In Western populations, a higher level of fruit consumption has been associated with a lower risk of cardiovascular disease, but little is known about such associations in China, where the ...consumption level is low and rates of stroke are high.
Between 2004 and 2008, we recruited 512,891 adults, 30 to 79 years of age, from 10 diverse localities in China. During 3.2 million person-years of follow-up, 5173 deaths from cardiovascular disease, 2551 incident major coronary events (fatal or nonfatal), 14,579 ischemic strokes, and 3523 intracerebral hemorrhages were recorded among the 451,665 participants who did not have a history of cardiovascular disease or antihypertensive treatments at baseline. Cox regression yielded adjusted hazard ratios relating fresh fruit consumption to disease rates.
Overall, 18.0% of participants reported consuming fresh fruit daily. As compared with participants who never or rarely consumed fresh fruit (the "nonconsumption" category), those who ate fresh fruit daily had lower systolic blood pressure (by 4.0 mm Hg) and blood glucose levels (by 0.5 mmol per liter 9.0 mg per deciliter) (P<0.001 for trend for both comparisons). The adjusted hazard ratios for daily consumption versus nonconsumption were 0.60 (95% confidence interval CI, 0.54 to 0.67) for cardiovascular death, and 0.66 (95% CI, 0.58 to 0.75), 0.75 (95% CI, 0.72 to 0.79), and 0.64 (95% CI, 0.56 to 0.74), respectively, for incident major coronary events, ischemic stroke, and hemorrhagic stroke. There was a strong log-linear dose-response relationship between the incidence of each outcome and the amount of fresh fruit consumed. These associations were similar across the 10 study regions and in subgroups of participants defined by baseline characteristics.
Among Chinese adults, a higher level of fruit consumption was associated with lower blood pressure and blood glucose levels and, largely independent of these and other dietary and nondietary factors, with significantly lower risks of major cardiovascular diseases. (Funded by the Wellcome Trust and others.).
In China, diabetes prevalence has increased substantially in recent decades, but there are no reliable estimates of the excess mortality currently associated with diabetes.
To assess the proportional ...excess mortality associated with diabetes and estimate the diabetes-related absolute excess mortality in rural and urban areas of China.
A 7-year nationwide prospective study of 512 869 adults aged 30 to 79 years from 10 (5 rural and 5 urban) regions in China, who were recruited between June 2004 and July 2008 and were followed up until January 2014.
Diabetes (previously diagnosed or detected by screening) recorded at baseline.
All-cause and cause-specific mortality, collected through established death registries. Cox regression was used to estimate adjusted mortality rate ratio (RR) comparing individuals with diabetes vs those without diabetes at baseline.
Among the 512 869 participants, the mean (SD) age was 51.5 (10.7) years, 59% (n = 302 618) were women, and 5.9% (n = 30 280) had diabetes (4.1% in rural areas, 8.1% in urban areas, 5.8% of men, 6.1% of women, 3.1% had been previously diagnosed, and 2.8% were detected by screening). During 3.64 million person-years of follow-up, there were 24 909 deaths, including 3384 among individuals with diabetes. Compared with adults without diabetes, individuals with diabetes had a significantly increased risk of all-cause mortality (1373 vs 646 deaths per 100 000; adjusted RR, 2.00 95% CI, 1.93-2.08), which was higher in rural areas than in urban areas (rural RR, 2.17 95% CI, 2.07-2.29; urban RR, 1.83 95% CI, 1.73-1.94). Presence of diabetes was associated with increased mortality from ischemic heart disease (3287 deaths; RR, 2.40 95% CI, 2.19-2.63), stroke (4444 deaths; RR, 1.98 95% CI, 1.81-2.17), chronic liver disease (481 deaths; RR, 2.32 95% CI, 1.76-3.06), infections (425 deaths; RR, 2.29 95% CI, 1.76-2.99), and cancer of the liver (1325 deaths; RR, 1.54 95% CI, 1.28-1.86), pancreas (357 deaths; RR, 1.84 95% CI, 1.35-2.51), female breast (217 deaths; RR, 1.84 95% CI, 1.24-2.74), and female reproductive system (210 deaths; RR, 1.81 95% CI, 1.20-2.74). For chronic kidney disease (365 deaths), the RR was higher in rural areas (18.69 95% CI, 14.22-24.57) than in urban areas (6.83 95% CI, 4.73-9.88). Among those with diabetes, 10% of all deaths (16% rural; 4% urban) were due to definite or probable diabetic ketoacidosis or coma (408 deaths).
Among adults in China, diabetes was associated with increased mortality from a range of cardiovascular and noncardiovascular diseases. Although diabetes was more common in urban areas, it was associated with greater excess mortality in rural areas.
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.
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.
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.
Few studies have assessed the relationship between multimorbidity patterns and mortality risk in the Chinese population. We aimed to identify multimorbidity patterns and examined the associations of ...multimorbidity patterns and the number of chronic diseases with the risk of mortality among Chinese middle-aged and older adults.
