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162. Influenza in old age

Author

STOTT, DAVID J., CARMAN, WILLIAM F., and ELDER, ALEXANDER G.

Published
2001

167. Diagnostic test accuracy of a novel smartphone application for the assessment of attention deficits in delirium in older hospitalised patients:a prospective cohort study protocol

Author

Rutter, Lisa-Marie, Nouzova, Eva, Stott, David J., Weir, Christopher J, Assi, Valentina, Barnett, Jennifer H, Clarke, Caoimhe, Duncan, Nikki, Evans, Jonathan, Green, Samantha, Hendry, Kirsty, McGinlay, Meigan, McKeever, Jenny, Middleton, Duncan G., Parks, Stuart, Shaw, Robert, Tang, Elaine, Walsh, Tim, Weir, Alexander J., Wilson, Elizabeth, Quasim, Tara, MacLullich, Alasdair M.J., Tieges, Zoë, Tieges, Zoë [0000-0002-3820-3917], and Apollo - University of Cambridge Repository

Subjects
Consecutive series, Male, Diagnostic accuracy study, lcsh:Geriatrics, Neuropsychological Tests, Cohort Studies, Cognition, Surveys and Questionnaires, mental disorders, Humans, Attention, Prospective Studies, Prospective study, Aged, Aged, 80 and over, Diagnostic Tests, Routine, Delirium, Neuropsychological test, Mobile Applications, Hospitalization, lcsh:RC952-954.6, Smartphone test, Case-Control Studies, Dementia, Female, Smartphone
Abstract

Background: \ud Delirium is a common and serious clinical syndrome which is often missed in routine clinical care. The core cognitive feature is inattention. We developed a novel bedside neuropsychological test for assessing inattention in delirium implemented on a smartphone platform (DelApp). We aim to evaluate the diagnostic performance of the DelApp in a representative cohort of older hospitalised patients.\ud \ud Methods: \ud This is a prospective study of older non-scheduled hospitalised patients (target n = 500, age ≥ 65), recruited from elderly care and acute orthopaedic wards. Exclusion criteria are: non-English speakers; severe vision or hearing impairment; photosensitive epilepsy.\ud \ud A structured reference standard delirium assessment based on DSM-5 criteria will be used, which includes a cognitive test battery administered by a trained assessor (Orientation-Memory-Concentration Test, Abbreviated Mental Test-10, Delirium Rating Severity Scale-Revised-98, digit span, months and days backwards, Vigilance A’ test) and assessment of arousal (Observational Scale of Level of Arousal, Richmond Agitation Sedation Scale). Prior change in cognition will be documented using the Informant Questionnaire on Cognitive Decline in the Elderly. Patients will be categorized as delirium (with/without dementia), possible delirium, dementia, no cognitive impairment, or undetermined.\ud \ud A separate assessor (blinded to diagnosis and assessments) will administer the DelApp index test within 3 h of the reference standard assessment. The DelApp comprises assessment of arousal (score 0-4) and sustained attention (score 0-6), yielding a total score between 0 and 10 (higher score = better performance). Outcomes (length of stay, mortality and discharge location) will be collected at 12 weeks.\ud \ud We will evaluate a priori cutpoints derived from a previous case-control study. Measures of the accuracy of DelApp will include sensitivity, specificity, positive and negative predictive values, and area under the ROC curve. We plan repeat assessments on up to 4 occasions in a purposive subsample of 30 patients (15 delirium, 15 no delirium) to examine changes over time.\ud \ud Discussion: \ud This study evaluates the diagnostic test accuracy of a novel smartphone test for delirium in a representative cohort of older hospitalised patients, including those with dementia. DelApp has the potential to be a convenient, objective method of improving delirium assessment for older people in acute care.\ud \ud Trial registration: \ud Clinical trials.gov, NCT02590796. Registered on 29 Oct 2015. Protocol version 5, dated 25 July 2016.

Published
2018

168. Genetic susceptibility loci for cardiovascular disease and their impact on atherosclerotic plaques

Author

van der Laan, Sander W., Siemelink, Marten A., Haitjema, Saskia, Foroughi Asl, Hassan, Perisic, Ljubica, Mokry, Michal, van Setten, Jessica, Malik, Rainer, Dichgans, Martin, Worrall, Bradford B, Samani, Nilesh J, Schunkert, Heribert, Erdmann, Jeanette, Hedin, Ulf, Paulsson-Berne, Gabrielle, Björkegrenn, Johan L.M, de Borst, Gert J., Asselbergs, Folkert W, den Ruijter, Folkert W, de Bakker, Paul I.W, Pasterkamp, Gerard, Ford, Ian, Sattar, Naveed, and Stott, David J.

Subjects
R1
Abstract

Background:\ud Atherosclerosis is a chronic inflammatory disease in part caused by lipid uptake in the vascular wall, but the exact underlying mechanisms leading to acute myocardial infarction and stroke remain poorly understood. Large consortia identified genetic susceptibility loci that associate with large artery ischemic stroke and coronary artery disease. However, deciphering their underlying mechanisms are challenging. Histological studies identified destabilizing characteristics in human atherosclerotic plaques that associate with clinical outcome. To what extent established susceptibility loci for large artery ischemic stroke and coronary artery disease relate to plaque characteristics is thus far unknown but may point to novel mechanisms.\ud \ud Methods:\ud We studied the associations of 61 established cardiovascular risk loci with 7 histological plaque characteristics assessed in 1443 carotid plaque specimens from the Athero-Express Biobank Study. We also assessed if the genotyped cardiovascular risk loci impact the tissue-specific gene expression in 2 independent biobanks, Biobank of Karolinska Endarterectomy and Stockholm Atherosclerosis Gene Expression.\ud \ud Results:\ud A total of 21 established risk variants (out of 61) nominally associated to a plaque characteristic. One variant (rs12539895, risk allele A) at 7q22 associated to a reduction of intraplaque fat, P=5.09×10−6 after correction for multiple testing. We further characterized this 7q22 Locus and show tissue-specific effects of rs12539895 on HBP1 expression in plaques and COG5 expression in whole blood and provide data from public resources showing an association with decreased LDL (low-density lipoprotein) and increase HDL (high-density lipoprotein) in the blood.\ud \ud Conclusions:\ud Our study supports the view that cardiovascular susceptibility loci may exert their effect by influencing the atherosclerotic plaque characteristics.

Published
2018

169. Association of alcohol consumption with allergic disease and asthma: a multi-centre Mendelian randomization analysis

Author

Skaaby, Tea, Kilpeläinen, Tuomas O, Taylor, Amy E, Mahendran, Yuvaraj, Wong, Andrew, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Trompet, Stella, Stott, David J, Flexeder, Claudia, Zhou, Ang, Brusselle, Guy, Sajjad, Ayesha, Lahousse, Lies, Tiemeier, Henning, Have, Christian Theil, Thuesen, Betina H, Kårhus, Line Lund, Møllehave, Line Tang, Leth-Møller, Katja Biering, Shabanzadeh, Daniel Mønsted, Gonzalez-Quintela, Arturo, Power, Chris, Hyppönen, Elina, Kuh, Diana, Hardy, Rebecca, Meitinger, Thomas, Jukema, J Wouter, Völker, Uwe, Nauck, Matthias, Völzke, Henry, Friedrich, Nele, Bonten, Tobias N, Noordam, Raymond, Mook-Kanamori, Dennis O, Tolstrup, Janne S, Taube, Christian, Peters, Annette, Grallert, Harald, Strauch, Konstantin, Schulz, Holger, Grarup, Niels, Hansen, Torben, Pedersen, Oluf, Burgess, Stephen, Munafò, Marcus R, Linneberg, Allan, Skaaby, Tea [0000-0003-0031-5726], Taylor, Amy E [0000-0003-1853-0563], Tolstrup, Janne S [0000-0002-9796-3967], Munafò, Marcus R [0000-0002-4049-993X], Apollo - University of Cambridge Repository, Epidemiology, Health Technology Assessment (HTA), and Child and Adolescent Psychiatry / Psychology

Subjects
Male, Adolescent, Alcohol Drinking, Genotype, Denmark, Medizin, allergic sensitization, Brain and Behaviour, Article, Young Adult, hay fever, Hypersensitivity, Humans, Alcohol, Allergic Disease, Allergic Sensitization, Asthma, Hay Fever, Mendelian Randomization, Aged, 80 and over, Tobacco and Alcohol, Alcohol Dehydrogenase, Rhinitis, Allergic, Seasonal, asthma, Immunoglobulin E, Mendelian Randomization Analysis, Respiratory Function Tests, allergic disease, mendelian randomization, Physical and Mental Health, Female
Abstract

AIMS: To use the rs1229984 variant associated with alcohol consumption as an instrument for alcohol consumption to test the causality of the association of alcohol consumption with hay fever, asthma, allergic sensitization and serum total immunoglobulin (Ig)E.DESIGN: Observational and Mendelian randomization analyses using genetic variants as unbiased markers of exposure to estimate causal effects, subject to certain assumptions.SETTING: Europe.PARTICIPANTS: We included a total of 466 434 people aged 15-82 years from 17 population-based studies conducted from 1997 to 2015.MEASUREMENTS: The rs1229984 (ADH1B) was genotyped; alcohol consumption, hay fever and asthma were self-reported. Specific and total IgE were measured from serum samples.FINDINGS: Observational analyses showed that ever-drinking versus non-drinking, but not amount of alcohol intake, was positively associated with hay fever and inversely associated with asthma but not with allergic sensitization or serum total immunoglobulin (Ig)E. However, Mendelian randomization analyses did not suggest that the observational associations are causal. The causal odds ratio (OR) per genetically assessed unit of alcohol/week was an OR = 0.907 [95% confidence interval (CI) = 0.806, 1.019; P = 0.101] for hay fever, an OR = 0.897 (95% CI = 0.790, 1.019; P = 0.095) for asthma, an OR = 0.971 (95% CI = 0.804, 1.174; P = 0.763) for allergic sensitization and a 4.7% change (95% CI = -5.5%, 14.9%; P = 0.366) for total IgE.CONCLUSIONS: In observational analyses, ever-drinking versus not drinking was positively associated with hay fever and negatively associated with asthma. However, the Mendelian randomization results were not consistent with these associations being causal.

