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1. COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

Author

Abbasizanjani, Hoda, Ahmed, Nida, Ahmed, Badar, Akbari, Ashley, Akinoso-Imran, Abdul Qadr, Allara, Elias, Allery, Freya, Angelantonio, Emanuele Di, Ashworth, Mark, Ayyar-Gupta, Vandana, Babu-Narayan, Sonya, Bacon, Seb, Ball, Steve, Banerjee, Ami, Barber, Mark, Barrett, Jessica, Bennie, Marion, Berry, Colin, Beveridge, Jennifer, Birney, Ewan, Bojanić, Lana, Bolton, Thomas, Bone, Anna, Boyle, Jon, Braithwaite, Tasanee, Bray, Ben, Briffa, Norman, Brind, David, Brown, Katherine, Buch, Maya, Canoy, Dexter, Caputo, Massimo, Carragher, Raymond, Carson, Alan, Cezard, Genevieve, Chang, Jen-Yu Amy, Cheema, Kate, Chin, Richard, Chudasama, Yogini, Cooper, Jennifer, Copland, Emma, Crallan, Rebecca, Cripps, Rachel, Cromwell, David, Curcin, Vasa, Curry, Gwenetta, Dale, Caroline, Danesh, John, Das-Munshi, Jayati, Dashtban, Ashkan, Davies, Alun, Davies, Joanna, Davies, Gareth, Davies, Neil, Day, Joshua, Delmestri, Antonella, Denaxas, Spiros, Denholm, Rachel, Dennis, John, Denniston, Alastair, Deo, Salil, Dhillon, Baljean, Docherty, Annemarie, Dong, Tim, Douiri, Abdel, Downs, Johnny, Dregan, Alexandru, Ellins, Elizabeth A, Elwenspoek, Martha, Falck, Fabian, Falter, Florian, Fan, Yat Yi, Firth, Joseph, Fraser, Lorna, Friebel, Rocco, Gavrieli, Amir, Gerstung, Moritz, Gilbert, Ruth, Gillies, Clare, Glickman, Myer, Goldacre, Ben, Goldacre, Raph, Greaves, Felix, Green, Mark, Grieco, Luca, Griffiths, Rowena, Gurdasani, Deepti, Halcox, Julian, Hall, Nick, Hama, Tuankasfee, Handy, Alex, Hansell, Anna, Hardelid, Pia, Hardy, Flavien, Harris, Daniel, Harrison, Camille, Harron, Katie, Hassaine, Abdelaali, Hassan, Lamiece, Healey, Russell, Hemingway, Harry, Henderson, Angela, Herz, Naomi, Heyl, Johannes, Hidajat, Mira, Higginson, Irene, Hinchliffe, Rosie, Hippisley-Cox, Julia, Ho, Frederick, Hocaoglu, Mevhibe, Hollings, Sam, Horne, Elsie, Hughes, David, Humberstone, Ben, Inouye, Mike, Ip, Samantha, Islam, Nazrul, Jackson, Caroline, Jenkins, David, Jiang, Xiyun, Johnson, Shane, Kadam, Umesh, Kallis, Costas, Karim, Zainab, Kasan, Jake, Katsoulis, Michalis, Kavanagh, Kim, Kee, Frank, Keene, Spencer, Kent, Seamus, Khalid, Sara, Khawaja, Anthony, Khunti, Kamlesh, Killick, Richard, Kinnear, Deborah, Knight, Rochelle, Kolamunnage-Dona, Ruwanthi, Kontopantelis, Evan, Kurdi, Amanj, Lacey, Ben, Lai, Alvina, Lambarth, Andrew, Larzjan, Milad Nazarzadeh, Lawler, Deborah, Lawrence, Thomas, Lawson, Claire, Li, Qiuju, Li, Ken, Llinares, Miguel Bernabeu, Lorgelly, Paula, Lowe, Deborah, Lyons, Jane, Lyons, Ronan, Machado, Pedro, Macleod, Mary Joan, Macleod, John, Malgapo, Evaleen, Mamas, Mamas, Mamouei, Mohammad, Manohar, Sinduja, Mapeta, Rutendo, Martelli, Javiera Leniz, Martos, David Moreno, Mateen, Bilal, McCarthy, Aoife, Melville, Craig, Milton, Rebecca, Mizani, Mehrdad, Moncusi, Marta Pineda, Morales, Daniel, Mordi, Ify, Morrice, Lynn, Morris, Carole, Morris, Eva, Mu, Yi, Mueller, Tanja, Murdock, Lars, Nafilyan, Vahé, Nicholson, George, Nikiphorou, Elena, Nolan, John, Norris, Tom, Norris, Ruth, North, Laura, North, Teri-Louise, O'Connell, Dan, Oliver, Dominic, Oluyase, Adejoke, Olvera-Barrios, Abraham, Omigie, Efosa, Onida, Sarah, Padmanabhan, Sandosh, Palmer, Tom, Pasea, Laura, Patel, Riyaz, Payne, Rupert, Pell, Jill, Petitjean, Carmen, Pherwani, Arun, Pickrell, Owen, Pierotti, Livia, Pirmohamed, Munir, Priedon, Rouven, Prieto-Alhambra, Dani, Proudfoot, Alastair, Quinn, Terry, Quint, Jennifer, Raffetti, Elena, Rahimi, Kazem, Rao, Shishir, Razieh, Cameron, Roberts, Brian, Rogers, Caroline, Rossdale, Jennifer, Salim, Safa, Samani, Nilesh, Sattar, Naveed, Schnier, Christian, Schwartz, Roy, Selby, David, Seminog, Olena, Shabnam, Sharmin, Shah, Ajay, Shelton, Jon, Sheppard, James, Sinha, Shubhra, Skrypak, Mirek, Slapkova, Martina, Sleeman, Katherine, Smith, Craig, Sofat, Reecha, Sosenko, Filip, Sperrin, Matthew, Steeg, Sarah, Sterne, Jonathan, Stoica, Serban, Sudell, Maria, Sudlow, Cathie, Sun, Luanluan, Suseeladevi, Arun Karthikeyan, Sweeting, Michael, Sydes, Matt, Takhar, Rohan, Tang, Howard, Thygesen, Johan, Tilston, George, Tochel, Claire, Toit, Clea du, Tomlinson, Christopher, Toms, Renin, Torabi, Fatemeh, Torralbo, Ana, Townson, Julia, Tufail, Adnan, Tungamirai, Tapiwa, Varma, Susheel, Vollmer, Sebastian, Walker, Venexia, Wang, Tianxiao, Wang, Huan, Warwick, Alasdair, Watkinson, Ruth, Watson, Harry, Whiteley, William, Whittaker, Hannah, Wilde, Harry, Wilkinson, Tim, Williams, Gareth, Williams, Michelle, Williams, Richard, Withnell, Eloise, Wolfe, Charles, Wood, Angela, Wright, Lucy, Wu, Honghan, Wu, Jinge, Wu, Jianhua, Yates, Tom, Zaccardi, Francesco, Zhang, Haoting, Zhang, Huayu, Zuccolo, Luisa, Thygesen, Johan H, Mizani, Mehrdad A, Banerjee, Amitava, Lai, Alvina G, Li, Kezhi, Mateen, Bilal A, Sterne, Jonathan A C, Pagel, Christina, and Whiteley, William N

Published
2022
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3. Clinical investigation of subclinical vascular disease in psychosocial stress and dyslipidaemia

