scholarly journals Transthyretin-stabilizing mutation T119M is not associated with protection against vascular disease or death in the UK Biobank

2019 ◽  
Author(s):  
Margaret M. Parker ◽  
Simina Ticau ◽  
James Butler ◽  
David Erbe ◽  
Madeline Merkel ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cerebrovascular Disease ◽  
Vascular Disease ◽  
Prospective Cohort ◽  
Proportional Hazards ◽  
Disease Diagnosis ◽  
Cox Proportional Hazards ◽  
Uk Biobank ◽  
The Uk ◽  
Large Prospective Cohort

AbstractBackgroundDestabilized transthyretin (TTR) can result in the progressive, fatal disease transthyretin-mediated (ATTR) amyloidosis. A stabilizing TTR mutation, T119M, is the basis for a therapeutic strategy to reduce destabilized TTR. Recently, T119M was associated with extended lifespan and lower risk of cerebrovascular disease in a Danish cohort. We aimed to determine whether this finding could be replicated in the UK Biobank.MethodsTTR T119M carriers were identified in the UK Biobank, a large prospective cohort of ∼500,000 individuals. Association between T119M genotype and inpatient diagnosis of vascular disease, cardiovascular disease, cerebrovascular disease, and mortality was analyzed.ResultsFrequency of T119M within the white UK Biobank population (n=337,148) was 0.4%. Logistic regression comparing T119M carriers to non-carriers found no association between T119M and vascular disease (odds ratio [OR]=1.08; p=.27), cardiovascular disease (OR=1.08; p=.31), cerebrovascular disease (OR=1.1; p=.42), or death (OR=1.2; p=.06). Cox proportional hazards regression showed similar results (hazard ratio>1, p>.05). Age at death and vascular disease diagnosis were similar between T119M carriers and non-carriers (p=.12 and p=.38, respectively).ConclusionsThere was no association between the TTR T119M genotype and risk of vascular disease or death in a large prospective cohort study, indicating that TTR tetramer stabilization through T119M is not protective in this setting.

scholarly journals A semi-supervised approach for rapidly creating clinical biomarker phenotypes in the UK Biobank using different primary care EHR and clinical terminology systems

JAMIA Open ◽  
2020 ◽  
Author(s):  
Spiros Denaxas ◽  
Anoop D Shah ◽  
Bilal A Mateen ◽  
Valerie Kuan ◽  
Jennifer K Quint ◽  
...  
Keyword(s):  
Primary Care ◽  
Proportional Hazards ◽  
Biomarker Discovery ◽  
Data Extraction ◽  
Cox Proportional Hazards ◽  
Research Quality ◽  
Uk Biobank ◽  
Expert Review ◽  
Cox Proportional Hazards Models ◽  
The Uk

Abstract Objectives The UK Biobank (UKB) is making primary care electronic health records (EHRs) for 500 000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: (a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and (b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers. Materials and Methods We describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving (a) bootstrapping definitions using existing phenotypes, (b) excluding generic, rare, or semantically distant terms, (c) forward-mapping terminology terms, (d) expert review, and (e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models. Results We created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID-19 complications, for example diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38 190 682 events and identified 220 978 participants with at least one biomarker measured. Discussion and conclusion Bootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.

scholarly journals Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study

2020 ◽  
pp. annrheumdis-2020-217176 ◽  
Author(s):  
Zhi-Hao Li ◽  
Xiang Gao ◽  
Vincent CH Chung ◽  
Wen-Fang Zhong ◽  
Qi Fu ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Digestive Disease ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Respiratory Mortality ◽  
All Cause Mortality ◽  
Specific Mortality ◽  
Large Prospective Cohort

ObjectivesTo evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort.MethodsThis population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables.ResultsAt baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3–9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080).ConclusionsRegular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

Osteoporosis and Its Association With Cardiovascular Disease, Respiratory Disease, and Cancer: Findings From the UK Biobank Prospective Cohort Study

2022 ◽  
Vol 97 (1) ◽  
pp. 110-121
Author(s):  
Irene Rodríguez-Gómez ◽  
Stuart R. Gray ◽  
Frederick K. Ho ◽  
Fanny Petermann-Rocha ◽  
Paul Welsh ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cohort Study ◽  
Respiratory Disease ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Uk Biobank ◽  
The Uk

scholarly journals Sex differences in the association between childhood maltreatment and cardiovascular disease in the UK Biobank

