Breastfeeding in Infancy in Relation to Subsequent Physical Size: A 20-year Follow-up of the Ibaraki Children's Cohort Study (IBACHIL).

BACKGROUND: Breastfeeding is said to prevent overweight and obesity in childhood but the evidence about its long-term impact on body size into adolescence and adulthood is scarce. We sought to examine the association between feeding types and subsequent physical size at the ages of 3, 6, 12, and 22 years. METHODS: The Ibaraki Children's Cohort (IBACHIL) Study, which began in 1992, involved a cohort of 4,592 Japanese children from 87 communities of a single prefecture whose parents answered health questionnaires about their child's health and life habits at the age of 3 years. Follow-up questionnaires were distributed to the same cohort when they were 6, 12, and 22 years old. Self-reported height and weight, body mass index (BMI), and overweight status at ages of 3 (n = 4,290), 6 (n = 1,999; proportion of participants analyzed = 47%), 12 (n = 2,227; 52%), and 22 (n = 1,459; 34%) years were compared according to feeding type (breastfeeding, formula feeding, and mixed feeding) during infancy. RESULTS: At the age of 3 years, multivariable adjusted-mean weight and prevalence of overweight were less for breastfed children than those formula-fed in both boys (weight: 14.6 kg vs 14.7 kg, P = 0.07, overweight: 6.3% vs 9.3%, P = 0.03) and in girls (14.0 kg vs 14.2 kg, P = 0.01 and 10.4% vs 13.6%, P = 0.06). However, there were no statistically significant differences in weight, BMI, and overweight at the ages of 6, 12, and 22 years according to feeding type. CONCLUSION: Breastfeeding may prevent overweight in childhood, but its impact is not significant in adolescence and adulthood.

Right bundle branch block and risk of cardiovascular mortality: the Ibaraki Prefectural Health Study.

Historically, a right bundle branch block has been considered a benign finding in asymptomatic individuals. However, this conclusion is based on a few old studies with small sample sizes. We examined the association between a complete right bundle branch block (CRBBB) and subsequent cardiovascular mortality in the general population in Japan. In this large community-based cohort study, data of 90,022 individuals (mean age, 58.5 ± 10.2 years; 66.2% women) who participated in annual community-based health check-ups were assessed. Subjects were followed up from 1993 to the end of 2016. Cox proportional hazards' models and log-rank tests were used for the data analysis. CRBBB was documented in 1,344 participants (1.5%). Among all included participants, CRBBB was associated with an increased risk of cardiovascular mortality after adjustment for all potential confounders (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.06-1.38). The increased risk of cardiovascular mortality was particularly evident in women aged < 65 years (HR 2.00; 95% CI 1.34-2.98) and men aged ≥ 65 years (HR 1.28; 95% CI 1.06-1.55). CRBBB is associated with an increased risk of cardiovascular mortality in women aged < 65 years and men aged ≥ 65 years. Clinicians should be aware of the presence of CRBBB in young women and elderly men, even if they exhibit no symptoms.

High Hematocrit Levels Are Associated with Risk of Cardiovascular Mortality among Middle-Aged Japanese Women: The Ibaraki Prefectural Health Study (IPHS).

In Japan, heart disease and cerebrovascular disease were the second and fourth leading cause of death, respectively in 2014. Hematocrit, the ratio of the red blood cells to the total volume of blood is known to play a role in cardiovascular diseases. However, the relationship between elevated hematocrit and the risk of cardiovascular disease based on sex has not been examined in Asian countries. We analyzed data from the Ibaraki Prefectural Health Study, a community-based large cohort study, which included 87,533 individuals, aged 40 to 79 years living in 38 municipalities of the Ibaraki Prefecture, who had completed an annual health checkup in 1993, and were followed until 2013. The hematocrit levels of the subjects were categorized into 5 quintiles (Q1-Q5), and hazard ratios for cause-specific mortality were calculated using the Cox proportional hazards regression models. Age and other cardiovascular risk factors were the covariates in the study. During the follow-up for a mean of 17.9 years, 1,207 deaths (615 men and 592 women) due to acute myocardial infarction (AMI) were reported in this population. The p values for the trend in the Q3-Q5 groups were 0.661 for men and 0.020 for women. Additionally, these values were significant in younger (40 to 59 years) women but not in older (60 to 79 years) women. This study is the first one to demonstrate an association between high hematocrit level and risk of AMI mortality in younger Japanese women, but not in men and older women.