We used data from the China Kadoorie Biobank and included 512,723 participants aged 30 to 79 years. Multimorbidity was defined as the presence of two or more of the 15 chronic diseases collected by self-report or physical examination at baseline. Multimorbidity patterns were identified using hierarchical cluster analysis. Cox regression was used to estimate the associations of multimorbidity patterns and the number of chronic diseases with all-cause and cause-specific mortality.
Overall, 15.8% of participants had multimorbidity. The prevalence of multimorbidity increased with age and was higher in urban than rural participants. Four multimorbidity patterns were identified, including cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), gastrointestinal and hepatorenal multimorbidity (gallstone disease, chronic kidney disease, cirrhosis, peptic ulcer, and cancer), and mental and arthritis multimorbidity (neurasthenia, psychiatric disorder, and rheumatoid arthritis). During a median of 10.8 years of follow-up, 49,371 deaths occurred. Compared with participants without multimorbidity, cardiometabolic multimorbidity (hazard ratios HR = 2.20, 95% confidence intervals CI: 2.14 - 2.26) and respiratory multimorbidity (HR = 2.13, 95% CI:1.97 - 2.31) demonstrated relatively higher risks of mortality, followed by gastrointestinal and hepatorenal multimorbidity (HR = 1.33, 95% CI:1.22 - 1.46). The mortality risk increased by 36% (HR = 1.36, 95% CI: 1.35 - 1.37) with every additional disease.
Cardiometabolic multimorbidity and respiratory multimorbidity posed the highest threat on mortality risk and deserved particular attention in Chinese adults.
Objectives: 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. Facilitated by the availability of large-scale genetic data, Mendelian randomization studies are increasingly used to ascertain the causal relevance of nutritional exposures and biomarkers for many NCDs. Methods: A narrative overview was conducted in order to demonstrate and describe the utility of Mendelian randomization studies, for individuals with little prior knowledge engaged in nutritional epidemiological research. Results: We provide an overview, rationale and basic description of the methods, as well as strengths and limitations of Mendelian randomization studies. We give selected examples from the contemporary nutritional literature where Mendelian randomization has provided useful evidence on the potential causal relevance of nutritional exposures. Conclusions: The selected exemplars demonstrate the importance of well-conducted Mendelian randomization studies as a robust tool to prioritize nutritional exposures for further investigation.
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.
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.
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.
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.
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.
Two genetic variants that alter alcohol metabolism, ALDH2‐rs671 and ADH1B‐rs1229984, can modify oesophageal cancer risk associated with alcohol consumption in East Asians, but their associations with ...other cancers remain uncertain. ALDH2‐rs671 G>A and ADH1B‐rs1229984 G>A were genotyped in 150 722 adults, enrolled from 10 areas in China during 2004 to 2008. After 11 years' follow‐up, 9339 individuals developed cancer. Cox regression was used to estimate hazard ratios (HRs) for site‐specific cancers associated with these genotypes, and their potential interactions with alcohol consumption. Overall, the A‐allele frequency was 0.21 for ALDH2‐rs671 and 0.69 for ADH1B‐rs1229984, with A‐alleles strongly associated with lower alcohol consumption. Among men, ALDH2‐rs671 AA genotype was associated with HR of 0.69 (95% confidence interval: 0.53‐0.90) for IARC alcohol‐related cancers (n = 1900), compared to GG genotype. For ADH1B‐rs1229984, the HRs of AG and AA vs GG genotype were 0.80 (0.69‐0.93) and 0.75 (0.64‐0.87) for IARC alcohol‐related cancers, 0.61 (0.39‐0.96) and 0.61 (0.39‐0.94) for head and neck cancer (n = 196) and 0.68 (0.53‐0.88) and 0.60 (0.46‐0.78) for oesophageal cancer (n = 546). There were no significant associations of these genotypes with risks of liver (n = 651), colorectal (n = 556), stomach (n = 725) or lung (n = 1135) cancers. Among male drinkers, the risks associated with higher alcohol consumption were greater among ALDH2‐rs671 AG than GG carriers for head and neck, oesophageal and lung cancers (Pinteraction < .02). Among women, only 2% drank alcohol regularly, with no comparable associations observed between genotype and cancer. These findings support the causal effects of alcohol consumption on upper aerodigestive tract cancers, with ALDH2‐rs671 AG genotype further exacerbating the risks.
What's new?
Alcohol consumption has been increasing among men in China, and is a major contributor to the total cancer burden. Two genetic variants that alter alcohol metabolism are associated with esophageal cancer risk in East Asians. Do these variants also play a role in other cancers, or influence the effect of alcohol on cancer risk? In this large Chinese study, the authors found that certain genotypes were associated with reduced upper aero‐digestive tract cancer risk, and that one of the variants may exacerbate the effects of alcohol on several cancers.
Few large studies in China have investigated total physical activity and sedentary leisure time and their associations with adiposity.
We investigated determinants of physical activity and sedentary ...leisure time and their associations with adiposity in China.
