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  • 301. Deloukas, Panos
    et al.
    Kanoni, Stavroula
    Willenborg, Christina
    Farrall, Martin
    Assimes, Themistocles L
    Thompson, John R
    Ingelsson, Erik
    Saleheen, Danish
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Erdmann, Jeanette
    Goldstein, Benjamin A
    Stirrups, Kathleen
    König, Inke R
    Cazier, Jean-Baptiste
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hall, Alistair S
    Lee, Jong-Young
    Willer, Cristen J
    Chambers, John C
    Esko, Tõnu
    Folkersen, Lasse
    Goel, Anuj
    Grundberg, Elin
    Havulinna, Aki S
    Ho, Weang K
    Hopewell, Jemma C
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kleber, Marcus E
    Kristiansson, Kati
    Lundmark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Lyytikäinen, Leo-Pekka
    Rafelt, Suzanne
    Shungin, Dmitry
    Strawbridge, Rona J
    Thorleifsson, Gudmar
    Tikkanen, Emmi
    van Zuydam, Natalie
    Voight, Benjamin F
    Waite, Lindsay L
    Zhang, Weihua
    Ziegler, Andreas
    Absher, Devin
    Altshuler, David
    Balmforth, Anthony J
    Barroso, Inês
    Braund, Peter S
    Burgdorf, Christof
    Claudi-Boehm, Simone
    Cox, David
    Dimitriou, Maria
    Do, Ron
    Doney, Alex S F
    Mokhtari, Noureddine El
    Eriksson, Per
    Fischer, Krista
    Fontanillas, Pierre
    Franco-Cereceda, Anders
    Gigante, Bruna
    Groop, Leif
    Gustafsson, Stefan
    Hager, Jörg
    Hallmans, Göran
    Han, Bok-Ghee
    Hunt, Sarah E
    Kang, Hyun M
    Illig, Thomas
    Kessler, Thorsten
    Knowles, Joshua W
    Kolovou, Genovefa
    Kuusisto, Johanna
    Langenberg, Claudia
    Langford, Cordelia
    Leander, Karin
    Lokki, Marja-Liisa
    Lundmark, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    McCarthy, Mark I
    Meisinger, Christa
    Melander, Olle
    Mihailov, Evelin
    Maouche, Seraya
    Morris, Andrew D
    Müller-Nurasyid, Martina
    Nikus, Kjell
    Peden, John F
    Rayner, N William
    Rasheed, Asif
    Rosinger, Silke
    Rubin, Diana
    Rumpf, Moritz P
    Schäfer, Arne
    Sivananthan, Mohan
    Song, Ci
    Stewart, Alexandre F R
    Tan, Sian-Tsung
    Thorgeirsson, Gudmundur
    Schoot, C Ellen van der
    Wagner, Peter J
    Wells, George A
    Wild, Philipp S
    Yang, Tsun-Po
    Amouyel, Philippe
    Arveiler, Dominique
    Basart, Hanneke
    Boehnke, Michael
    Boerwinkle, Eric
    Brambilla, Paolo
    Cambien, Francois
    Cupples, Adrienne L
    de Faire, Ulf
    Dehghan, Abbas
    Diemert, Patrick
    Epstein, Stephen E
    Evans, Alun
    Ferrario, Marco M
    Ferrières, Jean
    Gauguier, Dominique
    Go, Alan S
    Goodall, Alison H
    Gudnason, Villi
    Hazen, Stanley L
    Holm, Hilma
    Iribarren, Carlos
    Jang, Yangsoo
    Kähönen, Mika
    Kee, Frank
    Kim, Hyo-Soo
    Klopp, Norman
    Koenig, Wolfgang
    Kratzer, Wolfgang
    Kuulasmaa, Kari
    Laakso, Markku
    Laaksonen, Reijo
    Lee, Ji-Young
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ouwehand, Willem H
    Parish, Sarah
    Park, Jeong E
    Pedersen, Nancy L
    Peters, Annette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Quertermous, Thomas
    Rader, Daniel J
    Salomaa, Veikko
    Schadt, Eric
    Shah, Svati H
    Sinisalo, Juha
    Stark, Klaus
    Stefansson, Kari
    Trégouët, David-Alexandre
    Virtamo, Jarmo
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wareham, Nicholas
    Zimmermann, Martina E
    Nieminen, Markku S
    Hengstenberg, Christian
    Sandhu, Manjinder S
    Pastinen, Tomi
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Hovingh, G Kees
    Dedoussis, George
    Franks, Paul W
    Lehtimäki, Terho
    Metspalu, Andres
    Zalloua, Pierre A
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Schreiber, Stefan
    Ripatti, Samuli
    Blankenberg, Stefan S
    Perola, Markus
    Clarke, Robert
    Boehm, Bernhard O
    O'Donnell, Christopher
    Reilly, Muredach P
    März, Winfried
    Collins, Rory
    Kathiresan, Sekar
    Hamsten, Anders
    Kooner, Jaspal S
    Thorsteinsdottir, Unnur
    Danesh, John
    Palmer, Colin N A
    Roberts, Robert
    Watkins, Hugh
    Schunkert, Heribert
    Samani, Nilesh J
    Large-scale association analysis identifies new risk loci for coronary artery disease2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 1, p. 25-33Article in journal (Refereed)
    Abstract [en]

    Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

  • 302.
    den Hoed, Marcel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eijgelsheim, Mark
    Esko, Tonu
    Brundel, Bianca J. J. M.
    Peal, David S.
    Evans, David M.
    Nolte, Ilja M.
    Segre, Ayellet V.
    Holm, Hilma
    Handsaker, Robert E.
    Westra, Harm-Jan
    Johnson, Toby
    Isaacs, Aaron
    Yang, Jian
    Lundby, Alicia
    Zhao, Jing Hua
    Kim, Young Jin
    Go, Min Jin
    Almgren, Peter
    Bochud, Murielle
    Boucher, Gabrielle
    Cornelis, Marilyn C.
    Gudbjartsson, Daniel
    Hadley, David
    van der Harst, Pim
    Hayward, Caroline
    den Heijer, Martin
    Igl, Wilmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Jackson, Anne U.
    Kutalik, Zoltan
    Luan, Jian'an
    Kemp, John P.
    Kristiansson, Kati
    Ladenvall, Claes
    Lorentzon, Mattias
    Montasser, May E.
    Njajou, Omer T.
    O'Reilly, Paul F.
    Padmanabhan, Sandosh
    Pourcain, Beate St.
    Rankinen, Tuomo
    Salo, Perttu
    Tanaka, Toshiko
    Timpson, Nicholas J.
    Vitart, Veronique
    Waite, Lindsay
    Wheeler, William
    Zhang, Weihua
    Draisma, Harmen H. M.
    Feitosa, Mary F.
    Kerr, Kathleen F.
    Lind, Penelope A.
    Mihailov, Evelin
    Onland-Moret, N. Charlotte
    Song, Ci
    Weedon, Michael N.
    Xie, Weijia
    Yengo, Loic
    Absher, Devin
    Albert, Christine M.
    Alonso, Alvaro
    Arking, Dan E.
    de Bakker, Paul I. W.
    Balkau, Beverley
    Barlassina, Cristina
    Benaglio, Paola
    Bis, Joshua C.
    Bouatia-Naji, Nabila
    Brage, Soren
    Chanock, Stephen J.
    Chines, Peter S.
    Chung, Mina
    Darbar, Dawood
    Dina, Christian
    Doerr, Marcus
    Elliott, Paul
    Felix, Stephan B.
    Fischer, Krista
    Fuchsberger, Christian
    de Geus, Eco J. C.
    Goyette, Philippe
    Gudnason, Vilmundur
    Harris, Tamara B.
    Hartikainen, Anna-Liisa
    Havulinna, Aki S.
    Heckbert, Susan R.
    Hicks, Andrew A.
    Hofman, Albert
    Holewijn, Suzanne
    Hoogstra-Berends, Femke
    Hottenga, Jouke-Jan
    Jensen, Majken K.
    Johansson, Asa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Junttila, Juhani
    Kaeaeb, Stefan
    Kanon, Bart
    Ketkar, Shamika
    Khaw, Kay-Tee
    Knowles, Joshua W.
    Kooner, Angrad S.
    Kors, Jan A.
    Kumari, Meena
    Milani, Lili
    Laiho, Paeivi
    Lakatta, Edward G.
    Langenberg, Claudia
    Leusink, Maarten
    Liu, Yongmei
    Luben, Robert N.
    Lunetta, Kathryn L.
    Lynch, Stacey N.
    Markus, Marcello R. P.
    Marques-Vidal, Pedro
    Leach, Irene Mateo
    McArdle, Wendy L.
    McCarroll, Steven A.
    Medland, Sarah E.
    Miller, Kathryn A.
    Montgomery, Grant W.
    Morrison, Alanna C.
    Mueller-Nurasyid, Martina
    Navarro, Pau
    Nelis, Mari
    O'Connell, Jeffrey R.
    O'Donnell, Christopher J.
    Ong, Ken K.
    Newman, Anne B.
    Peters, Annette
    Polasek, Ozren
    Pouta, Anneli
    Pramstaller, Peter P.
    Psaty, Bruce M.
    Rao, Dabeeru C.
    Ring, Susan M.
    Rossin, Elizabeth J.
    Rudan, Diana
    Sanna, Serena
    Scott, Robert A.
    Sehmi, Jaban S.
    Sharp, Stephen
    Shin, Jordan T.
    Singleton, Andrew B.
    Smith, Albert V.
    Soranzo, Nicole
    Spector, Tim D.
    Stewart, Chip
    Stringham, Heather M.
    Tarasov, Kirill V.
    Uitterlinden, Andre G.
    Vandenput, Liesbeth
    Hwang, Shih-Jen
    Whitfield, John B.
    Wijmenga, Cisca
    Wild, Sarah H.
    Willemsen, Gonneke
    Wilson, James F.
    Witteman, Jacqueline C. M.
    Wong, Andrew
    Wong, Quenna
    Jamshidi, Yalda
    Zitting, Paavo
    Boer, Jolanda M. A.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    van Duijn, Cornelia M.
    Ekelund, Ulf
    Forouhi, Nita G.
    Froguel, Philippe
    Hingorani, Aroon
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kivimaki, Mika
    Kronmal, Richard A.
    Kuh, Diana
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Martin, Nicholas G.
    Oostra, Ben A.
    Pedersen, Nancy L.
    Quertermous, Thomas
    Rotter, Jerome I.
    van der Schouw, Yvonne T.
    Verschuren, W. M. Monique
    Walker, Mark
    Albanes, Demetrius
    Arnar, David O.
    Assimes, Themistocles L.
    Bandinelli, Stefania
    Boehnke, Michael
    de Boer, Rudolf A.
    Bouchard, Claude
    Caulfield, W. L. Mark
    Chambers, John C.
    Curhan, Gary
    Cusi, Daniele
    Eriksson, Johan
    Ferrucci, Luigi
    van Gilst, Wiek H.
    Glorioso, Nicola
    de Graaf, Jacqueline
    Groop, Leif
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Hsueh, Wen-Chi
    Hu, Frank B.
    Huikuri, Heikki V.
    Hunter, David J.
    Iribarren, Carlos
    Isomaa, Bo
    Jarvelin, Marjo-Riitta
    Jula, Antti
    Kahonen, Mika
    Kiemeney, Lambertus A.
    van der Klauw, Melanie M.
    Kooner, Jaspal S.
    Kraft, Peter
    Iacoviello, Licia
    Lehtimaki, Terho
    Lokki, Marja-Liisa L.
    Mitchell, Braxton D.
    Navis, Gerjan
    Nieminen, Markku S.
    Ohlsson, Claes
    Poulter, Neil R.
    Qi, Lu
    Raitakari, Olli T.
    Rimm, Eric B.
    Rioux, John D.
    Rizzi, Federica
    Rudan, Igor
    Salomaa, Veikko
    Sever, Peter S.
    Shields, Denis C.
    Shuldiner, Alan R.
    Sinisalo, Juha
    Stanton, Alice V.
    Stolk, Ronald P.
    Strachan, David P.
    Tardif, Jean-Claude
    Thorsteinsdottir, Unnur
    Tuomilehto, Jaako
    van Veldhuisen, Dirk J.
    Virtamo, Jarmo
    Viikari, Jorma
    Vollenweider, Peter
    Waeber, Gerard
    Widen, Elisabeth
    Cho, Yoon Shin
    Olsen, Jesper V.
    Visscher, Peter M.
    Willer, Cristen
    Franke, Lude
    Erdmann, Jeanette
    Thompson, John R.
    Pfeufer, Arne
    Sotoodehnia, Nona
    Newton-Cheh, Christopher
    Ellinor, Patrick T.
    Stricker, Bruno H. Ch
    Metspalu, Andres
    Perola, Markus
    Beckmann, Jacques S.
    Smith, George Davey
    Stefansson, Kari
    Wareham, Nicholas J.
    Munroe, Patricia B.
    Sibon, Ody C. M.
    Milan, David J.
    Snieder, Harold
    Samani, Nilesh J.
    Loos, Ruth J. F.
    Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 6, p. 621-+Article in journal (Refereed)
    Abstract [en]

    Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

  • 303. Dery, Jean-Pierre P.
    et al.
    Mahaffey, Kenneth
    Tricoci, Pierluigi
    White, Harvey
    Podder, Mohua
    Moliterno, David
    Harrington, Robert
    Chen, Edmond
    Strony, John
    Van de Werf, Frans
    Ziada, Khaled M.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Aylward, Philip
    Armstrong, Paul W.
    Rao, Sunil
    Arterial Access Site and Outcomes in Patients Undergoing Percutaneous Coronary Intervention With and Without Vorapaxar2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 304. Di Angelantonio, Emanuele
    et al.
    Gao, Pei
    Khan, Hassan
    Butterworth, Adam S.
    Wormser, David
    Kaptoge, Stephen
    Seshasai, Sreenivasa Rao Kondapally
    Thompson, Alex
    Sarwar, Nadeem
    Willeit, Peter
    Ridker, Paul M.
    Barr, Elizabeth L. M.
    Khaw, Kay-Tee
    Psaty, Bruce M.
    Brenner, Hermann
    Balkau, Beverley
    Dekker, Jacqueline M.
    Lawlor, Debbie A.
    Daimon, Makoto
    Willeit, Johann
    Njolstad, Inger
    Nissinen, Aulikki
    Brunner, Eric J.
    Kuller, Lewis H.
    Price, Jackie F.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Knuiman, Matthew W.
    Feskens, Edith J. M.
    Verschuren, W. M. M.
    Wald, Nicholas
    Bakker, Stephan J. L.
    Whincup, Peter H.
    Ford, Ian
    Goldbourt, Uri
    Gomez-de-la-Camara, Agustin
    Gallacher, John
    Simons, Leon A.
    Rosengren, Annika
    Sutherland, Susan E.
    Bjorkelund, Cecilia
    Blazer, Dan G.
    Wassertheil-Smoller, Sylvia
    Onat, Altan
    Ibanez, Alejandro Marin
    Casiglia, Edoardo
    Jukema, J. Wouter
    Simpson, Lara M.
    Giampaoli, Simona
    Nordestgaard, Borge G.
    Selmer, Randi
    Wennberg, Patrik
    Kauhanen, Jussi
    Salonen, Jukka T.
    Dankner, Rachel
    Barrett-Connor, Elizabeth
    Kavousi, Maryam
    Gudnason, Vilmundur
    Evans, Denis
    Wallace, Robert B.
    Cushman, Mary
    D'Agostino, Ralph B., Sr.
    Umans, Jason G.
    Kiyohara, Yutaka
    Nakagawa, Hidaeki
    Sato, Shinichi
    Gillum, Richard F.
    Folsom, Aaron R.
    van der Schouw, Yvonne T.
    Moons, Karel G.
    Griffin, Simon J.
    Sattar, Naveed
    Wareham, Nicholas J.
    Selvin, Elizabeth
    Thompson, Simon G.
    Danesh, John
    Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease2014In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 311, no 12, p. 1225-1233Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The value of measuring levels of glycated hemoglobin (HbA(1c)) for the prediction of first cardiovascular events is uncertain. OBJECTIVE To determine whether adding information on HbA(1c) values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS Analysis of individual-participant data available from 73 prospective studies involving 294 998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (>= 7.5%) risk. RESULTS During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20 840 incident fatal and nonfatal CVD outcomes (13 237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA(1c) values and CVD risk. The association between HbA(1c) values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA(1c) was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA(1c) assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes, additional assessment of HbA(1c) values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.

