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2. 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
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3. 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
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4. 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
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5. 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

6. 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

7. 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

8. 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
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9. A Terphenyl Scaffold for π-Stacked Guanidinium Recognition Elements

Author

Fraser Hof, Xing Wang, Olga V. Sarycheva, Bryan D. Koivisto, and and Aaron H. McKie

Subjects
Models, Molecular, Solvent system, Scaffold, Molecular Structure, Organic Chemistry, Carboxylic Acids, Molecular Conformation, Proteins, Arginine, Biochemistry, Combinatorial chemistry, Ion, chemistry.chemical_compound, chemistry, Terphenyl Compounds, Terphenyl, Organic chemistry, Methanol, Physical and Theoretical Chemistry, Guanidine
Abstract

A new synthetic model of arginine-carboxylate-aromatic triads-common motifs at sites of protein-protein interactions-is reported. Binding studies in mixed methanol/water solvent systems suggest that the carboxylate-binding ability of pi-stacked guanidinium ions is improved relative to a non-stacked control.

Published
2007
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10. 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
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11. 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
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12. 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
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13. 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
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14. Predictability of Designing Specific Binding Interactions for DNA Minor Groove Ligands from NMR Spectroscopy and Molecular Modeling: A Copper(II)-Activated DNA Cleaver Based on Hoechst 33258

Author

Amanda N. Wilton, Kenneth T. Douglas, J. Andrews, James H. McKie, John Parkinson, and S Sadat-Ebrahimi

Subjects
Models, Molecular, Magnetic Resonance Spectroscopy, Molecular model, Molecular Sequence Data, chemistry.chemical_element, Ligands, Biochemistry, chemistry.chemical_compound, Molecular dynamics, Cleave, Organometallic Compounds, Molecule, Electrophoresis, Agar Gel, Base Sequence, DNA, Nuclear magnetic resonance spectroscopy, Copper Chelation, Copper, Crystallography, Oligodeoxyribonucleotides, chemistry, Bisbenzimidazole, Nucleic Acid Conformation, DNA Damage
Abstract

Analogs of Hoechst 33258 have been designed and synthesized to incorporate a 3,4-catecholic or a 3,4,5-trihydroxyphenyl function in place of the 4-phenolic group of the template molecule. Molecular design was based on the three-dimensional models of the solution structures of the Hoechst 33258 and its m-hydroxy isomer which had been derived from high-field NMR spectroscopic analysis. The predicted solution structure of the catecholic analog as its minor groove complex with duplex d(CGCGAATTCGCG)2 was confirmed by direct high-resolution NMR spectroscopy combined with molecular dynamics, using NMR-derived distance restraints. While the 3,4-catecholic analog was unable to cleave DNA in the presence of Cu(II) ions, the 3,4,5-trihydroxyphenyl analog of Hoechst 33258 was found to be an effective cleaver of DNA at low concentration when activated by copper(II) ions, a difference ascribed to the inaccessibility for copper chelation of the 3,4-dihydroxy site in its minor groove complex with DNA.

Published
1995
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15. 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
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16. 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
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17. Molecular Design of DNA-Directed Ligands with Specific Interactions: Solution NMR Studies of the Interaction of a m-Hydroxy Analog of Hoechst 33258 with d(CGCGAATTCGCG)2

Author

John Parkinson, Kenneth T. Douglas, James H. McKie, and Seyed Esmaeil Sadat Ebrahimi

Subjects
Binding Sites, Magnetic Resonance Spectroscopy, Base Sequence, Molecular Structure, Hydrogen bond, Ligand, Stereochemistry, Chemistry, Chemical shift, Molecular Sequence Data, Intermolecular force, Temperature, Hydrogen Bonding, DNA, Nuclear magnetic resonance spectroscopy, Biochemistry, Solutions, Oligodeoxyribonucleotides, Bisbenzimidazole, Proton NMR, Thermodynamics, Molecule, Two-dimensional nuclear magnetic resonance spectroscopy
Abstract

