess the association between weight change and mortality due to cardiovascular diseases (CVDs) in a Japanese population. METHODS: We used the data of a population-based prospective cohort study that was conducted from 1988 to 1990 in 45 areas throughout Japan. Among a total of 69,681 men and women aged 40-79 with no history of CVD or cancer at baseline, the association between weight change from 20 years of age to baseline and CVD-related mortality was evaluated. RESULTS: During a median follow-up period of 19.1 years, we observed 4,274 deaths from total CVD. After adjusting for age, sex, and other potential confounding factors, compared with participants with a weight change of ＜2.5 kg (stable weight), participants with a greater weight change (either loss or gain) had an increased risk of mortality from total CVD (U-shaped association). The hazard ratios for the total CVD risk in participants with a weight loss and a weight gain of ≥ 12.5 kg were 1.50 (95% confidence interval [CI], 1.30-1.72) and 1.21 (95% CI, 1.07-1.36), respectively. The associations between weight change and risk of mortality from ischemic heart disease or stroke showed similar trends. The risk of intracerebral hemorrhage was associated with weight loss only. Weight change was not associated with mortality from subarachnoid hemorrhage. CONCLUSIONS: Weight loss or gain could be a risk factor for mortality from total or ischemic CVD, while weight loss could be a risk factor for intracerebral hemorrhage.

Overweight and Hypertension in Relation to Chronic Musculoskeletal Pain Among Community-Dwelling Adults: The Circulatory Risk in Communities Study (CIRCS).

BACKGROUND: The association between overweight and chronic musculoskeletal pain may vary by anatomical site and be modified by hypertension status. This study examined the associations between overweight and low back and knee pains and their effect modification by hypertension status. METHODS: We conducted a community-based cross-sectional study involving 2,845 adults (1,080 men and 1,765 women) aged 40-89 years. Chronic knee pain (CKP) and low back pain (CLBP) lasting more than 3 months were categorized into more or less severe pain. Odds ratios (ORs) and 95% confidence intervals (CIs) of the association between overweight and more or less severe CKP and CLBP were determined using logistic regression and stratified by hypertension status. Adjustment variables were age, sex, area, hypertension, smoking and drinking status, inactivity, job category, mental stress, depression, and overall CKP or CLBP. RESULTS: Overall, 288 (10.1%) and 631 (22.2%) adults had more and less severe CKP, respectively, and 284 (10.0%) and 830 (29.2%) had more and less severe CLBP, respectively. Overweight was associated with overall CKP and more or less severe CKP, regardless of hypertension status. Overweight was not associated with overall CLBP; its association was more pronounced for more severe CLBP. The association between overweight and more severe CLBP was evident among non-hypertensives (multivariable OR 1.72; 95% CI, 1.09-2.71); however, that between overweight and less severe CLBP was not evident (multivariable OR 1.07; 95% CI, 0.73-1.56). CONCLUSIONS: As hypertension may attenuate the association between overweight and CLBP, we should consider hypertension status for proper management of CLBP among overweight individuals.

Pain medications during pregnancy: data from the Japan environment and children's study.

PURPOSE: Analgesic medication epidemic during pregnancy is an important issue in Western countries. However, no large epidemiological study involving pregnant women with pain and their medication use has been conducted in Japan. This study examined the current situation of medication use for non-cancer pain during the perinatal period in Japan using national cohort data. METHODS: We analyzed 94,649 pregnant women who completed a self-report questionnaire investigating bodily pain and an interview-based medication use survey. Medication use before and during pregnancy and new medication administration/discontinuation during pregnancy were compared between women with and without pain during pregnancy using multivariable covariance analysis. RESULTS: Mild pain was reported by 50.4% of pregnant women in the first trimester (survey 1) and 61.8% in the second/third trimester (survey 2). Moderate-to-severe pain was reported by 15.4% of women in survey 1 and 22.4% in survey 2. In survey 1, 6.2% of women used prescribed analgesics and 1.6% used over-the-counter analgesics. In survey 2, prescribed and over the counter analgesics were used by 12.2% and 0.8% of women, respectively. Other pain-related medications were rarely used (< 1.0%). Pregnant women with moderate-to-severe pain showed a lower proportion of discontinuation of analgesics and a higher proportion of new administration of prescription and transdermal analgesics compared with those without pain. CONCLUSIONS: Although a large proportion of pregnant women experience pain, medication use for pain during pregnancy is low in Japan compared with Western countries (50-60%). Adequate treatment or support may be necessary for pregnant women experiencing pain in Japan.

