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1.
Int J Epidemiol ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33826715

RESUMO

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.

2.
Nutrients ; 13(4)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805392

RESUMO

A few prospective studies have suggested that tea, alcohol, and fruit consumption may reduce the risk of kidney stones. However, little is known whether such associations and their combined effect persist in Chinese adults, for whom the popular tea and alcohol drinks are different from those investigated in the aforementioned studies. The present study included 502,621 participants from the China Kadoorie Biobank (CKB). Information about tea, alcohol, and fruit consumption was self-reported at baseline. The first documented cases of kidney stones during follow-up were collected through linkage with the national health insurance system. Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). During a median of 11.1 years of follow-up, we collected 12,407 cases of kidney stones. After multivariable adjustment, tea, alcohol, and fruit consumption were found to be negatively associated with kidney stone risk, but the linear trend was only found in tea and fruit consumption. Compared with non-tea consumers, the HR (95% CI) for participants who drank ≥7 cups of tea per day was 0.73 (0.65-0.83). Compared with non-alcohol consumers, the HR (95% CI) was 0.79 (0.72-0.87) for participants who drank pure alcohol of 30.0-59.9 g per day but had no further decrease with a higher intake of alcohol. Compared with less-than-weekly consumers, the HR (95% CI) for daily fruit consumers was 0.81 (0.75-0.87). Even for those who did not drink alcohol excessively, increasing tea and fruit consumption could also independently reduce the stone risk. Among Chinese adults, tea, alcohol, and fruit consumption was associated with a lower risk of kidney stones.

3.
Eur Respir J ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33766948

RESUMO

Lung function is a heritable complex phenotype with obesity being one of its important risk factors. However, the knowledge of their shared genetic basis is limited. Most genome-wide association studies (GWASs) for lung function have been based on European populations, limiting the generalisability across populations. Large-scale lung function GWAS in other populations are lacking.We included 100 285 subjects from China Kadoorie Biobank (CKB). To identify novel loci for lung function, single-trait GWAS were performed on FEV1, FVC, FEV1/FVC in CKB. We then performed genome-wide cross-trait analysis between the lung function and obesity traits (body mass index [BMI], BMI-adjusted waist-to-hip ratio, and BMI-adjusted waist circumference) to investigate the shared genetic effects in CKB. Finally, polygenic risk scores (PRSs) of lung function were developed in CKB and its interaction with BMI's association on lung function were examined. We also conducted cross-trait analysis in parallel with CKB using 457 756 subjects from UK Biobank (UKB) for replication and investigation of ancestry specific effect.We identified 9 genome-wide significant novel loci for FEV1, 6 for FVC and 3 for FEV1/FVC in CKB. FEV1 and FVC showed significant negative genetic correlation with obesity traits in both CKB and UKB. Genetic loci shared between lung function and obesity traits highlighted important pathways, including cell proliferation, embryo and tissue development. Mendelian randomisation analysis suggested significant negative causal effect of BMI on FEV1 and on FVC in both CKB and UKB. Lung function PRSs significantly modified the effect of change-in-BMI on change-in-lung function during an average follow-up of 8 years.This large-scale GWAS of lung function identified novel loci and shared genetic etiology between lung function and obesity. Change-in-BMI might affect change-in-lung function differently according to a subject's polygenic background. These findings may open new avenue for the development of molecular-targeted therapies for obesity and lung function improvement.

4.
Twin Res Hum Genet ; : 1-8, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33645497

RESUMO

The objective of this study was to analyze differences in birth weight and overweight/obesity in a Shanghai twin cohort. We also wanted to study their association and explore possible risk factors for the discordance of overweight/obesity within twins. This was an internal case-control study designed for twins. The 2012 Shanghai Twin Registration System baseline survey data of a total of 3417 twin pairs were statistically analyzed using SPSS22 software. Results show that the body mass index (BMI) of the Shanghai twin population increased with age. Twins with a high birth weight had a higher BMI and a higher rate of overweight and obesity; 0- to 6-year-old twins, male twins and dizygotic (DZ) twins had higher rates of overweight/obesity than other groups. The greater the discordant birth weight rate of twins, the more obvious the difference in BMI (p < .05). There was a significant difference in overweight/obesity between twins with a relative difference of birth weight ≥15% in DZ twins (p < .05). DZ twins, male twins and 0- to 6-year-old twins were more likely to be discordant in overweight/obese than others. The discordant birth weight within twins was not a risk factor for discordant overweight/obesity. However, attention should be paid to childhood obesity, and appropriate interventions should be made at the appropriate time. Genetics may play an important role in the occurrence and development of overweight/obesity. In conclusion, discordant growth and development in the uterus early in life may not lead to discordant weight development in the future.