Published
2018

170. The association between blood pressure variability (BPV) with dementia and cognitive function: A systematic review and meta-analysis protocol 11 Medical and Health Sciences 1117 Public Health and Health Services

Author

Tully, Phillip J., Turnbull, Deborah A., Anstey, Kaarin J., Beckett, Nigel, Beiser, Alexa S., Birns, Jonathan, Brickman, Adam M., Burns, Nicholas R., Cosh, Suzanne, de Leeuw, Peter W., Dorstyn, Diana, Elias, Merrill F., Wouter Jukema, J., Kario, Kazuomi, Kikuya, Masahiro, Kroon, Abraham A., Launer, Lenore J., Mahajan, Rajiv, McGrath, Emer R., Mooijaart, Simon P., Moll van Charante, Eric P., Nagai, Michiaki, Ninomiya, Toshiharu, Ohara, Tomoyuki, Ohkubo, Takayoshi, Oishi, Emi, Peters, Ruth, Richard, Edo, Satoh, Michihiro, Seshadri, Sudha, Stott, David J., van Gool, Willem A., van Middelaar, Tessa, Trompet, Stella, Giles, Kristy, Drioli-Phillips, Phoebe, Aaimir, Umama, Connolly, Frank, Tzourio, Christophe, General practice, ACS - Diabetes & metabolism, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, and APH - Aging & Later Life

Abstract

Background: A body of empirical work demonstrates that wide fluctuations in a person's blood pressure across consecutive measures, known as blood pressure variability (BPV), hold prognostic value to predict stroke and transient ischemic attack. However, the magnitude of association between BPV and other neurological outcomes remains less clear. This systematic review aims to pool together data regarding BPV with respect to incident dementia, cognitive impairment, and cognitive function. Methods: Electronic databases (MEDLINE, EMBASE, and SCOPUS) will be searched for the key words blood pressure variability and outcomes of dementia, cognitive impairment, and cognitive function. Authors and reference lists of included studies will also be contacted to identify additional published and unpublished studies. Eligibility criteria are as follows: population - adult humans (over 18 years but with no upper age limit) without dementia at baseline, with or without elevated blood pressure, or from hypertensive populations (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or use of antihypertensive drug for hypertension) and from primary care, community cohort, electronic database registry, or randomized controlled trial (RCT); exposure - any metric of BPV (systolic, diastolic or both) over any duration; comparison - persons without dementia who do not have elevated BPV; and outcome - dementia, cognitive impairment, cognitive function at follow-up from standardized neurological assessment, or cognitive testing. Article screening will be undertaken by two independent reviewers with disagreements resolved through discussion. Data extraction will include original data specified as hazard ratios, odds ratios, correlations, regression coefficients, and original cell data if available. Risk of bias assessment will be undertaken by two independent reviewers. Meta-analytic methods will be used to synthesize the data collected relating to the neurological outcomes with Comprehensive Meta-Analysis Version 2.0 (Biostat Inc., Engelwood, NJ). Discussion: This systematic review aims to clarify whether BPV is associated with elevated risk for dementia, cognitive impairment, and cognitive function. An evaluation of the etiological links between BPV with incident dementia might inform evidence-based clinical practice and policy concerning blood pressure measurement and hypertension management. The review will identify sources of heterogeneity and may inform decisions on whether it is feasible and desirable to proceed with an individual participant data meta-analysis.

Published
2018

171. A pragmatic, multi-centered, stepped wedge, cluster randomized controlled trial pilot of the clinical and cost effectiveness of a complex Stroke Oral healthCare intervention pLan Evaluation II (SOCLE II) compared with usual oral healthcare in stroke wards

Author

Brady, Marian C, primary, Stott, David J, additional, Weir, Christopher J, additional, Chalmers, Campbell, additional, Sweeney, Petrina, additional, Barr, John, additional, Pollock, Alex, additional, Bowers, Naomi, additional, Gray, Heather, additional, Bain, Brenda Jean, additional, Collins, Marissa, additional, Keerie, Catriona, additional, and Langhorne, Peter, additional

Published
2019
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172. Equity and specific populations

Author

Welch, Vivian A, primary, Petkovic, Jennifer, additional, Jull, Janet, additional, Hartling, Lisa, additional, Klassen, Terry, additional, Kristjansson, Elizabeth, additional, Pardo, Jordi Pardo, additional, Petticrew, Mark, additional, Stott, David J, additional, Thomson, Denise, additional, Ueffing, Erin, additional, Williams, Katrina, additional, Young, Camilla, additional, and Tugwell, Peter, additional

Published
2019
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173. Common genetic variation indicates separate etiologies for periventricular and deep white matter hyperintensities

Author

Armstrong, Nicola J, primary, Mather, Karen A, additional, Sargurupremraj, Muralidharan, additional, Knol, Maria J, additional, Malik, Rainer, additional, Satizabal, Claudia L, additional, Yanek, Lisa R, additional, Wei, Wen, additional, Gudnason, Vilmundur, additional, Deuker, Nicole D, additional, Elliott, Lloyd T, additional, Hofer, Edith, additional, Jahanshad, Neda, additional, Li, Shuo, additional, Logue, Mark A, additional, Luciano, Michelle, additional, Scholz, Markus, additional, Smith, Albert, additional, Trompet, Stella S, additional, Vojinovic, Dina, additional, Xia, Rui, additional, Alfaro-Almagro, Fidel, additional, Ames, David, additional, Amin, Najaf, additional, Amouyel, Philippe, additional, Beiser, Alexa S, additional, Brodaty, Henry, additional, Deary, Ian J, additional, Fennema-Notestine, Christine, additional, Gampwar, Piyush G, additional, Gottesman, Rebecca, additional, Griffanti, Ludovica, additional, Jack, Clifford R, additional, Jenkinson, Mark, additional, Jain, Jiyang, additional, Kral, Brian G, additional, Kwok, John W, additional, Lampe, Leonie, additional, Liewald, David CM, additional, Maillard, Pauline, additional, Marchini, Jonathan, additional, Bastin, Mark E, additional, Mazoyer, Bernard, additional, Pirpamer, Lukas, additional, Romero, José Rafael, additional, Roshchupkin, Gennady V, additional, Schofield, Peter R, additional, Schroeter, Matthias L, additional, Stott, David J, additional, Thalamuth, Anbupalam, additional, Trollor, Julian, additional, Tzourio, Christophe, additional, van der Grond, Jeroen, additional, Vernooij, Meike W, additional, Witte, Veronica A, additional, Wright, Maragret J, additional, Yang, Qiong, additional, Zoe, Moris, additional, Siggurdsson, Siggi, additional, Villringer, Arno, additional, Schmidt, Helena, additional, Haberg, Asta L, additional, Van Duijn, Cornelia M, additional, Jukema, J Wouter, additional, Dichigans, Martin, additional, Sacco, Ralph L, additional, Wright, Clinton B, additional, Kremen, William S, additional, Becker, Lewis C, additional, Thompson, Paul M, additional, Launer, Lenore, additional, Mosley, Thomas H, additional, Wardlaw, Joanna M, additional, Ikram, M Afran, additional, Adams, Hieab HH, additional, Schmidt, Reinhold, additional, Smith, Stephen M, additional, Decarli, Charles, additional, Sachdev, Perminder S, additional, Fornage, Myriam, additional, Debbette, Stephanie, additional, Seshadri, Sudha, additional, and Nyquist, Paul A, additional

Published
2019
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177. Assessment of the Relationship Between Genetic Determinants of Thyroid Function and Atrial Fibrillation

Author

Ellervik, Christina, primary, Roselli, Carolina, additional, Christophersen, Ingrid E., additional, Alonso, Alvaro, additional, Pietzner, Maik, additional, Sitlani, Collen M., additional, Trompet, Stella, additional, Arking, Dan E., additional, Geelhoed, Bastiaan, additional, Guo, Xiuqing, additional, Kleber, Marcus E., additional, Lin, Henry J., additional, Lin, Honghuang, additional, MacFarlane, Peter, additional, Selvin, Elizabeth, additional, Shaffer, Christian, additional, Smith, Albert V., additional, Verweij, Niek, additional, Weiss, Stefan, additional, Cappola, Anne R., additional, Dörr, Marcus, additional, Gudnason, Vilmundur, additional, Heckbert, Susan, additional, Mooijaart, Simon, additional, März, Winfried, additional, Psaty, Bruce M., additional, Ridker, Paul M., additional, Roden, Dan, additional, Stott, David J., additional, Völzke, Henry, additional, Benjamin, Emelia J., additional, Delgado, Graciela, additional, Ellinor, Patrick, additional, Homuth, Georg, additional, Köttgen, Anna, additional, Jukema, Johan W., additional, Lubitz, Steven A., additional, Mora, Samia, additional, Rienstra, Michiel, additional, Rotter, Jerome I., additional, Shoemaker, M. Benjamin, additional, Sotoodehnia, Nona, additional, Taylor, Kent D., additional, van der Harst, Pim, additional, Albert, Christine M., additional, and Chasman, Daniel I., additional

