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Elevated blood pressure (BP) is major risk factor for cardiovascular diseases (CVD). Genome-wide association studies (GWAS) conducted predominantly in populations of European ancestry have identified >2,000 BP-associated loci, but other ancestries have been less well-studied. We conducted GWAS of systolic, diastolic, pulse, and mean arterial BP in 100,453 Chinese adults. We identified 128 non-overlapping loci associated with one or more BP traits, including 74 newly-reported associations. Despite strong genetic correlations between populations, we identified appreciably higher heritability and larger variant effect sizes in Chinese compared with European or Japanese ancestry populations. Using instruments derived from these GWAS, multivariable Mendelian randomisation demonstrated that BP traits contribute differently to the causal associations of BP with CVD. In particular, only pulse pressure was independently causally associated with carotid plaque. These findings reinforce the need for studies in diverse populations to understand the genetic determinants of BP traits and their roles in disease risk., (© 2024. The Author(s).)

Background: Healthy diet is essential for cardiovascular disease risk management, but its effects among Chinese patients, whose diets differ from Western diets, remain largely unknown., Methods: In this multicenter, patient- and outcome assessor-blind, randomized controlled feeding trial, 265 Chinese adults with baseline systolic blood pressure 130 to 159 mmHg were randomly assigned into Chinese heart-healthy (CHH) diet or usual diet for a 28-d intervention after a 7-d run-in period on usual diet. Blood lipids and glucose were measured from overnight fasting blood samples before and after the intervention. Ten-year cardiovascular disease risk was estimated using models previously developed and validated in Chinese. The changes in secondary outcomes of serum total cholesterol (TC), blood glucose, and 10-y cardiovascular disease risk over the intervention period were compared between intervention groups, adjusting for center, among participants with baseline and follow-up blood samples available. Sensitivity analyses were done with further adjustment for baseline values and covariables; missing data imputed; and among per-protocol population., Results: Among 256 eligible participants (130 on CHH diet, 126 on control diet), 42% had hypercholesterolemia and 15% had diabetes at baseline. In the control group, TC and 10-y cardiovascular disease risk decreased after the intervention by 0.16 mmol/L and 0.91%, respectively, but blood glucose increased by 0.25 mmol/L. Compared with usual diet, the CHH diet lowered TC (-0.14 mmol/L, P = 0.017) and 10-y cardiovascular disease risk (-1.24%, P = 0.001) further. No effect on blood glucose was found. All sensitivity analyses confirmed the results on TC and 10-y cardiovascular disease risk, and analysis with multiple variables adjusted showed a borderline significant effect on blood glucose (-0.17 mmol/L, P = 0.051). The differences in intake of nutrients and food groups between intervention groups explained the results., Conclusions: The CHH diet reduced TC and 10-y cardiovascular disease risk and was likely to reduce blood glucose among Chinese adults with mild hypertension. Further studies with longer terms are warranted. This trial was registered at clinicaltrials.gov as NCT03882645., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Genetic variants that affect alcohol use in East Asian populations could help assess the causal effects of alcohol consumption on cause-specific mortality. We aimed to investigate the associations between alcohol intake and cause-specific mortality using conventional and genetic epidemiological methods among more than 512 000 adults in China., Methods: The prospective China Kadoorie Biobank cohort study enrolled 512 724 adults (210 205 men and 302 519 women) aged 30-79 years, during 2004-08. Residents with no major disabilities from ten diverse urban and rural areas of China were invited to participate, and alcohol use was self-reported. During 12 years of follow-up, 56 550 deaths were recorded through linkage to death registries, including 23 457 deaths among 168 050 participants genotyped for ALDH2-rs671 and ADH1B-rs1229984. Adjusted hazard ratios (HRs) for cause-specific mortality by self-reported and genotype-predicted alcohol intake were estimated using Cox regression., Findings: 33% of men drank alcohol most weeks. In conventional observational analyses, ex-drinkers, non-drinkers, and heavy drinkers had higher risks of death from most major causes than moderate drinkers. Among current drinkers, each 100 g/week higher alcohol intake was associated with higher mortality risks from cancers (HR 1·18 [95% CI 1·14-1·22]), cardiovascular disease (CVD; HR 1·19 [1·15-1·24]), liver diseases (HR 1·51 [1·27-1·78]), non-medical causes (HR 1·15 [1·08-1·23]), and all causes (HR 1·18 [1·15-1·20]). In men, ALDH2-rs671 and ADH1B-rs1229984 genotypes predicted 60-fold differences in mean alcohol intake (4 g/week in the lowest group vs 255 g/week in the highest). Genotype-predicted alcohol intake was uniformly and positively associated with risks of death from all causes (n=12 939; HR 1·07 [95% CI 1·05-1·10]) and from pre-defined alcohol-related cancers (n=1274; 1·12 [1·04-1·21]), liver diseases (n=110; 1·31 [1·02-1·69]), and CVD (n=6109; 1·15 [1·10-1·19]), chiefly due to stroke (n=3285; 1·18 [1·12-1·24]) rather than ischaemic heart disease (n=2363; 1·06 [0·99-1·14]). Results were largely consistent using a polygenic score to predict alcohol intake, with higher intakes associated with higher risks of death from alcohol-related cancers, CVD, and all causes. Approximately 2% of women were current drinkers, and although power was low to assess observational associations of alcohol with mortality, the genetic evidence suggested that the excess risks in men were due to alcohol, not pleiotropy., Interpretation: Higher alcohol intake increased the risks of death overall and from major diseases for men in China. There was no genetic evidence of protection from moderate drinking for all-cause and cause-specific mortality, including CVD., Funding: Kadoorie Charitable Foundation, National Natural Science Foundation of China, British Heart Foundation, Cancer Research UK, GlaxoSmithKline, Wellcome Trust, Medical Research Council, and Chinese Ministry of Science and Technology., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: Type 2 diabetes (T2D) is caused by both genetic and cardiometabolic risk factors. However, the magnitude of the genetic predisposition of T2D in the Chinese population remains largely unknown., Methods: This study included 93,488 participants from the China Kadoorie Biobank, and multiple polygenic risk scores (PRS) were calculated. A common cardiometabolic risk score (CRS) using smoking, alcohol consumption, physical activity, diet, obesity, blood pressure, and blood lipids was constructed to investigate the effects of cardiometabolic risk factors on T2D. Furthermore, an equation based on ideal PRS, CRS, and their interaction was established to explore the combined effects on T2D., Results: An ideally fitting PRS model (variance explained, R 2  = 7.6%) was reached based on multiple PRS calculation methods. An additive interaction between PRS and CRS (coefficient = 28%, 95% CI: 0.20-0.36, p < 0.001) was found. The R 2 of the T2D predictive model could increase to 8.3% when CRS and the interaction terms of PRS × CRS were considered. In the etiological composition of T2D, the ratio of genetic risk effect, cardiometabolic risk effect, and interaction between genetic and cardiometabolic factors was 67:16:17., Conclusions: This study identified an ideally fitting PRS model for identifying and predicting the risk of T2D suitable for the Chinese population. The quantified proportional structure of genetic risk factors, cardiometabolic risk factors, and their interaction was detected, which elucidated the critical effect of genetic factors., (© 2023 The Obesity Society.)

Background: The association of incident cardiometabolic multimorbidity (CMM) with mortality risk is rarely studied, and neither are the durations of cardiometabolic diseases (CMDs). Whether the association patterns of CMD durations with mortality change as individuals progress from one CMD to CMM is unclear., Methods: Data from China Kadoorie Biobank of 512,720 participants aged 30-79 was used. CMM was defined as the simultaneous presence of two or more CMDs of interest, including diabetes, ischemic heart disease, and stroke. Cox regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the duration-dependent associations of CMDs and CMM with all-cause and cause-specific mortality. All information on exposures of interest was updated during follow-up., Results: During a median follow-up of 12.1 years, 99,770 participants experienced at least one incident CMD, and 56,549 deaths were documented. Among 463,178 participants free of three CMDs at baseline, compared with no CMD during follow-up, the adjusted HRs (95% CIs) between CMM and all-cause mortality, mortality from circulatory system diseases, respiratory system diseases, cancer, and other causes were 2.93 (2.80-3.07), 5.05 (4.74-5.37), 2.72 (2.35-3.14), 1.30 (1.16-1.45), and 2.30 (2.02-2.61), respectively. All CMDs exhibited a high mortality risk in the first year of diagnosis. Subsequently, with prolonged disease duration, mortality risk increased for diabetes, decreased for IHD, and sustained at a high level for stroke. With the presence of CMM, the above association estimates inflated, but the pattern of which remained., Conclusion: Among Chinese adults, mortality risk increased with the number of the CMDs and changed with prolonged disease duration, the patterns of which varied among the three CMDs., (© 2023. The Author(s).)

Objective: To validate the World Health Organization (WHO) non-laboratory-based cardiovascular disease risk prediction model in regions of China., Methods: We performed an external validation of the WHO model for East Asia using the data set of China Kadoorie Biobank, an ongoing cohort study with 512 725 participants recruited from 10 regions of China from 2004-2008. We also recalculated the recalibration parameters for the WHO model in each region and evaluated the predictive performance of the model before and after recalibration. We assessed discrimination performance by Harrell's C index., Findings: We included 412 225 participants aged 40-79 years. During a median follow-up of 11 years, 58 035 and 41 262 incident cardiovascular disease cases were recorded in women and men, respectively. Harrell's C of the WHO model was 0.682 in women and 0.700 in men but varied among regions. The WHO model underestimated the 10-year cardiovascular disease risk in most regions. After recalibration in each region, discrimination and calibration were both improved in the overall population. Harrell's C increased from 0.674 to 0.749 in women and from 0.698 to 0.753 in men. The ratios of predicted to observed cases before and after recalibration were 0.189 and 1.027 in women and 0.543 and 1.089 in men., Conclusion: The WHO model for East Asia yielded moderate discrimination for cardiovascular disease in the Chinese population and had limited prediction for cardiovascular disease risk in different regions in China. Recalibration for diverse regions greatly improved discrimination and calibration in the overall population., ((c) 2023 The authors; licensee World Health Organization.)