Heart ◽  
2020 ◽  
Vol 106 (17) ◽  
pp. 1310-1316 ◽  
Author(s):  
Ana Luiza Gonçalves Soares ◽  
Gemma Hammerton ◽  
Laura D Howe ◽  
Janet Rich-Edwards ◽  
Sarah Halligan ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Sexual Abuse ◽  
Cerebrovascular Disease ◽  
Age Differences ◽  
Childhood Maltreatment ◽  
Early Onset ◽  
Uk Biobank ◽  
Hypertensive Disease ◽  
The Uk ◽  
Socioeconomic And Demographic Factors

ObjectivesTo assess and compare associations between childhood maltreatment and cardiovascular disease (CVD) in men and women in the UK. In secondary analyses, we also explored possible age differences and associations with early onset CVD (<50 years).MethodsWe included 157 311 participants from the UK Biobank who had information on physical, sexual or emotional abuse, emotional or physical neglect. CVD outcomes were defined as any CVD, hypertensive disease, ischaemic heart disease (IHD) and cerebrovascular disease. These were extracted from self-report, blood pressure measurements, hospital register and death register. The associations between maltreatment and CVD were assessed using Poisson regression with robust variance to estimate risk ratios, stratified by sex and adjusted for socioeconomic and demographic factors.ResultsAll types of maltreatment were associated with increased risk of CVD and IHD in both sexes. Additionally, in women all types of maltreatment were associated with higher risk of hypertensive disease, and all, except emotional neglect, were associated with cerebrovascular disease. In men, all but sexual abuse, were associated with higher risk of hypertensive disease, and all, except physical and sexual abuse, were associated with cerebrovascular disease. Associations were generally stronger in women, and individuals who were younger at baseline had stronger associations of childhood maltreatment with any CVD and IHD, but age differences were less evident when only early onset CVD was considered.ConclusionsChildhood maltreatment was consistently associated with CVD and stronger associations were generally observed in women and seemed to be stronger for early onset CVD.

scholarly journals Association between physical activity, grip strength and sedentary behaviour with incidence of malignant melanoma: results from the UK Biobank

2021 ◽  
Author(s):  
Andrea Weber ◽  
Michael F. Leitzmann ◽  
Anja M. Sedlmeier ◽  
Hansjörg Baurecht ◽  
Carmen Jochem ◽  
...  
Keyword(s):  
Physical Activity ◽  
Malignant Melanoma ◽  
Grip Strength ◽  
Sedentary Behaviour ◽  
Proportional Hazards ◽  
Short Form ◽  
Positive Association ◽  
Cox Proportional Hazards ◽  
Uk Biobank ◽  
The Uk

Abstract Background Physical activity has been positively related to malignant melanoma. However, that association may be confounded by ultraviolet radiation (UV), a variable closely related to both outdoor physical activity and malignant melanoma. We examined physical activity, grip strength and sedentary behaviour in relation to risk of malignant melanoma, accounting for relevant confounders using data from a prospective cohort study. Methods In 350,512 UK Biobank participants aged 38–73 years at baseline, physical activity was assessed with a modified version of the International Physical Activity Questionnaire Short Form, grip strength was measured with a hand dynamometer, and sedentary behaviour was recorded with three specific questions. Multivariable hazard ratios (HR) and corresponding 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Results During 7 years of follow-up, 1239 incident malignant melanoma diagnoses were recorded. Physical activity and sedentary behaviour were unrelated to malignant melanoma (HRs 1.01 (95% CI 0.95–1.07) and 1.04 (95% CI 0.97–1.12), respectively), and the initially positive association with grip strength in the basic model (HR 1.23, 95% CI 1.08–1.40) was attenuated after full adjustment (HR 1.10, 95% CI 0.96–1.26). Conclusion Physical activity, grip strength and sedentary behaviour are not associated with malignant melanoma risk.

scholarly journals Hypertension Subtype Defined by the 2017 ACC/AHA Blood Pressure Guidelines and Risk of Cardiovascular Disease: A Large Prospective Cohort Study

2020 ◽  
Author(s):  
Fu-Rong Li ◽  
Xian-Bo Wu
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Cohort Study ◽  
Proportional Hazards ◽  
Blood Pressure Level ◽  
Cox Proportional Hazards ◽  
Cvd Risk ◽  
Increased Risk ◽  
Diastolic Hypertension ◽  
The Uk

