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.

Risk of herpes zoster according to past history in the general population: The Japanese Shozu herpes zoster study.

Immunity is known to persist after vaccination for varicella zoster virus, but the duration of immunity in patients who develop herpes zoster (HZ) remains unknown. To investigate the association between a past history of HZ and its occurrence in the general population. The Shozu HZ (SHEZ) cohort study included data for 12 299 individuals aged ≥50 years with information on their HZ history. Cross-sectional and 3-year follow-up studies were carried out to analyze the associations between a history of HZ (yes <10 years, yes ≥10 years, no) and the proportion of positive varicella zoster virus skin test results (erythema diameter ≥5 mm) and the risk of HZ after adjusting for potential confounding factors including age, sex, body mass index, smoking status, sleep duration, and mental stress. The incidences of positive skin test results were 87.7% (470/536) for individuals with a history of HZ <10 years ago, 82.2% (396/482) for those with a history of HZ ≥10 years, and 80.2% (3614/4509) for those with no history of HZ. The multivariable odds ratios (95% confidence intervals) of erythema diameter ≥5 mm were 2.07 (1.57-2.73) and 1. 39 (1.08-1.80) for individuals with a history <10 years and ≥10 years ago, respectively, compared with no history. The corresponding multivariable hazard ratios of HZ were 0.54 (0.34-0.85) and 1.16 (0.83-1.61), respectively. A past history of HZ <10 years ago may reduce the occurrence of HZ.

Total protein intake and subsequent risk of chronic kidney disease: the Circulatory Risk in Communities Study.

BACKGROUND: Whether dietary protein intake worsens renal function in the general population has been discussed but not yet determined. We aimed to examine the longitudinal association between dietary protein intake and risk of incident chronic kidney disease (CKD). METHODS: We conducted a 12-year follow-up study with 3,277 Japanese adults (1,150 men and 2,127 women) aged 40-74 years, initially free from CKD, who participated in cardiovascular risk surveys from two Japanese communities under the Circulatory Risk in Communities Study. The development of CKD was defined by the estimated glomerular filtration rate (eGFR) during the follow-up period. Protein intake was measured at baseline by using the brief-type self-administered diet history questionnaire. We estimated sex-, age-, community- and multivariate-adjusted hazard ratios (HR) for incident CKD were calculated using the Cox proportional hazards regression models according to quartiles of percentage of energy (%energy) from protein intake. RESULTS: During 26,422 person-years of follow-up, 300 participants developed CKD (137 men and 163 women). The sex-, age-, and community-adjusted HR (95% confidence interval, CI) for the highest (≥16.9%energy) versus lowest (≤13.4%energy) quartiles of total protein intake was 0.66 (0.48-0.90), p for trend = 0.007. The multivariable HR (95%CI) was 0.72 (0.52-0.99), p for trend = 0.016 after further adjustment for body mass index, smoking status, alcohol drinking status, diastolic blood pressure, antihypertensive medication use, diabetes mellitus, serum total cholesterol levels, cholesterol-lowering medication use, total energy intake, and baseline eGFR. The association did not vary by sex, age, and baseline eGFR. When examining animal and vegetable protein intake separately, the respective multivariable HRs (95%CIs) were 0.77 (0.56-1.08), p for trend = 0.036, and 1.24 (0.89-1.75), p for trend = 0.270. CONCLUSIONS: Higher protein intake, more specifically animal protein intake was associated with a lower risk of CKD.

Risk Factors for Hyperuricemia or Gout in Men and Women: The Circulatory Risk in Communities Study (CIRCS).

