Publications by authors named "Alun D Hughes"

314 Publications

Age matters: differences in exercise-induced cardiovascular remodelling in young and middle aged healthy sedentary individuals.

Eur J Prev Cardiol 2021 Jul;28(7):738-746

Institute of Cardiovascular Science, University College London, UK.

Aims: Remodelling of the cardiovascular system (including heart and vasculature) is a dynamic process influenced by multiple physiological and pathological factors. We sought to understand whether remodelling in response to a stimulus, exercise training, altered with healthy ageing.

Methods: A total of 237 untrained healthy male and female subjects volunteering for their first time marathon were recruited. At baseline and after 6 months of unsupervised training, race completers underwent tests including 1.5T cardiac magnetic resonance, brachial and non-invasive central blood pressure assessment. For analysis, runners were divided by age into under or over 35 years (U35, O35).

Results: Injury and completion rates were similar among the groups; 138 runners (U35: n = 71, women 49%; O35: n = 67, women 51%) completed the race. On average, U35 were faster by 37 minutes (12%). Training induced a small increase in left ventricular mass in both groups (3 g/m2, P < 0.001), but U35 also increased ventricular cavity sizes (left ventricular end-diastolic volume (EDV)i +3%; left ventricular end-systolic volume (ESV)i +8%; right ventricular end-diastolic volume (EDV)i +4%; right ventricular end-systolic volume (ESV)i +5%; P < 0.01 for all). Systemic aortic compliance fell in the whole sample by 7% (P = 0.020) and, especially in O35, also systemic vascular resistance (-4% in the whole sample, P = 0.04) and blood pressure (systolic/diastolic, whole sample: brachial -4/-3 mmHg, central -4/-2 mmHg, all P < 0.001; O35: brachial -6/-3 mmHg, central -6/-4 mmHg, all P < 0.001).

Conclusion: Medium-term, unsupervised physical training in healthy sedentary individuals induces measurable remodelling of both heart and vasculature. This amount is age dependent, with predominant cardiac remodelling when younger and predominantly vascular remodelling when older.
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http://dx.doi.org/10.1177/2047487320926305DOI Listing
July 2021

Blood pressure variability and night-time dipping assessed by 24-hour ambulatory monitoring: Cross-sectional association with cardiac structure in adolescents.

PLoS One 2021 16;16(6):e0253196. Epub 2021 Jun 16.

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.

Greater blood pressure (BP) is associated with greater left ventricular mass indexed to height2.7 (LVMi2.7) in adolescents. This study examined whether greater BP variability and reduced night-time dipping are associated with cardiac remodeling in a general population of adolescents. A cross-sectional analysis was undertaken in 587 UK adolescents (mean age 17.7 years; 43.1% male). BP was measured in a research clinic and using 24-hour ambulatory monitoring. We examined associations (for both systolic and diastolic BP) of: 1) clinic and 24-hour mean BP; 2) measures of 24-hour BP variability: standard deviation weighted for day/night (SDdn), variability independent of the mean (VIM) and average real variability (ARV); and 3) night-time dipping with cardiac structures. Cardiac structures were assessed by echocardiography: 1) LVMi2.7; 2) relative wall thickness (RWT); 3) left atrial diameter indexed to height (LADi) and 4) left ventricular internal diameter in diastole (LVIDD). Higher systolic BP was associated with greater LVMi2.7. Systolic and diastolic BP were associated with greater RWT. Associations were inconsistent for LADi and LVIDD. There was evidence for associations between both greater SDdn and ARV and higher RWT (per 1 SD higher diastolic ARV, mean difference in RWT was 0.13 SDs, 95% CI 0.045 to 0.21); these associations with RWT remained after adjustment for mean BP. There was no consistent evidence of associations between night-time dipping and cardiac structure. Measurement of BP variability, even in adolescents with blood pressure in the physiologic range, might benefit risk of cardiovascular remodeling assessment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253196PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208567PMC
June 2021

Fibrinogen-mimicking, multiarm nanovesicles for human thrombus-specific delivery of tissue plasminogen activator and targeted thrombolytic therapy.

Sci Adv 2021 Jun 2;7(23). Epub 2021 Jun 2.

Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, UK.

Clinical use of tissue plasminogen activator (tPA) in thrombolytic therapy is limited by its short circulation time and hemorrhagic side effects. Inspired by fibrinogen binding to activated platelets, we report a fibrinogen-mimicking, multiarm nanovesicle for thrombus-specific tPA delivery and targeted thrombolysis. This biomimetic system is based on the lipid nanovesicle coated with polyethylene glycol (PEG) terminally conjugated with a cyclic RGD (cRGD) peptide. Our experiments with human blood demonstrated its highly selective binding to activated platelets and efficient tPA release at a thrombus site under both static and physiological flow conditions. Its clot dissolution time in a microfluidic system was comparable to that of free tPA. Furthermore, we report a purpose-built computational model capable of simulating targeted thrombolysis of the tPA-loaded nanovesicle and with a potential in predicting the dynamics of thrombolysis in physiologically realistic scenarios. This combined experimental and computational work presents a promising platform for development of thrombolytic nanomedicines.
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http://dx.doi.org/10.1126/sciadv.abf9033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172176PMC
June 2021

Prognostic Value of Pulmonary Transit Time and Pulmonary Blood Volume Estimation Using Myocardial Perfusion CMR.

JACC Cardiovasc Imaging 2021 May 12. Epub 2021 May 12.

National Heart, Lung, and Blood Institute, National Institutes of Health, DHHS, Bethesda, Maryland, USA. Electronic address:

Objectives: The purpose of this study was to explore the prognostic significance of PTT and PBVi using an automated, inline method of estimation using CMR.

Background: Pulmonary transit time (PTT) and pulmonary blood volume index (PBVi) (the product of PTT and cardiac index), are quantitative biomarkers of cardiopulmonary status. The development of cardiovascular magnetic resonance (CMR) quantitative perfusion mapping permits their automated derivation, facilitating clinical adoption.

