Search

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. Conclusions Breastfeeding may prevent overweight in childhood, but its impact is not significant in adolescence and adulthood.

We conducted a study to investigate the proportion of patients with asymptomatic coronavirus disease 2019 (COVID-19) infected with the Delta variant compared with those infected with the wild-type strain at the time of confirmation. A total of 504 patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by viral transmission through household contact in Ibaraki, Japan were included. The proportion of asymptomatic COVID-19 patients at the time of confirmation was compared between patients infected with L452R mutation strain from June to September 2021 and those infected with the wild-type strain from November 2020 to January 2021, and was found to be 14.2% and 28.8%, respectively (relative risk, 0.49; 95% confidence interval, 0.35-0.70). The proportion of asymptomatic COVID-19 patients by viral transmission through household contact was lower among the Delta variant than those among the wild-type strain at the time of confirmation. It might contribute to attenuation of transmission.

To assess temporal changes to the risk of death in COVID-19 cases caused by the Omicron variant, we calculated age-standardized case fatality rates (CFR) in patients aged ≥40 years over nine diagnostic periods (3 January to 28 August 2022) in ten Japanese prefectures (14.8 million residents). Among 552,581 study subjects, we found that there were 1836 fatalities during the isolation period (up to 28 days from date of onset). The highest age-standardized CFR (0.85%, 95% confidence interval (CI):0.78–0.92) was observed in cases diagnosed in the second 4-week period (January 31 to February 27), after which it declined significantly up to the 6th 4-week period (0.23%, 95% CI: 0.13–0.33, May 23 to June 19). The CFR then increased again but remained at 0.39% in the eighth period (July 18 to August 28). The CFR in cases with the BA.2 or BA.5 sublineages in the age range 60–80 years was significantly lower than that with BA.1 infections (60 years: 0.19%, 0.02%, 0.053%, respectively; 70 years: 0.91%, 0.33%, 0.39%; ≥80 years: 3.78%, 1.96%, 1.81%, respectively). We conclude that the risk of death in Japanese COVID-19 patients infected with Omicron variants declined through February to mid-June 2022.

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

AIM: To examine the association between long-term exposure to suspended particulate matter (SPM) and cardiovascular mortality in Japan after controlling for known major confounding factors among a large middle and elderly cohort study in Ibaraki Prefecture, Japan. METHODS: We followed 91,808 residents (men 34%) who undertook a national health check-up at age 40-79 years for 17 years (1993-2010). Two different exposure indices were adopted: baseline SPM concentration (in the year 1990) and average SPM concentration for the first (average of 1990 and 1995) and the second half (average of 2005 to 2009) of the study period. Sex-specific adjusted risk ratios (RRs) for cardiovascular mortality were calculated using general mixed Poisson regression models after adjusting the age, BMI, history of diabetes mellitus and hypertension, creatinine, glutamic pyruvic transaminase, total cholesterol, high-density lipoprotein cholesterol, smoking, alcohol, and temperature. The variation between seven medical administration areas was also taken into account as a random effect. RESULTS: Baseline SPM concentration was associated with an increased risk of mortality from all cardiovascular diseases, coronary artery disease, and stroke. The adjusted RRs (95% confidence interval [CI]) per 10 µg/m3 increase in SPM concentration for all cardiovascular mortality were 1.147 (1.014-1.300) for men and 1.097 (0.985-1.222) for women. The point estimate of RR was highest for non-hemorrhagic stroke in men (1.248 [0.991-1.571]), although CI overlapped the unity. The RRs seemed slightly lower in the second half than in the first half, though the CIs widened in the second half. CONCLUSION: Our results suggest that long-term exposure to SPM is associated with an increased risk of all cardiovascular mortality for men in Ibaraki, Japan.

Aim: The association between atrial fibrillation (AF) and risk of stroke mortality among men and women without traditional cerebrocardiovascular risk factors (TCVRFs) is unclear. This study aimed to determine whether AF was a risk factor for stroke and total cardiovascular disease mortality among individuals without TCVRFs. Methods: A total of 90,629 Japanese subjects from the Ibaraki Prefectural Health Study aged 40–79 years, with and without TCVRFs, were studied from 1993 to 2013. Hazard ratios (HRs) were calculated using the Cox proportional hazard regression model stratified by sex and the presence of TCVRFs. Covariates were age, systolic blood pressure, anti-hypertensive medication use, and serum total cholesterol levels. A standard 12-lead electrocardiogram at rest was used to screen AF. Cause-specific mortality was classified according to the International Classification of Disease code. Results: Compared with participants without AF, multivariable-adjusted hazard ratios (with 95% confidence intervals) for stroke mortality among participants without TCVRFs were 4.3 (1.1–17.8) and 15.0 (5.5–40.8) for men and women with AF, respectively. HRs for total cardiovascular disease mortality were 6.2 (2.8–14.2) for men and 10.7 (4.8–24.1) for women. For participants with TCVRFs, multivariable-adjusted HRs for stroke mortality were 3.1 (2.2–4.6) and 4.3 (2.6–7.3), whereas HRs for total cardiovascular disease mortality were 2.9 (2.2–3.8) and 3.5 (2.4–5.1) for men and women, respectively. Conclusions: AF was found to be an independent risk factor for stroke and total cardiovascular mortality even in individuals without other TCVRFs.

