Publications by authors named "Wilby Williamson"

21 Publications

  • Page 1 of 1

Obesity is associated with reduced cerebral blood flow - modified by physical activity.

Neurobiol Aging 2021 Apr 22;105:35-47. Epub 2021 Apr 22.

The Irish Longitudinal Study on Ageing (TILDA), Trinity College Dublin, Dublin, Ireland; School of Medicine, Trinity College Dublin, Dublin, Ireland; The Global Brain Health Institute (GBHI), Trinity College Dublin, Dublin, Ireland; Mercer's Institute for Successful Ageing (MISA), St. James's Hospital, Dublin, Ireland.

This study examined the associations of body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and physical activity (PA) with gray matter cerebral blood flow (CBF) in older adults. Cross-sectional data was used from the Irish Longitudinal Study on Ageing (n = 495, age 69.0 ±7.4 years, 52.1% female). Whole-brain CBF was quantified using arterial spin labeling MRI. Results from multivariable regression analysis revealed that an increase in BMI of 0.43 kg/m, WHR of 0.01, or WC of 1.3 cm were associated with the same reduction in CBF as 1 year of advancing age. Participants overweight by BMI or with high WHR/WC reporting low/moderate PA had up to 3 ml/100g/min lower CBF (p ≤ .011); there was no significant reduction for those reporting high PA. Since PA could potentially moderate obesity/CBF associations, this may be a cost-effective and relatively easy way to help mitigate the negative impact of obesity in an older population, such as cerebral hypoperfusion, which is an early mechanism in vascular dementia and Alzheimer's disease.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.04.008DOI Listing
April 2021

Association of Systolic Blood Pressure Elevation With Disproportionate Left Ventricular Remodeling in Very Preterm-Born Young Adults: The Preterm Heart and Elevated Blood Pressure.

JAMA Cardiol 2021 May 12. Epub 2021 May 12.

Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, England.

Importance: Preterm-born individuals have higher blood pressure with an increased risk of hypertension by young adulthood, as well as potentially adverse cardiac remodeling even when normotensive. To what extent blood pressure elevation affects left ventricular (LV) structure and function in adults born preterm is currently unknown.

Objective: To investigate whether changes observed in LV structure and function in preterm-born adults make them more susceptible to cardiac remodeling in association with blood pressure elevation.

Design, Setting, And Participants: This cross-sectional cohort study, conducted at the Oxford Cardiovascular Clinical Research Facility and Oxford Centre for Clinical Magnetic Resonance Research, included 468 adults aged 18 to 40 years. Of these, 200 were born preterm (<37 weeks' gestation) and 268 were born at term (≥37 weeks' gestation). Cardiac magnetic resonance imaging was used to characterize LV structure and function, with clinical blood pressure readings measured to assess hypertension status. Demographic and anthropometric data, as well as birth history and family medical history information, were collected. Data were analyzed between January 2012 and February 2021.

Main Outcomes And Measures: Cardiac magnetic resonance measures of LV structure and function in response to systolic blood pressure elevation.

Results: The cohort was primarily White (>95%) with a balanced sex distribution (51.5% women and 48.5% men). Preterm-born adults with and without hypertension had higher LV mass index, reduced LV function, and smaller LV volumes compared with term-born individuals both with and without hypertension. In regression analyses of systolic blood pressure with LV mass index and LV mass to end-diastolic volume ratio, there was a leftward shift in the slopes in preterm-born compared with term-born adults. Compared with term-born adults, there was a 2.5-fold greater LV mass index per 1-mm Hg elevation in systolic blood pressure in very and extremely preterm-born adults (<32 weeks' gestation) (0.394 g/m2 vs 0.157 g/m2 per 1 mm Hg; P < .001) and a 1.6-fold greater LV mass index per 1-mm Hg elevation in systolic blood pressure in moderately preterm-born adults (32 to 36 weeks' gestation) (0.250 g/m2 vs 0.157 g/m2 per 1 mm Hg; P < .001). The LV mass to end-diastolic volume ratio per 1-mm Hg elevation in systolic blood pressure in the very and extremely preterm-born adults was 3.4-fold greater compared with those born moderately preterm (3.56 × 10-3 vs 1.04 × 10-3 g/mL per 1 mm Hg; P < .001) and 3.3-fold greater compared with those born at term (3.56 × 10-3 vs 1.08 × 10-3 g/mL per 1 mm Hg; P < .001).

