The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main ...stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China.
512 891 adults (59% women) aged 30–79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure.
During a median follow-up of 9 years (IQR 8–10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40–79 years (mean age at event 64 years SD 9), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120–180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 95% CI 1·28–1·34) and ischaemic stroke (1·30 1·29–1·31), but the association with intracerebral haemorrhage was about twice as steep (1·68 1·65–1·71). HRs for vascular disease were twice as steep at ages 40–49 years than at ages 70–79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 1·35–1·44) and diabetes (1·14 1·12–1·15). About half of all vascular deaths in China were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg), accounting for approximately 1 million deaths (<80 years of age) annually.
Among adults in China, systolic blood pressure was continuously related to major vascular disease with no evidence of a threshold down to 120 mm Hg. Unlike previous studies in high-income countries, blood pressure was more strongly associated with intracerebral haemorrhage than with ischaemic stroke. Even small reductions in mean blood pressure at a population level could be expected to have a major impact on vascular morbidity and mortality.
UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, and the National Science Foundation of China.
Integrated analyses of plasma proteomic and genetic markers in prospective studies can clarify the causal relevance of proteins and discover novel targets for ischemic heart disease (IHD) and other ...diseases.
The purpose of this study was to examine associations of proteomics and genetics data with IHD in population studies to discover novel preventive treatments.
We conducted a nested case-cohort study in the China Kadoorie Biobank (CKB) involving 1,971 incident IHD cases and 2,001 subcohort participants who were genotyped and free of prior cardiovascular disease. We measured 1,463 proteins in the stored baseline samples using the OLINK EXPLORE panel. Cox regression yielded adjusted HRs for IHD associated with individual proteins after accounting for multiple testing. Moreover, cis-protein quantitative loci (pQTLs) identified for proteins in genome-wide association studies of CKB and of UK Biobank were used as instrumental variables in separate 2-sample Mendelian randomization (MR) studies involving global CARDIOGRAM+C4D consortium (210,842 IHD cases and 1,378,170 controls).
Overall 361 proteins were significantly associated at false discovery rate <0.05 with risk of IHD (349 positively, 12 inversely) in CKB, including N-terminal prohormone of brain natriuretic peptide and proprotein convertase subtilisin/kexin type 9. Of these 361 proteins, 212 had cis-pQTLs in CKB, and MR analyses of 198 variants in CARDIOGRAM+C4D identified 13 proteins that showed potentially causal associations with IHD. Independent MR analyses of 307 cis-pQTLs identified in Europeans replicated associations for 4 proteins (FURIN, proteinase-activated receptor-1, Asialoglycoprotein receptor-1, and matrix metalloproteinase-3). Further downstream analyses showed that FURIN, which is highly expressed in endothelial cells, is a potential novel target and matrix metalloproteinase-3 a potential repurposing target for IHD.
Integrated analyses of proteomic and genetic data in Chinese and European adults provided causal support for FURIN and multiple other proteins as potential novel drug targets for treatment of IHD.
Worldwide 350 million people suffer from major depression, with the majority of cases occurring in low- and middle-income countries. We examined the patterns, correlates and care-seeking behaviour of ...adults suffering from major depressive episode (MDE) in China.
A nationwide study recruited 512 891 adults aged 30-79 years from 10 provinces across China during 2004-2008. The 12-month prevalence of MDE was assessed by the Modified Composite International Diagnostic Interview-short form. Logistic regression yielded adjusted odds ratios (ORs) of MDE associated with socio-economic, lifestyle and health-related factors and major stressful life events.
Overall, 0.7% of participants had MDE and a further 2.4% had major depressive symptoms. Stressful life events were strongly associated with MDE adjusted OR 14.7, 95% confidence interval (CI) 13.7-15.7, with a dose-response relationship with the number of such events experienced. Family conflict had the highest OR for MDE (18.9, 95% CI 16.8-21.2) among the 10 stressful life events. The risk of MDE was also positively associated with rural residency (OR 1.5, 95% CI 1.4-1.7), low income (OR 2.3, 95% CI 2.1-2.4), living alone (OR 2.6, 95% CI 2.3-3.0), smoking (OR 1.4, 95% CI 1.3-1.6) and certain other mental disorders (e.g. anxiety, phobia). Similar, albeit weaker, associations were observed with depressive symptoms. Among those with MDE, about 15% sought medical help or took psychiatric medication, 15% reported having suicidal ideation and 6% reported attempting suicide.