Few studies have assessed incubation periods of the severe acute respiratory syndrome coronavirus 2 Delta variant. This study aimed to elucidate the transmission dynamics, especially the incubation period, for the Delta variant compared with non-Delta strains. We studied unvaccinated coronavirus disease 2019 patients with definite single exposure date from August 2020 to September 2021 in Japan. The incubation periods were calculated and compared by Mann–Whitney U test for Delta (with L452R mutation) and non-Delta cases. We estimated mean and percentiles of incubation period by fitting parametric distribution to data in the Bayesian statistical framework. We enrolled 214 patients (121 Delta and 103 non-Delta cases) with one specific date of exposure to the virus. The mean incubation period was 3.7 days and 4.9 days for Delta and non-Delta cases, respectively (p-value = 0.000). When lognormal distributions were fitted, the estimated mean incubation periods were 3.7 (95% credible interval (CI) 3.4–4.0) and 5.0 (95% CI 4.5–5.6) days for Delta and non-Delta cases, respectively. The estimated 97.5th percentile of incubation period was 6.9 (95% CI 5.9–8.0) days and 10.4 (95% CI 8.6–12.7) days for Delta and non–Delta cases, respectively. Unvaccinated Delta variant cases had shorter incubation periods than non–Delta variant cases.

Aim Diabetes mellitus and hypertriglyceridemia may adversely interact with the development of ischemic cardiovascular disease, but epidemiological evidence on this issue is scarce. We hypothesized that the impact of hypertriglyceridemia on ischemic cardiovascular disease (ischemic heart disease and ischemic stroke) would differ according to the presence or absence of diabetes mellitus and tested our a priori hypothesis under a large population-based prospective study. Methods A total of 90,468 men and women aged 40-79 years in 1993 were enrolled in the Ibaraki Prefectural Health Study (IPHS), a community-based cohort study of Japanese. The participants' serum triglyceride levels (mostly nonfasting) were measured every 5 years, and the participants were followed up for mortality from ischemic cardiovascular disease through 2016. Hazard ratios (95% confidence intervals) were calculated according to 5-year updated triglyceride levels (＜100, 100-149, 150-199, 200-299, and ≥ 300 mg/dl). Results During 1,795,877 person-years, there were 3,323 deaths from ischemic cardiovascular diseases (1,968 ischemic heart diseases and 1,355 ischemic strokes). We found no association between triglyceride levels and the risk of mortality from ischemic cardiovascular disease after adjustment for known cardiovascular risk factors. However, when stratified by the presence or absence of diabetes mellitus, excess mortality from ischemic cardiovascular disease appeared among participants with diabetes mellitus with triglyceride levels of ≥ 300 mg/dl. Further adjustment for high-density lipoprotein-cholesterol attenuated the association toward being statistically nonsignificant. Conclusion The impact of high serum triglyceride levels on the risk of ischemic cardiovascular disease mortality was confined to participants with diabetes mellitus.

Household secondary attack rate (HSAR) by risk factor might have a higher transmission rate between spouses. We investigated risk factors for the HSAR among non-spousal household contacts of patients with coronavirus disease 2019 (COVID-19). We studied household contacts of index cases of COVID-19 in Tsuchiura, Japan, from August 2020 through February 2021. The HSARs of the whole household contacts and non-spousal household contacts were calculated and compared across risk factors. We used a generalized linear mixed regression model for multivariate analysis. We enrolled 496 household contacts of 236 index COVID-19 cases. The HSAR was higher for spousal household contacts (37.8%) than for other contacts (21.2%). The HSAR was lower for non-spousal household contacts with a household size (number of household members) of two (18.2%), compared to the HSAR for contacts with a household size ≥4. The HSAR was higher for non-spousal household contacts of index patients with ≥3 days of diagnostic delay (period between onset and diagnosis) (26.0%) compared to those with ≤2 days’ delay (12.5%) (p = 0.033). Among non-spousal household contacts, the HSAR was low for those with a household size of two and was high for contacts of index patients with a long diagnostic delay.