AIM: We aimed to examine sex-specific risk factors for hyperuricemia or gout in Japanese cohorts. METHODS: We followed up 3,188 men (mean age, 55.6 years) and 6,346 women (mean age, 54.1 years) without hyperuricemia, gout, or elevated liver enzymes at baseline from 1986 to 1990 for a median of 14.6 years. The participants were considered as having hyperuricemia or gout if their serum uric acid levels were ≥ 7.0 mg/dL or they were receiving treatment for hyperuricemia or gout during annual health checkups. The sex-specific multivariable hazard ratios (HRs) of hyperuricemia or gout incidence were calculated after adjustment for smoking and drinking status, body mass index, hypertension, diabetes, hypercholesterolemia, and hypertriglyceridemia using the Cox proportional-hazard model. RESULTS: During follow-up, 733 men and 355 women had hyperuricemia or gout. Among men, the multivariable HRs (95% confidence intervals) of hyperuricemia or gout were 1.23 (1.00-1.52) and 1.41 (1.13-1.75) for drinkers of ＜46 and ≥ 46 g ethanol/day, respectively, compared with non-drinkers; 1.00 (0.81-1.24) and 1.18 (0.93-1.50) for smokers of 1-19 and ≥ 20 cigarettes/day, respectively, compared with never smokers; and 1.41 (1.20-1.65) for hypertensive compared with non-hypertensive participants. The HRs for women were 1.02 (0.70-1.48), 1.66 (1.05-2.63), and 1.12 (0.88-1.42) for current drinkers, current smokers, and hypertensive participants, respectively. For both men and women, body mass index, diabetes, hypercholesterolemia, and hypertriglyceridemia were not associated with hyperuricemia or gout incidence. CONCLUSIONS: Hypertension and alcohol drinking are risk factors for hyperuricemia or gout among men and smoking among women.

Sex- and age-specific impacts of smoking, overweight/obesity, hypertension, and diabetes mellitus in the development of disabling dementia in a Japanese population.

BACKGROUND: Sex- and age-specific impacts of cardiovascular risk factors on the development of dementia have not been well evaluated. We investigated these impacts of smoking, overweight/obesity, hypertension, and diabetes mellitus on the risk of disabling dementia. METHODS: The study participants were 25,029 (10,134 men and 14,895 women) Japanese aged 40-74 years without disabling dementia at baseline (2008-2013). They were assessed on smoking status (non-current or current), overweight/obesity (body mass index ≥25 kg/m2 and ≥30 kg/m2, respectively), hypertension (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or any antihypertensive medication use), and diabetes mellitus (a fasting serum glucose ≥126 mg/dL, non-fasting glucose ≥200 mg/dL, hemoglobin A1c ≥6.5% by the National Glycohemoglobin Standardization Program or glucose-lowering medication use) at baseline. Disabling dementia was identified as the level of care required ≥1 and cognitive disability grade ≥IIa according to the National Long-term Care Insurance Database. We used a Cox proportional regression model to estimate hazard ratios and 95% confidence intervals (95% CIs) of disabling dementia according to the cardiovascular risk factors and calculated the population attributable fractions (PAFs). RESULTS: During a median follow-up of 9.1 years, 1,322 (606 men and 716 women) developed disabling dementia. Current smoking and hypertension were associated with a higher risk of disabling dementia in both sexes, whereas overweight or obesity was not associated with the risk in either sex. Diabetes mellitus was associated with a higher risk only in women (p for sex interaction = 0.04). The significant PAFs were 13% for smoking and 14% for hypertension in men and 3% for smoking, 12% for hypertension, and 5% for diabetes mellitus in women. The total PAFs of the significant risk factors were 28% in men and 20% in women. When stratified by age, hypertension in midlife (40-64 years) was associated with the increased risk in men, while diabetes mellitus in later-life (65-74 years) was so in women. CONCLUSIONS: A substantial burden of disabling dementia was attributable to smoking, and hypertension in both sexes and diabetes mellitus in women, which may require the management of these cardiovascular risk factors to prevent dementia.

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.

Dietary intake of beans and risk of disabling dementia: The Circulatory Risk in Communities Study (CIRCS).

