Conventional and genetic associations of BMI with major vascular and non-vascular disease incidence and mortality in a relatively lean Chinese population: U-shaped relationship revisited.

BACKGROUND: Higher body mass index (BMI) is associated with higher incidence of cardiovascular and some non-cardiovascular diseases (CVDs/non-CVDs). However, uncertainty remains about its associations with mortality, particularly at lower BMI levels. METHODS: The prospective China Kadoorie Biobank recruited >512 000 adults aged 30-79 years in 2004-08 and genotyped a random subset of 76 000 participants. In conventional and Mendelian randomization (MR) analyses, Cox regression yielded adjusted hazard ratios (HRs) associating measured and genetically predicted BMI levels with incident risks of major vascular events (MVEs; conventional/MR 68 431/23 621), ischaemic heart disease (IHD; 50 698/12 177), ischaemic stroke (IS; 42 427/11 897) and intracerebral haemorrhage (ICH; 7644/4712), and with mortality risks of CVD (15 427/6781), non-CVD (26 915/4355) and all causes (42 342/6784), recorded during ∼12 years of follow-up. RESULTS: Overall, the mean BMI was 23.8 (standard deviation: 3.2) kg/m2 and 13% had BMIs of <20 kg/m2. Measured and genetically predicted BMI showed positive log-linear associations with MVE, IHD and IS, but a shallower positive association with ICH in conventional analyses. Adjusted HRs per 5 kg/m2 higher genetically predicted BMI were 1.50 (95% CI 1.41-1.58), 1.49 (1.38-1.61), 1.42 (1.31-1.54) and 1.64 (1.58-1.69) for MVE, IHD, IS and ICH, respectively. These were stronger than associations in conventional analyses [1.21 (1.20-1.23), 1.28 (1.26-1.29), 1.31 (1.29-1.33) and 1.14 (1.10-1.18), respectively]. At BMIs of ≥20 kg/m2, there were stronger positive log-linear associations of BMI with CVD, non-CVD and all-cause mortality in MR than in conventional analyses. CONCLUSIONS: Among relatively lean Chinese adults, higher genetically predicted BMI was associated with higher risks of incident CVDs. Excess mortality risks at lower BMI in conventional analyses are likely not causal and may reflect residual reverse causality.

Genetic analyses of 104 phenotypes in 20,900 Chinese pregnant women reveal pregnancy-specific discoveries.

Monitoring biochemical phenotypes during pregnancy is vital for maternal and fetal health, allowing early detection and management of pregnancy-related conditions to ensure safety for both. Here, we conducted a genetic analysis of 104 pregnancy phenotypes in 20,900 Chinese women. The genome-wide association study (GWAS) identified a total of 410 trait-locus associations, with 71.71% reported previously. Among the 116 novel hits for 45 phenotypes, 83 were successfully replicated. Among them, 31 were defined as potentially pregnancy-specific associations, including creatine and HELLPAR and neutrophils and ESR1, with subsequent analysis revealing enrichments in estrogen-related pathways and female reproductive tissues. The partitioning heritability underscored the significant roles of fetal blood, embryoid bodies, and female reproductive organs in pregnancy hematology and birth outcomes. Pathway analysis confirmed the intricate interplay of hormone and immune regulation, metabolism, and cell cycle during pregnancy. This study contributes to the understanding of genetic influences on pregnancy phenotypes and their implications for maternal health.

Mosaic loss of chromosome Y, tobacco smoking, and risk of age-related lung diseases: insights from two prospective cohorts.

BACKGROUND: Little is known about the underlying relationship between mosaic loss of chromosome Y (mLOY), the most common chromosomal alterations in older men, and the risk of age-related lung diseases. METHODS: We included 217 780 participants from the UK Biobank and 42 859 participants from the China Kadoorie Biobank. The mLOY events were detected using the Mosaic Chromosomal Alterations pipeline. Outcomes included all lung diseases, chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF). Cox proportional hazard models were fitted to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of mLOY with lung diseases in both cohorts. The combined HRs were derived from meta-analysis. RESULTS: Results from two cohorts showed that expanded mLOY was associated with increased risks of all lung diseases [HR (95% CI): 1.19 (1.04, 1.37)], COPD [HR (95% CI): 1.20 (1.13, 1.28)], lung cancer [HR (95% CI): 1.34 (1.21, 1.48)], and IPF [HR (95% CI): 1.34 (1.16, 1.56) in UKB]. There was evidence of positive interactions between mLOY and smoking behavior [relative excess risk due to interaction (97.5%CI)>0]. Additionally, we observed that current smokers with expanded mLOY had the highest risk of incident lung diseases in both cohorts. CONCLUSION: mLOY may be a novel predictor for age-related lung diseases. For current smokers carrying mLOY, adopting quitting smoking behavior may contribute to substantially reduce their risk of incident lung diseases.