Validity of a Risk Prediction Equation for CKD After 10 Years of Follow-up in a Japanese Population: The Ibaraki Prefectural Health Study.

BACKGROUND: Chronic kidney disease (CKD) is an important health problem for which risk equations have been developed for Western populations. This study aimed to develop and validate a risk prediction equation for CKD in a Japanese population. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: The study included 135,007 participants who completed an annual health checkup in 1993 to 1996 in the Ibaraki Prefecture in Japan. Participants were initially free of CKD (defined as stage 3, 4, or 5 CKD or proteinuria [2+ or 3+] by dipstick). Follow-up information was available from health checkups 10 years after the initial evaluation. We used data from 40,963 women and 17,892 men in the northern region of the prefecture for the development of risk prediction equations and 53,042 women and 23,110 men in the southern region for external validation. PREDICTORS: Age, estimated glomerular filtration rate (eGFR), body mass index, proteinuria, hematuria, hypertension, diabetes mellitus, smoking, and drinking. OUTCOME: Occurrence of CKD (defined as eGFR<60mL/min/1.73m2 and/or proteinuria [2+ or 3+] by dipstick). ANALYTICAL APPROACH: Logistic regression analysis to estimate risk for CKD stratified by sex. RESULTS: During follow-up, 7,500 cases of CKD developed in the northern region and 8,964, in the southern region. Older age, proteinuria (1+), higher systolic blood pressure, medication for hypertension, and current smoking were associated with increased risk for CKD in both sexes, whereas higher eGFR and daily alcohol intake were associated with lower risk. C statistics of risk estimation equations for CKD at 10 years were >0.8 for both the development and external validation populations, and discrimination of the risk estimation was fairly good in women and men. LIMITATIONS: Fluctuations in variables were not evaluated because the study used annual health checkups. This study excluded a large number of people for whom a 10-year health checkup was not available. CONCLUSIONS: Estimations of risk for CKD after 10 years of follow-up in a general Japanese population can be achieved with a high level of validity.

Impact of Speed-Eating Habit on Subsequent Body Mass Index and Blood Pressure Among Schoolchildren　- The Ibaraki Children's Cohort Study (IBACHIL).

BACKGROUND: Habitual speed eating is a risk factor of obesity but evidence of this in children is limited. We examined the association between speed-eating habit and subsequent body mass index (BMI) and blood pressure (BP) among Japanese children.Methods and Results:The community-based study comprised 1,490 Japanese boys and girls who were born in 1989, involved in the Ibaraki Children's Cohort Study at age 3 years, and had returned questionnaires at both ages 6 and 12 years. In a subsample, we measured BP (n=263). Speed-eating habit was categorized into 4 groups: Never, Quit, Newly, and Continuous. Sex-specific mean values of questionnaire-based BMI and measured BPs at age 12 were examined according to speed-eating habit. Children with continuous speed eating had a higher BMI at age 12 than those who had never had a speed-eating habit (20.0 vs. 17.9 kg/m2for boys (P<0.001); 20.0 vs. 18.4 kg/m2(P<0.001) for girls). Systolic BP at age 12 was higher in boys with continuous speed eating than in those without (117 vs. 110 mmHg, P=0.01), but such a difference was not observed in girls (112 vs. 111 mmHg, P=0.95). CONCLUSIONS: Habitualspeed eating was positively associated with subsequent BMI among boys and girls as well as with systolic BP among boys.

A pooled analysis of the association of isolated low levels of high-density lipoprotein cholesterol with cardiovascular mortality in Japan.

Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown to be associated with increased risk of coronary heart disease (CHD). However, because this is usually observed in the context of other lipid abnormalities, it is not known whether isolated low serum HDL-C levels are an independent risk factor for CHD. We performed a large pooled analysis in Japan using data from nine cohorts with 41,206 participants aged 40-89 years who were free of cardiovascular disease at baseline. We divided participants into three groups: isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138 deaths, respectively, in these groups. Non-isolated low HDL-C was significantly associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 % confidence interval (CI) 1.04-1.80); however, isolated low HDL-C was not. Although isolated low HDL-C was significantly associated with decreased risk of CHD (HR 0.51, 95 % CI 0.29-0.89) in women, it was significantly associated with increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62, 95 % CI 1.04-2.53) and in men (HR 2.00, 95 % CI 1.04-3.83). In conclusion, isolated low HDL-C levels are not associated with increased risk of CHD in Japan. CHD risk may, therefore, be more strongly affected by serum total cholesterol levels in this population.