5.
Br J Cancer ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33772150

RESUMO

BACKGROUND: Gallstone disease (GSD) is associated with a higher risk of gastrointestinal (GI) cancer. However, it is unclear whether the associations are causal. METHODS: The prospective China Kadoorie Biobank (CKB) recorded 17,598 cases of GI cancer among 510,137 participants without cancer at baseline during 10 years of follow-up. Cox regression was used to estimate hazard ratios (HRs) for specific cancer by GSD status and duration. Mendelian randomisation was conducted to assess the genetic associations of GSD with specific cancer. RESULTS: Overall 6% of participants had symptomatic GSD at baseline. Compared with those without GSD, individuals with symptomatic GSD had adjusted HRs of 1.13 (1.01-1.29) for colorectal, 2.01 (1.78-2.26) for liver, 3.70 (2.88-4.87) for gallbladder, 2.31 (1.78-3.07) for biliary tract, and 1.38 (1.18-1.74) for pancreatic cancer. Compared with participants without GSD, the risks of colorectal, liver, gallbladder, biliary tract, and pancreatic cancer were highest during 0 to <5 years following disease diagnosis. There was evidence of genetic associations of GSD with these cancers, with odds ratios per 1-SD genetic score of 1.08 (1.05-1.11) for colorectal, 1.22 (1.19-1.25) for liver, 1.56 (1.49-1.64) for gallbladder, 1.39 (1.31-1.46) for biliary tract, and 1.16 (1.10-1.22) for pancreatic cancer. When meta-analysing the genetic estimates in CKB and UK Biobank, there was evidence of causal associations of GSD with colon cancer, gallbladder and biliary tract cancer (GBTC), and total GI cancer (RR per 1-SD: 1.05 [0.99-1.11], 2.00 [1.91-2.09], and 1.09 [1.05-1.13]). CONCLUSIONS: GSD was associated with higher risks of several GI cancers, warranting future studies on the underlying mechanisms.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33782052

RESUMO

BACKGROUND: The relationship between educational attainment and ischaemic heart disease (IHD) is limited in evidence in middle-income countries like China. Exploring lifestyle-related mediators, which might be not universal between socioeconomic status and health outcomes in diverse regions, can contribute to interventions targeted at the Chinese to narrow the educational gap in IHD. METHODS: Based on the China Kadoorie Biobank of 489 594 participants aged 30-79 years who did not have heart disease or stroke at baseline, this study examined the association of educational attainment with IHD. Total IHD cases were further divided into acute myocardial infarction (AMI) cases and non-AMI cases. The Cox proportional hazard model was performed to estimate the HRs and 95% CIs for mortality and incidence of IHD. Logistic regression was used to estimate the ORs and 95% CIs for case fatality. RESULTS: During the median follow-up period of 11.1 years, this study documented 45 946 (6668) incident IHD (AMI) cases and 5948 (3689) deaths altogether. Lower educational attainment was associated with increased risk of incident AMI as well as death and fatality of total IHD including its subtypes (ptrend <0.001). Although the risk of incident non-AMI was greater for participants with higher levels of education in the whole population (ptrend <0.001), an inverse association of education with its incidence was found in participants from <50 years age group and rural areas. Smoking and dietary habits were the two most potent mediating factors in the associations of education with mortality and AMI incidence; whereas, physical activity was the major mediating factor for non-AMI incidence in the whole population. DISCUSSION: Interventions targeting unhealthy lifestyles are ideal ways to narrow the educational gap in IHD while solving 'upstream' causes of health behaviours might be the most fundamental ones.