Background: Increased physical activity is associated with a reduced risk of cardiovascular disease, but outdoor physical activity can be accompanied by increased inhalation of fine particulate matter (PM 2·5 ). The extent to which long-term exposure to PM 2·5 can offset the cardiovascular benefits of physical activity is unknown. We aimed to evaluate whether the associations between active commuting or farming activity and incident risks of cerebrovascular disease and ischaemic heart disease were consistent between populations with different ambient PM 2·5 exposures., Methods: We did a prospective cohort study using data from people aged 30-79 years without cardiovascular disease at baseline from the China Kadoorie Biobank (CKB). Active commuting and farming activity were assessed at baseline using questionnaires. A high-resolution (1 × 1 km) satellite-based model was used to estimate annual average PM 2·5 exposure during the study period. Participants were stratified according to PM 2·5 exposure (54 μg/m 3 or greater vs less than 54 μg/m 3 ). Hazard ratios (HRs) and 95% CIs for incident cerebrovascular disease and ischaemic heart disease by active commuting and farming activity were estimated using Cox proportional hazard models. Effect modifications by PM 2·5 exposure were tested by likelihood ratio tests. Analyses were restricted to the period from Jan 1, 2005, to Dec 31, 2017., Findings: Between June 25, 2004, and July 15, 2008, 512 725 people were enrolled in the CKB cohort. 322 399 eligible participants completed the baseline survey and were included in the analysis of active commuting (118 274 non-farmers and 204 125 farmers). Among 204 125 farmers, 2985 reported no farming time and 201 140 were included in the farming activity analysis. During a median follow-up of 11 years, 39 514 cerebrovascular disease cases and 22 313 ischaemic heart disease cases were newly identified. Among non-farmers with exposure to annual average PM 2·5 concentrations of less than 54 μg/m 3 , increased active commuting was associated with lower risks of cerebrovascular disease (highest active commuting vs lowest active commuting HR 0·70, 95% CI 0·65-0·76) and ischaemic heart disease (0·60, 0·54-0·66). However, among non-farmers with exposure to annual average PM 2·5 concentrations of 54 μg/m 3 or greater, there was no association between active commuting and cerebrovascular disease or ischaemic heart disease. Among farmers with exposure to annual average PM 2·5 concentrations of less than 54 μg/m 3 , increased active commuting (highest active commuting vs lowest active commuting HR 0·77, 95% CI 0·63-0·93) and increased farming activity (highest activity vs lowest activity HR 0·85, 95% CI 0·79-0·92) were both associated with a lower cerebrovascular disease risk. However, among farmers with exposure to annual average PM 2·5 concentrations of 54 μg/m 3 or greater, increases in active commuting (highest active commuting vs lowest active commuting HR 1·12, 95% CI 1·05-1·19) and farming activity (highest activity vs lowest activity HR 1·18, 95% CI 1·09-1·28) were associated with an elevated cerebrovascular disease risk. The above associations differed significantly between PM 2·5 strata (all interaction p values <0·0001)., Interpretation: For participants with long-term exposure to higher ambient PM 2·5 concentrations, the cardiovascular benefits of active commuting and farming activity were significantly attenuated. Higher levels of active commuting and farming activity even increased the cerebrovascular disease risk among farmers with exposure to annual average PM 2·5 concentrations of 54 μg/m 3 or greater., Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Kadoorie Charitable Foundation, UK Wellcome Trust., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Existing evidence on long-term ambient air pollution (AAP) exposure and risk of cardio-respiratory diseases in China is mainly on mortality, and based on area average concentrations from fixed-site monitors for individual exposures. Substantial uncertainty persists, therefore, about the shape and strength of the relationship when assessed using more personalised individual exposure data. We aimed to examine the relationships between AAP exposure and risk of cardio-respiratory diseases using predicted local levels of AAP., Methods: A prospective study included 50,407 participants aged 30-79 years from Suzhou, China, with concentrations of nitrogen dioxide (NO 2 ), sulphur dioxide (SO 2 ), fine (PM 2.5 ), and inhalable (PM 10 ) particulate matter, ozone (O 3 ) and carbon monoxide (CO) and incident cases of cardiovascular disease (CVD) (n = 2,563) and respiratory disease (n = 1,764) recorded during 2013-2015. Cox regression models with time-dependent covariates were used to estimate adjusted hazard ratios (HRs) for diseases associated with local-level concentrations of AAP exposure, estimated using Bayesian spatio-temporal modelling., Results: The study period of 2013-2015 included a total of 135,199 person-years of follow-up for CVD. There was a positive association of AAP, particularly SO 2 and O 3 , with risk of major cardiovascular and respiratory diseases. Each 10 µg/m 3 increase in SO 2 was associated with adjusted hazard ratios (HRs) of 1.07 (95% CI: 1.02, 1.12) for CVD, 1.25 (1.08, 1.44) for COPD and 1.12 (1.02, 1.23) for pneumonia. Similarly, each 10 µg/m 3 increase in O 3 was associated with adjusted HR of 1.02 (1.01, 1.03) for CVD, 1.03 (1.02, 1.05) for all stroke, and 1.04 (1.02, 1.06) for pneumonia., Conclusions: Among adults in urban China, long-term exposure to ambient air pollution is associated with a higher risk of cardio-respiratory disease., (© 2023. The Author(s).)

