Search

Your search keyword '"H. McKie"' showing total 23 results
Start Over Author "H. McKie" Search Limiters Full Text
23 results on '"H. McKie"'

1. ASPIRE-3-PREVENT: a cross-sectional survey of preventive care after a coronary event across the UK

Author

Paul Bassett, Catriona S Jennings, J Shah, A Sutherland, N Singh, M Mohan, D Wood, K Orr, S Clark, C Morgan, A Taylor, C Gale, M Cunningham, A Nicholson, J Wright, C Edwards, J Harrison, K Lyons, C Mills, M Baker, N Hussain, J Porter, A Hunt, David Wood, Kornelia Kotseva, Agnieszka Adamska, A Adamska, S Adamska, C Jennings, K Kotseva, A Hoye, P Atkin, D Fellowes, A Negahban, A Daniels, L Zeidan, S Iyer, M Ocampo, A Sevillano, G Galasko, L Benham, S Preston, D Sebastian, S Lindsay, C Atkinson, C Kranilla, M Vinod, H Abbass, N Rhoualmi, Y Beerachee, C Bennett, M Broome, A Bwalya, Lindsay Caygill, L Dinning, A Gillespie, R Goodfellow, J Guy, T Idress, N Oustance, M Yare, J M Jagoda, H Bowyer, V Christenssen, A Groves, P I Jan, A Riaz, M Gill, T A Sewell, D Gorog, P De Sousa, T Mazenenga, A Banfield, R Encarnado, C Travill, S Gent, F Haines, T Peachey, J Taaffe, K Wells, D P Ripley, H Forward, H McKie, SL Pick, H E Thomas, P D Batin, D Exley, T Rank, A Kardos, S-B Sutherland, L Wren, P Leeson, D Barker, B Moreby, J Sawyer, J Sobolewska, D Adams, C Corbett, K Hallett, S Kaye, L Morby, L Winstanley, J Stirrup, M Brunton, M M Gandhi, L Adams, L Tapp, V Ansell, S Hyndman, A Brodison, J Craig, S Peters, R Kaprielian, A Bucaj, K Mahay, M Oblak, A Sultan, K Duell, M Gaskell, L Heaton, C Moore, V Parkinson, T Taylor, C Tierney, K Vandesnepscheut-Jones, A Broadley, C Buckley, L Matthews, L Pippard, M Pye, Y McGill, H Redfearn, M Fearnley, L Miskelly, S O Mullan, M Spencer, E McCart, P Donnelly, S Kelly, S Regan, D Turnbull, Dana Dawson, B Brikinns, K Oldroyd, F Teyhan, J Kelly, A Tewkesbury, D Newby, K Combe, L Derr, J Donnelly, L Flint, A Gill, M Glenwright, H Nailon, E McDonald, C Mahoney, F Morrow, K Paterson, B Poulose, B Rif, N Spath, H Spence, J Watt, C Barr, S Dekker, D McDonald, L O'Keeffe, I Shread, C C Lang, AM Choy, L Douglas, S Kalra, R Symon, J Halcox, K Baldwin, H Goldring, C Thomas, L Izzat, D Evans, Z Omar, and E Perkins

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Objective To quantify the implementation of the third Joint British Societies’ Consensus Recommendations for the Prevention of Cardiovascular Disease (JBS3) after coronary event.Methods Using a cross-sectional survey design, patients were consecutively identified in 36 specialist and district general hospitals between 6 months and 2 years, after acute coronary syndrome or revascularisation procedure and invited to a research interview. Outcomes included JBS3 lifestyle, risk factor and therapeutic management goals. Data were collected using standardised methods and instruments by trained study nurses. Blood was analysed in a central laboratory and a glucose tolerance test was performed.Results 3926 eligible patients were invited to participate and 1177 (23.3% women) were interviewed (30% response). 12.5% were from black and minority ethnic groups. 45% were persistent smokers, 36% obese, 52.9% centrally obese, 52% inactive; 30% had a blood pressure >140/90 mm Hg, 54% non-high-density lipoprotein ≥2.5 mmol/L and 44.3% had new dysglycaemia. Prescribing was highest for antiplatelets (94%) and statins (85%). 81% were advised to attend cardiac rehabilitation (86%

Published
2020
Full Text
View/download PDF

2. Impact of diabetes on the management and outcomes in atrial fibrillation:an analysis from the ESC-EHRA EORP-AF Long-Term General Registry

