The gut microbiota and coronary artery calcification in Japanese men.

BACKGROUND: The gut microbiota differs between patients with coronary artery disease (CAD) and healthy controls; however, it currently remains unclear whether these differences exist prior to the onset of CAD. We herein investigated the gut microbiota associated with subclinical coronary artery calcification (CAC) in a Japanese population. METHODS: A total of 663 Japanese men were enrolled in this cross-sectional study. Computed tomography and gut microbiology tests were performed, and CAC scores were calculated using the Agatston method. Participants were categorized into 4 groups based on their CAC scores: CAC = 0, 0

Relationship Between Hemoglobin Concentration and Cardiovascular Disease Mortality in a 25-Year Follow-up Study of a Japanese General Population　- NIPPON DATA90.

BACKGROUND: Deviations of hemoglobin from normal levels may be a factor in cardiovascular disease (CVD) risk; however, conclusive evidence is lacking. In addition, preclinical conditions may influence hemoglobin concentrations, but studies focusing on reverse causation are limited. Thus, we examined the relationship between hemoglobin concentrations and CVD mortality risk, considering reverse causation.Methods and Results: In a prospective cohort representative of the general Japanese population (1990-2015), we studied 7,217 individuals (mean age 52.3 years; 4,219 women) without clinical CVD at baseline. Participants were categorized into sex-specific hemoglobin quintiles (Q1-Q5) and data were analyzed using the Cox proportional hazards model adjusted for possible confounders. During a 25-year follow-up, 272 men and 334 women died from CVD. Adjusted hazard ratios for CVD mortality across sex-specific quintiles, using Q3 as the reference, were significantly higher for Q1 (1.40; 95% confidence interval [CI] 1.08-1.82) and Q5 (1.49; 95% CI 1.14-1.96), and remained significant after excluding deaths within the first 5 years of follow-up to consider reverse causation (1.35 [95% CI 1.02-1.79] and 1.45 [95% CI 1.09-1.94], respectively). A similar U-shaped association was seen between transferrin saturation levels and CVD mortality, but after excluding deaths within the first 5 years the association was significant only for Q1. CONCLUSIONS: Low and high hemoglobin concentrations were associated with an increased risk of CVD mortality.

GWAS meta-analysis of kidney function traits in Japanese populations.

BACKGROUND: Genetic epidemiological evidence for the kidney function traits in East Asian population including Japanese remain still relatively unclarified. Especially, the number of GWASs for kidney traits reported still remains limited, and the sample size of each independent study is relatively small. Given the genetic variability between ancestries/ethnicities, implementation of GWAS with sufficiently large sample sizes in specific population of Japanese is considered meaningful. METHODS: We conducted the GWAS meta-analyses of kidney traits by leveraging the GWAS summary data of the representative large genome cohort studies with about 200,000 Japanese participants (n = 202,406 for estimated glomerular filtration rate [eGFR] and n = 200,845 for serum creatinine [SCr]). RESULTS: In the present GWAS meta-analysis, we identified 110 loci with 169 variants significantly associated with eGFR (on chromosomes 1-13 and 15-22; p < 5×10-8), whereas we also identified 112 loci with 176 variants significantly associated with SCr (on chromosomes 1-22; p < 5×10-8), of which one locus (more than 1Mb distant from known loci) with one variant (CD36 rs146148222 on chromosome 7) for SCr was considered as the truly novel finding. CONCLUSIONS: The present GWAS meta-analysis of largest genome cohort studies in Japanese provided some original genomic loci associated with kidney function in Japanese, which may contribute to the possible development of personalized prevention of kidney diseases based on genomic information in the near future.

Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study.

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m2 , the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m2 were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m2 were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m2 revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m2 , with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.

Association between proprotein convertase subtilisin/kexin type 9 and subclinical cerebrovascular disease in the community.