Conclusions And Relevance: Preterm-born adults have a unique LV structure and function that worsens with systolic blood pressure elevation. Additional primary prevention strategies specifically targeting cardiovascular risk reduction in this population may be warranted.
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http://dx.doi.org/10.1001/jamacardio.2021.0961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117059PMC
May 2021

Gray matter volume in the right angular gyrus is associated with differential patterns of multisensory integration with aging.

Neurobiol Aging 2021 04 25;100:83-90. Epub 2020 Dec 25.

School of Psychology and Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.

Multisensory perception might provide an important marker of brain function in aging. However, the cortical structures supporting multisensory perception in aging are poorly understood. In this study, we compared regional gray matter volume in a group of middle-aged (n = 101; 49-64 years) and older (n = 116; 71-87 years) adults from The Irish Longitudinal Study on Aging using voxel-based morphometry. Participants completed a measure of multisensory integration, the sound-induced flash illusion, and were grouped as per their illusion susceptibility. A significant interaction was observed in the right angular gyrus; in the middle-aged group, larger gray matter volume corresponded to stronger illusion perception while in older adults larger gray matter corresponded to less illusion susceptibility. This interaction remained significant even when controlling for a range of demographic, sensory, cognitive, and health variables. These findings show that multisensory integration is associated with specific structural differences in the aging brain and highlight the angular gyrus as a possible "cross-modal hub" associated with age-related change in multisensory perception.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.12.004DOI Listing
April 2021

Age-related normative changes in cerebral perfusion: Data from The Irish Longitudinal Study on Ageing (TILDA).

Neuroimage 2021 04 14;229:117741. Epub 2021 Jan 14.

School of Medicine, Trinity College Dublin, Ireland; The Irish Longitudinal Study on Ageing (TILDA), Trinity College Dublin, Ireland. Electronic address:

Objective: To establish normative reference values for total grey matter cerebral blood flow (CBF) measured using pseudo-continuous arterial spin labelling (pCASL) MRI in a large cohort of community-dwelling adults aged 54 years and older.

Background: Quantitative assessment of CBF may provide an imaging biomarker for the early detection of those at risk of neurodegenerative diseases, such as Alzheimer's and dementia. However, the use of this method to differentiate normal age-related decline in CBF from pathological reduction has been hampered by the lack of reference values for cerebral perfusion.

Methods: The study cohort comprised a subset of wave 3 (2014-2015) participants from The Irish Longitudinal Study on Ageing (TILDA), a large-scale prospective cohort study of individuals aged 50 and over. Of 4309 participants attending for health centre assessment, 578 individuals returned for 3T multi-parametric MRI brain examinations. In total, CBF data acquired from 468 subjects using pCASL-MRI were included in this analysis. Normative values were estimated using Generalised Additive Models for Location Shape and Scale (GAMLSS) and are presented as percentiles, means and standard deviations.

Results: The mean age of the cohort was 68.2 ± 6.9 years and 51.7% were female. Mean CBF for the cohort was 36.5 ± 8.2 ml/100 g/min. CBF decreased by 0.2 ml/100 g/min for each year increase in age (95% CI = -0.3, -0.1; p ≤ 0.001) and was 3.1 ml/100 g/min higher in females (95% CI = 1.6, 4.5; p ≤ 0.001).

Conclusions: This study is by far the largest single-site study focused on an elderly community-dwelling cohort to present normative reference values for CBF measured at 3T using pCASL-MRI. Significant age- and sex-related differences exist in CBF.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117741DOI Listing
April 2021

A critical evaluation of systematic reviews assessing the effect of chronic physical activity on academic achievement, cognition and the brain in children and adolescents: a systematic review.

Int J Behav Nutr Phys Act 2020 06 22;17(1):79. Epub 2020 Jun 22.

Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK.

Background: International and national committees have started to evaluate the evidence for the effects of physical activity on neurocognitive health in childhood and adolescence to inform policy. Despite an increasing body of evidence, such reports have shown mixed conclusions. We aimed to critically evaluate and synthesise the evidence for the effects of chronic physical activity on academic achievement, cognitive performance and the brain in children and adolescents in order to guide future research and inform policy.

Methods: MedLine, Embase, PsycINFO, Cochrane Library, Web of Science, and ERIC electronic databases were searched from inception to February 6th, 2019. Articles were considered eligible for inclusion if they were systematic reviews with or without meta-analysis, published in peer-reviewed (English) journals. Reviews had to be on school-aged children and/or adolescents that reported on the effects of chronic physical activity or exercise interventions, with cognitive markers, academic achievement or brain markers as outcomes. Reviews were selected independently by two authors and data were extracted using a pre-designed data extraction template. The quality of reviews was assessed using AMSTAR-2 criteria.

