scholarly journals Long-Term Exposure to Elevated Lipoprotein(a) Levels, Parental Lifespan and Risk of Mortality

2019 ◽  
Author(s):  
Benoit J. Arsenault ◽  
William Pelletier ◽  
Yannick Kaiser ◽  
Nicolas Perrot ◽  
Christian Couture ◽  
...  
Keyword(s):  
Cardiovascular Mortality ◽  
Event Rate ◽  
Human Longevity ◽  
Uk Biobank ◽  
Lipoprotein A ◽  
The Uk ◽  
Genetically Determined ◽  
The Impact ◽  
Age Of Death

ABSTRACTBackgroundElevated Lipoprotein(a) (Lp[a]) levels are associated with a broad range of atherosclerotic cardiovascular diseases (CVD). The impact of high Lp(a) levels on human longevity is however controversial. Our objectives were to determine whether genetically-determined Lp(a) levels are associated with parental lifespan and to assess the association between measured and genetically-determined Lp(a) levels and long-term all-cause and cardiovascular mortality.MethodsWe determined the association between a genetic risk score of 26 single nucleotide polymorphisms weighted for their impact on Lp(a) levels (wGRS) and parental lifespan (at least one long-lived parent; father still alive and older than 90 or father’s age of death ≥90 or mother still alive and older than 93 or mother’s age of death ≥93) in 139,362 participants from the UK Biobank. A total of 17,686 participants were considered as having high parental lifespan. We also investigated the association between Lp(a) levels and all-cause and cardiovascular mortality in 18,720 participants from the EPIC-Norfolk study.ResultsIn the UK Biobank, increases in the wGRS (weighted for a 50 mg/dL increase in Lp(a) levels) were inversely associated with a high parental lifespan (odds ratio=0.92, 95% confidence interval [CI]=0.89-0.94, p=2.7×10−8). During the 20-year follow-up of the EPIC-Norfolk study, 5686 participants died (2412 from CVD-related causes). Compared to participants with Lp(a) levels <50 mg/dL, those with Lp(a) levels ≥50 mg/dL had an increased hazard ratio (HR) for all-cause (HR=1.17, 95% CI=1.08-1.27) and cardiovascular (HR=1.54, 95% CI=1.37-1.72) mortality. Compared to individuals with Lp(a) levels below the 50th percentile of the Lp(a) distribution (in whom event rates were 29.8% and 11.3%, respectively for all-cause and cardiovascular mortality), those with Lp(a) levels equal or above the 95th percentile of the population distribution (≥70 mg/dL) had HRs of 1.22 (95% CI=1.09-1.37, event rate 37.5%) and 1.71 (95% CI=1.46-2.00, event rate 20.0%), for all-cause mortality and cardiovascular mortality, respectively.ConclusionsResults of this study suggest a potentially causal effect of Lp(a) on human longevity, support the use of parental lifespan as a tool to study the genetic determinants of human longevity, and provide a rationale for a trial of Lp(a)-lowering therapy in individuals with high Lp(a) levels.

Long-Term Exposure to Elevated Lipoprotein(A) Levels Influences Human Longevity

2019 ◽  
Author(s):  
Benoit Arsenault ◽  
William Pelletier ◽  
Yannick Kaiser ◽  
Nicolas Perrot ◽  
Christian Couture ◽  
...  
Keyword(s):  
Human Longevity ◽  
Lipoprotein A

scholarly journals Machine Learning Prediction of Biomarkers from SNPs and of Disease Risk from Biomarkers in the UK Biobank

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 991
Author(s):  
Erik Widen ◽  
Timothy G. Raben ◽  
Louis Lello ◽  
Stephen D. H. Hsu
Keyword(s):  
Disease Risk ◽  
Smoking Status ◽  
Glycated Haemoglobin ◽  
European Ancestry ◽  
Risk Scores ◽  
Common Disease ◽  
Atherosclerotic Cardiovascular Disease ◽  
Uk Biobank ◽  
Lipoprotein A ◽  
The Uk

We use UK Biobank data to train predictors for 65 blood and urine markers such as HDL, LDL, lipoprotein A, glycated haemoglobin, etc. from SNP genotype. For example, our Polygenic Score (PGS) predictor correlates ∼0.76 with lipoprotein A level, which is highly heritable and an independent risk factor for heart disease. This may be the most accurate genomic prediction of a quantitative trait that has yet been produced (specifically, for European ancestry groups). We also train predictors of common disease risk using blood and urine biomarkers alone (no DNA information); we call these predictors biomarker risk scores, BMRS. Individuals who are at high risk (e.g., odds ratio of >5× population average) can be identified for conditions such as coronary artery disease (AUC∼0.75), diabetes (AUC∼0.95), hypertension, liver and kidney problems, and cancer using biomarkers alone. Our atherosclerotic cardiovascular disease (ASCVD) predictor uses ∼10 biomarkers and performs in UKB evaluation as well as or better than the American College of Cardiology ASCVD Risk Estimator, which uses quite different inputs (age, diagnostic history, BMI, smoking status, statin usage, etc.). We compare polygenic risk scores (risk conditional on genotype: PRS) for common diseases to the risk predictors which result from the concatenation of learned functions BMRS and PGS, i.e., applying the BMRS predictors to the PGS output.

