SGLT2 inhibition, acylcarnitines and heart failure: a Mendelian randomization study.

Objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are guideline-recommended agents for treating heart failure (HF), but the role of metabolomic biomarkers in underlying mechanisms, particularly acylcarnitines, remains unclear. This study examined the associations of acylcarnitines with SGLT2 inhibition and incident HF.

Methods: This subcohort study included 2178 participants from the prospective China Kadoorie Biobank without cardiovascular disease, diabetes or cancer at baseline.

Associations of Stressful Life Events With Diabetes Incidence in China: Insights From the China Kadoorie Biobank.

Background: Limited empirical evidence exists on the link between exposure to various stressful life events (SLEs) and the heightened risk of Diabetes Mellitus (DM) within the mainland Chinese population.

Methods: We conducted this prospective cohort study with 455,464 participants from the China Kadoorie Biobank (CKB); we examined associations between SLEs exposures and DM outcomes. We employed multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for potential confounders.

The mediating effect of blood pressure between healthy lifestyles and stroke: Results from the China Kadoorie Biobank study.

While a healthy lifestyle is known to reduce stroke risk, the extent to which blood pressure (BP) mediates this association remains unclear. The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence. Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline, we employed structural equation modeling to assess the mediating effects of systolic (SBP) and diastolic (DBP) blood pressure.

Patterns and correlates of visual impairment and ocular hypertension among older adults in the general Chinese population: results from the CKB Biobank.

Background: While numerous ophthalmology-specific cohort studies have been conducted in China, there is a significant lack of comprehensive, population-based study on the potential determinants of visual impairment and ocular hypertension (OHT) in the general Chinese population.

Methods: In the 2020-2021 resurvey of the China Kadoorie Biobank study, ~25 000 randomly selected participants from 10 diverse localities (5 urban and 5 rural) were surveyed. Presenting visual acuity (PVA) was measured using the Random E eye chart and intraocular pressure (IOP) was measured using a handheld Icare (ic100) tonometer.

Effect of Bariatric Surgery on Non-alcoholic Fatty Liver Disease: An Exploratory Metabolomics and Validation Study.

Background: Bariatric surgery presents a significant alleviation for non-alcoholic fatty liver disease (NAFLD), which relies in part on achieving substantial weight loss in post-surgical period. We aimed to understand the effect of bariatric surgery on NAFLD remission via metabolomics and to validate the results in a general population-based cohort.

Methods: In a pilot study, ten patients with NAFLD who underwent bariatric surgery were enrolled.

Genetic influences on the association between DNA methylation and obesity measures: insights from a twin study design.

Background: Both obesity and DNA methylation (DNAm) are influenced by genetic factors. Despite more than a thousand of obesity-related DNAm sites (CpGs) being identified, studies that account for genetic influences in these associations are limited.

Results: Using data from 1,074 twins in the Chinese National Twin Registry and bivariate structural equation models (SEMs), we investigated the phenotypic (Rph), genetic (Ra), and environmental (Re) correlations between genome-wide DNAm and three obesity indices: BMI, waist circumference (WC), and waist-to-hip ratio (WHR).

Phenome-wide association of physical activity with morbidity and mortality risk in China: A prospective cohort study.

Research in high-income countries has established the health benefits of physical activity (PA), but evidence from low- and middle-income countries, including China, where PA patterns vary from those in high-income countries, remains limited. Moreover, previous research, mainly focused on specific diseases, failing to fully capture the health impacts of PA. We investigated the associations of PA with 425 distinct diseases and 53 causes of death using data from 511,088 participants aged 30-79 years in the China Kadoorie Biobank.

Impact of genetic risk and lifestyles on cardiovascular disease-free and total life expectancy: a cohort study.

Background: Understanding the role of genetic risk and lifestyles on life expectancy (LE) without cardiovascular disease (CVD) and total LE may help optimize healthy aging strategies after taking genetic background into account.

Methods: The China Kadoorie Biobank recruited participants from five urban and five rural areas across China during 2004-2008 and followed them up till December 31, 2018. A polygenic risk score (PRS) comprising 3.

Prospective associations of diabetes with 15 cancers in 2.2 million UK and Chinese adults.

Background: Diabetes has been associated with the risk of numerous cancers but the causal relevance of many of these associations remains unclear.