Results: Of 908 retrieved, non-duplicated articles, 19 systematic reviews met inclusion criteria. One high-quality review reported inconsistent evidence for physical activity-related effects on cognitive- and academic performance in obese or overweight children and adolescents. Eighteen (critically) low-quality reviews presented mixed favourable and null effects, with meta-analyses showing small effect sizes (0.1-0.3) and high heterogeneity. Low-quality reviews suggested physical activity-related brain changes, but lacked an interpretation of these findings. Systematic reviews varied widely in their evidence synthesis, rarely took intervention characteristics (e.g. dose), intervention fidelity or study quality into account and suspected publication bias. Reviews consistently reported that there is a lack of high-quality studies, of studies that include brain imaging outcomes, and of studies that include adolescents or are conducted in South American and African countries.

Conclusions: Inconsistent evidence exists for chronic physical activity-related effects on cognitive-, academic-, and brain outcomes. The field needs to refocus its efforts towards improving study quality, transparency of reporting and dissemination, and is urged to differentiate between intervention characteristics for its findings to have a meaningful impact on policy.
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http://dx.doi.org/10.1186/s12966-020-00959-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310146PMC
June 2020

Impaired orthostatic heart rate recovery is associated with smaller thalamic volume: Results from The Irish Longitudinal Study on Aging (TILDA).

Hum Brain Mapp 2020 08 30;41(12):3370-3378. Epub 2020 Apr 30.

The Irish Longitudinal Study on Ageing, Trinity College, University of Dublin, Dublin, Ireland.

The thalamus is a central hub of the autonomic network and thalamic volume has been associated with high-risk phenotypes for sudden cardiac death. Heart rate response to physiological stressors (e.g., standing) and the associated recovery patterns provide reliable indicators of both autonomic function and cardiovascular risk. Here we examine if thalamic volume may be a risk marker for impaired heart rate recovery in response to orthostatic challenge. The Irish Longitudinal Study on Aging involves a nationally representative sample of older individuals aged ≥50 years. Multimodal brain magnetic resonance imaging and orthostatic heart rate recovery were available for a cross-sectional sample of 430 participants. Multivariable regression and linear mixed-effects models were adjusted for head size, age, sex, education, body mass index, blood pressure, history of cardiovascular diseases and events, cardiovascular medication, diabetes mellitus, smoking, alcohol intake, timed up-and-go (a measure of physical frailty), physical exercise and depression. Smaller thalamic volume was associated with slower heart rate recovery (-1.4 bpm per 1 cm thalamic volume, 95% CI -2.01 to -0.82; p < .001). In multivariable analysis, participants with smaller thalamic volumes had a mean heart rate recovery -2.7 bpm slower than participants with larger thalamic volumes (95% CI -3.89 to -1.61; p < .001). Covariates associated with smaller thalamic volume included age, history of diabetes, and heavy alcohol consumption. Thalamic volume may be an indicator of the structural integrity of the central autonomic network. It may be a clinical biomarker for stratification of individuals at risk of autonomic dysfunction, cardiovascular events, and sudden cardiac death.
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http://dx.doi.org/10.1002/hbm.25022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375046PMC
August 2020

Variations in Cardiovascular Structure, Function, and Geometry in Midlife Associated With a History of Hypertensive Pregnancy.

Hypertension 2020 06 20;75(6):1542-1550. Epub 2020 Apr 20.

From the Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine (H.B., M.L., A.V., R.U., A.B., R.D., C.S., Y.K., C.Y.L.A., W.W., O.H., A.J.L., P. Leeson), University of Oxford, United Kingdom.