Background: This study aimed to: 1) assess the associations of biological age acceleration based on Klemera and Doubal's method (KDM-AA) with long-term risk of all-cause mortality; and 2) compare the association of KDM-AA with all-cause mortality among participants potentially at different stages of the cardiovascular disease (CVD) continuum., Methods: The present study was based on a subpopulation of the China Kadoorie Biobank, with baseline survey during 2004-08. A total of 12,377 participants free of ischemic heart disease, stroke, or cancer at baseline were included, in which 8180 participants were identified to develop major coronary event (MCE), ischemic stroke (IS), intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH), and 4197 remained free of these cardiovascular diseases before 1 January 2014. These participants were followed up until 1 Jan 2018. KDM-AA was calculated by regressing biological age measurement, which was constructed based on baseline 16 physical and 9 biochemical markers using Klemera and Doubal's method, on chronological age. We estimated the associations of KDM-AA with the mortality risk using the hazard ratio (HR) and 95% confidence interval (CI) from Cox proportional hazard models. We assessed discrimination performance by Harrell's C-index and net reclassification index (NRI)., Findings: The participants who developed MCE (mean KDM-AA = 0.1 year, standard deviation [SD] = 1.6 years) or ICH/SAH (0.3 ± 1.5 years) during subsequent follow-up showed accelerated aging at baseline compared to those of IS (0.0 ± 1.2 years) and control (-0.3 ± 1.3 years) groups. The KDM-AA was positively associated with long-term risk of all-cause mortality (HR = 1.20; 95% CI: 1.17, 1.23), and the association was robust for participants potentially at different stages of the CVD continuum. Adding KDM-AA improved mortality prediction compared to the model only with sociodemographic and lifestyle factors in whole participants, with the Harrell's C-index increasing from 0.813 (0.807, 0.819) to 0.821 (0.815, 0.826) (NRI = 0.011; 95% CI: 0.003, 0.019)., Interpretation: In this middle-aged and elderly Chinese population, the KDM-AA is a promising measurement for biological age, and can capture the difference in cardiovascular health and predict the risk of all-cause mortality over a decade., Funding: This work was supported by National Natural Science Foundation of China (82192904, 82192901, 82192900, 81941018). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303), and Chinese Ministry of Science and Technology (2011BAI09B01)., Competing Interests: Declaration of interests The authors declare that there is no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The improvement of life expectancy is one of the aims of the Healthy China 2030 blueprint. We aimed to investigate the extent to which healthy lifestyles are associated with life expectancy in Chinese adults., Methods: We used the prospective China Kadoorie Biobank (CKB) study to examine the relative risk of mortality associated with individual and combined lifestyle factors (never smoking or quitting not for illness, no excessive alcohol use, being physically active, healthy eating habits, and healthy body shape). Participants with coronary heart disease, stroke, cancer, or missing values for body-mass index were excluded. For analysis of chronic respiratory diseases, participants with chronic obstructive pulmonary disease or asthma were excluded. We estimated the national prevalence of lifestyle factors using data from the China Nutrition and Health Surveillance (CNHS; 2015) and derived mortality rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (2015). All three data sources were combined to estimate the life expectancy of individuals at age 30 years following different levels of lifestyle factors by using the life table method. The cause-specific decomposition of the life expectancy differences was analysed using Arriaga's method., Findings: After the exclusion of CKB participants with coronary heart disease, stroke, cancer, or missing BMI data at baseline, 487 209 were included in the primary analysis. Participants with COPD or asthma at baseline were additionally excluded for chronic respiratory disease-related analysis, leaving 451 233 participants with data available for analysis. Data from 171 127 adults aged 30-84 years from the CNHS 2015 were used to estimate the sex-specific and age-specific prevalence of lifestyle-related factors. There were 42 496 deaths documented over a median follow-up of 11·1 years (IQR 10·2-12·1) in CKB. The adjusted hazard ratios (aHRs) of participants adopting five versus 0-1 low-risk factors was 0·38 (95% CI 0·34-0·43) for all-cause mortality, aHR 0·37 (0·30-0·46) for cardiovascular disease mortality, aHR 0·47 (0·39-0·56) for cancer mortality, and aHR 0·30 (0·14-0·64) for chronic respiratory disease mortality. The life expectancy at age 30 years for individuals with 0-1 low-risk factors was on average 41·7 years (95% CI 41·5-42·0) for men and 47·3 years (46·6-48·0) for women. For individuals with all five low-risk factors, the life expectancy at age 30 was 50·5 years (95% CI 48·5-52·4) for men and 55·4 years (53·5-57·4) for women; meaning a difference of 8·8 years (95% CI 6·8-10·7) for men and 8·1 years (6·5-9·9) for women. The estimated extended life expectancy for men and women was mainly attributable to reduced death from cardiovascular disease (2·4 years [27% of the total extended life expectancy] for men and 3·7 years [46%] for women), cancer (2·6 years [30%] for men and 0·9 years [11%] for women), and chronic respiratory disease (0·6 years [7%] for men and 1·2 years [15%] for women)., Interpretation: Our findings suggest that increasing the adoption of these five healthy lifestyle factors through public health interventions could be associated with substantial gains in life expectancy in the Chinese population., Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Kadoorie Charitable Foundation, UK Wellcome Trust., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Anxiety might be a potentially modifiable risk factor of cardiovascular diseases (CVDs). Evidence relating anxiety symptoms and generalized anxiety disorder (GAD) to CVDs from prospective cohort study was still lacking in China., Methods: Participants aged 30 to 79 years old from 10 areas across China were recruited during 2004-2008 and were followed up until 2017. 487,209 participants without CVDs at baseline remained for analyses. Anxiety symptoms (panic attacks and continuous anxiety) during the past 12 months were identified in a face-to-face interview. Participants with continuous anxiety were further assessed for GAD using Composite International Diagnostic Interview-Short Form. The primary outcomes were incident CVD, ischaemic heart disease (IHD), haemorrhagic stroke (HS), and ischaemic stroke (IS)., Results: During 4.7 million person-years of follow-up, we documented 140,365 incident cases of CVD. For panic attacks, the multivariable-adjusted HRs (95 % CI) were 1.08 (1.04-1.13), 1.10 (1.02-1.19), 1.20 (1.05-1.38) and 1.20 (1.11-1.30) for CVD, IHD, HS and IS, respectively. Continuous anxiety was positively associated with incident CVD and IHD, and the corresponding HRs were 1.12 (1.04-1.20) and 1.21 (1.07-1.37)., Limitations: Anxiety symptoms were examined according to self-reported questionnaires, which could constitute key study limitations., Conclusions: Among the Chinese adults, those with anxiety symptoms or GAD might be important at-risk population of CVD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: There is an evidence gap about whether a low-risk lifestyle is as important as achieving blood pressure (BP) and random blood glucose (RBG) control., Objectives: To explore the long-term impacts and relative importance of low-risk lifestyle and health factors on the risk of all-cause and cancer mortality and macrovascular and microvascular complications among patients with diabetes., Methods: This study included 26,004 diabetes patients in the China Kadoorie Biobank. We defined 5 lifestyle factors (smoking, alcohol drinking, physical activity, fruit and vegetable intake, and waist-to-hip ratio) and 2 health factors (BP and RBG). Cox regression was used to yield adjusted hazard ratios (HRs) and CIs for individual and combined lifestyle and health factors with the risks of diabetes-related outcomes., Results: There were 5063 deaths, 6848 macrovascular complications, and 2055 microvascular complications that occurred during a median follow-up of 10.2 years. Combined low-risk lifestyle factors were associated with lower risk of all main outcomes, with HRs (95% CIs) for participants having 4 to 5 low-risk factors vs 0 to 1 of 0.50 (0.44-0.57) for all-cause mortality, 0.55 (0.43-0.71) for cancer mortality, 0.60 (0.54-0.67) for macrovascular complications, and 0.75 (0.62-0.91) for microvascular complications. The combined 4 to 5 low-risk lifestyle factors showed relative importance in predicting all-cause and cancer mortality and macrovascular complications., Conclusions: Assuming causality exists, our findings suggest that adopting a low-risk lifestyle should be regarded as important as achieving ideal BP and glycemic goals in the prevention and management of diabetes-related adverse outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Lower consumption of whole grains is associated with higher risks of diabetes and coronary heart disease in Western populations, but evidence is still limited for stroke. Moreover, little is known in China, where the rates of cardiometabolic diseases are high and the grain types consumed are different from those in Western countries., Objectives: To examine the associations between coarse-grain (e.g., millet, corn, and sorghum) consumption and incident cardiometabolic diseases among Chinese adults., Methods: The prospective China Kadoorie Biobank enrolled >0.5 million adults aged 30-79 years from 10 urban and rural areas during 2004-2008. At baseline, consumption frequencies (in 5 categories from "never" to "daily") of 12 major food groups, including coarse grains, were collected using a validated FFQ. After a median of 11 years of follow-up, 17,149 cases of diabetes, 29,876 ischemic strokes, 6097 hemorrhagic strokes, and 6704 major coronary events were recorded among 461,047 participants without a prevalence of major chronic diseases at baseline. Cox regression analyses were used to yield adjusted HRs for each disease associated with coarse-grain consumption., Results: Overall, 13.8% of participants reported regularly consuming (i.e., ≥4 days/week, regular consumers) and 29.4% reported never or rarely consuming coarse grains (i.e., nonconsumers) at baseline. Compared with nonconsumers, regular consumers had lower risks of diabetes (adjusted HR, 0.88; 95% CI, 0.78-0.98) and ischemic stroke (adjusted HR, 0.86; 95% CI, 0.81-0.93), but not hemorrhagic stroke (adjusted HR, 0.96; 95% CI, 0.76-1.20) or major coronary events (adjusted HR, 0.95; 95% CI, 0.81-1.12). For diabetes and ischemic stroke, each 100 g/day increase in the usual intake of coarse grains was associated with 14% (adjusted HR, 0.86; 95% CI, 0.76-0.97) and 13% (adjusted HR, 0.87; 95% CI, 0.81-0.94) lower risks, respectively, with similar results in various subgroups., Conclusions: In Chinese adults, higher coarse-grain consumption is associated with lower risks of diabetes and ischemic stroke, supporting the promotion of coarse-grain consumption in China., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background and Objectives: Contemporary cardiovascular disease (CVD) risk prediction models are rarely applied in routine clinical practice in China due to substantial regional differences in absolute risks of major CVD types within China. Moreover, the inclusion of blood lipids in most risk prediction models also limits their use in the Chinese population. We developed 10-year CVD risk prediction models excluding blood lipids that may be applicable to diverse regions of China., Methods: We derived sex-specific models separately for ischemic heart disease (IHD), ischemic stroke (IS), and hemorrhagic stroke (HS) in addition to total CVD in the China Kadoorie Biobank. Participants were age 30-79 years without CVD at baseline. Predictors included age, systolic and diastolic blood pressure, use of blood pressure-lowering treatment, current daily smoking, diabetes, and waist circumference. Total CVD risks were combined in terms of conditional probability using the predicted risks of 3 submodels. Risk models were recalibrated in each region by 2 methods (practical and ideal) and risk prediction was estimated before and after recalibration., Results: Model derivation involved 489,596 individuals, including 45,947 IHD, 43,647 IS, and 11,168 HS cases during 11 years of follow-up. In women, the Harrell C was 0.732 (95% CI 0.706-0.758), 0.759 (0.738-0.779), and 0.803 (0.778-0.827) for IHD, IS, and HS, respectively. The Harrell C for total CVD was 0.734 (0.732-0.736), 0.754 (0.752-0.756), and 0.774 (0.772-0.776) for models before recalibration, after practical recalibration, and after ideal recalibration. The calibration performances improved after recalibration, with models after ideal recalibration showing the best model performances. The results for men were comparable to those for women., Discussion: Our CVD risk prediction models yielded good discrimination of IHD and stroke subtypes in addition to total CVD without including blood lipids. Flexible recalibration of our models for different regions could enable more widespread use using resident health records covering the overall Chinese population., Classification of Evidence: This study provides Class I evidence that a prediction model incorporating accessible clinical variables predicts 10-year risk of IHD, IS, and HS in the Chinese population age 30-79 years., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Few studies have assessed the role of individual plasma cholesterol levels in the association between egg consumption and the risk of cardiovascular diseases. This research aims to simultaneously explore the associations of self-reported egg consumption with plasma metabolic markers and these markers with the risk of cardiovascular disease (CVD)., Methods: Totally 4778 participants (3401 CVD cases subdivided into subtypes and 1377 controls) aged 30-79 were selected based on the China Kadoorie Biobank. Targeted nuclear magnetic resonance was used to quantify 225 metabolites in baseline plasma samples. Linear regression was conducted to assess associations between self-reported egg consumption and metabolic markers, which were further compared with associations between metabolic markers and CVD risk., Results: Egg consumption was associated with 24 out of 225 markers, including positive associations for apolipoprotein A1, acetate, mean HDL diameter, and lipid profiles of very large and large HDL, and inverse associations for total cholesterol and cholesterol esters in small VLDL. Among these 24 markers, 14 were associated with CVD risk. In general, the associations of egg consumption with metabolic markers and of these markers with CVD risk showed opposite patterns., Conclusions: In the Chinese population, egg consumption is associated with several metabolic markers, which may partially explain the protective effect of moderate egg consumption on CVD., Funding: This work was supported by the National Natural Science Foundation of China (81973125, 81941018, 91846303, 91843302). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 81390541, 81390544), and Chinese Ministry of Science and Technology (2011BAI09B01). The funders had no role in the study design, data collection, data analysis and interpretation, writing of the report, or the decision to submit the article for publication., Competing Interests: LP, LC, JL, YP, YG, PP, HD, LY, IM, RW, YC, WG, JC, CY, ZC, LL No competing interests declared, (© 2022, Pan et al.)