IMPORTANCE Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions.OBJECTIVE To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR).DESIGN, SETTING, AND PARTICIPANTS Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540).EXPOSURES Demographic and clinical factors.MAIN OUTCOMES AND MEASURES Incident eGFR of less than 60 mL/min/1.73 m(2).RESULTS Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A(1c), and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25.CONCLUSIONS AND RELEVANCE Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

Introduction: Those who are considered to be low risk in short term such as 10 year risk actually have high risk of cardiovascular disease for the remaining lifespan at younger age. Absolute risk of Lifetime risk (LTR) is more useful and understandable for lay audience compared with short term risk or relative risk. CKD (Chronic Kidney Disease) is global burden of cardiovascular disease (CVD) and hypertension is damaging complication of CKD for CVD. To date, there have been no reports of LTR with the outcome of CVD death based on CKD in Asian population. Hypothesis: We sought to estimate LTR of CVD death stratified by the status of CKD and hypertension. Methods: We used data from EPOCH-JAPAN (Evidence for Cardiovascular Prevention From Observational Cohorts in Japan) which is designed to pool data from nationwide and regional cohort studies in Japan. Modified Kaplan-Meier approach was used to estimate the remaining lifetime risk of cardiovascular death at each index age starting from 40 years according to CKD stratified by Hypertension. Participants were classified into four groups, which were those without CKD and hypertension (CKD-/HT-), those with CKD but without hypertension (CKD+/HT-), those without CKD but with hypertension (CKD-/HT+), and those with both CKD and hypertension (CKD+/HT+). Results: A total of 44,582 participants from 8 cohorts was included in the analysis. Mean follow-up period was 14.9 years with 662,488 person years and total CVD death was 1,035 in men and 1,160 in women. The LTRs at the index age of 40 years increased in groups with CKD and/or HT as follows: 12.6% (95% confidence interval: 9.4 - 14.5%) in CKD-/HT- group, 20.6% (11.4 - 25.9%) in CKD+/HT- group, 23.2% (19.9 - 25.2%) in CKD-/HT+ group, and 27.9% (21.7 - 32.9%) in CKD+/HT+ group for men; 11.3%(8.9 - 13.2%), 17.4%(13.2 - 20.4%) , 17.8%(15.3 - 19.8%) , and 22.7%(19.5 - 25.2%) for women. Conclusions: We observed that complication of CKD and hypertension are collectively responsible for lifetime risk due to CVD death. Management of blood pressure from an early age is important to reduce CVD mortality in CKD patients.

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.

Outbreaks of infectious diseases can occur after natural disasters as vital services are disrupted and populations move into evacuation centres. National notifiable disease surveillance may be inadequate in these situations because of resource-consuming disease confirmation or system interruptions. Although syndromic surveillance has been used as an alternative in post-disaster situations, no systematic evaluations of it have been published. We evaluated the ad hoc paper-based syndromic surveillance system implemented in evacuation centres in Ibaraki prefecture after the 2011 Great East Japan Earthquake and Tsunami. We assessed the simplicity, acceptability, data quality, timeliness and portability of this system and reviewed its usefulness. We concluded that the system was simple, acceptable, portable and useful. The documentation and monitoring of disease events and trends were useful for developing interventions in evacuation centres and have since been used to improve post-disaster infectious disease and surveillance knowledge in Japan. We believe timeliness was a challenge due to the chain of data transmission and communication passing through an intermediary. Future implementations of this system could consider a more direct chain of data transmission and communication from collectors to analysers. Too few key informant interviewees and the inability to obtain original paper-based data from evacuation centres limited our findings; we conducted this evaluation four years after the response occurred. Future evaluations should be completed closer to when operations cease. The usefulness of the system suggests adopting it in future disasters. A simple, plain-language manual should be developed to improve future employment.

AIM: Lifetime risk (LTR) indicates the absolute risk of disease during the remainder of an individual's lifetime. We aimed to assess the LTRs for coronary heart disease (CHD) mortality associated with blood pressure (BP) and total cholesterol levels in an Asian population using a meta-analysis of individual participant data because no previous studies have assessed this risk. METHODS: We analyzed data from 105,432 Japanese participants in 13 cohorts. Apart from grade 1 and 2-3 hypertension groups, we defined "normal BP" as systolic/diastolic BP ＜130/＜80 mmHg and "high BP" as 130-139/80-89 mmHg. The sex-specific LTR was estimated while considering the competing risk of death. RESULTS: During the mean follow-up period of 15 years (1,553,735 person-years), 889 CHD deaths were recorded. The 10-year risk of CHD mortality at index age 35 years was ≤ 0.11%, but the corresponding LTR was ≥ 1.84%. The LTR of CHD at index age 35 years steeply increased with an increase in BP of participants with high total cholesterol levels [≥ 5.7 mmol/L (220 mg/dL)]. This risk was 7.73%/5.77% (95% confidence interval: 3.53%-10.28%/3.83%-7.25%) in men/women with grade 2-3 hypertension and high total cholesterol levels. In normal and high BP groups, the absolute differences in LTRs between the low and high total cholesterol groups were ≤ 0.25% in men and ≤ 0.40% in women. CONCLUSIONS: High total cholesterol levels contributed to an elevated LTR of CHD mortality in hypertensive individuals. These findings could help guide high-risk young individuals toward initiating lifestyle changes or treatments. ispartof: JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS vol:28 issue:1 pages:6-24 ispartof: location:Japan status: published