Methods: In this retrospective 2-center study of patients referred for clinical myocardial perfusion assessment using CMR, analysis of right and left ventricular cavity arterial input function curves from first pass perfusion was performed automatically (incorporating artificial intelligence techniques), allowing estimation of PTT and subsequent derivation of PBVi. Association with major adverse cardiovascular events (MACE) and all-cause mortality were evaluated using Cox proportional hazard models, after adjusting for comorbidities and CMR parameters.

Results: A total of 985 patients (67% men, median age 62 years [interquartile range (IQR): 52 to 71 years]) were included, with median left ventricular ejection fraction (LVEF) of 62% (IQR: 54% to 69%). PTT increased with age, male sex, atrial fibrillation, and left atrial area, and reduced with LVEF, heart rate, diabetes, and hypertension (model r = 0.57). Over a median follow-up period of 28.6 months (IQR: 22.6 to 35.7 months), MACE occurred in 61 (6.2%) patients. After adjusting for prognostic factors, both PTT and PBVi independently predicted MACE, but not all-cause mortality. There was no association between cardiac index and MACE. For every 1 × SD (2.39-s) increase in PTT, the adjusted hazard ratio for MACE was 1.43 (95% confidence interval [CI]: 1.10 to 1.85; p = 0.007). The adjusted hazard ratio for 1 × SD (118 ml/m) increase in PBVi was 1.42 (95% CI: 1.13 to 1.78; p = 0.002).

Conclusions: Pulmonary transit time (and its derived parameter pulmonary blood volume index), measured automatically without user interaction as part of CMR perfusion mapping, independently predicted adverse cardiovascular outcomes. These biomarkers may offer additional insights into cardiopulmonary function beyond conventional predictors including ejection fraction.
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http://dx.doi.org/10.1016/j.jcmg.2021.03.029DOI Listing
May 2021

Effect of a multicomponent intervention on antihypertensive medication intensification in rural South Asia: post-hoc analysis of a cluster RCT.

Am J Hypertens 2021 May 20. Epub 2021 May 20.

Program in Health Services & Systems Research, Duke-NUS Medical School, Singapore.

Background: Inadequate treatment of hypertension is a widespread problem, especially in South Asian countries where cardiovascular disease mortality rates are high. We aimed to explore the effect of a multicomponent intervention (MCI) on antihypertensive medication intensification among rural South Asians with hypertension.

Methods: A post-hoc analysis of a two-year cluster-randomized controlled trial including 2645 hypertensives aged≥ 40 years from 30 rural communities, 10 each, in Bangladesh, Pakistan, and Sri Lanka. Independent assessors collected information on participants' self-reports and physical inspection of medications. The main outcomes were the changes from baseline to 24 months in the following: 1) the therapeutic intensity score (TIS) for all (and class specific) antihypertensive medications; 2) the number of antihypertensive medications in all trial participants.

Results: At 24 months, the mean increase in the TIS score of all antihypertensive medications was 0.11 in the MCI group and 0.03 in the control group, with a between-group difference in the increase of 0.08 (95% CI (0.03, 0.12); P=0.002). In MCI compared to controls, a greater increase in the TIS of renin angiotensin-aldosterone system blockers (0.05; 95% CI (0.02, 0.07); P<0.001) and calcium channel blockers (0.03; 95% CI (0.00, 0.05);p=0.031) , and in the number of antihypertensive medications (0.11, 95% CI (0.02, 0.19);P=0.016) was observed.

Conclusions: In rural communities in Bangladesh, Pakistan, and Sri Lanka, MCI led to a greater increase in antihypertensive medication intensification compared to the usual care among adults with hypertension.

Trial Registration: clinicaltrials.gov Identifier: NCT02657746.
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http://dx.doi.org/10.1093/ajh/hpab072DOI Listing
May 2021

Cardiorespiratory fitness, fatness, and the acute blood pressure response to exercise in adolescence.

Scand J Med Sci Sports 2021 Aug 8;31(8):1693-1698. Epub 2021 May 8.

Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

Objective: Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Cardiorespiratory fitness and adiposity (fatness) are independent contributors to cardiovascular risk, but their interrelated associations with exercise BP are unknown. This study aimed to determine the relationships between fitness, fatness, and the acute BP response to exercise in a large birth cohort of adolescents.

Methods: 2292 adolescents from the Avon Longitudinal Study of Parents and Children (aged 17.8 ± 0.4 years, 38.5% male) completed a sub-maximal exercise step test that allowed fitness (VO ) to be determined from workload and heart rate using a validated equation. Exercise BP was measured immediately on test cessation and fatness calculated as the ratio of total fat mass to total body mass measured by DXA.

Results: Post-exercise systolic BP decreased stepwise with tertile of fitness (146 (18); 142 (17); 141 (16) mmHg) but increased with tertile of fatness (138 (15); 142 (16); 149 (18) mmHg). In separate models, fitness and fatness were associated with post-exercise systolic BP adjusted for sex, age, height, smoking, and socioeconomic status (standardized β: -1.80, 95%CI: -2.64, -0.95 mmHg/SD and 4.31, 95%CI: 3.49, 5.13 mmHg/SD). However, when fitness and fatness were included in the same model, only fatness remained associated with exercise BP (4.65, 95%CI: 3.69, 5.61 mmHg/SD).

Conclusion: Both fitness and fatness are associated with the acute BP response to exercise in adolescence. The fitness-exercise BP association was not independent of fatness, implying the cardiovascular protective effects of cardiorespiratory fitness may only be realized with more favorable body composition.
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http://dx.doi.org/10.1111/sms.13976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611236PMC
August 2021

Study Protocol: The Heart and Brain Study.

Front Physiol 2021 31;12:643725. Epub 2021 Mar 31.

Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom.

Background: It is well-established that what is good for the heart is good for the brain. Vascular factors such as hypertension, diabetes, and high cholesterol, and genetic factors such as the apolipoprotein E4 allele increase the risk of developing both cardiovascular disease and dementia. However, the mechanisms underlying the heart-brain association remain unclear. Recent evidence suggests that impairments in vascular phenotypes and cerebrovascular reactivity (CVR) may play an important role in cognitive decline. The combines state-of-the-art vascular ultrasound, cerebrovascular magnetic resonance imaging (MRI) and cognitive testing in participants of the long-running Whitehall II Imaging cohort to examine these processes together. This paper describes the study protocol, data pre-processing and overarching objectives.