Published
2019
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180. Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection

Author

Adlam, David, primary, Olson, Timothy M., additional, Combaret, Nicolas, additional, Kovacic, Jason C., additional, Iismaa, Siiri E., additional, Al-Hussaini, Abtehale, additional, O'Byrne, Megan M., additional, Bouajila, Sara, additional, Georges, Adrien, additional, Mishra, Ketan, additional, Braund, Peter S., additional, d’Escamard, Valentina, additional, Huang, Siying, additional, Margaritis, Marios, additional, Nelson, Christopher P., additional, de Andrade, Mariza, additional, Kadian-Dodov, Daniella, additional, Welch, Catherine A., additional, Mazurkiewicz, Stephani, additional, Jeunemaitre, Xavier, additional, Wong, Claire Mei Yi, additional, Giannoulatou, Eleni, additional, Sweeting, Michael, additional, Muller, David, additional, Wood, Alice, additional, McGrath-Cadell, Lucy, additional, Fatkin, Diane, additional, Dunwoodie, Sally L., additional, Harvey, Richard, additional, Holloway, Cameron, additional, Empana, Jean-Philippe, additional, Jouven, Xavier, additional, Olin, Jeffrey W., additional, Gulati, Rajiv, additional, Tweet, Marysia S., additional, Hayes, Sharonne N., additional, Samani, Nilesh J., additional, Graham, Robert M., additional, Motreff, Pascal, additional, Bouatia-Naji, Nabila, additional, Belle, Loïc, additional, Dupouy, Patrick, additional, Barnay, Pierre, additional, Meneveau, Nicolas, additional, Gilard, Martine, additional, Rioufol, Gilles, additional, Range, Grégoire, additional, Brunel, Philippe, additional, Delarche, Nicolas, additional, Filippi, Emmanuelle, additional, Le Bivic, Louis, additional, Harbaoui, Brahim, additional, Benamer, Hakim, additional, Cayla, Guillaume, additional, Varenne, Olivier, additional, Manzo-Silberman, Stephane Peggy, additional, Silvain, Johanne, additional, Spaulding, Christian, additional, Caussin, Christophe, additional, Gerbaud, Edouard, additional, Valy, Yann, additional, Koning, René, additional, Lhermusier, Thibault, additional, Champin, Stanislas, additional, Salengro, Emmanuel, additional, Fluttaz, Arnaud, additional, Zabalawi, Amer, additional, Cottin, Yves, additional, Teiger, Emmanuel, additional, Saint-Etienne, Christophe, additional, Ducrocq, Grégory, additional, Marliere, Stéphanie, additional, Boiffard, Emmanuel, additional, Aubry, Pierre, additional, Georges, Jean Louis, additional, Bresson, Didier, additional, De Poli, Fabien, additional, Karrillon, Gaëtan, additional, Roule, Vincent, additional, Bali, Laurent, additional, Valla, Mathieu, additional, Gerbay, Antoine, additional, Houpe, David, additional, Dubreuil, Olivier, additional, Monnier, Arsène, additional, Mayaud, Norbert, additional, Manchuelle, Aurélie, additional, Commeau, Philippe, additional, Bedossa, Marc, additional, Nikpay, Majid, additional, Goel, Anuj, additional, Won, Hong-Hee, additional, Hall, Leanne M., additional, Willenborg, Christina, additional, Kanoni, Stavroula, additional, Saleheen, Danish, additional, Kyriakou, Theodosios, additional, Hopewell, Jemma C., additional, Webb, Thomas R., additional, Zeng, Lingyao, additional, Dehghan, Abbas, additional, Alver, Maris, additional, Armasu, Sebastian M., additional, Auro, Kirsi, additional, Bjonnes, Andrew, additional, Chasman, Daniel I., additional, Chen, Shufeng, additional, Ford, Ian, additional, Franceschini, Nora, additional, Gieger, Christian, additional, Grace, Christopher, additional, Gustafsson, Stefan, additional, Huang, Jie, additional, Hwang, Shih-Jen, additional, Kim, Yun Kyoung, additional, Kleber, Marcus E., additional, Lau, King Wai, additional, Lu, Xiangfeng, additional, Lu, Yingchang, additional, Lyytikäinen, Leo P., additional, Mihailov, Evelin, additional, Morrison, Alanna, additional, Pervjakova, Natalia, additional, Qu, Liming, additional, Rose, Lynda M., additional, Salfati, Elias, additional, Saxena, Richa, additional, Scholz, Markus, additional, Smith, Albert V., additional, Tikkanen, Emmi, additional, Uitterlinden, Andre, additional, Yang, Xueli, additional, Zhang, Weihua, additional, Zhao, Wei, additional, de Vries, Paul S., additional, van Zuydam, Natalie R., additional, Anand, Sonia S., additional, Bertram, Lars, additional, Beutner, Frank, additional, Dedoussis, George, additional, Frossard, Philippe, additional, Gauguier, Dominique, additional, Goodall, Alison H., additional, Gottesman, Omri, additional, Haber, Marc, additional, Han, Bok-Ghee, additional, Huang, Jianfeng, additional, Jalilzadeh, Shapour, additional, Kessler, Thorsten, additional, König, Inke R., additional, Lannfelt, Lars, additional, Lieb, Wolfgang, additional, Lind, Lars, additional, Lindgren, Cecilia M., additional, Lokki, Maisa, additional, Magnusson, Patrik K., additional, Mallick, Nadeem H., additional, Mehra, Narinder, additional, Meitinger, Thomas, additional, Memon, Fazal-ur-Rehman, additional, Morris, Andrew P., additional, Nieminen, Markku S., additional, Pedersen, Nancy L., additional, Peters, Annette, additional, Rallidis, Loukianos S., additional, Rasheed, Asif, additional, Samuel, Maria, additional, Shah, Svati H., additional, Sinisalo, Juha, additional, Stirrups, Kathleen E., additional, Trompet, Stella, additional, Wang, Laiyuan, additional, Zaman, Khan S., additional, Ardissino, Diego, additional, Boerwinkle, Eric, additional, Borecki, Ingrid B., additional, Bottinger, Erwin P., additional, Buring, Julie E., additional, Chambers, John C., additional, Collins, Rory, additional, Cupples, L Adrienne, additional, Danesh, John, additional, Demuth, Ilja, additional, Elosua, Roberto, additional, Epstein, Stephen E., additional, Esko, Tõnu, additional, Feitosa, Mary F., additional, Franco, Oscar H., additional, Franzosi, Maria Grazia, additional, Granger, Christopher B., additional, Gu, Dongfeng, additional, Gudnason, Vilmundur, additional, Hall, Alistair S., additional, Hamsten, Anders, additional, Harris, Tamara B., additional, Hazen, Stanley L., additional, Hengstenberg, Christian, additional, Hofman, Albert, additional, Ingelsson, Erik, additional, Iribarren, Carlos, additional, Jukema, J Wouter, additional, Karhunen, Pekka J., additional, Kim, Bong-Jo, additional, Kooner, Jaspal S., additional, Kullo, Iftikhar J., additional, Lehtimäki, Terho, additional, Loos, Ruth J., additional, Melander, Olle, additional, Metspalu, Andres, additional, März, Winfried, additional, Palmer, Colin N., additional, Perola, Markus, additional, Quertermous, Thomas, additional, Rader, Daniel J., additional, Ridker, Paul M., additional, Ripatti, Samuli, additional, Roberts, Robert, additional, Salomaa, Veikko, additional, Sanghera, Dharambir K., additional, Schwartz, Stephen M., additional, Seedorf, Udo, additional, Stewart, Alexandre F., additional, Stott, David J., additional, Thiery, Joachim, additional, Zalloua, Pierre A., additional, O'Donnell, Christopher J., additional, Reilly, Muredach P., additional, Assimes, Themistocles L., additional, Thompson, John R., additional, Erdmann, Jeanette, additional, Clarke, Robert, additional, Watkins, Hugh, additional, Kathiresan, Sekar, additional, McPherson, Ruth, additional, Deloukas, Panos, additional, Schunkert, Heribert, additional, and Farrall, Martin, additional

Published
2019
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181. Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

Author

Stott David J, Caslake Muriel, Sattar Naveed, Ford Ian, Postmus Iris, de Craen Anton JM, Trompet Stella, Buckley Brendan M, Sacks Frank, Devlin James J, Slagboom P, Westendorp Rudi GJ, and Jukema J

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly. Methods The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification. Results Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results. Conclusion With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.

