Imperial College London

ProfessorAlunHughes

Faculty of MedicineNational Heart & Lung Institute

Visiting Professor
 
 
 
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Contact

 

a.hughes Website

 
 
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Assistant

 

Mrs Kim Cyrus +44 (0)20 7594 6047

 
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Location

 

59/61 North Wharf RoadSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

1331 results found

Bann D, Wright L, Hughes A, Chaturvedi Net al., 2024, Socioeconomic inequalities in cardiovascular disease: a causal perspective., Nat Rev Cardiol, Vol: 21, Pages: 238-249

Socioeconomic inequalities in cardiovascular disease (CVD) persist in high-income countries despite marked overall declines in CVD-related morbidity and mortality. After decades of research, the field has struggled to unequivocally answer a crucial question: is the association between low socioeconomic position (SEP) and the development of CVD causal? We review relevant evidence from various study designs and disciplinary perspectives. Traditional observational, family-based and Mendelian randomization studies support the widely accepted view that low SEP causally influences CVD. However, results from quasi-experimental and experimental studies are both limited and equivocal. While more experimental and quasi-experimental studies are needed to aid causal understanding and inform policy, high-quality descriptive studies are also required to document inequalities, investigate their contextual dependence and consider SEP throughout the lifespan; no simple hierarchy of evidence exists for an exposure as complex as SEP. The COVID-19 pandemic illustrates the context-dependent nature of CVD inequalities, with the generation of potentially new causal pathways linking SEP and CVD. The linked goals of understanding the causal nature of SEP and CVD associations, their contextual dependence, and their remediation by policy interventions necessitate a detailed understanding of society, its change over time and the phenotypes of CVD. Interdisciplinary research is therefore key to advancing both causal understanding and policy translation.

Journal article

Rhead R, Wels J, Moltrecht B, Shaw RJ, Silverwood R, Zhu J, Hughes A, Chaturvedi N, Demou E, Katikireddi SV, Ploubidis Get al., 2024, Long COVID and financial outcomes: evidence from four longitudinal population surveys., J Epidemiol Community Health

BACKGROUND: Long-term sequelae of COVID-19 (long COVID) include muscle weakness, fatigue, breathing difficulties and sleep disturbance over weeks or months. Using UK longitudinal data, we assessed the relationship between long COVID and financial disruption. METHODS: We estimated associations between long COVID (derived using self-reported length of COVID-19 symptoms) and measures of financial disruption (subjective financial well-being, new benefit claims, changes in household income) by analysing data from four longitudinal population studies, gathered during the first year of the pandemic. We employed modified Poisson regression in a pooled analysis of the four cohorts adjusting for a range of potential confounders, including pre-pandemic (pre-long COVID) factors. RESULTS: Among the 20 112 observations across four population surveys, 13% reported having COVID-19 with symptoms that impeded their ability to function normally-10.7% had such symptoms for <4 weeks (acute COVID-19), 1.2% had such symptoms for 4-12 weeks (ongoing symptomatic COVID-19) and 0.6% had such symptoms for >12 weeks (post-COVID-19 syndrome). We found that post-COVID-19 syndrome was associated with worse subjective financial well-being (adjusted relative risk ratios (aRRRs)=1.57, 95% CI=1.25, 1.96) and new benefit claims (aRRR=1.79, CI=1.27, 2.53). Associations were broadly similar across sexes and education levels. These results were not meaningfully altered when scaled to represent the population by age. CONCLUSIONS: Long COVID was associated with financial disruption in the UK. If our findings reflect causal effects, extending employment protection and financial support to people with long COVID may be warranted.

Journal article

Leyden GM, Urquijo H, Hughes AD, Davey Smith G, Richardson TGet al., 2024, Characterizing the Causal Pathway From Childhood Adiposity to Right Heart Physiology and Pulmonary Circulation Using Lifecourse Mendelian Randomization., J Am Heart Assoc, Vol: 13

BACKGROUND: Observational epidemiological studies have reported an association between childhood adiposity and altered cardiac morphology and function in later life. However, whether this is due to a direct consequence of being overweight during childhood has been difficult to establish, particularly as accounting for other measures of body composition throughout the lifecourse can be exceptionally challenging. METHODS AND RESULTS: In this study, we used human genetics to investigate this using a causal inference technique known as lifecourse Mendelian randomization. This approach allowed us to evaluate the effect of childhood body size on 11 measures of right heart and pulmonary circulation independent of other anthropometric traits at various stages in the lifecourse. We found strong evidence that childhood body size has a direct effect on an enlarged right heart structure in later life (eg, right ventricular end-diastolic volume: β=0.24 [95% CI, 0.15-0.33]; P=3×10-7) independent of adulthood body size. In contrast, childhood body size effects on maximum ascending aorta diameter attenuated upon accounting for body size in adulthood, suggesting that this effect is likely attributed to individuals remaining overweight into later life. Effects of childhood body size on pulmonary artery traits and measures of right atrial function became weaker upon accounting for adulthood fat-free mass and childhood height, respectively. CONCLUSIONS: Our findings suggest that, although childhood body size has a long-term influence on an enlarged heart structure in adulthood, associations with the other structural components of the cardiovascular system and their function may be largely attributed to body composition at other stages in the lifecourse.