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 eGFR0.8 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.

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

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, Highlights • The highest population attributable fraction was for hypertension without obesity. • The total population attributable fraction of hypertension was 11.7%. • Hypertension could impose the greatest attribute on Japanese health expenditures.

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.

We investigated the effect of snacking habits in childhood on changes in body mass index (BMI) and high BMI in adolescence and adulthood. In total, 2141 Japanese children from the Ibaraki Children’s Cohort Study were evaluated at age 6 years (baseline), then at ages 12 and 22 years. We examined associations between snacking (scheduled times, when children wanted, and freely) at age 6 years and changes in BMI over time and the proportion of high BMI at ages 12 and 22 years, using time-dependent mixed-effects and logistic regression models. Compared with children who snacked at scheduled times, those provided snacks when they wanted experienced larger increases in BMI over time between ages 6 and 22 years (multivariable time-dependent effect: 0.03 kg/m2 for boys, p = 0.047; 0.04 kg/m2 for girls, p = 0.019). No differences were observed in children who snacked freely. A higher proportion of high BMI was found in boys who were provided snacks when they wanted compared with those who snacked at scheduled times. The multivariable odds ratio (95% confidence interval) was 1.52 (1.04–2.23) at age 12 years and 2.23 (1.12–4.45) at age 22 years. No differences were observed for girls at either age. Children who were provided snacks when they wanted showed larger increases in BMI over time compared with those who snacked at scheduled times. Boys who were provided snacks when they wanted showed the higher proportion of high BMI at follow-up.

The age-specific impact of atrial fibrillation (AF) on cardiovascular diseases remains unclear. A total of 90,629 participants who were from 40 to 79 years of age in 1993 were followed up until 2013 as part of the Ibaraki Prefectural Health Study. Hazard ratios for mortality stratified by gender and age groups were calculated using Cox's proportional hazards regression models. A total of 22,794 patients (11,329 men and 11,465 women) died during the follow-up period, including 6,684 patients who died of cardiovascular causes (2,951 men and 3,733 women). On multivariable analysis, participants with AF had an increased risk of cardiovascular-related mortality compared with those without AF. Among participants aged 40 to 64 years, the adjusted hazard ratios were 3.2 (95% confidence interval [CI] 2.0 to 5.3) for men and 7.1 (95% CI 3.2 to 16.0) for women; the corresponding adjusted hazard ratios among participants aged 65 to 79 years were 3.0 (95% CI 2.2 to 4.0) for men and 3.7 (95% CI 2.5 to 5.4) for women. No significant difference in hazard ratios between age groups was found for either gender. AF was significantly associated with all-cause mortality in each age and gender group; again, no significant difference in hazard ratios between the age groups was found in terms of AF. AF may be an independent risk factor for cardiovascular and all-cause mortalities regardless of age.

Lifetime risk (LTR) provides an absolute risk assessment during the remainder of one’s life. Few studies have focused on the LTRs of stroke and coronary heart disease (CHD), categorized by fine blood pressure in Asian populations. We aimed to assess it using a large database of a meta-analysis with the individual participant data. The present meta-analysis included 107 737 Japanese (42.4% men; mean age, 55.1 years) from 13 cohorts. During the mean follow-up of 15.2±5.3 years (1 559 136 person-years), 1922 died from stroke and 913 from CHD. We estimated risks after adjusting for competing risk of death other than the outcome of interest. The 10-year risk of stroke and CHD deaths at index age of 35 years was ≤1.9% and ≤0.3%, respectively. The LTRs of stroke death at the index age of 35 years (men/women) were 6.1%/4.8% for optimal, 5.7%/6.3% for normal, and 6.6%/6.0% for high-normal blood pressure groups, and 9.1%/7.9% for grade 1, 14.5%/10.3% for grade 2, and 14.6%/14.3% for grade 3 hypertension groups. The LTRs of CHD death similarly elevated with an increase in blood pressure but were lower (≤7.2%) than those of stroke death. In conclusion, blood pressure was clearly associated with an elevated LTR of stroke or CHD death, although the LTR of CHD death was one-half of that of stroke death in an Asian population. These results would help young people with hypertension to adopt a healthy lifestyle or start antihypertensive therapy early.

