scholarly journals Age- and sex-specific modifiable risk factor profiles of dementia: evidence from the UK Biobank

2021 ◽  
Author(s):  
Hui Chen ◽  
Yaying Cao ◽  
Yuan Ma ◽  
Geng Zong ◽  
Changzheng Yuan
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Alcohol Intake ◽  
Health Condition ◽  
Modifiable Risk Factors ◽  
Uk Biobank ◽  
Younger Adults ◽  
Moderate Alcohol Intake ◽  
The Uk ◽  
Age And Sex

Abstract Background: To inform targeted preventive strategies of dementia, systematic investigation in its age- and sex-specific modifiable risk factor profiles in the general adult population is warranted.Methods: We used data of 372,867 adults free from dementia at baseline (2006-2010) in the UK Biobank, and followed them up until March 2021. We assigned participants into five groups according to their age and into two groups according to their sex. We estimated the age- and sex-specific hazard ratios (HRs) using Cox proportional hazard models and calculated the corresponding population attributable fractions (PAFs) for dementia attributable to three major categories of modifiable risk factors, including socioeconomic (low education level, high Townsend deprivation index), lifestyle (non-moderate alcohol intake, current smoking, suboptimal diet, non-regular physical exercise, and sleep duration <=6 or >=8 hrs/d), and health condition (hypertension, diabetes, cardiovascular diseases, and depressive symptom) risk factors.Findings: During 4,338,030 person-years of follow-up, 113, 146, 360, 1,087, and 2,002 of participants across five increasing age groups (40-<50, 50-<55, 55-<60, 60-<65, or >=65 y), respectively, were newly diagnosed with dementia. Five out of eleven modifiable risk factors showed significantly stronger associations with dementia among younger adults than in relatively older adults (P-interactions < 0.05), including non-moderate alcohol intake (HR [95% confidence interval, CI]=1.90 [1.35, 2.68] for participants 50-<55 y vs. 1.22 [1.11, 1.35] for participants > 65 y), suboptimal diet (1.86 [1.26, 2.74] for participants 40-< 50 y vs. 0.96 [0.86, 1.06] for participants > 65 y), hypertension (1.52 [0.96, 2.42] vs. 1.08 [0.99, 1.19]), CVD (4.20 [2.15, 8.22] vs. 1.64 [1.45, 1.85]), and diabetes (3.09 [1.60, 6.00] vs. 1.73 [1.51, 2.00]). We observed no significant difference in dementia risk factor profiles between women and men. Dementia cases attributable to three categories of risk factors all decreased with age, with the PAFs (95% CI) for sociodemographic, lifestyle, and health condition risk factors being 52.56% (22.98%, 82.15%), 46.57% (8.08%, 85.06%), and 35.42% (24.09%, 46.75%) for participants aged 40-<50 y, and 12.29% (3.82%, 20.75%), 13.01% (2.53%, 23.49%), and 15.85% (11.81%, 19.90%) for those over 65 y.Interpretation: This study identified stronger association and greater attributable risk of several modifiable risk factors for dementia among younger adults, underscoring the importance of preventive strategies from an earlier age across adult life course to reduce the risk of dementia.

scholarly journals Moderate alcohol intake promotes pancreatic ductal adenocarcinoma development in mice expressing oncogenic Kras

2020 ◽  
Vol 318 (2) ◽  
pp. G265-G276
Author(s):  
Kinji Asahina ◽  
Steven Balog ◽  
Edward Hwang ◽  
Eugene Moon ◽  
Emily Wan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Alcohol Drinking ◽  
Calcium Binding ◽  
Alcohol Intake ◽  
Western Diet ◽  
Mutant Mice ◽  
Ductal Adenocarcinoma ◽  
Moderate Alcohol Intake