A prospective study of knee pain, low back pain, and risk of dementia: the JAGES project.

The aim of this prospective study was to investigate the associations of knee and low back pain with dementia development. Participants were 14,627 older people with no history of stroke, cancer, injuries, depression, Parkinson's disease, or dementia who did not require support for daily living completed self-administered questionnaires with 3-years follow-up. A Cox regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia development. Stratified analyses by age and regular walking were conducted. Dementia risk was higher in participants aged 65-79 years with knee pain and without low back pain than in those without knee and low back pain [HR: 1.73 (95% CI: 1.11-2.68)]. Dementia risk was lower in participants ≥80 years with low back pain but no knee pain than in those without low back or knee pain [HR: 0.50 (95% CI: 0.31-0.80)]. Participants with knee pain who did not walk regularly had the highest dementia risk [HR: 1.71 (95% CI: 1.26-2.33)]. Knee pain may increase dementia risk among individuals aged 65-79 years, and may further increase risk in non-regular walkers. Low back pain may be a marker of maintained cognitive function despite age for individuals ≥80 years.

Smoking is associated with greater pain intensity and pain-related occupational disability in Japanese workers.

PURPOSE: Pain symptom, such as that caused by musculoskeletal disorders, is a major cause of occupational disability. As nicotine intake from smoking increases pain sensitivity, smokers may experience stronger pain and be more likely to experience pain-related disability than non-smokers. The study aim was to examine whether smoking was associated with pain-related occupational disability via pain intensity. METHODS: Participants were 1189 workers with pain aged 20-74 years in Japan. Participants completed a self-report questionnaire, which included a question to measure pain-related occupational disability with ordinal-option: (1) without pain-related disability, (2) pain-related presenteeism, and (3) pain-related absenteeism. An ordinal logistic regression model was used to calculate multivariable-adjusted proportional odds ratios (OR) with 95% confidence intervals (CI) for the prevalence of pain-related occupational disability according to smoking status. A multiple mediation analysis was also conducted to assess whether pain sensitivity mediated the association between smoking and pain-related occupational disability. Adjusted variables were demographic variables, socioeconomic status, work-related psychosocial factors, general psychological factors, and pain duration. RESULTS: Current smoking and pain were associated with pain-related occupational disability compared with non-smoking and pain (multivariable OR 1.78; 95% CI 1.26-2.52). Greater pain intensity partially mediated the association of current smoking and pain with pain-related occupational disability. The mediation rate (indirect/total effect) was 25%. CONCLUSION: Smoking and pain were associated with pain-related occupational disability, partially through greater pain intensity, among Japanese workers.

Self-Reported Eczema in Relation with Mortality from Cardiovascular Disease in Japanese: the Japan Collaborative Cohort Study.

AIM: Previous studies suggested a positive association between eczema and cardiovascular disease (CVD), probably through enhanced systemic inflammation. However, several studies reported null findings about eczema and CVD, so the evidence is still controversial. METHODS: We asked 85,099 participants (35,489 men and 49,610 women), aged 40 to 79 years, without a history of CVD or cancer at baseline between 1988 and 1990, to complete a lifestyle questionnaire, including information eczema frequency (seldom, sometimes or often). RESULTS: During the 6,389,818 person-years of follow-up, there were 1,174 deaths from coronary heart disease (CHD), 979 from heart failure, 366 from cardiac arrhythmia, 2,454 from total stroke, 1,357 from ischemic stroke, 1,013 from hemorrhagic stroke, and 201 from aortic aneurysm or dissection. The multivariable-adjusted model showed that individuals who "sometimes" or "often" had eczema had 0.82 (95%confidence interval (CI): 0.69-0.97) or 1.26 (95%CI: 1.01-1.56) times the risk of mortality from CHD, respectively, compared to those who "seldom" did. Individuals who "often" had 1.30 (95%CI: 1.05-1.61) times the risk of mortality from CHD, compared to those who "seldom or sometimes" did. There was no association of eczema with mortality from other CVD, or no interaction between eczema and sex or age, in relation to any CVD mortality risk. CONCLUSIONS: Self-reported frequent eczema was associated with increased risk of mortality from CHD, but not other major CVD, in a Japanese general population. Since steroid usage was not considered, future studies should include it as a potential confounding factor.