scholarly journals Cardiovascular-related deaths at the beginning of the COVID-19 outbreak: a prospective analysis based on the UK Biobank

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e046931
Author(s):  
Junren Wang ◽  
Jianwei Zhu ◽  
Huazhen Yang ◽  
Yao Hu ◽  
Yajing Sun ◽  
...  
Keyword(s):  
Primary Diagnosis ◽  
Secondary Outcome ◽  
Hospital Inpatient ◽  
Reference Period ◽  
Stress Reactions ◽  
Uk Biobank ◽  
The Uk ◽  
The Impact ◽  
Distinct Increase ◽  
Related Mortality

ObjectiveTo assess the impact of the COVID-19 outbreak on cardiovascular disease (CVD) related mortality and hospitalisation.DesignCommunity-based prospective cohort study.SettingThe UK Biobank.Participants421 372 UK Biobank participants who were registered in England and alive as of 1 January 2020.Primary and secondary outcome measuresThe primary outcome of interest was CVD-related death, which was defined as death with CVD as a cause in the death register. We retrieved information on hospitalisations with CVD as the primary diagnosis from the UK Biobank hospital inpatient data. The study period was 1 January 2020 to June 30 2020, and we used the same calendar period of the three preceding years as the reference period. In order to control for seasonal variations and ageing of the study population, standardised mortality/incidence ratios (SMRs/SIRs) with 95% CIs were used to estimate the relative risk of CVD outcomes during the study period, compared with the reference period.ResultsWe observed a distinct increase in CVD-related deaths in March and April 2020, compared with the corresponding months of the three preceding years. The observed number of CVD-related deaths (n=218) was almost double in April, compared with the expected number (n=120) (SMR=1.82, 95% CI 1.58 to 2.07). In addition, we observed a significant decline in CVD-related hospitalisations from March onwards, with the lowest SIR observed in April (0.45, 95% CI 0.41 to 0.49).ConclusionsThere was a distinct increase in the number of CVD-related deaths in the UK Biobank population at the beginning of the COVID-19 outbreak. The shortage of medical resources for hospital care and stress reactions to the pandemic might have partially contributed to the excess CVD-related mortality, underscoring the need of sufficient healthcare resources and improved instructions to the public about seeking healthcare in a timely way.

scholarly journals The Association of Serum Lipid and Lipoprotein Levels with Total and Differential Leukocyte Counts: Results of a Cross-sectional and Longitudinal Analysis of the UK Biobank

2020 ◽  
Author(s):  
Bradley Tucker ◽  
Sonia Sawant ◽  
Hannah McDonald ◽  
Kerry-Anne Rye ◽  
Sanjay Patel ◽  
...  
Keyword(s):  
Longitudinal Analysis ◽  
Positive Association ◽  
Hdl Cholesterol ◽  
Uk Biobank ◽  
Cross Sectional ◽  
Lipoprotein A ◽  
Valid Data ◽  
Leukocyte Counts ◽  
The Uk ◽  
Relationship Of

Background and aims: There is some evidence of a cross-sectional, and possibly causal, relationship of lipid levels with leukocyte counts in mice and humans. This study investigates the cross-sectional and longitudinal relationship of blood lipid and lipoprotein levels with leukocyte counts in the UK Biobank cohort. Methods: The primary cross-sectional analysis included 417,132 participants with valid data on lipid measures and leukocyte counts. A subgroup analysis was performed in 333,668 participants with valid data on lipoprotein(a). The longitudinal analysis included 9,058 participants with valid baseline and follow-up data on lipid and lipoprotein levels and leukocyte counts. The association of lipid and lipoprotein levels with leukocyte counts was analysed by multivariable linear regression. Results: Several relationships were significant in both cross-sectional and longitudinal analysis. After adjustment for demographic, socioeconomic and other confounding factors a higher eosinophil count was associated with lower HDL cholesterol and apolipoproteinA-I concentration (p<0.001). Higher triglycerides levels were associated with higher total leukocyte, basophil, eosinophil, monocyte and neutrophil counts (all p<0.01). A higher lymphocyte count was associated with a higher apolipoprotein B level (p<0.001). In the longitudinal analysis lipoprotein(a) was inversely associated with basophil count in men but not women (p<0.001). Conclusion: Triglyceride levels demonstrate a robust positive association with total and differential leukocyte counts suggesting they may be directly involved in leuokogenesis. However, unlike in murine models, the remainder of these relationships are modest which suggests that cholesterol and lipoproteins are minimally involved in leukogenesis in humans.