OBJECTIVE: To examine whether bean intake (including soybeans) among Japanese adults is associated with risk of disabling dementia severe enough to require care under the national insurance system. METHODS: This cohort study involved 3739 individuals aged 40 to 64 years. The participants were categorized into five groups based on their dietary bean intake estimated by a 24h dietary recall. Hazard ratios and 95% confidence intervals of disabling dementia were estimated using Cox proportional hazard models adjusted for potential confounding factors (smoking, drinking, and intakes of energy and fish). RESULTS: During the 59,681 person-year follow-up, 670 cases of disabling dementia were observed. A weak inverse association between bean intake and risk of disabling dementia was found; the multivariable hazard ratios (95% CIs) were 0.79 (0.62-1.00), 0.80 (0.63-1.01), 0.84 (0.67-1.06), and 0.78 (0.62-0.99) for the four groups with higher bean intake, respectively, compared with the lowest group (P for trend = 0.21). A significant inverse association was observed for dementia without a history of stroke; for the four groups with higher bean intake the multivariable hazard ratios were 0.81 (0.61-1.08), 0.70 (0.52-0.95), 0.71 (0.52-0.95), and 0.69 (0.51-0.92), respectively, (P for trend = 0.03). No such association was observed for dementia with history of stroke. The group with increased natto intake were inversely associated with risk of disabling dementia (P for trend = 0.003), but tofu intake was not (P for trend = 0.19). CONCLUSIONS: Bean intake was inversely associated with risk of disabling dementia in those without a history of stroke.

Alcohol Consumption and Long-Term Mortality in Men with or without a History of Myocardial Infarction.

AIMS: The evidence for the impact of alcohol consumption on long-term mortality among myocardial infarction (MI) survivors was limited. We aimed to examine whether alcohol consumption was associated with cause-specific and all-cause mortality in men with or without a history of MI. METHODS: A total of 32,004 men aged 40-79 years with no history of MI and 1,137 male MI survivors, free of stroke and cancer, were followed through the end of 2009. Alcohol consumption was assessed using self-administered questionnaires at baseline and five years. RESULTS: In MI survivors, consuming 23-45 g/day of alcohol was associated with a lower risk of coronary heart disease (CHD) mortality compared to never drinkers: the multivariable hazard ratio was 0.36 (95% confidence interval: 0.16-0.80). In non-MI men, a 10-26% lower risk was observed at ＜23 or 23-45 g/day with the U-shaped association for CHD, cardiovascular disease, other causes, and all causes (P-quadratic ＜0.001). CONCLUSION: Alcohol consumption of 23-45 g/day was associated with a lower CHD mortality in MI survivors as so in men without MI.

Risk factors for pre-heart failure or symptomatic heart failure based on NT-proBNP.

AIMS: Evidence on the risk factors for incident heart failure in Asia has been limited. We sought to identify the risk factors for pre-heart failure or symptomatic heart failure, based on N-terminal pro-B-type natriuretic peptide (NT-proBNP), in the Japanese general population. METHODS: We performed a retrospective cohort study based on the Circulatory Risk in Communities Study involving 5335 Japanese individuals whose NT-proBNP levels were measured between 2010 and 2015. Of these, 2768 people aged between 30 and 69 years who undertook annual cardiovascular risk surveys at least once between 1990 and 2000 were retrospectively eligible to be participants in this study. We performed multivariable logistic regression analyses to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of pre-heart failure or symptomatic heart failure defined as NT-proBNP >400 pg/mL or as having a diagnosis of heart failure and taking medication for heart failure for several cardiovascular risk factors (body mass index, blood pressure, diabetes mellitus, total cholesterol, triglyceride, smoking status, drinking status). RESULTS: We identified 85 cases of heart failure. The multivariable ORs (95% CIs) were 5.70 (2.70-12.0) for body mass index of 27-29.9 kg/m2 and 5.91 (2.19-16.0) for ≥30 kg/m2 compared with 21-22.9 kg/m2 ; 2.49(1.01-6.13) for systolic blood pressure of ≥160 mmHg vs. <130 mmHg; 2.87(1.23-6.68) for diastolic blood pressure of ≥100 mmHg vs. <80 mmHg; 5.16(2.14-12.4) for diabetes vs. non-diabetes; and 2.24 (0.92-5.49) for current smokers of ≥20 cigarettes/day vs. never smokers. The multivariable ORs (95% CIs) of the number of risk factors, defined as the sum of four risk factors (obesity, hypertension, diabetes, and current smoker) was 6.80 (3.69-12.5) for ≥2 risk factors vs. no risk factors. CONCLUSIONS: The accumulation of these risk factors was associated with a graded higher risk of pre-heart failure or symptomatic heart failure.