Rationale & Objective Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework. Study Design Cross-sectional individual participant-level analyses in a global consortium. Setting & Study Populations 17 CKD and 38 general population and high-risk cohorts. Selection Criteria for Studies Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension. Data Extraction Data were obtained and analyzed between July 2015 and January 2018. Analytical Approach We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses. Results The CKD cohorts (n = 254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n = 1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59 mL/min/1.73 m 2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30 mg/g). Limitations Variations in study era, health care delivery system, typical diet, and laboratory assays. Conclusions Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD. © 2018. This is the authors’ accepted and refereed manuscript to the article. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ "

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

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.

Aim The levels of lipids, especially triglycerides (TG), and obesity are associated with diabetes mellitus (DM). Although typically measured in fasting individuals, non-fasting lipid measurements play an important role in predicting future DM. This study compared the predictive efficacy of lipid variables according to the fasting status and body mass index (BMI) category. Methods Data were collected for 39,196 nondiabetic men and 87,980 nondiabetic women 40-79years of age who underwent health checkups in Ibaraki-Prefecture, Japan in 1993 and were followed through 2007. The hazard ratios (HRs) for DM in relation to sex, the fasting status and BMI were estimated using a Cox proportional hazards model. Results A total of 8,867 participants, 4,012 men and 4,855 women, developed DM during a mean follow-up of 5.5 years. TG was found to be an independent predictor of incident DM in both fasting and non-fasting men and non-fasting women. The multivariable-adjusted HR for DM according to the TG quartile (Q) 4 vs. Q1 was 1.18 (95% confidence interval (CI): 1.05, 1.34) in the non-fasting men with a normal BMI (18.5-24.9). This trend was also observed in the non-fasting women with a normal BMI. That is, the multivariable-adjusted HRs for DM for TG Q2, Q3 and Q4 compared with Q1 were 1.07 (95% CI: 0.94, 1.23), 1.17 (95%CI: 1.03, 1.34) and 1.48 (95%CI: 1.30, 1.69), respectively. Conclusions The fasting and non-fasting TG levels in men and non-fasting TG levels in women are predictive of future DM among those with a normal BMI. Clinicians must pay attention to those individuals at high risk for DM.

The objective of this study was to examine the effect of age on the relationship between alcohol consumption and incident hypertension in a general Japanese population. A cohort of Japanese men (n=37 310) and women (n=78 426) aged 40 to 79 years who underwent community-based health checkups from 1993 to 2004 and were free of hypertension were followed up with annual examinations, including the measurement of blood pressure, until the end of 2010. Incident hypertension was defined as systolic blood pressure of ≥140 mm Hg, diastolic blood pressure of ≥90 mm Hg, or the initiation of treatment for hypertension. Hazard ratios for incident hypertension according to alcohol consumption were estimated using a Cox proportional hazards model adjusted for possible confounding variables. A total of 45 428 participants (39.3%) developed hypertension (16 155 men and 29 273 women) for a mean follow-up time of 3.9 (1–18) years. Significant associations between alcohol consumption and incident hypertension were found in both sexes and age groups ( P for trend was P for interaction, >0.05). Our results suggest that alcohol consumption is a similar risk factor for incident hypertension in both the middle-aged and the older populations.

Importance: Asia is home to the largest diabetic populations in the world. However, limited studies have quantified the association of diabetes with all-cause and cause-specific mortality in Asian populations. Objectives: To evaluate the association of diabetes with all-cause and cause-specific mortality in Asia and to investigate potential effect modifications of the diabetes-mortality associations by participants' age, sex, education level, body mass index, and smoking status. Design, Setting, and Participants: This pooled analysis incorporated individual participant data from 22 prospective cohort studies of the Asia Cohort Consortium conducted between 1963 and 2006. A total of 1 002 551 Asian individuals (from mainland China, Japan, South Korea, Singapore, Taiwan, India, and Bangladesh) were followed up for more than 3 years. Cohort-specific hazard ratios and 95% confidence intervals for all-cause and cause-specific mortality were estimated using Cox regression models and then pooled using random-effects meta-analysis. Analysis was conducted between January 10, 2018, and August 31, 2018. Exposures: Doctor-diagnosed diabetes, age, sex, education level, body mass index, and smoking status. Main Outcomes and Measures: All-cause and cause-specific mortality. Results: Of 1 002 551 participants (518 537 [51.7%] female; median [range] age, 54.0 [30.0-98.0] years), 148 868 deaths were ascertained during a median (range) follow-up of 12.6 (3.0-38.9) years. The overall prevalence of diabetes reported at baseline was 4.8% for men and 3.6% for women. Patients with diabetes had a 1.89-fold risk of all-cause death compared with patients without diabetes (hazard ratio [HR], 1.89; 95% CI, 1.74-2.04), with the highest relative risk of death due to diabetes itself (HR, 22.8; 95% CI, 18.5-28.1), followed by renal disease (HR, 3.08; 95% CI, 2.50-3.78), coronary heart disease (HR, 2.57; 95% CI, 2.19-3.02), and ischemic stroke (HR, 2.15; 95% CI, 1.85-2.51). The adverse diabetes-mortality associations were more evident among women (HR, 2.09; 95% CI, 1.89-2.32) than among men (HR, 1.74; 95% CI, 1.62-1.88) (P for interaction