Author

Wern Yew Ding, Agnieszka Kotalczyk, Giuseppe Boriani, Francisco Marin, Carina Blomström-Lundqvist, Tatjana S. Potpara, Laurent Fauchier, Gregory.Y.H. Lip, G. Boriani, G.Y.H. Lip, L. Tavazzi, A.P. Maggioni, G.-A. Dan, T. Potpara, M. Nabauer, F. Marin, Z. Kalarus, A. Goda, G. Mairesse, T. Shalganov, L. Antoniades, M. Taborsky, S. Riahi, P. Muda, I. García Bolao, O. Piot, K. Etsadashvili, E. Simantirakis, M. Haim, A. Azhari, J. Najafian, M. Santini, E. Mirrakhimov, K.A. Kulzida, A. Erglis, L. Poposka, M. Burg, H. Crijns, Ö. Erküner, D. Atar, R. Lenarczyk, M. Martins Oliveira, D. Shah, E. Serdechnaya, E. Diker, D. Lane, E. Zëra, U. Ekmekçiu, V. Paparisto, M. Tase, H. Gjergo, J. Dragoti, M. Ciutea, N. Ahadi, Z. el Husseini, M. Raepers, J. Leroy, P. Haushan, A. Jourdan, C. Lepiece, L. Desteghe, J. Vijgen, P. Koopman, G. Van Genechten, H. Heidbuchel, T. Boussy, M. De Coninck, H. Van Eeckhoutte, N. Bouckaert, A. Friart, J. Boreux, C. Arend, P. Evrard, L. Stefan, E. Hoffer, J. Herzet, M. Massoz, C. Celentano, M. Sprynger, L. Pierard, P. Melon, B. Van Hauwaert, C. Kuppens, D. Faes, D. Van Lier, A. Van Dorpe, A. Gerardy, O. Deceuninck, O. Xhaet, F. Dormal, E. Ballant, D. Blommaert, D. Yakova, M. Hristov, T. Yncheva, N. Stancheva, S. Tisheva, M. Tokmakova, F. Nikolov, D. Gencheva, B. Kunev, M. Stoyanov, D. Marchov, V. Gelev, V. Traykov, A. Kisheva, H. Tsvyatkov, R. Shtereva, S. Bakalska-Georgieva, S. Slavcheva, Y. Yotov, M. Kubíčková, A. Marni Joensen, A. Gammelmark, L. Hvilsted Rasmussen, P. Dinesen, S. Krogh Venø, B. Sorensen, A. Korsgaard, K. Andersen, C. Fragtrup Hellum, A. Svenningsen, O. Nyvad, P. Wiggers, O. May, A. Aarup, B. Graversen, L. Jensen, M. Andersen, M. Svejgaard, S. Vester, S. Hansen, V. Lynggaard, M. Ciudad, R. Vettus, A. Maestre, S. Castaño, S. Cheggour, J. Poulard, V. Mouquet, S. Leparrée, J. Bouet, J. Taieb, A. Doucy, H. Duquenne, A. Furber, J. Dupuis, J. Rautureau, M. Font, P. Damiano, M. Lacrimini, J. Abalea, S. Boismal, T. Menez, J. Mansourati, G. Range, H. Gorka, C. Laure, C. Vassalière, N. Elbaz, N. Lellouche, K. Djouadi, F. Roubille, D. Dietz, J. Davy, M. Granier, P. Winum, C. Leperchois-Jacquey, H. Kassim, E. Marijon, J. Le Heuzey, J. Fedida, C. Maupain, C. Himbert, E. Gandjbakhch, F. Hidden-Lucet, G. Duthoit, N. Badenco, T. Chastre, X. Waintraub, M. Oudihat, J. Lacoste, C. Stephan, H. Bader, N. Delarche, L. Giry, D. Arnaud, C. Lopez, F. Boury, I. Brunello, M. Lefèvre, R. Mingam, M. Haissaguerre, M. Le Bidan, D. Pavin, V. Le Moal, C. Leclercq, T. Beitar, I. Martel, A. Schmid, N. Sadki, C. Romeyer-Bouchard, A. Da Costa, I. Arnault, M. Boyer, C. Piat, N. Lozance, S. Nastevska, A. Doneva, B. Fortomaroska Milevska, B. Sheshoski, K. Petroska, N. Taneska, N. Bakrecheski, K. Lazarovska, S. Jovevska, V. Ristovski, A. Antovski, E. Lazarova, I. Kotlar, J. Taleski, S. Kedev, N. Zlatanovik, S. Jordanova, T. Bajraktarova Proseva, S. Doncovska, D. Maisuradze, A. Esakia, E. Sagirashvili, K. Lartsuliani, N. Natelashvili, N. Gumberidze, R. Gvenetadze, N. Gotonelia, N. Kuridze, G. Papiashvili, I. Menabde, S. Glöggler, A. Napp, C. Lebherz, H. Romero, K. Schmitz, M. Berger, M. Zink, S. Köster, J. Sachse, E. Vonderhagen, G. Soiron, K. Mischke, R. Reith, M. Schneider, W. Rieker, D. Boscher, A. Taschareck, A. Beer, D. Oster, O. Ritter, J. Adamczewski, S. Walter, A. Frommhold, E. Luckner, J. Richter, M. Schellner, S. Landgraf, S. Bartholome, R. Naumann, J. Schoeler, D. Westermeier, F. William, K. Wilhelm, M. Maerkl, R. Oekinghaus, M. Denart, M. Kriete, U. Tebbe, T. Scheibner, M. Gruber, A. Gerlach, C. Beckendorf, L. Anneken, M. Arnold, S. Lengerer, Z. Bal, C. Uecker, H. Förtsch, S. Fechner, V. Mages, E. Martens, H. Methe, T. Schmidt, B. Schaeffer, B. Hoffmann, J. Moser, K. Heitmann, S. Willems, C. Klaus, I. Lange, M. Durak, E. Esen, F. Mibach, H. Mibach, A. Utech, M. Gabelmann, R. Stumm, V. Ländle, C. Gartner, C. Goerg, N. Kaul, S. Messer, D. Burkhardt, C. Sander, R. Orthen, S. Kaes, A. Baumer, F. Dodos, A. Barth, G. Schaeffer, J. Gaertner, J. Winkler, A. Fahrig, J. Aring, I. Wenzel, S. Steiner, A. Kliesch, E. Kratz, K. Winter, P. Schneider, A. Haag, I. Mutscher, R. Bosch, J. Taggeselle, S. Meixner, A. Schnabel, A. Shamalla, H. Hötz, A. Korinth, C. Rheinert, G. Mehltretter, B. Schön, N. Schön, A. Starflinger, E. Englmann, G. Baytok, T. Laschinger, G. Ritscher, A. Gerth, D. Dechering, L. Eckardt, M. Kuhlmann, N. Proskynitopoulos, J. Brunn, K. Foth, C. Axthelm, H. Hohensee, K. Eberhard, S. Turbanisch, N. Hassler, A. Koestler, G. Stenzel, D. Kschiwan, M. Schwefer, S. Neiner, S. Hettwer, M. Haeussler-Schuchardt, R. Degenhardt, S. Sennhenn, M. Brendel, A. Stoehr, W. Widjaja, S. Loehndorf, A. Logemann, J. Hoskamp, J. Grundt, M. Block, R. Ulrych, A. Reithmeier, V. Panagopoulos, C. Martignani, D. Bernucci, E. Fantecchi, I. Diemberger, M. Ziacchi, M. Biffi, P. Cimaglia, J. Frisoni, I. Giannini, S. Boni, S. Fumagalli, S. Pupo, A. Di Chiara, P. Mirone, F. Pesce, C. Zoccali, V.L. Malavasi, A. Mussagaliyeva, B. Ahyt, Z. Salihova, K. Koshum-Bayeva, A. Kerimkulova, A. Bairamukova, B. Lurina, R. Zuzans, S. Jegere, I. Mintale, K. Kupics, K. Jubele, O. Kalejs, K. Vanhear, M. Cachia, E. Abela, S. Warwicker, T. Tabone, R. Xuereb, D. Asanovic, D. Drakalovic, M. Vukmirovic, N. Pavlovic, L. Music, N. Bulatovic, A. Boskovic, H. Uiterwaal, N. Bijsterveld, J. De Groot, J. Neefs, N. van den Berg, F. Piersma, A. Wilde, V. Hagens, J. Van Es, J. Van Opstal, B. Van Rennes, H. Verheij, W. Breukers, G. Tjeerdsma, R. Nijmeijer, D. Wegink, R. Binnema, S. Said, S. Philippens, W. van Doorn, T. Szili-Torok, R. Bhagwandien, P. Janse, A. Muskens, M. van Eck, R. Gevers, N. van der Ven, A. Duygun, B. Rahel, J. Meeder, A. Vold, C. Holst Hansen, I. Engset, B. Dyduch-Fejklowicz, E. Koba, M. Cichocka, A. Sokal, A. Kubicius, E. Pruchniewicz, A. Kowalik-Sztylc, W. Czapla, I. Mróz, M. Kozlowski, T. Pawlowski, M. Tendera, A. Winiarska-Filipek, A. Fidyk, A. Slowikowski, M. Haberka, M. Lachor-Broda, M. Biedron, Z. Gasior, M. Kołodziej, M. Janion, I. Gorczyca-Michta, B. Wozakowska-Kaplon, M. Stasiak, P. Jakubowski, T. Ciurus, J. Drozdz, M. Simiera, P. Zajac, T. Wcislo, P. Zycinski, J. Kasprzak, A. Olejnik, E. Harc-Dyl, J. Miarka, M. Pasieka, M. Ziemińska-Łuć, W. Bujak, A. Śliwiński, A. Grech, J. Morka, K. Petrykowska, M. Prasał, G. Hordyński, P. Feusette, P. Lipski, A. Wester, W. Streb, J. Romanek, P. Woźniak, M. Chlebuś, P. Szafarz, W. Stanik, M. Zakrzewski, J. Kaźmierczak, A. Przybylska, E. Skorek, H. Błaszczyk, M. Stępień, S. Szabowski, W. Krysiak, M. Szymańska, J. Karasiński, J. Blicharz, M. Skura, K. Hałas, L. Michalczyk, Z. Orski, K. Krzyżanowski, A. Skrobowski, L. Zieliński, M. Tomaszewska-Kiecana, M. Dłużniewski, M. Kiliszek, M. Peller, M. Budnik, P. Balsam, G. Opolski, A. Tymińska, K. Ozierański, A. Wancerz, A. Borowiec, E. Majos, R. Dabrowski, H. Szwed, A. Musialik-Lydka, A. Leopold-Jadczyk, E. Jedrzejczyk-Patej, M. Koziel, M. Mazurek, K. Krzemien-Wolska, P. Starosta, E. Nowalany-Kozielska, A. Orzechowska, M. Szpot, M. Staszel, S. Almeida, H. Pereira, L. Brandão Alves, R. Miranda, L. Ribeiro, F. Costa, F. Morgado, P. Carmo, P. Galvao Santos, R. Bernardo, P. Adragão, G. Ferreira da Silva, M. Peres, M. Alves, M. Leal, A. Cordeiro, P. Magalhães, P. Fontes, S. Leão, A. Delgado, A. Costa, B. Marmelo, B. Rodrigues, D. Moreira, J. Santos, L. Santos, A. Terchet, D. Darabantiu, S. Mercea, V. Turcin Halka, A. Pop Moldovan, A. Gabor, B. Doka, G. Catanescu, H. Rus, L. Oboroceanu, E. Bobescu, R. Popescu, A. Dan, A. Buzea, I. Daha, G. Dan, I. Neuhoff, M. Baluta, R. Ploesteanu, N. Dumitrache, M. Vintila, A. Daraban, C. Japie, E. Badila, H. Tewelde, M. Hostiuc, S. Frunza, E. Tintea, D. Bartos, A. Ciobanu, I. Popescu, N. Toma, C. Gherghinescu, D. Cretu, N. Patrascu, C. Stoicescu, C. Udroiu, G. Bicescu, V. Vintila, D. Vinereanu, M. Cinteza, R. Rimbas, M. Grecu, A. Cozma, F. Boros, M. Ille, O. Tica, R. Tor, A. Corina, A. Jeewooth, B. Maria, C. Georgiana, C. Natalia, D. Alin, D. Dinu-Andrei, M. Livia, R. Daniela, R. Larisa, S. Umaar, T. Tamara, M. Ioachim Popescu, D. Nistor, I. Sus, O. Coborosanu, N. Alina-Ramona, R. Dan, L. Petrescu, G. Ionescu, C. Vacarescu, E. Goanta, M. Mangea, A. Ionac, C. Mornos, D. Cozma, S. Pescariu, E. Solodovnicova, I. Soldatova, J. Shutova, L. Tjuleneva, T. Zubova, V. Uskov, D. Obukhov, G. Rusanova, N. Isakova, S. Odinsova, T. Arhipova, E. Kazakevich, O. Zavyalova, T. Novikova, I. Riabaia, S. Zhigalov, E. Drozdova, I. Luchkina, Y. Monogarova, D. Hegya, L. Rodionova, V. Nevzorova, O. Lusanova, A. Arandjelovic, D. Toncev, L. Vukmirovic, M. Radisavljevic, M. Milanov, N. Sekularac, M. Zdravkovic, S. Hinic, S. Dimkovic, T. Acimovic, J. Saric, S. Radovanovic, A. Kocijancic, B. Obrenovic-Kircanski, D. Kalimanovska Ostric, D. Simic, I. Jovanovic, I. Petrovic, M. Polovina, M. Vukicevic, M. Tomasevic, N. Mujovic, N. Radivojevic, O. Petrovic, S. Aleksandric, V. Kovacevic, Z. Mijatovic, B. Ivanovic, M. Tesic, A. Ristic, B. Vujisic-Tesic, M. Nedeljkovic, A. Karadzic, A. Uscumlic, M. Prodanovic, M. Zlatar, M. Asanin, B. Bisenic, V. Vasic, Z. Popovic, D. Djikic, M. Sipic, V. Peric, B. Dejanovic, N. Milosevic, S. Backovic, A. Stevanovic, A. Andric, B. Pencic, M. Pavlovic-Kleut, V. Celic, M. Pavlovic, M. Petrovic, M. Vuleta, N. Petrovic, S. Simovic, Z. Savovic, S. Milanov, G. Davidovic, V. Iric-Cupic, D. Djordjevic, M. Damjanovic, S. Zdravkovic, V. Topic, D. Stanojevic, M. Randjelovic, R. Jankovic-Tomasevic, V. Atanaskovic, S. Antic, D. Simonovic, M. Stojanovic, S. Stojanovic, V. Mitic, V. Ilic, D. Petrovic, M. Deljanin Ilic, S. Ilic, V. Stoickov, S. Markovic, A. Mijatovic, D. Tanasic, G. Radakovic, J. Peranovic, N. Panic-Jelic, O. Vujadinovic, P. Pajic, S. Bekic, S. Kovacevic, A. García Fernandez, A. Perez Cabeza, M. Anguita, L. Tercedor Sanchez, E. Mau, J. Loayssa, M. Ayarra, M. Carpintero, I. Roldán Rabadan, M. Gil Ortega, A. Tello Montoliu, E. Orenes Piñero, S. Manzano Fernández, F. Marín, A. Romero Aniorte, A. Veliz Martínez, M. Quintana Giner, G. Ballesteros, M. Palacio, O. Alcalde, I. García-Bolao, V. Bertomeu Gonzalez, F. Otero-Raviña, J. García Seara, J. Gonzalez Juanatey, N. Dayal, P. Maziarski, P. Gentil-Baron, M. Koç, E. Onrat, I.E. Dural, K. Yilmaz, B. Özin, S. Tan Kurklu, Y. Atmaca, U. Canpolat, L. Tokgozoglu, A.K. Dolu, B. Demirtas, D. Sahin, O. Ozcan Celebi, G. Gagirci, U.O. Turk, H. Ari, N. Polat, N. Toprak, M. Sucu, O. Akin Serdar, A. Taha Alper, A. Kepez, Y. Yuksel, A. Uzunselvi, S. Yuksel, M. Sahin, O. Kayapinar, T. Ozcan, H. Kaya, M.B. Yilmaz, M. Kutlu, M. Demir, C. Gibbs, S. Kaminskiene, M. Bryce, A. Skinner, G. Belcher, J. Hunt, L. Stancombe, B. Holbrook, C. Peters, S. Tettersell, A. Shantsila, K. Senoo, M. Proietti, K. Russell, P. Domingos, S. Hussain, J. Partridge, R. Haynes, S. Bahadur, R. Brown, S. McMahon, J. McDonald, K. Balachandran, R. Singh, S. Garg, H. Desai, K. Davies, W. Goddard, G. Galasko, I. Rahman, Y. Chua, O. Payne, S. Preston, O. Brennan, L. Pedley, C. Whiteside, C. Dickinson, J. Brown, K. Jones, L. Benham, R. Brady, L. Buchanan, A. Ashton, H. Crowther, H. Fairlamb, S. Thornthwaite, C. Relph, A. McSkeane, U. Poultney, N. Kelsall, P. Rice, T. Wilson, M. Wrigley, R. Kaba, T. Patel, E. Young, J. Law, C. Runnett, H. Thomas, H. McKie, J. Fuller, S. Pick, A. Sharp, A. Hunt, K. Thorpe, C. Hardman, E. Cusack, L. Adams, M. Hough, S. Keenan, A. Bowring, J. Watts, J. Zaman, K. Goffin, H. Nutt, Y. Beerachee, J. Featherstone, C. Mills, J. Pearson, L. Stephenson, S. Grant, A. Wilson, C. Hawksworth, I. Alam, M. Robinson, S. Ryan, R. Egdell, E. Gibson, M. Holland, D. Leonard, B. Mishra, S. Ahmad, H. Randall, J. Hill, L. Reid, M. George, S. McKinley, L. Brockway, W. Milligan, J. Sobolewska, J. Muir, L. Tuckis, L. Winstanley, P. Jacob, S. Kaye, L. Morby, A. Jan, T. Sewell, C. Boos, B. Wadams, C. Cope, P. Jefferey, N. Andrews, A. Getty, A. Suttling, C. Turner, K. Hudson, R. Austin, S. Howe, R. Iqbal, N. Gandhi, K. Brophy, P. Mirza, E. Willard, S. Collins, N. Ndlovu, E. Subkovas, V. Karthikeyan, L. Waggett, A. Wood, A. Bolger, J. Stockport, L. Evans, E. Harman, J. Starling, L. Williams, V. Saul, M. Sinha, L. Bell, S. Tudgay, S. Kemp, L. Frost, T. Ingram, A. Loughlin, C. Adams, M. Adams, F. Hurford, C. Owen, C. Miller, D. Donaldson, H. Tivenan, H. Button, A. Nasser, O. Jhagra, B. Stidolph, C. Brown, C. Livingstone, M. Duffy, P. Madgwick, P. Roberts, E. Greenwood, L. Fletcher, M. Beveridge, S. Earles, D. McKenzie, D. Beacock, M. Dayer, M. Seddon, D. Greenwell, F. Luxton, F. Venn, H. Mills, J. Rewbury, K. James, K. Roberts, L. Tonks, D. Felmeden, W. Taggu, A. Summerhayes, D. Hughes, J. Sutton, L. Felmeden, M. Khan, E. Walker, L. Norris, L. O'Donohoe, A. Mozid, H. Dymond, H. Lloyd-Jones, G. Saunders, D. Simmons, D. Coles, D. Cotterill, S. Beech, S. Kidd, B. Wrigley, S. Petkar, A. Smallwood, R. Jones, E. Radford, S. Milgate, S. Metherell, V. Cottam, C. Buckley, A. Broadley, D. Wood, J. Allison, K. Rennie, L. Balian, L. Howard, L. Pippard, S. Board, T. Pitt-Kerby, Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Océan du Large et Variabilité Climatique (OLVAC), Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Uppsala University, University of Belgrade [Belgrade], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Éducation Éthique Santé EA 7505 (EES), and Université de Tours (UT)

Subjects
Kardiologi, General Practice, Cohort, Anticoagulants, MACE, Endocrinology and Diabetes, Prognosis, [SHS]Humanities and Social Sciences, Allmänmedicin, Stroke, Risk Factors, Healthcare resource utilisation, Mortality, Prevalence, Endokrinologi och diabetes, Atrial Fibrillation, Internal Medicine, Diabetes Mellitus, Quality of Life, Humans, Cardiac and Cardiovascular Systems, Prospective Studies, Registries, Aged
Abstract

BACKGROUND: The prevalence of atrial fibrillation(AF) and diabetes mellitus is rising to epidemic proportions. We aimed to assess the impact of diabetes on the management and outcomes of patients with AF.METHODS: The EORP-AF General Long-Term Registry is a prospective, observational registry from 250 centres across 27 European countries. Outcomes of interest were as follows: i)rhythm control interventions; ii)quality of life; iii)healthcare resource utilisation; and iv)major adverse events.RESULTS: Of 11,028 patients with AF, the median age was 71 (63-77) years and 2537 (23.0%) had diabetes. Median follow-up was 24 months. Diabetes was related to increased use of anticoagulation but less rhythm control interventions. Using multivariable analysis, at 2-year follow-up, patients with diabetes were associated with greater levels of anxiety (p = 0.038) compared to those without diabetes. Overall, diabetes was associated with worse health during follow-up, as indicated by Health Utility Score and Visual Analogue Scale. Healthcare resource utilisation was greater with diabetes in terms of length of hospital stay (8.1 (±8.2) vs. 6.1 (±6.7) days); cardiology and internal medicine/general practitioner visits; and emergency room admissions. Diabetes was an independent risk factor of major adverse cardiovascular event (MACE; HR 1.26 [95% CI, 1.04-1.52]), all-cause mortality (HR 1.28 [95% CI, 1.08-1.52]), and cardiovascular mortality (HR 1.41 [95% CI, 1.09-1.83]).CONCLUSION: In this contemporary AF cohort, diabetes was present in 1 in 4 patients and it served as an independent risk factor for reduced quality of life, greater healthcare resource utilisation and excess MACE, all-cause mortality and cardiovascular mortality. There was increased use of anticoagulation therapy in diabetes but with less rhythm control interventions.