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Positive psychological factors and the risk of pneumonia-associated mortality: Japan Collaborative Cohort Study.

OBJECTIVE: To examine the association between positive psychological factors and the risk of pneumonia-associated mortality in a large prospective Japanese cohort. METHODS: The Japan Collaborative Cohort Study assessed 64,231 participants (26,293 men and 37,938 women), aged 40-79 years, without a history of stroke, myocardial infarction, cancer or tubercules at baseline (1988-1990). We used self-administered questionnaires about lifestyle, medical history, and mental states, including three positive psychological factors, and followed-up for mortality outcomes until the end of 2009. The Cox proportional hazard model was used to calculate the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of pneumonia-associated mortality after adjustment for potential confounding factors, mutually positive psychological factors, and consideration for the competing risk. RESULTS: Having Ikigai (in Japanese) was inversely associated with the risk of pneumonia-associated mortality in both men and women; the multivariable HRs (95% CIs) for high versus low levels were 0.68 (0.48-0.97), P trend =0.090 and 0.66 (0.43-1.00), P trend =0.146, respectively. Such inverse associations were more pronounced in working men and non-working women; the multivariable HRs (95% CIs) for high versus low levels were 0.52 (0.32-0.85), P trend =0.010 and 0.59 (0.37-0.94), P trend =0.079, respectively. Being relied upon by others and Enjoyment of life was not associated with the risk in both genders. CONCLUSION: Having Ikigai was associated with a lower risk of pneumonia-associated mortality in both genders, especially in working men and non-working women.

Impact of modifiable healthy lifestyle adoption on lifetime gain from middle to older age.

OBJECTIVE: this study explored whether the modification of selected lifestyles is likely to increase life expectancy from middle age onwards, regardless of the presence of major comorbidities. METHODS: we examined a prospective cohort of 20,373 men and 26,247 women aged 40-80 years. Eight modifiable lifestyle factors were assessed: consumption of fruit, fish and milk, walking and/or sports participation, body-mass index, smoking status, alcohol consumption and sleep duration. Modifiable healthy lifestyle factors scored one point each, for a maximum of eight points. The impact of modifiable healthy lifestyle adoption on lifetime gain during the ages of 40-102 years was analysed. FINDINGS: during the median 21 years of follow-up, 8,966 individuals (3,683 men and 5,283 women) died. Life expectancy at 40 years (95% confidence intervals) for 7-8 health lifestyle points was 46.8 (45.6-48.1) and 51.3 (50.0-52.6) years for men and women, respectively. The potential impact of modifiable healthy lifestyle adoption on lifetime gain persisted over the age of 80 years or more, in individuals with ≥5 factors (P < 0.001), particularly older men. The benefits were more pronounced among patients with major comorbidities, such as cardiovascular disease, cancer, hypertension, diabetes, kidney disease and those with multimorbidity throughout all age categories. CONCLUSION: adopting modifiable healthy lifestyles was associated with lifetime gain, even in individuals aged 80 years or more, regardless of the presence of any major comorbidities in each life stage since middle age. The findings imply the importance of improving the one's lifestyle for an increased lifespan, even among older patients and/or those with multimorbidity.

Leukocyte Count and Risks of Stroke and Coronary Heart Disease: The Circulatory Risk in Communities Study (CIRCS).

AIM: This study aimed to investigate the associations of leukocyte count with the risks of stroke and coronary heart disease among the general Japanese population. METHODS: A total of 5,242 residents aged 40-69 years living in two Japanese communities underwent leukocyte count measurements between 1991 and 2000, and the data were updated using 5- or 10-year follow-ups or both. Participants who had histories of stroke, coronary heart disease, or high values of leukocyte count (＞130×102 cells/mm3) were excluded. Hazard ratios with 95% confidence intervals (CIs) were calculated according to quartiles of cumulative average leukocyte count. RESULTS: During follow-up of 21 years, 327 stroke and 130 coronary heart disease cases were determined. After adjustments for age, sex, community, and updated cardiovascular risk factors, the multivariable hazard ratio (95% CI) for the highest versus lowest quartile of leukocyte count was 1.50 (1.08-2.08) for ischemic stroke, 1.59 (1.00-2.51) for lacunar infarction, 1.42 (0.90-2.26) for non-lacunar infarction, 2.17 (1.33-3.55) for coronary heart disease, and 1.40 (1.11-1.76) for total cardiovascular disease. In smoking status-stratified analyses, the corresponding multivariable hazard ratio (95% CI) was 2.45 (1.11-5.38) for ischemic stroke, 2.73 (1.37-5.44) for coronary heart disease in current smokers, 2.42 (1.07-5.46), 1.55 (0.58-4.15) in former smokers, and 1.17 (0.75-1.82), 1.78 (0.83-3.82) in never smokers. CONCLUSION: Leukocyte count was positively associated with the risks of ischemic stroke and coronary heart disease among the general Japanese population, especially in current smokers.