7.
Am J Clin Nutr ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33709113

RESUMO

BACKGROUND: Evidence from epidemiological studies remains inconsistent or limited about the associations of tea consumption with incident diabetes and risk of diabetic complications and death among patients with diabetes. OBJECTIVES: We aimed to investigate the associations of tea consumption with long-term risk of developing type 2 diabetes (T2D) and risks of diabetic complications and death among patients with diabetes. METHODS: This study included 482,425 diabetes-free participants and 30,300 patients with diabetes aged 30-79 y at study enrollment from the China Kadoorie Biobank. Tea consumption information was collected at baseline by interviewer-administered questionnaires. Incidences of diabetes, diabetic complications, and death were identified by linkages to the National Health Insurance system, disease registries, and death registries. Cox proportional hazard regression models were used to estimate HRs and 95% CIs. RESULTS: The mean ± SD age of participants free of diabetes was 51.2 ± 10.5 y and 41% were male. The mean ± SD age of patients with diabetes was 58.2 ± 9.6 y and 39% were male. Of all daily tea consumers, 85.8% preferred green tea. In the diabetes-free population, 17,434 participants developed incident T2D during 11.1 y of follow-up. Compared with participants who never consumed tea in the past year, the HR (95% CI) of T2D for daily consumers was 0.92 (0.88, 0.97). In patients with diabetes, we identified 6572 deaths, 12,677 diabetic macrovascular cases, and 2441 diabetic microvascular cases during follow-up. Compared with patients who never consumed tea in the past year, the HRs (95% CIs) of all-cause mortality and risk of microvascular complications for daily consumers were 0.90 (0.83, 0.97) and 0.88 (0.78, 1.00), respectively. Tea consumption was not associated with risk of macrovascular complications among patients with diabetes. With regard to tea consumed, the inverse associations between daily tea consumption and risks of T2D and all-cause mortality in patients with diabetes were only observed among daily green tea drinkers. CONCLUSIONS: In Chinese adults, daily green tea consumption was associated with a lower risk of incident T2D and a lower risk of all-cause mortality in patients with diabetes, but the associations for other types of tea were less clear. In addition, daily tea consumption was associated with a lower risk of diabetic microvascular complications, but not macrovascular complications.

8.
PLoS Med ; 18(3): e1003545, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33705376

RESUMO

BACKGROUND: Suicide is a leading cause of death in China and accounts for about one-sixth of all suicides worldwide. The objective of this study was to examine the recent distribution of suicide and risk factors for death by suicide. Identifying underlying risk factors could benefit development of evidence-based prevention and intervention programs. METHODS AND FINDINGS: We conducted a prospective study, the China Kadoorie Biobank, of 512,715 individuals (41% men, mean age 52 years) from 10 (5 urban, 5 rural) areas which are diverse across China in geographic locations, social economic developmental stages, and prevalence of disease patterns. After the baseline measurements of risk factors during 2004 to 2008, participants were followed up for suicide outcomes including suicide and possible suicide deaths. Risk factors, such as sociodemographic factors and physical and mental health status, were assessed by semistructured interviews and self-report questionnaires. Suicide and possible suicide deaths were identified through linkage to the local death registries using ICD-10 codes. We conducted Cox regression to calculate hazard ratios (HRs) for suicide and for possible suicide in sensitivity analyses. During an average follow-up period of 9.9 years, 520 (101 per 100,000) people died from suicide (51.3% male), and 79.8% of them lived in rural areas. Sociodemographic factors associated with increased suicide risk were male gender (adjusted hazard ratios [aHR] = 1.6 [95% CI 1.4 to 2.0], p < 0.001), older age (1.3 [1.2 to 1.5] by each 10-yr increase, p < 0.001), rural residence (2.6 [2.1 to 3.3], p < 0.001), and single status (1.7 [1.4 to 2.2], p < 0.001). Increased hazards were found for family-related stressful life events (aHR = 1.8 [1.2 to 1.9], p < 0.001) and for major physical illnesses (1.5 [1.3 to 1.9], p < 0.001). There were strong associations of suicide with a history of lifetime mental disorders (aHR = 9.6 [5.9 to 15.6], p < 0.001) and lifetime schizophrenia-spectrum disorders (11.0 [7.1 to 17.0], p < 0.001). Links between suicide risk and depressive disorders (aHR = 2.6 [1.4 to 4.8], p = 0.002) and generalized anxiety disorders (2.6 [1.0 to 7.1], p = 0.056) in the last 12 months, and sleep disorders (1.4 [1.2 to 1.7], p < 0.001) in the past month were also found. All HRs were adjusted for sociodemographic factors including gender, age, residence, single status, education, and income. The associations with possible suicide deaths were mostly similar to those with suicide deaths, although there was no clear link between possible suicide deaths and psychiatric factors such as depression and generalized anxiety disorders. A limitation of the study is that there is likely underreporting of mental disorders due to the use of self-report information for some diagnostic categories. CONCLUSIONS: In this study, we observed that a range of sociodemographic, lifestyle, stressful life events, physical, and mental health factors were associated with suicide in China. High-risk groups identified were elderly men in rural settings and individuals with mental disorders. These findings could form the basis of targeted approaches to reduce suicide mortality in China.

