This is a review article telling a 50-years old story about the studies on selenium deficiency and Keshan disease in China, an endemic heart disease with high case-fatality, as an example of ...translational research. Extensive cross-sectional epidemiological studies showed that low selenium concentrations in cereal grains and low selenium status of local residents were associated with the occurrence of Keshan disease. Several large populationbased intervention trials using oral administration of sodium selenite tablets showed significant reduction of Keshan disease incidence. Based on the above evidence, it was concluded that selenium deficiency is the major cause of Keshan disease, although other etiological factors could not be ruled out. The implications of the findings include: provided critical scientific evidence for selenium being an essential trace element for humans; as scientific basis for identifying minimum requirement and RDA/RNI for selenium; and as solid reference for the formulation of effective preventive measures for Keshan disease in China.
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.).
Summary Background Chinese men now smoke more than a third of the world's cigarettes, following a large increase in urban then rural usage. Conversely, Chinese women now smoke far less than in ...previous generations. We assess the oppositely changing effects of tobacco on male and female mortality. Methods Two nationwide prospective studies 15 years apart recruited 220 000 men in about 1991 at ages 40–79 years (first study) and 210 000 men and 300 000 women in about 2006 at ages 35–74 years (second study), with follow-up during 1991–99 (mid-year 1995) and 2006–14 (mid-year 2010), respectively. Cox regression yielded sex-specific adjusted mortality rate ratios (RRs) comparing smokers (including any who had stopped because of illness, but not the other ex-smokers, who are described as having stopped by choice) versus never-smokers. Findings Two-thirds of the men smoked; there was little dependence of male smoking prevalence on age, but many smokers had not smoked cigarettes throughout adult life. Comparing men born before and since 1950, in the older generation, the age at which smoking had started was later and, particularly in rural areas, lifelong exclusive cigarette use was less common than in the younger generation. Comparing male mortality RRs in the first study (mid-year 1995) versus those in the second study (mid-year 2010), the proportional excess risk among smokers (RR-1) approximately doubled over this 15-year period (urban: RR 1·32 95% CI 1·24–1·41 vs 1·65 1·53–1·79; rural: RR 1·13 1·09–1·17 vs 1·22 1·16–1·29), as did the smoking-attributed fraction of deaths at ages 40–79 years (urban: 17% vs 26%; rural: 9% vs 14%). In the second study, urban male smokers who had started before age 20 years (which is now typical among both urban and rural young men) had twice the never-smoker mortality rate (RR 1·98, 1·79–2·19, approaching Western RRs), with substantial excess mortality from chronic obstructive pulmonary disease (COPD RR 9·09, 5·11–16·15), lung cancer (RR 3·78, 2·78–5·14), and ischaemic stroke or ischaemic heart disease (combined RR 2·03, 1·66–2·47). Ex-smokers who had stopped by choice (only 3% of ever-smokers in 1991, but 9% in 2006) had little smoking-attributed risk more than 10 years after stopping. Among Chinese women, however, there has been a tenfold intergenerational reduction in smoking uptake rates. In the second study, among women born in the 1930s, 1940s, 1950s, and since 1960 the proportions who had smoked were, respectively, 10%, 5%, 2%, and 1% (3097/30 943, 3265/62 246, 2339/97 344, and 1068/111 933). The smoker versus non-smoker RR of 1·51 (1·40–1·63) for all female mortality at ages 40–79 years accounted for 5%, 3%, 1%, and <1%, respectively, of all the female deaths in these four successive birth cohorts. In 2010, smoking caused about 1 million (840 000 male, 130 000 female) deaths in China. Interpretation Smoking will cause about 20% of all adult male deaths in China during the 2010s. The tobacco-attributed proportion is increasing in men, but low, and decreasing, in women. Although overall adult mortality rates are falling, as the adult population of China grows and the proportion of male deaths due to smoking increases, the annual number of deaths in China that are caused by tobacco will rise from about 1 million in 2010 to 2 million in 2030 and 3 million in 2050, unless there is widespread cessation. Funding Wellcome Trust, MRC, BHF, CR-UK, Kadoorie Charitable Foundation, Chinese MoST and NSFC
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.
Blood lipids are established risk factors for myocardial infarction (MI), but uncertainty persists about the relevance of lipids, lipoprotein particles, and circulating metabolites for MI and stroke ...subtypes.
This study sought to investigate the associations of plasma metabolic markers with risks of incident MI, ischemic stroke (IS), and intracerebral hemorrhage (ICH).