Importance Understanding birth cohort–specific tobacco smoking patterns and their association with total and cause-specific mortality is important for projecting future deaths due to tobacco smoking across Asian populations. Objectives To assess secular trends of tobacco smoking by countries or regions and birth cohorts and evaluate the consequent mortality in Asian populations. Design, Setting, and Participants This pooled meta-analysis was based on individual participant data from 20 prospective cohort studies participating in the Asia Cohort Consortium. Between September 1, 2017, and March 31, 2018, a total of 1 002 258 Asian individuals 35 years or older were analyzed using Cox proportional hazards regression analysis and random-effects meta-analysis. The pooled results were presented for mainland China; Japan; Korea, Singapore, and Taiwan; and India. Exposures Tobacco use status, age at starting smoking, number of cigarettes smoked per day, and age at quitting smoking. Main Outcomes and Measures Country or region and birth cohort–specific mortality and the population attributable risk for deaths from all causes and from lung cancer. Results Of 1 002 258 participants (51.1% women and 48.9% men; mean [SD] age at baseline, 54.6 [10.4] years), 144 366 deaths (9158 deaths from lung cancer) were ascertained during a mean (SD) follow-up of 11.7 (5.3) years. Smoking prevalence for men steadily increased in China and India, whereas it plateaued in Japan and Korea, Singapore, and Taiwan. Among Asian male smokers, the mean age at starting smoking decreased in successive birth cohorts, while the mean number of cigarettes smoked per day increased. These changes were associated with an increasing relative risk of death in association with current smoking in successive birth cohorts of pre-1920, 1920s, and 1930 or later, with hazard ratios for all-cause mortality of 1.26 (95% CI, 1.17-1.37) for the pre-1920 birth cohort, 1.47 (95% CI, 1.35-1.61) for the 1920s birth cohort, and 1.70 (95% CI, 1.57-1.84) for the cohort born in 1930 or later. The hazard ratios for lung cancer mortality were 3.38 (95% CI, 2.25-5.07) for the pre-1920 birth cohort, 4.74 (95% CI, 3.56-6.32) for the 1920s birth cohort, and 4.80 (95% CI, 3.71-6.19) for the cohort born in 1930 or later. Tobacco smoking accounted for 12.5% (95% CI, 8.4%-16.3%) of all-cause mortality in the pre-1920 birth cohort, 21.1% (95% CI, 17.3%-24.9%) of all-cause mortality in the 1920s birth cohort, and 29.3% (95% CI, 26.0%-32.3%) of all-cause mortality for the cohort born in 1930 or later. Tobacco smoking among men accounted for 56.6% (95% CI, 44.7%-66.3%) of lung cancer mortality in the pre-1920 birth cohort, 66.6% (95% CI, 58.3%-73.5%) of lung cancer mortality in the 1920s birth cohort, and 68.4% (95% CI, 61.3%-74.4%) of lung cancer mortality for the cohort born in 1930 or later. For women, tobacco smoking patterns and lung cancer mortality varied substantially by countries and regions. Conclusions and Relevance In this study, mortality associated with tobacco smoking continued to increase among Asian men in recent birth cohorts, indicating that tobacco smoking will remain a major public health problem in most Asian countries in the coming decades. Implementing comprehensive tobacco-control programs is warranted to end the tobacco epidemic.