AbstractBackgroundThe 2017 American College of Cardiology/American Heart Association (ACC/ AHA) blood pressure (BP) guideline lowered the hypertension threshold from a systolic blood pressure/diastolic blood pressure level of ≥140/90 mm Hg to ≥130/80 mm Hg. The significance of hypertension subtype under the new definition has not been fully explored.ObjectiveTo examine the associations of isolated systolic hypertension (ISH) and isolated diastolic hypertension (IDH) by the 2017 ACC/AHA guidelines with risk of cardiovascular disease (CVD) among the UK population.DesignProspective population-based cohort studySettingUK BiobankParticipants and MethodsWe included 470,625 participants who were free of CVD at baseline and had available data on BP measures. Of these, 13,157 CVD events were recorded (median follow-up 8.1 years), including 6,865 nonfatal myocardial infarctions (MI), 3,415 nonfatal ischemic strokes (ISs), 1,118 nonfatal hemorrhagic strokes (HSs), and 2,971 CVD deaths. Participants were categorized into 5 groups: normal BP, normal high BP, ISH, IDH and systolic and diastolic hypertension (SDH). The associations of each type of hypertension for the risk of CVD were estimated using a Cox proportional hazards regression model with adjustment for potential confounding factors.ResultsAccording to the hypertension threshold of ≥130/80 mm Hg by ACC/AHA guideline, both ISH (HR 1.35, 95% CI 1.24-1.46) and IDH (HR 1.22, 95% CI 1.11-1.36) were significantly associated with higher risk of overall CVD risk, compared with those with normal BP. ISH was predictive of most CVD risk, except for IS; while the excess CVD risk associated with IDH appeared to be driven mainly by MI. We found heterogeneity by sex and age regarding the effects of IDH on overall CVD risk, with the associations stronger in women and younger adults (age < 60 years) and null in men and older adults (age ≥60 years).ConclusionsISH and IDH by the ACC/AHA BP guideline were both associated with increased risk of CVD, highlighting the justification to lower the criteria of hypertension definition in the UK. Further research is needed to identify participants with IDH who are at especially greater risk for developing CVD.

scholarly journals Metabolic Syndrome, Its Components and Risk of Cardiometabolic Multimorbidity: Findings From the UK Biobank Cohort

2021 ◽  
Author(s):  
Yanan Qiao ◽  
Siyuan Liu ◽  
Guochen Li ◽  
Yanqiang Lu ◽  
Ying Wu ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cardiometabolic Disease ◽  
Cox Proportional Hazards Models ◽  
Hazard Ratios ◽  
Previous Diagnosis ◽  
The Uk

Abstract Background: Metabolic syndrome (MetS) and its components have been acknowledged as risk factors for a single cardiometabolic disease, but their relationship with the risk of cardiometabolic multimorbidity is unclear. The present study aimed to prospectively investigate the association of MetS and its components with the risk of cardiometabolic multimorbidity.Methods: In this prospective cohort study, we analyzed data of 353,427 participants from the UK Biobank. Participants with a previous diagnosis of cardiometabolic disease or those with missing data on the items of MetS were not eligible. Cardiometabolic multimorbidity was defined as the co-existence of two and more conditions of type 2 diabetes, coronary heart disease (CHD), and stroke. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the relationship between MetS, components of MetS and cardiometabolic multimorbidity. Results: During a median of 8.9 years of follow-up, 3389 participants developed the cardiometabolic multimorbidity. Compared with individuals without MetS, individuals with MetS had a three times higher risk of developing cardiometabolic multimorbidity (adjusted HR: 3.02, 95% CI: 2.82-3.24). The accumulation of MetS components was associated, in a dose-response manner, with the risk of cardiometabolic multimorbidity (P for trend <0.0001). For the temporal sequences in the development of cardiometabolic diseases, the corresponding HRs (95% CIs) for individuals with ≥4 metabolic abnormalities were 1.57 (1.47-1.68) for cardiovascular disease only, 10.27 (7.62-13.84) for cardiovascular disease with subsequent diabetes, 25.34 (21.95-29.24) for diabetes only, and 42.97 (21.19-87.13) for diabetes with subsequent cardiovascular disease.Conclusions: MetS was independently associated with the risk of cardiometabolic multimorbidity, and the risk substantially increased with a greater number of MetS components. Our findings highlight the importance of screening and treatment of MetS in the prevention of cardiometabolic multimorbidity.

Sign in / Sign up

Export Citation Format

Share Document