  • 305. Di Angelantonio, Emanuele
    et al.
    Gao, Pei
    Pennells, Lisa
    Kaptoge, Stephen
    Caslake, Muriel
    Thompson, Alexander
    Butterworth, Adam S.
    Sarwar, Nadeem
    Wormser, David
    Saleheen, Danish
    Ballantyne, Christie M.
    Psaty, Bruce M.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ridker, Paul M.
    Nagel, Dorothea
    Gillum, Richard F.
    Ford, Ian
    Ducimetiere, Pierre
    Kiechl, Stefan
    Dullaart, Robin P. F.
    Assmann, Gerd
    D'Agostino, Ralph B.
    Dagenais, Gilles R.
    Cooper, Jackie A.
    Kromhout, Daan
    Onat, Altan
    Tipping, Robert W.
    Gomez-de-la-Camara, Agustin
    Rosengren, Annika
    Sutherland, Susan E.
    Gallacher, John
    Fowkes, F. Gerry R.
    Casiglia, Edoardo
    Hofman, Albert
    Salomaa, Veikko
    Barrett-Connor, Elizabeth
    Clarke, Robert
    Brunner, Eric
    Jukema, J. Wouter
    Simons, Leon A.
    Sandhu, Manjinder
    Wareham, Nicholas J.
    Khaw, Kay-Tee
    Kauhanen, Jussi
    Salonen, Jukka T.
    Howard, William J.
    Nordestgaard, Borge G.
    Wood, Angela M.
    Thompson, Simon G.
    Boekholdt, S. Matthijs
    Sattar, Naveed
    Packard, Chris
    Gudnason, Vilmundur
    Danesh, John
    Lipid-Related Markers and Cardiovascular Disease Prediction2012In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 307, no 23, p. 2499-2506Article in journal (Refereed)
    Abstract [en]

    Context

    The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated.

    Objective 

    To determine whether adding information on apolipoprotein B and apolipoprotein A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 to total cholesterol and high-density lipoprotein cholesterol (HDL-C) improves cardiovascular disease (CVD) risk prediction.

    Design, Setting, and Participants 

    Individual records were available for 165 544 participants without baseline CVD in 37 prospective cohorts (calendar years of recruitment: 1968-2007) with up to 15 126 incident fatal or nonfatal CVD outcomes (10 132 CHD and 4994 stroke outcomes) during a median follow-up of 10.4 years (interquartile range, 7.6-14 years).

    Main Outcome Measures 

    Discrimination of CVD outcomes and reclassification of participants across predicted 10-year risk categories of low (<10%), intermediate (10%-<20%), and high (≥20%) risk.

    Results 

    The addition of information on various lipid-related markers to total cholesterol, HDL-C, and other conventional risk factors yielded improvement in the model's discrimination: C-index change, 0.0006 (95% CI, 0.0002-0.0009) for the combination of apolipoprotein B and A-I; 0.0016 (95% CI, 0.0009-0.0023) for lipoprotein(a); and 0.0018 (95% CI, 0.0010-0.0026) for lipoprotein-associated phospholipase A2 mass. Net reclassification improvements were less than 1% with the addition of each of these markers to risk scores containing conventional risk factors. We estimated that for 100 000 adults aged 40 years or older, 15 436 would be initially classified at intermediate risk using conventional risk factors alone. Additional testing with a combination of apolipoprotein B and A-I would reclassify 1.1%; lipoprotein(a), 4.1%; and lipoprotein-associated phospholipase A2 mass, 2.7% of people to a 20% or higher predicted CVD risk category and, therefore, in need of statin treatment under Adult Treatment Panel III guidelines.

    Conclusion 

    In a study of individuals without known CVD, the addition of information on the combination of apolipoprotein B and A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 mass to risk scores containing total cholesterol and HDL-C led to slight improvement in CVD prediction.

  • 306. Di Angelantonio, Emanuele
    et al.
    Kaptoge, Stephen
    Wormser, David
    Willeit, Peter
    Butterworth, Adam S.
    Bansal, Narinder
    O'Keeffe, Linda M.
    Gao, Pei
    Wood, Angela M.
    Burgess, Stephen
    Freitag, Daniel F.
    Pennells, Lisa
    Peters, Sanne A.
    Hart, Carole L.
    Haheim, Lise Lund
    Gillum, Richard F.
    Nordestgaard, Borge G.
    Psaty, Bruce M.
    Yeap, Bu B.
    Knuiman, Matthew W.
    Nietert, Paul J.
    Kauhanen, Jussi
    Salonen, Jukka T.
    Kuller, Lewis H.
    Simons, Leon A.
    van der Schouw, Yvonne T.
    Barrett-Connor, Elizabeth
    Selmer, Randi
    Crespo, Carlos J.
    Rodriguez, Beatriz
    Verschuren, W. M. Monique
    Salomaa, Veikko
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    van der Harst, Pim
    Bjorkelund, Cecilia
    Wilhelmsen, Lars
    Wallace, Robert B.
    Brenner, Hermann
    Amouyel, Philippe
    Barr, Elizabeth L. M.
    Iso, Hiroyasu
    Onat, Altan
    Trevisan, Maurizio
    D'Agostino, Ralph B., Sr.
    Cooper, Cyrus
    Kavousi, Maryam
    Welin, Lennart
    Roussel, Ronan
    Hu, Frank B.
    Sato, Shinichi
    Davidson, Karina W.
    Howard, Barbara V.
    Leening, Maarten
    Rosengren, Annika
    Dorr, Marcus
    Deeg, Dorly J. H.
    Kiechl, Stefan
    Stehouwer, Coen D. A.
    Nissinen, Aulikki
    Giampaoli, Simona
    Donfrancesco, Chiara
    Kromhout, Daan
    Price, Jackie F.
    Peters, Annette
    Meade, Tom W.
    Casiglia, Edoardo
    Lawlor, Debbie A.
    Gallacher, John
    Nagel, Dorothea
    Franco, Oscar H.
    Assmann, Gerd
    Dagenais, Gilles R.
    Jukema, J. Wouter
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Woodward, Mark
    Brunner, Eric J.
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Whitsel, Eric A.
    Njolstad, Inger
    Hedblad, Bo
    Wassertheil-Smoller, Sylvia
    Engstrom, Gunnar
    Rosamond, Wayne D.
    Selvin, Elizabeth
    Sattar, Naveed
    Thompson, Simon G.
    Danesh, John
    Association of Cardiometabolic Multimorbidity With Mortality: The Emerging Risk Factors Collaboration2015In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 314, no 1, p. 52-60Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing.

    OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.

    DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).

    MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy.

    RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.

    CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

  • 307.
    Di Cesare, Mariachiara
    et al.
    Univ London Imperial Coll Sci Technol & Med, London, England.;Middlesex Univ, London N17 8HR, England..
    Bentham, James
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Stevens, Gretchen A.
    WHO, CH-1211 Geneva, Switzerland..
    Zhou, Bin
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Danaei, Goodarz
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Lu, Yuan
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Bixby, Honor
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Cowan, Melanie J.
    WHO, CH-1211 Geneva, Switzerland..
    Riley, Leanne M.
    WHO, CH-1211 Geneva, Switzerland..
    Hajifathalian, Kaveh
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Fortunato, Lea
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Taddei, Cristina
    Univ Florence, Florence, Italy..
    Bennett, James E.
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Ikeda, Nayu
    Natl Inst Hlth & Nutr, Tokyo 162, Japan..
    Khang, Young-Ho
    Seoul Natl Univ, Seoul, South Korea..
    Kyobutungi, Catherine
    African Populat & Hlth Res Ctr, Nairobi, Kenya..
    Laxmaiah, Avula
    Indian Council Med Res, New Delhi, India..
    Li, Yanping
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Lin, Hsien-Ho
    Natl Taiwan Univ, Taipei 10764, Taiwan..
    Miranda, J. Jaime
    Univ Peruana Cayetano Heredia, Lima, Peru..
    Mostafa, Aya
    Ain Shams Univ, Cairo, Egypt..
    Turley, Maria L.
    Minist Hlth, Wellington, New Zealand..
    Paciorek, Christopher J.
    Univ Calif Berkeley, Berkeley, CA 94720 USA..
    Gunter, Marc
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Ezzati, Majid
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Abdeen, Ziad A.
    Al Quds Univ, Jerusalem, Israel..
    Hamid, Zargar Abdul
    Ctr Diabet & Endocrine Care, Bengaluru, India..
    Abu-Rmeileh, Niveen M.
    Birzeit Univ, Bir Zayt, Israel..
    Acosta-Cazares, Benjamin
    Inst Mexicano Seguro Social, Rio Grande, Mexico..
    Adams, Robert
    Univ Adelaide, Adelaide, SA 5005, Australia..
    Aekplakorn, Wichai
    Mahidol Univ, Bangkok 10700, Thailand..
    Aguilar-Salinas, Carlos A.
    Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Rio Grande, Mexico..
    Ahmadvand, Alireza
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Ahrens, Wolfgang
    Leibniz Inst Prevent Res & Epidemiol BIPS, Leibniz, Germany..
    Ali, Mohamed M.
    World Hlth Org Reg Off Eastern Mediterranean, Giza, Egypt..
    Alkerwi, Ala'a
    Luxembourg Inst Hlth, Luxembourg, Luxembourg..
    Alvarez-Pedrerol, Mar
    Ctr Res Environm Epidemiol, Madrid, Spain..
    Aly, Eman
    World Hlth Org Reg Off Eastern Mediterranean, Giza, Egypt..
    Amouyel, Philippe
    Lille Univ & Hosp, Lille, France..
    Amuzu, Antoinette
    London Sch Hyg & Trop Med, London, England..
    Andersen, Lars Bo
    Univ Southern Denmark, Lyngby, Denmark..
    Anderssen, Sigmund A.
    Norwegian Sch Sport Sci, Oslo, Norway..
    Andrade, Dolores S.
    Univ Cuenca, Cuenca, Ecuador..
    Anjana, Ranjit Mohan
    Madras Diabet Res Fdn, Madras, Tamil Nadu, India..
    Aounallah-Skhiri, Hajer
    Natl Inst Publ Hlth, Tunis, Tunisia..
    Ariansen, Inger
    Norwegian Inst Publ Hlth, Oslo, Norway..
    Aris, Tahir
    Minist Hlth, Kuala Lumpur, Malaysia..
    Arlappa, Nimmathota
    Indian Council Med Res, New Delhi, India..
    Arveiler, Dominique
    Strasbourg Univ & Hosp, Strasbourg, France..
    Assah, Felix K.
    Univ Yaounde I, Yaounde, Cameroon..
    Avdicova, Maria
    Reg Author Publ Hlth, Banska Bystrica, Slovakia..
    Azizi, Fereidoun
    Shahid Beheshti Univ Med Sci, Tehran, Iran..
    Babu, Bontha V.
    Indian Council Med Res, New Delhi, India..
    Balakrishna, Nagalla
    Indian Council Med Res, New Delhi, India..
    Bandosz, Piotr
    Med Univ Gdansk, Gdansk, Poland..
    Banegas, Jose R.
    Univ Autonoma Madrid, E-28049 Madrid, Spain..
    Barbagallo, Carlo M.
    Univ Palermo, I-90133 Palermo, Italy..
    Barcelo, Alberto
    Pan Amer Hlth Org, El Paso, TX USA..
    Barkat, Amina
    Univ Mohammed V Rabat, Rabat, Morocco..
    Barros, Mauro V.
    Univ Pernambuco, Petrolina, PE, Brazil..
    Bata, Iqbal
    Dalhousie Univ, Halifax, NS B3H 3J5, Canada..
    Batieha, Anwar M.
    Jordan Univ Sci & Technol, Amman, Jordan..
    Batista, Rosangela L.
    Univ Fed Maranhao, Sao Luis, Brazil..
    Baur, Louise A.
    Univ Sydney, Sydney, NSW 2006, Australia..
    Beaglehole, Robert
    Univ Auckland, Auckland 1, New Zealand..