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.

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.

A method for measuring glycerol-blanked triglyceride concentrations by using gas chromatography-isotope dilution mass spectrometry.

BACKGROUND: Serum triglyceride concentrations are measured as total glycerides content in many Western countries. In Japan, glycerol-blanked triglycerides (TG-GB) are measured to identify postprandial hypertriglyceridaemia and to minimize the influence of glycerol formulation on serum triglyceride values. However, TG-GB measurements have not been standardized. Therefore, we developed an efficient quantification system for total glycerides and free glycerol that allows the calculation of TG-GB concentrations. METHODS: We measured total glycerides and free glycerol in human serum by using gas chromatography-isotope dilution mass spectrometry and compared its performance to the reference method of the US Centers for Disease Control and Prevention (CDC). RESULTS: Our practical method of total glycerides and free glycerol quantification achieved excellent precision for both within-run and among-run coefficients of variation (<1.5% and <2.7%, respectively), with an average recovery of 99.8% for free glycerol. However, we noted an average %bias of -0.26% for total glycerides and -3.15% for free glycerol between our TG-GB method and the CDC reference method. CONCLUSIONS: This practical method of total glycerides and free glycerol quantification enables traceability assessment of TG-GB measurements. Differences between the output values of TG-GB and the CDC reference method might result from the differences in free glycerol values.

Urinary 8-Hydroxy-2'-Deoxyguanosine Levels and Cardiovascular Disease Incidence in Japan.

AIM: The association between urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker, and the incidence of cardiovascular disease (CVD) has not been confirmed because no previous studies evaluated 24-hour 8-OHdG excretion levels in the general population. We aimed to confirm the association between 24-hour urinary 8-OHdG levels and CVD risk among Japanese men and women. METHODS: A nested case-control study was performed based on a 24-hour urine collection in a community-based cohort study performed from 1996 to 2005. Seventy-six cases (55 men and 21 women) who experienced their first CVD incidence during the follow-up period (median: 5.9 years) were recruited. The controls were frequency-matched 1:2, with each case for sex, age, area of residence, and baseline year. The 8-OHdG level was measured by enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression models adjusted for body mass index, ethanol intake, smoking status, and estimated glomerular filtration rate. RESULTS: The geometric mean and geometric standard deviation (SD) of 8-OHdG levels (nmol/day) for cases and controls were 35.5 (1.55) and 35.5 (1.54) for men and 32.1 (1.35) and 25.0 (1.39) for women, respectively. The multivariable OR (95% CI) of CVD incidence according to the 1-SD increment of the log-transformed 8-OHdG level was 2.08 (0.99-4.37) for women. The multivariable ORs (95% CIs) for the 1st (lowest) and 4th versus 2nd quartile according to 8-OHdG for men were 3.29 (1.02-10.61) and 2.77 (0.96-7.96), respectively. CONCLUSION: A high 8-OHdG level tended to be associated with CVD incidence among women.

Relationships Between Reproductive History and Mortality From Cardiovascular Diseases Among Japanese Women: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC) Study.