BACKGROUND AND PURPOSE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new target for reducing low-density lipoprotein cholesterol and incident cardiovascular disease, including stroke. However, the clinical relevance of circulating PCSK9 levels has been poorly elucidated in the general population, particularly in association with subclinical cerebrovascular disease including cerebral small vessel disease (CSVD) and intracranial artery stenosis (ICAS). METHODS: In community-dwelling Japanese men (n = 526) aged 46-82 years without a history of cardiovascular disease, the associations of serum PCSK9 levels with the prevalence of CSVD and ICAS were assessed using magnetic resonance imaging. CSVD included lacunar infarction, deep and subcortical white matter hyperintensity, periventricular hyperintensity and cerebral microbleeds. RESULTS: The median (interquartile range) age at baseline and serum PCSK9 levels were 69 (63-74) years and 240 (205-291) ng/ml, respectively. After adjusting for traditional cardiovascular risk factors including low-density lipoprotein cholesterol, multivariable Poisson regression with robust error variance revealed a significant association between PCSK9 levels (per 1 SD) and ICAS (relative risks 1.18, 95% confidence interval 1.02-1.37). Multivariable ordinal logistic regression for ICAS, with stenosis graded as mild (<50%) or moderate-severe (≥50%), revealed a similar association (common odds ratio 1.31, 95% confidence interval 1.04-1.64). However, no significant association was observed between serum PCSK9 levels and CSVD. CONCLUSIONS: Higher circulating PCSK9 levels were independently associated with an ICAS prevalence but not with CSVD prevalence. The quantification of circulating PCSK9 levels may help to identify individuals at high risk for cerebrovascular disease in the general population.

Control of Diabetes Mellitus and Long-Term Prognosis in Stroke Patients: The Shiga Stroke and Heart Attack Registry.

BACKGROUND: The relationship between diabetes control status and long-term prognosis after stroke incidence remains unclear. This study aimed to investigate the effect of diabetes status at admission on long-term survival in patients with first-ever stroke. METHODS: A retrospective cohort study was conducted based on the Shiga Stroke and Heart Attack Registry in Japan. Patients were classified according to their diabetes status and glycated hemoglobin (HbA1c) value at hospital admission into the following: (1) free of diabetes (no history of diabetes and HbA1c <6.5%); (2) good control (history of diabetes and HbA1c <7%; free of history and 6.5% ≤HbA1c <7%); and (3) poor control (with or without a history of diabetes and HbA1c ≥7%). Multivariable Cox regression models were used to evaluate the association between diabetes status and long-term survival from stroke onset. Additionally, we also evaluated the association between diabetes status and conditional survival, beginning 29 days after stroke onset. RESULTS: A total of 6,331 first-ever stroke patients were eligible for this study. Among study patients, the mean (±SD) age was 72.85 ± 13.19 years, and the mean (±SD) follow-up year was 2.76 ± 1.66 years; additionally, 42.09% of patients were women. Among patients with all strokes, considering the free-of-diabetes group as the reference group, the adjusted hazard ratio (95% confidence interval) for mortality was 1.26 (1.10, 1.44) in the good control group and 1.22 (1.05, 1.41) in the poor control group. Among patients with ischemic stroke, the adjusted hazard ratio was 1.24 (1.06, 1.46) in good control group and 1.27 (1.08, 1.50) in poor control group. After excluding patients who died within 28 days, the adjusted hazard ratio for conditional mortality in the poor control group was 1.31 (1.12, 1.54) among all stroke patients and 1.29 (1.08, 1.54) among ischemic stroke patients. No significant associations were observed between diabetic status and long-term mortality in intracerebral hemorrhage patients. CONCLUSIONS: The findings suggest that first-ever stroke patients with diabetes exhibited a higher risk of all-cause mortality than those without diabetes, particularly in the overall stroke and ischemic stroke populations. Additionally, in stroke populations after 28 days of onset, high risk of long-term mortality was stated in stroke patients with poor HbA1c control.

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

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

Impact of Resting Heart Rate on Cardiovascular Mortality According to Serum Albumin Levels in a 24-year Follow-up Study on a General Japanese Population: NIPPON DATA80.