Abstract 5772: The Impact of Aortic Plaque Morphology on Survival Rate and the Incidence of Subsequent Embolic Event: Very Long-Term Follow-Up Data

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Chisato Izumi ◽  
Shuichi Takahashi ◽  
Sumiyo Hashiwada ◽  
Koji Hanazawa ◽  
Jiro Sakamoto ◽  
...  
Keyword(s):  
Survival Rate ◽  
Event Rate ◽  
Plaque Morphology ◽  
Embolic Event ◽  
Aortic Plaque ◽  
Long Term Follow Up ◽  
The Impact ◽  
The Relationship

Atheromatous plaques of the aorta have been regarded as a potential source of emboli, but there are few reports about the frequency and prognosis of patients with thoracic aortic plaques and about the relationship between plaque morphology and prognosis, especially long-term follow-up data. The purpose of this study is to clarify the impact of aortic atheromatous plaque morphology on survival rate and the incidence of subsequent embolic event. We retrospectively investigated 1570 consecutive patients who underwent transesophageal echocardiography between 1991 and 2003. The presence of severe plaque (>5mm in thickness) in the thoracic aorta were examined. Survival rate and subsequent embolic event rate were compared between patients with severe plaque and 109 control patients. The control patients were selected from the patients who showed no or mild plaque and as they were matched for age, gender, and risk factors of atherosclerosis with the patients with severe aortic plaque. The relationship between aortic plaque morphology and prognosis was also estimated, according to the presence of ulceration, calcification, hypoechoic plaques, and mobile plaques. Mean follow-up period was 8.7 years. Among 1570 patients, severe aortic plaque was detected in 92 patients (5.9%). These 92 patients showed significantly low survival rate and high subsequent embolic event rate compared with control patients (8-year survival rate, 50% vs 87%, 8-year embolic event free rate, 57% vs 90%). The relative risk of death was significantly increased for ulceration (2.4, 95% CI;1.1–5.2) and the relative risk of embolic events was significantly increased for mobile plaques (2.2, 95% CI;1.1–5.1). In conclusion, aortic plaque > 5mm in thickness was a predictor of a low survival rate and a high embolic event rate. Among patients with aortic plaque >5mm in thickness, ulceration was a predictor of a low survival rate and mobile plaque was a predictor of a high embolic event rate.

Conclusion

2018 ◽  
pp. 222-234
Author(s):  
Stuart Aveyard ◽  
Paul Corthorn ◽  
Sean O’Connell
Keyword(s):  
Twentieth Century ◽  
Consumer Credit ◽  
Political Ideologies ◽  
European Consumer ◽  
Late Twentieth ◽  
Post War ◽  
The Uk ◽  
The Impact ◽  
Late Twentieth Century

The long-term perspective taken by The Politics of Consumer Credit in the UK affords fresh evidence on a number of significant historical debates. It indicates that Britain’s departure from pathways followed in other European consumer credit markets was not simply a by-product of neo-liberalism’s influence on late-twentieth-century governments. It has also allowed us to offer important contributions on questions such as the impact of political ideologies over policymaking, the validity of a right–left framework for analysing politics, the extent to which a post-war consensus existed (and was broken after 1979), and the question of how adept British political parties were in exploiting the emergence of a more affluent electorate....

scholarly journals Association of Antioxidants Use with All-Cause and Cause-Specific Mortality: A Prospective Study of the UK Biobank

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1287
Author(s):  
Inken Behrendt ◽  
Gerrit Eichner ◽  
Mathias Fasshauer
Keyword(s):  
Respiratory Disease ◽  
Mortality Risk ◽  
Cancer Mortality ◽  
Primary Objective ◽  
Inverse Association ◽  
Uk Biobank ◽  
Cancer Subtypes ◽  
Specific Mortality ◽  
The Uk ◽  
The Impact

Prospective studies and randomized controlled trials elucidating the impact of antioxidants supplementation on mortality risk are inconclusive. The present analysis determined association between regular antioxidants use and all-cause (primary objective), as well as cause-specific, mortality in 345,626 participants of the UK Biobank cohort using Cox proportional hazard models. All models were adjusted for confounders and multiple testing. Antioxidants users were defined as participants who indicated to regularly use at least one of the following: multivitamins, vitamin C, vitamin E, selenium, and zinc. Median age of antioxidants users (n = 101,159) and non-users (n = 244,467) at baseline was 57 years. During 3.9 million person-years and a median follow-up of 11.5 years, 19,491 deaths occurred. Antioxidants use was not significantly associated with all-cause, cancer, and non-cancer mortality including several cancer and non-cancer subtypes. Interestingly, mortality risk from respiratory disease was significantly 21% lower among antioxidants users as compared to non-users (hazard ratio: 0.79; 95% confidence interval: 0.67, 0.92). In conclusion, the present study findings do not support recommendations for antioxidants supplementation to prevent all-cause, cancer, or non-cancer mortality on a population level. The significant inverse association between antioxidants use and respiratory disease mortality needs further study.

