To comprehensively examine the potential impacts of prenatal experience of the Chinese Great Famine on chronic disease risks in the middle age.
This study included 92 284 participants aged 39-51 ...years from China Kadoorie Biobank born around the famine period and without major chronic diseases at baseline. We categorised participants into non-famine births (born between 1 October 1956 and 30 September 1958, and 1 October 1962 and 30 September 1964) and famine births (born between 1 October 1959 and 30 September 1961). The outcomes were incident cardiovascular disease, cancer and respiratory system disease. Cox regression was used to estimate adjusted HR and 95% CI for famine exposure. Subgroup analyses were performed according to baseline characteristics.
During a median 10.1 years of follow-up, we identified 4626 incident ischaemic heart disease (IHD) cases, 7332 cerebrovascular disease cases, 3111 cancer cases and 16 081 respiratory system disease cases. In the whole population, prenatal famine exposure was not statistically associated with the risks of developing any chronic diseases in adulthood. However, for urban participants, compared with non-famine births, famine births had a higher risk of cerebrovascular disease (HR 1.18; 95% CI 1.09 to 1.28); such association was not shown for rural participants (p for interaction <0.001). Also, we observed the associations of prenatal famine exposure with IHD (HR 1.15; 95% CI 1.05 to 1.26) and cerebrovascular disease (HR 1.13; 95% CI 1.05 to 1.21) in participants with lower physical activity level, but not in those with higher ones (all p for interaction=0.003).
Our findings indicate that prenatal exposure to the Chinese famine might be associated with an increased cardiovascular risk and such risk may be modified by adult lifestyle.
Background
Evidence for the association between environmental tobacco smoke (ETS) exposure and the risk of type 2 diabetes mellitus (T2DM) is limited. The aim of this study was to investigate this ...association in female never smokers.
Methods
We analyzed 28 177 female participants of the China Kadoorie Biobank (CKB) in the Suzhou area, who were never smokers and had no diabetes. ETS exposure was defined as being exposed to other people's tobacco smoke either at home, workplace, or in public places at least 1 d/wk. Cox proportional hazard regression models were used to assess the association between ETS exposure and incident T2DM according to the frequency and duration of ETS exposure.
Results
A total of 774 incident cases of T2DM were identified during a median 7.3‐year follow‐up. Compared with no ETS exposure, hazard ratios (95% CIs) for all ETS exposure, daily, and ≥14 h/wk ETS exposure were 1.17 (1.00‐1.37), 1.23 (1.04‐1.46), and 1.25 (1.03‐1.53), respectively. Moreover, a positive dose‐response relationship was observed between ETS exposure level and T2DM (all P <.05 for trend).
Conclusions
This prospective study suggests that ETS exposure increases the risk of T2DM incidence with dose‐response relationship in female never smokers. Thus, reducing ETS exposure may help decrease the burden of T2DM in Chinese females.
摘要
背景
关于环境烟雾暴露与2型糖尿病风险关联的证据有限, 本研究旨在在中国从未吸烟的女性中研究二者的关联。
方法
我们分析了中国慢性病前瞻性研究苏州地区28177名从未吸烟且无糖尿病女性参与者。环境烟雾暴露的定义为在家中、工作场所或公共场所至少1天/周暴露于他人的吸烟烟雾。使用Cox比例风险回归模型评估环境烟雾暴露频率和持续时间与2型糖尿病发病事件的关联。
结果
在平均7.5人年的随访期间, 共发现774例2型糖尿病事件。与无环境烟雾暴露者相比, 有环境烟雾暴露史、频率为每日和时长≥14h/周的人群2型糖尿病发病风险比(95%CI)分别为1.17(1.00‐1.37), 1.23 (1.04‐1.46)和 1.25 (1.03‐1.53)。此外, 环境烟雾暴露水平和2型糖尿病风险之间呈现剂量反应性的正关联(所有Ptrend<0.05)。
结论
这项前瞻性研究表明, 在从未吸烟的女性中, 环境烟雾暴露会增加2型糖尿病的发病风险, 并具有剂量反应关系。 因此, 减少环境烟雾暴露可能有助于减轻中国女性的2型糖尿病负担。
Highlights
This was the first report attempting to explore the association between environmental tobacco smoke (ETS) exposure and the risk of incident type 2 diabetes (T2DM) in a Chinese population cohort.
Daily ETS exposure was associated with an approximately 23% higher risk of T2DM.
Little is known about the effects of maintaining healthy sleep patterns on frailty transitions.
