10 research outputs found

    Contrasting male and female trends in tobacco-attributed mortality in China:evidence from successive nationwide prospective cohort studies

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    SummaryBackgroundChinese 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.MethodsTwo 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.FindingsTwo-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.InterpretationSmoking 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.FundingWellcome Trust, MRC, BHF, CR-UK, Kadoorie Charitable Foundation, Chinese MoST and NSF

    The Surtsey volcano geothermal system: An analogue for seawater-oceanic crust interaction with implications for the elemental budget of the oceanic crust

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    Pre-print (ĂłritrĂœnt handrit)Surtsey is a young volcanic island in the offshore extension of Iceland's southeast rift zone that grew from the seafloor during explosive and effusive eruptions in 1963–1967. In 1979, a cored borehole (SE-1) was drilled to 181 m depth and in 2017 three cored boreholes (SE-2a, SE-2b and SE-3) were drilled to successively greater depths. The basaltic deposits host a low-temperature (40–141 °C) seawater-dominated geothermal system. Surtsey provides an ideal environment to study water-rock interaction processes in a young seawater geothermal system. Elemental concentrations (SiO2, B, Na, Ca, Mg, F, dissolved inorganic carbon, SO4, Cl) and isotope contents (ÎŽD, ÎŽ18O) in borehole fluids indicate that associated geothermal waters in submarine deposits originated from seawater modified by reactions with the surrounding basalt. These processes produce authigenic minerals in the basaltic lapilli tuff and a corresponding depletion of certain elements in the residual waters. Coupling of measured and modelled concentrations investigates the effect of temperature and associated abundance of authigenic minerals on chemical fluxes from and to the igneous oceanic crust during low-temperature alteration. The annual chemical fluxes calculated at 50–150 °C range from −0.01 to +0.1×1012 mol yr−1 for SiO2, +0.2 to +129×1012 mol yr−1 for Ca, −129 to −0.8×1012 mol yr−1 for Mg and −21 to +0.4 × 1012 mol yr−1 for SO4 where negative values indicate chemical fluxes from the ocean into the oceanic crust and positive values indicate fluxes from the oceanic crust to the oceans. These flux calculations reveal that water-rock interaction at varying water-rock ratios and temperatures produces authigenic minerals that serve as important sinks of seawater-derived SiO2, Mg and SO4. In contrast, water rock interaction accompanied by dissolution of basaltic glass and primary crystal fragments provides a significant source of Ca. Such low-temperature alteration could effectively influence the elemental budget of the oceanic igneous crust and ocean waters. The modeling provides insights into water chemistries and chemical fluxes in low temperature MOR recharge zones. Surtsey also provides a valuable young analogue for assessing the chemical evolution of fluid discharge over the life cycles of seamounts in ridge flank systems.Funding for this project was provided by the University of Iceland Recruitment fund, the International Continental Scientific Drilling Program (ICDP) through a grant to the SUSTAIN project, the Icelandic Science Fund, ICF-RANNÍS, the Bergen Research Foundation and K.G. Jebsen Centre for Deep Sea Research at University of Bergen, Norway, the German Research Foundation (DFG), and DiSTAR, Federico II, University of Naples, Federico II, Italy. The University of Utah, USA and the two Icelandic power companies ReykjavĂ­k Energy and Landsvirkjun, contributed additional funds. The authors would like to thank P. Bergsten, A.M. di Stefano, C.F. Gorny, J. Gunnarsson-Robin, G.H. GuĂ°finsson, Þ. HögnadĂłttir, E.W. Marshall, R. ÓlafssdĂłttir, D.B. Ragnarsson and Þ.M. ÞorbjarnardĂłttir for their contribution and assistance during sampling, sample preparation, analyses and data evaluation. The authors would like to thank M. E. Böttcher for careful editorial handling. Two anonymous reviewers and J. Alt are thanked for their thoughtful and valuable reviews

    Vitamin D and cause-specific vascular disease and mortality:a Mendelian randomisation study involving 99,012 Chinese and 106,911 European adults