Published
2022
Full Text
View/download PDF

3. Cardiac troponins and adverse outcomes in European patients with atrial fibrillation: A report from the ESC-EHRA EORP atrial fibrillation general long-term registry

Author

Marco Vitolo, Vincenzo L. Malavasi, Marco Proietti, Igor Diemberger, Laurent Fauchier, Francisco Marin, Michael Nabauer, Tatjana S. Potpara, Gheorghe-Andrei Dan, Zbigniew Kalarus, Luigi Tavazzi, Aldo Pietro Maggioni, Deirdre A. Lane, Gregory Y.H. Lip, Giuseppe Boriani, G. Boriani, G.Y.H. Lip, L. Tavazzi, A.P. Maggioni, G-A. Dan, T. Potpara, M. Nabauer, F. Marin, Z. Kalarus, L. Fauchier, A. Goda, G. Mairesse, T. Shalganov, L. Antoniades, M. Taborsky, S. Riahi, P. Muda, I. García Bolao, O. Piot, K. Etsadashvili, M. Haim, A. Azhari, J. Najafian, M. Santini, E. Mirrakhimov, K. Kulzida, A. Erglis, L. Poposka, M.R. Burg, H. Crijns, Ö. Erküner, D. Atar, R. Lenarczyk, M. Martins Oliveira, D. Shah, E. Serdechnaya, E. Diker, E. Zëra, U. Ekmekçiu, V. Paparisto, M. Tase, H. Gjergo, J. Dragoti, M. Ciutea, N. Ahadi, Z. el Husseini, M. Raepers, J. Leroy, P. Haushan, A. Jourdan, C. Lepiece, L. Desteghe, J. Vijgen, P. Koopman, G. Van Genechten, H. Heidbuchel, T. Boussy, M. De Coninck, H. Van Eeckhoutte, N. Bouckaert, A. Friart, J. Boreux, C. Arend, P. Evrard, L. Stefan, E. Hoffer, J. Herzet, M. Massoz, C. Celentano, M. Sprynger, L. Pierard, P. Melon, B. Van Hauwaert, C. Kuppens, D. Faes, D. Van Lier, A. Van Dorpe, A. Gerardy, O. Deceuninck, O. Xhaet, F. Dormal, E. Ballant, D. Blommaert, D. Yakova, M. Hristov, T. Yncheva, N. Stancheva, S. Tisheva, M. Tokmakova, F. Nikolov, D. Gencheva, B. Kunev, M. Stoyanov, D. Marchov, V. Gelev, V. Traykov, A. Kisheva, H. Tsvyatkov, R. Shtereva, S. Bakalska-Georgieva, S. Slavcheva, Y. Yotov, M. Kubíčková, A. Marni Joensen, A. Gammelmark, L. Hvilsted Rasmussen, P. Dinesen, S. Krogh Venø, B. Sorensen, A. Korsgaard, K. Andersen, C. Fragtrup Hellum, A. Svenningsen, O. Nyvad, P. Wiggers, O. May, A. Aarup, B. Graversen, L. Jensen, M. Andersen, M. Svejgaard, S. Vester, S. Hansen, V. Lynggaard, M. Ciudad, R. Vettus, A. Maestre, S. Castaño, S. Cheggour, J. Poulard, V. Mouquet, S. Leparrée, J. Bouet, J. Taieb, A. Doucy, H. Duquenne, A. Furber, J. Dupuis, J. Rautureau, M. Font, P. Damiano, M. Lacrimini, J. Abalea, S. Boismal, T. Menez, J. Mansourati, G. Range, H. Gorka, C. Laure, C. Vassalière, N. Elbaz, N. Lellouche, K. Djouadi, F. Roubille, D. Dietz, J. Davy, M. Granier, P. Winum, C. Leperchois-Jacquey, H. Kassim, E. Marijon, J. Le Heuzey, J. Fedida, C. Maupain, C. Himbert, E. Gandjbakhch, F. Hidden-Lucet, G. Duthoit, N. Badenco, T. Chastre, X. Waintraub, M. Oudihat, J. Lacoste, C. Stephan, H. Bader, N. Delarche, L. Giry, D. Arnaud, C. Lopez, F. Boury, I. Brunello, M. Lefèvre, R. Mingam, M. Haissaguerre, M. Le Bidan, D. Pavin, V. Le Moal, C. Leclercq, T. Beitar, I. Martel, A. Schmid, N. Sadki, C. Romeyer-Bouchard, A. Da Costa, I. Arnault, M. Boyer, C. Piat, N. Lozance, S. Nastevska, A. Doneva, B. Fortomaroska Milevska, B. Sheshoski, K. Petroska, N. Taneska, N. Bakrecheski, K. Lazarovska, S. Jovevska, V. Ristovski, A. Antovski, E. Lazarova, I. Kotlar, J. Taleski, S. Kedev, N. Zlatanovik, S. Jordanova, T. Bajraktarova Proseva, S. Doncovska, D. Maisuradze, A. Esakia, E. Sagirashvili, K. Lartsuliani, N. Natelashvili, N. Gumberidze, R. Gvenetadze, N. Gotonelia, N. Kuridze, G. Papiashvili, I. Menabde, S. Glöggler, A. Napp, C. Lebherz, H. Romero, K. Schmitz, M. Berger, M. Zink, S. Köster, J. Sachse, E. Vonderhagen, G. Soiron, K. Mischke, R. Reith, M. Schneider, W. Rieker, D. Boscher, A. Taschareck, A. Beer, D. Oster, O. Ritter, J. Adamczewski, S. Walter, A. Frommhold, E. Luckner, J. Richter, M. Schellner, S. Landgraf, S. Bartholome, R. Naumann, J. Schoeler, D. Westermeier, F. William, K. Wilhelm, M. Maerkl, R. Oekinghaus, M. Denart, M. Kriete, U. Tebbe, T. Scheibner, M. Gruber, A. Gerlach, C. Beckendorf, L. Anneken, M. Arnold, S. Lengerer, Z. Bal, C. Uecker, H. Förtsch, S. Fechner, V. Mages, E. Martens, H. Methe, T. Schmidt, B. Schaeffer, B. Hoffmann, J. Moser, K. Heitmann, S. Willems, C. Klaus, I. Lange, M. Durak, E. Esen, F. Mibach, H. Mibach, A. Utech, M. Gabelmann, R. Stumm, V. Ländle, C. Gartner, C. Goerg, N. Kaul, S. Messer, D. Burkhardt, C. Sander, R. Orthen, S. Kaes, A. Baumer, F. Dodos, A. Barth, G. Schaeffer, J. Gaertner, J. Winkler, A. Fahrig, J. Aring, I. Wenzel, S. Steiner, A. Kliesch, E. Kratz, K. Winter, P. Schneider, A. Haag, I. Mutscher, R. Bosch, J. Taggeselle, S. Meixner, A. Schnabel, A. Shamalla, H. Hötz, A. Korinth, C. Rheinert, G. Mehltretter, B. Schön, N. Schön, A. Starflinger, E. Englmann, G. Baytok, T. Laschinger, G. Ritscher, A. Gerth, D. Dechering, L. Eckardt, M. Kuhlmann, N. Proskynitopoulos, J. Brunn, K. Foth, C. Axthelm, H. Hohensee, K. Eberhard, S. Turbanisch, N. Hassler, A. Koestler, G. Stenzel, D. Kschiwan, M. Schwefer, S. Neiner, S. Hettwer, M. Haeussler-Schuchardt, R. Degenhardt, S. Sennhenn, M. Brendel, A. Stoehr, W. Widjaja, S. Loehndorf, A. Logemann, J. Hoskamp, J. Grundt, M. Block, R. Ulrych, A. Reithmeier, V. Panagopoulos, C. Martignani, D. Bernucci, E. Fantecchi, I. Diemberger, M. Ziacchi, M. Biffi, P. Cimaglia, J. Frisoni, I. Giannini, S. Boni, S. Fumagalli, S. Pupo, A. Di Chiara, P. Mirone, F. Pesce, C. Zoccali, V.L. Malavasi, A. Mussagaliyeva, B. Ahyt, Z. Salihova, K. Koshum-Bayeva, A. Kerimkulova, A. Bairamukova, B. Lurina, R. Zuzans, S. Jegere, I. Mintale, K. Kupics, K. Jubele, O. Kalejs, K. Vanhear, M. Burg, M. Cachia, E. Abela, S. Warwicker, T. Tabone, R. Xuereb, D. Asanovic, D. Drakalovic, M. Vukmirovic, N. Pavlovic, L. Music, N. Bulatovic, A. Boskovic, H. Uiterwaal, N. Bijsterveld, J. De Groot, J. Neefs, N. van den Berg, F. Piersma, A. Wilde, V. Hagens, J. Van Es, J. Van Opstal, B. Van Rennes, H. Verheij, W. Breukers, G. Tjeerdsma, R. Nijmeijer, D. Wegink, R. Binnema, S. Said, S. Philippens, W. van Doorn, T. Szili-Torok, R. Bhagwandien, P. Janse, A. Muskens, M. van Eck, R. Gevers, N. van der Ven, A. Duygun, B. Rahel, J. Meeder, A. Vold, C. Holst Hansen, I. Engset, B. Dyduch-Fejklowicz, E. Koba, M. Cichocka, A. Sokal, A. Kubicius, E. Pruchniewicz, A. Kowalik-Sztylc, W. Czapla, I. Mróz, M. Kozlowski, T. Pawlowski, M. Tendera, A. Winiarska-Filipek, A. Fidyk, A. Slowikowski, M. Haberka, M. Lachor-Broda, M. Biedron, Z. Gasior, M. Kołodziej, M. Janion, I. Gorczyca-Michta, B. Wozakowska-Kaplon, M. Stasiak, P. Jakubowski, T. Ciurus, J. Drozdz, M. Simiera, P. Zajac, T. Wcislo, P. Zycinski, J. Kasprzak, A. Olejnik, E. Harc-Dyl, J. Miarka, M. Pasieka, M. Ziemińska-Łuć, W. Bujak, A. Śliwiński, A. Grech, J. Morka, K. Petrykowska, M. Prasał, G. Hordyński, P. Feusette, P. Lipski, A. Wester, W. Streb, J. Romanek, P. Woźniak, M. Chlebuś, P. Szafarz, W. Stanik, M. Zakrzewski, J. Kaźmierczak, A. Przybylska, E. Skorek, H. Błaszczyk, M. Stępień, S. Szabowski, W. Krysiak, M. Szymańska, J. Karasiński, J. Blicharz, M. Skura, K. Hałas, L. Michalczyk, Z. Orski, K. Krzyżanowski, A. Skrobowski, L. Zieliński, M. Tomaszewska-Kiecana, M. Dłużniewski, M. Kiliszek, M. Peller, M. Budnik, P. Balsam, G. Opolski, A. Tymińska, K. Ozierański, A. Wancerz, A. Borowiec, E. Majos, R. Dabrowski, H. Szwed, A. Musialik-Lydka, A. Leopold-Jadczyk, E. Jedrzejczyk-Patej, M. Koziel, M. Mazurek, K. Krzemien-Wolska, P. Starosta, E. Nowalany-Kozielska, A. Orzechowska, M. Szpot, M. Staszel, S. Almeida, H. Pereira, L. Brandão Alves, R. Miranda, L. Ribeiro, F. Costa, F. Morgado, P. Carmo, P. Galvao Santos, R. Bernardo, P. Adragão, G. Ferreira da Silva, M. Peres, M. Alves, M. Leal, A. Cordeiro, P. Magalhães, P. Fontes, S. Leão, A. Delgado, A. Costa, B. Marmelo, B. Rodrigues, D. Moreira, J. Santos, L. Santos, A. Terchet, D. Darabantiu, S. Mercea, V. Turcin Halka, A. Pop Moldovan, A. Gabor, B. Doka, G. Catanescu, H. Rus, L. Oboroceanu, E. Bobescu, R. Popescu, A. Dan, A. Buzea, I. Daha, G. Dan, I. Neuhoff, M. Baluta, R. Ploesteanu, N. Dumitrache, M. Vintila, A. Daraban, C. Japie, E. Badila, H. Tewelde, M. Hostiuc, S. Frunza, E. Tintea, D. Bartos, A. Ciobanu, I. Popescu, N. Toma, C. Gherghinescu, D. Cretu, N. Patrascu, C. Stoicescu, C. Udroiu, G. Bicescu, V. Vintila, D. Vinereanu, M. Cinteza, R. Rimbas, M. Grecu, A. Cozma, F. Boros, M. Ille, O. Tica, R. Tor, A. Corina, A. Jeewooth, B. Maria, C. Georgiana, C. Natalia, D. Alin, D. Dinu-Andrei, M. Livia, R. Daniela, R. Larisa, S. Umaar, T. Tamara, M. Ioachim Popescu, D. Nistor, I. Sus, O. Coborosanu, N. Alina-Ramona, R. Dan, L. Petrescu, G. Ionescu, C. Vacarescu, E. Goanta, M. Mangea, A. Ionac, C. Mornos, D. Cozma, S. Pescariu, E. Solodovnicova, I. Soldatova, J. Shutova, L. Tjuleneva, T. Zubova, V. Uskov, D. Obukhov, G. Rusanova, N. Isakova, S. Odinsova, T. Arhipova, E. Kazakevich, O. Zavyalova, T. Novikova, I. Riabaia, S. Zhigalov, E. Drozdova, I. Luchkina, Y. Monogarova, D. Hegya, L. Rodionova, V. Nevzorova, O. Lusanova, A. Arandjelovic, D. Toncev, L. Vukmirovic, M. Radisavljevic, M. Milanov, N. Sekularac, M. Zdravkovic, S. Hinic, S. Dimkovic, T. Acimovic, J. Saric, S. Radovanovic, A. Kocijancic, B. Obrenovic-Kircanski, D. Kalimanovska Ostric, D. Simic, I. Jovanovic, I. Petrovic, M. Polovina, M. Vukicevic, M. Tomasevic, N. Mujovic, N. Radivojevic, O. Petrovic, S. Aleksandric, V. Kovacevic, Z. Mijatovic, B. Ivanovic, M. Tesic, A. Ristic, B. Vujisic-Tesic, M. Nedeljkovic, A. Karadzic, A. Uscumlic, M. Prodanovic, M. Zlatar, M. Asanin, B. Bisenic, V. Vasic, Z. Popovic, D. Djikic, M. Sipic, V. Peric, B. Dejanovic, N. Milosevic, S. Backovic, A. Stevanovic, A. Andric, B. Pencic, M. Pavlovic-Kleut, V. Celic, M. Pavlovic, M. Petrovic, M. Vuleta, N. Petrovic, S. Simovic, Z. Savovic, S. Milanov, G. Davidovic, V. Iric-Cupic, D. Djordjevic, M. Damjanovic, S. Zdravkovic, V. Topic, D. Stanojevic, M. Randjelovic, R. Jankovic-Tomasevic, V. Atanaskovic, S. Antic, D. Simonovic, M. Stojanovic, S. Stojanovic, V. Mitic, V. Ilic, D. Petrovic, M. Deljanin Ilic, S. Ilic, V. Stoickov, S. Markovic, A. Mijatovic, D. Tanasic, G. Radakovic, J. Peranovic, N. Panic-Jelic, O. Vujadinovic, P. Pajic, S. Bekic, S. Kovacevic, A. García Fernandez, A. Perez Cabeza, M. Anguita, L. Tercedor Sanchez, E. Mau, J. Loayssa, M. Ayarra, M. Carpintero, I. Roldán Rabadan, M. Gil Ortega, A. Tello Montoliu, E. Orenes Piñero, S. Manzano Fernández, F. Marín, A. Romero Aniorte, A. Veliz Martínez, M. Quintana Giner, G. Ballesteros, M. Palacio, O. Alcalde, I. García-Bolao, V. Bertomeu Gonzalez, F. Otero-Raviña, J. García Seara, J. Gonzalez Juanatey, N. Dayal, P. Maziarski, P. Gentil-Baron, M. Koç, E. Onrat, I.E. Dural, K. Yilmaz, B. Özin, S. Tan Kurklu, Y. Atmaca, U. Canpolat, L. Tokgozoglu, A.K. Dolu, B. Demirtas, D. Sahin, O. Ozcan Celebi, G. Gagirci, U.O. Turk, H. Ari, N. Polat, N. Toprak, M. Sucu, O. Akin Serdar, A. Taha Alper, A. Kepez, Y. Yuksel, A. Uzunselvi, S. Yuksel, M. Sahin, O. Kayapinar, T. Ozcan, H. Kaya, M.B. Yilmaz, M. Kutlu, M. Demir, C. Gibbs, S. Kaminskiene, M. Bryce, A. Skinner, G. Belcher, J. Hunt, L. Stancombe, B. Holbrook, C. Peters, S. Tettersell, A. Shantsila, D. Lane, K. Senoo, M. Proietti, K. Russell, P. Domingos, S. Hussain, J. Partridge, R. Haynes, S. Bahadur, R. Brown, S. McMahon, J. McDonald, K. Balachandran, R. Singh, S. Garg, H. Desai, K. Davies, W. Goddard, G. Galasko, I. Rahman, Y. Chua, O. Payne, S. Preston, O. Brennan, L. Pedley, C. Whiteside, C. Dickinson, J. Brown, K. Jones, L. Benham, R. Brady, L. Buchanan, A. Ashton, H. Crowther, H. Fairlamb, S. Thornthwaite, C. Relph, A. McSkeane, U. Poultney, N. Kelsall, P. Rice, T. Wilson, M. Wrigley, R. Kaba, T. Patel, E. Young, J. Law, C. Runnett, H. Thomas, H. McKie, J. Fuller, S. Pick, A. Sharp, A. Hunt, K. Thorpe, C. Hardman, E. Cusack, L. Adams, M. Hough, S. Keenan, A. Bowring, J. Watts, J. Zaman, K. Goffin, H. Nutt, Y. Beerachee, J. Featherstone, C. Mills, J. Pearson, L. Stephenson, S. Grant, A. Wilson, C. Hawksworth, I. Alam, M. Robinson, S. Ryan, R. Egdell, E. Gibson, M. Holland, D. Leonard, B. Mishra, S. Ahmad, H. Randall, J. Hill, L. Reid, M. George, S. McKinley, L. Brockway, W. Milligan, J. Sobolewska, J. Muir, L. Tuckis, L. Winstanley, P. Jacob, S. Kaye, L. Morby, A. Jan, T. Sewell, C. Boos, B. Wadams, C. Cope, P. Jefferey, N. Andrews, A. Getty, A. Suttling, C. Turner, K. Hudson, R. Austin, S. Howe, R. Iqbal, N. Gandhi, K. Brophy, P. Mirza, E. Willard, S. Collins, N. Ndlovu, E. Subkovas, V. Karthikeyan, L. Waggett, A. Wood, A. Bolger, J. Stockport, L. Evans, E. Harman, J. Starling, L. Williams, V. Saul, M. Sinha, L. Bell, S. Tudgay, S. Kemp, L. Frost, T. Ingram, A. Loughlin, C. Adams, M. Adams, F. Hurford, C. Owen, C. Miller, D. Donaldson, H. Tivenan, H. Button, A. Nasser, O. Jhagra, B. Stidolph, C. Brown, C. Livingstone, M. Duffy, P. Madgwick, P. Roberts, E. Greenwood, L. Fletcher, M. Beveridge, S. Earles, D. McKenzie, D. Beacock, M. Dayer, M. Seddon, D. Greenwell, F. Luxton, F. Venn, H. Mills, J. Rewbury, K. James, K. Roberts, L. Tonks, D. Felmeden, W. Taggu, A. Summerhayes, D. Hughes, J. Sutton, L. Felmeden, M. Khan, E. Walker, L. Norris, L. O'Donohoe, A. Mozid, H. Dymond, H. Lloyd-Jones, G. Saunders, D. Simmons, D. Coles, D. Cotterill, S. Beech, S. Kidd, B. Wrigley, S. Petkar, A. Smallwood, R. Jones, E. Radford, S. Milgate, S. Metherell, V. Cottam, C. Buckley, A. Broadley, D. Wood, J. Allison, K. Rennie, L. Balian, L. Howard, L. Pippard, S. Board, and T. Pitt-Kerby