[Epidemiological characteristics of hemorrhoids in a healthy physical examination population in China].

OBJECTIVE: To describe the epidemiological distribution of hemorrhoids in a physical examination population in China, which could provide evidence for precision prevention and early intervention of hemorrhoids. METHODS: Chinese subjects over 18 years of age who underwent a physical examination in a nationwide chain of physical examination centers in 2018 were studied in a cross-sectional design, which collected information by a questionnaire and physical examination results from each subject. The epidemiological distribution of hemorrhoids was described using Logistic models. The gender-, age-, and region-detection rates of hemorrhoids were standardized to the Sixth National Population Census of the People's Republic of China (2010). RESULTS: A total of 2 940 295 adult subjects were included in the study, of whom the average age was (41.7±14.0) years, and 52.6% were females. The standardized detection rate of hemorrhoids was higher for females (43.7%) than that for males (17.7%; P < 0.001) in this study. In the females, the age distribution of hemorrhoids was inverted U-shaped, with the highest standardized detection rate of hemorrhoids in the age group of 30-39 years (63.5%). In the males, the standardized detection rate of hemorrhoids increased along with age, with the highest percentage of 17.2% in the age group of 50-59 years, and the standardized detection rate of hemorrhoids in the age group of 60 and above decreased slightly (P < 0.001 for trend test). The participants with hypertension had a higher standardized detection rate of hemorrhoids than those with normal blood pressure in both males and females (P < 0.001). The standardized detection rate of hemorrhoids showed a positive correlation with body mass index (P < 0.001 for trend test in males). CONCLUSION: The detection rate of hemorrhoids varied to gender, age, obesity, and hypertension status, which could help to identify the risk factors and the high-risk sub-groups, and hence to strengthen health education and early detection accordingly, which could eventually reduce the incidence of hemorrhoids and improve the quality of life and health in the Chinese population. This study was conducted in a physical examination population, and the conclusions of this study should be extrapolated with caution.

Association between dietary fat intake and the risk of Alzheimer's disease: Mendelian randomisation study.

BACKGROUND: Observational studies have shown a controversial relationship between dietary fat intake and Alzheimer's disease, and the causal effects are unclear. AIMS: To assess the causal effects of total fat, saturated fat and polyunsaturated fat (PUF) intakes on the risk of Alzheimer's disease. METHOD: A two-sample Mendelian randomisation analysis was performed using genome-wide association study summary statistics on different types of fat intake from UK Biobank (n = 51 413) and on late-onset Alzheimer's disease (LOAD; 4282 cases, n = 307 112) and all forms of Alzheimer's disease (6281 cases, n = 309 154) from the FinnGen consortium. In addition, a multivariable Mendelian randomisation (MVMR) analysis was conducted to estimate the effects independent of carbohydrate and protein intakes. RESULTS: Genetically predicted per standard deviation increase in the total fat and saturated fat intakes were associated with 44 and 38% higher risks of LOAD (total fat: odds ratio = 1.44, 95% CI 1.03-2.02; saturated fat: odds ratio = 1.38, 95% CI 1.002-1.90; P = 0.049). The associations remained significant in the MVMR analysis (total fat: odds ratio = 3.31, 95% CI 1.74-6.29; saturated fat: odds ratio = 2.04, 95% CI 1.16-3.59). Total fat and saturated fat intakes were associated with a higher risk of all forms of Alzheimer's disease in the MVMR analysis (total fat: odds ratio = 2.09, 95% CI 1.22-3.57; saturated fat: odds ratio = 1.60, 95% CI 1.01-2.52). The PUF intake was not associated with LOAD or all forms of Alzheimer's disease. CONCLUSIONS: This study indicated that total dietary fat intake, especially saturated fat, contributed to the risk of Alzheimer's disease, and the effects were independent of other nutrients. These findings informed prevention strategies and management for Alzheimer's disease directly towards reducing dietary saturated fat intake.