Methods And Design: The 775 participants of the Whitehall II Imaging cohort, aged 65 years or older in 2019, have received clinical and vascular risk assessments at 5-year-intervals since 1985, as well as a 3T brain MRI scan and neuropsychological tests between 2012 and 2016 (Whitehall II Wave MRI-1). Approximately 25% of this cohort are selected for the , which involves a single testing session at the University of Oxford (Wave MRI-2). Between 2019 and 2023, participants will undergo ultrasound scans of the ascending aorta and common carotid arteries, measures of central and peripheral blood pressure, and 3T MRI scans to measure CVR in response to 5% carbon dioxide in air, vessel-selective cerebral blood flow (CBF), and cerebrovascular lesions. The structural and diffusion MRI scans and neuropsychological battery conducted at Wave MRI-1 will also be repeated. Using this extensive life-course data, the will examine how 30-year trajectories of vascular risk throughout midlife (40-70 years) affect vascular phenotypes, cerebrovascular health, longitudinal brain atrophy and cognitive decline at older ages.

Discussion: The study will generate one of the most comprehensive datasets to examine the longitudinal determinants of the heart-brain association. It will evaluate novel physiological processes in order to describe the optimal window for managing vascular risk in order to delay cognitive decline. Ultimately, the will inform strategies to identify at-risk individuals for targeted interventions to prevent or delay dementia.
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http://dx.doi.org/10.3389/fphys.2021.643725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046163PMC
March 2021

Impact of lockdown on key workers: findings from the COVID-19 survey in four UK national longitudinal studies.

J Epidemiol Community Health 2021 Apr 9. Epub 2021 Apr 9.

MRC Unit for Lifelong Health and Ageing, University College London, London, UK

Background: Key workers played a pivotal role during the national lockdown in the UK's response to the COVID-19 pandemic. Although protective measures have been taken, the impact of the pandemic on key workers is yet to be fully elucidated.

Methods: Participants were from four longitudinal age-homogeneous British cohorts (born in 2001, 1990, 1970 and 1958). A web-based survey provided outcome data during the first UK national lockdown (May 2020) on COVID-19 infection status, changes in financial situation, trust in government, conflict with people around, household composition, psychological distress, alcohol consumption, smoking and sleep duration. Generalised linear models with logit link assessed the association between being a key worker and the above outcomes. Adjustment was made for cohort design, non-response, sex, ethnicity, adult socioeconomic position (SEP), childhood SEP, the presence of a chronic illness and receipt of a shielding letter. Meta-analyses were performed across the cohorts.

Findings: 13 736 participants were included. During lockdown, being a key worker was associated with increased chances of being infected with COVID-19 (OR 1.43, 95% CI 1.22 to 1.68) and experiencing conflict with people around (OR 1.19, 95% CI 1.03 to 1.37). However, key workers were less likely to be worse off financially (OR 0.32, 95% CI 0.24 to 0.65), to consume more alcohol (OR 0.88, 95% CI 0.79 to 0.98) or to smoke more (OR 0.60, 95% CI 0.44 to 0.80) during lockdown. Interestingly, being a key worker was not associated with psychological distress (OR 0.95, 95% CI 0.85 to 1.05).

Interpretation: Being a key worker during the first UK COVID-19 lockdown was a double-edged sword, with both benefits and downsides. The UK government had the basic duty to protect its key workers from SARS-CoV-2 infection, but it may have failed to do so, and there is an urgent need to rectify this in light of the ongoing third wave.
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http://dx.doi.org/10.1136/jech-2020-215889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042596PMC
April 2021

Patients with aortic stenosis exhibit early improved endothelial function following transcatheter aortic valve replacement: The eFAST study.

Int J Cardiol 2021 06 26;332:143-147. Epub 2021 Mar 26.

Monash Cardiovascular Research Centre, MonashHeart, Monash University and Monash Health, Melbourne, Australia. Electronic address:

Background: Patients with severe aortic stenosis (AS) exhibit systemic endothelial dysfunction, which can be associated with myocardial ischaemia in absence of obstructive coronary disease. Transcatheter aortic valve replacement (TAVR) is used to treat severe AS in patients with high or prohibitive surgical risk. However, it remains unknown whether endothelial function recovers post-TAVR. We therefore sought to assess the early and late changes in flow-mediated dilation (FMD), a measure of endothelial function, following TAVR.

Methods: Patients undergoing TAVR for severe AS had ultrasound assessment of brachial endothelial-independent and -dependent FMD. Measurements were performed pre-TAVR, at early follow-up (<48 h post-TAVR) and late follow-up (4-6 weeks post-TAVR).

Results: 27 patients (mean age 82.0 ± 7.0; 33.3% female) were recruited; 37.0% had diabetes mellitus and 59.3% had hypertension. Brachial artery FMD increased from 4.2 ± 1.6% (pre-TAVR) to 9.7 ± 3.5% at early follow-up (p < 0.0001). At late follow-up, improvement compared with early follow-up was sustained (8.7 ± 1.9%, p = 0.27). Resting brachial arterial flow velocities decreased significantly at late follow-up (11.24 ± 5.16 vs. 7.73 ± 2.79 cm/s, p = 0.003). Concordantly, at late follow-up, there was decrease in resting wall shear stress (WSS; 14.8 ± 7.8 vs. 10.6 ± 4.8dyne/cm2, p = 0.01), peak WSS (73.1 ± 34.1 vs. 58.8 ± 27.8dyne/cm2, p = 0.03) and cumulative WSS (3543 ± 1852 vs. 2504 ± 1089dyne·s/cm, p = 0.002). Additionally, a favourable inverse correlation between cumulative WSS and FMD was restored at late follow-up (r = -0.21 vs. r = 0.49).

Conclusion: Endothelial function in patients with AS improves early post-TAVR and this improvement is sustained. This likely occurs as a result of improved arterial haemodynamics, leading to lower localised WSS and release of vasoactive mediators that may also alleviate myocardial ischaemia.
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http://dx.doi.org/10.1016/j.ijcard.2021.03.062DOI Listing
June 2021

Physiological and clinical insights from reservoir-excess pressure analysis.