Subjects
Male, AF registry, Atrial fibrillation, Biomarkers, Death, Major adverse cardiovascular events, outcomes, Troponins, Troponin, Risk Factors, Atrial Fibrillation, Internal Medicine, Humans, Female, Prospective Studies, Registries, Aged
Abstract

BACKGROUND: Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear.AIM: To assess the factors associated with cTn testing in routine practice and evaluate the association with outcomes.METHODS: Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into 3 groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism /any acute coronary syndrome/cardiovascular (CV) death, defined as Major Adverse Cardiovascular Events (MACE) and all-cause death were the main endpoints.RESULTS: Among 10 445 AF patients (median age 71 years, 40.3% females) cTn were tested in 2834 (27.1%). cTn was elevated in 904/2834 (31.9%) and in-range in 1930/2834 (68.1%) patients. Female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease, and atypical AF symptoms were independently associated with cTn testing. Elevated cTn were independently associated with a higher risk for MACE (Model 1, hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.40-2.16, Model 2, HR 1.62, 95% CI 1.28-2.05; Model 3 HR 1.76, 95% CI 1.37-2.26) and all-cause death (Model 1, HR 1.45, 95% CI 1.21-1.74; Model 2, HR 1.36, 95% CI 1.12-1.66; Model 3, HR 1.38, 95% CI 1.12-1.71).CONCLUSIONS: Elevated cTn levels were associated with an increased risk of all-cause mortality and adverse CV events. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

Published
2022
Full Text
View/download PDF

4. Management of dyslipidaemia in patients with coronary heart disease: Results from the ESC-EORP EUROASPIRE V survey in 27 countries