Cost-Effectiveness of Salt Substitution and Antihypertensive Drug Treatment in Chinese Prehypertensive Adults.

BACKGROUND: Recent guidelines recommend antihypertensive drug treatment for prehypertensive individuals with blood pressure between 130/80 and 139/89 mm Hg. This study evaluates the cost-effectiveness of 3 interventions in Chinese prehypertensive adults: salt substitution, antihypertensive drug treatment, and their combination. METHODS: We developed a Markov cohort model to estimate cardiovascular disease (CVD) events, costs, and quality-adjusted life years (QALYs) over a lifetime. Data from the China Kadoorie Biobank informed the simulation. Costs and utilities were drawn from published sources. We evaluated the cost-effectiveness of salt substitution alone, antihypertensive drug treatment alone, and a combination of the 2, focusing on the overall prehypertensive population, those at high CVD risk, and different starting ages (40, 50, 60, and 70 years). Incremental cost-effectiveness ratios (ICERs) were calculated per QALY gained. RESULTS: Salt substitution at age 40 years is the only cost-effective strategy for prehypertensive individuals, with an ICER of $6413.62/QALY. For those at high CVD risk, the combination intervention starting at age 40 years is most cost-effective, with an ICER of $2913.30/QALY. Interventions initiated at younger ages yielded greater CVD reductions and lower ICERs. For example, a combined intervention at age 40 years reduces CVD events by 5.3% with an ICER of $2913.30/QALY, compared with 4.9% and $32 635.33/QALY at age 70 years. These results were consistent across sensitivity analyses. CONCLUSIONS: In China, replacing usual salt with a salt substitute is more cost-effective than treating prehypertensive individuals over the age of 40 years with antihypertensive drugs. Furthermore, starting intervention at a younger age in prehypertensive adults can result in even greater cost savings.

Proteo-genomic analyses in relatively lean Chinese adults identify proteins and pathways that affect general and central adiposity levels.

Adiposity is an established risk factor for multiple diseases, but the causal relationships of different adiposity types with circulating protein biomarkers have not been systematically investigated. We examine the causal associations of general and central adiposity with 2923 plasma proteins among 3977 Chinese adults (mean BMI = 23.9 kg/m²). Genetically-predicted body mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-to-hip ratio (WHR) are significantly (FDR < 0.05) associated with 399, 239, 436, and 283 proteins, respectively, with 80 proteins associated with all four and 275 with only one adiposity trait. WHR is associated with the most proteins (n = 90) after adjusting for other adiposity traits. These associations are largely replicated in Europeans (mean BMI = 27.4 kg/m²). Two-sample Mendelian randomisation (MR) analyses in East Asians using cis-protein quantitative trait locus (cis-pQTLs) identified in GWAS find 30/2 proteins significantly affect levels of BMI/WC, respectively, with 10 showing evidence of colocalisation, and seven (inter-alpha-trypsin inhibitor heavy chain H3, complement factor B, EGF-containing fibulin-like extracellular matrix protein 1, thioredoxin domain-containing protein 15, alpha-2-antiplasmin, fibronectin, mimecan) are replicated in separate MR using different cis-pQTLs identified in Europeans. These findings identified potential novel mechanisms and targets, to our knowledge, for improved treatment and prevention of obesity and associated diseases.

Association between sleep behaviors and stroke in Southwest China: a prospective cohort study.

BACKGROUND: Sleep can function as a potential modifiable risk factor in the control and prevention of stroke. Geography significantly influences sleep patterns. The association of sleep with stroke in population of Southwest China has not so far been investigated. METHODS: A total of 55,001 residents aged from 30 to 79 years in Southwest China were included in this study, obtaining their complete information of baseline survey and follow-up in China Kadoorie Biobank (CKB). Sleep-evaluating score was constructed on the basis of short/long sleep duration, insomnia, and snoring. The multivariate Cox proportional hazards regression was used to analyze the association between sleep behaviors and stroke. RESULTS: During 11.15 years of follow-up, 3410 stroke cases (572.78 cases/100,000 person-years) were documented. There exists no association of sleep-evaluating score with the risk of stroke in the total population. Male-predisposing association between sleep-evaluating score and risk of stroke was observed (for total stroke, HR = 1.52, 95% CI: 1.03-2.23; for hemorrhagic stroke, HR = 2.31, 95% CI: 1.22-4.34), with anisotropism in male residents with overweight and obesity (HR = 1.93, 95% CI: 1.03-3.63), and those without hypertension (HR = 1.76, 95% CI: 1.01-3.07) in the baseline survey. CONCLUSIONS: There exists the male-predisposing association between sleep-evaluating score and the risk of stroke in Southwest China. Improving sleep is required for reducing the risk of stroke.