BACKGROUND: Elevated resting heart rate (RHR) is associated with an increased risk of cardiovascular disease (CVD) and all-cause mortality. However, the findings of cohort studies differed. Thus, the impact of RHR on CVD mortality might be different according to the background of the population. Therefore, we examined the relationship of RHR and CVD mortality according to serum albumin (ALB) levels in a Japanese general population. METHODS: In total, 8,363 individuals without a history of CVD were followed for 24.0 years. The participants were divided into four groups according to the quartiles of RHR (Q1-Q4), and they were further classified into the high and low ALB groups based on a median value of 44 g/L. We estimated the multivariable-adjusted hazard ratios (HRs) of CVD mortality in each RHR group based on ALB levels, and the interaction between RHR and ALB groups on CVD mortality was evaluated. RESULTS: We found no significant association between RHR and CVD mortality. However, the Q4 of RHR was significantly associated with an increased risk for CVD mortality (HR 1.27; 95% confidence interval [CI], 1.02-1.57) in participants with a low ALB level. Meanwhile, the Q4 of RHR was significantly correlated with a decreased risk for CVD morality in those with a high ALB level (HR 0.61; 95% CI, 0.47-0.79) after adjusting for covariates. A significant interaction between RHR and ALB for CVD mortality was shown (P < 0.001). CONCLUSION: The impact of RHR on CVD mortality differed according to ALB levels in a general Japanese population.

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

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

Sex-specific Relationship Between Stress Coping Strategies and All-cause Mortality: Japan Multi-Institutional Collaborative Cohort Study.

BACKGROUND: Stress coping strategies are related to health outcomes. However, there is no clear evidence for sex differences between stress-coping strategies and mortality. We investigated the relationship between all-cause mortality and stress-coping strategies, focusing on sex differences among Japanese adults. METHODS: A total of 79,580 individuals aged 35-69 years participated in the Japan Multi-Institutional Collaborative Cohort Study between 2004 and 2014 and were followed up for mortality. The frequency of use of the five coping strategies was assessed using a questionnaire. Sex-specific, multivariable-adjusted hazard ratios (HRs) for using each coping strategy ("sometimes," and "often/very often" use versus "very few" use) were computed for all-cause mortality. Furthermore, relationships were analyzed in specific follow-up periods when the proportion assumption was violated. RESULTS: During the follow-up (median: 8.5 years), 1,861 mortalities were recorded. In women, three coping strategies were related to lower total mortality. The HRs for "sometimes" were 0.81 (95% confidence interval [CI], 0.67-0.97) for emotional expression, 0.79 (95% CI, 0.66-0.95) for emotional support-seeking, and 0.80 (95% CI, 0.66-0.98) for disengagement. Men who "sometimes" used emotional expression and sometimes or often used problem-solving and positive reappraisal had a 15-41% lower HRs for all-cause mortality. However, those relationships were dependent on the follow-up period. There was evidence that sex modified the relationships between emotional support-seeking and all-cause mortality (P for interaction = 0.03). CONCLUSION: In a large Japanese sample, selected coping strategies were associated with all-cause mortality. The relationship of emotional support-seeking was different between men and women.

Association between visceral fat accumulation and decline in the estimated glomerular filtration rate based on cystatin C in the Japanese urban population: the KOBE study.

Although metabolic syndrome, including visceral fat accumulation, causes kidney and cardiovascular diseases, the impact of visceral fat accumulation on mild decreased renal function remains unclear. This study examines the association between visceral fat area (VFA) measured by bioimpedance methods and the estimated glomerular filtration rate based on serum cystatin C (eGFRcys) in the Japanese urban population. This community-based cross-sectional study enrolled 952 individuals (287 men, 665 women) who participated in the second follow-up survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. We compared the multivariate-adjusted means of eGFRcys among VFA quartile groups by gender using the analysis of covariance. Models were adjusted for age, high blood pressure, hypercholesterolemia, glucose intolerance, smoking, and alcohol use, and further adjusted for body mass index (BMI). The highest VFA quartile group had lower eGFRcys than the lowest VFA quartile group after adjusted for cardiometabolic risk factors, except for BMI (93.1 [95% confidence interval (CI), 90.1-96.2] vs. 82.1 [95% CI, 79.1-85.0] in men and 95.8 [95% CI, 94.1-97.5] vs. 89.4 [95% CI, 87.8-90.9] in women). Moreover, further adjustment for BMI revealed a similar result in men (93.5 [95% CI, 89.8-97.2] vs. 81.6 [95% CI, 77.9-85.3]), while no significant association was found in women. This study suggests a significant association between increased VFA levels and lower eGFRcys levels independent of cardiometabolic risk factors, such as glucose intolerance and hypercholesterolemia in men and women, as well as independent of BMI in men.

Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes: An Individual-Participant Data Meta-Analysis.

Importance: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. Objective: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. Design, Setting, and Participants: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. Exposures: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). Main Outcomes and Measures: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. Results: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). Conclusions and Relevance: In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.

[Determinants of salt taste threshold among urban residents: the KOBE study].

Objectives　Though having a high salt taste threshold has been associated with hypertension, its exact determinants remains unclear. This study aimed to identify the determinants of salt taste threshold in a community-based population and to determine the relationship between salt taste thresholds and the simultaneous presence of multiple determinants.Methods　Of the 1,117 participants of the baseline survey of the Kobe study, a cohort study of healthy urban residents, aged 40-74 years, with no history of cancer or cardiovascular diseases, nor undergoing treatment for hypertension, diabetes, or dyslipidemia, was conducted. Among them, 1,116 underwent the salt taste threshold test, and urine samples were collected to determine their estimated salt intake. The salt taste threshold test was carried out using SALSAVE®, with a salt taste threshold of 0.6% defined as normal, and that of 0.8% or more defined as high. A binomial logistic regression model was used, with high salt taste threshold as the objective variable, and life and family status, education, smoking and alcohol drinking status, intake status of salt dried fish, stress indicators, and daily salt intake (estimated from the urine sample) as the explanatory variables. A binomial logistic regression analysis was conducted, through multivariate analysis using the forced entry method, with factors influencing salt taste threshold as explanatory variables, and salt taste threshold (normal/high) as the objective variable. This analysis was performed excluding the urinary sodium-to-potassium ratio to account for multicollinearity with the estimated daily salt intake.Results　The mean age was 60.9±9.0 years for men, and 58.0±8.7 years for women. The salt taste threshold was normal in 80.9% (n=903) of the participants (73.6% [n=251] men and 84.1% [n=652] women), and high in 19.1% (n=213) of the participants (26.3% [n=90] men and 15.9% [n=123] women). Multivariate analysis revealed that smoking habits were significantly associated with a higher salt taste threshold, with an odds ratio (95% confidence interval) of 2.51 (1.33-4.74) for all participants. The odds ratio for a high salt taste threshold was 1.45 (1.03-2.03) for the top 25% estimated daily salt intake group, showing a significant association with a high salt taste threshold. In the analysis by sex, smoking habits were associated with higher salt taste thresholds, while an association with estimated daily salt intake was observed only in men.Conclusion　Smoking status and estimated daily salt intake were associated with higher salt taste thresholds in healthy urban residents.

Differential Association of Serum n-3 Polyunsaturated Fatty Acids with Various Cerebrovascular Lesions in Japanese Men.

BACKGROUND: An association between a high intake of marine-derived n-3 polyunsaturated fatty acids (n-3 PUFAs) with a lower risk of coronary heart disease was previously reported. However, the association between n-3 PUFAs and cerebrovascular lesions remains unclear. We evaluated this association in a general-population-based sample of Japanese men. METHODS: Participants were community-dwelling men (40-79 years old) living in Kusatsu City, Shiga, Japan. Serum concentrations of n-3 PUFAs, defined as the sum of eicosapentaenoic and docosahexaenoic acids, were measured via gas-liquid chromatography between 2006 and 2008. Magnetic resonance imaging was used to assess cerebrovascular lesions (including intracerebral large-artery stenosis, lacunar infarction, and microbleeds) and white matter lesions between 2012 and 2015. Logistic regression adjusting for conventional cardiovascular risk factors was used to estimate the odds ratio of prevalent cerebrovascular lesions per 1 standard deviation higher serum concentration of n-3 PUFAs. RESULTS: Of a total of 739 men, the numbers (crude prevalence in %) of prevalent cerebral large-artery stenoses, lacunar infarctions, microbleeds, and white matter lesions were 222 (30.0), 162 (21.9), 103 (13.9), and 164 (22.2), respectively. A 1 standard deviation higher concentration of n-3 PUFAs (30.5 µmol/L) was independently associated with lower odds of cerebral large-artery stenosis (multivariable-adjusted odds ratio, 0.80; 95% confidential interval, 0.67-0.97). There were no significant associations of n-3 PUFAs with the other types of lesions. CONCLUSIONS: n-3 PUFAs may have protective effects against large-artery stenosis, but not small vessel lesions, in the brain.