Author

Ellins, Elizabeth Anne

Subjects
616.1, R Medicine (General)
Abstract

Cardiovascular disease is a major cause of death and ill health across the world. Psychosocial factors are increasingly being recognised as potential cardiovascular risk factors, contributing to the development and progression of atherosclerotic disease. However, the pathways between psychosocial factors and cardiovascular disease are not yet fully understood. The aims of this thesis were to explore the associations between psychosocial factors (both chronic and acute stress) and measures of subclinical vascular disease, and to further develop and validate, a new method of assessing vasomotor function. Women with both depression and anxiety were found to have increased carotid intima-media thickness and this relationship was found to be influenced by the presence of dyslipidaemia. When looking at the inflammatory responses to an acute mental stress challenge it was shown that those participants who had an elevated fibrinogen response 45 minutes after the stress challenge had poorer endothelial function 3 years later, as assessed by flow-mediated dilatation. These findings suggest that both chronic and acute stress may play a role in the development of cardiovascular disease. Good reproducibility was demonstrated with the new method for assessing vasomotor function following further development of the protocol for the method. The technique was able to detect differences in vasomotor function between a group of patients with Familial Hypercholesterolaemia compared with age and gender matched controls. In addition it was also able to detect improvement in vasomotor function following a single lipoprotein apheresis treatment in patients with Familial Hypercholesterolaemia undergoing long-term treatment. These studies demonstrated the potential of this method for use in non-specialist vascular research laboratories and out in the field for the assessment of vasomotor function.

Published
2016

4. Incident atrial fibrillation and adverse clinical outcomes during extended follow-up of participants recruited to the Remote Heart Rhythm Sampling Using the AliveCor Heart Monitor to Screen for Atrial Fibrillation The REHEARSE-AF Study

Author

Ellins, Elizabeth A, primary, Wareham, Kathie, additional, Harris, Daniel E, additional, Hanney, Matthew, additional, Akbari, Ashley, additional, Gilmore, Mark, additional, Barry, James P, additional, Phillips, Ceri J, additional, Gravenor, Michael B, additional, and Halcox, Julian P, additional

Published
2023
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6. COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

Author

Thygesen, Johan H, primary, Tomlinson, Christopher, additional, Hollings, Sam, additional, Mizani, Mehrdad A, additional, Handy, Alex, additional, Akbari, Ashley, additional, Banerjee, Amitava, additional, Cooper, Jennifer, additional, Lai, Alvina G, additional, Li, Kezhi, additional, Mateen, Bilal A, additional, Sattar, Naveed, additional, Sofat, Reecha, additional, Torralbo, Ana, additional, Wu, Honghan, additional, Wood, Angela, additional, Sterne, Jonathan A C, additional, Pagel, Christina, additional, Whiteley, William N, additional, Sudlow, Cathie, additional, Hemingway, Harry, additional, Denaxas, Spiros, additional, Abbasizanjani, Hoda, additional, Ahmed, Nida, additional, Ahmed, Badar, additional, Akinoso-Imran, Abdul Qadr, additional, Allara, Elias, additional, Allery, Freya, additional, Angelantonio, Emanuele Di, additional, Ashworth, Mark, additional, Ayyar-Gupta, Vandana, additional, Babu-Narayan, Sonya, additional, Bacon, Seb, additional, Ball, Steve, additional, Banerjee, Ami, additional, Barber, Mark, additional, Barrett, Jessica, additional, Bennie, Marion, additional, Berry, Colin, additional, Beveridge, Jennifer, additional, Birney, Ewan, additional, Bojanić, Lana, additional, Bolton, Thomas, additional, Bone, Anna, additional, Boyle, Jon, additional, Braithwaite, Tasanee, additional, Bray, Ben, additional, Briffa, Norman, additional, Brind, David, additional, Brown, Katherine, additional, Buch, Maya, additional, Canoy, Dexter, additional, Caputo, Massimo, additional, Carragher, Raymond, additional, Carson, Alan, additional, Cezard, Genevieve, additional, Chang, Jen-Yu Amy, additional, Cheema, Kate, additional, Chin, Richard, additional, Chudasama, Yogini, additional, Copland, Emma, additional, Crallan, Rebecca, additional, Cripps, Rachel, additional, Cromwell, David, additional, Curcin, Vasa, additional, Curry, Gwenetta, additional, Dale, Caroline, additional, Danesh, John, additional, Das-Munshi, Jayati, additional, Dashtban, Ashkan, additional, Davies, Alun, additional, Davies, Joanna, additional, Davies, Gareth, additional, Davies, Neil, additional, Day, Joshua, additional, Delmestri, Antonella, additional, Denholm, Rachel, additional, Dennis, John, additional, Denniston, Alastair, additional, Deo, Salil, additional, Dhillon, Baljean, additional, Docherty, Annemarie, additional, Dong, Tim, additional, Douiri, Abdel, additional, Downs, Johnny, additional, Dregan, Alexandru, additional, Ellins, Elizabeth A, additional, Elwenspoek, Martha, additional, Falck, Fabian, additional, Falter, Florian, additional, Fan, Yat Yi, additional, Firth, Joseph, additional, Fraser, Lorna, additional, Friebel, Rocco, additional, Gavrieli, Amir, additional, Gerstung, Moritz, additional, Gilbert, Ruth, additional, Gillies, Clare, additional, Glickman, Myer, additional, Goldacre, Ben, additional, Goldacre, Raph, additional, Greaves, Felix, additional, Green, Mark, additional, Grieco, Luca, additional, Griffiths, Rowena, additional, Gurdasani, Deepti, additional, Halcox, Julian, additional, Hall, Nick, additional, Hama, Tuankasfee, additional, Hansell, Anna, additional, Hardelid, Pia, additional, Hardy, Flavien, additional, Harris, Daniel, additional, Harrison, Camille, additional, Harron, Katie, additional, Hassaine, Abdelaali, additional, Hassan, Lamiece, additional, Healey, Russell, additional, Henderson, Angela, additional, Herz, Naomi, additional, Heyl, Johannes, additional, Hidajat, Mira, additional, Higginson, Irene, additional, Hinchliffe, Rosie, additional, Hippisley-Cox, Julia, additional, Ho, Frederick, additional, Hocaoglu, Mevhibe, additional, Horne, Elsie, additional, Hughes, David, additional, Humberstone, Ben, additional, Inouye, Mike, additional, Ip, Samantha, additional, Islam, Nazrul, additional, Jackson, Caroline, additional, Jenkins, David, additional, Jiang, Xiyun, additional, Johnson, Shane, additional, Kadam, Umesh, additional, Kallis, Costas, additional, Karim, Zainab, additional, Kasan, Jake, additional, Katsoulis, Michalis, additional, Kavanagh, Kim, additional, Kee, Frank, additional, Keene, Spencer, additional, Kent, Seamus, additional, Khalid, Sara, additional, Khawaja, Anthony, additional, Khunti, Kamlesh, additional, Killick, Richard, additional, Kinnear, Deborah, additional, Knight, Rochelle, additional, Kolamunnage-Dona, Ruwanthi, additional, Kontopantelis, Evan, additional, Kurdi, Amanj, additional, Lacey, Ben, additional, Lai, Alvina, additional, Lambarth, Andrew, additional, Larzjan, Milad Nazarzadeh, additional, Lawler, Deborah, additional, Lawrence, Thomas, additional, Lawson, Claire, additional, Li, Qiuju, additional, Li, Ken, additional, Llinares, Miguel Bernabeu, additional, Lorgelly, Paula, additional, Lowe, Deborah, additional, Lyons, Jane, additional, Lyons, Ronan, additional, Machado, Pedro, additional, Macleod, Mary Joan, additional, Macleod, John, additional, Malgapo, Evaleen, additional, Mamas, Mamas, additional, Mamouei, Mohammad, additional, Manohar, Sinduja, additional, Mapeta, Rutendo, additional, Martelli, Javiera Leniz, additional, Martos, David Moreno, additional, Mateen, Bilal, additional, McCarthy, Aoife, additional, Melville, Craig, additional, Milton, Rebecca, additional, Mizani, Mehrdad, additional, Moncusi, Marta Pineda, additional, Morales, Daniel, additional, Mordi, Ify, additional, Morrice, Lynn, additional, Morris, Carole, additional, Morris, Eva, additional, Mu, Yi, additional, Mueller, Tanja, additional, Murdock, Lars, additional, Nafilyan, Vahé, additional, Nicholson, George, additional, Nikiphorou, Elena, additional, Nolan, John, additional, Norris, Tom, additional, Norris, Ruth, additional, North, Laura, additional, North, Teri-Louise, additional, O'Connell, Dan, additional, Oliver, Dominic, additional, Oluyase, Adejoke, additional, Olvera-Barrios, Abraham, additional, Omigie, Efosa, additional, Onida, Sarah, additional, Padmanabhan, Sandosh, additional, Palmer, Tom, additional, Pasea, Laura, additional, Patel, Riyaz, additional, Payne, Rupert, additional, Pell, Jill, additional, Petitjean, Carmen, additional, Pherwani, Arun, additional, Pickrell, Owen, additional, Pierotti, Livia, additional, Pirmohamed, Munir, additional, Priedon, Rouven, additional, Prieto-Alhambra, Dani, additional, Proudfoot, Alastair, additional, Quinn, Terry, additional, Quint, Jennifer, additional, Raffetti, Elena, additional, Rahimi, Kazem, additional, Rao, Shishir, additional, Razieh, Cameron, additional, Roberts, Brian, additional, Rogers, Caroline, additional, Rossdale, Jennifer, additional, Salim, Safa, additional, Samani, Nilesh, additional, Schnier, Christian, additional, Schwartz, Roy, additional, Selby, David, additional, Seminog, Olena, additional, Shabnam, Sharmin, additional, Shah, Ajay, additional, Shelton, Jon, additional, Sheppard, James, additional, Sinha, Shubhra, additional, Skrypak, Mirek, additional, Slapkova, Martina, additional, Sleeman, Katherine, additional, Smith, Craig, additional, Sosenko, Filip, additional, Sperrin, Matthew, additional, Steeg, Sarah, additional, Sterne, Jonathan, additional, Stoica, Serban, additional, Sudell, Maria, additional, Sun, Luanluan, additional, Suseeladevi, Arun Karthikeyan, additional, Sweeting, Michael, additional, Sydes, Matt, additional, Takhar, Rohan, additional, Tang, Howard, additional, Thygesen, Johan, additional, Tilston, George, additional, Tochel, Claire, additional, Toit, Clea du, additional, Toms, Renin, additional, Torabi, Fatemeh, additional, Townson, Julia, additional, Tufail, Adnan, additional, Tungamirai, Tapiwa, additional, Varma, Susheel, additional, Vollmer, Sebastian, additional, Walker, Venexia, additional, Wang, Tianxiao, additional, Wang, Huan, additional, Warwick, Alasdair, additional, Watkinson, Ruth, additional, Watson, Harry, additional, Whiteley, William, additional, Whittaker, Hannah, additional, Wilde, Harry, additional, Wilkinson, Tim, additional, Williams, Gareth, additional, Williams, Michelle, additional, Williams, Richard, additional, Withnell, Eloise, additional, Wolfe, Charles, additional, Wright, Lucy, additional, Wu, Jinge, additional, Wu, Jianhua, additional, Yates, Tom, additional, Zaccardi, Francesco, additional, Zhang, Haoting, additional, Zhang, Huayu, additional, and Zuccolo, Luisa, additional