Hypertensive pregnancy is associated with increased maternal cardiovascular risk in later life. A range of cardiovascular adaptations after pregnancy have been reported to partly explain this risk. We used multimodality imaging to identify whether, by midlife, any pregnancy-associated phenotypes were still identifiable and to what extent they could be explained by blood pressure. Participants were identified by review of hospital maternity records 5 to 10 years after pregnancy and invited to a single visit for detailed cardiovascular imaging phenotyping. One hundred seventy-three women (age, 42±5 years, 70 after normotensive and 103 after hypertensive pregnancy) underwent magnetic resonance imaging of the heart and aorta, echocardiography, and vascular assessment, including capillaroscopy. Women with a history of hypertensive pregnancy had a distinct cardiac geometry with higher left ventricular mass index (49.9±7.1 versus 46.0±6.5 g/m; =0.001) and ejection fraction (65.6±5.4% versus 63.7±4.3%; =0.03) but lower global longitudinal strain (-18.31±4.46% versus -19.94±3.59%; =0.02). Left atrial volume index was also increased (40.4±9.2 versus 37.3±7.3 mL/m; =0.03) and E:A reduced (1.34±0.35 versus 1.52±0.45; =0.003). Aortic compliance (0.240±0.053 versus 0.258±0.063; =0.046) and functional capillary density (105.4±23.0 versus 115.2±20.9 capillaries/mm; =0.01) were reduced. Only differences in functional capillary density, left ventricular mass, and atrial volume indices remained after adjustment for blood pressure (<0.01, =0.01, and =0.04, respectively). Differences in cardiac structure and geometry, as well as microvascular rarefaction, are evident in midlife after a hypertensive pregnancy, independent of blood pressure. To what extent these phenotypic patterns contribute to cardiovascular disease progression or provide additional measures to improve risk stratification requires further study.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682801PMC
June 2020

Impaired myocardial reserve underlies reduced exercise capacity and heart rate recovery in preterm-born young adults.

Eur Heart J Cardiovasc Imaging 2021 Apr;22(5):572-580

Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Headley Way, John Radcliffe Hospital, Oxford OX39DU, UK.

Aims : We tested the hypothesis that the known reduction in myocardial functional reserve in preterm-born young adults is an independent predictor of exercise capacity (peak VO2) and heart rate recovery (HRR).

Methods And Results : We recruited 101 normotensive young adults (n = 47 born preterm; 32.8 ± 3.2 weeks' gestation and n = 54 term-born controls). Peak VO2 was determined by cardiopulmonary exercise testing (CPET), and lung function assessed using spirometry. Percentage predicted values were then calculated. HRR was defined as the decrease from peak HR to 1 min (HRR1) and 2 min of recovery (HRR2). Four-chamber echocardiography views were acquired at rest and exercise at 40% and 60% of CPET peak power. Change in left ventricular ejection fraction from rest to each work intensity was calculated (EFΔ40% and EFΔ60%) to estimate myocardial functional reserve. Peak VO2 and per cent of predicted peak VO2 were lower in preterm-born young adults compared with controls (33.6 ± 8.6 vs. 40.1 ± 9.0 mL/kg/min, P = 0.003 and 94% ± 20% vs. 108% ± 25%, P = 0.001). HRR1 was similar between groups. HRR2 decreased less in preterm-born young adults compared with controls (-36 ± 13 vs. -43 ± 11 b.p.m., P = 0.039). In young adults born preterm, but not in controls, EFΔ40% and EFΔ60% correlated with per cent of predicted peak VO2 (r2 = 0.430, P = 0.015 and r2 = 0.345, P = 0.021). Similarly, EFΔ60% correlated with HRR1 and HRR2 only in those born preterm (r2 = 0.611, P = 0.002 and r2 = 0.663, P = 0.001).

Conclusions : Impaired myocardial functional reserve underlies reductions in peak VO2 and HRR in young adults born moderately preterm. Peak VO2 and HRR may aid risk stratification and treatment monitoring in this population.
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http://dx.doi.org/10.1093/ehjci/jeaa060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081423PMC
April 2021

Thinking about dementia: is childhood too early?

Int Psychogeriatr 2019 12;31(12):1689-1690

Global Brain Health Institute, School of Medicine, Trinity College Dublin, Republic of Ireland.

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http://dx.doi.org/10.1017/S1041610219001157DOI Listing
December 2019

Trial of exercise to prevent HypeRtension in young adults (TEPHRA) a randomized controlled trial: study protocol.

BMC Cardiovasc Disord 2018 11 6;18(1):208. Epub 2018 Nov 6.

Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.

Background: Hypertension prevalence in young adults has increased and is associated with increased incidence of cerebrovascular and cardiovascular events in middle age. However, there is significant debate regards how to effectively manage young adult hypertension with recommendation to target lifestyle intervention. Surprisingly, no trials have investigated whether lifestyle advice developed for blood pressure control in older adults is effective in these younger populations.