J Hum Hypertens 2021 Mar 9. Epub 2021 Mar 9.

Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

There is a growing body of evidence indicating that reservoir-excess pressure model parameters provide physiological and clinical insights above and beyond standard blood pressure (BP) and pulse waveform analysis. This information has never been collectively examined and was the aim of this review. Cardiovascular disease is the leading cause of mortality worldwide, with BP as the greatest cardiovascular disease risk factor. However, brachial systolic and diastolic BP provide limited information on the underlying BP waveform, missing important BP-related cardiovascular risk. A comprehensive analysis of the BP waveform is provided by parameters derived via the reservoir-excess pressure model, which include reservoir pressure, excess pressure, and systolic and diastolic rate constants and Pinfinity. These parameters, derived from the arterial BP waveform, provide information on the underlying arterial physiology and ventricular-arterial interactions otherwise missed by conventional BP and waveform indices. Application of the reservoir-excess pressure model in the clinical setting may facilitate a better understanding and earlier identification of cardiovascular dysfunction associated with disease. Indeed, reservoir-excess pressure parameters have been associated with sub-clinical markers of end-organ damage, cardiac and vascular dysfunction, and future cardiovascular events and mortality beyond conventional risk factors. In the future, greater understanding is needed on how the underlying physiology of the reservoir-excess pressure parameters informs cardiovascular disease risk prediction over conventional BP and waveform indices. Additional consideration should be given to the application of the reservoir-excess pressure model in clinical practice using new technologies embedded into conventional BP assessment methods.
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http://dx.doi.org/10.1038/s41371-021-00515-6DOI Listing
March 2021

Longitudinal birth cohort study finds that life-course frailty associates with later-life heart size and function.

Sci Rep 2021 Mar 18;11(1):6272. Epub 2021 Mar 18.

UCL MRC Unit for Lifelong Health and Ageing, University College London, Fitzrovia, London, WC1E 7HB, UK.

A frailty index (FI) counts health deficit accumulation. Besides traditional risk factors, it is unknown whether the health deficit burden is related to the appearance of cardiovascular disease. In order to answer this question, the same multidimensional FI looking at 45-health deficits was serially calculated per participant at 4 time periods (0-16, 19-44, 45-54 and 60-64 years) using data from the 1946 Medical Research Council (MRC) British National Survey of Health and Development (NSHD)-the world's longest running longitudinal birth cohort with continuous follow-up. From these the mean and total FI for the life-course, and the step change in deficit accumulation from one time period to another was derived. Echocardiographic data at 60-64 years provided: ejection fraction (EF), left ventricular mass indexed to body surface area (LVmassi, BSA), myocardial contraction fraction indexed to BSA (MCF) and E/e'. Generalized linear models assessed the association between FIs and echocardiographic parameters after adjustment for relevant covariates. 1375 participants were included. For each single new deficit accumulated at any one of the 4 time periods, LVmass increased by 0.91-1.44% (p < 0.013), while MCF decreased by 0.6-1.02% (p < 0.05). A unit increase in FI at age 45-54 and 60-64, decreased EF by 11-12% (p < 0.013). A single health deficit step change occurring between 60 and 64 years and one of the earlier time periods, translated into higher odds (2.1-78.5, p < 0.020) of elevated LV filling pressure. Thus, the accumulation of health deficits at any time period of the life-course associates with a maladaptive cardiac phenotype in older age, dominated by myocardial hypertrophy and poorer function.
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http://dx.doi.org/10.1038/s41598-021-85435-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973558PMC
March 2021

Evaluating access to health and care services during lockdown by the COVID-19 survey in five UK national longitudinal studies.

BMJ Open 2021 03 18;11(3):e045813. Epub 2021 Mar 18.

School of Medicine, University College London, London, UK

Objective: Access to health services and adequate care is influenced by sex, ethnicity, socioeconomic position (SEP) and the burden of comorbidities. Our study aimed to assess whether the COVID-19 pandemic further deepened these already existing health inequalities.

Design: Cross-sectional study.

Setting: Data were collected from five longitudinal age-homogenous British cohorts (born in 2000-2002, 1989-1990, 1970, 1958 and 1946).

Participants: A web survey was sent to the cohorts. Anybody who responded to the survey was included, resulting in 14 891 eligible participants.

Main Outcomes Measured: The survey provided data on cancelled surgical or medical appointments, and the number of care hours received in a week during the first UK COVID-19 national lockdown.

Interventions: Using binary or ordered logistic regression, we evaluated whether these outcomes differed by sex, ethnicity, SEP and having a chronic illness. Adjustment was made for study design, non-response weights, psychological distress, presence of children or adolescents in the household, COVID-19 infection, key worker status, and whether participants had received a shielding letter. Meta-analyses were performed across the cohorts, and meta-regression was used to evaluate the effect of age as a moderator.

Results: Women (OR 1.40, 95% CI 1.27 to 1.55) and those with a chronic illness (OR 1.84, 95% CI 1.65 to 2.05) experienced significantly more cancellations during lockdown (all p<0.0001). Ethnic minorities and those with a chronic illness required a higher number of care hours during the lockdown (both OR≈2.00, all p<0.002). SEP was not associated with cancellation or care hours. Age was not independently associated with either outcome in the meta-regression.

Conclusion: The UK government's lockdown approach during the COVID-19 pandemic appears to have deepened existing health inequalities, impacting predominantly women, ethnic minorities and those with chronic illnesses. Public health authorities need to implement urgent policies to ensure equitable access to health and care for all in preparation for a fourthwave.
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http://dx.doi.org/10.1136/bmjopen-2020-045813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978270PMC
March 2021

Metformin and carotid intima-media thickness in never-smokers with type 1 diabetes: The REMOVAL trial.

Diabetes Obes Metab 2021 06 8;23(6):1371-1378. Epub 2021 Mar 8.

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.

Aim: To determine whether metformin's effects on carotid artery intima-media thickness (cIMT) in type 1 diabetes differ according to smoking status.

Methods: Regression model effect estimates for the effect of metformin versus placebo (double-blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial.