Background: The relative importance of healthy lifestyle factors and cardiovascular health metrics for the risk of heart failure is uncertain in Chinese populations. We aimed to compare the strength of associations between healthy lifestyle factors and ideal cardiovascular health metrics in the risk of heart failure in middle-aged Chinese adults., Methods: A healthy lifestyle score (HLS) was constructed using smoking, drinking, physical activity, diet, body mass index and waist circumference, and compared with a more comprehensive set of metrics that included cardiovascular-disease risk biomarkers (blood pressure, blood glucose and blood lipids) in addition to the HLS. This broader set of factors [called 'ideal cardiovascular health metrics' (ICVHMs)] was evaluated in 487 197 participants in the China Kadoorie Biobank., Results: A total of 4208 incident cases of heart failure were recorded during a median follow-up of 10 years. Both HLS [hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.85, 0.91] and ICVHMs (0.87: 0.84, 0.89) were inversely associated with risk of heart failure (P < 0.001 for linear trend). Compared with participants with 0-1 HLS, the multivariable-adjusted HR of those with 4-5 HLS was 0.68 (0.59, 0.77). Compared with participants with 0-2 ICVHMs, the adjusted HR (95% CIs) of those who had 7-8 ICVHMs was 0.47 (0.36, 0.60). ICVHMs were more strongly predictive of risk of heart failure (area under curve, 0.61 vs 0.58, P < 0.001) than healthy lifestyle factors alone., Conclusions: Higher levels of healthy lifestyle factors and ICVHMs were each inversely associated with heart failure, and lifestyle factors combined with cardiometabolic factors improved the prediction of heart failure compared with healthy lifestyle factors alone., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Context: Observational studies have suggested that higher resting heart rate (RHR) may be associated with increased cardiometabolic risk. However, causal associations are not fully understood., Objective: We aimed to examine the direction, strength, and causality of the associations of RHR with cardiometabolic traits., Methods: We assessed the strength of associations between measured RHR and cardiometabolic traits in 506 211 and 372 452 participants from China Kadoorie Biobank (CKB) and UK Biobank (UKB). Mendelian randomization (MR) analyses were used to make causal inferences in 99 228 and 371 508 participants from CKB and UKB, respectively., Results: We identified significant directionally concordant observational associations between RHR and higher total cholesterol, triglycerides (TG), low-density lipoprotein, C-reactive protein (CRP), glucose, body mass index, waist-hip ratio (WHR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) after the Bonferroni correction. MR analyses showed that 10 beat/min higher genetically predicted RHR was trans-ethnically associated with a higher DBP (beta 2.059 [95% CI 1.544, 2.574] mmHg in CKB; 2.037 [1.845, 2.229] mmHg in UKB), higher CRP (0.180 [0.057, 0.303] log mg/L in CKB; 0.154 [0.134, 0.174] log mg/L in UKB), higher TG (0.052 [-0.009, 0.113] log mmol/L in CKB; 0.020 [0.010, 0.030] log mmol/L in UKB) and higher WHR (0.218 [-0.033, 0.469] % in CKB; 0.225 [0.111, 0.339] % in UKB). In the opposite direction, higher genetically predicted SBP, TG, glucose, and WHR, and lower high-density lipoprotein, were associated with elevated RHR., Conclusion: Our large-scale analyses provide causal evidence for associations between RHR and cardiometabolic traits, highlighting the importance of monitoring heat rate as a means of alleviating the adverse effects of metabolic disorders., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Accumulating evidence has shown that poor oral hygiene is associated with increased risk of cardiometabolic diseases in Western populations. However, its relevance about the relationships in Chinese adults remains unclear. The China Kadoorie Biobank enrolled 512 715 adults aged 30-79 years in China during 2004-2008. Cox regression was used to estimate adjusted hazard ratios (HRs) for each disease associated with measures of oral hygiene. Overall 9.3% of the participants reported rarely or never brushing teeth at baseline. Participants who rarely or never brushed teeth had adjusted HR of 1.12 (95% CI: 1.09, 1.15) for MVE, with similar HRs for stroke (1.08, 1.05-1.12), intracerebral haemorrhage (1.18, 1.11-1.26) and pulmonary heart disease (1.22, 1.13-1.32) compared with those who brushed teeth regularly. Those who did not brush teeth also had increased risk of cancer (1.09, 1.04-1.14), chronic obstructive pulmonary disease (COPD) (1.12, 1.05-1.20), liver cirrhosis (1.25, 1.09-1.44) and all-cause death (1.25, 1.21-1.28) but not type 2 diabetes (0.94, 0.86-1.03) and chronic kidney disease (0.98, 0.81-1.18). Among Chinese adults, we found that poor oral hygiene is associated with higher risks of major vascular disease, cancer, COPD, liver cirrhosis and all-cause deaths, but not type 2 diabetes and chronic kidney disease., (© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Acute respiratory infections have been associated with a transient increase in cardiovascular risk. However, whether such an association persists beyond 1 month and the potential modifying effect of cardiovascular risk factors on such an association are less well established., Methods: The China Kadoorie Biobank enrolled 512 726 participants aged 30-79 years from 10 areas across China during 2004-2008. By the end of 2017, a total of 5444 participants with new-onset ischaemic heart disease (IHD) and 4846 with ischaemic stroke (IS) who also had at least a record of hospitalization for pneumonia during follow-up were included. We used a self-controlled case-series method and calculated the age- and season-adjusted relative incidences (RIs) and 95% confidence intervals (CIs) for ischaemic cardiovascular disease (CVD) after pneumonia., Results: The risk of ischaemic CVD increased during days 1-3 after pneumonia hospitalization, with an RI (95% CI) of 4.24 (2.92-6.15) for IHD and 1.85 (1.02-3.35) for IS. The risk gradually reduced with longer duration since pneumonia hospitalization but remained elevated until days 92-365 for IHD (1.23, 1.12-1.35) and days 29-91 for IS (1.25, 1.05-1.48). Pre-existing cardiovascular risk factors amplified the associations between pneumonia and ischaemic CVD risks, such as chronic obstructive pulmonary disease for both IHD and IS, and diabetes and smoking for IHD (all Pinteraction < 0.05). Besides, the risk of ischaemic CVD was also higher among the participants aged ≥70 years (Pinteraction < 0.001 for IHD and 0.033 for IS)., Conclusion: Among middle-aged and older Chinese adults, pneumonia hospitalization was associated with both short- and long-term increases in ischaemic CVD risk for ≤1 year., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: The effect of the overall diet quality on cardiometabolic diseases has been well studied in the Western population. However, evidence is still in need regarding dietary patterns depicting unique Chinese dietary habits and their associations with cardiometabolic diseases., Methods: A prospective cohort recruited around 0.5 million Chinese residents aged 30-79 years from 10 diverse survey sites during 2004-08. Dietary patterns were obtained using factor analysis based on the habitual consumption of 12 food groups collected at baseline. Among 477,465 eligible participants free of prior heart disease, stroke and cancer, linkages to multiple registries and health insurance database recorded 137,715 cardiovascular diseases (CVD) and 17,412 diabetes cases (among 451,846 non-diabetic participants) until 31 December 2017. Adjusted hazard ratios (HRs) were estimated to compare the risks of cardiometabolic diseases across quintiles of dietary pattern scores using the Cox regression., Results: Two dietary patterns were derived: the traditional northern pattern, characterised by wheat, other staples, egg and dairy products; and the modern pattern, featured with fresh fruit, meat, poultry, fish, dairy products and soybean. Adherence to either dietary pattern was associated with lower risks of major cardiometabolic diseases in a dose-response relationship way. After multivariate adjustment, participants adhering to the traditional northern pattern the most had an 8% (95%CI: 5-11%) lower risk of CVD in comparison with those adhering the least. Corresponding risk reductions were 12% (11-32%) for haemorrhagic stroke (HS), 14% (8-19%) for ischaemic stroke (IS), and 15% (6-24%) for diabetes, respectively. When comparing extreme quintiles of the modern pattern, the adjusted HR of HS was 0.67 (95%CI: 0.59-0.77). Corresponding HRs were 0.89 (0.86-0.92) for CVD, 0.88 (0.77-0.99) for MCE, 0.85 (0.80-0.89) for IS, and 0.89 (0.81, 0.97) for diabetes., Conclusion: Among Chinese adults, both traditional northern and modern dietary patterns were associated with lower risks of cardiovascular disease and diabetes beyond other risk factors., (© 2021. The Author(s).)

Background: Limited convincing evidence is available of the relationship between habitual snoring and cardiovascular diseases (CVDs)., Research Question: Is habitual snoring associated with total CVD and CVD subtypes in different age groups of Chinese adults?, Study Design and Methods: The China Kadoorie Biobank study enrolled more than 0.5 million adults aged 30 to 79 years from 10 regions in China. Snoring status and other baseline characteristics were collected from 2004 to 2008, using an interviewer-administered laptop-based questionnaire. The current analysis included 489,583 participants without stroke or coronary heart disease at baseline. Cox proportional hazards models were used to calculate the adjusted hazard ratios (HRs) and 95% CIs of cardiovascular diseases (CVDs) for habitual snoring vs nonhabitual snoring., Results: During a median follow-up of 9.6 years, 130,935 participants developed CVDs. Associations between habitual snoring and CVDs varied with age. Among participants aged younger than 50 years at baseline, habitual snoring was associated with an increased risk of total CVD (HR, 1.11; 95% CI, 1.07-1.14) after adjustment for known CVD risk factors, including systolic BP. The corresponding HRs (95% CIs) for ischemic heart disease, ischemic stroke, and hemorrhagic stroke were 1.18 (1.12-1.24), 1.12 (1.05-1.19), and 1.05 (0.92-1.19), respectively. However, such associations in adults aged 50 to 64 years were much weaker, and no statistically significant association was observed among individuals aged ≥65 years. Age-specific risk estimates were generally similar across sex and obesity subgroups., Interpretation: Habitual snoring was associated with increased risks of total CVD, ischemic heart disease, ischemic stroke, but not hemorrhagic stroke in Chinese, and these associations were mainly limited to those aged <50 years. Clinicians in China are encouraged to identify snoring, particularly in younger adults., (Copyright © 2021. Published by Elsevier Inc.)

Importance: Obesity is associated with a higher risk of cardiovascular disease (CVD), but little is known about the role that circulating protein biomarkers play in this association., Objective: To examine the observational and genetic associations of adiposity with circulating protein biomarkers and the observational associations of proteins with incident CVD., Design, Setting, and Participants: This subcohort study included 628 participants from the prospective China Kadoorie Biobank who did not have a history of cancer at baseline. The Olink platform measured 92 protein markers in baseline plasma samples. Data were collected from June 2004 to January 2016 and analyzed from January 2019 to June 2020., Exposures: Measured body mass index (BMI) obtained during the baseline survey and genetically instrumented BMI derived using 571 externally weighted single-nucleotide variants., Main Outcomes and Measures: Cross-sectional associations of adiposity with biomarkers were examined using linear regression. Associations of biomarkers with CVD risk were assessed using Cox regression among those without prior cancer or CVD at baseline. Mendelian randomization was conducted to derive genetically estimated associations of BMI with biomarkers., Findings: In observational analyses of 628 individuals (mean [SD] age, 52.2 [10.5] years; 385 women [61.3%]), BMI (mean [SD], 23.9 [3.6]) was positively associated with 27 proteins (per 1-SD higher BMI; eg, interleukin-6: 0.21 [95% CI, 0.12-0.29] SD; interleukin-18: 0.13 [95% CI, 0.05-0.21] SD; monocyte chemoattractant protein-1: 0.12 [95% CI, 0.04-0.20] SD; hepatocyte growth factor: 0.31 [95% CI, 0.24-0.39] SD), and inversely with 3 proteins (Fas ligand: -0.11 [95% CI, -0.19 to -0.03] SD; TNF-related weak inducer of apoptosis, -0.14 [95% CI, -0.23 to -0.06] SD; and carbonic anhydrase 9: (-0.14 [95% CI, -0.22 to -0.05] SD), with similar associations identified for other adiposity traits (eg, waist circumference [r = 0.96]). In mendelian randomization, the associations of genetically elevated BMI with specific proteins were directionally consistent with the observational associations. In meta-analyses of genetically elevated BMI with 8 proteins, combining present estimates with previous studies, the most robust associations were shown for interleukin-6 (per 1-SD higher BMI; 0.21 [95% CI, 0.13-0.29] SD), interleukin-18 (0.16 [95% CI, 0.06-0.26] SD), monocyte chemoattractant protein-1 (0.21 [95% CI, 0.11-0.30] SD), monocyte chemotactic protein-3 (0.12 [95% CI, 0.03-0.21] SD), TNF-related apoptosis-inducing ligand (0.23 [95% CI, 0.13-0.32] SD), and hepatocyte growth factor (0.14 [95% CI, 0.06-0.22] SD). Of the 30 BMI-associated biomarkers, 10 (including interleukin-6, interleukin-18, and hepatocyte growth factor) were nominally associated with incident CVD., Conclusions and Relevance: Mendelian randomization shows adiposity to be associated with a range of protein biomarkers, with some biomarkers also showing association with CVD risk. Future studies are warranted to validate these findings and assess whether proteins may be mediators between adiposity and CVD.