Author

De Backer, Guy Jankowski, Piotr Kotseva, Kornelia and Mirrakhimov, Erkin Reiner, Zeljko Ryden, Lars Tokgozoglu, Lale Wood, David De Bacquer, Dirk Abreu, A. Aguiar, C. and Badariene, J. Bruthans, J. Castro Conde, A. Cifkova, R. and Crowley, J. Davletov, K. De Smedt, D. De Sutter, J. and Deckers, J. W. Dilic, M. Dolzhenko, M. Druais, H. and Dzerve, V. Erglis, A. Fras, Z. Gaita, D. Gotcheva, N. and Grobbee, D. E. Gyberg, V. Ali, H. Hasan Heuschmann, P. and Hoes, A. W. Lalic, N. Lehto, S. Lovic, D. Maggioni, A. P. Mancas, S. Marques-Vidal, P. Mellbin, L. Milicic, D. Oganov, R. Pogosova, N. Stagmo, M. Stoerk, S. and Sundvall, J. Tsioufis, K. Vulic, D. Wood, D. A. and Jennings, C. Adamska, A. Adamska, S. Mellbin, L. and Tuomilehto, J. Schnell, O. Fiorucci, E. Glemot, M. and Larras, F. Missiamenou, V. Maggioni, A. Taylor, C. and Ferreira, T. Lemaitre, K. Raman, L. Sundvall, J. and DeSmedt, D. De Sutter, J. Willems, A. M. De Pauw, M. and Vervaet, P. Bollen, J. Dekimpe, E. Mommen, N. Van Genechten, G. Dendale, P. Bouvier, C. A. Chenu, P. and Huyberechts, D. Persu, A. Dilic, M. Begic, A. Nalbantic, A. Durak Dzubur, A. Hadzibegic, N. Iglica, A. Kapidjic, S. Bico, A. Osmanagic Resic, N. Bajramovic, N. Sabanovic and Zvizdic, F. Vulic, D. Kovacevic-Preradovic, T. and Popovic-Pejicic, S. Djekic, D. Gnjatic, T. Knezevic, T. and Kovacevic-Preradovic, T. Kos, Lj Popovic-Pejicic, S. and Stanetic, B. Topic, G. Gotcheva, N. Georgiev, Borislav and Terziev, A. Vladimirov, G. Angelov, A. Kanazirev, B. and Nikolaeva, S. Tonkova, D. Vetkova, M. Milicic, D. and Bosnic, A. Dubravcic, M. Glavina, M. Mance, M. and Pavasovic, S. Samardzic, J. Batinic, T. Crljenko, K. and Delic-Brkljacic, D. Dula, K. Golubic, K. Klobucar, I. and Kordic, K. Kos, N. Nedic, M. Olujic, D. Sedinic, V. and Blazevic, T. Pasalic, A. Percic, M. Sikic, J. Bruthans, J. Cifkova, R. Hasplova, K. Sulc, P. Wohlfahrt, P. and Mayer, Jr., O. Cvicela, M. Filipovsky, J. Gelzinsky, J. and Hronova, M. Hasan-Ali, H. Bakery, S. Mosad, E. Hamed, H. B. Ibrahim, A. Elsharef, M. A. Kholef, E. F. Shehata, A. and Youssef, M. Elhefny, E. Farid, H. Moustafa, T. M. and Sobieh, M. S. Kabil, H. Abdelmordy, A. Lehto, S. and Kiljander, E. Kiljander, P. Koukkunen, H. Mustonen, J. and Cremer, C. Frantz, S. Haupt, A. Hofmann, U. Ludwig, K. and Melnyk, H. Noutsias, M. Karmann, W. Prondzinsky, R. and Herdeg, C. Hoevelborn, T. Daaboul, A. Geisler, T. and Keller, T. Sauerbrunn, D. Walz-Ayed, M. Ertl, G. Leyh, R. Stoerk, S. Heuschmann, P. Ehlert, T. Klocke, B. and Krapp, J. Ludwig, T. Kaes, J. Starke, C. Ungethuem, K. and Wagner, M. Wiedmann, S. Tsioufis, K. Tolis, P. and Vogiatzi, G. Sanidas, E. Tsakalis, K. Kanakakis, J. and Koutsoukis, A. Vasileiadis, K. Zarifis, J. Karvounis, C. and Crowley, J. Gibson, I. Houlihan, A. Kelly, C. O'Donnell, M. Bennati, M. Cosmi, F. Mariottoni, B. Morganti, M. and Cherubini, A. Di Lenarda, A. Radini, D. Ramani, F. and Francese, M. G. Gulizia, M. M. Pericone, D. Davletov, K. and Aigerim, K. Bekbolat, Z. Amirov, B. Assembekov, B. and Chernokurova, E. Ibragimova, F. Kodasbayev, A. Markova, A. and Asanbaev, A. Toktomamatov, U. Tursunbaev, M. Zakirov, U. and Abilova, S. Arapova, R. Bektasheva, E. Esenbekova, J. and Neronova, K. Asanbaev, A. Baigaziev, K. Toktomamatov, U. and Zakirov, U. Baitova, G. Zheenbekov, T. Erglis, A. and Andrejeva, T. Bajare, I. Kucika, G. Labuce, A. Putane, L. Stabulniece, M. Dzerve, V. Klavins, E. Sime, I. and Badariene, J. Gedvilaite, L. Peciuraite, D. Sileikiene, V. and Skiauteryte, E. Solovjova, S. Sidabraite, R. Briedis, K. and Ceponiene, I. Jurenas, M. Kersulis, J. Martinkute, G. and Vaitiekiene, A. Vasiljevaite, K. Veisaite, R. Plisiene, J. Siurkaite, V. Vaiciulis, Z. Czarnecka, D. Koziel, P. and Podolec, P. Nessler, J. Gomula, P. Mirek-Bryniarska, E. and Bogacki, P. Wisniewski, A. Pajak, A. Wolfshaut-Wolak, R. and Bucko, J. Kaminski, K. Lapinska, M. Paniczko, M. and Raczkowski, A. Sawicka, E. Stachurska, Z. Szpakowicz, M. and Musial, W. Dobrzycki, S. Bychowski, J. Kosior, D. A. and Krzykwa, A. Setny, M. Kosior, D. A. Rak, A. Gasior, Z. and Haberka, M. Gasior, Z. Haberka, M. Szostak-Janiak, K. and Finik, M. Liszka, J. Botelho, A. Cachulo, M. Sousa, J. Pais, A. Aguiar, C. Durazzo, A. Matos, D. and Gouveia, R. Rodrigues, G. Strong, C. Guerreiro, R. and Aguiar, J. Abreu, A. Cruz, M. Daniel, P. Morais, L. and Moreira, R. Rosa, S. Rodrigues, I. Selas, M. Gaita, D. and Mancas, S. Apostu, A. Cosor, O. Gaita, L. Giurgiu, L. Hudrea, C. Maximov, D. Moldovan, B. Mosteoru, S. and Pleava, R. Ionescu, M. Parepa, I. Pogosova, N. and Arutyunov, A. Ausheva, A. Isakova, S. Karpova, A. and Salbieva, A. Sokolova, O. Vasilevsky, A. Pozdnyakov, Y. and Antropova, O. Borisova, L. Osipova, I. Lovic, D. and Aleksic, M. Crnokrak, B. Djokic, J. Hinic, S. Vukasin, T. Zdravkovic, M. Lalic, N. M. Jotic, A. Lalic, K. and Lukic, L. Milicic, T. Macesic, M. Gajovic, J. Stanarcic and Stoiljkovic, M. Djordjevic, D. Kostic, S. Tasic, I. and Vukovic, A. Fras, Z. Jug, B. Juhant, A. Krt, A. and Kugonjic, U. Chipayo Gonzales, D. Gomez Barrado, J. J. and Kounka, Z. Marcos Gomez, G. Mogollon Jimenez, M. V. Ortiz Cortes, C. Perez Espejo, P. Porras Ramos, Y. Colman, R. and Delgado, J. Otero, E. Perez, A. Fernandez-Olmo, M. R. and Torres-LLergo, J. Vasco, C. Barrenada, E. Botas, J. and Campuzano, R. Gonzalez, Y. Rodrigo, M. de Pablo, C. and Velasco, E. Hernandez, S. Lozano, C. Gonzalez, P. and Castro, A. Dalmau, R. Hernandez, D. Irazusta, F. J. and Velez, A. Vindel, C. Gomez-Doblas, J. J. Garcia Ruiz, V. and Gomez, L. Gomez Garcia, M. Jimenez-Navarro, M. Molina Ramos, A. Marzal, D. Martinez, G. Lavado, R. Vidal, A. and Bostrom-Nilsson, V. Kjellstrom, B. Shahim, B. Smetana, S. and Hansen, O. Stensgaard-Nake, E. Deckers, J. W. Klijn, A. J. Mangus, T. J. P. Peters, R. J. G. Reimer, W. Scholte Op and Snaterse, M. Aydogdu, S. Erol, C. Oturk, S. Kaya, C. Tulunay Ahmetoglu, Y. Ergene, O. Akdeniz, B. Cirgamis, D. Kultursay, S. Akkoyun H. Kayikcioglu, M. Catakoglu, A. B. and Cengel, A. Kocak, A. A. Agirbasli, M. A. Aciksari, G. and Cekin, M. E. Kaya, E. B. Kocyigit, D. Ongen, Z. and Ozmen, E. Sansoy, V. Kaya, A. Oktay, V. Temizhan, A. and Unal, S. Yakut, I. Kalkan, A. K. Bozkurt, E. Kasapkara, H. A. Dolzhenko, M. Faradzh, C. Hrubyak, L. Konoplianyk, L. Kozhuharyova, N. Lobach, L. Nesukai, V. Nudchenko, O. and Simagina, T. Yakovenko, L. Azarenko, V. Potabashny, V. and Bazylevych, A. Bazylevych, M. Kaminska, K. Panchenko, L. and Shershnyova, O. Ovrakh, T. Serik, S. Kolesnik, T. and Kosova, H. Adamska, A. Adamska, S. Jennings, C. Atkin, A. Hoye P. Fellowes, D. Lindsay, S. Atkinson, C. and Kranilla, C. Vinod, M. Beerachee, Y. Bennett, C. Broome, M. Bwalya, A. Caygill, Lindsay Dinning, L. Gillespie, A. and Goodfellow, R. Guy, J. Idress, T. Mills, C. Morgan, C. Oustance, N. Singh, N. Yare, M. Jagoda, J. M. and Bowyer, H. Christenssen, V. Groves, A. Jan, A. Riaz, A. and Gill, M. Sewell, T. A. Gorog, D. Baker, M. De Sousa, P. Mazenenga, T. Porter, J. Haines, F. Peachey, T. and Taaffe, J. Wells, K. Ripley, D. P. Forward, H. McKie, H. and Pick, S. L. Thomas, H. E. Batin, P. D. Exley, D. and Rank, T. Wright, J. Kardos, A. Sutherland, S. -B. Wren, L. Leeson, P. Barker, D. Moreby, B. Sawyer, J. and Stirrup, J. Brunton, M. Brodison, A. Craig, J. Peters, S. Kaprielian, R. Bucaj, A. Mahay, K. Oblak, M. and Gale, C. Pye, M. McGill, Y. Redfearn, H. Fearnley, M. and EUROASPIRE V Collaborators Writing Comm Sci Steering Executive Comm Coordinating Ctr Diabet Ctr Data Management Ctr Stat Anal Ctr Cent Lab Study Ctr Org Investigators Other

Abstract

Background and aims: One of the objectives of the ESC-EORP EUROASPIRE V survey is to determine how well European guidelines on the management of dyslipidaemias are implemented in coronary patients. Methods: Standardized methods were used by trained technicians to collect information on 7824 patients from 130 centers in 27 countries, from the medical records and at a visit at least 6 months after hospitalization for a coronary event. All lipid measurements were performed in one central laboratory. Patients were divided into three groups: on high-intensity LDL-C-lowering-drug therapy (LLT), on low or moderate-intensity LLT and on no LLT. Results: At the time of the visit, almost half of the patients were on a high-intensity LLT. Between hospital discharge and the visit, LLT had been reduced in intensity or interrupted in 20.8% of the patients and had been started or increased in intensity in 11.7%. In those who had interrupted LLT or had reduced the intensity, intolerance to LLT and the advice of their physician were reported as the reason why in 15.8 and 36.8% of the cases, respectively. LDL-C control was better in those on a high-intensity LLT compared to those on low or moderate intensity LLT. LDL-C control was better in men than women and in patients with self-reported diabetes. Conclusions: The results of the EUROASPIRE V survey show that most coronary patients have a less than optimal management of LDL-C. More professional strategies are needed, aiming at lifestyle changes and LLT adapted to the need of the individual patient.

Published
2019

5. Management of dyslipidaemia in patients with coronary heart disease : results from the ESC-EORP EUROASPIRE V survey in 27 countries