Modelling personal temperature exposure using household and outdoor temperature and questionnaire data: Implications for epidemiological studies.

Non-optimal temperature is a leading risk factor for global disease burden. Most epidemiological studies assessed only outdoor temperature, with important uncertainties on personal exposure misclassification. The CKB-Air study measured personal, household (kitchen and living room), and outdoor temperatures in the summer (MAY-SEP 2017) and winter (NOV 2017-JAN 2018) in 477 participants in China. After data cleaning, ∼88,000 person-hours of data were recorded across each microenvironment. Using multivariable linear regression (MLR) and random forest (RF) models, we identified key predictors and constructed personal temperature exposure prediction models. We used generalised additive mixed effect models to examine the relationships of personal and outdoor temperatures with heart rate. The 24-hour mean (SD) personal and outdoor temperatures were 29.2 (3.8) °C and 27.6 (6.4) °C in summer, and 12.0 (4.0) °C and 7.5 (4.2) °C in winter, respectively. The temperatures across microenvironments were strongly correlated (Spearman's ρ: 0.86-0.92) in summer. In winter, personal temperature was strongly related to household temperatures (ρ: 0.74-0.79) but poorly related to outdoor temperature (ρ: 0.30). RF algorithm identified household and outdoor temperatures and study date as top predictors of personal temperature exposure for both seasons, and heating-related factors were important in winter. The final MLR and RF models incorporating questionnaire and device data performed satisfactorily in predicting personal exposure in both seasons (R2summer: 0.92; R2winter: 0.68-0.70). We found consistent U-shaped associations between measured and predicted personal temperature exposures and heart rate (lowest at âˆ¼ 14.5 °C), but a weak positive linear association with outdoor temperature. Personal and outdoor temperatures differ substantially winter, but prediction models incorporating household and outdoor temperatures and questionnaire data performed satisfactorily. Exposure misclassification from using outdoor temperature may produce inappropriate epidemiological findings.

Association of autosomal mosaic chromosomal alterations with risk of bladder cancer in Chinese adults: a prospective cohort study.

Little is known about the prospective association between autosomal mosaic chromosomal alterations (mCAs), a group of large-scale somatic mutations on autosomes, and bladder cancer. Here we utilized data from 99,877 participants who were free of physician-diagnosed cancer at baseline (2004-2008) of the China Kadoorie Biobank to estimate the associations between autosomal mCAs and bladder cancer (ICD-10: C67). A total of 2874 autosomal mCAs events among 2612 carriers (2.6%) were detected. After a median follow-up of 12.4 years, we discovered that participants with all autosomal mCAs exhibited higher risks of bladder cancer, with a multivariable-adjusted hazard ratio (HR) (95% confidence interval [CI]) of 2.60 (1.44, 4.70). The estimate of such association was even stronger for mosaic loss events (HR [95% CI]: 6.68 [2.92, 15.30]), while it was not significant for CN-LOH events. Both expanded (cell fraction ≥10%) and non-expanded autosomal mCAs, as well as mosaic loss, were associated with increased risks of bladder cancer. Of interest, physical activity (PA) significantly modified the associations of autosomal mCAs and mosaic loss (Pinteraction = 0.038 and 0.012, respectively) with bladder cancer. The increased risks of bladder cancer were only observed with mCAs and mosaic loss among participants with a lower level of PA (HR [95% CI]: 5.11 [2.36, 11.09] and 16.30 [6.06, 43.81]), but not among participants with a higher level of PA. Our findings suggest that peripheral leukocyte autosomal mCAs may represent a novel risk factor for bladder cancer, and PA may serve as a potential intervention target for mCAs carriers.

DNA Methylation Age Mediates Effect of Metabolic Profile on Cardiovascular and General Aging.