Results: In 428 randomized participants (227 never-smokers, 201 ever-smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (-0.012 mm, 95% CI -0.021 to -0.002; p = .0137) but not in ever-smokers (0.003 mm, 95% CI -0.008 to 0.014; p = .5767); and similarly in non-current smokers (-0.008 mm, 95% CI -0.015 to -0.00001; p = .0497) but not in current smokers (0.013 mm, 95% CI -0.007 to 0.032; p = .1887). Three-way interaction terms (treatment*time*smoking status) were significant for never versus ever smoking (p = .0373, prespecified) and non-current versus current smoking (p = .0496, exploratory). Averaged maximal carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (-0.020 mm, 95% CI -0.034 to -0.006; p = .0067) but not in ever-smokers (-0.006 mm, 95% CI -0.020 to 0.008; p = .4067), although this analysis was not supported by a significant three-way interaction term.

Conclusions: This subgroup analysis of the REMOVAL trial provides additional support for a potentially wider role of adjunct metformin therapy in cardiovascular risk management in type 1 diabetes, particularly for individuals who have never smoked cigarettes.
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http://dx.doi.org/10.1111/dom.14350DOI Listing
June 2021

Sex differences in the contribution of different physiological systems to physical function in older adults.

Geroscience 2021 02 11;43(1):443-455. Epub 2021 Feb 11.

MRC Unit for Lifelong Health & Ageing at UCL, Department of Population Science & Experimental Medicine, Institute for Cardiovascular Science, University College London, 5th floor, 1-19 Torrington Place, London, WC1E 7HB, UK.

Having the physical function to undertake activities of daily living (ADLs) is essential in order to maintain independence. The aim of this study is to investigate factors associated with physical function in older adults and determine if these associations differ in men versus women. In total, 726 participants (57% men; 73±7 years old) from a population-based cohort, the Southall and Brent Revisited (SABRE) study, completed questionnaires permitting a physical function score (PFS) to be calculated. Detailed phenotyping was performed including cardiovascular (echocardiography and macrovascular and microvascular functions), skeletal muscle (grip strength and oxidative capacity) and lung (pulmonary) function measurements. In a sub-group, maximal aerobic capacity was estimated from a sub-maximal exercise test. In women versus men, the association between grip strength and PFS was nearly 3 times stronger, and the association between microvascular dysfunction and PFS was over 5 times stronger (standardized β-coefficient (95% CI) 0.34 (0.22, 0.45) versus 0.11 (0.01,0.22) and -0.27 (-0.37, -0.17) versus -0.05 (-0.14, 0.04), respectively). In men, the association between cardiorespiratory fitness and PFS was 3 times greater than that in women (standardized β-coefficient (95% CI) 0.33 (0.22, 0.45) versus 0.10 (-0.04, 0.25). Cardiovascular, skeletal muscle and pulmonary factors all contribute to self-reported physical function, but the relative pattern of contribution differs by sex. Grip strength and microvascular function are most strongly associated with physical function in women while cardiorespiratory fitness is most strongly associated with physical function in men. This is relevant to the design of effective interventions that target maintenance of physical function in old age.
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http://dx.doi.org/10.1007/s11357-021-00328-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050191PMC
February 2021

Identifying Isolated Systolic Hypertension From Upper-Arm Cuff Blood Pressure Compared With Invasive Measurements.

Hypertension 2021 02 4;77(2):632-639. Epub 2021 Jan 4.

From the Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia (D.S.P., M.G.S., M.K.A., J.A.B., N.D., P.R.-T., J.E.S.).

Isolated systolic hypertension (ISH) is the most common form of hypertension and is highly prevalent in older people. We recently showed differences between upper-arm cuff and invasive blood pressure (BP) become greater with increasing age, which could influence correct identification of ISH. This study sought to determine the difference between identification of ISH by cuff BP compared with invasive BP. Cuff BP and invasive aortic BP were measured in 1695 subjects (median 64 years, interquartile range [55-72], 68% male) from the INSPECT (Invasive Blood Pressure Consortium) database. Data were recorded during coronary angiography among 29 studies, using 21 different cuff BP devices. ISH was defined as ≥130/<80 mm Hg using cuff BP compared with invasive aortic BP as the reference. The prevalence of ISH was 24% (n=407) according to cuff BP but 38% (n=642) according to invasive aortic BP. There was fair agreement (Cohen κ, 0.36) and 72% concordance between cuff and invasive aortic BP for identifying ISH. Among the 28% of subjects (n=471) with misclassification of ISH status by cuff BP, 20% (n=96) of the difference was due to lower cuff systolic BP compared with invasive aortic systolic BP (mean, -16.4 mm Hg [95% CI, -18.7 to -14.1]), whereas 49% (n=231) was from higher cuff diastolic BP compared with invasive aortic diastolic BP (+14.2 mm Hg [95% CI, 11.5-16.9]). In conclusion, compared with invasive BP, cuff BP fails to identify ISH in a sizeable portion of older people and demonstrates the need to improve cuff BP measurements.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16109DOI Listing
February 2021

Feasibility and Validity of Computed Tomography-Derived Fractional Flow Reserve in Patients With Severe Aortic Stenosis: The CAST-FFR Study.

Circ Cardiovasc Interv 2021 01 16;14(1):e009586. Epub 2020 Dec 16.

Monash Cardiovascular Research Centre, Monash University and MonashHeart, Monash Health, Melbourne, Australia (M.M., A.-R.I., A.C., U.T., J.D.C., L.M.M., R.P.G., S.J.N., B.S.K., A.J.B.).

Background: Coronary artery disease is common in patients with severe aortic stenosis. Computed tomography-derived fractional flow reserve (CT-FFR) is a clinically used modality for assessing coronary artery disease, however, its use has not been validated in patients with severe aortic stenosis. This study assesses the safety, feasibility, and validity of CT-FFR in patients with severe aortic stenosis.

Methods: Prospectively recruited patients underwent standard-protocol invasive FFR and coronary CT angiography (CTA). CTA images were analyzed by central core laboratory (HeartFlow, Inc) for independent evaluation of CT-FFR. CT-FFR data were compared with FFR (ischemia defined as FFR ≤0.80).