Kras mutations are associated with pancreatic ductal adenocarcinoma (PDAC). Although tobacco smoking, pancreatitis, and obesity are known environmental risk factors for PDAC, the contribution of moderate alcohol intake to PDAC remains elusive. In the present study, we tested whether a combination of risk factors or moderate alcohol intake induces PDAC development in mice. Control Pdx1Cre and Pdx1Cre;LSL- KrasG12D mutant mice were fed a Western alcohol diet containing high levels of cholesterol and saturated fat, 3.5% alcohol, and lipopolysaccharide for 5 mo. In addition, mice were treated with cerulein, for induction of pancreatitis, and nicotine every month. Treatment with all of these risk factors promoted development of advanced pancreatic neoplasia and PDAC in the Pdx1Cre;LSL- KrasG12D mice but not in the control Pdx1Cre mice. Moderate alcohol intake or Western diet feeding also significantly promoted advanced neoplasia and PDAC development in Pdx1Cre;LSL- KrasG12D mice compared with mice fed a regular chow. Alcohol, but not Western diet, increased tumor development in the liver in the Pdx1Cre;LSL- KrasG12D mice, but its origin remained elusive due to leakiness of Pdx1Cre in hepatocytes. RNA-seq analysis revealed that alcohol feeding increases expression of markers for tumors ( Epcam, Krt19, Prom1, Wt1, and Wwtr1), stroma ( Dcn, Fn1, and Tnc), and cytokines ( Tgfb1 and Tnf) and decreases expression of Fgf21 and Il6 in the pancreatic tumor tissues. Immunostaining showed heterogeneous expression of nephronectin, S100 calcium-binding protein A6, and vascular cell adhesion molecule 1 in pancreatic tumors surrounded by podoplanin-positive stromal cells. Our data indicate that moderate alcohol drinking is a risk factor for development of PDAC. NEW & NOTEWORTHY Heavy alcohol intake has been suspected to be a risk factor of pancreatic ductal adenocarcinoma (PDAC) in humans. However, the contribution of moderate alcohol intake to PDAC development remains elusive. In the present study, we experimentally show that moderate alcohol feeding significantly induces advanced stages of pancreatic intraepithelial neoplasia development and invasive PDAC in Pdx1Cre;LSL- KrasG12D mutant mice. Our data indicate that moderate alcohol drinking is a risk factor for PDAC.

Variation of cardiac magnetic resonance radiomics features by age and sex in healthy participants from the UK Biobank

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Z Raisi-Estabragh ◽  
A Jaggi ◽  
N Aung ◽  
S Neubauer ◽  
S Piechnik ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiac Magnetic Resonance ◽  
Age Groups ◽  
Texture Features ◽  
Funding Source ◽  
Uk Biobank ◽  
Men And Women ◽  
The Uk ◽  
Age And Sex ◽  
Apparently Healthy

Abstract Introduction Cardiac magnetic resonance (CMR) radiomics use voxel-level data to derive quantitative indices of myocardial tissue texture, which may provide complementary risk information to traditional CMR measures. Purpose In this first stage of our work, establishing the performance characteristics of CMR radiomics in relation to disease outcomes, we aimed to elucidate differences in radiomic features by sex and age in apparently healthy adults. Methods We defined a healthy cohort from the first 5,065 individuals completing the UK Biobank Imaging Enhancement, limiting to white Caucasian ethnicity, and excluding those with major co-morbidities, or cardiovascular risk factors/symptoms. We created evenly distributed age groups: 45–54 years, 55–64 years, 65–74 years. Radiomics features were extracted from left ventricle segmentations, with normalisation to body surface area. We compared mean values of individual features between the sexes, stratified by age and separately between the oldest and youngest age groups for each sex. Results We studied 657 (309 men, 358 women) healthy individuals. There were significant differences between radiomics features of men and women. Different features appeared more important at different age groups. For instance, in the youngest age group “end-systolic coarseness” showed greatest difference between men and women, whilst “end-diastolic run percentage” and “end-diastolic high grey level emphasis” showed most variation in the oldest and middle age groups. In the oldest age groups, differences between men and women were most predominant in the texture features, whilst in the younger groups a mixture of shape and texture differences were observed. We demonstrate significant variation between radiomics features by age, these differences are exclusively in texture features with different features implicated in men and women (“end-diastolic mean intensity” in women, “end-systolic sum entropy in men”). Conclusions There are significant age and sex differences in CMR radiomics features of apparently healthy adults, demonstrating alterations in myocardial architecture not appreciated by conventional indices. In younger ages, shape and texture differences are observed, whilst in older ages texture differences dominate. Furthermore, texture features are the most different features between the youngest and oldest hearts. We provide proof-of-concept data indicating CMR radiomics has discriminatory value with regard to two characteristics strongly linked to cardiovascular outcomes. We will next elucidate relationships between CMR radiomics, cardiac risk factors, and clinical outcomes, establishing predictive value incremental to existing measures. Funding Acknowledgement Type of funding source: Other. Main funding source(s): European Union's Horizon 2020 research and innovation programme (825903),British Heart Foundation Clinical Research Training Fellowship (FS/17/81/33318)

scholarly journals Generalisability of Results from UK Biobank: Comparison With a Pooling of 18 Cohort Studies

2019 ◽  
Author(s):  
G. David Batty ◽  
Catharine R. Gale ◽  
Mika Kivimäki ◽  
Ian J. Deary ◽  
Steven Bell
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Health Surveys ◽  
Response Rate ◽  
P Value ◽  
Uk Biobank ◽  
Individual Level ◽  
Hazard Ratios ◽  
Nationally Representative ◽  
The Uk