Association of body mass index with chronic pain prevalence: a large population-based cross-sectional study in Japan.

PURPOSE: The aim of this study was to examine the association between body mass index and chronic pain. METHODS: The outcome was chronic pain prevalence by body mass index (BMI). BMIs of less than 18.5, 18.5-25.0, 25.0-30.0, and 30.0 or over kg/m2 were defined as underweight, normal weight, overweight, and obese. SUBJECTS: We used data from 4993 participants (2464 men and 2529 women aged 20-79 years) of the Pain Associated Cross-sectional Epidemiological survey in Japan. Sex-stratified multivariable-adjusted odds ratios were calculated with 95% confidence intervals using a logistic regression model including age, smoking, exercise, sleep time, monthly household expenditure, and presence of severe depression. We analyzed all ages and age subgroups, 20-49 and 50-79 years. RESULTS: The prevalence of chronic pain was higher among underweight, overweight, and obese male respondents than those reporting normal weight, with multivariable odds ratios of 1.52 (1.03-2.25), 1.55 (1.26-1.91), and 1.71 (1.12-2.60). According to underweight, only older men showed higher prevalence of chronic pain than normal weight men with odd ratios, 2.19 (1.14-4.20). Being overweight and obese were also associated with chronic pain in women; multivariable odds ratios were 1.48 (1.14-1.93) and 2.09 (1.20-3.64). Being underweight was not associated with chronic pain. CONCLUSION: There was a U-shaped association between BMI and chronic pain prevalence among men ≥ 50 years, and a dose-response association among women. Our finding suggests that underweight should be considered in older men suffering chronic pain.

Diabetes-related factors and abdominal aortic aneurysm events: the Atherosclerotic Risk in Communities Study.

PURPOSE: To test the hypothesis that diabetes-related factors (metabolic syndrome [MetS], glucose, insulin, and leptin) are inversely associated with abdominal aortic aneurysm (AAA) risk. METHODS: We followed 13,736 participants, aged 45-64 years, without prior AAA surgery at baseline (1987-1989), for AAA occurrence through 2011. Hazard ratios (HRs) and their 95% confidence intervals (CIs) of AAA were calculated using Cox regression. RESULTS: During 275,054 person-years of follow-up, we identified 518 AAA events. Fasting serum glucose was associated inversely with AAA risk (HR [95% CI] per one unit increment in log2(glucose), 0.54 [0.36-0.80]), but fasting insulin was not associated with AAA. Plasma leptin was also associated inversely with AAA occurrence (HR [95% CI] per one unit increment in log2(leptin), 0.83 [0.71-0.98]). Compared with individuals without MetS, those with MetS had increased risk of AAA (HR [95% CI], 1.24 [1.04-1.48]). Among individuals with or without diabetes, the HRs increased monotonically with a greater number of non-glucose MetS components. CONCLUSIONS: Diabetes, fasting glucose, and plasma leptin were inversely associated with risk of AAA. In contrast, the MetS was associated with increased risk of AAA, due to the influence of the non-glucose MetS components.

Lipoprotein(a) and abdominal aortic aneurysm risk: The Atherosclerosis Risk in Communities study.