Published
2011
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182. Developing and evaluating the implementation of a complex intervention: using mixed methods to inform the design of a randomised controlled trial of an oral healthcare intervention after stroke

Author

St George Bridget, Chalmers Campbell, Norrie John, Stott David J, Brady Marian C, Sweeney Petrina M, and Langhorne Peter

Subjects
Medicine (General), R5-920
Abstract

Abstract Background Many interventions delivered within the stroke rehabilitation setting could be considered complex, though some are more complex than others. The degree of complexity might be based on the number of and interactions between levels, components and actions targeted within the intervention. The number of (and variation within) participant groups and the contexts in which it is delivered might also reflect the extent of complexity. Similarly, designing the evaluation of a complex intervention can be challenging. Considerations include the necessity for intervention standardisation, the multiplicity of outcome measures employed to capture the impact of a multifaceted intervention and the delivery of the intervention across different clinical settings operating within varying healthcare contexts. Our aim was to develop and evaluate the implementation of a complex, multidimensional oral health care (OHC) intervention for people in stroke rehabilitation settings which would inform the development of a randomised controlled trial. Methods After reviewing the evidence for the provision of OHC following stroke, multi-disciplinary experts informed the development of our intervention. Using both quantitative and qualitative methods we evaluated the implementation of the complex OHC intervention across patients, staff and service levels of care. We also adopted a pragmatic approach to patient recruitment, the completion of assessment tools and delivery of OHC, alongside an attention to the context in which it was delivered. Results We demonstrated the feasibility of implementing a complex OHC intervention across three levels of care. The complementary nature of the mixed methods approach to data gathering provided a complete picture of the implementation of the intervention and a detailed understanding of the variations within and interactions between the components of the intervention. Information on the feasibility of the outcome measures used to capture impact across a range of components was also collected, though some process orientated uncertainties including eligibility and recruitment rates remain to be further explored within a Phase II exploratory trial. Conclusions Complex interventions can be captured and described in a manner which facilitates evaluation in the form of exploratory and subsequently definitive clinical trials. If effective, the evidence captured relating to the intervention context will facilitate translation into clinical practice.

Published
2011
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183. Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

Author

Ford Ian, Sattar Naveed, de Craen Anton JM, Jukema J Wouter, Slagboom P Eline, Frölich Marijke, Tobias Edward S, Rumley Ann, Brown E Ann, Robertson Michele, Freeman Dilys J, Gaw Allan, Greer Ian A, Lowe Gordon DO, and Stott David J

Subjects
Geriatrics, RC952-954.6
Abstract

Abstract Background Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables. Methods This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available. Results There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE. Conclusions Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk. Trial Registration Not applicable when study undertaken.

Published
2011
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184. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

Author

Ligthart, Symen, primary, Vaez, Ahmad, additional, Võsa, Urmo, additional, Stathopoulou, Maria G., additional, de Vries, Paul S., additional, Prins, Bram P., additional, Van der Most, Peter J., additional, Tanaka, Toshiko, additional, Naderi, Elnaz, additional, Rose, Lynda M., additional, Wu, Ying, additional, Karlsson, Robert, additional, Barbalic, Maja, additional, Lin, Honghuang, additional, Pool, René, additional, Zhu, Gu, additional, Macé, Aurélien, additional, Sidore, Carlo, additional, Trompet, Stella, additional, Mangino, Massimo, additional, Sabater-Lleal, Maria, additional, Kemp, John P., additional, Abbasi, Ali, additional, Kacprowski, Tim, additional, Verweij, Niek, additional, Smith, Albert V., additional, Huang, Tao, additional, Marzi, Carola, additional, Feitosa, Mary F., additional, Lohman, Kurt K., additional, Kleber, Marcus E., additional, Milaneschi, Yuri, additional, Mueller, Christian, additional, Huq, Mahmudul, additional, Vlachopoulou, Efthymia, additional, Lyytikäinen, Leo-Pekka, additional, Oldmeadow, Christopher, additional, Deelen, Joris, additional, Perola, Markus, additional, Zhao, Jing Hua, additional, Feenstra, Bjarke, additional, Amini, Marzyeh, additional, Lahti, Jari, additional, Schraut, Katharina E., additional, Fornage, Myriam, additional, Suktitipat, Bhoom, additional, Chen, Wei-Min, additional, Li, Xiaohui, additional, Nutile, Teresa, additional, Malerba, Giovanni, additional, Luan, Jian’an, additional, Bak, Tom, additional, Schork, Nicholas, additional, Del Greco M., Fabiola, additional, Thiering, Elisabeth, additional, Mahajan, Anubha, additional, Marioni, Riccardo E., additional, Mihailov, Evelin, additional, Eriksson, Joel, additional, Ozel, Ayse Bilge, additional, Zhang, Weihua, additional, Nethander, Maria, additional, Cheng, Yu-Ching, additional, Aslibekyan, Stella, additional, Ang, Wei, additional, Gandin, Ilaria, additional, Yengo, Loïc, additional, Portas, Laura, additional, Kooperberg, Charles, additional, Hofer, Edith, additional, Rajan, Kumar B., additional, Schurmann, Claudia, additional, den Hollander, Wouter, additional, Ahluwalia, Tarunveer S., additional, Zhao, Jing, additional, Draisma, Harmen H.M., additional, Ford, Ian, additional, Timpson, Nicholas, additional, Teumer, Alexander, additional, Huang, Hongyan, additional, Wahl, Simone, additional, Liu, YongMei, additional, Huang, Jie, additional, Uh, Hae-Won, additional, Geller, Frank, additional, Joshi, Peter K., additional, Yanek, Lisa R., additional, Trabetti, Elisabetta, additional, Lehne, Benjamin, additional, Vozzi, Diego, additional, Verbanck, Marie, additional, Biino, Ginevra, additional, Saba, Yasaman, additional, Meulenbelt, Ingrid, additional, O’Connell, Jeff R., additional, Laakso, Markku, additional, Giulianini, Franco, additional, Magnusson, Patrik K.E., additional, Ballantyne, Christie M., additional, Hottenga, Jouke Jan, additional, Montgomery, Grant W., additional, Rivadineira, Fernando, additional, Rueedi, Rico, additional, Steri, Maristella, additional, Herzig, Karl-Heinz, additional, Stott, David J., additional, Menni, Cristina, additional, Frånberg, Mattias, additional, St. Pourcain, Beate, additional, Felix, Stephan B., additional, Pers, Tune H., additional, Bakker, Stephan J.L., additional, Kraft, Peter, additional, Peters, Annette, additional, Vaidya, Dhananjay, additional, Delgado, Graciela, additional, Smit, Johannes H., additional, Großmann, Vera, additional, Sinisalo, Juha, additional, Seppälä, Ilkka, additional, Williams, Stephen R., additional, Holliday, Elizabeth G., additional, Moed, Matthijs, additional, Langenberg, Claudia, additional, Räikkönen, Katri, additional, Ding, Jingzhong, additional, Campbell, Harry, additional, Sale, Michele M., additional, Chen, Yii-Der I., additional, James, Alan L., additional, Ruggiero, Daniela, additional, Soranzo, Nicole, additional, Hartman, Catharina A., additional, Smith, Erin N., additional, Berenson, Gerald S., additional, Fuchsberger, Christian, additional, Hernandez, Dena, additional, Tiesler, Carla M.T., additional, Giedraitis, Vilmantas, additional, Liewald, David, additional, Fischer, Krista, additional, Mellström, Dan, additional, Larsson, Anders, additional, Wang, Yunmei, additional, Scott, William R., additional, Lorentzon, Matthias, additional, Beilby, John, additional, Ryan, Kathleen A., additional, Pennell, Craig E., additional, Vuckovic, Dragana, additional, Balkau, Beverly, additional, Concas, Maria Pina, additional, Schmidt, Reinhold, additional, Mendes de Leon, Carlos F., additional, Bottinger, Erwin P., additional, Kloppenburg, Margreet, additional, Paternoster, Lavinia, additional, Boehnke, Michael, additional, Musk, A.W., additional, Willemsen, Gonneke, additional, Evans, David M., additional, Madden, Pamela A.F., additional, Kähönen, Mika, additional, Kutalik, Zoltán, additional, Zoledziewska, Magdalena, additional, Karhunen, Ville, additional, Kritchevsky, Stephen B., additional, Sattar, Naveed, additional, Lachance, Genevieve, additional, Clarke, Robert, additional, Harris, Tamara B., additional, Raitakari, Olli T., additional, Attia, John R., additional, van Heemst, Diana, additional, Kajantie, Eero, additional, Sorice, Rossella, additional, Gambaro, Giovanni, additional, Scott, Robert A., additional, Hicks, Andrew A., additional, Ferrucci, Luigi, additional, Standl, Marie, additional, Lindgren, Cecilia M., additional, Starr, John M., additional, Karlsson, Magnus, additional, Lind, Lars, additional, Li, Jun Z., additional, Chambers, John C., additional, Mori, Trevor A., additional, de Geus, Eco J.C.N., additional, Heath, Andrew C., additional, Martin, Nicholas G., additional, Auvinen, Juha, additional, Buckley, Brendan M., additional, de Craen, Anton J.M., additional, Waldenberger, Melanie, additional, Strauch, Konstantin, additional, Meitinger, Thomas, additional, Scott, Rodney J., additional, McEvoy, Mark, additional, Beekman, Marian, additional, Bombieri, Cristina, additional, Ridker, Paul M., additional, Mohlke, Karen L., additional, Pedersen, Nancy L., additional, Morrison, Alanna C., additional, Boomsma, Dorret I., additional, Whitfield, John B., additional, Strachan, David P., additional, Hofman, Albert, additional, Vollenweider, Peter, additional, Cucca, Francesco, additional, Jarvelin, Marjo-Riitta, additional, Jukema, J. Wouter, additional, Spector, Tim D., additional, Hamsten, Anders, additional, Zeller, Tanja, additional, Uitterlinden, André G., additional, Nauck, Matthias, additional, Gudnason, Vilmundur, additional, Qi, Lu, additional, Grallert, Harald, additional, Borecki, Ingrid B., additional, Rotter, Jerome I., additional, März, Winfried, additional, Wild, Philipp S., additional, Lokki, Marja-Liisa, additional, Boyle, Michael, additional, Salomaa, Veikko, additional, Melbye, Mads, additional, Eriksson, Johan G., additional, Wilson, James F., additional, Penninx, Brenda W.J.H., additional, Becker, Diane M., additional, Worrall, Bradford B., additional, Gibson, Greg, additional, Krauss, Ronald M., additional, Ciullo, Marina, additional, Zaza, Gianluigi, additional, Wareham, Nicholas J., additional, Oldehinkel, Albertine J., additional, Palmer, Lyle J., additional, Murray, Sarah S., additional, Pramstaller, Peter P., additional, Bandinelli, Stefania, additional, Heinrich, Joachim, additional, Ingelsson, Erik, additional, Deary, Ian J., additional, Mägi, Reedik, additional, Vandenput, Liesbeth, additional, van der Harst, Pim, additional, Desch, Karl C., additional, Kooner, Jaspal S., additional, Ohlsson, Claes, additional, Hayward, Caroline, additional, Lehtimäki, Terho, additional, Shuldiner, Alan R., additional, Arnett, Donna K., additional, Beilin, Lawrence J., additional, Robino, Antonietta, additional, Froguel, Philippe, additional, Pirastu, Mario, additional, Jess, Tine, additional, Koenig, Wolfgang, additional, Loos, Ruth J.F., additional, Evans, Denis A., additional, Schmidt, Helena, additional, Smith, George Davey, additional, Slagboom, P. Eline, additional, Eiriksdottir, Gudny, additional, Morris, Andrew P., additional, Psaty, Bruce M., additional, Tracy, Russell P., additional, Nolte, Ilja M., additional, Boerwinkle, Eric, additional, Visvikis-Siest, Sophie, additional, Reiner, Alex P., additional, Gross, Myron, additional, Bis, Joshua C., additional, Franke, Lude, additional, Franco, Oscar H., additional, Benjamin, Emelia J., additional, Chasman, Daniel I., additional, Dupuis, Josée, additional, Snieder, Harold, additional, Dehghan, Abbas, additional, Alizadeh, Behrooz Z., additional, Boezen, H. Marike, additional, Navis, Gerjan, additional, Rots, Marianne, additional, Swertz, Morris, additional, Wolffenbuttel, Bruce H.R., additional, Wijmenga, Cisca, additional, Benjamin, Emelia, additional, Ahluwalia, Tarunveer Singh, additional, Meigs, James, additional, Tracy, Russell, additional, Ligthart, Symen, additional, Bis, Josh, additional, Pankratz, Nathan, additional, Rainer, Alex, additional, Wilson, James G., additional, Dupuis, Josee, additional, Prins, Bram, additional, Vaso, Urmo, additional, Stathopoulou, Maria, additional, Lehtimaki, Terho, additional, Jamshidi, Yalda, additional, Siest, Sophie, additional, Uitterlinden, Andre G., additional, Abdollahi, Mohammadreza, additional, Schnabel, Renate, additional, Schick, Ursula M., additional, Kraja, Aldi, additional, Hsu, Yi-Hsiang, additional, Tylee, Daniel S., additional, Zwicker, Alyson, additional, Uher, Rudolf, additional, Davey-Smith, George, additional, Hicks, Andrew, additional, van Duijn, Cornelia M., additional, Ward-Caviness, Cavin, additional, Rotter, J., additional, Rice, Ken, additional, Lange, Leslie, additional, de Geus, Eco, additional, Makela, Kari Matti, additional, Stacey, David, additional, Eriksson, Johan, additional, Frayling, Tim M., additional, and Slagboom, Eline P., additional