We have used one-dimensional (1D) and two-dimensional (2D) proton nuclear magnetic resonance spectroscopy at 600 MHz for structural analysis of the complex formed between d(CGCGAATTCGCG)2 and 2-[2-(3-hydroxyphenyl)-6-benzimidazoyl]-6-(1-methyl-4-piperazinyl) benzimidazole (meta-Hoechst). This analogue differs from Hoechst 33258 only in the location of its meta rather than para phenolic hydroxyl group and was designed to introduce the possibility of intermolecular hydrogen bonding to DNA via the phenol. Complex formation was shown to be 1:1 at 25 degrees C in phosphate buffer in D2O by 1D NMR spectroscopic titration of a solution of d(CGCGAATTCGCG)2 with meta-Hoechst. From 1D NMR spectroscopy the observed perturbations of the assigned chemical shifts of the oligonucleotide observed on binding meta-Hoechst could be used to locate the ligand in the central AATT stretch. By means of 2D NMR spectroscopic techniques, over 400 proton-proton NOEs were defined within the complex. DNA nonexchangeable resonance assignments were made using the sequential assignment method and NOESY. Binding the unsymmetrical ligand lifted the C2v symmetry of the DNA. Exchangeable hydrogens were assigned from NOESY data acquired in 85% H2O/15% D2O medium for the complex and showed differences between the Hoechst 33258 and meta-Hoechst complexes with d(CGCGAATTCGCG)2. The location of meta-Hoechst in the minor-groove AATT region was triangulated using 32 intermolecular NOEs determined for the complex. From the intermolecular NOEs involving the aromatic C-H protons of the phenolic ring of meta-Hoechst, it was clear that this region of the molecule did not rotate freely within the minor groove on the NMR time scale and was oriented with its hydroxyl group toward the floor of the minor groove, in line with the occurrence of the predicted hydrogen bonding between it and the DNA. The pKa of the N3H proton of meta-Hoechst in its bound state in this complex was measured as 6.1 by NMR spectroscopy, a value slightly elevated relative to estimates (approximately 5.2) of the pKa of this proton for the free ligand. Molecular mechanics and the distance restraints provided by the intermolecular NOEs were used in molecular modeling of the meta-Hoechst/d(CGCGAATTCGCG)2 complex, and the distances in the model were consistent with the formation of hydrogen bonds involving the m-OH group of meta-Hoechst and the DNA.

Published
1994
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18. 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
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20. Isolation and partial characterization of murineO6-alkyiguanine-DNA-alkyltransferase: Comparative sequence and structural properties

Author

Chun-Yang Fan, Geoffrey P. Margison, James H. McKie, Rhoderick H Elder, L Cawkwell, Kenneth T. Douglas, Mauro Santibanez-Koref, and Joseph A Rafferty

Subjects
Cancer Research, Protein Conformation, Molecular Sequence Data, Biology, medicine.disease_cause, Epitope, Mice, O(6)-Methylguanine-DNA Methyltransferase, Structure-Activity Relationship, Bacterial Proteins, Complementary DNA, medicine, Animals, Humans, Amino Acid Sequence, Molecular Biology, Escherichia coli, Base Sequence, Protein primary structure, RNA, Methyltransferases, Molecular biology, Rats, Liver, Polyclonal antibodies, biology.protein, Sequence Alignment, Nuclear localization sequence, Alkyltransferase
Abstract

A cDNA encoding murine O6-alkylguanine-DNA-alkyltransferase (ATase) has been sequenced after isolation from total liver RNA by the polymerase chain reaction using oligonucleotide primers derived from the rat ATase cDNA sequence. Functionally active murine ATase protein has been expressed in Escherichia coli at high levels (about 2% of total protein) and purified to apparent homogeneity (molecular mass 26 kDa). In liquid hybridization experiments, anti-human ATase polyclonal antibodies inhibited human but not rat or mouse ATase, whereas anti-rat polyclonal antibodies inhibited rat and mouse but not human ATase. Both antibodies detected all mammalian ATases tested by western analysis so far. These results indicate some common epitopes and at least one unique human epitope. We compared the amino-acid sequence of the murine ATase with those of other mammalian and bacterial ATases. The proteins of this family all have a large domain (approximately 70 amino acids) of highly conserved residues flanking the sequence PCHRV, which contains the alkyl-accepting cysteine residue of the active site. No evidence was found in the sequences for helix-turn-helix, leucine-zipper, or zinc-finger motifs for DNA recognition and binding. Nuclear localization signals (basic-residue-rich regions) could not be uniquely identified in the mammalian members of the family. Outside of the conserved PCHRV region, there were major differences between prokaryotic and eukaryotic proteins at the primary structure level: there was a series of proline-rich motifs, but these also varied between sequences. © 1992 wiley-Liss, Inc.