Methods: We investigated associations between diabetes and risks of 15 cancers using Cox-regression and individual-level data from 2.2 million adults (334,978 incident cancer cases) in three prospective cohorts, UK Biobank (UKB), Million Women Study (MWS), and China Kadoorie Biobank (CKB).

Risk thresholds for soft versus hard cardiovascular disease outcome models for initiating statin therapy among Chinese adults: a cost-utility analysis.

Background: Current guidelines for atherosclerotic cardiovascular disease (ASCVD) primary prevention mostly recommend risk scores that predict risk of non-fatal myocardial infarction, fatal ischemic heart disease (IHD), and fatal or non-fatal ischemic stroke (hard outcomes), ignoring the burden from other non-fatal IHD outcomes. We explored the optimal risk thresholds for statin initiation using non-laboratory-based soft and hard ASCVD outcome models and compared the cost-utility of such models in the Chinese population.

Methods: We constructed Markov cohort models to estimate the incidence of ASCVD events, costs, and quality-adjusted life years (QALYs) over a lifetime from a social perspective.

Genetic Risk and Prognosis of the First Incident Stroke Survivors: Findings from China Kadoorie Biobank and UK Biobank.

Background And Objectives: Stroke is known for its poor prognosis. Although genetic instruments have shown promise in stratifying first stroke risk in the general population, it is unknown whether they are associated with stroke prognosis. Our study aims to explore the role of genetic risk of stroke in the progression from stroke-free to first stroke and then to recurrent stroke, subsequent coronary heart disease (CHD), and death in China and the United Kingdom.

GDF15 and its receptors as pathways mediating smoking related weight change.

Background: Smokers have lower body weight than non-smokers, while smoking cessation results in weight gain. Understanding the mechanisms involved can help identify potential therapeutic targets to enhance smoking cessation.

Methods: We measured plasma levels of growth/differentiation factor 15 (GDF15), a stress-responsive protein, and its two receptors (proto-oncogene tyrosine-protein kinase receptor Ret [RET], GDNF family receptor alpha-like [GFRAL]) among 3936 Chinese adults (mean BMI 24.

Hyperuricemia, gout and the associated comorbidities in China: findings from a prospective study of 0.5 million adults.

Background: Despite the growing prevalence of hyperuricemia and gout, their epidemiology and associated comorbidity burden remains poorly studied in many populations, including China. We aimed to examine the patterns of plasma urate level, prevalence of hyperuricemia, and incidence of gout, and investigate the associations of gout with a range of comorbidities and all-cause mortality in Chinese adults.

Methods: The prospective China Kadoorie Biobank recruited 512,724 adults aged 30-79 years from ten diverse areas in 2004-2008 and measured plasma urate level among 16,817 participants.

Association of greenness with incidence of cardiovascular disease in China: Evidence from the China Kadoorie Biobank prospective cohort study with 0.5 million adults.

Prospective evidence on the relationship of greenness with cardiovascular disease (CVD) incidence is limited in low- and middle-income countries. In 512,691 participants of the China Kadoorie Biobank cohort across 10 regions in China, we calculated the levels of greenness exposure based on satellite-retrieved Normalized Difference Vegetation Index (NDVI) data. Annual maximum NDVI (NDVI) values were estimated within 500 ​m and 1000 ​m buffers around the locations for the participants during the follow-up periods.

All-cause and cause-specific mortality in individuals with COPD in China: a 16-year follow-up cohort study.

The prevalence of chronic obstructive pulmonary disease (COPD) is rising in China, yet population-based evidence on COPD-related mortality risk remains limited. This study examined the association between prevalent COPD and all-cause and cause-specific mortality in a large Chinese cohort. 484,301 adults aged 30 to 79 years who received spirometry at the baseline of the China Kadoorie Biobank Study (2004-2008) were included.

Associations of Alcohol Consumption and Genetic Predisposition to Hepatic Steatosis With Liver-Related Events: Results From Large Population-Based Cohort Studies.

Background & Aims: The new classification for steatotic liver disease identifies 3 phenotypes based on alcohol consumption. The aim of this study was to evaluate the associations between alcohol intake and liver-related events (LREs) across different drinking categories and whether genetic predisposition influences these associations.

Methods: Data from 301,673 UK Biobank participants were analyzed.