Based on 23,847 Chinese adults aged 30-79 in a prospective cohort study, we examined the associations ...between sleep patterns and frailty transitions. Healthy sleep patterns included sleep duration at 7 or 8 h/d, without insomnia disorder, and no snoring. Participants who persisted with a healthy sleep pattern in both surveys were defined as maintaining a healthy sleep pattern and scored one point. We used 27 phenotypes to construct a frailty index and defined three statuses: robust, prefrail, and frail. Frailty transitions were defined as the change of frailty status between the 2 surveys: improved, worsened, and remained. Log-binomial regression was used to calculate the prevalence ratio (PR) to assess the effect of sleep patterns on frailty transitions.
During a median follow-up of 8.0 years among 23,847 adults, 45.5% of robust participants, and 10.8% of prefrail participants worsened their frailty status, while 18.6% of prefrail participants improved. Among robust participants at baseline, individuals who maintained sleep duration of 7 or 8 h/ds, without insomnia disorder, and no-snoring were less likely to worsen their frailty status; the corresponding PRs (95% CIs) were 0.92 (0.89-0.96), 0.76 (0.74-0.77), and 0.85 (0.82-0.88), respectively. Similar results were observed among prefrail participants maintaining healthy sleep patterns. Maintaining healthy sleep duration and without snoring, also raised the probability of improving the frailty status; the corresponding PRs were 1.09 (1.00-1.18) and 1.42 (1.31-1.54), respectively. Besides, a dose-response relationship was observed between constantly healthy sleep scores and the risk of frailty transitions (P for trend < 0.001).
Maintaining a comprehensive healthy sleep pattern was positively associated with a lower risk of worsening frailty status and a higher probability of improving frailty status among Chinese adults.
Abstract
Background
The relative importance of healthy lifestyle factors and cardiovascular health metrics for the risk of heart failure is uncertain in Chinese populations. We aimed to compare the ...strength of associations between healthy lifestyle factors and ideal cardiovascular health metrics in the risk of heart failure in middle-aged Chinese adults.
Methods
A healthy lifestyle score (HLS) was constructed using smoking, drinking, physical activity, diet, body mass index and waist circumference, and compared with a more comprehensive set of metrics that included cardiovascular-disease risk biomarkers (blood pressure, blood glucose and blood lipids) in addition to the HLS. This broader set of factors called ‘ideal cardiovascular health metrics’ (ICVHMs) was evaluated in 487 197 participants in the China Kadoorie Biobank.
Results
A total of 4208 incident cases of heart failure were recorded during a median follow-up of 10 years. Both HLS hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.85, 0.91 and ICVHMs (0.87: 0.84, 0.89) were inversely associated with risk of heart failure (P < 0.001 for linear trend). Compared with participants with 0–1 HLS, the multivariable-adjusted HR of those with 4–5 HLS was 0.68 (0.59, 0.77). Compared with participants with 0–2 ICVHMs, the adjusted HR (95% CIs) of those who had 7–8 ICVHMs was 0.47 (0.36, 0.60). ICVHMs were more strongly predictive of risk of heart failure (area under curve, 0.61 vs 0.58, P < 0.001) than healthy lifestyle factors alone.
Conclusions
Higher levels of healthy lifestyle factors and ICVHMs were each inversely associated with heart failure, and lifestyle factors combined with cardiometabolic factors improved the prediction of heart failure compared with healthy lifestyle factors alone.
Higher fruit consumption is associated with lower risk of cardiovascular disease (CVD). Substantial uncertainties remain, however, about the associations of fruit consumption with all-cause mortality ...and mortality from subtypes of CVD and major non-vascular diseases, especially in China.
In 2004-08, the nationwide China Kadoorie Biobank Study recruited > 0.5 million adults aged 30-79 years from 10 diverse localities in China. Fresh fruit consumption was estimated using an interviewer-administered electronic questionnaire, and mortality data were collected from death registries. Among the 462 342 participants who were free of major chronic diseases at baseline, 17 894 deaths were recorded during ∼ 7 years of follow-up. Cox regression yielded adjusted rate ratios (RRs) for all-cause and cause-specific mortality associated with fruit consumption.
At baseline, 28% of participants reported consuming fruit ≥ 4 days/week (regular consumers) and 6% reported never/rarely consuming fruit (non-consumers). Compared with non-consumers, regular consumers had 27% RR = 0.73, 95% confidence interval (CI) 0.70-0.76 lower all-cause mortality, 34% lower CVD mortality (n = 6166; RR = 0.66, 0.61-0.71), 17% lower cancer mortality (n = 6796; RR = 0.83, 0.78-0.89) and 42% lower mortality from chronic obstructive pulmonary disease (COPD) (n = 1119; RR = 0.58, 0.47-0.71). For each of the above, there was an approximately log-linear dose-response relationship with amount consumed. For mortality from site-specific cancers, fruit consumption was inversely associated with digestive tract cancer (n = 2265; RR = 0.72, 0.64-0.81), particularly oesophageal cancer (n = 801; RR = 0.65, 0.50-0.83), but not with cancer of lung or liver.