Results: Forty-two patients (68 vessels) underwent FFR and CTA; 39 patients (92.3%) and 60 vessels (88.2%) had interpretable CTA enabling CT-FFR computation. Mean age was 76.2±6.7 years (71.8% male). No patients incurred complications relating to premedication, CTA, or FFR protocol. Mean FFR and CT-FFR were 0.83±0.10 and 0.77±0.14, respectively. CT calcium score was 1373.3±1392.9 Agatston units. On per vessel analysis, there was positive correlation between FFR and CT-FFR (Pearson correlation coefficient, =0.64, <0.0001). Sensitivity, specificity, positive predictive value, and negative predictive values were 73.9%, 78.4%, 68.0%, and 82.9%, respectively, with 76.7% diagnostic accuracy. The area under the receiver-operating characteristic curve for CT-FFR was 0.83 (0.72-0.93, <0.0001), which was higher than that of CTA and quantitative coronary angiography (=0.01 and <0.001, respectively). Bland-Altman plot showed mean bias between FFR and CT-FFR as 0.059±0.110. On per patient analysis, the sensitivity, specificity, positive predictive, and negative predictive values were 76.5%, 77.3%, 72.2%, and 81.0% with 76.9% diagnostic accuracy. The per patient area under the receiver-operating characteristic curve analysis was 0.81 (0.67-0.95, <0.0001).

Conclusions: CT-FFR is safe and feasible in patients with severe aortic stenosis. Our data suggests that the diagnostic accuracy of CT-FFR in this cohort potentially enables its use in clinical practice and provides the foundation for future research into the use of CT-FFR for coronary evaluation pre-aortic valve replacement.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116852PMC
January 2021

Imaging Protocol, Feasibility, and Reproducibility of Cardiovascular Phenotyping in a Large Tri-Ethnic Population-Based Study of Older People: The Southall and Brent Revisited (SABRE) Study.

Front Cardiovasc Med 2020 13;7:591946. Epub 2020 Nov 13.

MRC Unit for Lifelong Health and Ageing, Department of Population Science & Experimental Medicine, UCL Institute of Cardiovascular Science, University College London, London, United Kingdom.

People of South Asian and African Caribbean ethnicities living in UK have a high risk of cardiometabolic disease. Limited data exist regarding detailed cardiometabolic phenotyping in this population. Methods enabling this are widely available, but the practical aspects of undertaking such studies in large and diverse samples are seldom reported. The Southall and Brent Revisited (SABRE) study is the UK's largest tri-ethnic longitudinal cohort. Over 1,400 surviving participants (58-85 years) attended the 2nd study visit (2008-2011); during which, comprehensive cardiovascular phenotyping, including 3D-echocardiography [3D-speckle-tracking (3D-STE)], computed tomography, coronary artery calcium scoring, pulse wave velocity, central blood pressure, carotid artery ultrasound, and retinal imaging, were performed. We describe the methods used with the aim of providing a guide to their feasibility and reproducibility in a large tri-ethnic population-based study of older people. Conventional echocardiography and all vascular measurements showed high feasibility (>90% analyzable of clinic attendees), but 3D-echocardiography (3DE) and 3D-STE were less feasible (76% 3DE acquisition feasibility and 38% 3D-STE feasibility of clinic attendees). 3D-STE feasibility differed by ethnicity, being lowest in South Asian participants and highest in African Caribbean participants ( < 0.0001). Similar trends were observed in men ( < 0.0001) and women ( = 0.005); however, in South Asians, there were more women with unreadable 3D-images compared to men (67 vs. 58%). Intra- and inter-observer variabilities were excellent for most of conventional and advanced echocardiographic measures. The test-retest reproducibility was good-excellent and fair-good for conventional and advanced echocardiographic measures, respectively, but lower than when re-reading the same images. All vascular measures demonstrated excellent or fair-good reproducibility. We describe the feasibility and reproducibility of detailed cardiovascular phenotyping in an ethnically diverse population. The data collected will lead to a better understanding of why people of South Asian and African Caribbean ancestry are at elevated risk of cardiometabolic diseases.
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http://dx.doi.org/10.3389/fcvm.2020.591946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693529PMC
November 2020

Mechanisms of Aortic Flow Deceleration and the Effect of Wave Reflection on Left Ventricular Function.

Front Physiol 2020 5;11:578701. Epub 2020 Nov 5.

Brunel Institute for Bioengineering, Brunel University London, London, United Kingdom.

Increased wave reflection is an independent predictor of cardiovascular events, possibly due to effects on left ventricular (LV) function. We investigated the relationship between reflected waves in early systole, the forward decompression wave in mid-late systole and LV mechanical behavior. Invasively acquired ascending aortic velocity, pressure, and LV long and minor axes' dimensions were measured simultaneously in 11 anesthetized dogs during both control conditions and aortic occlusion to cause additional early wave reflection. Wave intensity analysis (WIA) was used to identify the arrival of the reflected wave and the onset of a forward decompression wave in mid-late systole. The arrival time of the reflected wave coincided with the time when minor axis shortening began to decline from its peak, even during aortic occlusion when this time is 12 ms earlier. The initial decline in long axis shortening corresponded to the time of the peak of the reflected wave. The forward decompression wave was consistently observed to have a slow and then rapid phase. The slow phase onset coincided with time of maximum shortening velocity of the long axis. The onset of the later larger rapid phase consistently coincided with an increased rate of deceleration of both axes during late systole. Forward decompression waves are generated by the LV when the long axis shortening velocity falls. Reflected wave arrival has a detrimental effect on LV function, particularly the minor axis. These observations lend support to suggestions that therapies directed toward reducing wave reflection may be of value in hypertension and cardiovascular disease.
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http://dx.doi.org/10.3389/fphys.2020.578701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676911PMC
November 2020

Metabolic profiles of socio-economic position: a multi-cohort analysis.

Int J Epidemiol 2021 07;50(3):768-782

Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.

Background: Low socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear.

Methods: We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in ∼30 000 adults and 4000 children across 10 UK and Finnish cohort studies.

Results: In risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared with non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids.

Conclusions: Our work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavourable metabolic profile, consistent across ages and cohorts. The metabolites we found to be associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities.
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http://dx.doi.org/10.1093/ije/dyaa188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271201PMC
July 2021

Cardiovascular disease recurrence and long-term mortality in a tri-ethnic British cohort.

