scholarly journals CAUSES OF FRAILTY: GENETIC ANALYSIS IN 164,000 UK BIOBANK PARTICIPANTS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S222-S222
Author(s):  
Janice Atkins ◽  
Luke C Pilling ◽  
Dylan Williams ◽  
Juulia Jylhävä ◽  
David Melzer
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Mendelian Randomization ◽  
Frailty Index ◽  
Geriatric Syndrome ◽  
Uk Biobank ◽  
Genomewide Association Study ◽  
European Descent ◽  
Ongoing Work

Abstract Frailty is an important and common geriatric syndrome, yet the mechanisms are multifactorial and not well understood. The Frailty Index (FI) is based on the Rockwood Index for accumulation of deficits, and we aimed to use genetics to gain mechanistic insights for interventions to prevent and delay frailty in older people. We performed a genomewide association study in 60 to 70 year old UK Biobank participants of European descent (n=164,610). We identified 26 independent genetic signals at 24 loci associated with the FI. Several of these signals have previously been associated with traits such as cardiovascular disease, intelligence, and educational attainment, but 6 of the signals appear to be novel. We will also present the results of ongoing work both to identify causal risk factors for FI using Mendelian randomization methods, and replication and functional follow-up in the TwinGene cohort, at the meeting.

scholarly journals 12 Being Non-Frail and Free From Cardiovascular Disease Reduces COVID-19 Risk in 269,164 Older UK Biobank Participants

2021 ◽  
Vol 50 (Supplement_1) ◽  
pp. i1-i6
Author(s):  
J Masoli ◽  
J Atkins ◽  
J Delgado ◽  
L Pilling ◽  
D Melzer
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Older Adults ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Frailty Index ◽  
Uk Biobank ◽  
Frail Older Adults ◽  
Increased Risk ◽  
Low Cardiovascular Risk

Abstract Background Older adults are at increased risk of COVID-19, resulting in public health shielding measures for all adults over 70 in the UK. Frailty has been proposed for risk stratification in COVID-19 with limited evidence. Cardiovascular risk factors hypertension, diabetes and raised BMI have been associated with increased COVID-19 risk. We sought to test if non-frail older adults with low cardiovascular risk had reduced COVID-19, to inform targeted shielding policies. Methods Fried and Rockwood frailty were ascertained at UK Biobank baseline (2006-2010) and electronic frailty index(eFI) in primary care data to 2017*. A cardiovascular disease risk score(CRS) consisting of smoking status, LDL-cholesterol, blood pressure, BMI, fasting glucose and physical activity was estimated at baseline. Frailty (baseline and eFI; eFI alone) and CRS were tested in logistic models against COVID-19 status and COVID-19 mortality to 14th June 2020 adjusted for demographics and technical covariates. Results N=269,164 UKB participants aged ≥65 at baseline (≥75years in 2020). 13.9% of COVID-19 positive were non-frail with low baseline CRS versus 41.8% frail with moderate/high CRS. Being non-frail and having low CRS were independently associated with reduced COVID-19. The composite of non-frail with low CRS compared to frail with moderate/high CRS had significantly reduced COVID-19 risk (composite non-frail with low CRS HR 0.61; 95% CI 0.45-0.84; p=0.0023; eFI non-frail with low CRS HR 0.16; 95%CI 0.07-0.36; p value=9.9x10-6) and COVID-19 mortality (composite non-frail HR 0.28; 95% CI 0.10-0.82; pvalue=0.02; eFI non-frail 0.07; 95% CI 0.02-0.28; pvalue=0.00014). Conclusion These results show that the COVID-19 risk in non-frail older adults with low cardiovascular risk was up to 84% lower than in those who were frail with cardiovascular risk factors. This could contribute to future work on stratification of shielding risk in older adults in future COVID-19 surges. *Planned data updates prior to the conference should enable updates to 2020.

scholarly journals COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors

2021 ◽  
Vol 36 (3) ◽  
pp. 299-309 ◽  
Author(s):  
Joshua Elliott ◽  
Barbara Bodinier ◽  
Matthew Whitaker ◽  
Cyrille Delpierre ◽  
Roel Vermeulen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Body Mass Index ◽  
Vitamin D ◽  
Regression Models ◽  
Oral Steroid ◽  
Uk Biobank ◽  
Steroid Use ◽  
Increased Risk ◽  
Male Sex

AbstractMost studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank cohort, we investigate risk factors for COVID-19 mortality in comparison with non-COVID-19 mortality. We investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N = 473,550) in relation to 459 COVID-19 and 2626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Age (OR = 2.76 [2.18–3.49] per S.D. [8.1 years], p = 2.6 × 10–17), male sex (OR = 1.47 [1.26–1.73], p = 1.3 × 10–6) and Black versus White ethnicity (OR = 1.21 [1.12–1.29], p = 3.0 × 10–7) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC = 0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants, renin–angiotensin–aldosterone system inhibitors may be explained by the aforementioned factors.