Background: Metabolically healthy obesity (MHO) and its transition to unhealthy metabolic status have been associated with risk of cardiovascular disease (CVD) in Western populations. However, it is unclear to what extent metabolic health changes over time and whether such transition affects risks of subtypes of CVD in Chinese adults. We aimed to examine the association of metabolic health status and its transition with risks of subtypes of vascular disease across body mass index (BMI) categories., Methods and Findings: The China Kadoorie Biobank was conducted during 25 June 2004 to 15 July 2008 in 5 urban (Harbin, Qingdao, Suzhou, Liuzhou, and Haikou) and 5 rural (Henan, Gansu, Sichuan, Zhejiang, and Hunan) regions across China. BMI and metabolic health information were collected. We classified participants into BMI categories: normal weight (BMI 18.5-23.9 kg/m²), overweight (BMI 24.0-27.9 kg/m²), and obese (BMI ≥ 28 kg/m²). Metabolic health was defined as meeting less than 2 of the following 4 criteria (elevated waist circumference, hypertension, elevated plasma glucose level, and dyslipidemia). The changes in obesity and metabolic health status were defined from baseline to the second resurvey with combination of overweight and obesity. Among the 458,246 participants with complete information and no history of CVD and cancer, the mean age at baseline was 50.9 (SD 10.4) years, and 40.8% were men, and 29.0% were current smokers. During a median 10.0 years of follow-up, 52,251 major vascular events (MVEs), including 7,326 major coronary events (MCEs), 37,992 ischemic heart disease (IHD), and 42,951 strokes were recorded. Compared with metabolically healthy normal weight (MHN), baseline MHO was associated with higher hazard ratios (HRs) for all types of CVD; however, almost 40% of those participants transitioned to metabolically unhealthy status. Stable metabolically unhealthy overweight or obesity (MUOO) (HR 2.22, 95% confidence interval [CI] 2.00-2.47, p < 0.001) and transition from metabolically healthy to unhealthy status (HR 1.53, 1.34-1.75, p < 0.001) were associated with higher risk for MVE, compared with stable healthy normal weight. Similar patterns were observed for MCE, IHD, and stroke. Limitations of the analysis included lack of measurement of lipid components, fasting plasma glucose, and visceral fat, and there might be possible misclassification., Conclusions: Among Chinese adults, MHO individuals have increased risks of MVE. Obesity remains a risk factor for CVD independent of major metabolic factors. Our data further suggest that metabolic health is a transient state for a large proportion of Chinese adults, with the highest vascular risk among those remained MUOO., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Unhealthy diet has been identified as the number one attributor of total mortality in China, accounting for more than 20% of total deaths. Although the Dietary Approach to Stop Hypertension (DASH) and Mediterranean diets have been proven beneficial in managing cardiovascular risk factors in Western countries, whether healthy diets with similar cardiovascular benefits can be developed that are consistent with Chinese food culture remains unknown., Methods/design: The Diet, ExerCIse and CarDiovascular hEalth (DECIDE)-Diet trial is a multicentre, single-blind, randomised controlled feeding trial to evaluate the effect of the Chinese Healthy Heart (CHH) diet, in comparison with the Chinese usual diet, in lowering cardiovascular risk factors among community residents with the increased cardiovascular risk. A total of 360 adults aged between 25 and 75 years old and with systolic blood pressure between 130 and 159 mm Hg will be recruited from four centres located in four areas representing four major Chinese cuisines: Beijing, Shanghai, Guangzhou and Chengdu. After 1 week of run-in period with local usual diet, the compliant participants will be randomised to the intervention group with the CHH diet or the control group with the usual local diet, on a 1:1 ratio, for 4 weeks. Body weight of study participants will be maintained during the entire study period. The primary outcome is the change in SBP from the baseline to the end of the study. DECIDE-Diet trial will be the first randomised controlled feeding trial to evaluate the effect of a CHH diet in lowering cardiovascular risk factors. This trial will provide compelling evidence on the CHH diet in effect of improving cardiovascular health among Chinese food consumers all around the world., Ethics and Dissemination: This trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Peking University Institutional Review Board (approval number: IRB00001052-18094). The results will be disseminated through academic conferences and publications in international peer-reviewed journals., Trail Registration Number: ClinicalTrials.gov Registry (NCT03882645); Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To comprehensively examine the potential impacts of prenatal experience of the Chinese Great Famine on chronic disease risks in the middle age., Methods: This study included 92 284 participants aged 39-51 years from China Kadoorie Biobank born around the famine period and without major chronic diseases at baseline. We categorised participants into non-famine births (born between 1 October 1956 and 30 September 1958, and 1 October 1962 and 30 September 1964) and famine births (born between 1 October 1959 and 30 September 1961). The outcomes were incident cardiovascular disease, cancer and respiratory system disease. Cox regression was used to estimate adjusted HR and 95% CI for famine exposure. Subgroup analyses were performed according to baseline characteristics., Results: During a median 10.1 years of follow-up, we identified 4626 incident ischaemic heart disease (IHD) cases, 7332 cerebrovascular disease cases, 3111 cancer cases and 16 081 respiratory system disease cases. In the whole population, prenatal famine exposure was not statistically associated with the risks of developing any chronic diseases in adulthood. However, for urban participants, compared with non-famine births, famine births had a higher risk of cerebrovascular disease (HR 1.18; 95% CI 1.09 to 1.28); such association was not shown for rural participants (p for interaction <0.001). Also, we observed the associations of prenatal famine exposure with IHD (HR 1.15; 95% CI 1.05 to 1.26) and cerebrovascular disease (HR 1.13; 95% CI 1.05 to 1.21) in participants with lower physical activity level, but not in those with higher ones (all p for interaction=0.003)., Conclusion: Our findings indicate that prenatal exposure to the Chinese famine might be associated with an increased cardiovascular risk and such risk may be modified by adult lifestyle., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: To examine the associations of individual insomnia symptoms with risks of incident cardio-cerebral vascular diseases (CVD) and possible moderating factors among Chinese adults., Methods: The China Kadoorie Biobank is a prospective cohort study that recruited participants from 10 areas across China. Data from 487,200 adults 30 to 79 years of age who were free of stroke, coronary heart disease, and cancer at baseline were analyzed. Three insomnia symptoms were assessed with self-reported difficulties in initiating or maintaining sleep, early morning awakening, and daytime dysfunction for at least 3 d/wk at baseline. Incidences of CVD were followed up through disease registries and national health insurance databases until 2016., Results: During a median of 9.6 years of follow-up, 130,032 cases of CVD were documented. Cox regressions showed that 3 insomnia symptoms were associated with increased risk of total CVD, with respective adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.09 (95% CI 1.07-1.11), 1.07 (95% CI 1.05-1.09), and 1.13 (95% CI 1.09-1.18). Participants with individual symptoms also had higher risks of ischemic heart disease (IHD; HR 1.13, 1.09, and 1.17) and ischemic stroke but not hemorrhagic stroke. Participants with all 3 symptoms were at an 18%, 22%, or 10% higher risk of CVD, IHD, or ischemic stroke compared to nonsymptomatic adults. Associations between 3 symptoms and CVD incidence were consistently stronger in younger adults or those without baseline hypertension ( p for interaction <0.05)., Conclusions: Individual and coexisting insomnia symptoms are independent risk factors for CVD incidence, especially among young adults or adults who have not developed hypertension., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background Active commuting is related to a higher level of physical activity but more exposure to ambient air pollutants. With the rather serious air pollution in urban China, we aimed to examine the association between active commuting and risk of incident cardiovascular disease in the Chinese population. Methods and Results A total of 104 170 urban commuters without major chronic diseases at baseline were included from China Kadoorie Biobank. Self-reported commuting mode was defined as nonactive commuting, work at home or near home, walking, and cycling. Multivariable Cox regression was used to examine associations between commuting mode and cardiovascular disease. Overall, 47.2% of the participants reported nonactive commuting, 13.4% reported work at home or work near home, 20.1% reported walking, and 19.4% reported cycling. During a median follow-up of 10 years, we identified 5374 incidents of ischemic heart disease, 664 events of hemorrhagic stroke, and 4834 events of ischemic stroke. After adjusting for sex, socioeconomic status, lifestyle factors, sedentary time, body mass index, comorbidities, household air pollution, passive smoking, and other domain physical activity, walking (hazard ratio, 0.90; 95% CI, 0.84-0.96) and cycling (hazard ratio, 0.81; 95% CI, 0.74-0.88) were associated with a lower risk of ischemic heart disease than nonactive commuting. Cycling was associated with a lower risk of ischemic stroke (hazard ratio, 0.92; 95% CI, 0.84-1.00). No significant association was found of walking or cycling with hemorrhagic stroke. The associations of commuting mode with major cardiovascular disease were consistent among men and women and across different levels of other domain physical activity. Conclusions In urban China, cycling was associated with a lower risk of ischemic heart disease and ischemic stroke. Walking was associated with a lower risk of ischemic heart disease.