Published
1992
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21. Tetrazoles are potent anion recognition elements that emulate the disfavored anti conformations of carboxylic acids

Author

Sayuri Friedland, Aaron H. McKie, and Fraser Hof

Subjects
chemistry.chemical_classification, Anions, Models, Molecular, Magnetic Resonance Spectroscopy, Stereochemistry, Carboxylic acid, Organic Chemistry, Carboxylic Acids, Molecular Conformation, Tetrazoles, Protonation, Biochemistry, Tautomer, Combinatorial chemistry, Ion, chemistry.chemical_compound, chemistry, Tetrazole, Physical and Theoretical Chemistry, Anion binding
Abstract

We report here the first study of the protonated, neutral form of tetrazoles as anion binding functional groups. Our studies reveal them to be capable of binding anions with extremely high potency in polar solutions. In studying carboxylic acid-containing congeners, we find a remarkable discrepancy: a strictly analogous acid-containing host binds anions > or = 50,000-fold more weakly than the tetrazole under study. We can explain this functional difference by considering tetrazole tautomerization equilibria and carboxylic acid conformational preferences.

Published
2008

22. A direct link between LY83583, a selective repressor of cyclic GMP formation, and glutathione metabolism

Author

James H. McKie, Rainer M. Lüönd, and Kenneth T. Douglas

Subjects
Glutathione reductase, Down-Regulation, Repressor, Biochemistry, chemistry.chemical_compound, Intestinal mucosa, Animals, Intestinal Mucosa, Cyclic GMP, Pharmacology, chemistry.chemical_classification, Dose-Response Relationship, Drug, Biological activity, Glutathione, Metabolism, Guanylate cyclase 2C, Kinetics, Glutathione Reductase, Enzyme, chemistry, Guanylate Cyclase, Drug Design, Aminoquinolines, Cattle
Abstract

LY83583 (6-anilino-5,8-quinolinedione), considered to be a relatively specific repressor of cyclic GMP formation, is shown in the present study to inhibit (K(i) = 3 microM) glutathione reductase from bovine intestinal mucosa. As glutathione disulphide has been reported to inhibit guanylate cyclase irreversibly [Braughler, Biochem Pharmacol 32: 811-818, 1983], the inhibition of glutathione reductase should affect the activity of guanylate cyclase and may thus have physiological implications in the action of endothelium-derived relaxation factor and the design of muscle relaxants. LY83583 is reduced by NADPH and glutathione reductase in aerobic media and this may offer a route to the metabolic activation of LY83583. These results may have significant implications for the design of heart-regulating drugs (e.g. those used in angina), such as glyceryl trinitrate, which act via guanylate cyclase.

Published
1993
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23. 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

24. 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
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25. 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

26. Rational drug design approach for overcoming drug resistance: application to pyrimethamine resistance in malaria

Author

James H. McKie, Kenneth T. Douglas, Simon A. Roser, Robert Yates, Worachart Sirawaraporn, Martin Read, Cecil Chan, John E. Hyde, Michael J. Dascombe, and Yongyuth Yuthavong

Subjects
Male, Plasmodium berghei, Plasmodium falciparum, Drug Resistance, Drug design, Drug resistance, Antimalarials, Mice, Multienzyme Complexes, parasitic diseases, Drug Discovery, Dihydrofolate reductase, medicine, Animals, biology, Chemistry, Biological activity, Thymidylate Synthase, biology.organism_classification, Molecular biology, Recombinant Proteins, Malaria, Tetrahydrofolate Dehydrogenase, Pyrimethamine, Biochemistry, Enzyme inhibitor, Drug Design, Mutation, biology.protein, Molecular Medicine, Folic Acid Antagonists, medicine.drug
Abstract