Methods/design: TEPHRA is an open label, parallel arm, randomised controlled trial in young adults with high normal and elevated blood pressure. The study will compare a supervised physical activity intervention consisting of 16 weeks structured exercise, physical activity self-monitoring and motivational coaching with a control group receiving usual care/minimal intervention. Two hundred young adults aged 18-35 years, including a subgroup of preterm born participants will be recruited through open recruitment and direct invitation. Participants will be randomised in a ratio of 1:1 to either the exercise intervention group or control group. Primary outcome will be ambulatory blood pressure monitoring at 16 weeks with measure of sustained effect at 12 months. Study measures include multimodal cardiovascular assessments; peripheral vascular measures, blood sampling, microvascular assessment, echocardiography, objective physical activity monitoring and a subgroup will complete multi-organ magnetic resonance imaging.

Discussion: The results of this trial will deliver a novel, randomised control trial that reports the effect of physical activity intervention on blood pressure integrated with detailed cardiovascular phenotyping in young adults. The results will support the development of future research and expand the evidence-based management of blood pressure in young adult populations.

Trial Registration: Clinicaltrials.gov registration number NCT02723552 , registered on 30 March, 2016.
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http://dx.doi.org/10.1186/s12872-018-0944-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220491PMC
November 2018

Association of Cardiovascular Risk Factors With MRI Indices of Cerebrovascular Structure and Function and White Matter Hyperintensities in Young Adults.

JAMA 2018 08;320(7):665-673

Oxford Cardiovascular Clinical Research Facility, University of Oxford, Oxford, United Kingdom.

Importance: Risk of stroke and brain atrophy in later life relate to levels of cardiovascular risk in early adulthood. However, it is unknown whether cerebrovascular changes are present in young adults.

Objective: To examine relationships between modifiable cardiovascular risk factors and cerebrovascular structure, function, and white matter integrity in young adults.

Design, Setting, And Participants: A cross-sectional observational study of 125 young adults (aged 18-40 years) without clinical evidence of cerebrovascular disease. Data collection was completed between August 2014 and May 2016 at the University of Oxford, United Kingdom. Final data collection was completed on May 31, 2016.

Exposures: The number of modifiable cardiovascular risk factors at recommended levels, based on the following criteria: body mass index (BMI) <25; highest tertile of cardiovascular fitness and/or physical activity; alcohol consumption <8 drinks/week; nonsmoker for >6 months; blood pressure on awake ambulatory monitoring <130/80 mm Hg; a nonhypertensive diastolic response to exercise (peak diastolic blood pressure <90 mm Hg); total cholesterol <200 mg/dL; and fasting glucose <100mg/dL. Each risk factor at the recommended level was assigned a value of 1, and participants were categorized from 0-8, according to the number of risk factors at recommended levels, with higher numbers indicating healthier risk categories.

Main Outcomes And Measures: Cerebral vessel density, caliber and tortuosity, brain white matter hyperintensity lesion count. In a subgroup (n = 52), brain blood arrival time and cerebral blood flow assessed by brain magnetic resonance imaging (MRI).

Results: A total of 125 participants, mean (SD) age 25 (5) years, 49% women, with a mean (SD) score of 6.0 (1.4) modifiable cardiovascular risk factors at recommended levels, completed the cardiovascular risk assessment and brain MRI protocol. Cardiovascular risk factors were correlated with cerebrovascular morphology and white matter hyperintensity count in multivariable models. For each additional modifiable risk factor categorized as healthy, vessel density was greater by 0.3 vessels/cm3 (95% CI, 0.1-0.5; P = .003), vessel caliber was greater by 8 μm (95% CI, 3-13; P = .01), and white matter hyperintensity lesions were fewer by 1.6 lesions (95% CI, -3.0 to -0.5; P = .006). Among the 52 participants with available data, cerebral blood flow varied with vessel density and was 2.5 mL/100 g/min higher for each healthier category of a modifiable risk factor (95% CI, 0.16-4.89; P = .03).

Conclusions And Relevance: In this preliminary study involving young adults without clinical evidence of cerebrovascular disease, a greater number of modifiable cardiovascular risk factors at recommended levels was associated with higher cerebral vessel density and caliber, higher cerebral blood flow, and fewer white matter hyperintensities. Further research is needed to verify these findings and determine their clinical importance.
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http://dx.doi.org/10.1001/jama.2018.11498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142949PMC
August 2018

Physiological Stress Elicits Impaired Left Ventricular Function in Preterm-Born Adults.

J Am Coll Cardiol 2018 03;71(12):1347-1356

Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom. Electronic address:

Background: Experimental and clinical studies show that prematurity leads to altered left ventricular (LV) structure and function with preserved resting LV ejection fraction (EF). Large-scale epidemiological data now links prematurity to increased early heart failure risk.