AbstractBackgroundThe UK Biobank cohort study has become a much-utilised and influential scientific resource. With a primary goal of understanding disease aetiology, the low response to the original survey of 5.5% has, however, led to debate as to the generalisability of these findings. We therefore compared risk factor–disease estimations in UK Biobank with those from 18 nationally representative studies with conventional response rates.MethodsWe used individual-level baseline data from UK Biobank (N=502,655) and a pooling of data from the Health Surveys for England (HSE) and the Scottish Health Surveys (SHS), comprising 18 studies and 89,895 individuals (mean response rate 68%). Both study populations were aged 40-69 years at study induction and linked to national cause-specific mortality registries.FindingsDespite a typically more favourable risk factor profile and lower mortality rates in UK Biobank participants relative to the HSE-SHS consortium, risk factors–endpoints associations were directionally consistent between studies, albeit with some heterogeneity in magnitude. For instance, for cardiovascular disease mortality, the age- and sex-adjusted hazard ratio (95% confidence interval) for ever having smoked cigarettes (versus never) was 2.04 (1.87, 2.24) in UK Biobank and 1.99 (1.78, 2.23) in HSE-SHS, yielding a ratio of hazard ratios close to unity (1.02, 0.88, 1.19; p-value 0.76). For hypertension (versus none), corresponding results were again in same direction but with a lower effect size in UK Biobank (1.89; 1.69, 2.11) than in HSE-SHS (2.56; 2.20, 2.98), producing a ratio of hazard ratios below unity (0.74; 0.62, 0.89; p-value 0.001). A similar pattern of observations were made for risk factors (smoking, obesity, educational attainment, and physical stature) in relation to different cancer presentations and suicide whereby the ratios of hazard ratios ranged from 0.57 (0.40, 0.81) and 1.07 (0.42, 2.74).InterpretationDespite a low response rate, aetiological findings from UK Biobank appear to be generalisable to England and Scotland.

scholarly journals Burden of cancers attributable to modifiable risk factors in Malaysia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
H. S. Teh ◽  
Y. L. Woon
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Tobacco Smoking ◽  
Physical Inactivity ◽  
Alcohol Intake ◽  
Population Attributable Fraction ◽  
Excess Weight ◽  
Modifiable Risk Factors ◽  
Systematic Assessment ◽  
Two Parameters

Abstract Background This is a systematic assessment of the burden of cancers in Malaysia in 2018 using epidemiologic approach. The purpose of this study was to identify the proportion of cancers in Malaysia that were attributable to the modifiable risk factors of excess weight, alcohol intake, physical inactivity, tobacco smoking and to estimate the number of cancer cases that could be prevented if the exposure to the modifiable risk factor was reduced. Methods We estimated the Population Attributable Fraction (PAF) of the modifiable risk factors to cancers incidences in Malaysia. The two parameters used for the estimation were exposure prevalence from national representative surveys and the relative risk of getting the cancers from worldwide literature review. Results Among 38,426 cancer incidences in 2018 from Globocan data, we estimated that 22.2% (95% confidence interval (CI):14.9 to 29.6%) of the cancer incidences included in this study were attributable to the investigated modifiable risk factors. 39.1% (95% CI:27.2 to 49.7%) and 10.5% (95% CI:5.8 to 15.7%) of cancers in male and female respectively, were attributable to the studied modifiable risk factors. The top main cancers attributed by the risk factors were lung cancer (65.1%; 95% CI:56.4 to 72.9%), laryngeal cancer (63.6%; 95% CI:39.9 to 80.5%), and oesophageal cancer (51.5%; 95% CI:39.9 to 62.0%). For each risk factor studied across genders, tobacco smoking contributed the most (14.3%; 95% CI:9.9 to 17.3%), followed by excess weight (7.0%; 95% CI:4.1 to 10.2%), physical inactivity (1.0%; 95% CI:0.4 to 1.7%) and alcohol intake (0.6%; 95% CI:0.2 to 1.0%). Conclusion Findings from this study suggests that tobacco smoking and excess weight are the two predominant factors out of the four studied risk factors for cancer cases in Malaysia. Nationwide public health prevention campaigns tailored to these risk factors are recommended. However, the other risk factors such as physical inactivity and alcohol intake shall not be neglected. PAFs are estimated based on the best available data that we have currently. Regular collection of other risk factor exposure prevalence data is vital for future analyses.

scholarly journals Age and sex specific effects of APOE genotypes on ischemic heart disease and its risk factors in the UK Biobank