BACKGROUND AND AIMS: No prospective study has investigated whether elevated lipoprotein(a) concentrations are associated with an increased risk of abdominal aortic aneurysm (AAA). We aimed to prospectively investigate this association. METHODS: In 1987-1989, the Atherosclerosis Risk in Communities study measured plasma lipoprotein(a) in 13,683 participants aged 45-64 years, without a history of AAA surgery. We followed them for incident, clinical AAA events through 2011. RESULTS: During the 272,914 person-years of follow-up, over a median of 22.6 years, we documented 505 incident AAA events. The age-, sex-, and race-adjusted model showed that individuals in the highest quintile of plasma lipoprotein(a) had an increased risk of AAA. Further adjustment for the other potential confounding factors, including other plasma lipids (high- and low-density lipoprotein cholesterol and triglyceride concentrations), attenuated the association, but individuals in the highest versus lowest quintile of plasma lipoprotein(a) still had a significantly increased risk of AAA [hazard ratio (95% confidence interval): 1.57 (1.19-2.08)]. Interaction testing suggested no difference in the associations for whites and African Americans (p for interaction = 0.96). A restricted cubic spline analysis demonstrated a positive dose-response relation of plasma lipoprotein(a) with AAA, with a steep increase in AAA risk above the 75th percentile (p for overall association = 0.0086, p for non-linear association = 0.097). CONCLUSIONS: In this population-based cohort study, elevated lipoprotein(a) concentrations were independently associated with an increased risk of AAA. The association reflected a threshold of increased AAA risk at high lipoprotein(a) concentrations, rather than a steady monotonic association.

Prospective study of lung function and abdominal aortic aneurysm risk: The Atherosclerosis Risk in Communities study.

BACKGROUND AND AIMS: No prospective study has investigated whether individuals with respiratory impairments, including chronic obstructive pulmonary disease (COPD) and restrictive lung disease (RLD), are at increased risk of abdominal aortic aneurysm (AAA). We aimed to prospectively investigate whether those respiratory impairments are associated with increased AAA risk. METHODS: In 1987-1989, the Atherosclerosis Risk in Communities (ARIC) study followed 14,269 participants aged 45-64 years, without a history of AAA surgery, through 2011. Participants were classified into four groups, "COPD" [forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)

Daily Total Physical Activity and Incident Stroke: The Japan Public Health Center-Based Prospective Study.

BACKGROUND AND PURPOSE: There is limited evidence on the association between total physical activity and stroke in Asian populations experiencing a greater burden of hemorrhagic stroke than Western populations. We aimed to understand their optimal level of physical activity for stroke prevention. METHODS: A total of 74 913 Japanese people 50 to 79 years of age without histories of cardiovascular disease or cancer were followed from 2000 to 2012. RESULTS: During the 698 946 person-years of follow-up, we documented a total of 2738 incident cases of stroke, including 1007 hemorrhagic strokes (747 intraparenchymal and 260 subarachnoid hemorrhages) and 1721 ischemic strokes (1206 nonembolic and 515 embolic infarctions). Individuals in the second or third metabolic equivalents of task-hours per day quartile had the lowest risks of total stroke (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.75-0.93), intraparenchymal hemorrhage (HR, 0.79; 95% CI, 0.64-0.97), subarachnoid hemorrhage (HR, 0.78; CI, 0.55-1.11), and nonembolic infarction (HR, 0.78; CI, 0.67-0.92), whereas those in the fourth quartile had the lowest risk of embolic infarction (HR, 0.76; CI, 0.59-0.97). Cubic spline graphs revealed a steep decrease in stroke risk (30% risk reduction) from the lowest level to a plateau at 5 to 10 metabolic equivalents of task-hours per day (50th percentile). The associations of total physical activity level with hemorrhage stroke showed U or J shape, which were because of vigorous-intensity activities, whereas the association with ischemic stroke showed L shape. CONCLUSIONS: For Japanese people, moderate levels of total physical activity, particularly achieved by moderate-intensity activities, may be optimal for stroke prevention because excessive vigorous-intensity activities might not be beneficial or even disadvantageous for prevention of hemorrhagic stroke.

Physical Activity and Lifetime Risk of Cardiovascular Disease and Cancer.