Journal article

Joy G, Lopes LR, Webber M, Ardissino AM, Wilson J, Chan F, Pierce I, Hughes RK, Moschonas K, Shiwani H, Jamieson R, Velazquez PP, Vijayakumar R, Dall'Armellina E, Macfarlane PW, Manisty C, Kellman P, Davies RH, Tome M, Koncar V, Tao X, Guger C, Rudy Y, Hughes AD, Lambiase PD, Moon JC, Orini M, Captur Get al., 2024, Electrophysiological Characterization of Subclinical and Overt Hypertrophic Cardiomyopathy by Magnetic Resonance Imaging-Guided Electrocardiography., J Am Coll Cardiol, Vol: 83, Pages: 1042-1055

BACKGROUND: Ventricular arrhythmia in hypertrophic cardiomyopathy (HCM) relates to adverse structural change and genetic status. Cardiovascular magnetic resonance (CMR)-guided electrocardiographic imaging (ECGI) noninvasively maps cardiac structural and electrophysiological (EP) properties. OBJECTIVES: The purpose of this study was to establish whether in subclinical HCM (genotype [G]+ left ventricular hypertrophy [LVH]-), ECGI detects early EP abnormality, and in overt HCM, whether the EP substrate relates to genetic status (G+/G-LVH+) and structural phenotype. METHODS: This was a prospective 211-participant CMR-ECGI multicenter study of 70 G+LVH-, 104 LVH+ (51 G+/53 G-), and 37 healthy volunteers (HVs). Local activation time (AT), corrected repolarization time, corrected activation-recovery interval, spatial gradients (GAT/GRTc), and signal fractionation were derived from 1,000 epicardial sites per participant. Maximal wall thickness and scar burden were derived from CMR. A support vector machine was built to discriminate G+LVH- from HV and low-risk HCM from those with intermediate/high-risk score or nonsustained ventricular tachycardia. RESULTS: Compared with HV, subclinical HCM showed mean AT prolongation (P = 0.008) even with normal 12-lead electrocardiograms (ECGs) (P = 0.009), and repolarization was more spatially heterogenous (GRTc: P = 0.005) (23% had normal ECGs). Corrected activation-recovery interval was prolonged in overt vs subclinical HCM (P < 0.001). Mean AT was associated with maximal wall thickness; spatial conduction heterogeneity (GAT) and fractionation were associated with scar (all P < 0.05), and G+LVH+ had more fractionation than G-LVH+ (P = 0.002). The support vector machine discriminated subclinical HCM from HV (10-fold cross-validation accuracy 80% [95% CI: 73%-85%]) and identified patients at higher risk of sudden cardiac death (accuracy 82% [95% CI: 78%-86%]). CONCLUSIONS: In the absence of LVH or 12-lead ECG abnormalities

Journal article

Ahmadi MN, Blodgett JM, Atkin AJ, Chan H-W, Del Pozo Cruz B, Suorsa K, Bakker EA, Pulsford RM, Mielke GI, Johansson PJ, Hettiarachchi P, Thijssen DHJ, Stenholm S, Mishra GD, Teixeira-Pinot A, Rangul V, Sherar LB, Ekelund U, Hughes AD, Lee I-M, ProPASS collaboration, Holtermann A, Koster A, Hamer M, Stamatakis Eet al., 2024, Relationship of device measured physical activity type and posture with cardiometabolic health markers: pooled dose-response associations from the Prospective Physical Activity, Sitting and Sleep Consortium., Diabetologia

AIMS/HYPOTHESIS: The aim of this study was to examine the dose-response associations of device-measured physical activity types and postures (sitting and standing time) with cardiometabolic health. METHODS: We conducted an individual participant harmonised meta-analysis of 12,095 adults (mean ± SD age 54.5±9.6 years; female participants 54.8%) from six cohorts with thigh-worn accelerometry data from the Prospective Physical Activity, Sitting and Sleep (ProPASS) Consortium. Associations of daily walking, stair climbing, running, standing and sitting time with a composite cardiometabolic health score (based on standardised z scores) and individual cardiometabolic markers (BMI, waist circumference, triglycerides, HDL-cholesterol, HbA1c and total cholesterol) were examined cross-sectionally using generalised linear modelling and cubic splines. RESULTS: We observed more favourable composite cardiometabolic health (i.e. z score <0) with approximately 64 min/day walking (z score [95% CI] -0.14 [-0.25, -0.02]) and 5 min/day stair climbing (-0.14 [-0.24, -0.03]). We observed an equivalent magnitude of association at 2.6 h/day standing. Any amount of running was associated with better composite cardiometabolic health. We did not observe an upper limit to the magnitude of the dose-response associations for any activity type or standing. There was an inverse dose-response association between sitting time and composite cardiometabolic health that became markedly less favourable when daily durations exceeded 12.1 h/day. Associations for sitting time were no longer significant after excluding participants with prevalent CVD or medication use. The dose-response pattern was generally consistent between activity and posture types and individual cardiometabolic health markers. CONCLUSIONS/INTERPRETATION: In this first activity type-specific analysis of device-based physical activity, ~64 min/day of walking and ~5.0 min/day of stair climbing were associated with a favo

Journal article

Lathe J, Silverwood RJ, Hughes AD, Patalay Pet al., 2024, Examining how well economic evaluations capture the value of mental health., Lancet Psychiatry, Vol: 11, Pages: 221-230

Health economics evidence informs health-care decision making, but the field has historically paid insufficient attention to mental health. Economic evaluations in health should define an appropriate scope for benefits and costs and how to value them. This Health Policy provides an overview of these processes and considers to what extent they capture the value of mental health. We suggest that although current practices are both transparent and justifiable, they have distinct limitations from the perspective of mental health. Most social value judgements, such as the exclusion of interindividual outcomes and intersectoral costs, diminish the value of improving mental health, and this reduction in value might be disproportionate compared with other types of health. Economic analyses might have disadvantaged interventions that improve mental health compared with physical health, but research is required to test the size of such differential effects and any subsequent effect on decision-making systems such as health technology assessment systems. Collaboration between health economics and the mental health sciences is crucial for achieving mental-physical health parity in evaluative frameworks and, ultimately, improving population mental health.