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

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

Relationship of leisure-time and household physical activity level and type with cardiovascular disease: secondary analysis of the Takashima Study data.

BACKGROUND: High levels of participation in leisure-time and household physical activity lower the risk of cardiovascular disease (CVD), although it is unclear whether the number of activity types is related to new-onset CVD. We aimed to evaluate the effect of the amount of leisure-time physical activity and the number of types of leisure-time physical activities on the risk of CVD incidence. METHODS: From 2002 to 2003, 3,741 participants without any history of CVD participated in the Takashima Study. Data on the amount of leisure-time and household physical activity and the types of leisure-time and household physical activity were obtained from a self-administered questionnaire. Hazard ratios for CVD (acute myocardial infarction and stroke) incidence (follow-up data from 2002 to 2013), according to the participation level and number of activity types, were calculated using Cox proportional hazards models. RESULTS: The mean age of the subjects was 58.7 ± 13.1 years. During the mean follow-up period of 8.0 ± 1.1 years, 92 participants developed CVD. An inverse dose-response relationship was noted between the amount of leisure-time and household physical activity and CVD events. After adjusting for baseline characteristics, lifestyle-related diseases, and the amount of physical activity other than leisure-time and household, the risk of CVD onset was compared by dividing the participants into two groups by the level of participation; the highest activity group had an adjusted hazard ratio (95% confidence interval) of 0.40 (0.20-0.82) compared to the lowest activity group. Compared to participants who engaged in 0-1 type of activity, participants who engaged in two or more types of activities had a multivariable-adjusted hazard ratio (95% confidence interval) of 0.31 (0.12-0.79). CONCLUSION: Increasing the amount of leisure-time and household physical activity and promoting engagement in two or more types of such activities may reduce the rate of CVD incidence in the Japanese general population.

Relationship Between Non-fasting Triglycerides and Cardiovascular Disease Mortality in a 20-year Follow-up Study of a Japanese General Population: NIPPON DATA90.

BACKGROUND: Non-fasting triglycerides (TG) are considered a better predictor of cardiovascular disease (CVD) than fasting TG. However, the effect of non-fasting TG on fatal CVD events remains unclear. In the present study, we aimed to explore the relationship between non-fasting TG and CVD mortality in a Japanese general population. METHODS: A total of 6,831 participants without a history of CVD, in which those who had a blood sampling over 8 hours or more after a meal were excluded, were followed for 18.0 years. We divided participants into seven groups according to non-fasting TG levels: ≤59 mg/dL, 60-89 mg/dL, 90-119 mg/dL, 120-149 mg/dL, 150-179 mg/dL, 180-209 mg/dL, and ≥210 mg/dL, and estimated the multivariable-adjusted hazard ratios (HRs) of each TG group for CVD mortality after adjusting for potential confounders, including high density lipoprotein cholesterol. Additionally, we performed analysis stratified by age <65 and ≥65 years. RESULTS: During the follow-up period, 433 deaths due to CVD were detected. Compared with a non-fasting TG of 150-179 mg/dL, non-fasting TG ≥210 mg/dL was significantly associated with increased risk for CVD mortality (HR 1.56: 95% CI, 1.01-2.41). Additionally, lower levels of non-fasting TG were also significantly associated with increased risk for fatal CVD. In participants aged ≥65 years, lower levels of non-fasting TG had a stronger impact on increased risk for CVD mortality, while higher levels of non-fasting TG had a stronger impact in those aged <65 years. CONCLUSION: In a general Japanese population, we observed a U-shaped association between non-fasting TG and fatal CVD events.

Association between Stress-Coping Strategy and Functional Disability in the General Older Adult Population: The Takashima Study.