Published
2018
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186. Association of circulating metabolites in plasma or serum and risk of stroke: Meta-analysis from seven prospective cohorts.

Author

Vojinovic, Dina, Kalaoja, Marita, Trompet, Stella, Fischer, Krista, Shipley, Martin J., Shuo Li, Havulinna, Aki S., Perola, Markus, Salomaa, Veikko, Qiong Yang, Sattar, Naveed, Jousilahti, Pekka, Amin, Najaf, Satizabal, Claudia L., Taba, Nele, Sabayan, Behnam, Vasan, Ramachandran S., Ikram, M. Arfan, Stott, David J., and Ala-Korpela, Mika

Published
2021
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187. High-sensitivity cardiac troponin concentration and risk of first-ever cardiovascular outcomes: literature-based meta-analysis involving 154,052 participants

Author

Willeit, Peter, Welsh, Paul, Evans, Jonathan D.W., Tschiderer, Lena, Boachie, Charles, Jukema, J. Wouter, Ford, Ian, Trompet, Stella, Stott, David J., Kearney, Patricia M., Mooijaart, Simon P., Kiechl, Stefan, Di Angelantonio, Emanuele, and Sattar, Naveed

Subjects
cardiovascular diseases
Abstract

Background: \ud \ud High-sensitivity assays can quantify cardiac troponins I and T (hs-cTnI, hs-cTnT) in individuals with no clinically manifest myocardial injury.\ud \ud Objectives: \ud \ud The goal of this study was to assess associations of cardiac troponin concentration with cardiovascular disease (CVD) outcomes in primary prevention studies.\ud \ud Methods: \ud \ud A search was conducted of PubMed, Web of Science, and EMBASE for prospective studies published up to September 2016, reporting on associations of cardiac troponin concentration with first-ever CVD outcomes (i.e., coronary heart disease [CHD], stroke, or the combination of both). Study-specific estimates, adjusted for conventional risk factors, were extracted by 2 independent reviewers, supplemented with de novo data from PROSPER (Pravastatin in Elderly Individuals at Risk of Vascular Disease Study), then pooled by using random effects meta-analysis.\ud \ud Results: \ud \ud A total of 28 relevant studies were identified involving 154,052 participants. Cardiac troponin was detectable in 80.0% (hs-cTnI: 82.6%; hs-cTnT: 69.7%). In PROSPER, positive associations of log-linear shape were observed between hs-cTnT and CVD outcomes. In the meta-analysis, the relative risks comparing the top versus the bottom troponin third were 1.43 (95% confidence interval [CI]: 1.31 to 1.56) for CVD (11,763 events), 1.67 (95% CI: 1.50 to 1.86) for fatal CVD (7,775 events), 1.59 (95% CI: 1.38 to 1.83) for CHD (7,061 events), and 1.35 (95% CI: 1.23 to 1.48) for stroke (2,526 events). For fatal CVD, associations were stronger in North American studies (p = 0.010) and those measuring hs-cTnT rather than hs-cTnI (p = 0.027).\ud \ud Conclusions: \ud \ud In the general population, high cardiac troponin concentration within the normal range is associated with increased CVD risk. This association is independent of conventional risk factors, strongest for fatal CVD, and applies to both CHD and stroke.

Published
2017

189. Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Author

Warren, Helen R., Evangelou, Evangelos, Cabrera, Claudia P., Gao, He, Ren, Meixia, Mifsud, Borbala, Ntalla, Ioanna, Surendran, Praveen, Liu, Chunyu, Cook, James P., Kraja, Aldi T., Drenos, Fotios, Loh, Marie, Verweij, Niek, Marten, Jonathan, Karaman, Ibrahim, Lepe, Marcelo P. Segura, O'Reilly, Paul F., Knight, Joanne, Snieder, Harold, Kato, Norihiro, He, Jiang, Tai, E Shyong, Said, M. Abdullah, Porteous, David, Alver, Maris, Poulter, Neil, Farrall, Martin, Gansevoort, Ron T., Padmanabhan, Sandosh, Mägi, Reedik, Stanton, Alice, Connell, John, Bakker, Stephan J.L., Metspalu, Andres, Shields, Denis C., Thom, Simon, Brown, Morris, Sever, Peter, Esko, Tõnu, Hayward, Caroline, van der Harst, Pim, Saleheen, Danish, Chowdhury, Rajiv, Chambers, John C., Chasman, Daniel I., Chakravarti, Aravinda, Newton-Cheh, Christopher, Lindgren, Cecilia M., Levy, Daniel, Kooner, Jaspal S., Keavney, Bernard, Tomaszewski, Maciej, Samani, Nilesh J., Howson, Joanna M.M., Tobin, Martin D., Munroe, Patricia B., Ehret, Georg B., Wain, Louise V., Barnes, Michael R., Tzoulaki, Ioanna, Caulfield, Mark J., Elliott, Paul, and Stott, David J.

Abstract

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure–raising genetic variants on future cardiovascular disease risk.