9.
Int J Cancer ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33634874

RESUMO

Alcohol drinking is associated with increased risks of several site-specific cancers, but its role in many other cancers remains inconclusive. Evidence is more limited from China, where cancer rates, drinking patterns and alcohol tolerability differ importantly from Western populations. The prospective China Kadoorie Biobank recruited >512 000 adults aged 30 to 79 years from 10 diverse areas during 2004 to 2008, recording alcohol consumption patterns by a standardised questionnaire. Self-reported alcohol consumption was estimated as grams of pure alcohol per week based on beverage type, amount consumed per occasion and drinking frequency. After 10 years of follow-up, 26 961 individuals developed cancer. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) relating alcohol consumption to incidence of site-specific cancers. Overall, 33% (n = 69 734) of men drank alcohol regularly (ie, ≥weekly) at baseline. Among male current regular drinkers, alcohol intake showed positive dose-response associations with risks of cancers in the oesophagus (655 events; HR = 1.98 [95%CI 1.79-2.18], per 280 g/wk), mouth and throat (236; 1.74 [1.48-2.05]), liver (573; 1.52 [1.31-1.76]), colon-rectum (575; 1.19 [1.00-1.43]), gallbladder (107; 1.60 [1.16-2.22]) and lung (1017; 1.25 [1.10-1.42]), similarly among never- and ever-regular smokers. After adjustment for total alcohol intake, there were greater risks of oesophageal cancer in daily drinkers than nondaily drinkers and of liver cancer when drinking without meals. The risks of oesophageal cancer and lung cancer were greater in men reporting flushing after drinking than not. In this male population, alcohol drinking accounted for 7% of cancer cases. Among women, only 2% drank regularly, with no clear associations between alcohol consumption and cancer risk. Among Chinese men, alcohol drinking is associated with increased risks of cancer at multiple sites, with certain drinking patterns (eg, daily, drinking without meals) and low alcohol tolerance further exacerbating the risks.

10.
Elife ; 102021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33558007

RESUMO

Adherence to healthy lifestyles is associated with reduced risk of coronary heart disease (CHD), but uncertainty persists about the underlying lipid pathway. In a case-control study of 4681 participants nested in the prospective China Kadoorie Biobank, 61 lipidomic markers in baseline plasma were measured by targeted nuclear magnetic resonance spectroscopy. Baseline lifestyles included smoking, alcohol consumption, dietary habit, physical activity, and adiposity levels. Genetic instrument was used to mimic the lipid-lowering effect of statins. We found that 35 lipid metabolites showed statistically significant mediation effects in the pathway from healthy lifestyles to CHD reduction, including very low-density lipoprotein (VLDL) particles and their cholesterol, large-sized high-density lipoprotein (HDL) particle and its cholesterol, and triglyceride in almost all lipoprotein subfractions. The statins genetic score was associated with reduced intermediate- and low-density lipoprotein, but weak or no association with VLDL and HDL. Lifestyle interventions and statins may improve different components of the lipid profile.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33596318

RESUMO

BACKGROUND: Observational studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels were associated with favorable serum lipids and related metabolites. However, if such observations reflect causality remains unclear. OBJECTIVE: We aimed to investigate the causal effect of elevated 25(OH)D with the detailed systemic metabolite profile in Chinese adults. METHODS: A total of 225 lipid and other metabolites were quantified in 4,662 individuals in China Kadoorie Biobank. Instrumental variable analyses were performed to test the causal associations of plasma 25(OH)D with the lipids and metabolites. RESULTS: Higher plasma 25(OH)D was related to favorable lipid profiles in observational analyses. The genetic risk score was robustly correlated with observed 25(OH)D (beta[SE]= 3.54 [0.32]; P<1×10 -5, F-statistic =122.3) and explained 8.4% of the variation in 25(OH)D in the Chinese population. For all individual metabolites, the causal estimates were not significant for at the threshold P<5×10 -4 (multiple testing corrected). However, the MR estimate showed that per 1-SD increase in genetically determined 25(OH)D was suggestive associated with decreased levels of cholesterol, lipoprotein particle, phospholipids within very small very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) (P≤0.05, nominal significance). For amino acids, fatty acids, ketone bodies, glycoprotein acetyls, fatty acids and other traits, we did not observe any significant causal association. CONCLUSIONS: The MR analysis of metabolic data based a population-based cohort suggested a potential causal association of plasma 25(OH)D with cholesterol, lipoprotein particle, phospholipids concentrations and total lipids within very small VLDL and IDL. Our findings highlight long-term effect of 25(OH)D levels in maintaining healthy lipid metabolism.