Journal article

Chiesa ST, Norris T, Garfield V, Richards M, Hughes ADet al., 2024, Early-life cumulative exposure to excess bodyweight and midlife cognitive function: longitudinal analysis in three British birth cohorts., Lancet Healthy Longev, Vol: 5, Pages: e204-e213

BACKGROUND: Excess bodyweight (BMI >25 kg/m2) in midlife (age 40-65 years) has been linked to future cognitive decline and an increased risk of dementia. Whether chronic exposure to excess bodyweight in the early decades of life (<40 years) is associated with compromised cognitive function by midlife, however, remains unclear. This study therefore aimed to test potential bidirectional direct and indirect pathways linking cumulative exposure to excess bodyweight and cognitive function in the early decades of life. METHODS: In this longitudinal analysis, harmonised measures of BMI and cognitive function were available in 19 742 participants aged 47-53 years recruited to the 1946 National Survey of Health and Development (n=2131), the 1958 National Child Development Study (n=9385), and the 1970 British Cohort Study (n=8226). Individual BMI trajectories spanning three decades from age 10-40 years were created for each participant and excess bodyweight duration, BMI change between ages, and cumulative excess bodyweight exposure were calculated. Harmonised measures of verbal and non-verbal ability, mathematical ability, and reading ability were used to create a latent factor for childhood cognitive function, and immediate and delayed recall, animal naming, and letter-search speed tests were used for midlife cognitive function. Multivariable linear regression and structural equation models (SEM) were used to test for potential bidirectional relationships between cognition and excess bodyweight in both individual cohorts and pooled datasets while accounting for other potential early-life confounders. FINDINGS: Increases in BMI during adolescence and greater cumulative exposure to excess bodyweight across early life were associated with lower midlife cognitive function in all cohorts (eg, pooled difference in cognitive function per 10 years excess bodyweight duration -0·10; 95% CI -0·12 to -0·08; p<0·001). Further adjustment for childhood

Journal article

Anbar R, Jones S, Chaturvedi N, Sudre C, Richards M, Sultan SR, Hughes ADet al., 2024, Associations of carotid atherosclerosis with cognitive function and brain health: Findings from a UK tri-ethnic cohort study (Southall and Brent Revisited)., Atheroscler Plus, Vol: 55, Pages: 39-46

BACKGROUND: Cognitive function has an important role in determining the quality of life of older adults. Cardiovascular disease (CVD) is common in older people and may compromise cognitive performance; however, the extent to which this is related to carotid atherosclerosis is unclear. AIM: We investigated associations between carotid atherosclerosis and cognitive function and neuroimaging markers of brain health in a UK multi-ethnic community-based sample including older people of European, South Asian, and African-Caribbean ethnicity. METHODS: Carotid plaques and intima-media thickness (cIMT) were assessed using ultrasound in 985 people (mean age 73.2y, 56 % male). Associations of carotid atherosclerosis with cognitive function (memory, executive function, language and CSI-D, a global measure of cognitive state) and neuroimaging measures (total brain volume, hippocampal volume, white matter (WM) lesion volume and coalescence score) were analysed using regression analyses, with and without adjustment for potential confounders using two models: 1) adjustment for age, sex, and ethnicity; 2) model 1 plus education, physical activity category, body mass index, hypertension, diabetes, total and high density lipoprotein cholesterol, atrial fibrillation, smoking, previous CVD, alcohol consumption, and presence of chronic kidney disease. RESULTS: People with carotid plaque or higher cIMT had lower CSI-D score, poorer memory poorer executive function and higher WM lesion volume and coalescence. Language was poorer in people with plaque but was not correlated with cIMT. Associations with plaque were preserved after full adjustment (model 2) but relationships for cIMT were attenuated. Associations with other plaque characteristics were generally unconvincing after adjustment. CONCLUSIONS: This multi-ethnic cohort study provides evidence that presence of carotid plaque, is associated with poorer cognitive function and brain health.

Journal article

Green RE, Sudre CH, Warren-Gash C, Butt J, Waterboer T, Hughes AD, Schott JM, Richards M, Chaturvedi N, Williams DMet al., 2024, Common infections and neuroimaging markers of dementia in three UK cohort studies., Alzheimers Dement, Vol: 20, Pages: 2128-2142

INTRODUCTION: We aimed to investigate associations between common infections and neuroimaging markers of dementia risk (brain volume, hippocampal volume, white matter lesions) across three population-based studies. METHODS: We tested associations between serology measures (pathogen serostatus, cumulative burden, continuous antibody responses) and outcomes using linear regression, including adjustments for total intracranial volume and scanner/clinic information (basic model), age, sex, ethnicity, education, socioeconomic position, alcohol, body mass index, and smoking (fully adjusted model). Interactions between serology measures and apolipoprotein E (APOE) genotype were tested. Findings were meta-analyzed across cohorts (Nmain  = 2632; NAPOE-interaction  = 1810). RESULTS: Seropositivity to John Cunningham virus associated with smaller brain volumes in basic models (β = -3.89 mL [-5.81, -1.97], Padjusted  < 0.05); these were largely attenuated in fully adjusted models (β = -1.59 mL [-3.55, 0.36], P = 0.11). No other relationships were robust to multiple testing corrections and sensitivity analyses, but several suggestive associations were observed. DISCUSSION: We did not find clear evidence for relationships between common infections and markers of dementia risk. Some suggestive findings warrant testing for replication.