Among Chinese adults, the patterns and correlates of MDE were generally consistent with those observed in the West. The low rates of seeking professional help and treatment highlight the great gap in mental health services in China.
High body mass index (BMI) has been associated with an increased risk of several cancers. Evidence relating body fatness, especially based on different anthropometric measures, to risk of major ...cancers in China from prospective cohort studies is lacking. The prospective China Kadoorie Biobank study recruited 0.5 million adults aged 30–79 years from 10 diverse areas across China during 2004–2008, recording 21,474 incident cancers during 8.95 years of follow‐up. BMI, body fat percentage (BFP), waist circumference (WC) and waist‐to‐hip ratio (WHR) were measured at baseline. We assessed the associations of body fatness with 15 major cancers by calculating Cox regression yielded adjusted hazard ratios (HRs). Each 5 kg/m2 increase in BMI was associated with an increased risk of endometrial (HR, 2.01; 95% CI, 1.72–2.35), postmenopausal breast (HR, 1.29; 95% CI, 1.18–1.40), colorectal (HR, 1.17; 95% CI, 1.10–1.25) and cervical (HR, 1.15; 95% CI, 1.03–1.29) cancer, whereas it was associated with a reduced risk of esophageal (HR, 0.73; 95% CI, 0.67–0.79), lung (HR, 0.78; 95% CI, 0.74–0.82), liver (HR, 0.85; 95% CI, 0.79–0.92) and gastric (HR, 0.88; 95% CI, 0.82–0.94) cancer. Significant linear trends of BMI‐cancer associations were observed, excluding for lung, gastric and cervical cancer (both overall and nonlinear p < 0.05). The relation between BFP, WC and WHR and the above cancers was similar to that of BMI. Our study indicates that either high or low body fatness contributes to the incidence of different types of cancer in China.
What's new?
Obesity and overweight are associated with an increased risk of several cancers. However, most studies have focused only on Caucasian populations. In this large, prospective study of people in China, the authors found that a high BMI was again associated with significantly increased risks, specifically for endometrial, breast, colorectal, and cervical cancers. (Surprisingly, high BMI appeared to reduce the risk of esophageal, lung, liver, and gastric cancers.) These results highlight the importance of encouraging healthy levels of body fat in the Chinese population.
Abstract
Background
The relevance of folic acid for stroke prevention in low-folate populations such as in China is uncertain. Genetic studies of the methylenetetrahydrofolate reductase (MTHFR) C677T ...polymorphism, which increases plasma homocysteine (tHcy) levels, could clarify the causal relevance of elevated tHcy levels for stroke, ischaemic heart disease (IHD) and other diseases in populations without folic acid fortification.
Methods
In the prospective China Kadoorie Biobank, 156 253 participants were genotyped for MTHFR and 12 240 developed a stroke during the 12-year follow-up. Logistic regression was used to estimate region-specific odds ratios (ORs) for total stroke and stroke types, IHD and other diseases comparing TT genotype for MTHFR C677T (two thymine alleles at position 677 of MTHFR C677T polymorphism) vs CC (two cytosine alleles) after adjustment for age and sex, and these were combined using inverse-variance weighting.
Results
Overall, 21% of participants had TT genotypes, but this varied from 5% to 41% across the 10 study regions. Individuals with TT genotypes had 13% (adjusted OR 1.13, 95% CI 1.09–1.17) higher risks of any stroke with a 2-fold stronger association with intracerebral haemorrhage (1.24, 1.17–1.32) than for ischaemic stroke (1.11, 1.07–1.15) than the reference CC genotype. In contrast, MTHFR C677T was unrelated to risk of IHD or any other non-vascular diseases, including cancer, diabetes and chronic obstructive lung disease.
Conclusions
In Chinese adults, the MTHFR C677T polymorphism was associated with higher risks of stroke. The findings warrant corroboration by further trials of folic acid and implementation of mandatory folic acid fortification programmes for stroke prevention in low-folate populations.
Little is known about the long-term risks of stroke and ischemic heart disease (IHD) in women who had a hysterectomy alone (HA) or with bilateral oophorectomy (HBO) for benign diseases, particularly ...in China where the burden of cardiovascular diseases (CVD) is high. We assessed mean levels of cardiovascular risk factors and relative risks of stroke and IHD in Chinese women who had a HA or HBO.