Heart 2020 Oct 16. Epub 2020 Oct 16.

MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, UK

Objective: Ethnic differences in cardiovascular disease incidence, but not cardiovascular disease recurrence, are reported. We characterised long-term risk of major adverse cardiovascular event (MACE) and mortality following a non-fatal cardiovascular event in a British cohort of South Asians, African Caribbeans and Europeans.

Methods: We identified index and recurrent cardiovascular events and mortality between 1988 and 2017 using hospital records and death registry. Using multivariable hazards models, we separately calculated the adjusted HR of MACE and death following index event, adjusting for demographics, vascular and lifestyle risk factors. Using interaction terms, we evaluated if decade of index event modified the association between ethnicity and outcomes.

Results: South Asians were younger at the index event (median age 66 years, n=396) than Europeans (69 years, n=335) and African Caribbeans (70 years, n=70). During 4228 person-years, of the 801 patients, 537 developed MACE and 338 died, with the highest crude rate of MACE in South Asians. On adjustment of baseline factors, compared with the Europeans, the higher risk of MACE (HR 0.97, 95% CI 0.77 to 1.21) and the lower risk of mortality (HR 0.95, 95% CI 0.72 to 1.26) in South Asians was eliminated. African Caribbeans had similar outcomes to Europeans (HR MACE 1.04, 95% CI 0.74 to 1.47; and HR death 1.07, 95% CI 0.70 to 1.64). Long-term survival following an index event improved in South Asians (p 0.02) and African Caribbeans (p 0.07) compared with Europeans.

Conclusions: Baseline vascular risk factors explained the observed ethnic variation in cardiovascular disease recurrence and long-term mortality, with a relative improvement in survival of minority ethnic groups over time.
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http://dx.doi.org/10.1136/heartjnl-2020-317641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165149PMC
October 2020

Joint Modeling of Individual Trajectories, Within-Individual Variability, and a Later Outcome: Systolic Blood Pressure Through Childhood and Left Ventricular Mass in Early Adulthood.

Am J Epidemiol 2021 04;190(4):652-662

Within-individual variability of repeatedly measured exposures might predict later outcomes (e.g., blood pressure (BP) variability (BPV) is an independent cardiovascular risk factor above and beyond mean BP). Because 2-stage methods, known to introduce bias, are typically used to investigate such associations, we introduce a joint modeling approach, examining associations of mean BP and BPV across childhood with left ventricular mass (indexed to height; LVMI) in early adulthood with data (collected 1990-2011) from the UK Avon Longitudinal Study of Parents and Children cohort. Using multilevel models, we allowed BPV to vary between individuals (a "random effect") as well as to depend on covariates (allowing for heteroskedasticity). We further distinguished within-clinic variability ("measurement error") from visit-to-visit BPV. BPV was predicted to be greater at older ages, at higher body weights, and in female participants and was positively correlated with mean BP. BPV had a weak positive association with LVMI (10% increase in within-individual BP variance was predicted to increase LVMI by 0.21%, 95% credible interval: -0.23, 0.69), but this association became negative (-0.78%, 95% credible interval: -2.54, 0.22) once the effect of mean BP on LVMI was adjusted for. This joint modeling approach offers a flexible method of relating repeatedly measured exposures to later outcomes.
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http://dx.doi.org/10.1093/aje/kwaa224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024053PMC
April 2021

Excess pressure as an analogue of blood flow velocity.

J Hypertens 2021 Mar;39(3):421-427

Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

Introduction: Derivation of blood flow velocity from a blood pressure waveform is a novel technique, which could have potential clinical importance. Excess pressure, calculated from the blood pressure waveform via the reservoir-excess pressure model, is purported to be an analogue of blood flow velocity but this has never been examined in detail, which was the aim of this study.

Methods: Intra-arterial blood pressure was measured sequentially at the brachial and radial arteries via fluid-filled catheter simultaneously with blood flow velocity waveforms recorded via Doppler ultrasound on the contralateral arm (n = 98, aged 61 ± 10 years, 72% men). Excess pressure was derived from intra-arterial blood pressure waveforms using pressure-only reservoir-excess pressure analysis.

Results: Brachial and radial blood flow velocity waveform morphology were closely approximated by excess pressure derived from their respective sites of measurement (median cross-correlation coefficient r = 0.96 and r = 0.95 for brachial and radial comparisons, respectively). In frequency analyses, coherence between blood flow velocity and excess pressure was similar for brachial and radial artery comparisons (brachial and radial median coherence = 0.93 and 0.92, respectively). Brachial and radial blood flow velocity pulse heights were correlated with their respective excess pressure pulse heights (r = 0.53, P < 0.001 and r = 0.43, P < 0.001, respectively).

Conclusion: Excess pressure is an analogue of blood flow velocity, thus affording the opportunity to derive potentially important information related to arterial blood flow using only the blood pressure waveform.
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http://dx.doi.org/10.1097/HJH.0000000000002662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116698PMC
March 2021

Role of the Metabolic Profile in Mediating the Relationship Between Body Mass Index and Left Ventricular Mass in Adolescents: Analysis of a Prospective Cohort Study.

J Am Heart Assoc 2020 10 8;9(20):e016564. Epub 2020 Oct 8.

MRC Integrative Epidemiology Unit Population Health Sciences University of Bristol United Kingdom.