Background: Physical inactivity and sedentary behavior are associated with higher risk of cardiovascular disease (CVD). Little is known about the relevance of circulating metabolites for these associations., Methods: A nested case-control study within the prospective China Kadoorie Biobank included 3195 incident CVD cases (2057 occlusive CVD and 1138 intracerebral hemorrhage) and 1465 controls aged 30 to 79 years without prior CVD or statin use at baseline. Nuclear magnetic resonance spectroscopy was used to measure 225 metabolic markers and derived traits in baseline plasma samples. Linear regression was used to relate self-reported physical activity and sedentary leisure time to biomarkers, adjusting for potential confounders. These were contrasted with associations of biomarkers with occlusive CVD risk., Results: Physical activity and sedentary leisure time were associated with >100 metabolic markers, with patterns of associations generally mirroring each other. Physical activity was inversely associated with very low and low-density and positively with large and very large HDL (high-density lipoprotein) particle concentrations. Physical activity was also inversely associated with alanine, glucose, lactate, acetoacetate, and the inflammatory marker glycoprotein acetyls. In general, associations of physical activity and sedentary leisure time with specific metabolic markers were directionally consistent with the associations of these metabolic markers with occlusive CVD risk. Overall, metabolic markers potentially explained ≈70% of the protective associations of physical activity and ≈50% of the positive associations of sedentary leisure time with occlusive CVD., Conclusions: Among Chinese adults, physical activity and sedentary behavior have opposing associations with a diverse range of circulating metabolites, which may partially explain their associations with CVD risk.

Objective: To examine the associations between egg consumption and cardiovascular disease (CVD), ischaemic heart disease (IHD), major coronary events (MCE), haemorrhagic stroke as well as ischaemic stroke., Methods: During 2004-2008, over 0.5 million adults aged 30-79 years were recruited from 10 diverse survey sites in China. Participants were asked about the frequency of egg consumption and were followed up via linkages to multiple registries and active investigation. Among 461 213 participants free of prior cancer, CVD and diabetes, a total of 83 977 CVD incident cases and 9985 CVD deaths were documented, as well as 5103 MCE. Stratified Cox regression was performed to yield adjusted hazard ratios for CVD endpoints associated with egg consumption., Results: At baseline, 13.1% of participants reported daily consumption (usual amount 0.76 egg/day) and 9.1% reported never or very rare consumption (usual amount 0.29 egg/day). Compared with non-consumers, daily egg consumption was associated with lower risk of CVD (HR 0.89, 95% CI 0.87 to 0.92). Corresponding multivariate-adjusted HRs (95% CI) for IHD, MCE, haemorrhagic stroke and ischaemic stroke were 0.88 (0.84 to 0.93), 0.86 (0.76 to 0.97), 0.74 (0.67 to 0.82) and 0.90 (0.85 to 0.95), respectively. There were significant dose-response relationships of egg consumption with morbidity of all CVD endpoints (P for linear trend <0.05). Daily consumers also had an 18% lower risk of CVD death and a 28% lower risk of haemorrhagic stroke death compared to non-consumers., Conclusion: Among Chinese adults, a moderate level of egg consumption (up to <1 egg/day) was significantly associated with lower risk of CVD, largely independent of other risk factors., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China., Methods: 512 891 adults (59% women) aged 30-79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure., Findings: During a median follow-up of 9 years (IQR 8-10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40-79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120-180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28-1·34]) and ischaemic stroke (1·30 [1·29-1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65-1·71]). HRs for vascular disease were twice as steep at ages 40-49 years than at ages 70-79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35-1·44]) and diabetes (1·14 [1·12-1·15]). About half of all vascular deaths in China were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg), accounting for approximately 1 million deaths (<80 years of age) annually., Interpretation: Among adults in China, systolic blood pressure was continuously related to major vascular disease with no evidence of a threshold down to 120 mm Hg. Unlike previous studies in high-income countries, blood pressure was more strongly associated with intracerebral haemorrhage than with ischaemic stroke. Even small reductions in mean blood pressure at a population level could be expected to have a major impact on vascular morbidity and mortality., Funding: UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, and the National Science Foundation of China., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: China has high COPD rates, even among never-regular smokers. Little is known about nonrespiratory disease risks, especially vascular morbidity and mortality after developing airflow obstruction (AFO) in Chinese adults., Objective: We aimed to investigate the prospective association of prevalent AFO with major vascular morbidity and mortality., Materials and Methods: In 2004-2008, a nationwide prospective cohort study recruited 512,891 men and women aged 30-79 years from 10 diverse localities across China, tracking cause-specific mortality and coded episodes of hospitalization for 9 years. Cox regression yielded adjusted HRs for vascular diseases comparing individuals with spirometry-defined prevalent AFO at baseline to those without., Results: Of 489,382 participants with no vascular disease at baseline, 6.8% had AFO, with prevalence rising steeply with age. Individuals with prevalent AFO had significantly increased vascular mortality (n=1,429, adjusted HR 1.29, 95% CI 1.21-1.36). There were also increased risks of hemorrhagic stroke (n=823, HR 1.18, 95% CI 1.09-1.27), major coronary events (n=635, HR 1.33, 95% CI 1.22-1.45), and heart failure (n=543, HR 2.19, 95% CI 1.98-2.41). For each outcome, the risk increased progressively with increasing COPD severity and persisted among never-regular smokers., Conclusion: Among adult Chinese, AFO was associated with significantly increased risks of major vascular morbidity and mortality. COPD management should be integrated with vascular disease prevention and treatment programs to improve long-term prognosis., Competing Interests: Disclosure KJD is a full-time employee of, and owns shares in, GlaxoSmithKline. The authors report no other conflicts of interest in this work.

Importance: Increasing levels of high-density lipoprotein (HDL) cholesterol through pharmacologic inhibition of cholesteryl ester transfer protein (CETP) is a potentially important strategy for prevention and treatment of cardiovascular disease (CVD)., Objective: To use genetic variants in the CETP gene to assess potential risks and benefits of lifelong lower CETP activity on CVD and other outcomes., Design, Setting, and Participants: This prospective biobank study included 151 217 individuals aged 30 to 79 years who were enrolled from 5 urban and 5 rural areas of China from June 25, 2004, through July 15, 2008. All participants had baseline genotype data, 17 854 of whom had lipid measurements and 4657 of whom had lipoprotein particle measurements. Median follow-up of 9.2 years (interquartile range, 8.2-10.1 years) was completed January 1, 2016, through linkage to health insurance records and death and disease registries., Exposures: Five CETP variants, including an East Asian loss-of-function variant (rs2303790), combined in a genetic score weighted to associations with HDL cholesterol levels., Main Outcomes and Measures: Baseline levels of lipids and lipoprotein particles, cardiovascular risk factors, incidence of carotid plaque and predefined major vascular and nonvascular diseases, and a phenome-wide range of diseases., Results: Among the 151 217 individuals included in this study (58.4% women and 41.6% men), the mean (SD) age was 52.3 (10.9) years. Overall, the mean (SD) low-density lipoprotein (LDL) cholesterol level was 91 (27) mg/dL; HDL cholesterol level, 48 (12) mg/dL. CETP variants were strongly associated with higher concentrations of HDL cholesterol (eg, 6.1 [SE, 0.4] mg/dL per rs2303790-G allele; P = 9.4 × 10-47) but were not associated with lower LDL cholesterol levels. Within HDL particles, cholesterol esters were increased and triglycerides reduced, whereas within very low-density lipoprotein particles, cholesterol esters were reduced and triglycerides increased. When scaled to 10-mg/dL higher levels of HDL cholesterol, the CETP genetic score was not associated with occlusive CVD (18 550 events; odds ratio [OR], 0.98; 95% CI, 0.91-1.06), major coronary events (5767 events; OR, 1.08; 95% CI, 0.95-1.22), myocardial infarction (3118 events; OR, 1.14; 95% CI, 0.97-1.35), ischemic stroke (13 759 events; OR, 0.94; 95% CI, 0.86-1.02), intracerebral hemorrhage (6532 events; OR, 0.94; 95% CI, 0.83-1.06), or other vascular diseases or carotid plaque. Similarly, rs2303790 was not associated with any vascular diseases or plaque. No associations with nonvascular diseases were found other than an increased risk for eye diseases with rs2303790 (4090 events; OR, 1.43; 95% CI, 1.13-1.80; P = .003)., Conclusions and Relevance: CETP variants were associated with altered HDL metabolism but did not lower LDL cholesterol levels and had no significant association with risk for CVD. These results suggest that in the absence of reduced LDL cholesterol levels, increasing HDL cholesterol levels by inhibition of CETP may not confer significant benefits for CVD.

Background: Higher fruit consumption is associated with lower risk of cardiovascular disease (CVD). Substantial uncertainties remain, however, about the associations of fruit consumption with all-cause mortality and mortality from subtypes of CVD and major non-vascular diseases, especially in China., Methods: In 2004-08, the nationwide China Kadoorie Biobank Study recruited > 0.5 million adults aged 30-79 years from 10 diverse localities in China. Fresh fruit consumption was estimated using an interviewer-administered electronic questionnaire, and mortality data were collected from death registries. Among the 462 342 participants who were free of major chronic diseases at baseline, 17 894 deaths were recorded during ∼ 7 years of follow-up. Cox regression yielded adjusted rate ratios (RRs) for all-cause and cause-specific mortality associated with fruit consumption., Results: At baseline, 28% of participants reported consuming fruit ≥ 4 days/week (regular consumers) and 6% reported never/rarely consuming fruit (non-consumers). Compared with non-consumers, regular consumers had 27% [RR = 0.73, 95% confidence interval (CI) 0.70-0.76] lower all-cause mortality, 34% lower CVD mortality (n = 6166; RR = 0.66, 0.61-0.71), 17% lower cancer mortality (n = 6796; RR = 0.83, 0.78-0.89) and 42% lower mortality from chronic obstructive pulmonary disease (COPD) (n = 1119; RR = 0.58, 0.47-0.71). For each of the above, there was an approximately log-linear dose-response relationship with amount consumed. For mortality from site-specific cancers, fruit consumption was inversely associated with digestive tract cancer (n = 2265; RR = 0.72, 0.64-0.81), particularly oesophageal cancer (n = 801; RR = 0.65, 0.50-0.83), but not with cancer of lung or liver., Conclusions: Among Chinese adults, higher fresh fruit consumption was associated with significantly lower mortality from several major vascular and non-vascular diseases. Given the current low population level of fruit consumption, substantial health benefits could be gained from increased fruit consumption in China., (© The Author 2017; Published by Oxford University Press on behalf of the International Epidemiological Association)

Background: Pregnancy and pregnancy loss may be linked to cardiovascular disease (CVD). However, the evidence is still inconsistent, especially in East Asians, whose reproductive patterns differ importantly from those in the West. We examined the associations of pregnancy, miscarriage, induced abortion, and stillbirth with CVD incidence among Chinese women., Methods: In 2004-2008, the nationwide China Kadoorie Biobank recruited 302,669 women aged 30-79 years from ten diverse localities. During 7 years of follow-up, 43,968 incident cases of circulatory disease, 14,440 of coronary heart disease, and 19,925 of stroke (including 11,430 ischaemic and 2170 haemorrhagic strokes), were recorded among 289,573 women without prior CVD at baseline. Cox regression yielded multiple adjusted hazard ratios (HRs) for CVD risks associated with pregnancy outcomes., Results: Overall, 99% of women had been pregnant, and among them 10%, 53%, and 7% reported having a history of miscarriage, induced abortion, and stillbirth, respectively. Each additional pregnancy was associated with an adjusted HR of 1.03 (95% confidence interval, CI: 1.02; 1.04) for circulatory disease. A history of miscarriage, induced abortion, and stillbirth, respectively, were associated with adjusted HRs of 1.04 (1.01; 1.07), 1.04 (1.02; 1.07), and 1.07 (1.03; 1.11) for circulatory disease. The relationship was stronger with recurrent pregnancy loss; adjusted HRs for each additional loss being 1.04 (1.00; 1.09) for miscarriage, 1.02 (1.01; 1.04) for induced abortion, and 1.04 (1.00; 1.08) for stillbirth., Conclusions: Among Chinese women, increases in pregnancy, and a history and recurrence of miscarriage, induced abortion, and stillbirth are each associated with a higher risk of CVD.