PURPOSE: Although the World Health Organization has recommended moderate- to vigorous-intensity physical activity (MVPA) to prevent cardiovascular disease (CVD) and some cancers, there are no estimates of lifetime risk of these noncommunicable diseases according to PA levels. We aimed to estimate the lifetime risk of CVD and cancers according to PA levels. METHODS: We followed 5807 men and 7252 women in the United States, 45-64 yr old, initially free of CVD and cancer from 1987 through 2012, and used a life table approach to estimate lifetime risks of CVD (coronary heart disease, heart failure, and stroke) and total cancer according to PA levels: poor (0 min·wk of MVPA), intermediate (1-74 min·wk of VPA or 1-149 min·wk of MVPA), or recommended (≥75 min·wk of VPA or ≥150 min·wk of MVPA). RESULTS: During the 246,886 person-years of follow-up, we documented 4065 CVD and 3509 cancer events and 2062 non-CVD and 2326 noncancer deaths. In men, the lifetime risks of CVD from 45 through 85 yr were 52.7% (95% confidence interval = 49.4-55.5) for poor PA and 45.7% (42.7-48.3) for recommended PA. In women, the respective lifetime risks of CVD were 42.4% (39.5-44.9) and 30.5% (27.5-33.1). Lifetime risks of total cancer were 40.1% (36.9-42.7) for poor PA and 42.6% (39.7-45.2) for recommended activity in men and 31.4% (28.7-33.8) and 30.4% (27.7-32.9), respectively, in women. CONCLUSIONS: Compared with a poor PA level, the PA recommended by the World Health Organization was associated with lower lifetime risk of CVD, but not total cancer, in both men and women.

Association of Breakfast Intake With Incident Stroke and Coronary Heart Disease: The Japan Public Health Center-Based Study.

BACKGROUND AND PURPOSE: The association between breakfast intake and the risk of cardiovascular disease, including stroke, among Asian people remains unknown. We sought to prospectively investigate whether the omission of breakfast is related to increased risks of stroke and coronary heart disease in general Japanese populations. METHODS: A total of 82,772 participants (38,676 men and 44,096 women) aged 45 to 74 years without histories of cardiovascular disease or cancer were followed up from 1995 to 2010. Participants were classified as having breakfast 0 to 2, 3 to 4, 5 to 6, or 7 times/wk. The hazard ratios of cardiovascular disease were estimated using Cox proportional hazards models. RESULTS: During the 1 050 030 person-years of follow-up, we documented a total of 4642 incident cases, 3772 strokes (1051 cerebral hemorrhages, 417 subarachnoid hemorrhages, and 2286 cerebral infarctions), and 870 coronary heart disease. Multivariable analysis showed that those consuming no breakfast per week compared with those consuming breakfast everyday had hazard ratios (95% confidence interval; P for trend) of 1.14 (1.01-1.27; 0.013) for total cardiovascular disease, 1.18 (1.04-1.34; 0.007) for total stroke, and 1.36 (1.10-1.70; 0.004) for cerebral hemorrhage. Similar results were observed even after exclusion of early cardiovascular events. No significant association between the frequency of breakfast intake and the risk of coronary heart disease was observed. CONCLUSIONS: The frequency of breakfast intake was inversely associated with the risk of stroke, especially cerebral hemorrhage in Japanese, suggesting that eating breakfast everyday may be beneficial for the prevention of stroke.

Bowel Movement Frequency, Laxative Use, and Mortality From Coronary Heart Disease and Stroke Among Japanese Men and Women: The Japan Collaborative Cohort (JACC) Study.

BACKGROUND: The associations of bowel movement frequency and laxative use with cardiovascular disease (CVD) are unclear. METHODS: A total of 72 014 subjects (29 668 men and 42 346 women) aged 40 to 79 years, without a history of CVD or cancer, completed a lifestyle questionnaire at baseline between 1988 and 1990 that included information on bowel movement frequency (daily, every 2-3 days, or once every 4 or more days) and laxative use (yes or no), and were followed-up until 2009. RESULTS: During the subjects' 1 165 569 person-years of follow-up, we documented 977 deaths from coronary heart disease (561 men and 416 women), 2024 from total stroke (1028 men and 996 women), 1127 from ischemic stroke (606 men and 521 women), and 828 from hemorrhagic stroke (388 men and 440 women). The prevalence of CVD risk factors, such as diabetes, stress, depression, and physical inactivity, was higher in laxative users and in those with a lower frequency of bowel movements. The multivariable HRs (95% confidence intervals [CIs]) of laxative users were as follows: 1.56 (95% CI, 1.21-2.03) for coronary heart disease and 1.37 (95% CI, 1.07-1.76) for ischemic stroke in men, and 1.27 (95% CI, 1.08-1.49) for total stroke, and 1.45 (95% CI, 1.17-1.79) for ischemic stroke in women. Similar results were observed even after the exclusion of deaths that occurred early in the follow-up period. A significant association between bowel movement frequency and mortality from CVD was not observed. CONCLUSIONS: Constipation could be a marker of exposure to CVD risk factors, and laxative use could be a risk factor for mortality from coronary heart disease and ischemic stroke.