In a nested case-control study (912 MI, 1,146 IS, and 1,138 ICH cases, and 1,466 common control subjects) 30 to 79 years of age in China Kadoorie Biobank, nuclear magnetic resonance spectroscopy measured 225 metabolic markers in baseline plasma samples. Logistic regression was used to estimate adjusted odds ratios (ORs) for a 1-SD higher metabolic marker.
Very low-, intermediate-, and low-density lipoprotein particles were positively associated with MI and IS. High-density lipoprotein (HDL) particles were inversely associated with MI apart from small HDL. In contrast, no lipoprotein particles were associated with ICH. Cholesterol in large HDL was inversely associated with MI and IS (OR: 0.79 and 0.88, respectively), whereas cholesterol in small HDL was not (OR: 0.99 and 1.06, respectively). Triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI, with a similar pattern for IS. Glycoprotein acetyls, ketone bodies, glucose, and docosahexaenoic acid were associated with all 3 diseases. The 225 metabolic markers showed concordant associations between MI and IS, but not with ICH.
Lipoproteins and lipids showed similar associations with MI and IS, but not with ICH. Within HDL particles, cholesterol concentrations were inversely associated, whereas triglyceride concentrations were positively associated with MI. Glycoprotein acetyls and several non–lipid-related metabolites associated with all 3 diseases.
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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.
Objective To examine the associations between the regular consumption of spicy foods and total and cause specific mortality.Design Population based prospective cohort study.Setting China Kadoorie ...Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008.Participants 199 293 men and 288 082 women aged 30 to 79 years at baseline after excluding participants with cancer, heart disease, and stroke at baseline.Main exposure measures Consumption frequency of spicy foods, self reported once at baseline.Main outcome measures Total and cause specific mortality.Results During 3 500 004 person years of follow-up between 2004 and 2013 (median 7.2 years), a total of 11 820 men and 8404 women died. Absolute mortality rates according to spicy food consumption categories were 6.1, 4.4, 4.3, and 5.8 deaths per 1000 person years for participants who ate spicy foods less than once a week, 1 or 2, 3 to 5, and 6 or 7 days a week, respectively. Spicy food consumption showed highly consistent inverse associations with total mortality among both men and women after adjustment for other known or potential risk factors. In the whole cohort, compared with those who ate spicy foods less than once a week, the adjusted hazard ratios for death were 0.90 (95% confidence interval 0.84 to 0.96), 0.86 (0.80 to 0.92), and 0.86 (0.82 to 0.90) for those who ate spicy food 1 or 2, 3 to 5, and 6 or 7 days a week, respectively. Compared with those who ate spicy foods less than once a week, those who consumed spicy foods 6 or 7 days a week showed a 14% relative risk reduction in total mortality. The inverse association between spicy food consumption and total mortality was stronger in those who did not consume alcohol than those who did (P=0.033 for interaction). Inverse associations were also observed for deaths due to cancer, ischemic heart diseases, and respiratory diseases.Conclusion In this large prospective study, the habitual consumption of spicy foods was inversely associated with total and certain cause specific mortality, independent of other risk factors of death.
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.
Simultaneously adhering to multiple healthy lifestyle factors has been related to up to 90% reduction in type 2 diabetes (T2DM) incidence in White populations; however, little is known about whether ...such protective effects persist in other non-White populations.
We examined the associations of six lifestyle factors with T2DM in the China Kadoorie Biobank of 461 211 participants aged 30-79 years without diabetes, cardiovascular diseases or cancer at baseline. We defined low-risk lifestyle factors as non-smoking or having stopped for reasons other than illness; alcohol consumption of <30 g/day; upper quarter of the physical activity level; diet rich in vegetables and fruits, low in red meat and with some degree of replacement of rice with wheat; body mass index (BMI) of 18.5-23.9 kg/m2; and waist-to-hip ratio (WHR) <0.90 (men)/<0.85 (women).
During a median of 7.2 years of follow-up, we identified 8784 incident T2DM. In multivariable-adjusted analyses, two important risk factors for developing T2DM were higher BMI and WHR. Compared with participants without any low-risk factors, the hazard ratio 95% confidence interval (CI) for those with at least three low-risk factors was 0.20 (0.19, 0.22). Approximately 72.6% (64.2%, 79.3%) of the incident diabetes were attributable to the combination of BMI, WHR, diet and physical activity. The population attributable risk percentage (PAR%) of diabetes appeared to be similar for men and women, and higher among urban, older and obese participants.
Our findings indicate that adherence to a healthy lifestyle may substantially lower the burden of T2DM in the Chinese population.
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.
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