12.
Int J Cancer ; 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33521941

RESUMO

China has made rapid progress in reducing the incidence of HBV infection in the past three decades, along with a rapidly changing lifestyle and aging population. We aimed to develop and validate an up-to-date liver cancer risk prediction model with routinely available predictors and evaluate its applicability for screening guidance. Using data from the China Kadoorie Biobank, we included 486 285 participants in this analysis. Fifteen risk factors were included in the model. Flexible parametric survival models were used to estimate the 10-year absolute risk of liver cancer. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. A total of 2706 participants occurred liver cancer over the 4 814 320 person-years of follow-up. Excellent discrimination of the model was observed in both development and validation datasets, with c-statistics (95% CI) of 0.80 (0.79-0.81) and 0.80 (0.78-0.82) respectively, as well as excellent calibration of observed and predicted risks. Decision curve analysis revealed that use of the model in selecting participants for screening improved benefit at a threshold of 2% 10-year risk, compared to current guideline of screening all HBsAg carriers. Our model was more sensitive than current guideline for cancer screening (28.17% vs 25.96%). We developed and validated a CKB-PLR (Prediction for Liver cancer Risk Based on the China Kadoorie Biobank Study) model to predict the absolute risk of liver cancer for both HBsAg seropositive and seronegative populations. Application of the model is beneficial for precisely identifying the high-risk groups among the general population.

13.
Ecotoxicol Environ Saf ; 209: 111826, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360592

RESUMO

BACKGROUND: Excessive fluoride exposure is related to adverse health outcomes, but whether dopamine (DA) relative genes are involved in the health effect of low-moderate fluoride exposure on children's intelligence remain unclear. OBJECTIVES: We conducted a cross-sectional study to explore the role of DA relative genes in the health effect of low-moderate fluoride exposure in drinking water. METHODS: We recruited 567 resident children, aged 6-11 years old, randomly from endemic and non-endemic fluorosis areas in Tianjin, China. Spot urine samples were tested for urinary fluoride concentration, combined Raven`s test was used for intelligence quotient test. Fasting venous blood were collected to analyze ANKK1 Taq1A (rs1800497), COMT Val158Met (rs4680), DAT1 40 bp VNTR and MAOA uVNTR. Multivariable linear regression models were used to assess associations between fluoride exposure and IQ scores. We applied multiplicative and additive models to appraise single gene-environment interaction. Generalized multifactor dimensionality reduction (GMDR) was used to evaluate high-dimensional interactions of gene-gene and gene-environment. RESULTS: In adjusted model, fluoride exposure was inversely associated with IQ scores (ß = -5.957, 95% CI: -9.712, -2.202). The mean IQ scores of children with high-activity MAOA genotype was significantly lower than IQ scores of those with low-activity (P = 0.006) or female heterozygote (P = 0.016) genotype. We detected effect modification by four DA relative genes (ANKK1, COMT, DAT1 and MAOA) on the association between UF and IQ scores. We also found a high-dimensional gene-environment interaction among UF, ANKK1, COMT and MAOA on the effect of IQ (testing balanced accuracy = 0.5302, CV consistency: 10/10, P = 0.0107). CONCLUSIONS: Our study suggests DA relative genes may modify the association between fluoride and intelligence, and a potential interaction among fluoride exposure and DA relative genes on IQ.


Assuntos
Dopamina/genética , Exposição Ambiental/estatística & dados numéricos , Fluoretos/toxicidade , Inteligência/efeitos dos fármacos , Criança , China/epidemiologia , Estudos Transversais , Água Potável , Feminino , Fluoretos/análise , Genótipo , Humanos , Testes de Inteligência , Masculino , Polimorfismo Genético
14.
JAMA Cardiol ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33263724

RESUMO

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.