Pyrimethamine acts by selectively inhibiting malarial dihydrofolate reductase-thymidylate synthase (DHFR-TS). Resistance in the most important human parasite, Plasmodium falciparum, initially results from an S108N mutation in the DHFR domain, with additional mutation (most commonly C59R or N51I or both) imparting much greater resistance. From a homology model of the 3-D structure of DHFR-TS, rational drug design techniques have been used to design and subsequently synthesize inhibitors able to overcome malarial pyrimethamine resistance. Compared to pyrimethamine (Ki 1.5 nM) with purified recombinant DHFR fromP. falciparum, the Ki value of the m-methoxy analogue of pyrimethamine was 1.07 nM, but against the DHFR bearing the double mutation (C59R + S108N), the Ki values for pyrimethamine and the m-methoxy analogue were 71.7 and 14.0 nM, respectively. The m-chloro analogue of pyrimethamine was a stronger inhibitor of both wild-type DHFR (with Ki 0.30 nM) and the doubly mutant (C59R +S108N) purified enzyme (with Ki 2.40 nM). Growth of parasite cultures of P. falciparum in vitro was also strongly inhibited by these compounds with 50% inhibition of growth occurring at 3.7 microM for the m-methoxy and 0.6 microM for the m-chloro compounds with the K1 parasite line bearing the double mutation (S108N + C59R), compared to 10.2 microM for pyrimethamine. These inhibitors were also found in preliminary studies to retain antimalarial activity in vivo in P. berghei-infected mice.

Published
1998

27. Inhibitors of trypanothione reductase as potential antitrypanosomal drugs

Author

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

Subjects
Binding Sites, Glutathione Disulfide, Chemistry, Spermidine, Biochemistry, Glutathione, Trypanocidal Agents, Phenothiazines, Drug Design, Animals, Humans, NADH, NADPH Oxidoreductases, Trypanothione reductase, Enzyme Inhibitors
Published
1995

28. Site-directed mutagenesis of a serine residue in cinnamyl alcohol dehydrogenase, a plant NADPH-dependent dehydrogenase, affects the specificity for the coenzyme

Author

James H. McKie, M Baltas, Jacqueline Grima-Pettenati, Alain-Michel Boudet, Virginie Lauvergeat, Kenneth T. Douglas, L Gorrichon, Catherine Feuillet, and K Kennedy

Subjects
Models, Molecular, Cinnamyl-alcohol dehydrogenase, Dehydrogenase, Biochemistry, Cofactor, Substrate Specificity, Serine, chemistry.chemical_compound, Structure-Activity Relationship, Phenols, Escherichia coli, Binding site, chemistry.chemical_classification, Eucalyptus, Plants, Medicinal, biology, Chemistry, NAD, Recombinant Proteins, Isoenzymes, Alcohol Oxidoreductases, Kinetics, Enzyme, biology.protein, Mutagenesis, Site-Directed, Branched-chain alpha-keto acid dehydrogenase complex, NADP, Coniferyl alcohol
Abstract

Using recombinant cinnamyl alcohol dehydrogenase isoform 2 (CAD2, EC 1.1.1.195), an NADPH-dependent aromatic alcohol dehydrogenase involved in lignification in vascular plants, we have investigated the detailed steady-state kinetic mechanism of CAD2 and the role of a serine residue in determining the cofactor specificity of CAD2. Site-directed mutagenesis (S212D) and overexpression of the WT and mutant S212D forms of CAD2 in Escherichia coli, followed by kinetic studies on the purified WT and mutant proteins, confirmed the involvement of S212D in recognizing the phosphate group of NADPH and provided information on the structural requirements for NADPH specificity. From substrate kinetic patterns and product inhibition studies both WT and S212D mutant forms of CAD2 have been shown to follow rapid equilibrium random bireactant kinetics with the value of the interaction factor (alpha) for WT (0.25) being significantly less than that for S212D CAD2 (0.45). The changes in binding energy arising from the mutation on the binding of the 2'-phosphate site of the coenzyme were assessed. A marked degree of physical interaction was detected between the enzymatic binding sites of the coniferyl alcohol substrate and the 2'-phosphate binding region, which are quite distant in the three-dimensional structure. The inhibition by 2',5'-ADP and 5'-AMP was found to be weak for both WT and S212D CAD2. Strong substrate inhibition was detected for CAD2, and its implications for plant physiological studies were assessed.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1995

29. A homology model of the three-dimensional structure of human O6-alkylguanine-DNA alkyltransferase based on the crystal structure of the C-terminal domain of the Ada protein from Escherichia coli

Author

J E, Wibley, J H, McKie, K, Embrey, D S, Marks, K T, Douglas, M H, Moore, and P C, Moody

Subjects
Models, Molecular, Binding Sites, Sequence Homology, Amino Acid, Protein Conformation, Escherichia coli Proteins, Molecular Sequence Data, Stereoisomerism, Methyltransferases, Crystallography, X-Ray, O(6)-Methylguanine-DNA Methyltransferase, Bacterial Proteins, Humans, Amino Acid Sequence, Software, Transcription Factors
Abstract