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

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 (

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

Objective: The aim of this study was to examine the association between BMI and risk of incident hypertension among Japanese men and women who are middle-aged and older. Design: Prospective, population-based cohort study. Patients: A total of 68 205 nonhypertensive adults (18 336 men and 49 869 women) aged 40–79 years who completed health check-ups in the Ibaraki prefecture, Japan, in 1993 were followed up through 2006. To exclude the impact of BMI change during the follow-up period, a time-dependent covariate Cox proportional hazards model was used to compute the hazard ratios of incident hypertension according to BMI categories. Incident hypertension was defined as a SBP of at least 140 mmHg, a diastolic BP of at least 90 mmHg, and/or hypertensive medication use. Results: A total of 30 982 adults (45.4%) developed hypertension (9331 men and 21 651 women) during a mean of 3.9 years of follow-up. Compared with a BMI of less than 19.0, time-dependent covariates adjusted hazard ratios [95% confidence interval (CI)] for hypertension among participants with a BMI of at least 25.0 were 1.42 (1.17–1.73) for men aged 40–59 years, 1.34 (1.19–1.51) for men aged 60–79 years, 1.47 (1.33–1.62) for women aged 40–59 years, and 1.29 (1.18–1.41) for women aged 60–79 years. Conclusion: The baseline BMI is associated with future risk for incident hypertension even after accounting for weight change during the follow-up period. Weight loss may be recommended to nonhypertensive obese adults to prevent the development of hypertension.

Background— It is unclear whether mild hypertensive retinopathy is a risk factor for mortality. This study examined whether mild hypertensive retinopathy could be a risk factor for cardiovascular mortality in subjects with and without hypertension. Methods and Results— In this cohort study, 87 890 individuals (29 917 men and 57 973 women) 40 to 79 years of age in 1993 were followed up until 2008. Retinal photography was classified as normal, grade 1, or grade 2 based on the Keith-Wagener-Barker system. Risk ratios for all-cause and cause-specific mortality for each classification were calculated with Cox proportional hazards regression models. Covariates included age, systolic blood pressure, antihypertensive medication use, and other cardiovascular risk factors. Multivariable hazard ratios for total cardiovascular disease mortality were 1.24 (95% confidence interval [CI], 1.12–1.38) and 1.23 (95% CI, 1.03–1.47) for grades 1 and 2 among men and 1.12 (95% CI, 1.01–1.24) and 1.44 (95% CI, 1.24–1.68) for grades 1 and 2 among women, respectively. Hazard ratios for total stroke mortality were 1.31 (95% CI, 1.13–1.53) and 1.38 (95% CI, 1.08–1.77) for grades 1 and 2 among men and 1.30 (95% CI, 1.12–1.50) and 1.70 (95% CI, 1.36–2.11) for grades 1 and 2 among women, respectively. For both hypertensive and normotensive subjects of each sex, multivariable hazard ratios for all-cause mortality, total cardiovascular mortality, and total stroke mortality were significantly higher for grade 1 or 2 compared with normal. Conclusions— Mild hypertensive retinopathy is a risk factor for cardiovascular mortality independently of cardiovascular risk factors among men and women with and without hypertension.

Background The effect of very high or extremely high levels of high-density lipoprotein cholesterol (HDL-C) on cardiovascular disease (CVD) is not well described. Although a few recent studies have reported the adverse effects of extremely high levels of HDL-C on CVD events, these did not show a statistically significant association between extremely high levels of HDL-C and cause-specific CVD mortality. In addition, Asian populations have not been studied. Objective We examine the impact of extremely high levels of HDL-C on cause-specific CVD mortality using pooled data of Japanese cohort studies. Methods We performed a large-scale pooled analysis of 9 Japanese cohorts including 43,407 participants aged 40–89 years, dividing the participants into 5 groups by HDL-C levels, including extremely high levels of HDL-C ≥2.33 mmol/L (≥90 mg/dL). We estimated the adjusted hazard ratio of each HDL-C category for all-cause death and cause-specific deaths compared with HDL-C 1.04–1.55 mmol/L (40–59 mg/dL) using a cohort-stratified Cox proportional hazards model. Results During a 12.1-year follow-up, 4995 all-cause deaths and 1280 deaths due to overall CVD were identified. Extremely high levels of HDL-C were significantly associated with increased risk of atherosclerotic CVD mortality (hazard ratio = 2.37, 95% confidence interval: 1.37–4.09 for total) and increased risk for coronary heart disease and ischemic stroke. In addition, the risk for extremely high HDL-C was more evident among current drinkers. Conclusion We showed extremely high levels of HDL-C had an adverse effect on atherosclerotic CVD mortality in a pooled analysis of Japanese cohorts.

