The active cohort: a population-based smartphone intervention for health outcomes.

Background: The Clalit Active Cohort Study (CACS) assess the impact of lifestyle factors, particularly physical activity, on short- and long-term health outcomes using real-world data. Launched in January 2021, CACS focuses on Clalit Health Services members with supplemental health insurance who use the Clalit Active smartphone app.

Methods: The study integrates data from the Clalit Active app with electronic health records from CHS, covering primary and secondary care, hospitalizations, medications, laboratory results, and imaging.

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.

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).

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.

Corrigendum to Associations of reallocating sedentary leisure-time to alternative discretionary movement behaviours with incident cardiometabolic diseases in 0.5 million Chinese adults. The Lancet Regional Health-Western Pacific, Volume 57, 101524.

[This corrects the article DOI: 10.1016/j.lanwpc.

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.

Associations of reallocating sedentary leisure-time to alternative discretionary movement behaviours with incident cardiometabolic diseases in 0.5 million Chinese adults.

Background: In Chinese adults, there is a considerable burden of sedentary behaviour. This study aimed to estimate the implications of reallocating sedentary leisure-time to non-sedentary behaviours for incident cardiometabolic diseases.

Methods: A prospective cohort study of 462,370 Chinese adults (mean age 51 years; 59% female) who were free from diabetes and cardiovascular diseases at baseline.

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.

Associations of total, domain-specific, and intensity-specific physical activity with all-cause and cause-specific mortality in China: A population-based cohort study.

Background: Evidence of an association between physical activity (PA) and mortality has mainly focused on leisure-time physical activity (LTPA) and moderate-to-vigorous-intensity physical activity (MVPA). We aimed to assess the associations of total, domain-specific, and intensity-specific PA with all-cause and cause-specific mortality.

Methods: We used baseline PA data from the China Kadoorie Biobank, including 482,067 participants aged 30-79 years from 10 areas in China.

Normal-weight obesity subtypes and 10-year risks of major vascular diseases in 0.3 million adults.

Background & Aims: Obesity directly contributes to the progression of cardiovascular disease, but little is known about the association and risk attribution of normal-weight obesity subtypes with the incidence of major vascular events (MVEs) and their subtypes.

Methods: This is a prospective cohort study based on the China Kadoorie Biobank (CKB). A total of 308,071 individuals with no prior vascular diseases or cancer were included at baseline.

Risk prediction of ischemic heart disease using plasma proteomics, conventional risk factors and polygenic scores in Chinese and European adults.

Plasma proteomics could enhance risk prediction for multiple diseases beyond conventional risk factors or polygenic scores (PS). To assess utility of proteomics for risk prediction of ischemic heart disease (IHD) compared with conventional risk factors and PS in Chinese and European populations. A nested case-cohort study measured plasma levels of 2923 proteins using Olink Explore panel in ~ 4000 Chinese adults (1976 incident IHD cases and 2001 sub-cohort controls).

Measured and genetically predicted protein levels and cardiovascular diseases in UK Biobank and China Kadoorie Biobank.

Several large-scale studies have measured plasma levels of the proteome in individuals with cardiovascular diseases (CVDs). However, since the majority of such proteins are interrelated, it is difficult for observational studies to distinguish which proteins are likely to be of etiological relevance. Here we evaluate whether plasma levels of 2,919 proteins measured in 52,164 UK Biobank participants are associated with incident myocardial infarction, ischemic stroke or heart failure.

Iron Status and Risk of Heart Disease, Stroke, and Diabetes: A Mendelian Randomization Study in European Adults.

Background: The relevance of iron status biomarkers for coronary artery disease (CAD), heart failure (HF), ischemic stroke (IS), and type 2 diabetes (T2D) is uncertain. We compared the observational and Mendelian randomization (MR) analyses of iron status biomarkers and hemoglobin with these diseases.

Methods And Results: Observational analyses of hemoglobin were compared with genetically predicted hemoglobin with cardiovascular diseases and diabetes in the UK Biobank.

Use of Artificial Intelligence in Improving Outcomes in Heart Disease: A Scientific Statement From the American Heart Association.

A major focus of academia, industry, and global governmental agencies is to develop and apply artificial intelligence and other advanced analytical tools to transform health care delivery. The American Heart Association supports the creation of tools and services that would further the science and practice of precision medicine by enabling more precise approaches to cardiovascular and stroke research, prevention, and care of individuals and populations. Nevertheless, several challenges exist, and few artificial intelligence tools have been shown to improve cardiovascular and stroke care sufficiently to be widely adopted.

PCSK9 genetic variants and risk of vascular and non-vascular diseases in Chinese and UK populations.

Aims: Lowering low-density lipoprotein cholesterol (LDL-C) through PCSK9 inhibition represents a new therapeutic approach to preventing and treating cardiovascular disease (CVD). Phenome-wide analyses of PCSK9 genetic variants in large biobanks can help to identify unexpected effects of PCSK9 inhibition.

Methods And Results: In the prospective China Kadoorie Biobank, we constructed a genetic score using three variants at the PCSK9 locus associated with directly measured LDL-C [PCSK9 genetic score (PCSK9-GS)].

Global heterogeneity in folic acid fortification policies and implications for prevention of neural tube defects and stroke: a systematic review.

Background: Folic acid (pteroylmonoglutamic acid) supplements are highly effective for prevention of neural tube defects (NTD) prompting implementation of mandatory or voluntary folic acid fortification for prevention of NTDs. We used plasma folate levels in population studies by country and year to compare effects of folic acid fortification types (mandatory or voluntary folic acid fortification policies) on plasma folate levels, NTD prevalence and stroke mortality rates.

Methods: We conducted systematic reviews of (i) implementation of folic acid fortification in 193 countries that were member states of the World Health Organization by country and year, and (ii) estimated population mean plasma folate levels by year and type of folic acid fortification.

Plasma Proteomics to Identify Drug Targets for Ischemic Heart Disease.

Background: Integrated analyses of plasma proteomic and genetic markers in prospective studies can clarify the causal relevance of proteins and discover novel targets for ischemic heart disease (IHD) and other diseases.

Objectives: The purpose of this study was to examine associations of proteomics and genetics data with IHD in population studies to discover novel preventive treatments.

Methods: We conducted a nested case-cohort study in the China Kadoorie Biobank (CKB) involving 1,971 incident IHD cases and 2,001 subcohort participants who were genotyped and free of prior cardiovascular disease.

MTHFR and risk of stroke and heart disease in a low-folate population: a prospective study of 156 000 Chinese adults.

Background: The relevance of folic acid for stroke prevention in low-folate populations such as in China is uncertain. Genetic studies of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, which increases plasma homocysteine (tHcy) levels, could clarify the causal relevance of elevated tHcy levels for stroke, ischaemic heart disease (IHD) and other diseases in populations without folic acid fortification.

Methods: In the prospective China Kadoorie Biobank, 156 253 participants were genotyped for MTHFR and 12 240 developed a stroke during the 12-year follow-up.

An Overview of Methods and Exemplars of the Use of Mendelian Randomisation in Nutritional Research.

It is crucial to elucidate the causal relevance of nutritional exposures (such as dietary patterns, food intake, macronutrients intake, circulating micronutrients), or biomarkers in non-communicable diseases (NCDs) in order to find effective strategies for NCD prevention. Classical observational studies have found evidence of associations between nutritional exposures and NCD development, but such studies are prone to confounding and other biases. This has direct relevance for translation research, as using unreliable evidence can lead to the failure of trials of nutritional interventions.