Journal article

Blodgett JM, Ahmadi MN, Atkin AJ, Chastin S, Chan H-W, Suorsa K, Bakker EA, Hettiarcachchi P, Johansson PJ, Sherar LB, Rangul V, Pulsford RM, Mishra G, Eijsvogels TMH, Stenholm S, Hughes AD, Teixeira-Pinto AM, Ekelund U, Lee I-M, Holtermann A, Koster A, Stamatakis E, Hamer M, ProPASS Collaborationet al., 2024, Device-measured physical activity and cardiometabolic health: the Prospective Physical Activity, Sitting, and Sleep (ProPASS) consortium., Eur Heart J, Vol: 45, Pages: 458-471

BACKGROUND AND AIMS: Physical inactivity, sedentary behaviour (SB), and inadequate sleep are key behavioural risk factors of cardiometabolic diseases. Each behaviour is mainly considered in isolation, despite clear behavioural and biological interdependencies. The aim of this study was to investigate associations of five-part movement compositions with adiposity and cardiometabolic biomarkers. METHODS: Cross-sectional data from six studies (n = 15 253 participants; five countries) from the Prospective Physical Activity, Sitting and Sleep consortium were analysed. Device-measured time spent in sleep, SB, standing, light-intensity physical activity (LIPA), and moderate-vigorous physical activity (MVPA) made up the composition. Outcomes included body mass index (BMI), waist circumference, HDL cholesterol, total:HDL cholesterol ratio, triglycerides, and glycated haemoglobin (HbA1c). Compositional linear regression examined associations between compositions and outcomes, including modelling time reallocation between behaviours. RESULTS: The average daily composition of the sample (age: 53.7 ± 9.7 years; 54.7% female) was 7.7 h sleeping, 10.4 h sedentary, 3.1 h standing, 1.5 h LIPA, and 1.3 h MVPA. A greater MVPA proportion and smaller SB proportion were associated with better outcomes. Reallocating time from SB, standing, LIPA, or sleep into MVPA resulted in better scores across all outcomes. For example, replacing 30 min of SB, sleep, standing, or LIPA with MVPA was associated with -0.63 (95% confidence interval -0.48, -0.79), -0.43 (-0.25, -0.59), -0.40 (-0.25, -0.56), and -0.15 (0.05, -0.34) kg/m2 lower BMI, respectively. Greater relative standing time was beneficial, whereas sleep had a detrimental association when replacing LIPA/MVPA and positive association when replacing SB. The minimal displacement of any behaviour into MVPA for improved cardiometabolic health ranged from 3.8 (HbA1c) to 12.7 (triglycerides) min/day. CONCLUSIONS: Compositional data analyses

Journal article

Jamieson A, Al Saikhan L, Alghamdi L, Hamill Howes L, Purcell H, Hillman T, Heightman M, Treibel T, Orini M, Bell R, Scully M, Hamer M, Chaturvedi N, Montgomery H, Hughes AD, Astin R, Jones Set al., 2024, Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction., Physiol Rep, Vol: 12

The pathogenesis of exercise intolerance and persistent fatigue which can follow an infection with the SARS-CoV-2 virus ("long COVID") is not fully understood. Cases were recruited from a long COVID clinic (N = 32; 44 ± 12 years; 10 (31%) men), and age-/sex-matched healthy controls (HC) (N = 19; 40 ± 13 years; 6 (32%) men) from University College London staff and students. We assessed exercise performance, lung and cardiac function, vascular health, skeletal muscle oxidative capacity, and autonomic nervous system (ANS) function. Key outcome measures for each physiological system were compared between groups using potential outcome means (95% confidence intervals) adjusted for potential confounders. Long COVID participant outcomes were compared to normative values. When compared to HC, cases exhibited reduced oxygen uptake efficiency slope (1847 (1679, 2016) vs. 2176 (1978, 2373) mL/min, p = 0.002) and anaerobic threshold (13.2 (12.2, 14.3) vs. 15.6 (14.4, 17.2) mL/kg/min, p < 0.001), and lower oxidative capacity, measured using near infrared spectroscopy (τ: 38.7 (31.9, 45.6) vs. 24.6 (19.1, 30.1) s, p = 0.001). In cases, ANS measures fell below normal limits in 39%. Long COVID is associated with reduced measures of exercise performance and skeletal muscle oxidative capacity in the absence of evidence of microvascular dysfunction, suggesting mitochondrial pathology. There was evidence of attendant ANS dysregulation in a significant proportion. These multisystem factors might contribute to impaired exercise tolerance in long COVID sufferers.

Journal article

Murray-Smith H, Barker S, Barkhof F, Barnes J, Brown TM, Captur G, R E Cartlidge M, Cash DM, Coath W, Davis D, Dickson JC, Groves J, Hughes AD, James S-N, Keshavan A, Keuss SE, King-Robson J, Lu K, Malone IB, Nicholas JM, Rapala A, Scott CJ, Street R, Sudre CH, Thomas DL, Wong A, Wray S, Zetterberg H, Chaturvedi N, Fox NC, Crutch SJ, Richards M, Schott JMet al., 2024, Updating the study protocol: Insight 46 - a longitudinal neuroscience sub-study of the MRC National Survey of Health and Development - phases 2 and 3., BMC Neurol, Vol: 24

