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.

Change over Time in the Risk of Death among Japanese COVID-19 Cases Caused by the Omicron Variant Depending on Prevalence of Sublineages.

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.

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.

A low proportion of asymptomatic COVID-19 patients with the Delta variant infection by viral transmission through household contact at the time of confirmation in Ibaraki, Japan.

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.

Shorter Incubation Period among Unvaccinated Delta Variant Coronavirus Disease 2019 Patients in Japan.

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.

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.

Diabetes Mellitus Modifies the Association of Serum Triglycerides with Ischemic Cardiovascular Disease Mortality: The Ibaraki Prefectural Health Study (IPHS).

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.

Prediction of Lifetime Risk of Cardiovascular Disease Deaths Stratified by Sex in the Japanese Population.

Background Lifetime risk is an informative estimate for driving lifestyle and behavioral changes especially for young adults. The impact of composite risk factors for cardiovascular disease on lifetime risk stratified by sex has not been investigated in the Japanese population, which has a much lower mortality of coronary heart disease compared with the Western population. We aimed to estimate lifetime risk of death from cardiovascular disease attributable to traditional risk factors. Methods and Results We analyzed pooled individual data from the Evidence for Cardiovascular Prevention from Observational Cohorts in a Japanese cohort study. A modified Kaplan-Meier approach was used to estimate the remaining lifetime risk of cardiovascular death. In total, 41 002 Japanese men and women with 537 126 person-years of follow-up were included. The lifetime risk at the index-age of 45 years for those with optimal risk factors (total cholesterol <4.65 mmol/L, systolic blood pressure <120 mm Hg, diastolic blood pressure <80 mm Hg, absence of diabetes, and absence of smoking habit) was lower compared with the highest risk profile of ≥2 risk factors (6.8% [95% CI, 0%-11.9%] versus 19.4% [16.7%-21.4%] for men and 6.9% [1.2%-11.5%] versus 15.4% [12.6%-18.1%] for women). Conclusions The magnitude and the number of risk factors were progressively associated with increased lifetime risk even in individuals in early adulthood who tend to have low short-term risk. The degree of established cardiovascular risk factors can be converted into lifetime risk. Our findings may be useful for risk communication in the early detection of future cardiovascular disease risk.

Secondary Attack Rate among Non-Spousal Household Contacts of Coronavirus Disease 2019 in Tsuchiura, Japan, August 2020-February 2021.

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.

Atrial Fibrillation With and Without Cardiovascular Risk Factors and Stroke Mortality.

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.

A Combination of Blood Pressure and Total Cholesterol Increases the Lifetime Risk of Coronary Heart Disease Mortality: EPOCH-JAPAN.

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.

Long-Term Exposure to Particulate Matter and Mortality from Cardiovascular Diseases in Japan: The Ibaraki Prefectural Health Study (IPHS).

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.

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.

Age-Specific Impact of Atrial Fibrillation on Cardiovascular Mortality Among Japanese Men and Women (The Ibaraki Prefectural Health Study [IPHS]).

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.

Long-term effect of feeding snacks at age 6 years on body mass index at ages 12 and 22 years.

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.

Association of Diabetes With All-Cause and Cause-Specific Mortality in Asia: A Pooled Analysis of More Than 1 Million Participants.

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 < .001) and more evident among adults aged 30 to 49 years (HR, 2.43; 95% CI, 2.08-2.84) than among adults aged 70 years and older (HR, 1.51; 95% CI, 1.40-1.62) (P for interaction < .001). A similar pattern of association was found between diabetes and cause-specific mortality, with significant variations noted by sex and age. Conclusions and Relevance: This study found that diabetes was associated with increased risk of death from several diseases among Asian populations. Development and implementation of diabetes management programs are urgently needed to reduce the burden of diabetes in Asia.

Tobacco Smoking and Mortality in Asia: A Pooled Meta-analysis.

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.

Lifetime Risk of Stroke and Coronary Heart Disease Deaths According to Blood Pressure Level: EPOCH-JAPAN (Evidence for Cardiovascular Prevention From Observational Cohorts in Japan)

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 metaanalysis 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.