Published
2022
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7. Achievement of European Society of Cardiology/European Atherosclerosis Society lipid targets in very high-risk patients: Influence of depression and sex

Author

Ellins, Elizabeth A., primary, Harris, Daniel E., additional, Lacey, Arron, additional, Akbari, Ashley, additional, Torabi, Fatemeh, additional, Smith, Dave, additional, Jenkins, Geraint, additional, Obaid, Daniel, additional, Chase, Alex, additional, John, Ann, additional, Gravenor, Michael B., additional, and Halcox, Julian P., additional

Published
2022
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11. Active Children Through Individual Vouchers Evaluation: A Mixed-Method RCT

Author

James, Michaela, Christian, Danielle, Scott, Samantha, Todd, Charlotte, Stratton, Gareth, McCoubrey, Sarah, Halcox, Julian, Audrey, Suzanne, Ellins, Elizabeth, Brophy, Sinead, James, Michaela, Christian, Danielle, Scott, Samantha, Todd, Charlotte, Stratton, Gareth, McCoubrey, Sarah, Halcox, Julian, Audrey, Suzanne, Ellins, Elizabeth, and Brophy, Sinead

Abstract

Introduction Physical activity declines in adolescence, especially among those in deprived areas. Research suggests this may result from accessibility barriers (e.g., cost and locality). The Active Children Through Individual Vouchers Evaluation RCT aimed to improve the fitness and heart health of teenagers in Wales with the help of teenagers who co-produced the study. Study design This study was a mixed-method RCT. Setting/participants Before data collection, which took place at baseline, 6 months, and 12 months for both arms, 7 schools were randomized by an external statistician (4 intervention schools, n=524; 3 control schools, n=385). Intervention The Active Children Through Individual Vouchers Evaluation intervention included provision of activity vouchers (£20 per month), a peer mentoring scheme, and support worker engagement for 12 months between January and December 2017. Data analysis occurred February–April 2018. Main outcome measures Data included measures of cardiovascular fitness, cardiovascular health (blood pressure and pulse wave analysis), motivation, and focus groups. Results The intervention showed a trend to improve the distance ran (primary outcome) and was significant in improving the likelihood of intervention teenagers being fit (OR=1.21, 95% CI=1.07, 1.38, p=0.002). There was a reduction in teenagers classified as having high blood pressure (secondary outcome) in the intervention group (baseline, 5.3% [28/524]; 12 months, 2.7% [14/524]). Data on where teenagers used vouchers and evidence from focus groups showed that teenagers wanted to access more unstructured, informal, and social activities in their local areas. Conclusions Active Children Through Individual Vouchers Evaluation identified methods that may have a positive impact on cardiovascular fitness, cardiovascular health, and perspectives of activity. Consulting with teenagers, empowering them, and providing more local opportunities for them to take part in activities that are fun, u

Published
2020

12. The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis

Author

Davies, Ruth, primary, Williams, Jessica, additional, Sime, Katie, additional, Jin, Hyun-Sun, additional, Thompson, Charlotte, additional, Jordan, Lauren, additional, Lang, Derek, additional, Halcox, Julian P, additional, Ellins, Elizabeth, additional, Jones, Gareth W, additional, Jones, Simon A, additional, Rose-John, Stefan, additional, Williams, Anwen, additional, and Choy, Ernest, additional