15.
Lancet Public Health ; 5(12): e650-e660, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33271078

RESUMO

BACKGROUND: The fraily index is a useful proxy measure of accelerated biological ageing and in estimating all-cause and cause-specific mortality in older individuals in European and US populations. However, the predictive value of the frailty index in other populations outside of Europe and the USA and in adults younger than 50 years is unknown. We aimed to examine the association between the frailty index and mortality in a population of Chinese adults. METHODS: In this prospective cohort study, we used data from the China Kadoorie Biobank. We included adults aged 30-79 years from ten areas (five urban areas and five rural areas) of China who had no missing values for the items that made up the frailty index. We did not exclude participants on the basis of baseline morbidity status. We calculated the follow-up person-years from the baseline date to either the date of death, loss to follow-up, or Dec 31, 2017, whichever came first, through linkage with the registries of China's Disease Surveillance Points system and local residential records. Active follow-up visits to local communities were done annually for participants who were not linked to any established registries. Causes of death from official death certificates were supplemented, if necessary, by reviewing medical records or doing standard verbal autopsy procedures. The frailty index was calculated using 28 baseline variables, all of which were health status deficits measured by use of questionnaires and physical examination. We defined three categories of frailty status: robust (frailty index ≤0·10), prefrail (frailty index >0·10 to <0·25), and frail (frailty index ≥0·25). The primary outcomes were all-cause mortality and cause-specific mortality in Chinese adults aged 30-79 years. We used a Cox proportional hazards model to estimate the associations between the frailty index and all-cause and cause-specific mortality, adjusting for chronological age, education, and lifestyle factors. FINDINGS: 512 723 participants, recruited between June 25, 2004, and July 15, 2008, were followed up for a median of 10·8 years (IQR 10·2-13·1; total follow-up 5 551 974 person-years). 291 954 (56·9%) people were categorised as robust, 205 075 (40·0%) people were categorised as prefrail, and 15 694 (3·1%) people were categorised as frail. Women aged between 45 years and 79 years had a higher mean frailty index and a higher prevalence of frailty than did men. During follow-up, 49 371 deaths were recorded. After adjustment for established and potential risk factors for death, each 0·1 increment in the frailty index was associated with a higher risk of all-cause mortality (hazard ratio [HR] 1·68, 95% CI 1·66-1·71). Such associations were stronger among younger adults than among older adults (pinteraction<0·0001), with HRs per 0·1 increment of the frailty index of 1·95 (95% CI 1·87-2·03) for those younger than 50 years, 1·80 (1·76-1·83) for those aged 50-64 years, and 1·56 (1·53-1·59) for those 65 years and older. After adjustments, there was no difference between the sexes in the association between the frailty index and all-cause mortality (pinteraction=0·75). For each 0·1 increment of the frailty index, the corresponding HRs for risk of death were 1·89 (95% CI 1·83-1·94) from ischaemic heart disease, 1·84 (1·79-1·89) from cerebrovascular disease, 1·19 (1·16-1·22) from cancer, 2·54 (2·45-2·63) from respiratory disease, 1·78 (1·59-2·00) from infection, and 1·78 (1·73-1·83) from all other causes. INTERPRETATION: The frailty index is associated with all-cause and cause-specific mortality independent of chronological age in younger and older Chinese adults. The identification of younger adults with accelerated ageing by use of surrogate measures could be useful for the prevention of premature death and the extension of healthy active life expectancy. FUNDING: The National Natural Science Foundation of China, the National Key R&D Program of China, the Chinese Ministry of Science and Technology, the Kadoorie Charitable Foundation, and the Wellcome Trust.

16.
Int J Food Sci Nutr ; : 1-8, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33207985

RESUMO

This study aimed to describe the characteristics and lifestyle differences of spicy food consumption in 0.5 million adults. Participants were recruited from 2004 to 2008 in the baseline research of the CKB study. Higher frequency and stronger pungency degree in spicy food positively correlated with preference for salty taste, eating snacks/deep-fried foods, tea/alcohol drinking and tobacco smoking. Among weekly tea/alcohol drinkers and current regular smokers, participants with a higher frequency of spicy food consumption or preference for stronger pungency degree were more likely to prefer strong tea, drink alcohol exceed the healthy amount, drink alcohol in the morning every day, smoke ≥ 40 cigarettes per day, consume a larger amount of tea leaves, alcohol and cigarettes each day, and start habitual tea/alcohol drinking or smoking at an earlier age. Differences existed in lifestyle factors related to major chronic diseases according to spicy food consumption frequency and pungency degree among the Chinese population.