A total of 302 510 women, aged 30 to 79 years were enrolled in the China Kadoorie Biobank from 2004 to 2008 and followed up for a mean of 9.8 years. The analysis involved premenopausal women without prior cardiovascular disease or cancer at enrollment. We calculated adjusted hazard ratios for incident cases of CVD and their pathological types (ischemic stroke, hemorrhagic stroke, and IHD) after HA and HBO. Analyses were stratified by age and region and adjusted for levels of education, household income, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diabetes, self-reported health, and number of pregnancies.
Among 282 722 eligible women, 8478 had HA, and 1360 had HBO. Women who had HA had 9% higher risk of CVD after HA (hazard ratio, 1.09 95% CI, 1.06-1.12) and 19% higher risk of CVD after HBO (1.19 95% CI, 1.12-1.26) compared with women who did not. Both HA and HBO were associated with higher risks of ischemic stroke and IHD but not with hemorrhagic stroke. The relative risks of CVD associated with HA and HBO were more extreme at younger age of surgery.
Women who had either HA or HBO have higher risks of ischemic stroke and IHD, and these risks should be evaluated when discussing these interventions. Additional screening for risk factors for CVD should be considered in women following HA and HBO operations, especially if such operations are performed at younger age.
Early-life development plays a key role in adult type 2 diabetes (T2D), but the extent to which this can be attenuated by lifestyle is unknown.
The aim was to investigate the independent relevance of ...genetic predisposition to low birth weight and childhood obesity for T2D, and their attenuation, by adherence to a healthy lifestyle in adulthood.
Genetic risk scores (GRSs) were estimated for birth weight and childhood BMI with genetic risk categories according to their quintiles in 90,029 and 321,225 participants from the China Kadoorie Biobank (CKB; mean age, 53.0 y) and UK Biobank (UKB; 56.1 y). Healthy lifestyle scores were defined on noncurrent smoking, moderate alcohol consumption, healthy diet, regular physical activity, and nonobesity, and categorized into healthy (4∼5 factors), intermediate (2∼3 factors), and unhealthy (0∼1 factor) lifestyle.
GRSs for low birth weight and childhood BMI were associated with higher T2D risks. Healthy lifestyle was related to lower T2D risk, and there was an additive interaction with increasing childhood BMI GRS and decreasing healthy lifestyle factors on T2D risk, whereas no additive interaction was observed for birth weight. Participants with a healthy compared with an unhealthy lifestyle had a 68% (HR: 0.32; 95% CI: 0.22, 0.47) and 77% (0.23; 0.19, 0.28) lower T2D risk among participants at high genetic risk (lowest quintile) of low birth weight in the CKB and UKB. Among participants with high genetic risk (highest quintile) of childhood obesity, compared with those with an unhealthy lifestyle, adherence to a healthy lifestyle was associated with a 69% (0.31; 0.22, 0.46) and 80% (0.20; 0.17, 0.25) lower risk of T2D in the CKB and UKB.
Genetic predisposition to low birth weight and childhood obesity were associated with higher risk of adult T2D and these excess risks were attenuated by adherence to a healthy lifestyle in adulthood, particularly among those at high genetic risk of childhood obesity.
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Lower consumption of whole grains is associated with higher risks of diabetes and coronary heart disease in Western populations, but evidence is still limited for stroke. Moreover, little is known in ...China, where the rates of cardiometabolic diseases are high and the grain types consumed are different from those in Western countries.
To examine the associations between coarse-grain (e.g., millet, corn, and sorghum) consumption and incident cardiometabolic diseases among Chinese adults.
The prospective China Kadoorie Biobank enrolled >0.5 million adults aged 30–79 years from 10 urban and rural areas during 2004–2008. At baseline, consumption frequencies (in 5 categories from “never” to “daily”) of 12 major food groups, including coarse grains, were collected using a validated FFQ. After a median of 11 years of follow-up, 17,149 cases of diabetes, 29,876 ischemic strokes, 6097 hemorrhagic strokes, and 6704 major coronary events were recorded among 461,047 participants without a prevalence of major chronic diseases at baseline. Cox regression analyses were used to yield adjusted HRs for each disease associated with coarse-grain consumption.