Assessment of Package Performance During Long-Term Storage of Intermediate-Level Radioactive Waste

2003 ◽  
Author(s):  
A. V. Chambers ◽  
W. R. Rodwell ◽  
M. Kelly ◽  
A. R. Hoch ◽  
A. J. Baker
Keyword(s):  
Extended Period ◽  
Intermediate Level ◽  
Passive Safety ◽  
Long Term Storage ◽  
Waste Storage ◽  
Disposal Option ◽  
Intermediate Level Radioactive Waste ◽  
The Uk ◽  
The Impact

In the UK, the need for the long-term management of intermediate-level radioactive wastes arises from the absence of an established deep disposal option. As a consequence there is a requirement to demonstrate the ‘passive safety’ of waste packages in stores over a necessarily lengthy period (perhaps 150 years or more). ‘Passive safety’ is taken here to imply that the waste packages themselves would remain safe without intervention; it is assumed however, that the store building and associated infrastructure would need to be actively maintained and that the store may need to be ventilated. Importantly, methods for waste storage also need to ensure that possible future options for disposal are not foreclosed. An extended period of storage suggests that emphasis will need to be placed by waste producers on understanding a number of issues such as: • the impact of corrosion on container integrity; • the assessment of container vents and other features as a pathway for the release of radioactivity; • the extent to which wastes are conditioned for storage and the selection of appropriate methods; • the generation and behaviour of toxic or flammable gases in the storage facility; and the mitigating steps that might be needed to address adverse impacts (e.g. the type of ventilation that the store requires). In this paper, we review the requirements and current state of knowledge relevant to the assessment of operational releases of radioactive, flammable and toxic gases from wastes in long-term interim storage.

scholarly journals Association of central adiposity with psoriasis, psoriatic arthritis and rheumatoid arthritis: a cross-sectional study of the UK Biobank

Rheumatology ◽  
2019 ◽  
Vol 58 (12) ◽  
pp. 2137-2142 ◽  
Author(s):  
Lyn D Ferguson ◽  
Rosemary Brown ◽  
Carlos Celis-Morales ◽  
Paul Welsh ◽  
Donald M Lyall ◽  
...  
Keyword(s):  
Waist Circumference ◽  
Smoking Status ◽  
Cross Sectional Study ◽  
Central Adiposity ◽  
Uk Biobank ◽  
Sectional Study ◽  
Cross Sectional ◽  
Independent Association ◽  
The Uk

AbstractObjectivesTo determine the independent association of central adiposity, assessed by waist circumference, with odds of psoriasis, PsA and RA prevalence after controlling for general adiposity (BMI).MethodsA cross-sectional study of UK Biobank participants aged 40–70 years was performed. Logistic regression was used to calculate the odds of psoriasis, PsA and RA occurrence compared with controls without these conditions by waist circumference, adjusting for covariates: age, sex, smoking status, socioeconomic deprivation and self-reported physical activity (Model 1), followed additionally by BMI (Model 2).ResultsA total of 502 417 participants were included; 5074 with psoriasis (1.02%), 905 with PsA (0.18%), 5532 with RA (1.11%) and 490 906 controls without these conditions. Adjusted odds ratios (ORs) (Model 1) for psoriasis, PsA and RA, per s.d. (13.5 cm) higher waist circumference were 1.20 (95% CI 1.16, 1.23), 1.30 (95% CI 1.21, 1.39) and 1.21 (95% CI 1.17, 1.24), respectively (all P < 0.001). These ORs remained significant after further adjustment for BMI (Model 2) in psoriasis [OR 1.19 (95% CI 1.12, 1.27), P < 0.001] and RA [OR 1.19 (95% CI 1.12, 1.26), P < 0.001], but not in PsA [OR 1.11 (95% CI 0.95, 1.29), P = 0.127].ConclusionCentral adiposity as measured by waist circumference is associated with greater odds of psoriasis and RA prevalence after adjustment for confounders and for BMI. Our findings add support for central adiposity as a long-term clinically relevant component of these conditions.

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