    Ben Romdhane, Habiba
    Univ Tunis El Manar, Tunis, Tunisia..
    Benet, Mikhail
    Univ Med Sci, Havana, Cuba..
    Bernabe-Ortiz, Antonio
    Univ Peruana Cayetano Heredia, Lima, Peru..
    Bernotiene, Gailute
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Bettiol, Heloisa
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Bhagyalaxmi, Aroor
    BJ Med Coll, New Delhi, India..
    Bharadwaj, Sumit
    Chirayu Med Coll, Bhopal, India..
    Bhargava, Santosh K.
    Sunder Lal Jain Hosp, New Delhi, India..
    Bhatti, Zaid
    Aga Khan Univ, Lahore, Pakistan..
    Bhutta, Zulfiqar A.
    Aga Khan Univ, Lahore, Pakistan..
    Bi, HongSheng
    Shandong Univ Tradit Chinese Med, Jinan, Peoples R China..
    Bi, Yufang
    Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China..
    Bjerregaard, Peter
    Univ Southern Denmark, Lyngby, Denmark..
    Bjertness, Espen
    Univ Oslo, N-0316 Oslo, Norway..
    Bjertness, Marius B.
    Univ Oslo, N-0316 Oslo, Norway..
    Bjorkelund, Cecilia
    Gothenburg Univ, S-41124 Gothenburg, Sweden..
    Blake, Margaret
    NatCen Social Res, London, England..
    Blokstra, Anneke
    Natl Inst Publ Hlth & Environm, Amsterdam, Netherlands..
    Bo, Simona
    Univ Turin, I-10124 Turin, Italy..
    Bobak, Martin
    UCL, London WC1E 6BT, England..
    Boddy, Lynne M.
    Liverpool John Moores Univ, Liverpool L3 5UX, Merseyside, England..
    Boehm, Bernhard O.
    Nanyang Technol Univ, Singapore 639798, Singapore..
    Boeing, Heiner
    German Inst Human Nutr, Berlin, Germany..
    Boissonnet, Carlos P.
    CEMIC, Buenos Aires, DF, Argentina..
    Bongard, Vanina
    Toulouse Univ, Sch Med, Toulouse, France..
    Bovet, Pascal
    Minist Hlth, Victoria, Seychelles.;Univ Lausanne, CH-1015 Lausanne, Switzerland..
    Braeckman, Lutgart
    Univ Ghent, B-9000 Ghent, Belgium..
    Bragt, Marjolijn C. E.
    FrieslandCampina, Singapore, Singapore..
    Brajkovich, Imperia
    Cent Univ Venezuela, Caracas, Venezuela..
    Branca, Francesco
    WHO, CH-1211 Geneva, Switzerland..
    Breckenkamp, Juergen
    Univ Bielefeld, Bielefeld, Germany..
    Brenner, Hermann
    German Canc Res Ctr, Berlin, Germany..
    Brewster, Lizzy M.
    Univ Amsterdam, NL-1012 WX Amsterdam, Netherlands..
    Brian, Garry R.
    Fred Hollows Fdn New Zealand, Auckland, New Zealand..
    Bruno, Graziella
    Univ Turin, I-10124 Turin, Italy..
    Bueno-de-Mesquita, H. B(as)
    Natl Inst Publ Hlth & Environm, Amsterdam, Netherlands..
    Bugge, Anna
    Univ Southern Denmark, Lyngby, Denmark..
    Burns, Con
    Cork Inst Technol, Cork, Ireland..
    Cabrera de Leon, Antonio
    Univ La Laguna, E-38207 San Cristobal la Laguna, Spain..
    Cacciottolo, Joseph
    Univ Malta, Msida, Malta..
    Cama, Tilema
    Minist Hlth, Nukualofa, Tonga..
    Cameron, Christine
    Canadian Fitness & Lifestyle Res Inst, Toronto, ON, Canada..
    Camolas, Jose
    Hosp Santa Maria, CHLN, Lisbon, Portugal..
    Can, Gunay
    Istanbul Univ, Istanbul, Turkey..
    Candido, Ana Paula C.
    Univ Fed Juiz de Fora, Juiz De Fora, Brazil..
    Capuano, Vincenzo
    Cardiol Mercato S Severino, Mercato San Severino, Italy..
    Cardoso, Viviane C.
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Carvalho, Maria J.
    Univ Porto, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Casanueva, Felipe F.
    Univ Santiago de Compostela, Santiago De Compostela, Spain..
    Casas, Juan-Pablo
    UCL, London WC1E 6BT, England..
    Caserta, Carmelo A.
    Assoc Calabrese Epatol, Rome, Italy..
    Castetbon, Katia
    French Inst Hlth Surveillance, Lyon, France..
    Chamukuttan, Snehalatha
    India Diabet Res Fdn, New Delhi, India..
    Chan, Angelique W.
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Chan, Queenie
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Chaturvedi, Himanshu K.
    Natl Inst Med Stat, New Delhi, India..
    Chaturvedi, Nishi
    UCL, London WC1E 6BT, England..
    Chen, Chien-Jen
    Acad Sinica, Taipei, Taiwan..
    Chen, Fangfang
    Capital Inst Pediat, Beijing, Peoples R China..
    Chen, Huashuai
    Duke Univ, Durham, NC 27706 USA..
    Chen, Shuohua
    Kailuan Gen Hosp, Beijing, Peoples R China..
    Chen, Zhengming
    Univ Oxford, Oxford OX1 2JD, England..
    Cheng, Ching-Yu
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Chetrit, Angela
    Gertner Inst Epidemiol & Hlth Policy Res, Tel Aviv, Israel..
    Chiolero, Arnaud
    Univ Lausanne Hosp, Lausanne, Switzerland..
    Chiou, Shu-Ti
    Minist Hlth & Welf, Taipei, Taiwan..
    Chirita-Emandi, Adela
    Victor Babes Univ Med & Pharm, Cluj Napoca, Romania..