Published
2017

190. STROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease

Author

Sachdev, Perminder S, Lo, Jessica W, Bae, Hee-Joon, Linden, Thomas, Blomstrand, Christian, Fagerberg, Björn, Skoog, Ingmar, Godefroy, Olivier, Barbay, Mélanie, Roussel, Martine, Lee, Byung-Chul, Yu, Kyung-Ho, Lim, Jae-Sung, Wardlaw, Joanna, Makin, Stephen J, Doubal, Fergus N, Chappell, Francesca M, Srikanth, Velandai K, Thrift, Amanda G, Donnan, Geoffrey A, Kandiah, Nagaendran, Chander, Russell J, Lin, Xuling, Brodtmann, Amy, Cordonnier, Charlotte, Moulin, Solene, Rossi, Costanza, Sabayan, Behnam, Stott, David J, Jukema, J Wouter, Melkas, Susanna, Jokinen, Hanna, Erkinjuntti, Timo, Mok, Vincent Ct, Werden, Emilio, Wong, Adrian, Lam, Bonnie Yk, Leys, Didier, Hénon, Hilde, Bombois, Stéphanie, Sachdev, Perminder, Cumming, Toby, Köhler, Sebastian, Verhey, Frans R J, Dong, Yan-Hong, Tan, Hui Hui, Chen, Christopher, Crawford, John D, Xin, Xu, Kalaria, Raj N, Allan, Louise M, Akinyemi, Rufus O, Ogunniyi, Adesola, Klimkowicz-Mrowiec, Aleksandra, Dichgans, Martin, Wollenweber, Frank A, Zietemann, Vera, Hoffmann, Michael, Mellon, Lisa, Desmond, David W, Hickey, Anne, Williams, David, Mok, Vincent C T, Bordet, Régis, Lam, Bonnie Y K, Lipnicki, Darren M, Kochan, Nicole A, STROKOG, Mendyk, Anne-Marie, Gelé, Patrick, Deplanque, Dominique, Verhey, Frans Rj, Xu, Jing, Akinyemi, Rufus, Kalariai, Raj N, Metacohorts Consortium, Department of Chemistry, Indiana University, Indiana University [Bloomington], Indiana University System-Indiana University System, School of Civil Engineering, The University of Queensland, School of Civil Engineering, Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], McGill University = Université McGill [Montréal, Canada], University of Ibadan, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Department of Computer Science [ETH Zürich] (D-INFK), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Institute of Neuroscience and Physiology [Göteborg], Service de neurologie [Amiens], CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), University of Edinburgh, Harvard Medical School [Boston] (HMS), Interuniversity Cardiology Institute Netherlands, Helsinki University Central Hospital, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, HUCH, Neurologian yksikkö, Clinicum, Department of Neurosciences, University of Helsinki, and HUS Neurocenter

Subjects
Gerontology, endocrine system, medicine.medical_specialty, [SDV]Life Sciences [q-bio], education, International consortium, 030204 cardiovascular system & hematology, Post-stroke dementia, Special Section: Vascular Contributions to Alzheimer's Disease, Vascular dementia, 3124 Neurology and psychiatry, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, ddc:610, Stroke, Data harmonization, Post stroke dementia, 3112 Neurosciences, Cognition, medicine.disease, 3. Good health, Small vessel disease, Psychiatry and Mental health, Vascular cognitive disorder, Cohort studies, Neurology (clinical), Psychology, Neurocognitive, 030217 neurology & neurosurgery, Cohort study
Abstract

Introduction: \ud \ud The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD).\ud \ud Methods: \ud \ud Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia.\ud \ud Results: \ud \ud Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3 months to 21 years.\ud \ud Discussion: \ud \ud Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes.

Published
2017

192. The management of hypertension in people with dementia

Author

Harrison, Jennifer Kirsty, Van Der Wardt, Veronika, Conroy, Simon Paul, Stott, David J, Dening, Tom, Gordon, Adam Lee, Logan, Pip, Welsh, Tomas, Taggar, Jaspal, Harwood, Rowan, and Gladman, John

Published
2016

193. A Prospective Study of Pravastatin in the Elderly at Risk (PROSPER): Screening Experience and Baseline Characteristics

Author

Lagaay A Margot, Gaw Allan, Hyland Michael, Jukema J Wouter, Buckley Brendan M, Bollen Edward LEM, Cobbe Stuart M, Shepherd James, Murphy Michael B, Blauw Gerard, Ford Ian, Perry Ivan J, Macfarlane Peter, Norrie John, Meinders A Edo, Sweeney Brian J, Packard Chris J, Westendorp Rudi GJ, Twomey Cillian, and Stott David J

Subjects
clinical trial, elderly, pravastatin, baseline characteristics, Medicine (General), R5-920
Abstract

Abstract Background PROSPER was designed to investigate the benefits of treatment with pravastatin in elderly patients for whom a typical doctor might consider the prescription of statin therapy to be a realistic option. Methods The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomised, double blind, placebo-controlled trial to test the hypothesis that treatment with pravastatin (40 mg/day) will reduce the risk of coronary heart disease death, non-fatal myocardial infarction, and fatal or non-fatal stroke in elderly men and women with pre-existing vascular disease or with significant risk of developing this condition. Results In Scotland, Ireland, and the Netherlands, 23,770 individuals were screened, and 5,804 subjects (2,804 men and 3,000 women), aged 70 to 82 years (average 75 years) and with baseline cholesterol 4.0–9.0 mmol/l, were randomised. Randomised subjects had similar distributions with respect to age, blood pressure, and body mass index when compared to the entire group of screenees, but had a higher prevalence of smoking, diabetes, hypertension, and a history of vascular disease. The average total cholesterol level at baseline was 5.4 mmol/l (men) and 6.0 mmol/l (women). Conclusions Compared with previous prevention trials of cholesterol-lowering drugs, the PROSPER cohort is significantly older and for the first time includes a majority of women. The study, having achieved its initial goal of recruiting more than 5,500 elderly high-risk men and women, aims to complete all final subject follow-up visits in the first half of 2002 with the main results being available in the fourth quarter of 2002.

Published
2002
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194. Whole genome analysis of plasma fibrinogen reveals population-differentiated genetic regulators with putative liver role.

Author

Huffman, Jennifer E, Nicholas, Jayna, Hahn, Julie, Heath, Adam S, Raffield, Laura M, Yanek, Lisa R, Brody, Jennifer A, Thibord, Florian, Almasy, Laura, Bartz, Traci M, Bielak, Lawrence F., Bowler, Russell P, Carrasquilla, Germán D, Chasman, Daniel I, Chen, Ming-Huei, Emmert, David B, Ghanbari, Mohsen, Haessler, Jeffery, Hottenga, Jouke- Jan, Kleber, Marcus E, Le, Ngoc-Quynh, Lee, Jiwon, Lewis, Joshua P, Li-Gao, Ruifang, Luan, Jian'an, Malmberg, Anni, Mangino, Massimo, Marioni, Riccardo E, Martinez-Perez, Angel, Pankratz, Nathan, Polasek, Ozren, Richmond, Anne, Rodriguez, Benjamin AT, Rotter, Jerome I, Steri, Maristella, Suchon, Pierre, Trompet, Stella, Weiss, Stefan, Zare, Marjan, Auer, Paul, Cho, Michael H, Christofidou, Paraskevi, Davies, Gail, de Geus, Eco, Deleuze, Jean-François, Delgado, Graciela E, Ekunwe, Lynette, Faraday, Nauder, Gögele, Martin, Greinacher, Andreas, He, Gao, Howard, Tom, Joshi, Peter K, Kilpeläinen, Tuomas O, Lahti, Jari, Linneberg, Allan, Naitza, Silvia, Noordam, Raymond, Paüls-Vergés, Ferran, Rich, Stephen S, Rosendaal, Frits R, Rudan, Igor, Ryan, Kathleen A, Souto, Juan Carlos, van Rooij, Frank JA, Wang, Heming, Zhao, Wei, Becker, Lewis C, Beswick, Andrew, Brown, Michael R, Cade, Brian E, Campbell, Harry, Cho, Kelly, Crapo, James D, Curran, Joanne E, de Maat, Moniek PM, Doyle, Margaret, Elliott, Paul, Floyd, James S, Fuchsberger, Christian, Grarup, Niels, Guo, Xiuqing, Harris, Sarah E, Hou, Lifang, Kolcic, Ivana, Kooperberg, Charles, Menni, Cristina, Nauck, Matthias, O'Connell, Jeffrey R, Orrù, Valeria, Psaty, Bruce M, Räikkönen, Katri, Smith, Jennifer A, Soria, Jose Manuel, Stott, David J, van Hylckama Vlieg, Astrid, Watkins, Hugh, Willemsen, Gonneke, Wilson, Peter WF, Ben-Shlomo, Yoav, Blangero, John, Boomsma, Dorret, Cox, Simon R, Dehghan, Abbas, Eriksson, Johan G, Fiorillo, Edoardo, ornage, Myriam F, Hansen, Torben, Hayward, Caroline, Ikram, M. Arfan, Jukema, J Wouter, Kardia, Sharon LR, Lange, Leslie A, März, Winfried, Mathias, Rasika A, Mitchell, Braxton D, Mook-Kanamori, Dennis O, Morange, Pierre-Emmanuel, Pedersen, Oluf, Pramstaller, Peter P, Redline, Susan, Reiner, Alexander, Ridker, Paul M, Silverman, Edwin K, Spector, Tim D, Völker, Uwe, Wareham, Nick, Wilson, James F, Yao, Jie, Trégouët, David-Alexandre, Johnson, Andrew D, Wolberg, Alisa S, de Vries, Paul S, Sabater-Lleal, Maria, Morrison, Alanna C, and Smith, Nicholas L

Abstract

•Largest and most diverse genetic study of plasma fibrinogen identifies 54 regions (18 novel), housing 69 conditionally distinct variants (20 novel).•Links to (1) liver enzyme, blood cell and lipid genetic signals, (2) liver regulatory elements, and (3) thrombotic and inflammatory disease.•Sufficient power achieved to identify signals driven by African population variants.