O6-Alkylguanine-DNA alkyltransferase (EC 2.1.1.63) repairs O6-alkylguanine lesions in DNA. A homology model of the human protein (hAT) was built, based on the crystal structure of the C-terminal domain of the Ada protein, which carries out a similar repair in Escherichia coli. Sequence alignments of known O6-alkylguanine-DNA alkyltransferases were used to aid the model building using QUANTA and CHARMm software. Despite low homology in the N-terminal half (hAT residues 1-85), a well-defined topology over this region in Ada permitted successful modelling. The C-terminal half of hAT (residues 92-207) was modelled almost entirely by residue-for-residue superposition onto the Ada structure up to residue hAT175. The model was solvated to a residue radius of 8.0 A [corrected] and then minimized using CHARMm. This structural model was used to rationalize findings from site-directed mutagenesis experiments on hAT, to make further predictions on the relationship between structure and function for the alkyltransferase family of proteins, and to explain the specificity towards known small-molecule inhibitors of the protein.

Published
1995

30. 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

31. Homology modelling of the dihydrofolate reductase-thymidylate synthase bifunctional enzyme of Leishmania major, a potential target for rational drug design in leishmaniasis

Author

J H, McKie

Subjects
Tetrahydrofolate Dehydrogenase, Sequence Homology, Amino Acid, Drug Design, Molecular Sequence Data, Animals, Folic Acid Antagonists, Amino Acid Sequence, Thymidylate Synthase, Leishmaniasis, Leishmania major
Abstract

A homology model of the dimeric Leishmania major dihydrofolate reductase-thymidylate synthase bifunctional enzyme was built based upon the available crystallographic structures of the dihydrofolate reductase and thymidylate synthase monofunctional enzymes. The corresponding substrates, cofactors and inhibitors of the monofunctional enzymes were modelled in the active-sites of the homodimeric model of the bifunctional enzyme. The small number of residues in the interdomain region of the L. major sequence, compared to the other DHFR-TS sequences, imposed severe constraints on the relative locations of the two functional domains. The DHFR and TS domains in the malarial, trypanosomal and toxoplasmia structures are likely to have comparable locations. The leishmanial model reveals features which may be of use in designing novel antifolates for leishmaniasis and protozoal parasites in general.

Published
1994

32. A homology-derived structural model of the murine macrophage inflammatory protein, MIP-1 alpha

Author

J H, McKie and K T, Douglas

Subjects
Sequence Homology, Amino Acid, Heparin, Swine, Monokines, Interleukin-8, Molecular Sequence Data, Macrophage Inflammatory Proteins, Rats, Models, Structural, Mice, HLA-A2 Antigen, Animals, Cytokines, Humans, Amino Acid Sequence, Chemokine CCL4, Chickens, Sequence Alignment, Chemokine CCL3
Abstract

Macrophage inflammatory protein 1 alpha (MIP-1 alpha), a monocyte cytokine, has roles postulated for it in neutrophil chemoattraction, the inflammatory response and the control of haemopoietic stem cell proliferation. The three-dimensional structure of MIP-1 alpha has been modelled structurally, based on its sequence similarity to interleukin-8 and related proteins. The predicted dimeric form of MIP-1 alpha contains two symmetry-related antiparallel alpha-helices lying at an angle across a beta-sheet. The interhelical region and the beta-sheet flooring it are discussed as the potential receptor-binding site in terms of the distribution of negatively charged amino-acid side-chains, which contrasts remarkably with the corresponding positively-charged locations for IL-8. The general topographical features of this (alpha + beta) structural family of cytokines and related proteins (including HLA-A2, PF-4) are discussed. The members of this cytokine family fall into two structural groups as the antiparallel helices (N to C directed) mounted across the beta-sheet platform can be located in a clockwise (e.g. HLA-A2) or anticlockwise (e.g. MIP-1 alpha) sense with respect to the beta-floor).