Author

Guy De Backer, Piotr Jankowski, Kornelia Kotseva, Erkin Mirrakhimov, Željko Reiner, Lars Rydén, Lale Tokgözoğlu, David Wood, Dirk De Bacquer, G. De Backer, P. Jankowski, K. Kotseva, E. Mirrakhimov, Z. Reiner, L. Rydén, L. Tokgözoğlu, D. Wood, D. De Bacquer, A. Abreu, C. Aguiar, J. Badariene, J. Bruthans, A. Castro Conde, R. Cifkova, J. Crowley, K. Davletov, D. De Smedt, J. De Sutter, J.W. Deckers, M. Dilic, M. Dolzhenko, H. Druais, V. Dzerve, A. Erglis, Z. Fras, D. Gaita, N. Gotcheva, D.E. Grobbee, V. Gyberg, H. Hasan Ali, P. Heuschmann, A.W. Hoes, N. Lalic, S. Lehto, D. Lovic, A.P. Maggioni, S. Mancas, P. Marques-Vidal, L. Mellbin, D. Miličić, R. Oganov, N. Pogosova, Ž. Reiner, M. Stagmo, S. Störk, J. Sundvall, K. Tsioufis, D. Vulic, D.A. Wood, C. Jennings, A. Adamska, S. Adamska, J. Tuomilehto, O. Schnell, E. Fiorucci, M. Glemot, F. Larras, V. Missiamenou, A. Maggioni, C. Taylor, T. Ferreira, K. Lemaitre, L. Raman, D. DeSmedt, A.M. Willems, M. De Pauw, P. Vervaet, J. Bollen, E. Dekimpe, N. Mommen, G. Van Genechten, P. Dendale, C.A. Bouvier, P. Chenu, D. Huyberechts, A. Persu, A. Begic, A. Durak Nalbantic, A. Dzubur, N. Hadzibegic, A. Iglica, S. Kapidjic, A. Osmanagic Bico, N. Resic, N. Sabanovic Bajramovic, F. Zvizdic, T. Kovacevic-Preradovic, S. Popovic-Pejicic, D. Djekic, T. Gnjatic, T. Knezevic, Lj Kos, B. Stanetic, G. Topic, Borislav Georgiev, A. Terziev, G. Vladimirov, A. Angelov, B. Kanazirev, S. Nikolaeva, D. Tonkova, M. Vetkova, D. Milicic, A. Bosnic, M. Dubravcic, M. Glavina, M. Mance, S. Pavasovic, J. Samardzic, T. Batinic, K. Crljenko, D. Delic-Brkljacic, K. Dula, K. Golubic, I. Klobucar, K. Kordic, N. Kos, M. Nedic, D. Olujic, V. Sedinic, T. Blazevic, A. Pasalic, M. Percic, J. Sikic, R. Cífková, K. Hašplová, P. Šulc, P. Wohlfahrt, O. Mayer, M. Cvíčela, J. Filipovský, J. Gelžinský, M. Hronová, H. Hasan-Ali, S. Bakery, E. Mosad, H.B. Hamed, A. Ibrahim, M.A. Elsharef, E.F. Kholef, A. Shehata, M. Youssef, E. Elhefny, H. Farid, T.M. Moustafa, M.S. Sobieh, H. Kabil, A. Abdelmordy, E. Kiljander, P. Kiljander, H. Koukkunen, J. Mustonen, C. Cremer, S. Frantz, A. Haupt, U. Hofmann, K. Ludwig, H. Melnyk, M. Noutsias, W. Karmann, R. Prondzinsky, C. Herdeg, T. Hövelborn, A. Daaboul, T. Geisler, T. Keller, D. Sauerbrunn, M. Walz-Ayed, G. Ertl, R. Leyh, T. Ehlert, B. Klocke, J. Krapp, T. Ludwig, J. Käs, C. Starke, K. Ungethüm, M. Wagner, S. Wiedmann, P. Tolis, G. Vogiatzi, E. Sanidas, K. Tsakalis, J. Kanakakis, A. Koutsoukis, K. Vasileiadis, J. Zarifis, C. Karvounis, I. Gibson, A. Houlihan, C. Kelly, M. O'Donnell, M. Bennati, F. Cosmi, B. Mariottoni, M. Morganti, A. Cherubini, A. Di Lenarda, D. Radini, F. Ramani, M.G. Francese, M.M. Gulizia, D. Pericone, K. Aigerim, B. Zholdin, B. Amirov, B. Assembekov, E. Chernokurova, F. Ibragimova, A. Kodasbayev, A. Markova, A. Asanbaev, U. Toktomamatov, M. Tursunbaev, U. Zakirov, S. Abilova, R. Arapova, E. Bektasheva, J. Esenbekova, K. Neronova, K. Baigaziev, G. Baitova, T. Zheenbekov, T. Andrejeva, I. Bajare, G. Kucika, A. Labuce, L. Putane, M. Stabulniece, E. Klavins, I. Sime, L. Gedvilaite, D. Pečiuraite, V. Sileikienė, E. Skiauteryte, S. Solovjova, R. Sidabraite, K. Briedis, I. Ceponiene, M. Jurenas, J. Kersulis, G. Martinkute, A. Vaitiekiene, K. Vasiljevaite, R. Veisaite, J. Plisienė, V. Šiurkaitė, Ž. Vaičiulis, D. Czarnecka, P. Kozieł, P. Podolec, J. Nessler, P. Gomuła, E. Mirek-Bryniarska, P. Bogacki, A. Wiśniewski, A. Pająk, R. Wolfshaut-Wolak, J. Bućko, K. Kamiński, M. Łapińska, M. Paniczko, A. Raczkowski, E. Sawicka, Z. Stachurska, M. Szpakowicz, W. Musiał, S. Dobrzycki, J. Bychowski, D.A. Kosior, A. Krzykwa, M. Setny, A. Rak, Z. Gąsior, M. Haberka, K. Szostak-Janiak, M. Finik, J. Liszka, A. Botelho, M. Cachulo, J. Sousa, A. Pais, A. Durazzo, D. Matos, R. Gouveia, G. Rodrigues, C. Strong, R. Guerreiro, J. Aguiar, M. Cruz, P. Daniel, L. Morais, R. Moreira, S. Rosa, I. Rodrigues, M. Selas, A. Apostu, O. Cosor, L. Gaita, L. Giurgiu, C. Hudrea, D. Maximov, B. Moldovan, S. Mosteoru, R. Pleava, M. Ionescu, I. Parepa, A. Arutyunov, A. Ausheva, S. Isakova, A. Karpova, A. Salbieva, O. Sokolova, A. Vasilevsky, Y. Pozdnyakov, O. Antropova, L. Borisova, I. Osipova, M. Aleksic, B. Crnokrak, J. Djokic, S. Hinic, T. Vukasin, M. Zdravkovic, N.M. Lalic, A. Jotic, K. Lalic, L. Lukic, T. Milicic, M. Macesic, J. Stanarcic Gajovic, M. Stoiljkovic, D. Djordjevic, S. Kostic, I. Tasic, A. Vukovic, B. Jug, A. Juhant, A. Krt, U. Kugonjič, D. Chipayo Gonzales, J.J. Gómez Barrado, Z. Kounka, G. Marcos Gómez, M.V. Mogollón Jiménez, C. Ortiz Cortés, P. Perez Espejo, Y. Porras Ramos, R. Colman, J. Delgado, E. Otero, A. Pérez, M.R. Fernández-Olmo, J. Torres-LLergo, C. Vasco, E. Barreñada, J. Botas, R. Campuzano, Y. González, M. Rodrigo, C. de Pablo, E. Velasco, S. Hernández, C. Lozano, P. González, A. Castro, R. Dalmau, D. Hernández, F.J. Irazusta, A. Vélez, C. Vindel, J.J. Gómez-Doblas, V. García Ruíz, L. Gómez, M Gómez García, M. Jiménez-Navarro, A. Molina Ramos, D. Marzal, G. Martínez, R. Lavado, A. Vidal, V. Boström-Nilsson, B. Kjellström, B. Shahim, S. Smetana, O. Hansen, E. Stensgaard-Nake, A.J. Klijn, T.J.P. Mangus, R.J.G. Peters, W. Scholte op Reimer, M. Snaterse, S. Aydoğdu, null Ç Erol, S. Otürk, C. Tulunay Kaya, Y. Ahmetoğlu, O. Ergene, B. Akdeniz, D. Çırgamış, S. Akkoyun H Kültürsay, M. Kayıkçıoğlu, A.B. Çatakoğlu, A. Çengel, A.A. Koçak, M.A. Ağırbaşlı, G. Açıksarı, M.E. Çekin, E.B. Kaya, D. Koçyiğit, Z. Öngen, E. Özmen, V. Sansoy, A. Kaya, V. Oktay, A. Temizhan, S. Ünal, null İ Yakut, A.K. Kalkan, E. Bozkurt, H.A. Kasapkara, C. Faradzh, L. Hrubyak, L. Konoplianyk, N. Kozhuharyova, L. Lobach, V. Nesukai, O. Nudchenko, T. Simagina, L. Yakovenko, V. Azarenko, V. Potabashny, A. Bazylevych, M. Bazylevych, K. Kaminska, L. Panchenko, O. Shershnyova, T. Ovrakh, S. Serik, T. Kolesnik, H. Kosova, A. Hoye P Atkin, D. Fellowes, S. Lindsay, C. Atkinson, C. Kranilla, M. Vinod, Y. Beerachee, C. Bennett, M. Broome, A. Bwalya, Lindsay Caygill, L. Dinning, A. Gillespie, R. Goodfellow, J. Guy, T. Idress, C. Mills, C. Morgan, N. Oustance, N. Singh, M. Yare, J.M. Jagoda, H. Bowyer, V. Christenssen, A. Groves, A. Jan, A. Riaz, M. Gill, T.A. Sewell, D. Gorog, M. Baker, P. De Sousa, T. Mazenenga, J. Porter, F. Haines, T. Peachey, J. Taaffe, K. Wells, D.P. Ripley, H. Forward, H. McKie, S.L. Pick, H.E. Thomas, P.D. Batin, D. Exley, T. Rank, J. Wright, A. Kardos, S.-B. Sutherland, L. Wren, P. Leeson, D. Barker, B. Moreby, J. Sawyer, J. Stirrup, M. Brunton, A. Brodison, J. Craig, S. Peters, R. Kaprielian, A. Bucaj, K. Mahay, M. Oblak, C. Gale, M. Pye, Y. McGill, H. Redfearn, M. Fearnley, Cardiology, ACS - Atherosclerosis & ischemic syndromes, Graduate School, ACS - Heart failure & arrhythmias, Ege Üniversitesi, and Erasmus MC other

Subjects
0301 basic medicine, Male, medicine.medical_specialty, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, Dyslipidaemia, Coronary Disease, 030204 cardiovascular system & hematology, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, LDL-Cholesterol, Diabetes mellitus, Hospital discharge, Medicine, Humans, In patient, EUROASPIRE, Coronary heart disease, Lipid lowering therapy, Secondary prevention, Aged, Dyslipidemias, Coronary event, business.industry, Medical record, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, Anticholesteremic Agents, Cholesterol, LDL, Middle Aged, medicine.disease, Optimal management, Europe, 030104 developmental biology, Health Care Surveys, Emergency medicine, Female, Guideline Adherence, business, Cardiology and Cardiovascular Medicine
Abstract

WOS: 000468732700018, PubMed ID: 31054483, Background and aims: One of the objectives of the ESC-EORP EUROASPIRE V survey is to determine how well European guidelines on the management of dyslipidaemias are implemented in coronary patients. Methods: Standardized methods were used by trained technicians to collect information on 7824 patients from 130 centers in 27 countries, from the medical records and at a visit at least 6 months after hospitalization for a coronary event. All lipid measurements were performed in one central laboratory. Patients were divided into three groups: on high-intensity LDL-C-lowering-drug therapy (LLT), on low or moderate-intensity LLT and on no LLT. Results: At the time of the visit, almost half of the patients were on a high-intensity LLT. Between hospital discharge and the visit, LLT had been reduced in intensity or interrupted in 20.8% of the patients and had been started or increased in intensity in 11.7%. In those who had interrupted LLT or had reduced the intensity, intolerance to LLT and the advice of their physician were reported as the reason why in 15.8 and 36.8% of the cases, respectively. LDL-C control was better in those on a high-intensity LLT compared to those on low or moderate intensity LLT. LDL-C control was better in men than women and in patients with self-reported diabetes. Conclusions: The results of the EUROASPIRE V survey show that most coronary patients have a less than optimal management of LDL-C. More professional strategies are needed, aiming at lifestyle changes and LLT adapted to the need of the individual patient., ESC - EORP; AmgenAmgen; Eli LillyEli Lilly; PfizerPfizer; SanofiSanofi-Aventis; Ferrer; Novo NordiskNovo Nordisk, The EUROASPIRE V survey was carried out under the auspices of the ESC - EORP. Since the start of EORP, the following companies have supported the programme: Amgen, Eli Lilly, Pfizer, Sanofi, Ferrer and Novo Nordisk. The sponsors of the EUROASPIRE surveys had no role in the design, data collection, data analysis, data interpretation, decision to publish, or writing the manuscript.

Published
2019

6. Synonymous codon bias as a basis for novel antibiotic design: from nucleotide wobble constraint to ribosomal garrotte

Author

Samuel A McKie and James H McKie

Subjects
0301 basic medicine, Pharmacology, Genetics, Rossmann fold, Speed wobble, Base Sequence, Nucleotides, Shine-Dalgarno sequence, Translation (biology), Wobble base pair, Ribosomal RNA, Biology, Anti-Bacterial Agents, 03 medical and health sciences, 030104 developmental biology, Codon usage bias, Drug Design, Drug Discovery, Nucleic acid, Molecular Medicine, RNA, Messenger, Codon, Ribosomes
Abstract

Aim: The observation of low guanine frequencies at wobble position codons over Rossmann-fold GXGXXG motifs, led to the discovery of sequence-wide synonymous codon bias, from this we propose novel ribosomal inhibitors. Methodology & results: The wobble bases of multiple sequence alignments of diverse Rossmann-fold enzymes were counted, A, C, T and G wobble frequencies of consecutive codons were displayed as wobble plots. Synonymous codon constraints were found throughout the length of proteins, particularly at Rossmann folds. Prokaryote mRNAs have disallowed nucleotide sequences with wobble bases, evolutionary tailored to safeguard translation. We propose one such editing mechanism ensures that glycine motifs avoid becoming Shine–Dalgarno motifs. Conclusion: We propose using peptide nucleic acids and cyclic peptidyl scaffolds as a means of presenting disallowed chemical interactions to the anti-Shine–Dalgarno.