Published
2020
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14. Carotid artery wave intensity in mid- to late-life predicts cognitive decline: the Whitehall II study

Author

Chiesa, Scott T, Masi, Stefano, Shipley, Martin J, Ellins, Elizabeth A, Fraser, Alan G, Hughes, Alun D, Patel, Riyaz S, Khir, Ashraf W, Halcox, Julian P, Singh-Manoux, Archana, Kivimaki, Mika, Celermajer, David S, and Deanfield, John E

Subjects
Male, cardiovascular risk factors, Prevention and Epidemiology, Carotid Artery, Common, Age Factors, Fast Track Clinical Research, Cognitive decline, Middle Aged, wave intensity, Prognosis, cognitive decline, Cohort Studies, Wave intensity, Cognition, Whitehall II study, Pulsatile Flow, Humans, Female, Cognitive Dysfunction, Cardiovascular risk factors, Aged
Abstract

© The Author(s) 2019. Aims: Excessive arterial pulsatility may contribute to cognitive decline and risk of dementia via damage to the fragile cerebral microcirculation. We hypothesized that the intensity of downstream-travelling pulsatile waves measured by wave intensity analysis in the common carotid artery during mid- to late-life would be associated with subsequent cognitive decline. ......................................................................................................................................................... Methods and results: Duplex Doppler ultrasound was used to calculate peak forward-travelling compression wave intensity (FCWI) within the common carotid artery in 3191 individuals [mean ± standard deviation (SD), age = 61 ± 6 years; 75% male] assessed as part of the Whitehall II study in 2003–05. Serial measures of cognitive function were taken between 2002–04 and 2015–16. The relationship between FCWI and cognitive decline was adjusted for sociodemographic variables, genetic and health-related risk factors, and health behaviours. Mean (SD) 10-year change in standardized global cognitive score was -0.39 (0.18). Higher FCWI at baseline was associated with accelerated cognitive decline during follow-up [difference in 10-year change of global cognitive score per 1 SD higher FCWI = -0.02 (95% confidence interval -0.04 to -0.00); P = 0.03]. This association was largely driven by cognitive changes in individuals with the highest FCWI [Q4 vs. Q1–Q3 = -0.05 (-0.09 to -0.01), P = 0.01], equivalent to an age effect of 1.9 years. Compared to other participants, this group was 50% more likely to exhibit cognitive decline (defined as the top 15% most rapid reductions in cognitive function during follow-up) even after adjustments for multiple potential confounding factors [odds ratio 1.49 (1.17–1.88)]. ............................................................................................................................................... Conclusion: Elevated carotid artery wave intensity in mid- to late-life predicts faster cognitive decline in long-term follow-up independent of other cardiovascular risk factors. Whitehall II study was supported by the UK Medical Research Council [MR/R024227/1]; the US National Institute on Aging [NIA, R01AG056477], the British Heart Foundation [32334]; and European Commission [LIFEPATH 633666]. S.T.C. receives research funding from the Brain Protection Company Ltd (Australia). M.K. was supported by the Medical Research Council, NIA, NordForsk, and Helsinki Institute of Life Sciences (Finland). J.E.D. was a BHF-funded Professor from 2003 to 2017. A.D.H. receives support from the British Heart Foundation [PG/15/75/31748, CS/15/6/31468, and CS/13/1/30327], the National Institute for Health Research University College London Hospitals Biomedical Research Centre, and works in a unit that receives support from the UK Medical Research Council [Programme Code MC_UU_12019/1].

Published
2019

15. Predictors of cardiovascular health in teenagers (aged 13–14 years): a cross-sectional study linked with routine data

Author

James, Michaela, Christian, Danielle, Scott, Samantha, Todd, Charlotte, Stratton, Gareth, Demmler, Joanne, McCoubrey, Sarah, Halcox, Julian P, Audrey, Suzanne, Ellins, Elizabeth Anne, Brophy, Sinead, James, Michaela, Christian, Danielle, Scott, Samantha, Todd, Charlotte, Stratton, Gareth, Demmler, Joanne, McCoubrey, Sarah, Halcox, Julian P, Audrey, Suzanne, Ellins, Elizabeth Anne, and Brophy, Sinead

Abstract

Objective To examine the predictors of cardiovascular health in teenagers (aged 13–14 years). Methods Measures of arterial stiffness (augmentation index [AI]), blood pressure and cardiovascular fitness were taken from 234 teenage children (n=152 boys) and subsequently linked to routine data (birth and general practice records, education data and hospital admission data). Deprivation at school and at individual level was measured at birth, at 1 year old, at 13 years old and at secondary school using the Welsh Index of Multiple Deprivation (WIMD) Multivariate regression analysis determined associations between routinely collected data and cardiovascular measures. Results Teenagers had higher augmentation index (2.41 [95% CI: 1.10 to 3.72]), ran fewer metres (-130.08 metres [95% CI: -234.35 to -25.78]) in the Cooper Run Test if they attended a more deprived school. However, higher individual level deprivation was associated with greater fitness (199.38 metres [95% CI: 83.90 to 314.84]). Higher systolic blood pressure was observed in first born children (10.23 mmHg [95% CI: 1.58 to 18.88]) and in those who were never breastfed (4.77 mmHg [95% CI: 1.10 to 8.42]). Conclusions Improving heart health in deprived areas requires multi-level action across childhood namely, active play and programmes that promote physical activity and fitness and, the promotion of breastfeeding. Recognition of the important early indicators and determinants of cardiovascular health supports further development of the evidence base to encourage policy-makers to implement preventative measures in young people.

Published
2019

16. What works best when implementing a physical activity intervention for teenagers? Reflections from the ACTIVE Project: a qualitative study

Author

James, Michaela, Christian, Danielle, Scott, Samantha, Todd, Charlotte, Stratton, Gareth, Demmler, Joanne, McCoubrey, Sarah, Halcox, Julian, Audrey, Suzanne, Ellins, Elizabeth A, Irvine, Elizabeth, Brophy, Sinead, James, Michaela, Christian, Danielle, Scott, Samantha, Todd, Charlotte, Stratton, Gareth, Demmler, Joanne, McCoubrey, Sarah, Halcox, Julian, Audrey, Suzanne, Ellins, Elizabeth A, Irvine, Elizabeth, and Brophy, Sinead

Abstract

Objective This paper explores what aspects of a multicomponent intervention were deemed strengths and weaknesses by teenagers and the local council when promoting physical activity to young people. Design Qualitative findings at 12 months from a mixed method randomised control trial. Methods Active Children Through Incentive Vouchers—Evaluation (ACTIVE) gave teenagers £20 of activity enabling vouchers every month for a year. Peer mentors were also trained and a support worker worked with teenagers to improve knowledge of what was available. Semistructured focus groups took place at 12 months to assess strengths and weaknesses of the intervention. Eight focus groups (n=64 participants) took place with teenagers and one additional focus group was dedicated to the local council’s sport development team (n=8 participants). Thematic analysis was used to analyse the data. Results Teenagers used the vouchers on three main activities: trampolining, laser tag or the water park. These appeal to both genders, are social, fun and require no prior skill or training. Choice and financial support for teenagers in deprived areas was considered a strength by teenagers and the local council. Teenagers did not engage with a trained peer mentor but the support worker was considered helpful. Conclusions The ACTIVE Project’s delivery had both strengths and weakness that could be used to underpin future physical activity promotion. Future interventions should focus on improving access to low cost, fun, unstructured and social activities rather than structured organised exercise/sport. The lessons learnt from this project can help bridge the gap between what is promoted to teenagers and what they actually want from activity provision.