BACKGROUND: Alterations in lipid metabolism and DNA methylation are 2 hallmarks of aging. Connecting metabolomic, epigenomic, and aging outcomes help unravel the complex mechanisms underlying aging. We aimed to assess whether DNA methylation clocks mediate the association of circulating metabolites with incident atherosclerotic cardiovascular disease (ASCVD) and frailty. METHODS: The China Kadoorie Biobank is a prospective cohort study with a baseline survey from 2004 to 2008 and a follow-up period until December 31, 2018. We used the Infinium Methylation EPIC BeadChip to measure the methylation levels of 988 participants' baseline blood leukocyte DNA. Metabolite profiles, including lipoprotein particles, lipid constituents, and various circulating metabolites, were measured using quantitative nuclear magnetic resonance. The pace of DNA methylation age acceleration (AA) was calculated using 5 widely used epigenetic clocks (the first generation: Horvath, Hannum, and Li; the second generation: Grim and Pheno). Incident ASCVD was ascertained through linkage with local death and disease registries and national health insurance databases, supplemented by active follow-up. The frailty index was constructed using medical conditions, symptoms, signs, and physical measurements collected at baseline. RESULTS: A total of 508 incident cases of ASCVD were documented during a median follow-up of 9.5 years. The first generation of epigenetic clocks was associated with the risk of ASCVD (P<0.05). For each SD increment in LiAA, HorvathAA, and HannumAA, the corresponding hazard ratios for ASCVD risk were 1.16 (1.05-1.28), 1.10 (1.00-1.22), and 1.17 (1.04-1.31), respectively. Only LiAA mediated the association of various metabolites (lipids, fatty acids, histidine, and inflammatory biomarkers) with ASCVD, with the mediating proportion reaching up to 15% for the diameter of low-density lipoprotein (P=1.2×10-2). Regarding general aging, a 1-SD increase in GrimAA was associated with an average increase of 0.10 in the frailty index (P=2.0×10-3), and a 33% and 63% increased risk of prefrailty and frailty at baseline (P=1.5×10-2 and 5.8×10-2), respectively; this association was not observed with other clocks. GrimAA mediated the effect of various lipids, fatty acids, glucose, lactate, and inflammatory biomarkers on the frailty index, with the mediating proportion reaching up to 22% for triglycerides in very small-sized very low-density lipoprotein (P=6.0×10-3). CONCLUSIONS: These findings suggest that epigenomic mechanisms may play a role in the associations between circulating metabolites and the aging process. Different mechanisms underlie the first and second generations of DNA methylation age in cardiovascular and general aging.

Phenotypic age mediates effects of Life's Essential 8 on reduced mortality risk in US adults.

Objective: This study aimed to find out whether phenotypic age could mediate the protective effects of a healthy lifestyle on mortality. Methods: We included adult participants with available data for individual phenotypic age (PhenoAge) and Life's Essential 8 (LE8) scores from the National Health and Nutrition Examination Survey 2005-2010 (three cycles) and linked mortality records until 31 December 2019. Adjusted hazard ratios (HR) were estimated to evaluate the associations of PhenoAge and LE8 scores with all-cause and cardiovascular mortality risk. Mediation analyses were performed to estimate the proportional contribution of PhenoAge to the effect of LE8 on mortality risks. Results: A 1-year increment in PhenoAge was associated with a higher risk of all-cause (HR = 1.04 [95% confidence interval, 1.04-1.05]) and cardiovascular (HR = 1.04 [95% confidence interval, 1.04-1.05]) mortality, independent of chronological age, demographic characteristics, and disease history. High level of LE8 (score: 80-100) was associated with a 3.30-year younger PhenoAge. PhenoAge was estimated to mediate 36 and 22% of the effect of LE8 on all-cause and cardiovascular mortality, respectively (all P < 0.001). As for single-metric scores of LE8, PhenoAge mediated 30%, 11%, 9%, and 7% of the effects of the healthy diet, smoking status, blood pressure, and physical activity on all-cause mortality risk, respectively (all P < 0.05). Conclusion: Adherence to LE8 recommendations slows phenotypic aging. PhenoAge could mediate the effect of LE8 on mortality risk.

The Role of Active and Passive Smoking in Chronic Obstructive Pulmonary Disease and Systemic Inflammation: A 12-year Prospective Study in China.