Objectives: The authors performed echocardiographic imaging at prescribed exercise intensities to determine whether preterm-born adults have impaired LV functional response to physical exercise.

Methods: We recruited 101 normotensive young adults born preterm (n = 47; mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) for detailed cardiovascular phenotyping. Full clinical resting and exercise stress echocardiograms were performed, with apical 4-chamber views collected while exercising at 40%, 60%, and 80% of peak exercise capacity, determined by maximal cardiopulmonary exercise testing.

Results: Preterm-born individuals had greater LV mass (p = 0.015) with lower peak systolic longitudinal strain (p = 0.038) and similar EF to term-born control subjects at rest (p = 0.62). However, by 60% exercise intensity, EF was 6.7% lower in preterm subjects (71.9 ± 8.7% vs 78.6 ± 5.4%; p = 0.004) and further declined to 7.3% below the term-born group at 80% exercise intensity (69.8 ± 6.4% vs 77.1 ± 6.3%; p = 0.004). Submaximal cardiac output reserve was 56% lower in preterm-born subjects versus term-born control subjects at 40% of peak exercise capacity (729 ± 1,162 ml/min/m vs. 1,669 ± 937 ml/min/m; p = 0.021). LV length and resting peak systolic longitudinal strain predicted EF increase from rest to 60% exercise intensity in the preterm group (r = 0.68, p = 0.009 and r = 0.56, p = 0.031, respectively).

Conclusions: Preterm-born young adults had impaired LV response to physiological stress when subjected to physical exercise, which suggested a reduced myocardial functional reserve that might help explain their increased risk of early heart failure. (Young Adult Cardiovascular Health sTudy [YACHT]; NCT02103231).
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http://dx.doi.org/10.1016/j.jacc.2018.01.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864965PMC
March 2018

Aortic stiffness and blood pressure variability in young people: a multimodality investigation of central and peripheral vasculature.

J Hypertens 2017 03;35(3):513-522

aOxford Cardiovascular Clinical Research Facility bOxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

Introduction: Increased blood pressure (BP) variability is a cardiovascular risk marker for young individuals and may relate to the ability of their aorta to buffer cardiac output. We used a multimodality approach to determine relations between central and peripheral arterial stiffness and BP variability.

Methods: We studied 152 adults (mean age of 31 years) who had BP variability measures based on SD of awake ambulatory BPs, 24-h weighted SD and average real variability (ARV). Global and regional aortic distensibility was measured by cardiovascular magnetic resonance, arterial stiffness by cardio-ankle vascular index (CAVI) and pulse wave velocity (PWV) by SphygmoCor (carotid-femoral) and Vicorder (brachial-femoral).

Results: In young people, free from overt cardiovascular disease, all indices of SBP and DBP variability correlated with aortic distensibility (global aortic distensibility versus awake SBP SD: r = -0.39, P < 0.001; SBP ARV: r = -0.34, P < 0.001; weighted 24-h SBP SD: r = -0.42, P < 0.001). CAVI, which closely associated with aortic distensibility, also related to DBP variability, as well as awake SBP SD (r = 0.19, P < 0.05) and weighted 24-h SBP SD (r = 0.24, P < 0.01), with a trend for SBP ARV (r = 0.17, P = 0.06). In contrast, associations with PWV were only between carotid-femoral PWV and weighted SD of SBP (r = 0.20, P = 0.03) as well as weighted and ARV of DBP.

Conclusion: Greater BP variability in young people relates to increases in central aortic stiffness, strategies to measure and protect aortic function from a young age may be important to reduce cardiovascular risk.
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http://dx.doi.org/10.1097/HJH.0000000000001192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278891PMC
March 2017

Will Exercise Advice Be Sufficient for Treatment of Young Adults With Prehypertension and Hypertension? A Systematic Review and Meta-Analysis.

Hypertension 2016 07 23;68(1):78-87. Epub 2016 May 23.

From the Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine (W.W., A.J.L., H.B., O.H., P.L.), British Heart Foundation Centre on Population Approaches for Non-Communicable Disease Prevention, Nuffield Department of Population Health (C.F., H.R.), Bodleian Health Care Libraries (N.R.), Department of Primary Care Health Sciences (D.M.C.), Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences (J.N.), and Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (S.G.), University of Oxford, Oxford, United Kingdom; Institute for Sport, Physical Education and Health Sciences, University of Edinburgh, Edinburgh, United Kingdom (P.K.); and Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, United Kingdom (H.D.).