Impact and attribute of each obesity-related cardiovascular risk factor in combination with abdominal obesity on total health expenditures in adult Japanese National Health insurance beneficiaries: The Ibaraki Prefectural health study.

BACKGROUND: The aim of this study was to examine the attribution of each cardiovascular risk factor in combination with abdominal obesity (AO) on Japanese health expenditures. METHODS: The health insurance claims of 43,469 National Health Insurance beneficiaries aged 40-75 years in Ibaraki, Japan, from the second cohort of the Ibaraki Prefectural Health Study were followed-up from 2009 through 2013. Multivariable health expenditure ratios (HERs) of diabetes mellitus (DM), high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), and hypertension with and without AO were calculated with reference to no risk factors using a Tweedie regression model. RESULTS: Without AO, HERs were 1.58 for DM, 1.06 for high LDL-C, 1.27 for low HDL-C, and 1.31 for hypertension (all P < 0.05). With AO, HERs were 1.15 for AO, 1.42 for DM, 1.03 for high LDL-C, 1.11 for low HDL-C, and 1.26 for hypertension (all P < 0.05, except high LDL-C). Without AO, population attributable fractions (PAFs) were 2.8% for DM, 0.8% for high LDL-C, 0.7% for low HDL-C, and 6.5% for hypertension. With AO, PAFs were 1.0% for AO, 2.3% for DM, 0.4% for low HDL-C, and 5.0% for hypertension. CONCLUSIONS: Of the obesity-related cardiovascular risk factors, hypertension, independent of AO, appears to impose the greatest burden on Japanese health expenditures.

Prognostic impact of supraventricular premature complexes in community-based health checkups: the Ibaraki Prefectural Health Study.

AIMS: The long-term prognosis of subjects with supraventricular premature complexes (SVPCs) remains unclear in the general population. The aim of this study was to examine the prognostic significance of SVPCs in community-based health checkups. METHODS AND RESULTS: We assessed 63 197 individuals (mean age, 58.8 ± 9.9 years; 67.6% women) who participated in annual community-based health checkups in 1993 and were followed until 2008. The primary endpoint was stroke death, cardiovascular death (CVD), or all-cause death during a 14-year mean follow-up, and the secondary endpoint was first atrial fibrillation (AF) event in subjects without self-reported heart diseases or AF at baseline. Compared with subjects without SVPCs, the multivariate-adjusted hazard ratios (HRs) [95% confidence interval (CI)] of stroke death, CVD, and all-cause death in subjects with SVPCs were 1.24 (0.98-1.56) for men and 1.63 (1.30-2.05) for women, 1.22 (1.04-1.44) for men and 1.48 (1.25-1.74) for women, and 1.08 (0.99-1.18) for men and 1.21 (1.09-1.34) for women, respectively. Atrial fibrillation occurred in 386 subjects during the follow-up (1.05/1000 person-years). The presence of SVPCs at baseline was the significant predictor of AF onset [HRs (95% CI): 4.87 (3.61-6.57) for men and 3.87 (2.69-5.57) for women]. Propensity score matched analyses also revealed the presence of SVPCs was significantly associated with increased risks of AF incidence and CVD even after adjusting the potential confounders. CONCLUSION: The presence of SVPCs in 12-lead electrocardiograms was a strong predictor of AF development, and associated with increased risk of CVD in general population.

Impact of Caregiver Type for 3-Year-Old Children on Subsequent Between-Meal Eating Habits and Being Overweight From Childhood to Adulthood: A 20-Year Follow-up of the Ibaraki Children's Cohort (IBACHIL) Study.