BACKGROUND: There is no consensus on the cause and effect of systemic chronic inflammation (SCI) regarding chronic obstructive pulmonary disease (COPD). The impact of second-hand smoke (SHS) on COPD has reached inconsistent conclusions. METHODS: The China Kadoorie Biobank cohort was followed up from the 2004-08 baseline survey to 31 December 2018. Among the selected 445,523 participants in the final analysis, Cox and linear regressions were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of tobacco exposure with COPD risk and baseline levels of log-transformed inflammatory factors [ßs (95% CIs)], respectively. RESULTS: Participants were followed up for a median of 12.1 years and 11,825 incident COPD events were documented. Ever-smokers were associated with a higher risk of COPD than non-smokers with non-weekly SHS exposure. A younger age to start smoking, a greater amount of daily tobacco consumption, and deeper inhalation were associated with increased risk of COPD and correlated with elevated levels of plasma high-sensitivity C-reactive protein (hs-CRP, all Ptrend < 0.001) even two years before COPD onset. Among former smokers, COPD risk declined with longer smoking cessation (Ptrend < 0.001) and those quitting smoking for over ten years presented no difference in COPD risk and hs-CRP level from non-smokers [HR (95% CI) = 1.05 (0.89, 1.25), ß (95% CI) = 0.17 (- 0.09, 0.43)]. Among non-smokers, weekly SHS exposure was associated with a slightly higher COPD risk [HR (95% CI) = 1.06 (1.01, 1.12)]. CONCLUSIONS: Incremental exposure to tobacco smoke was related to elevated SCI level before COPD onset, then an increase in COPD susceptibility. Quitting smoking as early as possible is suggested as a practical approach to reducing COPD risk in smokers. Given the high prevalence of both COPD and SHS exposure, the risk associated with SHS exposure deserves attention.

The metabolic signature of blood lipids: a causal inference study using twins.

Dyslipidemia is one of the cardiometabolic risk factors that influences mortality globally. Unraveling the causality between blood lipids and metabolites and the complex networks connecting lipids, metabolites, and other cardiometabolic traits can help to more accurately reflect the body's metabolic disorders and even cardiometabolic diseases. We conducted targeted metabolomics of 248 metabolites in 437 twins from the Chinese National Twin Registry. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) analysis was used for causal inference between metabolites and lipid parameters. Bidirectional mediation analysis was performed to explore the linkages between blood lipids, metabolites, and other seven cardiometabolic traits. We identified 44, 1, and 31 metabolites associated with triglyceride (TG), total cholesterol (TC), and high-density lipoprotein-cholesterol (HDL-C), most of which were gut microbiota-derived metabolites. There were 9, 1, and 14 metabolites that showed novel associations with TG, TC, and HDL-C, respectively. ICE FALCON analysis found that TG and HDL-C may have a predicted causal effect on 23 and six metabolites, respectively, and one metabolite may have a predicted causal effect on TG. Mediation analysis discovered 14 linkages connecting blood lipids, metabolites, and other cardiometabolic traits. Our study highlights the significance of gut microbiota-derived metabolites in lipid metabolism. Most of the identified cross-sectional associations may be due to the lipids having a predicted causal effect on metabolites, but not vice versa, nor are they due to family confounding. These findings shed new light on lipid metabolism and personalized management of cardiometabolic diseases.

Prevalence and Incidence of Hepatitis E Infection in China.

BACKGROUND AND AIMS: China is an endemic area for hepatitis E virus (HEV) infection. Estimating the prevalence and incidence of HEV infection in China plays a pivotal role in informing public health policies to prevent and control hepatitis E. This study aimed to investigate the prevalence of anti-HEV IgG and incidence of HEV seroconversion in China. METHODS: This study was based on the Meinian health check-up database in China. Participants who underwent testing for anti-HEV IgG at check-up centers in 24 provinces between 2017 and 2022 were included. In the cross-sectional analyses, overall prevalence and stratified prevalence in subpopulations with various characteristics were estimated and standardized according to the 2020 census of the Chinese population. In the longitudinal analyses, the occurrence of anti-HEV IgG positivity during the follow-up was defined as an incident HEV seroconversion. Overall and stratified incidence rates were estimated and expressed as per 100 person-years. Poisson regression was used to explore risk factors associated with HEV seroconversion. RESULTS: A total of 85,238 and 11,154 participants were included in the cross-sectional and longitudinal analyses, respectively. The prevalence of anti-HEV IgG in the general population was 18.02%. During a median follow-up of 1.2 years, the incidence rate of HEV seroconversion was 1.79 per 100 person-years. Age ≥60 years, low socioeconomic status, living in coastal areas, living in areas with high drainage density, and living in areas with high anti-HEV IgG prevalence were independent risk factors for HEV seroconversion. CONCLUSIONS: Our findings would help inform policymaking for hepatitis E prevention and control in China as well as in other endemic regions of the world.