Published
2017

7. Inscribing the Perimeter of the PagP Hydrocarbon Ruler by Site-Specific Chemical Alkylation

Author

Thomas Pinter, Russell E. Bishop, Patrick J. Mott, Mary Vu, Fraser Hof, Joel Moktar, Aaron H. McKie, and M. Adil Khan

Subjects
Models, Molecular, Spectrometry, Mass, Electrospray Ionization, Alkylation, Protein Conformation, Stereochemistry, Phospholipid, Peptide, Biochemistry, Article, Lipid A, chemistry.chemical_compound, Protein structure, Palmitoylation, Escherichia coli, Nuclear Magnetic Resonance, Biomolecular, DNA Primers, chemistry.chemical_classification, Binding Sites, Base Sequence, Protein Stability, Chemistry, Circular Dichroism, Escherichia coli Proteins, Recombinant Proteins, Amino Acid Substitution, Acyltransferases, Mutagenesis, Site-Directed, Mutant Proteins, lipids (amino acids, peptides, and proteins), Bacterial outer membrane, Bacterial Outer Membrane Proteins
Abstract

The Escherichia coli outer membrane phospholipid:lipid A palmitoyltransferase PagP selects palmitate chains using its β-barrel-interior hydrocarbon ruler and interrogates phospholipid donors by gating them laterally through an aperture known as the crenel. Lipid A palmitoylation provides antimicrobial peptide resistance and modulates inflammation signaled through the host TLR4/MD2 pathway. Gly88 substitutions can raise the PagP hydrocarbon ruler floor to correspondingly shorten the selected acyl chain. To explore the limits of hydrocarbon ruler acyl chain selectivity, we have modified the single Gly88Cys sulfhydryl group with linear alkyl units and identified C10 as the shortest acyl chain to be efficiently utilized. Gly88Cys-S-ethyl, S-n-propyl, and S-n-butyl PagP were all highly specific for C12, C11, and C10 acyl chains, respectively, and longer aliphatic or aminoalkyl substitutions could not extend acyl chain selectivity any further. The donor chain length limit of C10 coincides with the phosphatidylcholine transition from displaying bilayer to micellar properties in water, but the detergent inhibitor lauryldimethylamine N-oxide also gradually became ineffective in a micellar assay as the selected acyl chains were shortened to C10. The Gly88Cys-S-ethyl and norleucine substitutions exhibited superior C12 acyl chain specificity compared to that of Gly88Met PagP, thus revealing detection by the hydrocarbon ruler of the Met side chain tolerance for terminal methyl group gauche conformers. Although norleucine substitution was benign, selenomethionine substitution at Met72 was highly destabilizing to PagP. Within the hydrophobic and van der Waals-contacted environment of the PagP hydrocarbon ruler, side chain flexibility, combined with localized thioether-aromatic dispersion attraction, likely influences the specificity of acyl chain selection.

Published
2010
Full Text
View/download PDF

8. Peptoid inhibition of trypanothione reductase as a potential antitrypanosomal and antileishmanial drug lead

Author

James H. McKie, Kenneth T. Douglas, Alan H. Fairlamb, Cecil Chan, and Hong Yin

Subjects
Stereochemistry, Trypanosoma cruzi, Clinical Biochemistry, Glutathione reductase, Antiprotozoal Agents, Protozoan Proteins, Drug design, Biology, Biochemistry, law.invention, Peptoids, chemistry.chemical_compound, Non-competitive inhibition, law, Animals, Humans, NADH, NADPH Oxidoreductases, chemistry.chemical_classification, Organic Chemistry, Peptoid, Glutathione, biology.organism_classification, Trypanocidal Agents, Recombinant Proteins, Glutathione Reductase, Enzyme, chemistry, Drug Design, Recombinant DNA, Leishmania donovani
Abstract

One route to the design of lead compounds for rational drug design approaches to developing drugs against trypanosomiasis, Chagas' disease and leishmaniasis is to develop novel inhibitors of the parasite-specific enzyme trypanothione reductase. A lead inhibitor based on a peptoid structure was designed in the present study based on the known strong competitive inhibition of trypanothione reductase by N-benzoyl-Leu-Arg-Arg-beta-naphthylamide and N-benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy- beta-naphthylamide. In the target peptoid the arginyl residues were replaced by alkylimidazolium units and the benzyloxycarbonyl group by the benzylaminocarbonyl function. The peptoid was synthesised using t-butoxycarbonyl protection chemistry and couplings were activated by 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate. The resulting peptoid was shown to be a competitive inhibitor of recombinant trypanothione reductase from Trypanosoma cruzi with a K(i) value of 179 microM and with only weak inhibition of human erythrocyte glutathione reductase (the inhibition of glutathione reductase was at least 291-fold weaker than of trypanothione reductase).

Published
2002
Full Text
View/download PDF

9. Synthesis and enzymology of modifiedN-benzyloxycarbonyl-L-cysteinylglycyl-3,3-dimethylaminopropylamide disulphides as alternative substrates for trypanothione reductase fromTrypanosoma crud: Part 3

Author

Alan H. Fairlamb, Jacqui Garforth, T. Besheya, C. T. Yuen, Kenneth T. Douglas, James H. McKie, and Rabih Jaouhari

Subjects
Stereochemistry, Trypanosoma cruzi, Clinical Biochemistry, Trypanothione, Biochemistry, law.invention, chemistry.chemical_compound, law, Animals, NADH, NADPH Oxidoreductases, Disulfides, Enzyme kinetics, Amino Acids, chemistry.chemical_classification, biology, Organic Chemistry, Dipeptides, Glutathione, biology.organism_classification, Amino acid, Oxygen, Kinetics, Models, Chemical, chemistry, Recombinant DNA, Trypanothione reductase, Cysteine
Abstract

Kinetic data for alternative substrates of recombinant trypanothione reductase from Trypanosoma cruzi were measured for a series of N-substituted-L-cysteinylglycyl-3-dimethylaminopropylamides, in which the cysteine N-substituent was either a variant of the benzyloxycarbonyl group or was L-phenylalanine or L-tryptophan. Replacing the benzylic ether oxygen atom by CH2 or NH had relatively minor effects on kcat, but raised the value of K(m) 4.5- and 10-fold, respectively. Similarly, relative to the carbobenzoxy group, an N-L-phenylalanyl or N-L-tryptophanyl replacement on the cysteine hardly altered kcat, but increased K(m) values by 16.6 and 7.4 fold, respectively. These observations were consistent with the K(m) values referring primarily to binding for this series of nonspecific substrates.

Published
1999
Full Text
View/download PDF

10. Rational Inhibitor Design, Synthesis and NMR Spectroscopic Study by Transferred Nuclear Overhauser Spectroscopy of Novel Inhibitors of Cinnamyl Alcohol Dehydrogenase, a Critical Enzyme in Lignification

Author

Karen Kennedy, Liliane Gorrichon, James H. McKie, Jacqueline Grima-Pettenati, Jean Guillaume Giraudon, Kevin J. Embrey, Hubert Duran, Kenneth T. Douglas, and Michel Baltas

Subjects
Vinyl Compounds, Propanols, Stereochemistry, Cinnamyl-alcohol dehydrogenase, Molecular Conformation, Organophosphonates, Nuclear Overhauser effect, Lignin, Biochemistry, chemistry.chemical_compound, Benzylamine, Enzyme Inhibitors, Nuclear Magnetic Resonance, Biomolecular, Alcohol dehydrogenase, chemistry.chemical_classification, Eucalyptus, Plants, Medicinal, biology, Chemistry, Iminium, Active site, Recombinant Proteins, Alcohol Oxidoreductases, Enzyme, Drug Design, biology.protein, Proton NMR, Molecular Medicine
Abstract

Cinnamyl alcohol dehydrogenase is one of the enzymes controlling the first two committed steps of lignification. Using a 3-dimensional similarity model of this enzyme, a series of novel phosphonates (1-5) was designed as potential inhibitors. Phosphonates 1-5 were synthesized in good yield by reaction of the corresponding cinnamaldehydes with tetraethylmethylene diphosphonate. Monophosphonic acids 6 and 7 were obtained by basic hydrolysis of the corresponding phosphonates while phosphonamidate 8 was synthesized by reacting benzylamine with the iminium salt intermediate of the monophosphonic acid. Using recombinant cinnamyl alcohol dehydrogenase (CAD, EC 1.1.1.195) the inhibitory activity of these compounds was evaluated and compared with that of the carbonyl analogues. Inhibition kinetic studies showed compounds 2 and 3 to be mixed type linear inhibitors while compound 4 was uncompetitive. 1H NMR studies of inhibitor 2, for which Ki and Ki' were 20 and 86 microM, respectively, in the presence of CAD based on selective line-broadening showed an increased interaction of the 3-OMe group of the aromatic ring of the inhibitor with the active site of the CAD. A transferred nuclear overhauser effect spectroscopy (TRNOESY) experiment for inhibitor 2 with CAD was used to determine the conformation of this compound bound to CAD. These results were found to be consistent with the 3-dimensional structural model of the enzyme.

Published
1999
Full Text
View/download PDF

11. Rational design of selective ligands for trypanothione reductase fromtrypanosoma cruzStructural effects on the inhibition by dibenzazepines based on imipramine

Author

Hong Yin, Kenneth T. Douglas, Jacqueline Garforth, Alan H. Fairlamb, and James H. McKie

Subjects
Imipramine, Erythrocytes, Stereochemistry, Trypanosoma cruzi, Trypanothione, Drug design, Antidepressive Agents, Tricyclic, Reductase, Biology, Ligands, Biochemistry, chemistry.chemical_compound, Dibenzazepines, Computer Graphics, medicine, Animals, NADH, NADPH Oxidoreductases, Enzyme Inhibitors, chemistry.chemical_classification, Osmolar Concentration, Rational design, biology.organism_classification, Recombinant Proteins, chemistry, Drug Design, Lipophilicity, Molecular Medicine, Tricyclic, medicine.drug
Abstract

Trypanothione reductase, the enzyme which in trypanosomal and leishmanial parasites catalyses the reduction of trypanothione disulphide to the redox-protective dithiol and has been identified as a potential target for rational antiparasite drug design, has been found to be strongly inhibited by tricyclic compounds containing the saturated dibenzazepine (imipramine) nucleus, with Ki values in the low micromolar range. This drug lead structure was designed by molecular graphics analysis of a three-dimensional homology model, focussing on the active-site. Inhibition studies were carried out to determine the effect of inhibitor structure on the inhibitory strength towards recombinant trypanothione reductase from Trypanosoma cruzi. Hansch analysis showed that inhibitory strength depended on terms in pi, pi 2 and sigma m indicating dependence on both lipophilicity and inductive effect for ring-substituted analogues of imipramine. The side-chain omega-aminoalkyl chain had to be longer than 2-carbon units for inhibition. The effect on inhibition strength of the substituent at the omega-amino position on the side-chain of the central ring nitrogen atom depended markedly on the detailed substitution pattern of the rest of the molecule. This provides kinetic evidence studies of multiple binding modes within a single, blanket binding site for the inhibitor with the tricyclic ring system in the general region of the hydrophobic pocket lined by Trp21, Tyr110, Met113 and Phe114. This aspect of the structural sensitivity of the precise active-site triangulation adopted by the inhibitor is probably a function of the use of hydrophobic interactions of low directional specificity in this pocket combined with an electrostatic anchoring by the omega-N+ HMe2 function of the inhibitor, presumably with a glutamate side-chain, such as Glu-18, Glu-466' and/or Glu-467'.

Published
1997
Full Text
View/download PDF

12. Synthesis of asymmetric disulfides as potential alternative substrates for trypanothione reductase and glutathione reductase: Part 2

Author

R, Jaouhari, T, Besheya, J H, McKie, and K T, Douglas

Subjects
Organic Chemistry, Clinical Biochemistry, Biochemistry
Abstract

The synthesis of asymmetrical disulfides, based on Zervas' inter-mediate, monocarbobenzoxy-L-cystine, has been developed. A series of substrate analogues of trypanothione disulfide (TSST) and glutathione disulfide (GSSG) are described, where the spermidine ring of (TSST) has been replaced by 3-dimethylaminopropylamine (DMAPA). The free amino group in Zervas' product was condensed with phenylalanyl, tryptophanyl or glutamyl residues, while the carbobenzoxy group was unaffected under the reaction conditions employed. The same synthetic approach was applied in the design of analogues of glutathione disulfide (GSSG).

Published
1995
Full Text
View/download PDF

13. Synthesis of symmetric disulfides as potential alternative substrates for trypanothione reductase and glutathione reductase: Part 1

Author

Rabih Jaouhari, Kenneth T. Douglas, James H. McKie, and T. Besheya

Subjects
chemistry.chemical_classification, Stereochemistry, Organic Chemistry, Clinical Biochemistry, Glutathione reductase, Trypanothione, Substrate (chemistry), Biochemistry, Amino acid, Spermidine, chemistry.chemical_compound, chemistry, Glutaredoxin, Glutathione disulfide, Trypanothione reductase
Abstract

The synthesis of asymmetrical disulfides, based on Zervas' inter-mediate, monocarbobenzoxy-L-cystine, has been developed. A series of substrate analogues of trypanothione disulfide (TSST) and glutathione disulfide (GSSG) are described, where the spermidine ring of (TSST) has been replaced by 3-dimethylaminopropylamine (DMAPA). The free amino group in Zervas' product was condensed with phenylalanyl, tryptophanyl or glutamyl residues, while the carbobenzoxy group was unaffected under the reaction conditions employed. The same synthetic approach was applied in the design of analogues of glutathione disulfide (GSSG).