BACKGROUND: Both physical and psychological factors have been associated with functional disability. However, the associations between stress-coping strategies and future functional disability remain unclear. METHODS: We analyzed 2,924 participants who did not have incidence of functional disability or death within the first 3 years of the baseline survey and were aged 65 years or more at the end of follow-up. Stress-coping strategies were assessed via a self-administered questionnaire (emotional expression, emotional support seeking, positive thought, problem-solving, and disengagement) in a baseline survey from 2006 to 2014. Levels of coping strategies were classified as low, middle, and high based of frequency. Functional disability decline was followed up using the long-term-care insurance program until November 1, 2019. Functional disability decline was defined as a new long-term-care insurance program certification. Cox proportional hazards model with competing risk analysis for death was used to evaluate associations between coping strategy levels and functional disability. RESULTS: During the follow-up period, we observed 341 cases of functional disability and 73 deaths without previous incidence of functional disability. A significant inverse association between "positive thought" and "problem-solving" and future functional disability was observed. Multivariable adjusted hazard ratios (95% confidence interval) for functional disability were 0.68 (0.51-0.92) for high levels of "positive thought" and 0.73 (0.55-0.95) for high levels of "problem-solving," compared with low levels of the coping strategies. The inverse association was stronger in men. CONCLUSIONS: Some subcomponents of stress-coping strategies might be associated with future incidence of functional disability among older adults.

A genome-wide association study on confection consumption in a Japanese population: the Japan Multi-Institutional Collaborative Cohort Study.

Differences in individual eating habits may be influenced by genetic factors, in addition to cultural, social or environmental factors. Previous studies suggested that genetic variants within sweet taste receptor genes family were associated with sweet taste perception and the intake of sweet foods. The aim of this study was to conduct a genome-wide association study (GWAS) to find genetic variations that affect confection consumption in a Japanese population. We analysed GWAS data on confection consumption using 14 073 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a semi-quantitative FFQ to estimate food intake that was validated previously. Association of the imputed variants with confection consumption was performed by linear regression analysis with adjustments for age, sex, total energy intake and principal component analysis components 1-3. Furthermore, the analysis was repeated adjusting for alcohol intake (g/d) in addition to the above-described variables. We found 418 SNP located in 12q24 that were associated with confection consumption. SNP with the ten lowest P-values were located on nine genes including at the BRAP, ACAD10 and aldehyde dehydrogenase 2 regions on 12q24.12-13. After adjustment for alcohol intake, no variant was associated with confections intake with genome-wide significance. In conclusion, we found a significant number of SNP located on 12q24 genes that were associated with confections intake before adjustment for alcohol intake. However, all of them lost statistical significance after adjustment for alcohol intake.

Relationship of Ambient Temperature Parameters to Stroke Incidence in a Japanese Population　- Takashima Stroke Registry, Japan, 1988-2010.

BACKGROUND: Using a population-based stroke registry system, we evaluated the relationship between ambient temperature parameters and stroke incidence in a Japanese population.Methods and Results:We analyzed data from the Takashima Stroke Registry, which records all stroke occurrences in Takashima City, Japan. The study period of 8,401 days was divided into quintiles of daily weather parameters, and the middle quintile was used as the reference category. Incidence rates (IR per 100,000 person-years) were calculated across the quintiles. Poisson regression analysis was used to calculate the effect of temperature parameters on stroke incidence. There were 2,405 first-ever strokes (1,294 men), including 1,625 ischemic, 545 cerebral hemorrhages, 213 subarachnoid hemorrhages, and 22 unclassified strokes. The stroke IR was higher in the middle quintile of average temperature, 357.3 (328.4-388.8), and for other parameters. After adjustment for age and sex, for all stroke, the incidence rate ratio (IRR) in the highest (Q5: IRR 0.81, 95% confidence interval (CI) 0.71-0.92) and the second-highest (Q4: IRR 0.80, 95% CI 0.71-0.91) quintile was lower than that in the middle quintile (Q3: Reference). Analogous results were observed for the minimum, maximum, and lag-days temperatures, also in the subtypes and across ≥65 years of age, also in females. CONCLUSIONS: Higher temperatures, irrespective of the parameter (average, minimum, or maximum), had a protective effect against stroke occurrence in Japan.