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    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    Evaluation of type 2 diabetes genetic risk variants in Chinese adults: findings from 93,000 individuals from the China Kadoorie Biobank

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    Genome-wide association studies (GWAS) have discovered many risk variants for type 2 diabetes. However, estimates of the contributions of risk variants to type 2 diabetes predisposition are often based on highly selected case-control samples, and reliable estimates of population-level effect sizes are missing, especially in non-European populations.The individual and cumulative effects of 59 established type 2 diabetes risk loci were measured in a population-based China Kadoorie Biobank (CKB) study of 93,000 Chinese adults, including &gt;7,100 diabetes cases.Association signals were directionally consistent between CKB and the original discovery GWAS: of 56 variants passing quality control, 48 showed the same direction of effect (binomial test, p = 2.3 × 10(-8)). We observed a consistent overall trend towards lower risk variant effect sizes in CKB than in case-control samples of GWAS meta-analyses (mean 19-22% decrease in log odds, p ≀ 0.0048), likely to reflect correction of both 'winner's curse' and spectrum bias effects. The association with risk of diabetes of a genetic risk score, based on lead variants at 25 loci considered to act through beta cell function, demonstrated significant interactions with several measures of adiposity (BMI, waist circumference [WC], WHR and percentage body fat [PBF]; all p interaction &lt; 1 × 10(-4)), with a greater effect being observed in leaner adults.Our study provides further evidence of shared genetic architecture for type 2 diabetes between Europeans and East Asians. It also indicates that even very large GWAS meta-analyses may be vulnerable to substantial inflation of effect size estimates, compared with those observed in large-scale population-based cohort studies.Details of how to access China Kadoorie Biobank data and details of the data release schedule are available from www.ckbiobank.org/site/Data+Access

    Adiposity and risk of ischaemic and haemorrhagic stroke in 0·5 million Chinese men and women: a prospective cohort study

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    Summary: Background: 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. Methods: 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. Findings: 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). Interpretation: 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. Funding: 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

    Causal association between snoring and stroke: a Mendelian randomization study in a Chinese populationResearch in context

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    Summary: Background: Previous observational studies established a positive relationship between snoring and stroke. We aimed to investigate the causal effect of snoring on stroke. Methods: Based on 82,339 unrelated individuals with qualified genotyping data of Asian descent from the China Kadoorie Biobank (CKB), we conducted a Mendelian randomization (MR) analysis of snoring and stroke. Genetic variants identified in the genome-wide association analysis (GWAS) of snoring in CKB and UK Biobank (UKB) were selected for constructing genetic risk scores (GRS). A two-stage method was applied to estimate the associations of the genetically predicted snoring with stroke and its subtypes. Besides, MR analysis among the non-obese group (body mass index, BMI <24.0 kg/m2), as well as multivariable MR (MVMR), were performed to control for potential pleiotropy from BMI. In addition, the inverse-variance weighted (IVW) method was applied to estimate the causal association with genetic variants identified in CKB GWAS. Findings: Positive associations were found between snoring and total stroke, hemorrhagic stroke (HS), and ischemic stroke (IS). With GRS of CKB, the corresponding HRs (95% CIs) were 1.56 (1.15, 2.12), 1.50 (0.84, 2.69), 2.02 (1.36, 3.01), and the corresponding HRs (95% CIs) using GRS of UKB were 1.78 (1.30, 2.43), 1.94 (1.07, 3.52), and 1.74 (1.16, 2.61). The associations remained stable in the MR among the non-obese group, MVMR analysis, and MR analysis using the IVW method. Interpretation: This study suggests that, among Chinese adults, genetically predicted snoring could increase the risk of total stroke, IS, and HS, and the causal effect was independent of BMI. Funding: National Natural Science Foundation of China, Kadoorie Charitable Foundation Hong Kong, UK Wellcome Trust, National Key R&D Program of China, Chinese Ministry of Science and Technology

    Age-specific association between blood pressure and vascular and non-vascular chronic diseases in 0·5 million adults in China: a prospective cohort study

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    Summary: Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: 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
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