A total of 466,605 generally healthy participants (age: 30-79 y, 60% female) in the China Kadoorie Biobank were included in this cross-sectional analysis. Self-reported information on a range of activities was collected by interviewer-administered questionnaire. Physical activity was calculated as metabolic equivalent task hours per day (MET-h/d) spent on work, transportation, housework, and nonsedentary recreation. Sedentary leisure time was quantified as hours per day. Adiposity measures included BMI, waist circumference, and percentage body fat (by bioimpedance analysis). Associations were estimated by linear and logistic regression.
The mean physical activity was 22 MET-h/d, and the mean sedentary leisure time was 3.0 h/d. For each sex, physical activity was about one-third lower among professionals/administrators than among factory workers, with intermediate levels for other occupational categories. A 1-SD (14 MET-h/d) greater physical activity was associated with a 0.15-unit (95% CI: 0.14, 0.16) lower BMI (in kg/m(2)), a 0.58-cm (95% CI: 0.55, 0.61) smaller waist circumference, and 0.48 (95% CI: 0.45, 0.50) percentage points less body fat. In contrast, a 1-SD (1.5 h/d) greater sedentary leisure time was associated with a 0.19-unit higher BMI (95% CI: 0.18, 0.20), a 0.57-cm larger waist circumference (95% CI: 0.54, 0.59), and 0.44 (95% CI: 0.42, 0.46) percentage points more body fat. For any given physical activity level, greater sedentary leisure time was associated with a greater prevalence of increased BMI, as was lower physical activity for any given sedentary leisure time.
In adult Chinese, physical activity varies substantially by occupation, and lack of physical activity and excess sedentary leisure time are independently and jointly associated with greater adiposity.
Aims/hypothesis
Previous evidence linking red meat consumption with diabetes risk mainly came from western countries, with little evidence from China, where patterns of meat consumption are ...different. Moreover, global evidence remains inconclusive about the associations of poultry and fish consumption with diabetes. Therefore we investigated the associations of red meat, poultry and fish intake with incidence of diabetes in a Chinese population.
Methods
The prospective China Kadoorie Biobank recruited ~512,000 adults (59% women, mean age 51 years) from ten rural and urban areas across China in 2004–2008. At the baseline survey, a validated interviewer-administered laptop-based questionnaire was used to collect information on the consumption frequency of major food groups including red meat, poultry, fish, fresh fruit and several others. During ~9 years of follow-up, 14,931 incidences of new-onset diabetes were recorded among 461,036 participants who had no prior diabetes, cardiovascular diseases or cancer at baseline. Cox regression analyses were performed to calculate adjusted HRs for incident diabetes associated with red meat, poultry and fish intake.
Results
At baseline, 47.0%, 1.3% and 8.9% of participants reported a regular consumption (i.e. ≥4 days/week) of red meat, poultry and fish, respectively. After adjusting for adiposity and other potential confounders, each 50 g/day increase in red meat and fish intake was associated with 11% (HR 1.11 95% CI 1.04, 1.20) and 6% (HR 1.06 95% CI 1.00, 1.13) higher risk of incident diabetes, respectively. For both, the associations were more pronounced among men and women from urban areas, with an HR (95% CI) of 1.42 (1.15, 1.74) and 1.18 (1.03, 1.36), respectively, per 50 g/day red meat intake and 1.15 (1.02, 1.30) and 1.11 (1.01, 1.23), respectively, per 50 g/day fish intake. There was no significant association between diabetes and poultry intake, either overall (HR 0.96 95% CI 0.83, 1.12 per 50 g/day intake) or in specific population subgroups.
Conclusions/interpretation
In Chinese adults, both red meat and fish, but not poultry, intake were positively associated with diabetes risk, particularly among urban participants. Our findings add new evidence linking red meat and fish intake with cardiometabolic diseases.
Data availability
Details of how to access the China Kadoorie Biobank data and rules of China Kadoorie Biobank data release are available from
www.ckbiobank.org/site/Data+Access
.
Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the ...first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in the Asian population.
We did a nested case-control study comprising incident CHD cases and 1:1 matched controls who were identified from the 10 year follow-up of the China Kadoorie Biobank. Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip. We performed the single cytosine-phosphate-guanine (CpG) site association analysis and network approach to identify CHD-associated CpG sites and co-methylation gene module.
After quality control, 982 participants (mean age 50.1 years) were retained. Methylation level at 25 CpG sites across the genome was associated with incident CHD (genome-wide false discovery rate FDR < 0.05 or module-specific FDR < 0.01). One SD increase in methylation level of identified CpGs was associated with differences in CHD risk, ranging from a 47 % decrease to a 118 % increase. Mediation analyses revealed 28.5 % of the excessed CHD risk associated with smoking was mediated by methylation level at the promoter region of
gene (P for mediation effect = 0.036). Methylation level at the promoter region of
was associated with blood pressure and subsequent risk of CHD, with the mediating proportion to be 7.7 % (
= 0.003) via systolic blood pressure and 6.4 % (
= 0.006) via diastolic blood pressure. Network analysis revealed a co-methylation module associated with CHD.
We identified novel blood methylation alterations associated with incident CHD in the Asian population and provided evidence of the possible role of epigenetic regulations in the smoking- and blood pressure-related pathways to CHD risk.
This work was supported by National Natural Science Foundation of China (81390544 and 91846303). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), grant (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01).
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