Published
1995
Full Text
View/download PDF

14. Use of transferred nuclear-Overhauser-effect spectroscopy to measure the bound conformation of a disulphide-replaced analogue of glutathione disulphide as an inhibitor of yeast glutathione reductase

Author

Kevin J. Embrey, James H. McKie, Kenneth T. Douglas, Rabih Jaouhari, Simon J. Carrington, and Anita Mehta

Subjects
chemistry.chemical_classification, Binding Sites, Erythrocytes, Magnetic Resonance Spectroscopy, Glutathione Disulfide, biology, Stereochemistry, Glutathione reductase, Molecular Conformation, Nuclear Overhauser effect, Glutathione, Nuclear magnetic resonance spectroscopy, Hydrogen-Ion Concentration, Ligand (biochemistry), Biochemistry, Chemical synthesis, chemistry.chemical_compound, Glutathione Reductase, Enzyme, chemistry, Enzyme inhibitor, Yeasts, biology.protein, Humans
Abstract

The analogue of glutathione disulphide (GSSG) in which the disulphide bridge of GSSG is replaced by -CH2-S- was synthesised from L-cystathionine using t-butoxycarbonyl and t-butyl ester protection with triethylsilane-promoted deprotection. This analogue (GCSG) was found to be a linear, competitive inhibitor of yeast glutathione reductase (Ki value 981 microM at pH 7.0), a very poor substrate and not to act as an irreversible inhibitor of glutathione reductase. The weak binding of GCSG to glutathione reductase permitted the use of transferred nuclear Overhauser effect spectroscopy (TRNOESY) to investigate the bound conformation of GCSG in its complex with glutathione reductase. The solution structure of free GCSG was investigated by NMR spectroscopy using a range of NMR techniques. The TRNOESY experiment allowed a range of conformations to be determined for the central bridge region (containing the -CH2-S- replacement) of GCSG bound to yeast glutathione reductase. Using the nuclear Overhauser effect constraints thus derived, in combination with molecular graphics and energy minimisation based on the known crystal coordinates of glutathione disulphide (GSSG) bound to human erythrocyte glutathione reductase, allowed an explanation of the lack of substrate activity of GCSG, its inactivity as a suicide inactivator and its relatively weak binding in terms of the enforced mislocation of the -CH2-S- bridge with respect to the catalytic residues (relative to GSSG). Thus, the simple replacement of -S- by -CH2-, common in medicinal chemistry, can lead to poor receptor binding if the replacement occurs in a central, rather than peripheral, part of the ligand under modification.

Published
1994
Full Text
View/download PDF

15. Specific peptide inhibitors of trypanothione reductase with backbone structures unrelated to that of substrate: potential rational drug design lead frameworks

Author

Kenneth T. Douglas, Jacqui Garforth, Hong Yin, Alan H. Fairlamb, T. Besheya, Cecil Chan, James H. McKie, and Rabih Jaouhari

Subjects
Models, Molecular, Stereochemistry, Spermidine, Clinical Biochemistry, Glutathione reductase, Drug design, Peptide, Biology, Biochemistry, chemistry.chemical_compound, Inhibitory Concentration 50, Structure-Activity Relationship, Non-competitive inhibition, Structure–activity relationship, NADH, NADPH Oxidoreductases, Enzyme Inhibitors, chemistry.chemical_classification, Oligopeptide, Organic Chemistry, Glutathione, Enzyme, Glutathione Reductase, chemistry, Drug Design, Peptides, Oligopeptides
Abstract

By introducing cationic charge sites novel peptide lead inhibitor structures for trypanothione reductase have been designed using molecular modelling methods. The inhibitors showed reversible, linear competitive inhibition and the strongest peptide inhibitor to date was found to be N-benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-beta-naphthylamide with a Ki value of 2.4 microM and a selectivity for parasitic enzyme (trypanothione reductase) over the host enzyme (human glutathione reductase) of over 3 orders of magnitude.

Published
2001

16. Rationally designed selective inhibitors of trypanothione reductase. Phenothiazines and related tricyclics as lead structures

Author

Alan H. Fairlamb, Timothy Benson, Jacqui Garforth, Adolfo Borges, Kenneth T. Douglas, and James H. McKie

Subjects
Models, Molecular, Protein Conformation, Spermidine, Stereochemistry, Trypanosoma cruzi, Glutathione reductase, Antiprotozoal Agents, Trypanothione, Drug design, Biochemistry, chemistry.chemical_compound, Phenothiazines, Animals, NADH, NADPH Oxidoreductases, Amino Acid Sequence, Binding site, Molecular Biology, chemistry.chemical_classification, Binding Sites, biology, Cell Biology, Glutathione, Recombinant Proteins, Kinetics, Enzyme, chemistry, Enzyme inhibitor, Drug Design, biology.protein, Research Article, Antipsychotic Agents, Tricyclic
Abstract

Trypanothione reductase, an essential component of the anti-oxidant defences of parasitic trypanosomes and Leishmania, differs markedly from the equivalent host enzyme, glutathione reductase, in the binding site for the disulphide substrate. Molecular modelling of this region suggested that certain tricyclic compounds might bind selectively to trypanothione reductase without inhibiting host glutathione reductase. This was confirmed by testing 30 phenothiazine and tricyclic antidepressants, of which clomipramine was found to be the most potent, with a K(i) of 6 microM, competitive with respect to trypanothione. Many of these compounds have been noted previously to have anti-trypanosomal and anti-leishmanial activity and thus they can serve as lead structures for rational drug design.

Published
1992
Full Text
View/download PDF

17. Inhibitors of glutathione reductase as potential antimalarial drugs. Kinetic cooperativity and effect of dimethyl sulphoxide on inhibition kinetics

Author

Kenneth T. Douglas, Janet Vale, Rainer M. Lüönd, James H. McKie, and Michael J. Dascombe

Subjects
chemistry.chemical_classification, Vitamin K, Stereochemistry, Glutathione reductase, Cooperativity, Glutathione, Saccharomyces cerevisiae, Nile blue, Biochemistry, Thionine, Malaria, chemistry.chemical_compound, Antimalarials, Mice, Enzyme, Glutathione Reductase, chemistry, Menadione, Phenothiazines, Oxazines, Molecular Medicine, Animals, Phenazines, Dimethyl Sulfoxide, Uncompetitive inhibitor
Abstract

We have developed inhibitors of glutathione reductase that improve on the inhibition of literature lead compounds by up to three orders of magnitude. Thus, analogues of Safranine O and menadione were found to be strong, reversible inhibitors of yeast glutathione reductase. Safranine O exhibited partial, uncompetitive inhibition with Ki and alpha values of 0.5 mM and 0.15, respectively. Thionine O was a partial (hyperbolic) uncompetitive inhibitor with Ki and alpha values of 0.4 microM and 0.15, respectively. LY83583 and 2-anilino-1,4-naphthoquinone also showed (hyperbolic) partial, uncompetitive inhibition with micromolar Ki values. For Nile Blue A a model for two-site binding with (parabolic) uncompetitive inhibition fitted the data with a Ki value of 11 microM and a kinetic cooperativity between the sites of 0.12, increased to 0.46 by preincubation of the enzyme and Nile Blue A in the presence of glutathione disulphide. Analysis of the effects of preincubation on the kinetics and cooperativity indicated the possibility of a slow conformational change in the homodimeric enzyme, the first such indication of kinetic cooperativity in the native enzyme to our knowledge. Further evidence of conformational changes for this enzyme came from studies of the effects of dimethyl sulphoxide which indicated that this co-solvent, which at low concentrations has no apparent effect on initial velocities under normal assay conditions, induced a slow conformational change in the enzyme. Thionine O, Nile Blue A and LY83583 were redox-cycling substrates producing superoxide ion, detectable by means of cytochrome c reduction, but leading to no loss of glutathione reductase activity, under aerobic or anaerobic conditions. The water-soluble Safranine analogues Methylene Blue, Methylene Green, Nile Blue A and Thionine O (5 mg/kg i.p. x 5) were effective antimalarial agents in vivo against P. berghei, but their effect was small and a higher dose (50 mg/kg i.p. x 1) was toxic in mice. Comparison was made with human glutathione reductase and its literature-reported interactions with several tricyclic inhibitors as studied by X-ray diffraction. It is possible that the conformational changes detected in the present study from alterations in detailed kinetic inhibition mechanisms may shed light on information transfer through the glutathione reductase molecule from the dimer interface ligand pocket to the active-site.

Published
1998

18. Photoaffinity labelling of the active site of the rat glutathione transferases 3-3 and 1-1 and human glutathione transferase A1-1

Author

Robert Björnestedt, Bengt Mannervik, R J Cooke, James H. McKie, B Coles, Brian Ketterer, M D King, and Kenneth T. Douglas

Subjects
Male, Azides, Recombinant Fusion Proteins, Molecular Sequence Data, Biochemistry, Isozyme, Chromatography, Affinity, chemistry.chemical_compound, Labelling, Mole, Animals, Humans, Amino Acid Sequence, Rats, Wistar, Molecular Biology, Chromatography, High Pressure Liquid, Glutathione Transferase, chemistry.chemical_classification, Binding Sites, biology, Active site, Affinity Labels, Cell Biology, Glutathione, Enzyme assay, Rats, Isoenzymes, Enzyme, chemistry, Liver, biology.protein, Digestion, Research Article
Abstract

The glutathione transferases (GSTs) form a group of enzymes responsible for a wide range of molecular detoxications. The photoaffinity label S-(2-nitro-4-azidophenyl)glutathione was used to study the hydrophobic region of the active site of the rat liver GST 1-1 and 2-2 isoenzymes (class Alpha) as well as the rat class-Mu GST 3-3. Photoaffinity labelling was carried out using a version of S-(2-nitro-4-azidophenyl)glutathione tritiated in the arylazido ring. The labelling occurred with higher levels of radioisotope incorporation for the Mu than the Alpha families. Taking rat GST 3-3, 1.18 (+/- 0.05) mol of radiolabel from S-(2-nitro-4-azidophenyl)glutathione was incorporated per mol of dimeric enzyme, which could be blocked by the presence of the strong competitive inhibitor, S-tritylglutathione (Ki = 1.4 x 10(-7) M). Radiolabelling of the protein paralleled the loss of enzyme activity. Photoaffinity labelling by tritiated S-(2-nitro-4-azidophenyl)glutathione on a preparative scale (in the presence and absence of S-tritylglutathione) followed by tryptic digestion and purification of the labelled peptides indicated that GST 3-3 was specifically photolabelled; the labelled peptides were sequenced. Similarly, preparative photoaffinity labelling by S-(2-nitro-4-azidophenyl)glutathione of the rat liver 1-1 isoenzyme, the human GST A1-1 and the human-rat chimaeric GST, H1R1/1, was carried out with subsequent sequencing of radiolabelled h.p.l.c.-purified tryptic peptides. The results were interpreted by means of molecular-graphics analysis to locate photoaffinity-labelled peptides using the X-ray-crystallographic co-ordinates of rat GST 3-3 and human GST A1-1. The molecular-graphical analysis indicated that the labelled peptides are located within the immediate vicinity of the region occupied by S-substituted glutathione derivatives bound in the active-site cavity of the GSTs investigated.

Published
1994

19. Evidence for gene duplication forming similar binding folds for NAD(P)H and FAD in pyridine nucleotide-dependent flavoenzymes

Author

James H. McKie and Kenneth T. Douglas

Subjects
Models, Molecular, Gene duplication, Swine, Glutathione reductase, Molecular Sequence Data, Biophysics, Trypanothione, Reductase, Biochemistry, chemistry.chemical_compound, Structural Biology, Sequence Homology, Nucleic Acid, Genetics, Escherichia coli, Animals, Humans, Lippamide, Amino Acid Sequence, Molecular Biology, chemistry.chemical_classification, Binding Sites, biology, Flavoenzyme, Bacteria, NADH dehydrogenase, Cell Biology, Nitrite reductase, Glutathione, Enzyme, Glycerol-3-phosphate dehydrogenase, chemistry, Multigene Family, biology.protein, Flavin-Adenine Dinucleotide, NAD+ kinase, Oxidoreductases, NADP
Abstract

For pyridine nucleotide-dependent flavoezymes, binding both FAD and NAD(P)H on a single amino-acids chain, we have found a high degree of internal sequence similarity for certain regions of FAD and NAD (P)H binding portions of the chain for any given protein. This was the case for a range of enzymes classes, including disulphide oxidoreductases (such as glutathione reductase, trypanothione reductase, lipoamide dehydrogenase, mercuric reductase), mono- and dioxygenases, nitrite reductaSE, alkyl hydroperoxidase and NADH dehydrogenase from E. coli. This provides strong support for gene duplication as the origin of at least part of the FAD and NAD(P)H recognising domains of such enzymes.

Published
1991

Catalog

Books, media, physical & digital resources
See catalog results