Objectives: To assess the associations of fresh fruit consumption and total physical activity with all-cause and cardiovascular mortality among Chinese adults who have been diagnosed with cardiovascular disease (CVD) or hypertension., Methods: During 2004-08, the China Kadoorie Biobank study recruited 70,047 adults, aged 30-79 years, with physician-diagnosed stroke or transient ischaemic attack, ischemic heart disease, or hypertension. Information on diet and physical activity was collected using an interviewer-administered electronic questionnaire. Cox regression was used to yield hazard ratios (HRs) for the independent and joint associations of fresh fruit consumption and total physical activity with mortality., Results: At baseline, 32.9% of participants consumed fresh fruit regularly (i.e. >3 days/week) and the mean total physical activity were 15.8 (SD = 11.8) MET-hr/day. During ~7-years follow-up, 6569 deaths occurred with 3563 from CVD. Compared to participants with <1 day/week fruit consumption, regular consumers had HR (95% CI) of 0.84 (0.79-0.89) for all-cause mortality and 0.79 (0.73-0.86) for CVD mortality. The HRs for the top vs bottom tertile of physical activity were 0.68 (0.64-0.72) and 0.65 (0.60-0.71), respectively, with no clear evidence of reverse causality. After correcting for regression dilution, each 100 g/day usual consumption of fresh fruit or 10 MET-hr/day usual levels of physical activity was associated with 23-29% lower mortality. The combination of regular fruit consumption with top 3rd of physical activity (>16.53 MET-hr/day) was associated with about 40% lower mortality., Conclusion: Among Chinese adults with pre-existing vascular disease, higher physical activity and fruit consumption were both independently and jointly associated with lower mortality.

Background: Adherence to a combination of healthy lifestyle factors has been related to a considerable reduction of cardiovascular risk in white populations; however, little is known whether such associations persist in nonwhite populations like the Asian population., Objectives: This study aimed to examine the associations of a combination of modifiable, healthy lifestyle factors with the risks of ischemic cardiovascular diseases and estimate the proportion of diseases that could potentially be prevented by adherence to these healthy lifestyle patterns., Methods: This study examined the associations of 6 lifestyle factors with ischemic heart disease and ischemic stroke (IS) in the China Kadoorie Biobank of 461,211 participants 30 to 79 years of age who did not have cardiovascular diseases, cancer, or diabetes at baseline. Low-risk lifestyle factors were defined as nonsmoking status or having stopped smoking for reasons other than illness, alcohol consumption of <30 g/day, a median or higher level of physical activity, a diet rich in vegetables and fruits and limited in red meat, a body mass index of 18.5 to 23.9 kg/m 2 , and a waist-to-hip ratio <0.90 for men and <0.85 for women., Results: During a median of 7.2 years (3.3 million person-years) of follow-up, this study documented 3,331 incident major coronary events (MCE) and 19,348 incident ISs. In multivariable-adjusted analyses, current nonsmoking status, light to moderate alcohol consumption, high physical activity, a diet rich in vegetables and fruits and limited in red meat, and low adiposity were independently associated with reduced risks of MCE and IS. Compared with participants without any low-risk factors, the hazard ratio for participants with ≥4 low-risk factors was 0.42 (95% confidence interval: 0.34 to 0.52) for MCE and 0.61 (95% confidence interval: 0.56 to 0.66) for IS. Approximately 67.9% (95% confidence interval: 46.5% to 81.9%) of the MCE and 39.1% (95% confidence interval: 26.4% to 50.4%) of the IS cases were attributable to poor adherence to healthy lifestyle., Conclusions: Adherence to healthy lifestyle may substantially lower the burden of cardiovascular diseases in Chinese., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Diabetes is a known risk factor for cardiovascular disease (CVD). Substantial uncertainty remains, however, about the relevance to CVD risk for blood glucose levels below the diabetes threshold., Objective: To examine the association of random plasma glucose (RPG) levels with the risk for major CVD in Chinese adults without known diabetes., Design, Setting, and Participants: This prospective cohort study included 467 508 men and women aged 30 to 79 years with no history of diabetes, ischemic heart disease (IHD), stroke, or transient ischemic attack. Participants were recruited from 5 urban and 5 rural diverse locations across China from June 25, 2004, to July 15, 2008, and followed up to January 1, 2014., Exposures: Baseline and usual (longer-term average) RPG level., Main Outcomes and Measures: Cardiovascular deaths, major coronary events (MCE) (including fatal IHD and nonfatal myocardial infarction), ischemic stroke (IS), major occlusive vascular disease (MOVD) (including MCE or IS), and intracerebral hemorrhage. Preliminary validation of stroke and IHD events demonstrated positive predictive values of approximately 90% and 85%, respectively. Cox regression yielded adjusted hazard ratios (aHRs) for CVD associated with RPG levels., Results: Among the 467 508 participants (41.0% men; 59.0% women; mean [SD] age, 51 [11] years), a significant positive association of baseline RPG levels with CVD risks continued to 4.0 mmol/L (72 mg/dL). After adjusting for regression dilution bias, each 1-mmol/L (18-mg/dL) higher usual RPG level above 5.9 mmol/L (106 mg/dL) was associated with an 11% higher risk for cardiovascular death (6645 deaths; aHR, 1.11; 95% CI, 1.10-1.13). Similarly strong positive associations were seen for MCE (3270 events; aHR, 1.10; 95% CI, 1.08-1.13), IS (19 153 events; aHR, 1.08; 95% CI, 1.07-1.09), and MOVD (22 023 events; aHR, 1.08; 95% CI, 1.07-1.09). For intracerebral hemorrhage, the association was weaker, but also significant (4326 events; aHR, 1.05; 95% CI, 1.02-1.07). These associations persisted after excluding participants who developed diabetes during follow-up., Conclusions and Relevance: Among adult Chinese without diabetes, lower RPG levels are associated with lower risks for major CVDs, even within a normal range of blood glucose levels.

Background: In China, diabetes prevalence is rising rapidly, but little is known about the associated risks and population burden of cardiovascular diseases. We assess associations of diabetes with major cardiovascular diseases and the relevance of diabetes duration and other modifiable risk factors to these associations., Methods and Findings: A nationwide prospective study recruited 512,891 men and women aged 30-79 y between 25 June 2004 and 15 July 2008 from ten diverse localities across China. During ~7 y of follow-up, 7,353 cardiovascular deaths and 25,451 non-fatal major cardiovascular events were recorded among 488,760 participants without prior cardiovascular disease at baseline. Cox regression yielded adjusted hazard ratios (HRs) comparing disease risks in individuals with diabetes to those without. Overall, 5.4% (n = 26,335) of participants had self-reported (2.7%) or screen-detected (2.7%) diabetes. Individuals with self-reported diabetes had an adjusted HR of 2.07 (95% CI 1.90-2.26) for cardiovascular mortality. There were significant excess risks of major coronary event (2.44, 95% CI 2.18-2.73), ischaemic stroke (1.68, 95% CI 1.60-1.77), and intracerebral haemorrhage (1.24, 95% CI 1.07-1.44). Screen-detected diabetes was also associated with significant, though more modest, excess cardiovascular risks, with corresponding HRs of 1.66 (95% CI 1.51-1.83), 1.62 (95% CI 1.40-1.86), 1.48 (95% CI 1.40-1.57), and 1.17 (95% CI 1.01-1.36), respectively. Misclassification of screen-detected diabetes may have caused these risk estimates to be underestimated, whilst lack of data on lipids may have resulted in residual confounding of diabetes-associated cardiovascular disease risks. Among individuals with diabetes, cardiovascular risk increased progressively with duration of diabetes and number of other presenting modifiable cardiovascular risk factors. Assuming a causal association, diabetes now accounts for ~0.5 million (489,676, 95% CI 335,777-681,202) cardiovascular deaths annually in China., Conclusions: Among Chinese adults, diabetes is associated with significantly increased risks of major cardiovascular diseases. The increasing prevalence and younger age of onset of diabetes foreshadow greater diabetes-attributable disease burden in China.

Background: In Western populations, a higher level of fruit consumption has been associated with a lower risk of cardiovascular disease, but little is known about such associations in China, where the consumption level is low and rates of stroke are high., Methods: Between 2004 and 2008, we recruited 512,891 adults, 30 to 79 years of age, from 10 diverse localities in China. During 3.2 million person-years of follow-up, 5173 deaths from cardiovascular disease, 2551 incident major coronary events (fatal or nonfatal), 14,579 ischemic strokes, and 3523 intracerebral hemorrhages were recorded among the 451,665 participants who did not have a history of cardiovascular disease or antihypertensive treatments at baseline. Cox regression yielded adjusted hazard ratios relating fresh fruit consumption to disease rates., Results: Overall, 18.0% of participants reported consuming fresh fruit daily. As compared with participants who never or rarely consumed fresh fruit (the "nonconsumption" category), those who ate fresh fruit daily had lower systolic blood pressure (by 4.0 mm Hg) and blood glucose levels (by 0.5 mmol per liter [9.0 mg per deciliter]) (P<0.001 for trend for both comparisons). The adjusted hazard ratios for daily consumption versus nonconsumption were 0.60 (95% confidence interval [CI], 0.54 to 0.67) for cardiovascular death, and 0.66 (95% CI, 0.58 to 0.75), 0.75 (95% CI, 0.72 to 0.79), and 0.64 (95% CI, 0.56 to 0.74), respectively, for incident major coronary events, ischemic stroke, and hemorrhagic stroke. There was a strong log-linear dose-response relationship between the incidence of each outcome and the amount of fresh fruit consumed. These associations were similar across the 10 study regions and in subgroups of participants defined by baseline characteristics., Conclusions: Among Chinese adults, a higher level of fruit consumption was associated with lower blood pressure and blood glucose levels and, largely independent of these and other dietary and nondietary factors, with significantly lower risks of major cardiovascular diseases. (Funded by the Wellcome Trust and others.).