Published
2019

17. Influence of Maternal Lifestyle and Diet on Perinatal DNA Methylation Signatures Associated With Childhood Arterial Stiffness at 8 to 9 Years.

Author

Murray, Robert, Kitaba, Negusse, Antoun, Elie, Titcombe, Philip, Barton, Sheila, Cooper, Cyrus, Inskip, Hazel M., Burdge, Graham C., Mahon, Pamela A., Deanfield, John, Halcox, Julian P., Ellins, Elizabeth A., Bryant, Jennifer, Peebles, Charles, Lillycrop, Karen, Godfrey, Keith M., Hanson, Mark A., and EpiGen Consortium

Abstract

[Figure: see text]. [ABSTRACT FROM AUTHOR]

Published
2021
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18. Objectively measured physical activity, sedentary time and subclinical vascular disease: Cross-sectional study in older British men

Author

Parsons, Tessa J., Sartini, Claudio, Ellins, Elizabeth A., Halcox, Julian P.J., Smith, Kirsten E., Ash, Sarah, Lennon, Lucy T., Wannamethee, S. Goya, Lee, I-Min, Whincup, Peter H., and Jefferis, Barbara J.

Subjects
Accelerometer, Physical activity, Epidemiology, Public Health, Environmental and Occupational Health, Sedentary behaviour, Cardiovascular disease
Abstract

Low physical activity (PA) and high levels of sedentary time (ST) are associated with higher cardiovascular disease (CVD) risk among older people. However, their independent contribution and importance of duration of PA and ST bouts remain unclear. We investigated associations between objectively measured PA, ST and non-invasive vascular measures, markers of CVD risk.Cross-sectional study of 1216 men from the British Regional Heart Study, mean age 78.5years, measured in 2010–2012. Carotid intima thickness (CIMT), distensibility coefficient (DC) and plaque presence were measured using ultrasound; pulse wave velocity (cfPWV) and augmentation index (AIx) using a Vicorder. PA and ST were measured using hip-worn ActiGraph GT3X accelerometers.After adjusting for covariates, each additional 1000 steps per day was associated with a 0.038m/s lower cfPWV (95% CI=−0.076, 0.0003), 0.095 10−3 kPa−1 higher DC (95% CI=0.006, 0.185), 0.26% lower AIx (95% CI=−0.40, −0.12) and a 0.005mm lower CIMT (95% CI=−0.008, −0.001). Moderate and vigorous PA (MVPA) was associated with lower AIx and CIMT, light PA (LPA) with lower cfPWV and CIMT and ST with higher cfPWV, AIx and CIMT and lower DC. LPA and ST were highly correlated (r=−0.62). The independence of MVPA and ST or MVPA and LPA was inconsistent across vascular measures. Bout lengths for both PA and ST were not associated with vascular measures.In our cross-sectional study of older men, all PA regardless of intensity or bout duration was beneficially associated with vascular measures, as was lower ST. LPA was particularly relevant for cfPWV and CIMT.

Published
2016
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19. The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis.

Author

Davies, Ruth, Williams, Jessica, Sime, Katie, Jin, Hyun-Sun, Thompson, Charlotte, Jordan, Lauren, Lang, Derek, Halcox, Julian P, Ellins, Elizabeth, Jones, Gareth W, Jones, Simon A, Rose-John, Stefan, Williams, Anwen, and Choy, Ernest

Subjects
INTERLEUKINS, BIOMARKERS, DISEASE progression, INFECTIOUS arthritis, SCIENTIFIC observation, CAROTID intima-media thickness, ANIMAL experimentation, MUSCLES, CROSS-sectional method, CARDIOVASCULAR diseases, CELLULAR signal transduction, ATHEROSCLEROSIS, DIAGNOSIS, MICE, LONGITUDINAL method, CHEMICAL inhibitors
Abstract

Objectives Cardiovascular (CV) mortality in RA patients is 50% higher than in the general population. There is increasing recognition that systemic inflammation is a major driver of this. IL-6 is implicated in cardiovascular disease (CVD) in the general population but its role in CVD in RA is undefined. Of the two modes of IL-6 signalling, trans-signalling is pro-inflammatory whereas classical signalling is linked with inflammation resolution. This study examines the role of IL-6 trans-signalling in CVD in a mouse model and patients with RA. Methods Myography determined the effect of IL-6 trans-signalling blockade, using sgp130Fc, on aortic constriction in murine collagen-induced arthritis. Serum CCL2 and sVCAM-1 as soluble biomarkers of sIL-6R trans-signalling were investigated in a human cross-sectional study. An observational longitudinal study investigated the association between these biomarkers and progression of subclinical atherosclerosis in early RA by measuring carotid intima-media thickness (CIMT). Results sgp130Fc reduced arthritis severity, serum CCL2 and sVCAM-1 and restored vascular function in collagen-induced arthritis (CIA). In established RA, sVCAM-1 correlated with the 28-joint DAS (DAS28) and CV risk. In early RA, baseline DAS28 was associated with CIMT change at 6 months. CIMT 'rapid progressors' at 12 months had higher baseline sVCAM-1, haemoglobin A1c, cholesterol:high-density lipoprotein cholesterol ratio and LDL cholesterol. Conclusions IL-6 trans-signalling plays a pivotal role in vascular dysfunction in CIA. In early RA, sVCAM-1 was associated with progression of subclinical atherosclerosis. Inflammation from RA onset in CVD-susceptible individuals may accelerate atherosclerosis. IL-6 trans-signalling blockade may be beneficial to RA patients and perhaps for atherosclerosis in the general population. [ABSTRACT FROM AUTHOR]

Published
2021
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20. Additional file 1: of Teenage recommendations to improve physical activity for their age group: a qualitative study

Author

James, Michaela, Todd, Charlotte, Scott, Samantha, Stratton, Gareth, McCoubrey, Sarah, Christian, Danielle, Halcox, Julian, Audrey, Suzanne, Ellins, Elizabeth, Anderson, Samantha, Copp, Isabel, and Sinead Brophy

Abstract

ACTIVE Focus Group Topic Guide PUBH-D-17-02284R2. ACTIVE Focus Group Questions The topic guides for the ACTIVE focus groups for both intervention and control schools. (DOCX 14 kb)

Published
2018
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21. Predictors of cardiovascular health in teenagers (aged 13–14 years): a cross-sectional study linked with routine data

Author

James, Michaela, primary, Christian, Danielle, additional, Scott, Samantha, additional, Todd, Charlotte, additional, Stratton, Gareth, additional, Demmler, Joanne, additional, McCoubrey, Sarah, additional, Halcox, Julian P, additional, Audrey, Suzanne, additional, Ellins, Elizabeth Anne, additional, and Brophy, Sinead, additional

Published
2019
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22. What works best when implementing a physical activity intervention for teenagers? Reflections from the ACTIVE Project: a qualitative study