BACKGROUND: Because of the increasing number of mothers who continue to work after childbirth, participation in childcare has diversified. However, the impact of the main caregiver on children's habits has not been determined. We sought to examine the effect of caregiver differences on childhood habituation of between-meal eating and body mass index (BMI). METHODS: The Ibaraki Children's Cohort Study involved 4592 Japanese children whose parents answered health questionnaires at age 3. Follow-up questionnaires were distributed to parents when children were 6 and 12 years old and to study subjects directly when they were 22 years old. We compared prevalence of between-meal eating and overweight as well as mean BMI at ages 6, 12, and 22 years, by their main daytime caregiver at age 3. RESULTS: Compared to children cared for by mothers, those cared for by grandparents had a higher prevalence of between-meal eating before dinner for boys and girls at ages 6 and 12 years. At age 22 years, boys cared for by grandparents had a higher prevalence of overweight than those cared for by mothers (18.5% versus 11.2%, P = 0.037), but no such difference was noted in girls. However, both boys and girls cared for by grandparents had higher mean BMI over time than those cared for by mothers (coefficient = 0.47 kg/m(2) for boys and coefficient = 0.35 kg/m(2) for girls). CONCLUSIONS: Being cared for by grandparents at age 3 was associated with subsequent between-meal eating habits, being overweight, and increased mean BMI from childhood to adulthood.

Burden of total and cause-specific mortality related to tobacco smoking among adults aged ≥ 45 years in Asia: a pooled analysis of 21 cohorts.

BACKGROUND: Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest. METHODS AND FINDINGS: We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan-accounting for ∼71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37-1.51) and 1.48-fold (1.38-1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%-17.2%) and 3.3% (2.6%-4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000-1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y. CONCLUSIONS: Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented. Please see later in the article for the Editors' Summary.

Association between body-mass index and risk of death in more than 1 million Asians.

BACKGROUND: Most studies that have evaluated the association between the body-mass index (BMI) and the risks of death from any cause and from specific causes have been conducted in populations of European origin. METHODS: We performed pooled analyses to evaluate the association between BMI and the risk of death among more than 1.1 million persons recruited in 19 cohorts in Asia. The analyses included approximately 120,700 deaths that occurred during a mean follow-up period of 9.2 years. Cox regression models were used to adjust for confounding factors. RESULTS: In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI (the weight in kilograms divided by the square of the height in meters) in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range--by a factor of up to 1.5 among those with a BMI of more than 35.0 and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI. CONCLUSIONS: Underweight was associated with a substantially increased risk of death in all Asian populations. The excess risk of death associated with a high BMI, however, was seen among East Asians but not among Indians and Bangladeshis.

The dose-response relationship between body mass index and the risk of incident stage ≥3 chronic kidney disease in a general japanese population: the Ibaraki prefectural health study (IPHS).

PURPOSE: To examine the relationship between body mass index (BMI) and the risk of stage ≥3 chronic kidney disease (CKD) in a general Japanese population. METHODS: A total of 105 611 participants aged 40-79 years who completed health checkups in Ibaraki Prefecture, Japan, and were free of CKD in 1993 were followed-up through 2006. Stage ≥3 CKD was defined by an estimated glomerular filtration rate <60 mL/min/1.73 m(2) reported during at least 2 successive annual surveys or as treatment for kidney disease. Hazard ratios (HRs) for the development of stage ≥3 CKD relative to the BMI categories were calculated using the Cox proportional hazards regression model, which was adjusted for possible confounders and mediators. RESULTS: During a mean follow-up of 5 years, 19 384 participants (18.4%) developed stage ≥3 CKD. Compared to a BMI of 21.0-22.9 kg/m(2), elevated multivariable-adjusted HRs were observed among men with a BMI ≥23.0 kg/m(2) and women with a BMI ≥27.0 kg/m(2). Significant dose-response relationships between BMI and the incidence of stage ≥3 CKD were observed in both sexes (P for trend <0.001). CONCLUSIONS: Obesity was associated with the risk of developing stage ≥3 CKD among men and women.

Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event. OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.

Particulate Matter and Incident Chronic Kidney Disease in Japan: The Ibaraki Prefectural Health Study (IPHS).