BACKGROUND: Reproductive history has been addressed as a risk factor for cardiovascular disease (CVD). We examined the relationship between reproductive history and CVD mortality in Japanese women. METHODS: We followed 53,836 women without previous CVD or cancer history from 1988-1990 to 2009 in a prospective cohort study. Hazard ratios (HRs) and 95% confidence intervals (CIs) of CVD mortality were estimated according to the number of deliveries and maternal age at first delivery. RESULTS: During the follow-up, 2,982 CVD-related deaths were identified. There was U-shaped association between the number of deliveries and risk of CVD mortality with reference to three deliveries, although the excess risk of CVD mortality associated with ≥5 deliveries was of borderline statistical significance. The corresponding multivariable HRs were 1.33 (95% CI, 1.12-1.58) and 1.11 (95% CI, 0.99-1.24). In addition, higher CVD mortality was associated with maternal age ≥28 years at first delivery than maternal age of 24-27 years at first delivery. The multivariable HRs were 1.22 (95% CI, 1.10-1.36) for 28-31 years at first delivery and 1.26 (95% CI, 1.04-1.52) for ≥32 years at first delivery. Moreover, among women with ≥3 deliveries, maternal age ≥28 years at first delivery was associated with 1.2- to 1.5-fold increased CVD mortality. CONCLUSION: The number of deliveries showed a U-shaped association with risk of CVD mortality. Higher maternal age at first delivery was associated with an increased risk of CVD mortality, and excessive risk in women aged ≥28 years at first delivery was noted in those with ≥3 deliveries.

Effects of Low-Dose Therapist-Led Self-Exercise Education on the Management of Chronic Low Back Pain: Protocol for a Community-Based, Randomized, 6-Month Parallel-Group Study.

INTRODUCTION: Chronic low back pain (CLBP), defined as low back pain persisting for at least 3 months, leads to limitations in the activities of daily living and decreased quality of life. Individualized self-exercise education could be a preferable treatment option, especially in community-dwelling people with CLBP. Previous studies, however, did not directly compare the effects of therapist-led self-exercise education and material-only education, and there are only a few studies investigating the effects of low-dose (comprising a few sessions) self-exercise education on CLBP. We present a protocol of community-based, randomized study to evaluate the effects of low-dose (comprising a few sessions), therapist-led self-exercise education on CLBP. METHODS: Forty-eight participants with CLBP (men and women, aged 40-74 years) will be allocated to therapeutic self-exercise education programs, either a therapist-led group (2-week therapist's consultation and material use) or material-only group (material use only), in a randomized controlled trial. Pain intensity (NRS, numeric rating scale), pain disability (RDQ, Roland-Morris disability questionnaire), pain self-efficacy (PSEQ, pain self-efficacy questionnaire), and quality of life score (EQ-5D, European quality of life-5 dimensions) will be measured at baseline and at 4, 12, and 24 weeks. We will apply a repeated-measures design with mixed-effect models to estimate group differences from the baseline. Ethics/Trial registration number: The protocol was approved by the Ethics Committees of the Osaka Center for Cancer and Cardiovascular Disease Prevention and Osaka University. The trial registration number is registered on the University Hospital Medical Information Network (UMIN000024537).

The Association of Having a Late Dinner or Bedtime Snack and Skipping Breakfast with Overweight in Japanese Women.

Background: We aimed to assess the association of habitually eating in the late evening and skipping breakfast with the prevalence of overweight/obesity. Methods: A total of 19,687 Japanese women, aged 40-74 years, were asked about their height, weight, and habitual eating behaviors such as having a late dinner and a bedtime snack and skipping breakfast, using a self-administered questionnaire. We defined overweight/obesity as body mass index greater than or equal to 25 kg/m2. Results: Among the participants, 11% regularly had a late dinner, 22% had bedtime snacks, and 8% skipped breakfast. After adjusting for age, exercise, smoking, sleep duration, and employment, the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of skipping breakfast were 2.47 (2.18-2.81) for having a late dinner and 1.71 (1.53-1.91) for having a bedtime snack. These eating behaviors were associated with an increased risk of overweight/obesity: the multivariable-adjusted ORs (95% CIs) of obesity/overweight were 1.43 (1.27-1.62) for having a late dinner, 1.47 (1.34-1.62) for having a bedtime snack, and 1.23 (1.06-1.42) for skipping breakfast. Conclusions: Japanese women who consumed late dinners or bedtime snacks were more likely to skip breakfast. Having a late dinner or bedtime snack was associated with a higher probability of overweight/obesity.