Methods and participant characteristics in the Cancer Risk in Vegetarians Consortium: a cross-sectional analysis across 11 prospective studies.

BACKGROUND: The associations of vegetarian diets with risks for site-specific cancers have not been estimated reliably due to the low number of vegetarians in previous studies. Therefore, the Cancer Risk in Vegetarians Consortium was established. The aim is to describe and compare the baseline characteristics between non-vegetarian and vegetarian diet groups and between the collaborating studies. METHODS: We harmonised individual-level data from 11 prospective cohort studies from Western Europe, North America, South Asia and East Asia. Comparisons of food intakes, sociodemographic and lifestyle factors were made between diet groups and between cohorts using descriptive statistics. RESULTS: 2.3 million participants were included; 66% women and 34% men, with mean ages at recruitment of 57 (SD: 7.8) and 57 (8.6) years, respectively. There were 2.1 million meat eaters, 60,903 poultry eaters, 44,780 pescatarians, 81,165 vegetarians, and 14,167 vegans. Food intake differences between the diet groups varied across the cohorts; for example, fruit and vegetable intakes were generally higher in vegetarians than in meat eaters in all the cohorts except in China. BMI was generally lower in vegetarians, particularly vegans, except for the cohorts in India and China. In general, but with some exceptions, vegetarians were also more likely to be highly educated and physically active and less likely to smoke. In the available resurveys, stability of diet groups was high in all the cohorts except in China. CONCLUSIONS: Food intakes and lifestyle factors of both non-vegetarians and vegetarians varied markedly across the individual cohorts, which may be due to differences in both culture and socioeconomic status, as well as differences in questionnaire design. Therefore, care is needed in the interpretation of the impacts of vegetarian diets on cancer risk.

Role of lifestyle factors on the development and long-term prognosis of pneumonia and cardiovascular disease in the Chinese population.

BACKGROUND: Whether adherence to a healthy lifestyle is associated with a lower risk of developing pneumonia and a better long-term prognosis remains unclear. This study aimed to investigate associations of individual and combined lifestyle factors (LFs) with the incidence risk and long-term prognosis of pneumonia hospitalization. METHODS: Using data from the China Kadoorie Biobank study, we used the multistate models to investigate the role of five high-risk LFs, including smoking, excessive alcohol drinking, unhealthy dietary habits, physical inactivity, and unhealthy body shape, alone or in combination in the transitions from a generally healthy state at baseline to pneumonia hospitalization or cardiovascular disease (CVD, regarded as a reference outcome), and subsequently to mortality. RESULTS: Most of the five high-risk LFs were associated with increased risks of transitions from baseline to pneumonia and from pneumonia to death, but with different risk estimates. The greater the number of high-risk LFs, the higher the risk of developing pneumonia and long-term mortality risk after pneumonia, with the strength of associations comparable to that of LFs and CVD. Compared to participants with 0-1 high-risk LF, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for transitions from baseline to pneumonia and from pneumonia to death in those with five high-risk LFs were 1.43 (1.28-1.60) and 1.98 (1.61-2.42), respectively. Correspondingly, the respective HRs (95% CIs) for transitions from baseline to CVD and from CVD to death were 2.00 (1.89-2.11) and 1.44 (1.30-1.59), respectively. The risk estimates changed slightly when further adjusting for the presence of major chronic diseases. CONCLUSION: In this Chinese population, unhealthy LFs were associated with an increased incidence and long-term mortality risk of pneumonia.

Genome-wide DNA methylation profiling in blood reveals epigenetic signature of incident acute coronary syndrome.

DNA methylation (DNAm) has been implicated in acute coronary syndrome (ACS), but the causality remains unclear in cross-sectional studies. Here, we conduct a prospective epigenome-wide association study of incident ACS in two Chinese cohorts (discovery: 751 nested case-control pairs; replication: 476 nested case-control pairs). We identified and validated 26 differentially methylated positions (DMPs, false discovery rate [FDR] <0.05), including three mapped to known cardiovascular disease genes (PRKCZ, PRDM16, EHBP1L1) and four with causal evidence from Mendelian randomization (PRKCZ, TRIM27, EMC2, EHBP1L1). Two hypomethylated DMPs were negatively correlated with the expression in blood of their mapped genes (PIGG and EHBP1L1), which were further found to overexpress in leukocytes and/or atheroma plaques. Finally, our DMPs could substantially improve the prediction of ACS over traditional risk factors and polygenic scores. These findings demonstrate the importance of DNAm in the pathogenesis of ACS and highlight DNAm as potential predictive biomarkers and treatment targets.