Published
2024
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195. A genetic-association study of circulating coagulation factor VIII and von Willebrand factor levels

Author

de Vries, Paul S., Reventun, Paula, Brown, Michael R., Heath, Adam S., Huffman, Jennifer E., Le, Ngoc-Quynh, Bebo, Allison, Brody, Jennifer A., Temprano-Sagrera, Gerard, Raffield, Laura M., Ozel, Ayse Bilge, Thibord, Florian, Jain, Deepti, Lewis, Joshua P., Rodriguez, Benjmain A. T., Pankratz, Nathan, Taylor, Kent D., Polasek, Ozren, Chen, Ming-Huei, Yanek, Lisa R., Carrasquilla, German D., Marioni, Riccardo E., Kleber, Marcus E., Trégouët, David-Alexandre, Yao, Jie, Li-Gao, Ruifang, Joshi, Peter K., Trompet, Stella, Martinez-Perez, Angel, Ghanbari, Mohsen, Howard, Tom E., Reiner, Alex P., Arvanitis, Marios, Ryan, Kathleen A., Bartz, Traci M., Rudan, Igor, Faraday, Nauder, Linneberg, Allan, Ekunwe, Lynette, Davies, Gail, Delgado, Graciela E., Suchon, Pierre, Guo, Xiuqing, Rosendaal, Frits R., Klaric, Lucija, Noordam, Raymond, van Rooij, Frank, Curran, Joanne E., Wheeler, Marsha M., Osburn, William O., O'Connell, Jeffrey R., Boerwinkle, Eric, Beswick, Andrew, Psaty, Bruce M., Kolcic, Ivana, Souto, Juan Carlos, Becker, Lewis C., Hansen, Torben, Doyle, Margaret F., Harris, Sarah E., Moissl, Angela P., Deleuze, Jean-François, Rich, Stephen S., van Hylckama Vlieg, Astrid, Campbell, Harry, Stott, David J., Soria, Jose Manuel, de Maat, Moniek P. M., Almasy, Laura, Brody, Lawrence C., Auer, Paul L., Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Albert, Christine, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Diane, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Blue, Nathan, Boerwinkle, Eric, Bowden, Donald W., Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April P., Carty, Cara, Casaburi, Richard, Casas Romero, Juan P, Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Chung, Ren-Hua, Clish, Clary, Comhair, Suzy, Conomos, Matthew, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, de las Fuentes, Lisa, de Vries, Paul, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Dinh, Huyen, Doddapaneni, Harsha, Duan, Qing, Dugan-Perez, Shannon, Duggirala, Ravi, Durda, Jon Peter, Dutcher, Susan K., Eaton, Charles, Ekunwe, Lynette, El Boueiz, Adel, Ellinor, Patrick, Emery, Leslie, Erzurum, Serpil, Farber, Charles, Farek, Jesse, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Frazar, Chris, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Shanshan, Gao, Yan, Gass, Margery, Geiger, Heather, Gelb, Bruce, Geraci, Mark, Germer, Soren, Gerszten, Robert, Ghosh, Auyon, Gibbs, Richard, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Graw, Sharon, Gray, Kathryn J., Grine, Daniel, Gross, Colin, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Gupta, Namrata, Haessler, Jeff, Hall, Michael, Han, Yi, Hanly, Patrick, Harris, Daniel, Hawley, Nicola L., He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hobbs, Brian, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Hu, Jianhong, Hung, Yi-Jen, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Khan, Ziad, Kim, Wonji, Kimoff, John, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Jiwon, Lee, Sandra, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Xiaohui, Li, Yun, Lin, Henry, Lin, Honghuang, Lin, Xihong, Liu, Simin, Liu, Yongmei, Liu, Yu, Loos, Ruth J. F., Lubitz, Steven, Lunetta, Kathryn, Luo, James, Magalang, Ulysses, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manning, Alisa, Manson, JoAnn, Martin, Lisa, Marton, Melissa, Mathai, Susan, Mathias, Rasika, May, Susanne, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, McGoldrick, Daniel, McHugh, Caitlin, McNeil, Becky, Mei, Hao, Meigs, James, Menon, Vipin, Mestroni, Luisa, Metcalf, Ginger, Meyers, Deborah A, Mignot, Emmanuel, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L, Mitchell, Braxton D., Moll, Matt, Momin, Zeineen, Montasser, May E., Montgomery, Courtney, Muzny, Donna, Mychaleckyj, Josyf C, Nadkarni, Girish, Naik, Rakhi, Naseri, Take, Natarajan, Pradeep, Nekhai, Sergei, Nelson, Sarah C., Neltner, Bonnie, Nessner, Caitlin, Nickerson, Deborah, Nkechinyere, Osuji, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Okwuonu, Geoffrey, Pack, Allan, Paik, David T., Palmer, Nicholette, Pankow, James, Papanicolaou, George, Parker, Cora, Peloso, Gina, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S, Pleiness, Jacob, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Rajendran, Mahitha, Ramachandran, Vasan S., Rao, D. C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Reeves, Catherine, Regan, Elizabeth, Reiner, Alex, Reupena, Muagututi‘a Sefuiva, Rice, Ken, Rich, Stephen, Robillard, Rebecca, Robine, Nicolas, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Runnels, Alexi, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sabino, Ester Cerdeira, Saleheen, Danish, Salimi, Shabnam, Salvi, Sejal, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay G., Santibanez, Jireh, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sériès, Frédéric, Sheehan, Vivien, Sherman, Stephanie L., Shetty, Amol, Shetty, Aniket, Hui-Heng Sheu, Wayne, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Skomro, Robert, Smith, Albert Vernon, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Snyder, Michael, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne M., Storm, Garrett, Streeten, Elizabeth, Su, Jessica Lasky, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent D., Taylor, Matthew, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Threlkeld, Machiko, Tinker, Lesley, Tirschwell, David, Tishkoff, Sarah, Tiwari, Hemant, Tong, Catherine, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, Van Den Berg, David, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wang, Fei Fei, Wang, Heming, Wang, Jiongming, Watson, Karol, Watt, Jennifer, Weeks, Daniel E., Weinstock, Joshua, Weir, Bruce, Weiss, Scott T, Weng, Lu-Chen, Wessel, Jennifer, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, Wu, Joseph, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yu, Ketian, Zekavat, Seyedeh Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zhu, Xiaofeng, Ziv, Elad, Zody, Michael, Zoellner, Sebastian, Lindstrom, Sara, Wang, Lu, Smith, Erin N., Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A., Pattee, Jack W., Haessler, Jeffrey, Brumpton, Ben M., Chasman, Daniel I., Suchon, Pierre, Chen, Ming-Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri L., MacDonald, James, Braekkan, Sigrid K., Armasu, Sebastian M., Pankratz, Nathan, Jackson, Rabecca D., Nielsen, Jonas B., Giulianini, Franco, Puurunen, Marja K., Ibrahim, Manal, Heckbert, Susan R., Bammler, Theo K., Frazer, Kelly A., McCauley, Bryan M., Taylor, Kent, Pankow, James S., Reiner, Alexander P., Gabrielsen, Maiken E., Deleuze, Jean-François, O'Donnell, Chris J., Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R., Heit, John A., Psaty, Bruce M., Tang, Weihong, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M., Morange, Pierre-Emmanuel, Johnson, Andrew D., Kabrhel, Christopher, AlexandreTrégouët, David, Smith, Nicholas L., Mitchell, Braxton D., Ben-Shlomo, Yoav, Fornage, Myriam, Hayward, Caroline, Mathias, Rasika A., Kilpeläinen, Tuomas O., Lange, Leslie A., Cox, Simon R., März, Winfried, Morange, Pierre-Emmanuel, Rotter, Jerome I., Mook-Kanamori, Dennis O., Wilson, James F., van der Harst, Pim, Jukema, J. Wouter, Ikram, M. Arfan, Blangero, John, Kooperberg, Charles, Desch, Karl C., Johnson, Andrew D., Sabater-Lleal, Maria, Lowenstein, Charles J., Smith, Nicholas L., and Morrison, Alanna C.

Abstract

•We identified 7 new genetic regions for factor VIII levels, 1 for von Willebrand factor levels, and 3 in a combined analysis.•Silencing B3GNT2and CD36reduced factor VIII release in vitro.Silencing B3GNT2, CD36, and PDIA3reduced von Willebrand factor release.

Published
2024
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196. Effect of Thyroid Hormone Therapy on Fatigability in Older Adults With Subclinical Hypothyroidism: A Nested Study Within a Randomized Placebo-Controlled Trial.

Author

Stuber, Mirah J, Moutzouri, Elisavet, Feller, Martin, Giovane, Cinzia Del, Bauer, Douglas C, Blum, Manuel R, Collet, Tinh-Hai, Gussekloo, Jacobijn, Mooijaart, Simon P, McCarthy, Vera J C, Aujesky, Drahomir, Westendorp, Rudi, Stott, David J, Glynn, Nancy W, Kearney, Patricia M, Rodondi, Nicolas, and Del Giovane, Cinzia

Subjects
OLDER people, HORMONE therapy, CORONARY disease, THYROID hormones, HYPOTHYROIDISM, THYROTROPIN, RESEARCH, THYROXINE, RESEARCH methodology, EVALUATION research, MEDICAL cooperation, COMPARATIVE studies, RANDOMIZED controlled trials, SYMPTOMS, IMPACT of Event Scale, FATIGUE (Physiology), DISEASE complications
Abstract