Background We aimed to quantify the role of the plasma metabolic profile in explaining the effect of adiposity on cardiac structure. Methods and Results Body mass index (BMI) was measured at age 11 in the Avon Longitudinal Study of Parents and Children. Left ventricular mass indexed to height (LVMI) was assessed by echocardiography at age 17. The metabolic profile was quantified via H-nuclear magnetic resonance spectroscopy at age 15. Multivariable confounder (maternal age, parity, highest qualification, maternal smoking, prepregnancy BMI, prepregnancy height, household social class, adolescent birthweight, adolescent smoking, fruit and vegetable consumption, and physical activity)-adjusted linear regression estimated the association of BMI with LVMI and mediation by metabolic traits. We considered 156 metabolomic traits individually and jointly as principal components explaining 95% of the variance in the nuclear magnetic resonance platform and assessed whether the principal components for the metabolic traits added to the proportion of the association explained by putative cardiovascular risk factors (systolic and diastolic blood pressures, insulin, triglycerides, low-density lipoprotein cholesterol, and glucose). A 1 kg/m higher BMI was associated with a 0.70 g/m (95% CI, 0.53-0.88 g/m) and 0.66 g/m (95% CI, 0.53-0.79 g/m) higher LVMI in males (n=437) and females (n=536), respectively. Putative risk factors explained 3% (95% CI, 2%-5%) of this association in males, increasing to 10% (95% CI, 8%-13%) when including metabolic principal components. In females, the standard risk factors explained 3% (95% CI, 2%-5%) of the association and did not increase when including the metabolic principal components. Conclusions The addition of the nuclear magnetic resonance-measured metabolic traits appears to mediate more of the association of BMI on LVMI than the putative risk factors alone in adolescent males, but not females.
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http://dx.doi.org/10.1161/JAHA.120.016564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763376PMC
October 2020

Subclinical macro and microvascular disease is differently associated with depressive symptoms in men and women: Findings from the SABRE population-based study.

Atherosclerosis 2020 11 13;312:35-42. Epub 2020 Sep 13.

MRC Unit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, United Kingdom.

Background And Aims: Mechanisms underlying the association between cardiovascular disease (CVD) and depression are unknown, and sex differences understudied. We investigated associations between a comprehensive set of measures of macro and microvascular disease and depressive symptoms in older men and women.

Methods: We performed cross-sectional analyses of the SABRE (Southall And Brent REvisited) population-based study. Participants (1396) attended clinic between 2008 and 2011 for assessment of subclinical macrovascular (carotid ultrasound, echocardiography, cerebral magnetic resonance imaging) and microvascular (retinopathy, nephropathy) disease, and depression.

Results: Mean age of 1396 participants was 69.5 years, and 76.2% were male. The median (interquartile range) of depression score was 1 [0, 2] for men and 1 [0, 3] for women. All measures of subclinical macro and microvascular disease were adversely associated with depressive symptoms, even when known CVD was excluded. Physical activity partly explained some of these relationships. The association between left atrial dimension index (LADI), a measure of chronic elevated left ventricular filling pressure, and depressive symptoms was stronger in women (regression coefficient 0.23 [95% CI 0.11, 0.35]) than men (0.07 [-0.01, 0.15]), p for interaction 0.06, on multivariable adjustment.

Conclusions: Subclinical macro and microvascular disease is associated with depressive symptoms, even in the absence of established CVD. These were in part accounted for by physical activity. We observed stronger association between LADI and depressive symptoms in women than in men. The beneficial role of physical activity in abrogating the association between subclinical CVD and depression warrants further investigation.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594642PMC
November 2020

Cuff Under Pressure for Greater Accuracy.

Curr Hypertens Rep 2020 09 22;22(11):93. Epub 2020 Sep 22.

Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Private Bag 23, Hobart, 7000, Australia.

Purpose Of Review: To present the evidence that describes what is being measured by upper-arm cuff blood pressure (BP) and the level of accuracy compared with invasive central aortic and brachial BP. Potential causes of inaccuracy and emerging methods are also discussed.

Recent Findings: On average cuff systolic BP systematically underestimates invasive brachial systolic BP, although in a given individual it may substantially under- or over-estimate central aortic systolic BP. Such errors may affect individual health management outcomes and distort population level data on hypertension prevalence and control. Oscillometric cuff BP is particularly susceptible to inaccuracy in people with high arterial stiffness and with pathophysiological BP waveform shapes. Emerging cuff-less BP methods will be susceptible to inaccuracy if oscillometric cuff BP is used for calibration. The original purpose of cuff BP was to estimate central aortic BP. Recent evidence has shown substantial inaccuracy of oscillometric cuff BP exists for the measurement of invasive central aortic and brachial BP. Thus, development of more accurate BP methods, through better understanding of oscillometric and BP waveform morphology, is needed to improve health outcomes related to high BP.
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http://dx.doi.org/10.1007/s11906-020-01103-8DOI Listing
September 2020

Establishing reference intervals for triglyceride-containing lipoprotein subfraction metabolites measured using nuclear magnetic resonance spectroscopy in a UK population.

Ann Clin Biochem 2021 01 21;58(1):47-53. Epub 2020 Oct 21.

Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, UK.

Background: Nuclear magnetic resonance (NMR) spectroscopy allows triglycerides to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these subfractions have differential associations with cardiovascular disease events. Here we report the distributions and define reference interval ranges for 14 triglyceride-containing lipoprotein subfraction metabolites.

Methods: Lipoprotein subfractions using the Nightingale NMR platform were measured in 9073 participants from four cohort studies contributing to the UCL-Edinburgh-Bristol consortium. The distribution of each metabolite was assessed, and reference interval ranges were calculated for a disease-free population, by sex and age group (<55, 55-65, >65 years), and in a subgroup population of participants with cardiovascular disease or type 2 diabetes. We also determined the distribution across body mass index and smoking status.

Results: The largest reference interval range was observed in the medium very-low density lipoprotein subclass (2.5th 97.5th percentile; 0.08 to 0.68 mmol/L). The reference intervals were comparable among male and female participants, with the exception of triglyceride in high-density lipoprotein. Triglyceride subfraction concentrations in very-low density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein and high-density lipoprotein subclasses increased with increasing age and increasing body mass index. Triglyceride subfraction concentrations were significantly higher in ever smokers compared to never smokers, among those with clinical chemistry measured total triglyceride greater than 1.7 mmol/L, and in those with cardiovascular disease, and type 2 diabetes as compared to disease-free subjects.

Conclusion: This is the first study to establish reference interval ranges for 14 triglyceride-containing lipoprotein subfractions in samples from the general population measured using the nuclear magnetic resonance platform. The utility of nuclear magnetic resonance lipid measures may lead to greater insights for the role of triglyceride in cardiovascular disease, emphasizing the importance of appropriate reference interval ranges for future clinical decision making.
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http://dx.doi.org/10.1177/0004563220961753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791273PMC
January 2021
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