Author

James, Michaela, primary, Christian, Danielle, additional, Scott, Samantha, additional, Todd, Charlotte, additional, Stratton, Gareth, additional, Demmler, Joanne, additional, McCoubrey, Sarah, additional, Halcox, Julian, additional, Audrey, Suzanne, additional, Ellins, Elizabeth A, additional, Irvine, Elizabeth, additional, and Brophy, Sinead, additional

Published
2019
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23. Carotid artery wave intensity in mid- to late-life predicts cognitive decline: the Whitehall II study

Author

Chiesa, Scott T, primary, Masi, Stefano, additional, Shipley, Martin J, additional, Ellins, Elizabeth A, additional, Fraser, Alan G, additional, Hughes, Alun D, additional, Patel, Riyaz S, additional, Khir, Ashraf W, additional, Halcox, Julian P, additional, Singh-Manoux, Archana, additional, Kivimaki, Mika, additional, Celermajer, David S, additional, and Deanfield, John E, additional

Published
2019
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24. Teenage recommendations to improve physical activity for their age group: a qualitative study

Author

James, Michael, Todd, Charlotte, Scott, Samantha, Stratton, Gareth, McCoubrey, Sarah, Christian, Danielle, Halcox, Julian, Audrey, Suzanne, Ellins, Elizabeth, Anderson, Samantha, Copp, Isabel, Brophy, Sinead, James, Michael, Todd, Charlotte, Scott, Samantha, Stratton, Gareth, McCoubrey, Sarah, Christian, Danielle, Halcox, Julian, Audrey, Suzanne, Ellins, Elizabeth, Anderson, Samantha, Copp, Isabel, and Brophy, Sinead

Abstract

Background It is recommended that young people should engage in 60 min of moderate-to-vigorous activity (MVPA) a day for health benefits, but few teenagers actually meet this recommendation. Policy-makers play a vital role in designing physical activity initiatives, but they generally do this with little or no input from the intervention recipients. This study explores the recommendations made by teenagers to improve activity provision, uptake and sustainability of physical activity engagement for both themselves and their peers. Methods Thirteen focus groups were carried out in seven secondary schools in South Wales, United Kingdom. Participants (n = 78) were recruited from a larger mixed-method randomised control trial, which involved the implementation of a voucher scheme to promote physical activity in teenagers (aged 13–14). Thematic analysis was undertaken to identify key issues from the perspective of the teenage participants. Results Six key recommendations were identified following analysis of the focus groups: i) Lower/remove the cost of activities without sacrificing the quality, ii) Make physical activity opportunities more locally accessible, iii) Improve the standards of existing facilities, iv) Make activities more specific to teenagers v) Give teenagers a choice of activities/increase variety of activity and vi) Provide activities that teenage girls enjoy (e.g., fun, sociable and not competitive sport). Throughout the focus groups, the increased opportunity to participate in unstructured activity was a key recommendation echoed by both boys and girls in all themes. Conclusion There is a disconnect between what is available and what teenagers want to do. Policy-makers and those involved in physical activity delivery (e.g., schools, local council and local activity providers) should include young people in designing interventions and facilities to ensure they are meeting the needs of this age group and providing the right opportunities for teenagers to

Published
2018

25. Self-reported sleep duration and napping, cardiac risk factors and markers of subclinical vascular disease: cross-sectional study in older men

Author

Zonoozi, Shahrzad, Ramsay, Sheena E, Papacosta, Olia, Lennon, Lucy, Ellins, Elizabeth A, Halcox, Julian P J, Whincup, Peter H, and Goya Wannamethee, S

Subjects
Blood Glucose, Male, Time Factors, Epidemiology, subclinical atherosclerosis, Disorders of Excessive Somnolence, Pulse Wave Analysis, Carotid Intima-Media Thickness, Vascular Stiffness, Risk Factors, Forced Expiratory Volume, Natriuretic Peptide, Brain, von Willebrand Factor, Humans, Insulin, Aged, Aged, 80 and over, Glycated Hemoglobin, Heart Failure, Research, sleep patterns, Atherosclerosis, Peptide Fragments, Troponin, Cross-Sectional Studies, Asymptomatic Diseases, Self Report, cardiac function, Sleep, Biomarkers
Abstract

STUDYOBJECTIVES: Daytime sleep has been associated with increased risk of cardiovascular disease and heart failure (HF), but the mechanisms remain unclear. We have investigated the association between daytime and night-time sleep patterns and cardiovascular risk markers in older adults including cardiac markers and subclinical markers of atherosclerosis (arterial stiffness and carotid intima-media thickness (CIMT)). METHODS: Cross-sectional study of 1722 surviving men aged 71-92 examined in 2010-2012 across 24 British towns from a prospective study initiated in 1978-1980. Participants completed a questionnaire and were invited for a physical examination. Men with a history of heart attack or HF (n=251) were excluded from the analysis. RESULTS: Self-reported daytime sleep duration was associated with higher fasting glucose and insulin levels (p=0.02 and p=0.01, respectively) even after adjustment for age, body mass index, physical activity and social class. Compared with those with no daytime sleep, men with daytime sleep >1 hour, defined as excessive daytime sleepiness (EDS), had a higher risk of raised N-terminal pro-brain natriuretic peptide of ≥400 pg/mL, the diagnostic threshold for HF (OR (95% CI)=1.88 (1.15 to 3.1)), higher mean troponin, reduced lung function (forced expiratory volume in 1 s) and elevated von Willebrand factor, a marker of endothelial dysfunction. However, EDS was unrelated to CIMT and arterial stiffness. By contrast, night-time sleep was only associated with HbA1c (short or long sleep) and arterial stiffness (short sleep). CONCLUSIONS: Daytime sleep duration of >1 hour may be an early indicator of HF.

Published
2017

27. Active children through individual vouchers– evaluation (ACTIVE): protocol for a mixed method randomised control trial to increase physical activity levels in teenagers

Author

James, Michaela, Christian, Danielle, Scott, Samantha, Todd, Charlotte, Stratton, Gareth, McCoubrey, Sarah, Halcox, Julian, Audrey, Suzanne, Ellins, Elizabeth, Brophy, Sinead, James, Michaela, Christian, Danielle, Scott, Samantha, Todd, Charlotte, Stratton, Gareth, McCoubrey, Sarah, Halcox, Julian, Audrey, Suzanne, Ellins, Elizabeth, and Brophy, Sinead

Abstract

Background: Many teenagers are insufficiently active despite the health benefits of physical activity (PA). There is strong evidence to show that inactivity and low fitness levels increase the risk of non-communicable diseases such as coronary heart disease (CHD), type 2 diabetes and breast and colon cancers (Lee et al. Lancet 380:219–29, 2012). A major barrier facing adolescents is accessibility (e.g. cost and lack of local facilities). The ACTIVE project aims to tackle this barrier through a multi-faceted intervention, giving teenagers vouchers to spend on activities of their choice and empowering young people to improve their fitness and PA levels. Design: ACTIVE is a mixed methods randomised control trial in 7 secondary schools in Swansea, South Wales. Quantitative and qualitative measures including PA (cooper run test (CRT), accelerometery over 7 days), cardiovascular (CV) measures (blood pressure, pulse wave analysis) and focus groups will be undertaken at 4 separate time points (baseline, 6 months,12 months and follow-up at 18 months). Intervention schools will receive a multi-component intervention involving 12 months of £20 vouchers to spend on physical activities of their choice, a peer mentor scheme and opportunities to attend advocacy meetings. Control schools are encouraged to continue usual practice. The primary aim is to examine the effect of the intervention in improving cardiovascular fitness. Discussion: This paper describes the protocol for the ACTIVE randomised control trial, which aims to increase fitness, physical activity and socialisation of teenagers in Swansea, UK via a voucher scheme combined with peer mentoring. Results can contribute to the evidence base on teenage physical activity and, if effective, the intervention has the potential to inform future physical activity interventions and policy.