Overall, 13.8% of participants reported regularly consuming (i.e., ≥4 days/week, regular consumers) and 29.4% reported never or rarely consuming coarse grains (i.e., nonconsumers) at baseline. Compared with nonconsumers, regular consumers had lower risks of diabetes (adjusted HR, 0.88; 95% CI, 0.78–0.98) and ischemic stroke (adjusted HR, 0.86; 95% CI, 0.81–0.93), but not hemorrhagic stroke (adjusted HR, 0.96; 95% CI, 0.76–1.20) or major coronary events (adjusted HR, 0.95; 95% CI, 0.81–1.12). For diabetes and ischemic stroke, each 100 g/day increase in the usual intake of coarse grains was associated with 14% (adjusted HR, 0.86; 95% CI, 0.76–0.97) and 13% (adjusted HR, 0.87; 95% CI, 0.81–0.94) lower risks, respectively, with similar results in various subgroups.
In Chinese adults, higher coarse-grain consumption is associated with lower risks of diabetes and ischemic stroke, supporting the promotion of coarse-grain consumption in China.
Randomised control trials and genetic analyses have demonstrated that vitamin D or 25-hydroxyvitamin D (25OHD) levels may not play a causal role in the development of cardiovascular disease. However, ...it is unclear if 25(OH)D is causally associated with cause-specific vascular disease and lipids. Therefore, we examined the causal association of 25(OH)D with myocardial infarction, stroke, ischaemic heart disease, ischaemic stroke, subarachnoid haemorrhage, intracerebral haemorrhage, and lipid levels among both Chinese and Europeans.
We used a Mendelian randomisation (MR) design in the China Kadoorie Biobank, the Copenhagen City Heart Study, and the Copenhagen General Population Study. The 25(OH)D-related genetic variants in the CYP2R1 and DCHR7 genes were genotyped in 99,012 Chinese adults and 106,911 Danish adults.
In Chinese adults, plasma 25(OH)D levels were not significantly associated with cause-specific vascular disease or mortality, with the exception of intracerebral haemorrhage (HR, 1.09 95% CI, 1.01,1.18 per 25 nmol/L higher plasma 25(OH)D). In Europeans, plasma 25(OH)D levels were inversely associated with all types of vascular diseases and mortality. However, MR analysis did not demonstrate causal associations of genetically increased 25(OH)D levels with cause-specific vascular diseases, or mortality in both Chinese and European adults. In addition, each 25 nmol/L higher 25(OH)D was observationally associated with lower total cholesterol and low-density lipoprotein cholesterol levels, but higher high-density lipoprotein cholesterol levels. Likewise, MR analysis showed that 25(OH)D levels were not causally associated with lipids in both Chinese and European adults after Bonferroni correction.
We found no evidence to support that genetically increased 25(OH)D was associated with a lower risk of ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and lipid levels in both Chinese and European adults. These results suggest that the inverse associations of vitamin D with vascular disease could be the result of confounding.
Current experimental and epidemiological studies provide inconsistent evidence toward the association between tea consumption and cancer incidence. We investigated whether tea consumption was ...associated with the incidence of all cancers and six leading types of cancer (lung cancer, stomach cancer, colorectal cancer, liver cancer, female breast cancer and cervix uteri cancer) among 455,981 participants aged 30–79 years in the prospective cohort China Kadoorie Biobank. Tea consumption was assessed at baseline (2004–2008) with an interviewer-administered questionnaire. Cancer cases were identified by linkage to the national health insurance system. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In the present population, daily tea consumers were more likely to be current smokers and daily alcohol consumers. 22,652 incident cancers occurred during 10.1 years follow-up (5.04 cases/1000 person-years). When we restricted analyses to non-smokers and non-excessive alcohol consumers to minimize confounding, tea consumption was not associated with all cancers (daily consumers who added tea leaves > 4.0 g/day vs. less-than-weekly consumers: HR, 1.03; 95% CI, 0.93–1.13), lung cancer (HR, 1.08; CI, 0.84–1.40), colorectal cancer (HR, 1.08; CI, 0.81–1.45) and liver cancer (HR, 1.08; CI, 0.75–1.55), yet might be associated with increased risk of stomach cancer (HR, 1.46; CI, 1.07–1.99). In both less-than-daily and daily tea consumers, all cancer risk increased with the amount of tobacco smoked or alcohol consumed. Our findings suggest tea consumption may not provide preventive effect against cancer incidence.
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