BACKGROUND: Although age is the biggest known risk factor for dementia, there remains uncertainty about other factors over the life course that contribute to a person's risk for cognitive decline later in life. Furthermore, the pathological processes leading to dementia are not fully understood. The main goals of Insight 46-a multi-phase longitudinal observational study-are to collect detailed cognitive, neurological, physical, cardiovascular, and sensory data; to combine those data with genetic and life-course information collected from the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort); and thereby contribute to a better understanding of healthy ageing and dementia. METHODS/DESIGN: Phase 1 of Insight 46 (2015-2018) involved the recruitment of 502 members of the NSHD (median age = 70.7 years; 49% female) and has been described in detail by Lane and Parker et al. 2017. The present paper describes phase 2 (2018-2021) and phase 3 (2021-ongoing). Of the 502 phase 1 study members who were invited to a phase 2 research visit, 413 were willing to return for a clinic visit in London and 29 participated in a remote research assessment due to COVID-19 restrictions. Phase 3 aims to recruit 250 study members who previously participated in both phases 1 and 2 of Insight 46 (providing a third data time point) and 500 additional members of the NSHD who have not previously participated in Insight 46. DISCUSSION: The NSHD is the oldest and longest continuously running British birth cohort. Members of the NSHD are now at a critical point in their lives for us to investigate successful ageing and key age-related brain morbidities. Data collected from Insight 46 have the potential to greatly contribute to and impact the field of healthy ageing and dementia by combining unique life course data with longitudinal multiparametric clinical, imaging, and biomarker measurements. Further protocol enhancements are planned, including in-home s

Journal article

Lord JM, Veenith T, Sullivan J, Sharma-Oates A, Richter AG, Greening NJ, McAuley HJC, Evans RA, Moss P, Moore SC, Turtle L, Gautam N, Gilani A, Bajaj M, Wain LV, Brightling C, Raman B, Marks M, Singapuri A, Elneima O, Openshaw PJM, Duggal NA, PHOSP-COVID Study collaborative group, ISARIC4C investigatorset al., 2024, Accelarated immune ageing is associated with COVID-19 disease severity, Immunity and Ageing, Vol: 21, ISSN: 1742-4933

BACKGROUND: The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. RESULTS: We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3-5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28-ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 sur

Journal article

Spronck B, Terentes-Printzios D, Avolio AP, Boutouyrie P, Guala A, Jerončić A, Laurent S, Barbosa ECD, Baulmann J, Chen C-H, Chirinos JA, Daskalopoulou SS, Hughes AD, Mahmud A, Mayer CC, Park JB, Pierce GL, Schutte AE, Urbina EM, Wilkinson IB, Segers P, Sharman JE, Tan I, Vlachopoulos C, Weber T, Bianchini E, Bruno RM, Association for Research into Arterial Structure and Physiology ARTERY, the European Society of Hypertension Working Group on Large Arteries, European Cooperation in Science and Technology COST Action VascAgeNet, North American Artery Society, ARTERY LATAM, Pulse of Asia, and Society for Arterial StiffnessGermany-Austria-Switzerland DeGAGet al., 2024, 2024 Recommendations for Validation of Noninvasive Arterial Pulse Wave Velocity Measurement Devices., Hypertension, Vol: 81, Pages: 183-192

BACKGROUND: Arterial stiffness, as measured by arterial pulse wave velocity (PWV), is an established biomarker for cardiovascular risk and target-organ damage in individuals with hypertension. With the emergence of new devices for assessing PWV, it has become evident that some of these devices yield results that display significant discrepancies compared with previous devices. This discrepancy underscores the importance of comprehensive validation procedures and the need for international recommendations. METHODS: A stepwise approach utilizing the modified Delphi technique, with the involvement of key scientific societies dedicated to arterial stiffness research worldwide, was adopted to formulate, through a multidisciplinary vision, a shared approach to the validation of noninvasive arterial PWV measurement devices. RESULTS: A set of recommendations has been developed, which aim to provide guidance to clinicians, researchers, and device manufacturers regarding the validation of new PWV measurement devices. The intention behind these recommendations is to ensure that the validation process can be conducted in a rigorous and consistent manner and to promote standardization and harmonization among PWV devices, thereby facilitating their widespread adoption in clinical practice. CONCLUSIONS: It is hoped that these recommendations will encourage both users and developers of PWV measurement devices to critically evaluate and validate their technologies, ultimately leading to improved consistency and comparability of results. This, in turn, will enhance the clinical utility of PWV as a valuable tool for assessing arterial stiffness and informing cardiovascular risk stratification and management in individuals with hypertension.

Journal article

Sudre CH, Van Wijnen K, Dubost F, Adams H, Atkinson D, Barkhof F, Birhanu MA, Bron EE, Camarasa R, Chaturvedi N, Chen Y, Chen Z, Chen S, Dou Q, Evans T, Ezhov I, Gao H, Girones Sanguesa M, Gispert JD, Gomez Anson B, Hughes AD, Ikram MA, Ingala S, Jaeger HR, Kofler F, Kuijf HJ, Kutnar D, Lee M, Li B, Lorenzini L, Menze B, Molinuevo JL, Pan Y, Puybareau E, Rehwald R, Su R, Shi P, Smith L, Tillin T, Tochon G, Urien H, van der Velden BHM, van der Velpen IF, Wiestler B, Wolters FJ, Yilmaz P, de Groot M, Vernooij MW, de Bruijne M, ALFA studyet al., 2024, Where is VALDO? VAscular Lesions Detection and segmentatiOn challenge at MICCAI 2021.