Background This retrospective cohort study examined the sex- and age-specific impact of hypertension on medical expenditures. Methods In 2006, we analyzed the medical expenditure records of 42 426 Japanese National Health Insurance beneficiaries (16 169 men, 26 257 women) who lived in Ibaraki, Japan, were aged 40 to 69 years, and underwent health checkups in 2002. Blood pressure was classified into 4 categories according to the criteria outlined in the seventh report of the Joint National Committee. Results The difference in median total expenditure between the hypertension categories and the normotension category was 119 585 yen (140 360 yen vs 20 775 yen) for men aged 40 to 54 years, 126 160 yen (204 070 yen vs 77 910 yen) for men aged 55 to 69 years, 125 495 yen (158 025 yen vs 32 530 yen) for women aged 40 to 54 years, and 122 370 yen (208 700 yen vs 86 330 yen) for women aged 55 to 69 years. The median total and outpatient medical expenditures markedly differed between patients with stage 1 hypertension and stage 2 hypertension (which included people on antihypertensive medication) in both sexes and all age subgroups. The median total and outpatient medical expenditures were higher among women than among men in all blood pressure categories. Conclusions The impact of hypertension on medical expenditures was similar in all age groups. Therefore, from the perspective of medical economics, prevention of the onset of hypertension seems equally important for all age subgroups.

OBJECTIVE To investigate the age-specific relationship between body mass index (BMI) and risk of diabetes in a Japanese general population. PARTICIPANTS AND METHODS A cohort of Japanese men (N=19,926) and women (N=41,489) (aged 40-79 years) who under went community-based health checkups in 1993 and were free of diabetes was followed up by annual examinations with measurement of blood glucose concentrations until the end of 2006. Incident diabetes mellitus was defined as a blood glucose concentration of 126 mg/dL or greater under fasting conditions, 200 mg/dL or greater under nonfasting conditions, or diabetic medication use at baseline. Hazard ratios (HRs) for diabetes according to BMI were estimated using a Cox proportional hazard model. The model was adjusted for possible confounding variables. RESULTS A total of 4429 participants (7.2%) developed diabetes (2065 men and 2364 women) during a mean follow-up of 5.5 years. Compared with those with a BMI of less than 25.0, the multivariate HRs for diabetes among participants with a BMI of 30.0 or greater were 1.40 (95% confidence interval [CI], 0.89-2.20) for men aged 40 to 59 years and 1.26 (95% CI, 0.81-1.96) for men aged 60 to 79 years ( P= .002 for interaction). The HRs were 2.50 (95% CI, 2.01-3.11) for women aged 40 to 59 years and 1.80 (95% CI, 1.41-2.30) for women aged 60 to 79 years ( P =.04 for interaction). CONCLUSION The effect of obesity on the risk of diabetes is greater for middle-aged than for older adults.

Noda H, Iso H, Irie F, Sairenchi T, Ohtaka E, Ohta H (Osaka University, Osaka, Japan; Harvard School of Public Health, Cambridge, MA, USA; Ibaraki Prefectural Office, Ibaraki; Dokkyo Medical University School of Medicine, Tochigi; Ibaraki Health Service Association, Ibaraki; Japan). Gender difference of association between LDL cholesterol concentrations and mortality from coronary heart disease amongst Japanese: the Ibaraki Prefectural Health Study. J Intern Med 2010; 267:576–587. Objective. The aim of this study was to examine whether LDL cholesterol raises the risk of coronary heart disease in a dose–response fashion in a population with low LDL-cholesterol levels. Design. Population-based prospective cohort study in Japan. Subjects and main outcome measures. A total of 30 802 men and 60 417 women, aged 40 to 79 years with no history of stroke or coronary heart disease, completed a baseline risk factor survey in 1993. Systematic mortality surveillance was performed through 2003 and 539 coronary heart disease deaths were identified. Results. The mean values for LDL-cholesterol were 110.5 mg dL−1 (2.86 mmol L−1) for men and 123.9 mg dL−1 (3.20 mmol L−1) for women. Men with LDL-cholesterol ≥140 mg dL−1 (≥3.62 mmol L−1) had two-fold higher age-adjusted risk of mortality from coronary heart disease than did those with LDL-cholesterol

Background— Few studies have examined the association between low levels of low-density lipoprotein (LDL) cholesterol and risk of intraparenchymal hemorrhage. Methods and Results— A total of 30 802 men and 60 417 women, 40 to 79 years of age with no history of stroke or coronary heart disease, completed a baseline risk factor survey in 1993 under the auspices of the Ibaraki Prefectural Health Study. Systematic mortality surveillance was performed through 2003, and 264 intraparenchymal hemorrhage deaths were identified. LDL cholesterol levels were calculated with the Friedewald formula. Persons with LDL cholesterol ≥140 mg/dL had half the sex- and age-adjusted risk of death due to intraparenchymal hemorrhage of those with LDL cholesterol Conclusions— Low LDL cholesterol levels are associated with elevated risk of death due to intraparenchymal hemorrhage.