Isotemporal Substitution Effects of Daily Time Use on Cardiorespiratory Fitness of Children in the OptiChild Study: A Mediation Analysis with Diet Quality.

(1) Background: Although daily time-use is associated with diet quality and cardiorespiratory fitness (CRF) in children, their interdependence remains unexplored. This study first examined the associations between reallocating daily movement time and diet quality and CRF, and second the mediating role of diet quality in the relationship between daily time-use and CRF. (2) Methods: This study included 1131 Chinese children (aged 8 to 10 years; median [interquartile range]: 8.5 [8.3, 8.8]) at baseline (September 2022) and 1268 children at the 9-month follow-up (June 2023) from the OptiChild study. Daily durations of moderate-to-vigorous physical activity (MVPA), sleep, and sedentary behavior (e.g., screen time) were self-reported or proxy-reported by parents. Diet quality was assessed via the Diet Quality Questionnaire (DQQ), which uses a 24 h dietary recall and is categorized according to the Global Dietary Recommendations (GDR) score and Food Group Diversity Score (FGDS). The CRF was measured using VO2max after the 20 m shuttle run test. Longitudinal associations between daily time-use, diet quality, and CRF were calculated using isotemporal substitution models. Mediation analyses were used to determine whether diet quality mediated the associations between daily time-use and CRF. (3) Results: Reallocation of 30 min from screen time to MVPA resulted in significant improvements in the GDR score (ß baseline = 0.11, p = 0.024; ß follow-up = 0.26, p < 0.001), FGDS (ß baseline = 0.11, p = 0.006; ß follow-up = 0.19, p < 0.001), and CRF (ß baseline = 0.40, p < 0.001; ß follow-up = 0.26, p = 0.001). Diet quality partially mediated the associations between MVPA, screen time, and CRF. Substituting 30 min of screen time for MVPA led to diet quality mediating a proportion of the association with CRF (GDR score: 11.4%, FGDS: 6.6%). (4) Conclusions: These findings underscore the importance of optimizing daily time-use of MVPA and screen time and improving diet quality to promote physical fitness in school-aged children.

Associations between circulating proteins and cardiometabolic diseases: a systematic review and meta-analysis of observational and Mendelian randomisation studies.

BACKGROUND: Integration of large proteomics and genetic data in population-based studies can provide insights into discovery of novel biomarkers and potential therapeutic targets for cardiometabolic diseases (CMD). We aimed to synthesise existing evidence on the observational and genetic associations between circulating proteins and CMD. METHODS: PubMed, Embase and Web of Science were searched until July 2023 for potentially relevant prospective observational and Mendelian randomisation (MR) studies investigating associations between circulating proteins and CMD, including coronary heart disease, stroke, type 2 diabetes, heart failure, atrial fibrillation and atherosclerosis. Two investigators independently extracted study characteristics using a standard form and pooled data using random effects models. RESULTS: 50 observational, 25 MR and 10 studies performing both analyses were included, involving 26 414 160 non-overlapping participants. Meta-analysis of observational studies revealed 560 proteins associated with CMD, of which 133 proteins were associated with ≥2 CMDs (ie, pleiotropic). There were 245 potentially causal protein biomarkers identified in MR pooled results, involving 23 pleiotropic proteins. IL6RA and MMP12 were each causally associated with seven diseases. 22 protein-disease pairs showed directionally concordant associations in observational and MR pooled estimates. Addition of protein biomarkers to traditional clinical models modestly improved the accuracy of predicting incident CMD, with the highest improvement for heart failure (ΔC-index ~0.2). Of the 245 potentially causal proteins (291 protein-disease pairs), 3 pairs were validated by evidence of drug development from existing drug databases, 288 pairs lacked evidence of drug development and 66 proteins were drug targets approved for other indications. CONCLUSIONS: Combined analyses of observational and genetic studies revealed the potential causal role of several proteins in the aetiology of CMD. Novel protein biomarkers are promising targets for drug development and risk stratification. PROSPERO REGISTRATION NUMBER: CRD42022350327.