Published
2017

28. Objectively measured physical activity and sedentary behaviour and ankle brachial index: Cross-sectional and longitudinal associations in older men

Author

Parsons, Tessa J., Sartini, Claudio, Ellins, Elizabeth A., Halcox, Julian P.J., Smith, Kirsten E., Ash, Sarah, Lennon, Lucy T., Wannamethee, S. Goya, Lee, I-Min, Whincup, Peter H., and Jefferis, Barbara J.

Subjects
Male, Aging, Epidemiology, Article, Peripheral Arterial Disease, Sex Factors, Vascular Stiffness, Predictive Value of Tests, Risk Factors, Odds Ratio, Humans, Ankle Brachial Index, Longitudinal Studies, Prospective Studies, cardiovascular diseases, Exercise, Aged, Aged, 80 and over, Physical activity, Age Factors, Men, Actigraphy, United Kingdom, Accelerometer, body regions, Cross-Sectional Studies, Logistic Models, Sedentary Behavior, Cardiology and Cardiovascular Medicine, human activities
Abstract

Background Associations between bouts of physical activity (PA), sedentary behaviour (SB) and cardiovascular disease, and their mutual independence are not well defined. A low ankle brachial index (ABI ≤0.9) indicates peripheral arterial disease (PAD) and is predictive of cardiovascular events and functional impairment. We investigated the independence of PA and SB and the importance of bout duration in relation to ABI using objective measures. Methods 945 men from the British Regional Heart Study, mean age 78.4 y, had concurrent measurements of ABI (Vicorder) and physical activity (Actigraph GT3X accelerometer); 427 men also had accelerometer measurements one year previously and contributed data to longitudinal analyses. Results and conclusion In cross-sectional analyses, after adjusting for covariates each extra 10 min of moderate and vigorous PA per day was associated with an OR of 0.81 (95% CI 0.72, 0.91) for a low ABI, a stronger association than for light PA (OR 0.85, 95% CI 0.75, 0.98). Each extra 30 min of SB was associated with an OR of 1.19 (95% CI 1.07, 1.33) for a low ABI. Associations between moderate and vigorous PA and ABI persisted after adjustment for light PA or SB. Bout lengths for PA and SB were not associated with a low ABI. One year changes in PA or SB were not associated with low ABI. All physical activity and lower levels of SB, regardless of bout duration were inversely associated with ABI; more intense PA showed a stronger association. No associations between changes in PA and ABI were observed, but power may have been limited., Highlights • Physical activity (PA) and ABI were objectively measured in British men (mean age 78y). • PA was associated with a lower odds of a low ABI (OR 0.81, 95% CI 0.72, 0.91). • Sedentary behaviour (SB) was associated with a higher odds (1.19) of a low ABI. • Higher intensity PA showed a stronger association with ABI than lighter intensity PA. • Total time spent in PA or SB, but not duration of bouts was associated with ABI.

Published
2016

29. Active children through individual vouchers – evaluation (ACTIVE): protocol for a mixed method randomised control trial to increase physical activity levels in teenagers

Author

James, Michaela, primary, Christian, Danielle, additional, Scott, Samantha, additional, Todd, Charlotte, additional, Stratton, Gareth, additional, McCoubrey, Sarah, additional, Halcox, Julian, additional, Audrey, Suzanne, additional, Ellins, Elizabeth, additional, and Brophy, Sinead, additional

Published
2017
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35. Where Are We Heading with Noninvasive Clinical Vascular Physiology? Why and How Should We Assess Endothelial Function?

Author

Ellins, Elizabeth A. and Halcox, Julian P. J.

Subjects
Article Subject
Abstract

There are several invasive and noninvasive methods available to the clinical researcher for the assessment of endothelial function. The first investigations in humans involved invasive pharmacological vascular function testing, which have been used to gain a detailed understanding of the mechanisms involved in the pathogenesis of endothelial dysfunction and atherosclerosis as well as novel targets for intervention. Techniques for endothelial function testing have evolved over time from these invasive methods, which, by their nature, are restricted to small studies in the research laboratory, to more standardized noninvasive methods, which are suitable for use in large prospective cohort studies and clinical trials. This paper describes currently available methods for assessment of endothelial function and their potential application in cardiovascular research and clinical practice.

Published
2011
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37. Ready-to-Use Supplementary Food Supplements Improve Endothelial Function, Hemoglobin and Growth in Tanzanian Children with Sickle Cell Anaemia: The Vascular Function Intervention Study (V-FIT), a Random Order Crossover Trial

Author

Cox, Sharon E., primary, Makani, Julie, additional, Walter, Gurishaeli, additional, Mtunguja, Selemani, additional, Kamala, Beatrice A, additional, Ellins, Elizabeth, additional, Newton, Charles RJ, additional, Kirkham, Fenella J., additional, Prentice, Andrew M, additional, and Halcox, Julian P, additional

Published
2014
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42. Erratum: Extended extraocular phenotype of PROM1 mutation in kindreds with known autosomal dominant macular dystrophy

Author

Arrigoni, Francesca I, primary, Matarin, Mar, additional, Thompson, Pamela J, additional, Michaelides, Michel, additional, McClements, Michelle E, additional, Redmond, Elizabeth, additional, Clarke, Lindsey, additional, Ellins, Elizabeth, additional, Mohamed, Saifullah, additional, Pavord, Ian, additional, Klein, Nigel, additional, Hunt, David M, additional, Moore, Anthony T, additional, Halcox, Julian, additional, and Sisodiya, Sanjay M, additional

Published
2011
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43. Extended extraocular phenotype of PROM1 mutation in kindreds with known autosomal dominant macular dystrophy

Author

Arrigoni, Francesca I, primary, Matarin, Mar, additional, Thompson, Pamela J, additional, Michaelides, Michel, additional, McClements, Michelle E, additional, Redmond, Elizabeth, additional, Clarke, Lindsey, additional, Ellins, Elizabeth, additional, Mohamed, Saifullah, additional, Pavord, Ian, additional, Hunt, David M, additional, Moore, Anthony T, additional, Halcox, Julian, additional, and Sisodiya, Sanjay M, additional

Published
2010
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46. Extended extraocular phenotype of PROM1 mutation in kindreds with known autosomal dominant macular dystrophy.

Author

Arrigoni, Francesca I., Matarin, Mar, Thompson, Pamela J., Michaelides, Michel, McClements, Michelle E., Redmond, Elizabeth, Clarke, Lindsey, Ellins, Elizabeth, Mohamed, Saifullah, Pavord, Ian, Hunt, David M., Moore, Anthony T., Halcox, Julian, and Sisodiya, Sanjay M.