scholarly journals Coffee Consumption and Cardiovascular Diseases: A Mendelian Randomization Study

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2218
Author(s):  
Shuai Yuan ◽  
Paul Carter ◽  
Amy M. Mason ◽  
Stephen Burgess ◽  
Susanna C. Larsson
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Intracerebral Hemorrhage ◽  
Genetic Variants ◽  
Odds Ratio ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Coffee Consumption ◽  
Uk Biobank ◽  
The Uk

Coffee consumption has been linked to a lower risk of cardiovascular disease in observational studies, but whether the associations are causal is not known. We conducted a Mendelian randomization investigation to assess the potential causal role of coffee consumption in cardiovascular disease. Twelve independent genetic variants were used to proxy coffee consumption. Summary-level data for the relations between the 12 genetic variants and cardiovascular diseases were taken from the UK Biobank with up to 35,979 cases and the FinnGen consortium with up to 17,325 cases. Genetic predisposition to higher coffee consumption was not associated with any of the 15 studied cardiovascular outcomes in univariable MR analysis. The odds ratio per 50% increase in genetically predicted coffee consumption ranged from 0.97 (95% confidence interval (CI), 0.63, 1.50) for intracerebral hemorrhage to 1.26 (95% CI, 1.00, 1.58) for deep vein thrombosis in the UK Biobank and from 0.86 (95% CI, 0.50, 1.49) for subarachnoid hemorrhage to 1.34 (95% CI, 0.81, 2.22) for intracerebral hemorrhage in FinnGen. The null findings remained in multivariable Mendelian randomization analyses adjusted for genetically predicted body mass index and smoking initiation, except for a suggestive positive association for intracerebral hemorrhage (odds ratio 1.91; 95% CI, 1.03, 3.54) in FinnGen. This Mendelian randomization study showed limited evidence that coffee consumption affects the risk of developing cardiovascular disease, suggesting that previous observational studies may have been confounded.

Physical activity less than the recommended amount may prevent the onset of major biological risk factors for cardiovascular disease: a cohort study of 198 919 adults

2018 ◽  
Vol 54 (4) ◽  
pp. 238-244 ◽  
Author(s):  
David Martinez-Gomez ◽  
Irene Esteban-Cornejo ◽  
Esther Lopez-Garcia ◽  
Esther García-Esquinas ◽  
Kabir P Sadarangani ◽  
...  
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Highly Active ◽  
Atherogenic Dyslipidaemia

ObjectivesWe examined the dose–response relationship between physical activity (PA) and incidence of cardiovascular disease (CVD) risk factors in adults in Taiwan.MethodsThis study included 1 98 919 participants, aged 18–97 years, free of CVD, cancer and diabetes at baseline (1997–2013), who were followed until 2016. At baseline, participants were classified into five PA levels: inactive’ (0 metabolic equivalent of task (MET)-h/week), ‘lower insufficiently active’ (0.1–3.75 MET-h/week), ‘upper insufficiently active’ (3.75–7.49 MET-h/week), ‘active’ (7.5–14.99 MET-h/week) and ‘highly active’ (≥15 MET-h/week]. CVD risk factors were assessed at baseline and at follow-up by physical examination and laboratory tests. Analyses were performed with Cox regression and adjusted for the main confounders.ResultsDuring a mean follow-up of 6.0±4.5 years (range 0.5–19 years), 20 447 individuals developed obesity, 19 619 hypertension, 21 592 hypercholesterolaemia, 14 164 atherogenic dyslipidaemia, 24 275 metabolic syndrome and 8548 type 2 diabetes. Compared with inactive participants, those in the upper insufficiently active (but not active) category had a lower risk of obesity (HR 0.92; 95% CI 0.88 to 0.95), atherogenic dyslipidaemia (0.96; 0.90 to 0.99), metabolic syndrome (0.95; 0.92 to 0.99) and type 2 diabetes (0.91; 0.86 to 0.97). Only highly active individuals showed a lower incidence of CVD risk factors than their upper insufficiently active counterparts.ConclusionCompared with being inactive, doing half the recommended amount of PA is associated with a lower incidence of several common biological CVD risk factors. Given these benefits, half the recommended amount of PA is an evidence based target for inactive adults.

scholarly journals Circulating Proangiogenic Cell Activity Is Associated with Cardiovascular Disease Risk

2012 ◽  
Vol 17 (9) ◽  
pp. 1163-1170 ◽  
Author(s):  
Kreton Mavromatis ◽  
Konstantinos Aznaouridis ◽  
Ibhar Al Mheid ◽  
Emir Veledar ◽  
Saurabh Dhawan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Bone Marrow ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cell Activity ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cvd Risk ◽  
The Relationship