Introduction: Global health hazards caused by air pollution, such as chronic kidney disease (CKD), have been gaining attention; however, air pollution-associated CKD has not been explored in Japan. Methods: We examined 77,770 men and women with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 in the Ibaraki Prefecture who participated in annual community-based health checkups from 1993 at 40-75 years old and were followed up through December 2020. The outcome was newly developed kidney dysfunction with eGFR of <60 ml/min/1.73 m2 during follow-up. To assess air pollution, a PM2.5 exposure model was employed to estimate yearly means at 1 × 1-km resolution, converted into means at the municipal level. Hazard modeling was employed to examine PM2.5 concentrations in residential areas as a risk factor for outcomes. Results: Participants were distributed across 23 municipalities in the Ibaraki Prefecture, with PM2.5 concentrations between 16.2 and 33.4 µg/m3 (mean, 22.7 µg/m3) in 1987-1995 as the exposure period. There were 942 newly developed kidney dysfunctions during follow-up. Based on 1987-1995 PM2.5 concentrations as the baseline exposure, the multivariate-adjusted hazard ratio per 10-µg/m3 increase in PM2.5 for newly developed kidney dysfunction was 1.02 (95%CI, 0.80-1.24) in men and 1.19 (95%CI, 0.95-1.44) in women. Conclusions: Elevated PM2.5 did not represent a significant risk factor for incident CKD in a prefecture in Japan.

Risk of death in old Japanese COVID-19 cases infected with the Omicron variant: a population-based study.

We assessed case fatality rates (CFRs) in cases aged ≥70 years in 10 Japanese prefectures (14.8 million residents) diagnosed between January 2022 and March 2023, when the Omicron variant was dominant in Japan. We selected incident reports on 283,052 study subjects from participating Public Health Centers adhering to the Infectious Diseases Control Law. Cases were passively followed up until the end of their isolation, date of death or 28 days after the COVID-19 diagnosis, whichever occurred first. We calculated age-standardized CFRs with 95% confidence intervals (CI) using the Japanese population aged 70-79, 80-89 and ≥90 in 2022 divided into 16 subgroups according to the period of COVID-19 diagnosis. The total overall CFR was 1.59% (95% CI 1.55-1.64); it ranged between 0.67% (95% CI 0.38-0.96, May 23-June 19) and 2.58% (95% CI 2.36-2.80, January 31-February 27). We observed three peaks of age-standardized CFRs paralleling the 6th, 7th and 8th endemic COVID-19 waves driven by Omicron in Japan (2.2% January 31-February 27, 1.0% July 18-August 14 and 1.6% December 26-January 22, 2023, respectively). Population-based CFRs for Omicron variant COVID-19 in Japanese aged ≥70 years remained <3% throughout the period January 2022-March 2023, including during three large endemic waves in this country.

Prediction of cardiovascular disease mortality by proteinuria and reduced kidney function: pooled analysis of 39,000 individuals from 7 cohort studies in Japan.

There are limited studies addressing whether proteinuria and estimated glomerular filtration rate (eGFR) are independently associated with cardiovascular disease in Asia. Using data from 7 prospective cohorts recruited between 1980 and 1994 in Japan, we assessed the influence of proteinuria (≥1+ on dipstick) and reduced eGFR on the risk of cardiovascular disease mortality in 39,405 participants (40-89 years) without kidney failure. During a 10.1-year follow-up, 1,927 subjects died from cardiovascular disease. Proteinuria was associated with a 1.75-fold (95% confidence interval (CI): 1.44, 2.11) increased risk of cardiovascular disease mortality after adjustment for potential confounding factors. Additionally, the multivariate-adjusted hazard ratio of cardiovascular disease mortality increased linearly with lower eGFR levels (P(trend) < 0.001): Subjects with eGFR of <45 mL/minute/1.73 m² had a 2.22-fold (95% CI: 1.60, 3.07) greater risk of cardiovascular disease mortality than those with eGFR of ≥90 mL/minute/1.73 m². Subjects with both proteinuria and eGFR of <45 mL/minute/1.73 m² had a 4.05-fold (95% CI: 2.55, 6.43) higher risk of cardiovascular disease mortality compared with those with neither of these risk factors. There was no evidence of interaction in the relationship between proteinuria and lower eGFR (P(interaction) = 0.77). The present results suggest that proteinuria and lower eGFR are independent risk factors for cardiovascular disease mortality in the Japanese population.

Relationship between cold temperature and cardiovascular mortality, with assessment of effect modification by individual characteristics: Ibaraki Prefectural Health Study.