Imaging markers of cerebral small vessel disease provide valuable information on brain health, but their manual assessment is time-consuming and hampered by substantial intra- and interrater variability. Automated rating may benefit biomedical research, as well as clinical assessment, but diagnostic reliability of existing algorithms is unknown. Here, we present the results of the VAscular Lesions DetectiOn and Segmentation (Where is VALDO?) challenge that was run as a satellite event at the international conference on Medical Image Computing and Computer Aided Intervention (MICCAI) 2021. This challenge aimed to promote the development of methods for automated detection and segmentation of small and sparse imaging markers of cerebral small vessel disease, namely enlarged perivascular spaces (EPVS) (Task 1), cerebral microbleeds (Task 2) and lacunes of presumed vascular origin (Task 3) while leveraging weak and noisy labels. Overall, 12 teams participated in the challenge proposing solutions for one or more tasks (4 for Task 1-EPVS, 9 for Task 2-Microbleeds and 6 for Task 3-Lacunes). Multi-cohort data was used in both training and evaluation. Results showed a large variability in performance both across teams and across tasks, with promising results notably for Task 1-EPVS and Task 2-Microbleeds and not practically useful results yet for Task 3-Lacunes. It also highlighted the performance inconsistency across cases that may deter use at an individual level, while still proving useful at a population level.

Other

Webber M, Joy G, Bennett J, Chan F, Falconer D, Shiwani H, Davies RH, Krausz G, Tanackovic S, Guger C, Gonzalez P, Martin E, Wong A, Rapala A, Direk K, Kellman P, Pierce I, Rudy Y, Vijayakumar R, Chaturvedi N, Hughes AD, Moon JC, Lambiase PD, Tao X, Koncar V, Orini M, Captur Get al., 2023, Technical development and feasibility of a reusable vest to integrate cardiovascular magnetic resonance with electrocardiographic imaging., J Cardiovasc Magn Reson, Vol: 25

BACKGROUND: Electrocardiographic imaging (ECGI) generates electrophysiological (EP) biomarkers while cardiovascular magnetic resonance (CMR) imaging provides data about myocardial structure, function and tissue substrate. Combining this information in one examination is desirable but requires an affordable, reusable, and high-throughput solution. We therefore developed the CMR-ECGI vest and carried out this technical development study to assess its feasibility and repeatability in vivo. METHODS: CMR was prospectively performed at 3T on participants after collecting surface potentials using the locally designed and fabricated 256-lead ECGI vest. Epicardial maps were reconstructed to generate local EP parameters such as activation time (AT), repolarization time (RT) and activation recovery intervals (ARI). 20 intra- and inter-observer and 8 scan re-scan repeatability tests. RESULTS: 77 participants were recruited: 27 young healthy volunteers (HV, 38.9 ± 8.5 years, 35% male) and 50 older persons (77.0 ± 0.1 years, 52% male). CMR-ECGI was achieved in all participants using the same reusable, washable vest without complications. Intra- and inter-observer variability was low (correlation coefficients [rs] across unipolar electrograms = 0.99 and 0.98 respectively) and scan re-scan repeatability was high (rs between 0.81 and 0.93). Compared to young HV, older persons had significantly longer RT (296.8 vs 289.3 ms, p = 0.002), ARI (249.8 vs 235.1 ms, p = 0.002) and local gradients of AT, RT and ARI (0.40 vs 0.34 ms/mm, p = 0,01; 0.92 vs 0.77 ms/mm, p = 0.03; and 1.12 vs 0.92 ms/mm, p = 0.01 respectively). CONCLUSION: Our high-throughput CMR-ECGI solution is feasible and shows good reproducibility in younger and older participants. This new technology is now scalable for high throughput research to provide novel insig

Journal article

Rajput S, Jamieson A, Chaturvedi N, Hughes A, Orini Met al., 2023, Assessment of Consumer-grade Wearable Devices to Track Sleep in Healthy Individuals in Free-living Conditions, 2023 Computing in Cardiology Conference, Publisher: Computing in Cardiology, ISSN: 2325-887X

Conference paper

Thornton GD, Bennett JB, Nitsche C, Gama F, Mravljak R, Abiodun AT, Aziminia N, Tapia L, Knott K, Pierce I, Lloyd G, Hughes A, Davies RH, Gonzalez A, Moon J, Kellman P, Treibel Tet al., 2023, Abstract 13882: Myocardial Hypoperfusion in Severe Aortic Stenosis is Reversed by Aortic Valve Replacement, Circulation, Vol: 148, ISSN: 0009-7322

<jats:p> <jats:bold>Background:</jats:bold> Myocardial hypoperfusion in severe aortic stenosis (AS) without obstructive coronary disease may be secondary to hemodynamic influences (and therefore readily reversible by aortic valve replacement[AVR]) or structural alterations in the left ventricle (LV) such as increased mass and reduction in capillary density. </jats:p> <jats:p> <jats:bold>Aim:</jats:bold> To evaluate the early effect of AVR on myocardial blood flow (MBF) in patients with severe symptomatic AS without flow-limiting coronary artery disease. </jats:p> <jats:p> <jats:bold>Methods:</jats:bold> Prospective case-control study of severe symptomatic AS without obstructive coronary disease referred for surgical or transcatheter AVR and propensity matched to a control cohort with unobstructed coronary arteries. Patients underwent adenosine stress cardiovascular magnetic resonance at baseline and 8-weeks (median) post-operatively. Histology from 9 myocardial septal biopsies taken at AVR were compared against necropsy controls (n=5). </jats:p> <jats:p> <jats:bold>Results:</jats:bold> 52 patients were included; 26 with severe AS (median [IQR] age 71[66-75], 73% male) and 26 age, sex and co-morbidity matched controls. In AS, peak velocity(Vmax) was 4.3m/s[4.1-4.5] and AVA 0.8cm <jats:sup>2</jats:sup> [0.6-0.9]. AS patients had greater LV mass and late gadolinium enhancement. AS patients had lower stress MBF than controls (1.63ml/g/min[1.38-2.08] vs 2.13[1.76-2.52], p=0.003) which increased to 1.97ml/g/min after AVR (p=0.7 post-AVR vs. Controls). This was driven by a 40% increase in subendocardial MBF (1.26ml/g/min[1.18-1.78] to 1.77[1.62-2.32]). Capillary density was reduced almost threefold in AS (495/mm