Among Chinese adults, higher fresh fruit consumption was associated with significantly lower mortality from several major vascular and non-vascular diseases. Given the current low population level of fruit consumption, substantial health benefits could be gained from increased fruit consumption in China.
In China, the patterns and levels of physical activity differed from those in high-income countries. Substantial uncertainty remains about the relevance, both qualitatively and quantitatively, of ...domain-specific physical activity for cardiovascular disease (CVD) subtypes in Chinese adults.
To assess the shape and strength of the associations of total, occupational, and nonoccupational physical activity with CVD subtypes in Chinese men and women.
This population-based prospective cohort study in 10 (5 urban, 5 rural) areas across China included 487 334 adults who were aged 30 to 79 (mean 51) years with no prior CVD history when enrolled from June 2004 to July 2008.
Self-reported total, occupational, and nonoccupational physical activity, quantified as metabolic equivalent of task hours per day (MET-h/d) based on the type, frequency, and duration of specific activities.
Major vascular events (n = 36 184) and their components, including major coronary events (n = 5082), ischemic stroke (n = 25 647), intracerebral hemorrhage (n = 5252), and CVD death (n = 8437). Cox regression yielded adjusted hazard ratios for each disease that was associated with physical activity.
Of the 487 334 study participants, 287 527 (59%) were women and the mean (SD) age was 51 (10.5) years. The overall mean (SD) total physical activity was 21.5 (12.8) MET-h/d, mainly from occupational activity, especially among men (75% vs 50% in women). Total physical activity was inversely associated with the risk of major vascular events, with the adjusted hazard ratio that compared the top vs bottom quintiles of physical activity being 0.77 (95% CI, 0.74-0.80). Throughout the range of total physical activity studied, the association with CVD with each 4 MET-h/d higher usual total physical activity (approximately 1 hour of brisk walking per day) associated with a 6% (95% CI, 5%-7%) lower risk of major vascular events, and a 9%, 5%, 6%, and 12% lower risk of major coronary events, ischemic stroke, intracerebral hemorrhage, and CVD death, respectively. The strength of the associations was similar and independent of each other for occupational and nonoccupational physical activity. However, for occupational physical activity, the associations with CVD subtypes were greatly attenuated above 20 MET-h/d, especially for intracerebral hemorrhage. The associations of total physical activity with major vascular events were similar among men and women and across different levels of sedentary leisure time but were much weaker among individuals with high blood pressure.
Among Chinese adults, higher occupational or nonoccupational physical activity was associated with significantly lower risks of major CVD.
China has high stroke rates despite the population being relatively lean. Uncertainty persists about the relevance of adiposity to risk of stroke types. We aimed to assess the associations of ...adiposity with incidence of stroke types and effect mediation by blood pressure in Chinese men and women.
The China Kadoorie Biobank enrolled 512 891 adults aged 30–79 years from ten areas (five urban and five rural) during 2004–08. During a median 9 years (IQR 8–10) of follow-up, 32 448 strokes (about 90% confirmed by neuroimaging) were recorded among 489 301 participants without previous cardiovascular disease. Cox regression analysis was used to produce adjusted hazard ratios (HRs) for ischaemic stroke (n=25 210) and intracerebral haemorrhage (n=5380) associated with adiposity.
Mean baseline body-mass index (BMI) was 23·6 kg/m2 (SD 3·2), and 331 723 (67·8%) participants had a BMI of less than 25 kg/m2. Throughout the range examined (mean 17·1 kg/m2 SD 0·9 to 31·7 kg/m2 2·0), each 5 kg/m2 higher BMI was associated with 8·3 mm Hg (SE 0·04) higher systolic blood pressure. BMI was positively associated with ischaemic stroke, with an HR of 1·30 (95% CI 1·28–1·33 per 5 kg/m2 higher BMI), which was generally consistent with that predicted by equivalent differences in systolic blood pressure (1·25 1·24–1·26). The HR for intracerebral haemorrhage (1·11 1·07–1·16 per 5 kg/m2 higher BMI) was less extreme, and much weaker than that predicted by the corresponding difference in systolic blood pressure (1·48 1·46–1·50). Other adiposity measures showed similar associations with stroke types. After adjustment for usual systolic blood pressure, the positive associations with ischaemic stroke were attenuated (1·05 1·03–1·07 per 5 kg/m2 higher BMI); for intracerebral haemorrhage, they were reversed (0·73 0·70–0·77). High adiposity (BMI >23 kg/m2) accounted for 14·7% of total stroke (16·5% of ischaemic stroke and 6·7% of intracerebral haemorrhage).