Previous studies report benefits of exercise for blood pressure control in middle age and older adults, but longer-term effectiveness in younger adults is not well established. We performed a systematic review and meta-analysis of published randomized control trials with meta-regression of potential effect modifiers. An information specialist completed a comprehensive search of available data sources, including studies published up to June 2015. Authors applied strict inclusion and exclusion criteria to screen 9524 titles. Eligible studies recruited younger adults with a cardiovascular risk factor (with at least 25% of cohort aged 18-40 years); the intervention had a defined physical activity strategy and reported blood pressure as primary or secondary outcome. Meta-analysis included 14 studies randomizing 3614 participants, mean age 42.2±6.3 (SD) years. At 3 to 6 months, exercise was associated with a reduction in systolic blood pressure of -4.40 mm Hg (95% confidence interval, -5.78 to -3.01) and in diastolic blood pressure of -4.17 mm Hg (95% confidence interval, -5.42 to -2.93). Intervention effect was not significantly influenced by baseline blood pressure, body weight, or subsequent weight loss. Observed intervention effect was lost after 12 months of follow-up with no reported benefit over control, mean difference in systolic blood pressure -1.02 mm Hg (95% confidence interval, -2.34 to 0.29), and in diastolic blood pressure -0.91 mm Hg (95% confidence interval, -1.85 to 0.02). Current exercise guidance provided to reduce blood pressure in younger adults is unlikely to benefit long-term cardiovascular risk. There is need for continued research to improve age-specific strategies and recommendations for hypertension prevention and management in young adults.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.07431DOI Listing
July 2016

Time to rethink physical activity advice and blood pressure: A role for occupation-based interventions?

Eur J Prev Cardiol 2016 07 26;23(10):1051-3. Epub 2016 Apr 26.

Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, UK

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http://dx.doi.org/10.1177/2047487316645008DOI Listing
July 2016

Behavioural physical activity interventions in participants with lower-limb osteoarthritis: a systematic review with meta-analysis.

BMJ Open 2015 Aug 10;5(8):e007642. Epub 2015 Aug 10.

Nuffield Department of Population Health, British Heart Foundation Centre on Population Approaches for Non-Communicable Disease Prevention, University of Oxford, Oxford, UK.

Objective: To assess effectiveness of osteoarthritis interventions to promote long-term physical activity behaviour change.

Design: A systematic review and meta-analysis. Protocol registration PROSPERO CRD4201300444 5 (http://www.crd.york.ac.uk/prospero/).

Study Selection: Randomised controlled trials (RCTs) comparing physical activity interventions with placebo, no/or minimal intervention in community-dwelling adults with symptomatic knee or hip osteoarthritis. Primary outcomes were change in physical activity or cardiopulmonary fitness after a minimum follow-up of 6 months.

Data Extraction: Outcomes were measures of physical activity (self-reported and objectively measured) and cardiovascular fitness. Standard mean differences between postintervention values were used to describe the effect sizes.

Results: 27,984 titles were screened and 180 papers reviewed in full. Eleven RCTs satisfied inclusion criteria, total study population of 2741 participants, mean age 62.2. The commonest reasons for study exclusion were follow-up less than 6 months and no physical activity measures. The majority of included interventions implement an arthritis self-management programme targeting coping skills and self-efficacy. Seven studies used self-report measures, the pooled effect of these studies was small with significant heterogeneity between studies (SMD 0.22 with 95% CI -0.11 to 0.56, z=1.30 (p=0.19) I(2) statistic of 85%). Subgroup analysis of 6-12 month outcome reduced heterogeneity and increased intervention effect compared to control (SMD 0.53, 95% CI 0.41 to 0.65, z=8.84 (p<0.00001) I(2) of 66%).

Conclusions: Arthritis self-management programmes achieve a small but significant improvement in physical activity in the short term. Effectiveness of intervention declines with extended follow-up beyond 12 months with no significant benefit compared to control. The small number of studies (11 RCTs) limited ability to define effective delivery methods. Investigation of behavioural lifestyle interventions for lower limb osteoarthritis populations would benefit from consensus on methodology and outcome reporting. This includes use of validated physical activity reporting tools and planning for long-term follow-up.
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http://dx.doi.org/10.1136/bmjopen-2015-007642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4538274PMC
August 2015

Clinical cardiovascular risk during young adulthood in offspring of hypertensive pregnancies: insights from a 20-year prospective follow-up birth cohort.