Published
1994

33. Structural relationships between glyoxalase I and membrane transport proteins

Author

James H. McKie and Kenneth T. Douglas

Subjects
chemistry.chemical_classification, biology, Membrane transport protein, Molecular Sequence Data, Lactoylglutathione Lyase, Membrane Proteins, Sequence Homology, Sequence alignment, Membrane transport, Biochemistry, Lactoylglutathione lyase, Structure-Activity Relationship, Enzyme, chemistry, Carrier protein, biology.protein, Amino Acid Sequence, Carbon-Sulfur Lyases, Carrier Proteins, Sequence Alignment
Published
1993

34. 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

37. Studies of the interaction of a meta-hydroxy analogue of hoechst 33258 with DNA by melting temperature, footprinting and high-resolution 1H NMR spectroscopy

Author

John Parkinson, Keith R. Fox, James H. McKie, Kenneth T. Douglas, Jill Barber, and Seyed Esmaeil Sadat Ebrahimi

Subjects
endocrine system, 1h nmr spectroscopy, animal structures, Chemistry, Stereochemistry, Melting temperature, Analytical chemistry, High resolution, Ligand (biochemistry), Footprinting, chemistry.chemical_compound, Nucleic acid thermodynamics, Molecular Medicine, Molecule, heterocyclic compounds, biological phenomena, cell phenomena, and immunity, neoplasms, DNA
Abstract

A new analogue of Hoechst 33258 1 with a small structural change, i.e., the phenolic OH group being located meta rather than para, has been shown by footprinting, DNA melting studies and high-field 1H NMR spectroscopy to bind to the AATT sequences of DNA in a manner grossly similar to Hoechst 33258, although analysis by 1H NMR spectroscopy indicates that the phenolic end of the ligand could be prised away from the minor groove relative to Hoechst 33258, and that the major groove structure of d(CGCGAATTCGCG)2 is significantly perturbed by the binding of this Hoechst 33258 analogue.

Published
1992
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38. Tetrazoles are Potent Anion Recognition Elements That Emulate the Disfavored AntiConformations of Carboxylic Acids.

Author

Aaron H. McKie, Sayuri Friedland, and Fraser Hof

Subjects
*TETRAZOLES, *FUNCTIONAL groups, *SOLUTION (Chemistry), *SCIENTIFIC method
Abstract

We report here the first study of the protonated, neutral form of tetrazoles as anion binding functional groups. Our studies reveal them to be capable of binding anions with extremely high potency in polar solutions. In studying carboxylic acid-containing congeners, we find a remarkable discrepancy: a strictly analogous acid-containing host binds anions ≥50 000-fold more weakly than the tetrazole under study. We can explain this functional difference by considering tetrazole tautomerization equilibria and carboxylic acid conformational preferences. [ABSTRACT FROM AUTHOR]

Published
2008
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42. A menu for health: changes to New York City school food, 2001 to 2011.

Author

Perlman SE, Nonas C, Lindstrom LL, Choe-Castillo J, McKie H, and Alberti PM

Subjects
Beverages standards, Community Participation, Food Services economics, Food Services trends, Humans, Interinstitutional Relations, New York City epidemiology, Obesity prevention & control, Obesity therapy, Prevalence, Schools, Food Dispensers, Automatic standards, Food Services standards, Nutrition Policy, Obesity epidemiology
Abstract

Background: The high prevalence of obesity puts children at risk for chronic diseases, increases health care costs, and threatens to reduce life expectancy. As part of the response to this epidemic, the New York City (NYC) Department of Education (DOE)--the nation's largest school district--has worked to improve the appeal and nutritional quality of school food. This article highlights some of the structural and policy changes that have improved the school food environment over the past decade, with the aim to share lessons learned and provide recommendations and resources for other districts interested in making similar modifications., Methods: This article details changes DOE has implemented over 10 years, including revised nutrition standards for school meals and competitive foods; new school food department staffing; food reformulations, substitutions, and additions; and transitions to healthier beverages., Results: NYC's revised nutrition standards and hiring of expert staff increased availability of fruits and vegetables, whole grains, and low-fat dairy and decreased sugary beverages, and foods high in saturated fats and added sugars--the major contributors to discretionary calorie intake. DOE also introduced healthier beverages: switching from high-calorie, high-fat whole milk to low-fat milk and increasing access to water., Conclusions: NYC has successfully improved the quality of its school food environment and shown that healthier food service is possible, even under budgetary constraints. Several broad factors facilitated these efforts: fostering community partnerships and inter-agency collaboration, implementing policies and initiatives that target multiple sectors for greater impact, and working to make incremental improvements each year., (© 2012, American School Health Association.)

Published
2012
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