BACKGROUND: Cold temperature has been reported to contribute to cardiovascular mortality, but it is not clear which people are more susceptible to cold temperature. METHODS AND RESULTS: The relationship between ambient temperature and mortality was examined in 3,593 subjects from the Ibaraki Prefectural Health Study who died of cardiovascular disease during a mean follow-up period of 9.7±4.0 years. Daily values of meteorological variables were obtained from the Japan Meteorological Agency. Time-stratified case cross-over analysis was used. The multivariate odds ratios (ORs; 95% confidence interval) per 1°C decrease in daily maximum temperature over the day of death and the 2 days prior to this day adjusted for relative humidity were 1.018 (1.003-1.034) for all cardiovascular deaths and 1.025 (1.003-1.048) for stroke deaths. Risk-stratified analysis showed that younger subjects aged <80 years and those with hyperglycemia were more susceptible to cold temperature. The OR of all cardiovascular deaths related to cold temperature was 1.034 (1.012-1.056) for subjects aged <80 years, and that of stroke deaths was 1.076 (1.023-1.131) for those with hyperglycemia. CONCLUSIONS: Exposure to cold temperature triggers cardiovascular deaths. Additionally, younger age and hyperglycemia could enhance susceptibility to cold temperature.

Low serum LDL cholesterol levels are associated with elevated mortality from liver cancer in Japan: the Ibaraki Prefectural health study.

Liver cancer a global public health concern and well known for poor prognosis. The association between low total cholesterol level and liver cancer has been reported. However, the association between low low-density lipoprotein (LDL) cholesterol levels and liver cancer is still unclear. The aim of this study was to examine the relationship between LDL cholesterol level and liver cancer mortality. A total of 16,217 persons (5,551 men and 10,666 women) aged 40-79 years in 1993 were followed until 2008. LDL cholesterol levels were divided into four categories (<80 mg/dl, 80-99 mg/dl, 100-119 mg/dl, and ≥120 mg/dl). Hazard ratio of LDL cholesterol level for liver cancer mortality was calculated using a multivariable Cox proportional hazards model. Covariates were age, sex, alanine transaminase, body mass index, alcohol intake and smoking status, all of which were correlated with LDL cholesterol levels. There were 51 deaths (32 men and 19 women) from liver cancer. Multivariable hazard ratios of liver cancer deaths for LDL cholesterol levels of <80 mg/dl was 4.33 (95% confident interval [CI]: 1.94, 9.68), for LDL cholesterol levels of 80-99 mg/dl was 1.03 (95% CI: 0.42, 2.53), and for LDL cholesterol levels of ≥120 mg/dl was 0.43 (95% CI: 0.20, 0.92) compared with LDL cholesterol levels of 100-199 mg/dl (p for trend<0.01). Therefore, low LDL cholesterol levels are associated with elevated risk of liver cancer mortality. Low LDL cholesterol may be a predictive marker for death due to liver cancer.

Risk Factors for Mortality From Aortic Aneurysm and Dissection: Results From a 26-Year Follow-Up of a Community-Based Population.

Background Aortic aneurysm rupture and acute aortic dissection are life-threatening conditions and represent an ever-growing public health challenge. Comprehensive epidemiologic investigations for their risk factors are scant. We aimed to investigate risk factors associated with mortality from aortic diseases through analysis of a community-based Japanese cohort. Methods and Results IPHS (Ibaraki Prefectural Health Study) comprises 95 723 participants who took part in municipal health checkups in 1993. Factors considered for analysis included age, sex, body mass index, blood pressure, serum lipids (high-density lipoprotein [HDL] cholesterol, non-HDL cholesterol, and triglycerides), diabetes, antihypertensive and lipid-lowering drug use, and smoking and drinking habits. Cox proportional hazards models were applied to evaluate the associations between these variables and mortality from aortic diseases. During the median 26-year follow-up, 190 participants died of aortic aneurysm rupture, and 188 died of aortic dissection. An increased multivariable hazard ratio (HR) for mortality from total aortic diseases was observed for high systolic blood pressure (1.61 [1.00-2.59]), diastolic blood pressure (2.95 [1.95-4.48]), high non-HDL cholesterol (1.63 [1.19-2.24]), low HDL cholesterol (1.86 [1.29-2.68]), and heavy (>20 cigarettes/day) smoking habit (2.46 [1.66-3.63]). A lower multivariable HR was observed for diabetes (0.50 [0.28-0.89]). Conclusions Smoking habit, higher systolic blood pressure and diastolic blood pressure levels, higher non-HDL, and lower HDL cholesterol levels were positively associated with mortality from total aortic diseases, whereas diabetes was inversely associated.