BMJ Open 2015 Jun 23;5(6):e008136. Epub 2015 Jun 23.

Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, Oxford, UK.

Objectives: Offspring of hypertensive pregnancies have increased cardiovascular risk factors during childhood. We hypothesised that offspring of hypertensive pregnancies would demonstrate increased clinical levels of hypertension by young adult life, which would be proportional to the severity of the pregnancy complication.

Design: Prospective birth cohort study

Setting: Tertiary obstetric hospital.

Participants: 2868 young adult offspring of women enrolled during pregnancy into the Western Australia Pregnancy Cohort (Raine) Study.

Main Outcome Measures: Cardiovascular risk, including incidence of hypertension and metabolic disease, in those born to hypertensive compared to normotensive pregnancies.

Results: Young adult offspring of hypertensive pregnancies were 2.5 times (95% CI 1.32 to 4.56, p=0.004) more likely to have global lifetime risk (QRISK) scores above the 75th centile. Thirty per cent of 20 year olds with hypertensive blood pressures were born following a hypertensive pregnancy. Pre-eclampsia or hypertension resulting in preterm birth associated with a threefold (95% CI 1.3 to 7.0, p=0.01) greater risk of being hypertensive by age 20 years, with no differences in body mass index. Whereas pregnancy-induced hypertension associated with a smaller 3 ± 1 mm Hg blood pressure rise (p=0.001) and a twofold (95% CI 1.5 to 2.8, p=0.001) greater risk of being obese or overweight. Risk factor associations were consistent throughout early life and independent of other birth-factors.

Conclusions: Incidence of offspring hypertension was significantly increased in those whose mothers had a more complicated pregnancy history, including preterm birth and pre-eclampsia.
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http://dx.doi.org/10.1136/bmjopen-2015-008136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480003PMC
June 2015

Validity of reporting oxygen uptake efficiency slope from submaximal exercise using respiratory exchange ratio as secondary criterion.

Pulm Med 2012 14;2012:874020. Epub 2012 May 14.

Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Box 285, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.

Background. Oxygen uptake efficiency slope (OUES) is a reproducible, objective marker of cardiopulmonary function. OUES is reported as being relatively independent of exercise intensity. Practical guidance and criteria for reporting OUES from submaximal tests has not been established. Objective. Evaluate the use of respiratory exchange ratio (RER) as a secondary criterion for reporting OUES. Design. 100 healthy volunteers (53 women) completed a ramped treadmill protocol to exhaustive exercise. OUES was calculated from data truncated to RER levels from 0.85 to 1.2 and compared to values generated from full test data. Results. Mean (sd) OUES from full test data and data truncated to RER 1.0 and RER 0.9 was 2814 (718), 2895 (730), and 2810 (789) mL/min per 10-fold increase in VE, respectively. Full test OUES was highly correlated with OUES from RER 1.0 (r = 0.9) and moderately correlated with OUES from RER 0.9 (r = 0.79). Conclusion. OUES values peaked in association with an RER level of 1.0. Sub-maximal OUES values are not independent of exercise intensity. There is a significant increase in OUES value as exercise moves from low to moderate intensity. RER can be used as a secondary criterion to define this transition.
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http://dx.doi.org/10.1155/2012/874020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361344PMC
August 2012

Early vs late tracheostomy in critical care.

Br J Hosp Med (Lond) 2009 Sep;70(9):510-3

University College Hospital, London.

This article reviews the current literature and practice of tracheostomy with consideration of timing and the benefits of early tracheostomy, taking account of the results from the recent TracMan study.
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http://dx.doi.org/10.12968/hmed.2009.70.9.43867DOI Listing
September 2009

Carbon monoxide poisoning in a patient with carbon dioxide retention: a therapeutic challenge.

Cases J 2008 Aug 18;1(1):102. Epub 2008 Aug 18.

Central Middlesex Hospital, Acton Lane, London, NW10 7NS, UK.

We present the case of a 70 year-old man with carbon monoxide poisoning following a house fire. A significant smoking history and likely underlying chronic lung pathology complicated treatment, as due to symptomatic retention of carbon dioxide we were unable to use high-flow oxygen to facilitate the elimination of carbon monoxide. We suggest that patients with risk factors for obstructive lung disease be monitored extremely carefully during treatment for carbon monoxide toxicity.
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http://dx.doi.org/10.1186/1757-1626-1-102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2533003PMC
August 2008