Importance: Hypertension is a leading cause of premature death in China, but limited evidence is available on the prevalence and management of hypertension and its effect on mortality from cardiovascular disease (CVD)., Objectives: To examine the prevalence, diagnosis, treatment, and control of hypertension and to assess the CVD mortality attributable to hypertension in China., Design, Setting and Participants: This prospective cohort study (China Kadoorie Biobank Study) recruited 500 223 adults, aged 35 to 74 years, from the general population in China. Blood pressure (BP) measurements were recorded as part of the baseline survey from June 25, 2004, to August 5, 2009, and 7028 deaths due to CVD were recorded before January 1, 2014 (mean duration of follow-up: 7.2 years). Data were analyzed from June 9, 2014, to July 17, 2015., Exposures: Prevalence and diagnosis of hypertension (systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or receiving treatment for hypertension) and treatment and control rates overall and in various population subgroups., Main Outcomes and Measures: Cox regression analysis yielded age- and sex-specific rate ratios for deaths due to CVD comparing participants with and without uncontrolled hypertension, which were used to estimate the number of CVD deaths attributable to hypertension., Results: The cohort included 205 167 men (41.0%) and 295 056 women (59.0%) with a mean (SD) age of 52 (10) years for both sexes. Overall, 32.5% of participants had hypertension; the prevalence increased with age (from 12.6% at 35-39 years of age to 58.4% at 70-74 years of age) and varied substantially by region (range, 22.7%-40.7%). Of those with hypertension, 30.5% had received a diagnosis from a physician; of those with a diagnosis of hypertension, 46.4% were being treated; and of those treated, 29.6% had their hypertension controlled (ie, systolic BP <140 mm Hg; diastolic BP <90 mm Hg), resulting in an overall control rate of 4.2%. Even among patients with hypertension and prior CVD, only 13.0% had their hypertension controlled. Uncontrolled hypertension was associated with relative risks for CVD mortality of 4.1 (95% CI, 3.7-4.6), 2.6 (95% CI, 2.4-2.9) and 1.9 (95% CI, 1.8-2.0) at ages 35 to 59, 60 to 69, and 70 to 79 years, respectively, and accounted for about one-third of deaths due to CVD (approximately 750 000) at 35 to 79 years of age in 2010., Conclusions and Relevance: About one-third of Chinese adults in this national cohort population had hypertension. The levels of diagnosis, treatment, and control were much lower than in Western populations, and were associated with significant excess mortality.

Aims: Relatively little is known about the use of medication for the secondary prevention of cardiovascular disease (CVD) events in China, and the relevance to it of socioeconomic, lifestyle and health-related factors., Methods and Results: We analysed cross-sectional data from the China Kadoorie Biobank (CKB) of 512,891 adults aged 30-79 years recruited from 1737 rural and urban communities in China. Information about doctor-diagnosed ischaemic heart disease (IHD) and stroke, and the use of medication for the secondary prevention of CVD events, were recorded by interview. Multivariate logistic regression was used to estimate odds ratios (ORs) for use of secondary preventive treatment, adjusting simultaneously for age, sex, area and education. Overall, 23,129 (4.5%) participants reported a history of CVD (3.0% IHD, 1.7% stroke). Among them, 35% reported current use of any of 6 classes of drug (anti-platelet, statins, diuretics, ACE-I, β-blockers or calcium-channel blockers) for the prevention of CVD events, with the rate of usage greater in those with older age, higher levels of income, education, BMI or blood pressure. The use of these agents was associated positively with history of diagnosed hypertension (OR 7.5; 95% confidence intervals: 7.08-8.06) and diabetes (1.40; 1.28-1.52) and inversely with self-rated health status, but there was no association with years since diagnosis., Conclusions: Despite recent improvements in hospital care in China, only one in three individuals with prior CVD was routinely treated with any proven secondary preventive drugs. The treatment rates were correlated with the existence of other risk factors, in particular evidence of hypertension., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Supplemental Digital Content is available in the text. Background: Physical inactivity and sedentary behavior are associated with higher risk of cardiovascular disease (CVD). Little is known about the relevance of circulating metabolites for these associations. Methods: A nested case-control study within the prospective China Kadoorie Biobank included 3195 incident CVD cases (2057 occlusive CVD and 1138 intracerebral hemorrhage) and 1465 controls aged 30 to 79 years without prior CVD or statin use at baseline. Nuclear magnetic resonance spectroscopy was used to measure 225 metabolic markers and derived traits in baseline plasma samples. Linear regression was used to relate self-reported physical activity and sedentary leisure time to biomarkers, adjusting for potential confounders. These were contrasted with associations of biomarkers with occlusive CVD risk. Results: Physical activity and sedentary leisure time were associated with >100 metabolic markers, with patterns of associations generally mirroring each other. Physical activity was inversely associated with very low and low-density and positively with large and very large HDL (high-density lipoprotein) particle concentrations. Physical activity was also inversely associated with alanine, glucose, lactate, acetoacetate, and the inflammatory marker glycoprotein acetyls. In general, associations of physical activity and sedentary leisure time with specific metabolic markers were directionally consistent with the associations of these metabolic markers with occlusive CVD risk. Overall, metabolic markers potentially explained ≈70% of the protective associations of physical activity and ≈50% of the positive associations of sedentary leisure time with occlusive CVD. Conclusions: Among Chinese adults, physical activity and sedentary behavior have opposing associations with a diverse range of circulating metabolites, which may partially explain their associations with CVD risk. [ABSTRACT FROM AUTHOR]

Background Acute respiratory infections have been associated with a transient increase in cardiovascular risk. However, whether such an association persists beyond one month, and the potential modifying effect of cardiovascular risk factors on such an association is less well established. Methods The China Kadoorie Biobank study enrolled 512,726 participants from 10 areas across China during 2004-08. By the end of 2017, a total of 5,444 participants with ischemic heart disease (IHD) and 4,846 with ischemic stroke (IS) who also had at least a record of hospitalization for pneumonia during follow-up were included. We used a self-controlled case series method and calculated the age- and season-adjusted relative incidences (RIs) and 95% confidence intervals (CIs) for ischemic cardiovascular disease (CVD) after pneumonia. Results The risk of ischemic CVD increased during days 1-3 after pneumonia hospitalization, with a RI (95% CI) of 4.24 (2.92-6.15) for IHD and 1.85 (1.02-3.35) for IS. The risk gradually reduced with longer duration since pneumonia hospitalization but remained elevated until days 92-365 for IHD (1.23, 1.12-1.35), and days 29-91 for IS (1.25, 1.05-1.48). Pre-existing cardiovascular risk factors amplified the associations between pneumonia and ischemic CVD risks. Besides, the risk of ischemic CVD was also higher among the participants aged ≥70 years (P interaction<0.001 for IHD and =0.033 for IS). Conclusions Among middle-aged and older Chinese adults, pneumonia hospitalization was associated with both short- and long-term increases in ischemic CVD risk for up to one year. Key messages Pneumonia hospitalizations were associated with increased subsequent risk of ischemic CVD. [ABSTRACT FROM AUTHOR]

Chinese tea and the major health effects include: antimicrobial, anti-ultraviolet radiation, anticancer, lowering blood lipid and glucose, and protecting against coronary heart diseases. In contrast to the extensive studies on the protective effects of tea on cancer, fewer studies on the health effects of tea on cardiovascular diseases (CVD) have been published. This paper summarises the research results on the possible protective effects of tea on CVD available in China. The results from animal studies clearly demonstrated that tea pigments are effective in lowering blood lipid levels and preventing plaque formation in the aorta. However, the evidence of tea pigments in protecting ischemia heart disease (IHD) in humans is less convincing. One large well-designed ecological study reported an inverse correlation between tea drinking and IHD mortality; but the inverse correlation disappeared after controlling possible confounding factors. However, the effects in improving blood lipid levels and rheology biomarkers in hyperlipidemia subjects or CVD patients by tea pigments seem promising. However, these studies were not well-designed, controlled randomized clinical trials. This made the assessment difficult and inconclusive. [ABSTRACT FROM AUTHOR]

Introduction: Active commuting is related to higher level of physical activity but more exposure to ambient air pollutants. Little is known about the relations of long-term active commuting with cardiovascular events, especially in developing countries with severe air pollution. Methods: The prospective China Kadoorie Biobank study enrolled over 0.5 million adults aged 30-79 years during 2004-08 from ten diverse areas across China. Cox regression yielded adjusted HRs and 95% CIs for incident cardiovascular events by active commuting time. Active commuting was defined as commuting by walking or cycling. Results: During a median follow-up of 9.6 years, there were 39,987 ischemic heart disease, 8,784 hemorrhagic stroke and 37,300 ischemic stroke events recorded among 487,197 participants without major chronic diseases at baseline. Compared with participants who reported noncommuting or non-active commuting, the multivariable-adjusted HRs (95%CIs) for ischemic heart disease were 0.96 (0.92, 1.00) for those who reported active commuting 1~29 min/day and 0.94 (0.90, 0.98) for ≥30 min/day, respectively; the respective HRs (95% CIs) were 0.87 (0.80, 0.95) and 0.88 (0.80, 0.96) for hemorrhagic stroke. After multivariable adjustment, active commuting was not associated with ischemic stroke. The associations between active commuting and cardiovascular diseases were independent of total physical activity level and were modified by sex, region, smoking status, and alcohol consumption. For ischemic heart disease, the inverse associations with active commuting were only observed among those aged less than sixty. For hemorrhagic stroke, the inverse associations with active commuting appeared to be somewhat greater among current regular smoker. Conclusions: Our data indicate that daily active commuting is related to a reduced risk of ischemic heart disease and hemorrhagic stroke, suggesting the health benefit of higher commuting physical activity level outweigh the risk due to air pollution exposures. [ABSTRACT FROM AUTHOR]