Subjects
RETINAL degeneration, GENETIC mutation, DEVELOPMENTAL neurobiology, ENDOTHELIUM physiology, BRAIN physiology
Abstract

Mutations in prominin 1 (PROM1) have been shown to result in retinitis pigmentosa, macular degeneration and cone-rod dystrophy. Because of the putative role of PROM1 in hippocampal neurogenesis, we examined two kindreds with the same R373C PROM1 missense mutation using our established paradigm to study brain structure and function. As the protein encoded by PROM1, known as CD133, is used to identify stem/progenitor cells that can be found in peripheral blood and reflect endothelial reparatory mechanisms, other parameters were subsequently examined that included measures of vascular function, endothelial function and angiogenic capacity. We found that aspects of endothelial function assayed ex vivo were abnormal in patients with the R373C PROM1 mutation, with impaired adhesion capacity and higher levels of cellular damage. We also noted renal infections, haematuria and recurrent miscarriages possibly reflecting consequences of abnormal tubular modelling. Further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Published
2011
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47. Abstract 11343: Accelerated Aortic Stiffening Relative to Carotid Stiffness is Associated With Cognitive Decline: The Whitehall II Study

Author

Chiesa, Scott T, Masi, Stefano, Shipley, Martin J, Ellins, Elizabeth, Halcox, Julian P, Fraser, Alan, Hughes, Alun D, Patel, Riyaz S, Khir, Ashraf W, Brunner, Eric J, Singh-Manoux, Archana, Kivimaki, Mika, Celermajer, David, and Deanfield, John E

Abstract

Introduction:Excessive stiffening of the highly elastic aorta relative to the carotid artery may reduce impedance mismatch at their bifurcation and increase transmission of potentially-damaging pulsatile energy towards the fragile microcirculation of the brain.Hypothesis:Accelerated stiffening of the aorta relative to carotid artery stiffness will be associated with an increased rate of cognitive decline over long-term follow-up.Methods:Carotid stiffness, aortic stiffness, and cognitive function were available in 2248 individuals aged 58-74 years taking part in the Whitehall II Study. Carotid stiffness (pulse wave velocity [PWV] calculated using Bramwell-Hill equation) was assessed on a single occasion between 2002-2004 using duplex Doppler ultrasound, whereas rate of aortic stiffening (change in carotid-femoral PWV per year; ?PWV/year) was assessed on two occasions between 2007-2013 using applanation tonometry. Cognitive function - assessed using a global z-score incorporating multiple cognitive domains - was measured on up to four occasions between 2002-2016.Results:Mean (SD) 10-year change in standardized global cognitive score was -0.38(0.19). In multivariable models adjusting for a wide-range of potential confounders, accelerated aortic stiffening was associated with an increased rate of cognitive decline (change in 10 year cognitive score [95%CI] per 1SD increased ?PWV/year = -0.011 [-0.018,-0.003]; p=0.006). In contrast, individuals with a stiffer carotid artery at baseline showed some evidence of a slower rate of decline following adjustment for aortic stiffness (0.006 [-0.001,0.013]; p=0.114). As a result, individuals with higher rates of aortic stiffening demonstrated an increased risk of developing the most rapid cognitive decline (categorized as top 15% of cohort) during follow-up (Odds Ratio per 1SD increase = 1.12 [1.01,1.26]), whereas those with higher carotid stiffness had a reduced risk (Odds Ratio = 0.87 [0.77,0.99]).Conclusions:Accelerated aortic stiffening relative to carotid stiffness in mid- to late-life may be important in the pathogenesis and transmission of high intensity arterial waves towards the cerebral circulation, a potentially important risk factor for late-life cognitive decline.

Published
2019
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48. Abstract 14729: Does Addition of Non-Invasive Vascular Measures Improve Identification of Those With Elevated NT-ProBNP?

Author

Ellins, Elizabeth A, Papacosta, Olia, Lennon, Lucy T, Wannamethee, S G, Whincup, Peter H, and Halcox, Julian P

Subjects
*LEFT ventricular hypertrophy, *MULTIPLE regression analysis, *BLOOD pressure, *HEART failure, *HEART failure patients
Abstract

Background: Heart failure is a common condition that increases in prevalence with age. Better predictive models which remain suitable for routine general clinical care, may improve identification of those patients requiring further specialist input. Our aim was to investigate whether the addition of simple, non-invasive measures of vascular characteristics derived from peripheral pulse-waveforms improve prediction of heart failure in the clinic setting when added to routinely held clinical information. Methods: Men from the British Regional Heart Study 30 year visit (1,722) underwent 12 lead ECG, non-invasive vascular assessment (augmentation pressure [AP], augmentation index [AIx], central blood pressure [CBP] and pulse wave velocity [PWV]) and measurement of NT-proBNP. Associations between vascular measures, Minnesota coded ECG abnormality (ECGab: defined as ≥1 of: left branch bundle block, definite or probable myocardial infarction/ischemia/left ventricular hypertrophy) and NT-ProBNP as a continuous or categorical variable were evaluated using multiple regression analysis. Results: A total of 1,601 men (78.6 ± 4.7 years) were included in the analysis. AP was a significant predictor of NT-proBNP (β 0.019, 95% CI 0.004-0.035) but AIx, CBP and PWV were not. Presence of significant ECGab also predicted NT-proBNP levels (β 0.35, 95% CI 0.19-0.51). When ECGab and each vascular measure were included in the same model only ECGab and AP were significant predictors of NT-ProBNP levels (β 0.340, 95% CI 0.176-0.504 & β 0.018, 95% CI 0.002-0.033 respectively). When using a cut-off for elevated NT-ProBNP of (≥100pg/ml) ECGab, AP and AIx were all strongly associated with elevated NT-ProBNP (OR 1.52, 95% CI 1.13-2.05, OR 1.05 95% CI 1.02-1.08 & OR 1.03 95% CI 1.01-1.05 respectively). Conclusion: These results show that AP and AIx are predictors of NT-ProBNP in elderly men, indicating the importance of the augmentation of blood pressure on the loading of the heart. Simple non-invasive vascular measures have the potential to refine identification of those patients at risk of heart failure who could benefit from further specialist investigation. [ABSTRACT FROM AUTHOR]

Published
2018

50. Clinical investigation of subclinical vascular disease in psychosocial stress and dyslipidaemia

Author

Ellins, Elizabeth Anne and Ellins, Elizabeth Anne

Abstract

Cardiovascular disease is a major cause of death and ill health across the world. Psychosocial factors are increasingly being recognised as potential cardiovascular risk factors, contributing to the development and progression of atherosclerotic disease. However, the pathways between psychosocial factors and cardiovascular disease are not yet fully understood. The aims of this thesis were to explore the associations between psychosocial factors (both chronic and acute stress) and measures of subclinical vascular disease, and to further develop and validate, a new method of assessing vasomotor function. Women with both depression and anxiety were found to have increased carotid intima-media thickness and this relationship was found to be influenced by the presence of dyslipidaemia. When looking at the inflammatory responses to an acute mental stress challenge it was shown that those participants who had an elevated fibrinogen response 45 minutes after the stress challenge had poorer endothelial function 3 years later, as assessed by flow-mediated dilatation. These findings suggest that both chronic and acute stress may play a role in the development of cardiovascular disease. Good reproducibility was demonstrated with the new method for assessing vasomotor function following further development of the protocol for the method. The technique was able to detect differences in vasomotor function between a group of patients with Familial Hypercholesterolaemia compared with age and gender matched controls. In addition it was also able to detect improvement in vasomotor function following a single lipoprotein apheresis treatment in patients with Familial Hypercholesterolaemia undergoing long-term treatment. These studies demonstrated the potential of this method for use in non-specialist vascular research laboratories and out in the field for the assessment of vasomotor function.

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