Vascular injury mobilizes bone marrow–derived proangiogenic cells into the circulation, where these cells can facilitate vascular repair and new vessel formation. We sought to determine the relationship between a new biomarker of circulating bone marrow–derived proangiogenic cell activity, the presence of atherosclerotic cardiovascular disease (CVD) and its risk factors, and clinical outcomes. Circulating proangiogenic cell activity was estimated using a reproducible angiogenic colony-forming unit (CFU-A) assay in 532 clinically stable subjects aged 20 to 90 years and ranging in the CVD risk spectrum from those who are healthy without risk factors to those with active CVD. CFU-A counts increased with the burden of CVD risk factors ( p < 0.001). CFU-A counts were higher in subjects with symptomatic CVD than in those without ( p < 0.001). During follow-up of 232 subjects with CVD, CFU-A counts were higher in those with death, myocardial infarction, or stroke than in those without (110 [70–173] vs 84 [51–136], p = 0.01). Therefore, we conclude that circulating proangiogenic cell activity, as estimated by CFU-A counts, increases with CVD risk factor burden and in the presence of established CVD. Furthermore, higher circulating proangiogenic cell activity is associated with worse clinical outcome in those with CVD.

scholarly journals Evaluating the effects of alcohol and tobacco use on cardiovascular disease using multivariable Mendelian randomization

2019 ◽  
Author(s):  
Daniel B. Rosoff ◽  
George Davey Smith ◽  
Nehal Mehta ◽  
Toni-Kim Clarke ◽  
Falk W. Lohoff
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Alcohol Use ◽  
Tobacco Use ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Density Lipoprotein ◽  
Genome Wide Association Studies ◽  
Cvd Risk ◽  
Increased Risk

ABSTRACTAlcohol and tobacco use, two major modifiable risk factors for cardiovascular disease (CVD), are often consumed together. Using large publicly available genome-wide association studies (results from > 940,000 participants), we conducted two-sample multivariable Mendelian randomization (MR) to simultaneously assess the independent effects of alcohol and tobacco use on CVD risk factors and events. We found genetic instruments associated with increased alcohol use, controlling for tobacco use, associated with increased high-density-lipoprotein-cholesterol (HDL-C), decreased triglycerides, but not with coronary heart disease (CHD), myocardial infarction (MI), nor stroke; and instruments for increased tobacco use, controlling for alcohol use, associated with decreased HDL-C, increased triglycerides, and increased risk of CHD and MI. Exploratory analysis found associations with HDL-C, LDL-C, and intermediate-density-lipoprotein metabolites. Consistency of results across complementary methods accommodating different MR assumptions strengthened causal inference, providing strong genetic evidence for the causal effects of modifiable lifestyle risk factors on CVD risk.

scholarly journals Epidemiology of Heart Failure Stages in Middle‐Aged Black People in the Community: Prevalence and Prognosis in the Atherosclerosis Risk in Communities Study

2021 ◽  
Author(s):  
Ramachandran S. Vasan ◽  
Solomon K. Musani ◽  
Kunihiro Matsushita ◽  
Walter Beard ◽  
Olushola B. Obafemi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Left Ventricular ◽  
Study Cohort ◽  
Atherosclerosis Risk In Communities ◽  
Cardiovascular Morbidity And Mortality ◽  
Atherosclerosis Risk

Background Black individuals have a higher burden of risk factors for heart failure (HF) and subclinical left ventricular remodeling. Methods and Results We evaluated 1871 Black participants in the Atherosclerosis Risk in Communities Study cohort who attended a routine examination (1993–1996, median age 58 years) when they underwent echocardiography. We estimated the prevalences of 4 HF stages: (1) Stage 0 : no risk factors; (2) Stage A : presence of HF risk factors (hypertension, diabetes mellitus, obesity, smoking, dyslipidemia, coronary artery disease without clinical myocardial infarction), no cardiac structural/functional abnormality; (3) Stage B : presence of prior myocardial infarction, systolic dysfunction, left ventricular hypertrophy, regional wall motion abnormality, or left ventricular enlargement; and (4) Stage C/D : prevalent HF. We assessed the incidence of clinical HF, atherosclerotic cardiovascular disease events, and all‐cause mortality on follow‐up according to HF stage. The prevalence of HF Stages 0, A, B, and C/D were 3.8%, 20.6%, 67.0%, and 8.6%, respectively, at baseline. On follow‐up (median 19.0 years), 309 participants developed overt HF, 390 incurred new‐onset cardiovascular disease events, and 651 individuals died. Incidence rates per 1000 person‐years for overt HF, cardiovascular disease events, and death, respectively, were Stage 0, 2.4, 0.8, and 7.6; Stage A, 7.4, 9.7, and 13.5; Stage B 13.6, 15.9, and 22.0. Stage B HF was associated with a 1.5‐ to 2‐fold increased adjusted risk of HF, cardiovascular disease events and death compared with Stages 0/A. Conclusions In our large community‐based sample of Black individuals, we observed a strikingly high prevalence of Stage B HF in middle age that was a marker of high cardiovascular morbidity and mortality.

Sign in / Sign up

Export Citation Format

Share Document