    Cho, Yumi
    Korea Ctr Dis Control & Prevent, Seoul, South Korea..
    Christensen, Kaare
    Univ Southern Denmark, Lyngby, Denmark..
    Chudek, Jerzy
    Med Univ Silesia, Katowice, Poland..
    Cifkova, Renata
    Charles Univ Prague, Prague, Czech Republic..
    Claessens, Frank
    Katholieke Univ Leuven, Louvain, Belgium..
    Clays, Els
    Univ Ghent, B-9000 Ghent, Belgium..
    Concin, Hans
    Agcy Prevent & Social Med, Vienna, Austria..
    Cooper, Cyrus
    Univ Southampton, Southampton SO9 5NH, Hants, England..
    Cooper, Rachel
    UCL, London WC1E 6BT, England..
    Coppinger, Tara C.
    Cork Inst Technol, Cork, Ireland..
    Costanzo, Simona
    IRCCS Ist Neurol Mediterraneo Neuromed, Rome, Italy..
    Cottel, Dominique
    Inst Pasteur, Lille, France..
    Cowell, Chris
    Westmead Univ Sydney, Sydney, NSW, Australia..
    Craig, Cora L.
    Canadian Fitness & Lifestyle Res Inst, Toronto, ON, Canada..
    Crujeiras, Ana B.
    CIBEROBN, Madrid, Spain..
    D'Arrigo, Graziella
    CNR, Rome, Italy..
    d'Orsi, Eleonora
    Univ Fed Santa Catarina, BR-88040900 Florianopolis, SC, Brazil..
    Dallongeville, Jean
    Inst Pasteur, Lille, France..
    Damasceno, Albertino
    Eduardo Mondlane Univ, Maputo, Mozambique..
    Damsgaard, Camilla T.
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Dankner, Rachel
    Gertner Inst Epidemiol & Hlth Policy Res, Tel Aviv, Israel..
    Dauchet, Luc
    Lille Univ Hosp, Lille, France..
    De Backer, Guy
    Univ Ghent, B-9000 Ghent, Belgium..
    De Bacquer, Dirk
    Univ Ghent, B-9000 Ghent, Belgium..
    de Gaetano, Giovanni
    IRCCS Ist Neurol Mediterraneo Neuromed, Rome, Italy..
    De Henauw, Stefaan
    Univ Ghent, B-9000 Ghent, Belgium..
    De Smedt, Delphine
    Univ Ghent, B-9000 Ghent, Belgium..
    Deepa, Mohan
    Madras Diabet Res Fdn, Madras, Tamil Nadu, India..
    Deev, Alexander D.
    Natl Res Ctr Prevent Med, Moscow, Russia..
    Dehghan, Abbas
    Erasmus MC, Rotterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands..
    Delisle, Helene
    Univ Montreal, Montreal, PQ H3C 3J7, Canada..
    Delpeuch, Francis
    Inst Rech Dev, Lyon, France..
    Dhana, Klodian
    Erasmus MC, Rotterdam, Netherlands..
    Di Castelnuovo, Augusto F.
    IRCCS Ist Neurol Mediterraneo Neuromed, Rome, Italy..
    Dias-da-Costa, Juvenal Soares
    Univ Vale Rio dos Sinos, Sao Leopoldo, RS, Brazil..
    Diaz, Alejandro
    Natl Council Sci & Tech Res, Buenos Aires, DF, Argentina..
    Djalalinia, Shirin
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Do, Ha T. P.
    Natl Inst Nutr, Hanoi, Vietnam..
    Dobson, Annette J.
    Univ Queensland, Brisbane, Qld 4072, Australia..
    Donfrancesco, Chiara
    Ist Super Sanita, Rome, Italy..
    Doering, Angela
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Doua, Kouamelan
    Minist Sante & Lutte Sida, Yamoussoukro, Cote Ivoire..
    Drygas, Wojciech
    Cardinal Wyszynski Inst Cardiol, Warsaw, Poland..
    Egbagbe, Eruke E.
    Univ Benin, Coll Med Sci, Benin, Nigeria..
    Eggertsen, Robert
    Gothenburg Univ, S-41124 Gothenburg, Sweden..
    Ekelund, Ulf
    Norwegian Sch Sport Sci, Oslo, Norway..
    El Ati, Jalila
    Natl Inst Nutr & Food Technol, Tunis, Tunisia..
    Elliott, Paul
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Engle-Stone, Reina
    Univ Calif Davis, Davis, CA USA..
    Erasmus, Rajiv T.
    Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa..
    Erem, Cihangir
    Karadeniz Tech Univ, Trabzon, Turkey..
    Eriksen, Louise
    Univ Southern Denmark, Lyngby, Denmark..
    Escobedo-de la Pena, Jorge
    Inst Mexicano Seguro Social, Rio Grande, Mexico..
    Evans, Alun
    Queens Univ Belfast, Belfast BT7 1NN, Antrim, North Ireland..
    Faeh, David
    Univ Zurich, CH-8006 Zurich, Switzerland..
    Fall, Caroline H.
    Univ Southampton, Southampton SO9 5NH, Hants, England.;Univ Tehran Med Sci, Tehran, Iran..
    Farzadfar, Farshad
    Felix-Redondo, Francisco J.
    Ferguson, Trevor S.
    Univ W Indies, Kingston, Jamaica..
    Fernandez-Berges, Daniel
    Ferrante, Daniel
    Minist Hlth, Buenos Aires, DF, Argentina..
    Ferrari, Marika
    Council Agr Res & Econ, Rome, Italy..
    Ferreccio, Catterina
    Ferrieres, Jean
    Toulouse Univ, Sch Med, Toulouse, France..
    Finn, Joseph D.
    Univ Manchester, Manchester M13 9PL, Lancs, England..
    Fischer, Krista
    Univ Tartu, Tartu, Estonia..
    Monterubio Flores, Eric
    Inst Nacl Salud Publ, Mexico City, DF, Mexico..
    Foeger, Bernhard
    Agcy Prevent & Social Med, Vienna, Austria..