17.
Sci Rep ; 10(1): 19507, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33177548

RESUMO

Exhaled carbon monoxide (COex) level has been proposed as a noninvasive and easily-obtainable cardiovascular risk marker, however, with limited prospective evidence, and its association with stroke risk has been rarely explored. Measurements of COex were performed during 2004-2008 baseline examinations in the China Kadoorie Biobank study among 512,891 adults aged 30-79 years from 10 diverse study areas. After excluding participants with baseline cardiopulmonary diseases, stroke and cancer, 178,485 men and 267,202 women remained. Cox regression yielded hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of cardio-cerebral-vascular disease (CCVD) associated with COex levels, with sequential addition of adjustment for proxy variables for CO exposure, including study area indexing ambient CO variations at large, and smoking and solid fuel use, apart from adjusting for traditional cardiovascular risk factors. During 7-year follow-up, we documented 1744 and 1430 major coronary events (myocardial infarction plus fatal ischemic heart disease), 8849 and 10,922 ischemic strokes, and 2492 and 2363 hemorrhagic strokes among men and women, respectively. The HRs with 95% CIs comparing the highest with lowest COex quintile were 2.15 [1.72, 2.69] for major coronary events, 1.65 [1.50, 1.80] for ischemic stroke, and 1.35 [1.13, 1.61] for hemorrhagic stroke among men, while among women higher associated risk was only observed for major coronary events (1.64 [1.35, 2.00]) and ischemic stroke (1.87 [1.73, 2.01]). The elevated risks were consistent when COex level was over 3 ppm. However, these associations were all attenuated until null by sequential addition of stratification by study areas, and adjustments of smoking and solid fuel use. Nevertheless, the association with ischemic stroke was maintained among the subgroup of male smokers even with adjustment for the depth and amount of cigarette smoking (HR [95% CI]: 1.37 [1.06, 1.77]), while a negative association with hemorrhagic stroke also appeared within this subgroup. Higher COex level (over 3 ppm) was associated with elevated risk of ischemic CCVD, but not independently of CO exposure. Our finding suggests that, though not an independent risk factor, COex could potentially provide a cost-effective biomarker for ischemic cardio-cerebral-vascular risk, given that CO exposure is ubiquitous.

18.
Lancet Oncol ; 21(10): 1378-1386, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002439

RESUMO

BACKGROUND: Genetic variants and lifestyle factors have been associated with gastric cancer risk, but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unknown. We aimed to establish a genetic risk model for gastric cancer and assess the benefits of adhering to a healthy lifestyle in individuals with a high genetic risk. METHODS: In this meta-analysis and prospective cohort study, we first did a fixed-effects meta-analysis of the association between genetic variants and gastric cancer in six independent genome-wide association studies (GWAS) with a case-control study design. These GWAS comprised 21 168 Han Chinese individuals, of whom 10 254 had gastric cancer and 10 914 geographically matched controls did not. Using summary statistics from the meta-analysis, we constructed five polygenic risk scores in a range of thresholds (p=5 × 10-4 p=5 × 10-5 p=5 × 10-6 p=5 × 10-7, and p=5 × 10-8) for gastric cancer. We then applied these scores to an independent, prospective, nationwide cohort of 100 220 individuals from the China Kadoorie Biobank (CKB), with more than 10 years of follow-up. The relative and absolute risk of incident gastric cancer associated with healthy lifestyle factors (defined as not smoking, never consuming alcohol, the low consumption of preserved foods, and the frequent intake of fresh fruits and vegetables), was assessed and stratified by genetic risk (low [quintile 1 of the polygenic risk score], intermediate [quintile 2-4 of the polygenic risk score], and high [quintile 5 of the polygenic risk score]). Individuals with a favourable lifestyle were considered as those who adopted all four healthy lifestyle factors, those with an intermediate lifestyle adopted two or three factors, and those with an unfavourable lifestyle adopted none or one factor. FINDINGS: The polygenic risk score derived from 112 single-nucleotide polymorphisms (p<5 × 10-5) showed the strongest association with gastric cancer risk (p=7·56 × 10-10). When this polygenic risk score was applied to the CKB cohort, we found that there was a significant increase in the relative risk of incident gastric cancer across the quintiles of the polygenic risk score (ptrend<0·0001). Compared with individuals who had a low genetic risk, those with an intermediate genetic risk (hazard ratio [HR] 1·54 [95% CI 1·22-1·94], p=2·67 × 10-4) and a high genetic risk (2·08 [1·61-2·69], p<0·0001) had a greater risk of gastric cancer. A similar increase in the relative risk of incident gastric cancer was observed across the lifestyle categories (ptrend<0·0001), with a higher risk of gastric cancer in those with an unfavourable lifestyle than those with a favourable lifestyle (2·03 [1·46-2·83], p<0·0001). Participants with a high genetic risk and a favourable lifestyle had a lower risk of gastric cancer than those with a high genetic risk and an unfavourable lifestyle (0·53 [0·29-0·99], p=0·048), with an absolute risk reduction of 1·12% (95% CI 0·62-1·56). INTERPRETATION: Chinese individuals at an increased risk of incident gastric cancer could be identified by use of our newly developed polygenic risk score. Compared with individuals at a high genetic risk who adopt an unhealthy lifestyle, those who adopt a healthy lifestyle could substantially reduce their risk of incident gastric cancer. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, 333 High-Level Talents Cultivation Project of Jiangsu Province, and China Postdoctoral Science Foundation.