Association of short-term air pollution with risk of major adverse cardiovascular event mortality and modification effects of lifestyle in Chinese adults.

Background: Previous evidence showed that ambient air pollution and cardiovascular mortality are related. However, there is a lack of evidence towards the modification effect of long-term lifestyle on the association between short-term ambient air pollution and death from cardiovascular events.

Method: A total of 14,609 death from major adverse cardiovascular events (MACE) were identified among the China Kadoorie Biobank participants from 2013 to 2018.

Systematic evaluation of patient-reported outcomes in clinical trials of digital health in cardiovascular diseases.

The integration of patient-reported outcomes (PROs) in digital health (DH) trials for cardiovascular diseases (CVDs) remains unknown. We searched ClinicalTrials.gov for randomized trials that tested DH interventions in CVDs from 2004 to 2024.

Proteome-Wide Genetic Study in East Asians and Europeans Identified Multiple Therapeutic Targets for Ischemic Stroke.

Background: Analyses of genomic and proteomics data in prospective biobank studies in diverse populations may discover novel or repurposing drug targets for stroke.

Methods: We extracted individual -protein quantitative trait locus for 2923 proteins measured using Olink Explore panel from a genome-wide association study in prospective China Kadoorie Biobank and UK Biobank, both established ≈20 years ago. These -protein quantitative trait loci were used in ancestry-specific 2-sample Mendelian randomization analyses of ischemic stroke (IS) in East Asians (n=22 664 cases) and Europeans (n=62 100 cases).

Causal Relevance of Lp(a) for Coronary Heart Disease and Stroke Types in East Asian and European Ancestry Populations: A Mendelian Randomization Study.

Background: Elevated plasma levels of Lp(a) [lipoprotein(a)] are a causal risk factor for coronary heart disease and stroke in European individuals, but the causal relevance of Lp(a) for different stroke types and in East Asian individuals with different Lp(a) genetic architecture is uncertain.

Methods: We measured plasma levels of Lp(a) in a nested case-control study of 18 174 adults (mean [SD] age, 57 [10] years; 49% female) in the China Kadoorie Biobank (CKB) and performed a genome-wide association analysis to identify genetic variants affecting Lp(a) levels, with replication in ancestry-specific subsets in UK Biobank. We further performed 2-sample Mendelian randomization analyses, associating ancestry-specific Lp(a)-associated instrumental variants derived from CKB or from published data in European individuals with risk of myocardial infarction (n=17 091), ischemic stroke (IS [n=29 233]) and its subtypes, or intracerebral hemorrhage (n=5845) in East Asian and European individuals using available data from CKB and genome-wide association analysis consortia.

Patterns and Correlates of Bone Mineral Density Parameters Measured Using Calcaneus Quantitative Ultrasound in Chinese Adults.

Monitoring bone mineral density (BMD) in adults is critical for early detection of osteoporosis and prevention of fracture, for which quantitative ultrasound (QUS) is a good non-invasive tool. We examined the associations of QUS measures, including stiffness index (SI) and T-score, with socio-demographic, lifestyle, and anthropometric correlates and risk of subsequent fracture. : Calcaneal QUS was performed using GE's Lunar Achilles EXPII among 24,651 adults (mean age 59.

Acute Impact of Nonoptimal Ambient Temperatures on Plasma Levels of 3000 Proteins in Chinese Adults.

Nonoptimal ambient temperatures (i.e., cold and heat) are leading environmental determinants of major diseases worldwide, but the underlying pathological mechanisms are still poorly understood.

Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank.

Background: Polygenic risk scores (PRSs) have been extensively developed for cancer risk prediction in European populations, but their effectiveness in the Chinese population remains uncertain.

Methods And Findings: We constructed 80 PRSs for the 13 most common cancers using seven schemes and evaluated these PRSs in 100,219 participants from the China Kadoorie Biobank (CKB). The optimal PRSs with the highest discriminatory ability were used to define genetic risk, and their site-specific and cross-cancer associations were assessed.

Comparative studies of 2168 plasma proteins measured by two affinity-based platforms in 4000 Chinese adults.

Proteomics offers unique insights into human biology and drug development, but few studies have directly compared the utility of different proteomics platforms. We measured plasma levels of 2168 proteins in 3976 Chinese adults using both Olink Explore and SomaScan platforms. The correlation of protein levels between platforms was modest (median rho = 0.