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mengyu Li ◽  
Jie V. Zhao ◽  
Man Ki Kwok ◽  
C. Mary Schooling
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Pulse Pressure ◽  
Glycated Haemoglobin ◽  
Ischemic Heart ◽  
Uk Biobank ◽  
The Uk ◽  
Age And Sex

AbstractAPOE genotypes are associated with ischemic heart disease (IHD), several other cardiovascular diseases and dementia. Previous studies have not comprehensively considered all genotypes, especially ε2ε2, nor associations by age and sex, although IHD incidence differs by sex. In the UK Biobank, including 391,992 white British participants, we compared effects of APOE genotypes on IHD and its risk factors. Compared to the ε3ε3 genotype, ε2ε2 was not clearly associated with IHD but was associated with lower plasma apolipoprotein B (apoB). The ε2ε3 genotype conferred lower IHD risk, systolic blood pressure (SBP), pulse pressure and plasma apoB than ε3ε3. ε3ε4 and ε4ε4 conferred higher IHD risk, higher pulse pressure and plasma apoB, but lower glycated haemoglobin (HbA1c) than ε3ε3. The associations by age and sex were fairly similar, except ε2ε2 compared to ε3ε3 was marginally positively associated with IHD in the younger age group and nominally inversely associated with SBP in men. ε3ε4 compared to ε3ε3 was nominally positively associated with SBP in women. APOE genotypes affect IHD risk increasingly from ε2ε3, ε3ε3, ε3ε4 to ε4ε4, with similar patterns for pulse pressure and plasma apoB, but not for diabetes. Associations with blood pressure differed by sex. Greater understanding of products of APOE and their effects might generate targets of intervention.

scholarly journals Calcification of abdominal aorta is an underappreciated cardiovascular disease risk factor

2020 ◽  
Author(s):  
Anurag Sethi ◽  
Leland Taylor ◽  
J Graham Ruby ◽  
Jagadish Venkataraman ◽  
Madeleine Cule ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Disease Risk ◽  
Cardiovascular Outcomes ◽  
Whole Body ◽  
Uk Biobank ◽  
Clinical Biomarkers ◽  
Wide Range ◽  
The Uk

AbstractBackgroundCalcification of the abdominal artery is an important contributor to cardiovascular disease in diabetic and chronic kidney disease (CKD) populations. However, prevalence of the pathology, risk factors, and long term disease outcomes in a general population have not been systematically analyzed.MethodWe developed machine learning models to quantify levels of abdominal aortic calcification (AAC) in 29,957 whole body dual-energy X-ray absorptiometry (DEXA) scans from the UK Biobank cohort. Using regression techniques we associated severity of calcification across a wide range of physiological parameters, clinical biomarkers, and environmental risk factors (406 in total). We performed a common variant genetic association study spanning 9,572,557 single-nucleotide polymorphisms to identify genetic loci relevant to AAC. We evaluated the prognostic value of AAC across 151 disease classes using Cox proportional hazard models. We further examined an epidemiological model of calcification on cardiovascular morbidity with and without LDL interactions.FindingsWe find evidence for AAC in >10.4% of the cohort despite low prevalence of diabetes (2.5%) and CKD (0.5%). Increased level of AAC is a strong prognostic indicator of cardiovascular outcomes for stenosis of precerebral arteries (HR~1.5), Myocardial Infarction (HR~1.5), & Ischemic Heart Disease (HR~1.33). We find that AAC is genetically correlated with cardiovascular-related traits and that the genetic signals are enriched in vascular and adipose tissue. We report three loci associated with AAC, with the strongest association occuring at the TWIST1/HDAC9 locus (beta=0.078, p-value=1.4e-11) in a region also associated with coronary artery disease. Surprisingly, we find that elevated but still within clinically normal levels of serum phosphate and glycated hemoglobin are linked to increased vascular calcification. Furthermore, we show AAC arises in the absence of hypercholesterolemia. By our estimate, AAC is an LDL-independent risk factor for cardiovascular outcomes, with risk similar to elevated LDL.DataThis research has been conducted using the UK Biobank Resource.

scholarly journals 699 Sleep Health Traits and COVID-19: Mortality Risk from the UK Biobank

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A273-A273
Author(s):  
Xi Zheng ◽  
Ma Cherrysse Ulsa ◽  
Peng Li ◽  
Lei Gao ◽  
Kun Hu
Keyword(s):  
Risk Factors ◽  
Sleep Apnea ◽  
Sleep Duration ◽  
Sex Education ◽  
Mortality Risk ◽  
Self Report ◽  
Severe Illness ◽  
Uk Biobank ◽  
Sleep Health ◽  
The Uk