Journal article

Orini M, van Duijvenboden S, Young WJ, Ramírez J, Jones AR, Hughes AD, Tinker A, Munroe PB, Lambiase PDet al., 2023, Long-term association of ultra-short heart rate variability with cardiovascular events., Sci Rep, Vol: 13

Heart rate variability (HRV) is a cardiac autonomic marker with predictive value in cardiac patients. Ultra-short HRV (usHRV) can be measured at scale using standard and wearable ECGs, but its association with cardiovascular events in the general population is undetermined. We aimed to validate usHRV measured using ≤ 15-s ECGs (using RMSSD, SDSD and PHF indices) and investigate its association with atrial fibrillation, major adverse cardiac events, stroke and mortality in individuals without cardiovascular disease. In the National Survey for Health and Development (n = 1337 participants), agreement between 15-s and 6-min HRV, assessed with correlation analysis and Bland-Altman plots, was very good for RMSSD and SDSD and good for PHF. In the UK Biobank (n = 51,628 participants, 64% male, median age 58), after a median follow-up of 11.5 (11.4-11.7) years, incidence of outcomes ranged between 1.7% and 4.3%. Non-linear Cox regression analysis showed that reduced usHRV from 15-, 10- and 5-s ECGs was associated with all outcomes. Individuals with low usHRV (< 20th percentile) had hazard ratios for outcomes between 1.16 and 1.29, p < 0.05, with respect to the reference group. In conclusion, usHRV from ≤ 15-s ECGs correlates with standard short-term HRV and predicts increased risk of cardiovascular events in a large population-representative cohort.

Journal article

C-MOREPHOSP-COVID Collaborative Group, 2023, Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study, The Lancet Respiratory Medicine, Vol: 11, Pages: 1003-1019, ISSN: 2213-2600

INTRODUCTION: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. METHODS: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. FINDINGS: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2-6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MR

Journal article

Brightling CE, Evans RA, Singapuri A, Smith N, Wain LV, PHOSP-COVID Collaborative Groupet al., 2023, Long COVID research: an update from the PHOSP-COVID Scientific Summit., Lancet Respir Med, Vol: 11, Pages: e93-e94

Journal article

Topriceanu C-C, Dev E, Ahmad M, Hughes R, Shiwani H, Webber M, Direk K, Wong A, Ugander M, Moon JC, Hughes AD, Maddock J, Schlegel TT, Captur Get al., 2023, Accelerated DNA methylation age plays a role in the impact of cardiovascular risk factors on the human heart., Clin Epigenetics, Vol: 15

BACKGROUND: DNA methylation (DNAm) age acceleration (AgeAccel) and cardiac age by 12-lead advanced electrocardiography (A-ECG) are promising biomarkers of biological and cardiac aging, respectively. We aimed to explore the relationships between DNAm age and A-ECG heart age and to understand the extent to which DNAm AgeAccel relates to cardiovascular (CV) risk factors in a British birth cohort from 1946. RESULTS: We studied four DNAm ages (AgeHannum, AgeHorvath, PhenoAge, and GrimAge) and their corresponding AgeAccel. Outcomes were the results from two publicly available ECG-based cardiac age scores: the Bayesian A-ECG-based heart age score of Lindow et al. 2022 and the deep neural network (DNN) ECG-based heart age score of Ribeiro et al. 2020. DNAm AgeAccel was also studied relative to results from two logistic regression-based A-ECG disease scores, one for left ventricular (LV) systolic dysfunction (LVSD), and one for LV electrical remodeling (LVER). Generalized linear models were used to explore the extent to which any associations between biological cardiometabolic risk factors (body mass index, hypertension, diabetes, high cholesterol, previous cardiovascular disease [CVD], and any CV risk factor) and the ECG-based outcomes are mediated by DNAm AgeAccel. We derived the total effects, average causal mediation effects (ACMEs), average direct effects (ADEs), and the proportion mediated [PM] with their 95% confidence intervals [CIs]. 498 participants (all 60-64 years) were included, with the youngest ECG heart age being 27 and the oldest 90. When exploring the associations between cardiometabolic risk factors and Bayesian A-ECG cardiac age, AgeAccelPheno appears to be a partial mediator, as ACME was 0.23 years [0.01, 0.52] p = 0.028 (i.e., PM≈18%) for diabetes, 0.34 [0.03, 0.74] p = 0.024 (i.e., PM≈15%) for high cholesterol, and 0.34 [0.03, 0.74] p = 0.024 (P

Journal article

Fonseca R, Palmer AJ, Picone DS, Cox IA, Schultz MG, Black JA, Bos WJW, Cheng H-M, Chen C-H, Cremer A, Dwyer N, Hughes AD, Lacy P, Omboni S, Ott C, Pereira T, Pucci G, Schmieder R, Wang J-G, Weber T, Westerhof BE, Williams B, Sharman JEet al., 2023, Cardiovascular and health cost impacts of cuff blood pressure underestimation and overestimation of invasive aortic systolic blood pressure, JOURNAL OF HYPERTENSION, Vol: 41, Pages: 1585-1594, ISSN: 0263-6352

Journal article

Taylor HCM, Chaturvedi N, Davey Smith G, Ferreira DLS, Fraser A, Howe LD, Hughes AD, Lawlor DA, Timpson NJ, Park CMet al., 2023, Is Height2.7 Appropriate for Indexation of Left Ventricular Mass in Healthy Adolescents? The Importance of Sex Differences., Hypertension, Vol: 80, Pages: 2033-2042