Assuntos
Predisposição Genética para Doença/genética , Estilo de Vida Saudável , Neoplasias Gástricas/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Feminino , Seguimentos , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/psicologia , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/psicologia
19.
JAMA Netw Open ; 3(10): e2018721, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33006619

RESUMO

Importance: There is some support for the existence of genetic associations between adiposity and certain hepatobiliary diseases in Western populations. However, there is little evidence of such genetic associations in China, where the causes of these diseases may differ from those in Western populations and the mean body mass index (BMI) is much lower. Objectives: To compare the observational associations of BMI with hepatobiliary diseases and liver biomarkers with the genetic associations between BMI and these factors and to assess whether the genetic associations of BMI with liver diseases differed by hepatitis B virus infection status. Design, Setting, and Participants: This cohort study used data from the prospective China Kadoorie Biobank, including 473 938 adults aged 30 to 79 years without hepatobiliary diseases at baseline from 10 diverse areas in China from June 25, 2004, to July 15, 2008. A random sample of 75 736 participants with genotyping data was included in the Mendelian randomization analysis. Follow-up was completed January 1, 2017 (median [interquartile range] length of follow-up, 10.2 [9.2-11.1] years). Data were analyzed from January to October 2019. Exposures: Measured BMI obtained during the baseline survey and genetically instrumented BMI derived using 92 single-nucleotide variations. Main Outcomes and Measures: Incident cases of hepatobiliary diseases, liver enzymes, fatty liver index, and fibrosis score. Results: Among 473 938 individuals (276 041 [58.2%] women), the mean (SD) age was 52 (10.9) years and mean (SD) BMI was 23.8 (3.4). Baseline BMI was associated with higher risks of chronic liver disease (adjusted risk ratio per 1-SD increase, 1.14; 95% CI, 1.11 to 1.17) and gallbladder disease (adjusted risk ratio per 1-SD increase, 1.29; 95% CI, 1.27 to 1.31), with heterogeneity by disease subtype (P < .001). Genetically instrumented BMI was associated with higher risks of chronic liver disease (risk ratio per 1-SD increase, 1.55; 95% CI, 1.08 to 2.24) and gallbladder disease (risk ratio per 1-SD increase, 1.40; 95% CI, 1.11 to 1.76), with no heterogeneity between subtypes. A meta-analysis of the genetic associations in China Kadoorie Biobank and those calculated in UK Biobank gave a risk ratio of 1.55 (95% CI, 1.30 to 1.84) for chronic liver disease and 1.42 (95% CI, 1.22 to 1.64) for gallbladder disease. In the China Kadoorie Biobank study, there were positive genetic associations of BMI with liver enzymes, steatosis, and fibrosis scores, consistent with observational associations. The genetic associations of BMI with liver diseases and biomarkers did not differ by hepatitis B virus infection status. Conclusions and Relevance: In this cohort study of a relatively lean Chinese population, there were positive genetic associations of BMI with hepatobiliary diseases. These results suggest that maintaining a healthy weight through diet and physical activity may help prevent hepatobiliary diseases.

20.
PLoS Med ; 17(10): e1003351, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33125374

RESUMO

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.

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