Abstract Introduction While there is emerging evidence for acute sleep disruption in the aftermath of coronavirus disease 2019 (COVID-19), it is unknown whether sleep traits contribute to mortality risk. In this study, we tested whether earlier-life sleep duration, chronotype, insomnia, napping or sleep apnea were associated with increased 30-day COVID-19 mortality. Methods We included 34,711 participants from the UK Biobank, who presented for COVID-19 testing between March and October 2020 (mean age at diagnosis: 69.4±8.3; range 50.2–84.6). Self-reported sleep duration (less than 6h/6-9h/more than 9h), chronotype (“morning”/”intermediate”/”evening”), daytime dozing (often/rarely), insomnia (often/rarely), napping (often/rarely) and presence of sleep apnea (ICD-10 or self-report) were obtained between 2006 and 2010. Multivariate logistic regression models were used to adjust for age, sex, education, socioeconomic status, and relevant risk factors (BMI, hypertension, diabetes, respiratory diseases, smoking, and alcohol). Results The mean time between sleep measures and COVID-19 testing was 11.6±0.9 years. Overall, 5,066 (14.6%) were positive. In those who were positive, 355 (7.0%) died within 30 days (median = 8) after diagnosis. Long sleepers (&gt;9h vs. 6-9h) [20/103 (19.4%) vs. 300/4,573 (6.6%); OR 2.09, 95% 1.19–3.64, p=0.009), often daytime dozers (OR 1.68, 95% 1.04–2.72, p=0.03), and nappers (OR 1.52, 95% 1.04–2.23, p=0.03) were at greater odds of mortality. Prior diagnosis of sleep apnea also saw a two-fold increased odds (OR 2.07, 95% CI: 1.25–3.44 p=0.005). No associations were seen for short sleepers, chronotype or insomnia with COVID-19 mortality. Conclusion Data across all current waves of infection show that prior sleep traits/disturbances, in particular long sleep duration, daytime dozing, napping and sleep apnea, are associated with increased 30-day mortality after COVID-19, independent of health-related risk factors. While sleep health traits may reflect unmeasured poor health, further work is warranted to examine the exact underlying mechanisms, and to test whether sleep health optimization offers resilience to severe illness from COVID-19. Support (if any) NIH [T32GM007592 and R03AG067985 to L.G. RF1AG059867, RF1AG064312, to K.H.], the BrightFocus Foundation A2020886S to P.L. and the Foundation of Anesthesia Education and Research MRTG-02-15-2020 to L.G.

scholarly journals Sex differences in the association between major cardiovascular risk factors in midlife and dementia: a cohort study using data from the UK Biobank

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jessica Gong ◽  
Katie Harris ◽  
Sanne A. E. Peters ◽  
Mark Woodward
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Sex Differences ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Sex Difference ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Uk Biobank ◽  
The Uk

Abstract Background Sex differences in major cardiovascular risk factors for incident (fatal or non-fatal) all-cause dementia were assessed in the UK Biobank. The effects of these risk factors on all-cause dementia were explored by age and socioeconomic status (SES). Methods Cox proportional hazards models were used to estimate hazard ratios (HRs) and women-to-men ratio of HRs (RHR) with 95% confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP), smoking, diabetes, adiposity, stroke, SES and lipids with dementia. Poisson regression was used to estimate the sex-specific incidence rate of dementia for these risk factors. Results 502,226 individuals in midlife (54.4% women, mean age 56.5 years) with no prevalent dementia were included in the analyses. Over 11.8 years (median), 4068 participants (45.9% women) developed dementia. The crude incidence rates were 5.88 [95% CI 5.62–6.16] for women and 8.42 [8.07–8.78] for men, per 10,000 person-years. Sex was associated with the risk of dementia, where the risk was lower in women than men (HR = 0.83 [0.77–0.89]). Current smoking, diabetes, high adiposity, prior stroke and low SES were associated with a greater risk of dementia, similarly in women and men. The relationship between blood pressure (BP) and dementia was U-shaped in men but had a dose-response relationship in women: the HR for SBP per 20 mmHg was 1.08 [1.02–1.13] in women and 0.98 [0.93–1.03] in men. This sex difference was not affected by the use of antihypertensive medication at baseline. The sex difference in the effect of raised BP was consistent for dementia subtypes (vascular dementia and Alzheimer’s disease). Conclusions Several mid-life cardiovascular risk factors were associated with dementia similarly in women and men, but not raised BP. Future bespoke BP-lowering trials are necessary to understand its role in restricting cognitive decline and to clarify any sex difference.

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