Association of Body Mass Index and Mortality in Japanese Diabetic Men and Women Based on Self-Reports: The Japan Collaborative Cohort (JACC) Study.

BACKGROUND: The association between body mass index (BMI) and mortality among Asian diabetic people, especially with respect to the obesity paradox (ie, higher BMI is associated with lower mortality risk), remains unresolved. METHODS: We followed a cohort of 3851 self-reported Japanese diabetics (2115 men and 1736 women) in the Japan Collaborative Cohort Study from 1988-1990 through 2009. Individuals were aged 40 to 79 years and free from a history of cardiovascular disease, cancer, renal disease, or tuberculosis. BMI was grouped into the following four categories: <20.0, 20.0-22.9, 23.0-24.9, and ≥25.0 kg/m2. RESULTS: During 54 707 person-years of follow-up, 1457 deaths from all causes, 445 from cardiovascular disease, 421 from cancer, 43 from renal disease, and 148 from infectious disease were documented. Mortality from all causes, cardiovascular disease, cancer, and renal disease showed L-shaped associations with BMI. Compared to diabetics with BMI of 20.0-22.9 kg/m2, those with BMIs of 23.0-24.9 kg/m2 and ≥25.0 kg/m2 had lower risks of mortality from infectious disease (i.e., obesity paradox). The multivariable HRs for mortality from infectious disease were 0.50 (95% confidence interval, 0.31-0.81) and 0.51 (95% confidence interval, 0.32-0.82) among participants with BMIs of 23.0-24.9 kg/m2 and ≥25.0 kg/m2, respectively. Similar results were observed after stratification by smoking status and age and exclusion of early deaths. CONCLUSIONS: We observed L-shaped associations between BMI and mortality from all causes, cardiovascular disease, cancer, and renal disease, while the association between BMI and mortality from infectious disease manifested the obesity paradox.

Association of measles and mumps with cardiovascular disease: The Japan Collaborative Cohort (JACC) study.

OBJECTIVE: Although it has been suggested that exposure to infections during childhood could decrease risk of atherosclerotic cardiovascular disease (CVD), the evidence is scarce. We investigated the association of measles and mumps with CVD. METHODS: 43,689 men and 60,147 women aged 40-79 years at baseline (1988-1990) completed a lifestyle questionnaire, including their history of measles and mumps, and were followed until 2009. Histories of infections were categorized as having no infection (reference), measles only, mumps only, or both infections. Hazard ratios (HR) for mortality from CVD across histories of infections were calculated. RESULTS: Men with measles only had multivariable HR (95% confidence interval) of 0.92 (0.85-0.99) for total CVD, those with mumps only had 0.52 (0.28-0.94) for total stroke and 0.21 (0.05-0.86) for hemorrhagic stroke, and those with both infections had 0.80 (0.71-0.90) for total CVD, 0.71 (0.53-0.93) for myocardial infarction, and 0.83 (0.69-0.98) for total stroke. Women with both infections had 0.83 (0.74-0.92) for total CVD and 0.84 (0.71-0.99) for total stroke. We also compared subjects with measles only or mumps only (reference) and those with both infections. Men with both infections had 0.88 (0.78-0.99) for total CVD. Women with both infections had 0.85 (0.76-0.94) for total CVD, 0.79 (0.67-0.93) for total stroke, 0.78 (0.62-0.98) for ischemic stroke and 0.78 (0.62-0.98) for hemorrhagic stroke. CONCLUSIONS: Measles and mumps, especially in case of both infections, were associated with lower risks of mortality from atherosclerotic CVD.