BACKGROUND: Left ventricular mass (LVM) is an important predictor of cardiovascular risk. In adolescence, LVM is commonly indexed to height2.7, although some evidence suggests that this may not fully account for sex differences. METHODS: We investigated appropriate allometric scaling of LVM to height, total lean mass, and body surface area, in a UK birth cohort of 2039 healthy adolescents (17±1 years). Allometric relationships were determined by linear regression stratified by sex, following log transformation of x and y variables [log(y)=a+b×log(x)], b is the allometric exponent. RESULTS: Log (LVM) showed linear relationships with log(height) and log(lean mass). Biased estimates of slope resulted when the sexes were pooled. The exponents were lower than the conventional estimate of 2.7 for males (mean [95% CI]=1.66 [1.30-2.03]) and females (1.58 [1.27-1.90]). When LVM was indexed to lean mass, the exponent was 1.16 (1.05-1.26) for males and 1.07 (0.97-1.16) for females. When LVM was indexed to estimated body surface area, the exponent was 1.53 (1.40-1.66) for males and 1.34 (1.24-1.45) for females. CONCLUSIONS: Allometric exponents derived from pooled data, including men and women without adjustment for sex were biased, possibly due to sex differences in body composition. We suggest that when assessing LVM, clinicians should consider body size, body composition, sex, and age. Our observations may also have implications for the identification of young individuals with cardiac hypertrophy.

Journal article

Bennett J, van Dinther M, Voorter P, Backes W, Barnes J, Barkhof F, Captur G, Hughes AD, Sudre C, Treibel TAet al., 2023, Assessment of Microvascular Disease in Heart and Brain by MRI: Application in Heart Failure with Preserved Ejection Fraction and Cerebral Small Vessel Disease, MEDICINA-LITHUANIA, Vol: 59, ISSN: 1010-660X

Journal article

Jones SH, Park C, Chaturvedi N, Hughes ADet al., 2023, Physical Activity Throughout Adolescence Is An Important Determinant Of VO2Max In Early Adulthood, Medicine &amp; Science in Sports &amp; Exercise, Vol: 55, Pages: 680-680, ISSN: 0195-9131

Journal article

Jamieson A, Astin R, Bell R, Hamer M, Howes LH, Heightman M, Hillman T, Montgomery H, Al Saikhan L, Scully MA, Treibel T, Hughes AD, Jones Set al., 2023, Cardiopulmonary Fitness, Skeletal Muscle Oxidative Capacity And Microvascular Function In People Living With Long Covid Compared With Healthy Controls, Medicine &amp; Science in Sports &amp; Exercise, Vol: 55, Pages: 817-817, ISSN: 0195-9131

Journal article

Ioannou A, Massa P, Patel RK, Razvi Y, Porcari A, Rauf MU, Jiang A, Cabras G, Filisetti S, Bolhuis RE, Bandera F, Venneri L, Martinez-Naharro A, Law S, Kotecha T, Virsinskaite R, Knight DS, Emdin M, Petrie A, Lachmann H, Wechelakar A, Petrie M, Hughes A, Freemantle N, Hawkins PN, Whelan C, McMurray JJ, Gillmore JD, Fontana Met al., 2023, Conventional heart failure therapy in cardiac ATTR amyloidosis, EUROPEAN HEART JOURNAL, Vol: 44, Pages: 2893-2907, ISSN: 0195-668X

Journal article

Jackson C, Stewart ID, Plekhanova T, Cunningham PS, Hazel AL, Al-Sheklly B, Aul R, Bolton CE, Chalder T, Chalmers JD, Chaudhuri N, Docherty AB, Donaldson G, Edwardson CL, Elneima O, Greening NJ, Hanley NA, Harris VC, Harrison EM, Ho L-P, Houchen-Wolloff L, Howard LS, Jolley CJ, Jones MG, Leavy OC, Lewis KE, Lone NI, Marks M, McAuley HJC, McNarry MA, Patel BV, Piper-Hanley K, Poinasamy K, Raman B, Richardson M, Rivera-Ortega P, Rowland-Jones SL, Rowlands AV, Saunders RM, Scott JT, Sereno M, Shah AM, Shikotra A, Singapuri A, Stanel SC, Thorpe M, Wootton DG, Yates T, Gisli Jenkins R, Singh SJ, Man WD-C, Brightling CE, Wain LV, Porter JC, Thompson AAR, Horsley A, Molyneaux PL, Evans RA, Jones SE, Rutter MK, Blaikley JF, PHOSP-COVID Study Collaborative Groupet al., 2023, Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study, The Lancet Respiratory Medicine, Vol: 11, Pages: 673-684, ISSN: 2213-2600

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended

Journal article

Hudson LD, Al-Khairulla H, Maicoo M, Borja MC, Rapala A, Viner R, Nicholls D, Taylor A, Muthurangu V, Hughes Aet al., 2023, Pulse wave velocity during re-feeding and with weight gain in underweight female adolescents with anorexia nervosa, Journal of Human Hypertension, Pages: 1-3, ISSN: 0950-9240

Anorexia Nervosa (AN) causes harmful underweight and important cardiovascular acute complications however less is known about longer-term cardiovascular risk. We measured carotid femoral pulse wave velocity (PWV) in a group of underweight young women with AN at baseline and weekly as they were refed and gained weight. PWV decreased over time and was negatively associated with increasing BMI and calorific meal content suggesting potential positive cardiovascular benefits for refeeding and weight gain in AN and supports current consensus for the importance of weight gain in underweight young women with AN.

Journal article

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