In Chinese adults, adiposity was strongly positively associated with ischaemic stroke, chiefly through its effect on blood pressure. For intracerebral haemorrhage, leanness, either per se or through some other factor (or factors), might increase risk, offsetting the protective effects of lower blood pressure.
UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, Chinese National Natural Science Foundation.
Adiposity is increasing rapidly in China but little is known about the relevance to it of women's reproductive factors, which differ inter-generationally and from that in the West. We assess ...associations of adiposity with life-course reproductive factors in Chinese women.
In 2004-08, the nationwide China Kadoorie Biobank recruited 303 000 women aged 30-79 (mean 50) years from 10 diverse regions. Multivariable linear regression was used to examine associations of reproductive factors (e.g. age at menarche/first birth/menopause, parity, breastfeeding and reproductive years) with measures of general e.g. body mass index (BMI) and central e.g. waist circumference (WC) adiposity in adulthood.
Overall, the mean BMI was 23.7 (standard deviation 3.3) kg/m 2 , mean age at menarche was 15 (2) years and nearly all had given birth (99%) and breastfed children (98%). Adiposity was associated inversely with age at menarche and at first birth, with 0.19 and 0.05 kg/m 2 lower BMI and 0.38 and 0.12 cm lower WC per 1-year delay respectively ( P < 0.001). Among 128 259 post-menopausal women, adiposity was associated positively with age at menopause and reproductive years, with 0.05 and 0.07 kg/m 2 higher BMI and 0.12 and 0.17 cm higher WC per 1-year increase, respectively ( P < 0.001). The proportion with overweight/obesity had similar associations with these reproductive factors. Adiposity had a non-linear positive association with parity, but no association with breastfeeding duration.
Among Chinese women, earlier age at menarche and at first birth, later age at menopause and longer reproductive years were independently associated with increased adiposity late in life.
Lowering low-density lipoprotein cholesterol (LDL-C) through PCSK9 inhibition represents a new therapeutic approach to preventing and treating cardiovascular disease (CVD). Phenome-wide analyses of ...PCSK9 genetic variants in large biobanks can help to identify unexpected effects of PCSK9 inhibition.
In the prospective China Kadoorie Biobank, we constructed a genetic score using three variants at the PCSK9 locus associated with directly measured LDL-C PCSK9 genetic score (PCSK9-GS). Logistic regression gave estimated odds ratios (ORs) for PCSK9-GS associations with CVD and non-CVD outcomes, scaled to 1 SD lower LDL-C. PCSK9-GS was associated with lower risks of carotid plaque n = 8340 cases; OR = 0.61 (95% confidence interval: 0.45-0.83); P = 0.0015, major occlusive vascular events n = 15 752; 0.80 (0.67-0.95); P = 0.011, and ischaemic stroke n = 11 467; 0.80 (0.66-0.98); P = 0.029. However, PCSK9-GS was also associated with higher risk of hospitalization with chronic obstructive pulmonary disease COPD: n = 6836; 1.38 (1.08-1.76); P = 0.0089 and with even higher risk of fatal exacerbations amongst individuals with pre-existing COPD n = 730; 3.61 (1.71-7.60); P = 7.3 × 10-4. We also replicated associations for a PCSK9 variant, reported in UK Biobank, with increased risks of acute upper respiratory tract infection (URTI) pooled OR after meta-analysis of 1.87 (1.38-2.54); P = 5.4 × 10-5 and self-reported asthma pooled OR of 1.17 (1.04-1.30); P = 0.0071. There was no association of a polygenic LDL-C score with COPD hospitalization, COPD exacerbation, or URTI.
The LDL-C-lowering PCSK9 genetic variants are associated with lower risk of subclinical and clinical atherosclerotic vascular disease but higher risks of respiratory diseases. Pharmacovigilance studies may be required to monitor patients treated with therapeutic PCSK9 inhibitors for exacerbations of respiratory diseases or respiratory tract infections.
Genetic analyses of over 100 000 participants of the China Kadoorie Biobank, mimicking the effect of new drugs intended to reduce cholesterol by targeting the PCSK9 protein, have identified potential severe effects of lower PCSK9 activity in patients with existing respiratory disease.PCSK9 genetic variants that are associated with lower cholesterol and reduced rates of cardiovascular disease are also associated with increased risk of a range of respiratory diseases, including asthma, upper respiratory tract infections, and hospitalization with chronic obstructive pulmonary disease (COPD).These genetic variants are not associated with whether or not individuals have COPD; instead, they are specifically associated with an increase in the chance of those who already have COPD being hospitalized and even dying, suggesting that careful monitoring of such patients should be considered during development of and treatment with anti-PCSK9 medication.
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