Background: Fatigue often triggers screening for and treatment of subclinical hypothyroidism. However, data on the impact of levothyroxine on fatigue is limited and previous studies might not have captured all aspects of fatigue.Method: This study is nested within the randomized, placebo-controlled, multicenter TRUST trial, including community-dwelling participants aged ≥65 and older, with persistent subclinical hypothyroidism (TSH 4.60-19.99 mIU/L, normal free thyroxine levels) from Switzerland and Ireland. Interventions consisted of daily levothyroxine starting with 50 μg (25 μg if weight <50 kg or known coronary heart diseases) together with dose adjustments to achieve a normal TSH and mock titration in the placebo group. Main outcome was the change in physical and mental fatigability using the Pittsburgh Fatigability Scale over 1 year, assessed through multivariable linear regression with adjustment for country, sex, and levothyroxine starting dose.Results: Among 230 participants, the mean ± standard deviation (SD) TSH was 6.2 ± 1.9 mIU/L at baseline and decreased to 3.1 ± 1.3 with LT4 (n = 119) versus 5.3 ± 2.3 with placebo (n = 111, p < .001) after 1 year. After adjustment we found no between-group difference at 1 year on perceived physical (0.2; 95% CI -1.8 to 2.1; p = .88), or mental fatigability (-1.0; 95% CI -2.8 to 0.8; p = .26). In participants with higher fatigability at baseline (≥15 points for the physical score [n = 88] or ≥13 points for the mental score [n = 41]), the adjusted between-group differences at 1 year were 0.4 (95% CI -3.6 to 2.8, p = .79) and -2.2 (95% CI -8.8 to 4.5, p = .51).Conclusions: Levothyroxine in older adults with mild subclinical hypothyroidism provides no change in physical or mental fatigability. [ABSTRACT FROM AUTHOR]

Published
2020
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197. A pragmatic, multi-centered, stepped wedge, cluster randomized controlled trial pilot of the clinical and cost effectiveness of a complex Stroke Oral healthCare intervention pLan Evaluation II (SOCLE II) compared with usual oral healthcare in stroke wards

Author

Brady, Marian C, Stott, David J, Weir, Christopher J, Chalmers, Campbell, Sweeney, Petrina, Barr, John, Pollock, Alex, Bowers, Naomi, Gray, Heather, Bain, Brenda Jean, Collins, Marissa, Keerie, Catriona, and Langhorne, Peter

Subjects
*CLUSTER randomized controlled trials, *CLINICAL trials, *DENTAL health education, *COST effectiveness, *MEDICAL care
Abstract

Background: Patients with stroke-associated pneumonia experience poorer outcomes (increased hospital stays, costs, discharge dependency, and risk of death). High-quality, organized oral healthcare may reduce the incidence of stroke-associated pneumonia and improve oral health and quality of life. Aims: We piloted a pragmatic, stepped-wedge, cluster randomized controlled trial of clinical and cost effectiveness of enhanced versus usual oral healthcare for people in stroke rehabilitation settings. Methods: Scottish stroke rehabilitation wards were randomly allocated to stepped time-points for conversion from usual to enhanced oral healthcare. All admissions and nursing staff were eligible for inclusion. We piloted the viability of randomization, intervention, data collection, record linkage procedures, our sample size, screening, and recruitment estimates. The stepped-wedge trial design prevented full blinding of outcome assessors and staff. Predetermined criteria for progression included the validity of enhanced oral healthcare intervention (training, oral healthcare protocol, assessment, equipment), data collection, and stroke-associated pneumonia event rate and relationship between stroke-associated pneumonia and plaque. Results: We screened 1548/2613 (59%) admissions to four wards, recruiting n = 325 patients and n = 112 nurses. We observed marked between-site diversity in admissions, recruitment populations, stroke-associated pneumonia events (0% to 21%), training, and resource use. No adverse events were reported. Oral healthcare documentation was poor. We found no evidence of a difference in stroke-associated pneumonia between enhanced versus usual oral healthcare (P = 0.62, odds ratio = 0.61, confidence interval: 0.08 to 4.42). Conclusions: Our stepped-wedge cluster randomized control trial accommodated between-site diversity. The stroke-associated pneumonia event rate did not meet our predetermined progression criteria. We did not meet our predefined progression criteria including the SAP event rate and consequently were unable to establish whether there is a relationship between SAP and plaque. A wide confidence interval did not exclude the possibility that enhanced oral healthcare may result in a benefit or detrimental effect. Trial Registration: NCT01954212. [ABSTRACT FROM AUTHOR]

Published
2020
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198. The association of kidney function and cognitive decline in older patients at risk of cardiovascular disease: a longitudinal data analysis.

Author

Zijlstra, Laurien E., Trompet, Stella, Mooijaart, Simon P., van Buren, Marjolijn, Sattar, Naveed, Stott, David J., and Jukema, J. Wouter

Subjects
COGNITIVE testing, OLDER patients, COGNITIVE ability, COGNITION disorders, CHRONIC kidney failure, MONTREAL Cognitive Assessment, CHRONIC kidney failure complications, GLOMERULAR filtration rate, DISEASE progression, RESEARCH, RESEARCH methodology, CARDIOVASCULAR diseases, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, RESEARCH funding, LONGITUDINAL method, DISEASE complications
Abstract

Background: Chronic kidney disease (CKD) has been identified as a significant direct marker for cognitive decline, but controversy exists regarding the magnitude of the association of kidney function with cognitive decline across the different CKD stages. Therefore, the aim of this study was to investigate the association of kidney function with cognitive decline in older patients at high risk of cardiovascular disease, using data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).Methods: Data of 5796 patients of PROSPER were used. Strata were made according to clinical stages of CKD based on estimated glomerular filtration rate; < 30 ml/min/1.73m2 (stage 4), 30-45 ml/min/1.73m2 (stage 3b), 45-60 ml/min/1.73m2 (stage 3a) and ≥ 60 ml/min/1.73m2 (stage 1-2). Cognitive function and functional status was assessed at six different time points and means were compared at baseline and over time, adjusted for multiple prespecified variables. Stratified analyses for history of vascular disease were executed.Results: Mean age was 75.3 years and 48.3% participants were male. Mean follow-up was 3.2 years. For all cognitive function tests CKD stage 4 compared to the other stages had the worst outcome at baseline and a trend for faster cognitive decline over time. When comparing stage 4 versus stage 1-2 over time the estimates (95% CI) were 2.23 (0.60-3.85; p = 0.009) for the Stroop-Colour-Word test, - 0.33 (- 0.66-0.001; p = 0.051) for the Letter-Digit-Coding test, 0.08 (- 0.06-0.21; p = 0.275) for the Picture-Word-Learning test with immediate recall and - 0.07 (- 0.02-0.05; p = 0.509) for delayed recall. This association was most present in patients with a history of vascular disease. No differences were found in functional status.Conclusion: In older people with vascular burden, only severe kidney disease (CKD stage 4), but not mild to modest kidney disease (CKD stage 3a and b), seem to be associated with cognitive impairment at baseline and cognitive decline over time. The association of severe kidney failure with cognitive impairment and decline over time was more outspoken in patients with a history of vascular disease, possibly due to a higher probability of polyvascular damage, in both kidney and brain, in patients with proven cardiovascular disease. [ABSTRACT FROM AUTHOR]

Published
2020
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200. Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume

Author

Vojinovic, Dina, primary, Adams, Hieab H., additional, Jian, Xueqiu, additional, Yang, Qiong, additional, Smith, Albert Vernon, additional, Bis, Joshua C., additional, Teumer, Alexander, additional, Scholz, Markus, additional, Armstrong, Nicola J., additional, Hofer, Edith, additional, Saba, Yasaman, additional, Luciano, Michelle, additional, Bernard, Manon, additional, Trompet, Stella, additional, Yang, Jingyun, additional, Gillespie, Nathan A., additional, van der Lee, Sven J., additional, Neumann, Alexander, additional, Ahmad, Shahzad, additional, Andreassen, Ole A., additional, Ames, David, additional, Amin, Najaf, additional, Arfanakis, Konstantinos, additional, Bastin, Mark E., additional, Becker, Diane M., additional, Beiser, Alexa S., additional, Beyer, Frauke, additional, Brodaty, Henry, additional, Bryan, R. Nick, additional, Bülow, Robin, additional, Dale, Anders M., additional, De Jager, Philip L., additional, Deary, Ian J., additional, DeCarli, Charles, additional, Fleischman, Debra A., additional, Gottesman, Rebecca F., additional, van der Grond, Jeroen, additional, Gudnason, Vilmundur, additional, Harris, Tamara B., additional, Homuth, Georg, additional, Knopman, David S., additional, Kwok, John B., additional, Lewis, Cora E., additional, Li, Shuo, additional, Loeffler, Markus, additional, Lopez, Oscar L., additional, Maillard, Pauline, additional, El Marroun, Hanan, additional, Mather, Karen A., additional, Mosley, Thomas H., additional, Muetzel, Ryan L., additional, Nauck, Matthias, additional, Nyquist, Paul A., additional, Panizzon, Matthew S., additional, Pausova, Zdenka, additional, Psaty, Bruce M., additional, Rice, Ken, additional, Rotter, Jerome I., additional, Royle, Natalie, additional, Satizabal, Claudia L., additional, Schmidt, Reinhold, additional, Schofield, Peter R., additional, Schreiner, Pamela J., additional, Sidney, Stephen, additional, Stott, David J., additional, Thalamuthu, Anbupalam, additional, Uitterlinden, Andre G., additional, Valdés Hernández, Maria C., additional, Vernooij, Meike W., additional, Wen, Wei, additional, White, Tonya, additional, Witte, A. Veronica, additional, Wittfeld, Katharina, additional, Wright, Margaret J., additional, Yanek, Lisa R., additional, Tiemeier, Henning, additional, Kremen, William S., additional, Bennett, David A., additional, Jukema, J. Wouter, additional, Paus, Tomas, additional, Wardlaw, Joanna M., additional, Schmidt, Helena, additional, Sachdev, Perminder S., additional, Villringer, Arno, additional, Grabe, Hans Jörgen, additional, Longstreth, W T, additional, van Duijn, Cornelia M., additional, Launer, Lenore J., additional, Seshadri, Sudha, additional, Ikram, M Arfan, additional, and Fornage, Myriam, additional

Published
2018
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