    Foo, Leng Huat
    Univ Sains Malaysia, Shah Alam, Malaysia..
    Forslund, Ann-Sofie
    Univ Lulea, S-97187 Lulea, Sweden..
    Fortmann, Stephen P.
    Stanford Univ, Stanford, CA 94305 USA..
    Fouad, Heba M.
    Francis, Damian K.
    Franco, Maria do Carmo
    Franco, Oscar H.
    Erasmus MC, Rotterdam, Netherlands.;Univ Fed Sao Paulo, Sao Paulo, Brazil..
    Frontera, Guillermo
    Fuchs, Flavio D.
    Fuchs, Sandra C.
    Univ Fed Rio Grande do Sul, BR-90046900 Porto Alegre, RS, Brazil..
    Fujita, Yuki
    Kinki Univ, Fac Med, Higashiosaka, Osaka 577, Japan..
    Furusawa, Takuro
    Kyoto Univ, Kyoto 6068501, Japan..
    Gaciong, Zbigniew
    Med Univ Warsaw, Warsaw, Poland..
    Gafencu, Mihai
    Victor Babes Univ Med & Pharm, Cluj Napoca, Romania..
    Gareta, Dickman
    Garnett, Sarah P.
    Univ Sydney, Sydney, NSW 2006, Australia..
    Gaspoz, Jean-Michel
    Univ Hosp Geneva, Geneva, Switzerland..
    Gasull, Magda
    Gates, Louise
    Geleijnse, Johanna M.
    Wageningen Univ, NL-6700 AP Wageningen, Netherlands..
    Ghasemian, Anoosheh
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Giampaoli, Simona
    Ist Super Sanita, Rome, Italy..
    Gianfagna, Francesco
    Univ Insubria, Varese, Italy..
    Giovannelli, Jonathan
    Lille Univ Hosp, Lille, France..
    Giwercman, Aleksander
    Lund Univ, S-22100 Lund, Sweden..
    Goldsmith, Rebecca A.
    Gonzalez Gross, Marcela
    Univ Politecn Madrid, E-28040 Madrid, Spain..
    Gonzalez Rivas, Juan P.
    Andes Clin Cardiometab Studies, Caracas, Venezuela..
    Bonet Gorbea, Mariano
    Natl Inst Hyg Epidemiol & Microbiol, Havana, Cuba..
    Gottrand, Frederic
    Univ Lille 2, F-59800 Lille, France..
    -Iversen, Sidsel Graff
    Norwegian Inst Publ Hlth, Oslo, Norway..
    Grafnetter, Dusan
    Inst Clin & Expt Med, Prague, Czech Republic..
    Grajda, Aneta
    Childrens Mem Hlth Inst, Warsaw, Poland..
    Grammatikopoulou, Maria G.
    Alexander Technol Educ Inst, Athens, Greece..
    Gregor, Ronald D.
    Dalhousie Univ, Halifax, NS B3H 3J5, Canada..
    Grodzicki, Tomasz
    Jagiellonian Univ, Coll Med, PL-31007 Krakow, Poland..
    Grontved, Anders
    Univ Southern Denmark, Lyngby, Denmark..
    Gruden, Grabriella
    Univ Turin, I-10124 Turin, Italy..
    Grujic, Vera
    Inst Publ Hlth Vojvodina, Belgrade, Serbia..
    Gu, Dongfeng
    Natl Ctr Cardiovasc Dis, Beijing, Peoples R China..
    Guan, Ong Peng
    Singapore Eye Res Inst, Singapore, Singapore..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland..
    Guerrero, Ramiro
    Univ Icesi, Cali, Colombia..
    Guessous, Idris
    Univ Hosp Geneva, Geneva, Switzerland..
    Guimaraes, Andre L.
    Gulliford, Martin C.
    Kings Coll London, London WC2R 2LS, England..
    Gunnlaugsdottir, Johanna
    Guo, Xiu H.
    Capital Med Univ, Beijing, Peoples R China..
    Guo, Yin
    Capital Med Univ, Beijing, Peoples R China..
    Gupta, Prakash C.
    Healis Sekhsaria Inst Publ Hlth, New Delhi, India..
    Gureje, Oye
    Univ Ibadan, Ibadan, Nigeria..
    Gurzkowska, Beata
    Childrens Mem Hlth Inst, Warsaw, Poland..
    Gutierrez, Laura
    Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina..
    Gutzwiller, Felix
    Univ Zurich, CH-8006 Zurich, Switzerland..
    Halkjaer, Jytte
    Danish Canc Soc Res Ctr, Lyngby, Denmark..
    Hardy, Rebecca
    UCL, London WC1E 6BT, England..
    Kumar, Rachakulla Hari
    Indian Council Med Res, New Delhi, India..
    Hayes, Alison J.
    Univ Sydney, Sydney, NSW 2006, Australia.;Tulane Univ, New Orleans, LA 70118 USA..
    He, Jiang
    Hendriks, Marleen Elisabeth
    Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands..
    Hernandez Cadena, Leticia
    Natl Inst Publ Hlth, Mexicali, Baja California, Mexico..
    Heshmat, Ramin
    Hihtaniemi, Ilpo Tapani
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Ho, Sai Yin
    Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Ho, Suzanne C.
    Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Hobbs, Michael
    Univ Western Australia, Nedlands, WA 6009, Australia..
    Hofman, Albert
    Erasmus MC, Rotterdam, Netherlands..
    Hormiga, Claudia M.
    Horta, Bernardo L.
    Univ Fed Pelotas, Pelotas, Brazil..
    Houti, Leila
    Univ Oran 1, Oran, Algeria..
    Htay, Thein Thein
    Htet, Aung Soe
    Univ Oslo, N-0316 Oslo, Norway..
    Htike, Maung Maung Than
    Minist Hlth, Naypyidaw, Myanmar..
    Hu, Yonghua
    Peking Univ, Hlth Sci Ctr, Beijing, Peoples R China..
    Hussieni, Abdullatif S.
    Birzeit Univ, Bir Zayt, Israel..
    Huu, Chinh Nguyen
    Huybrechts, Inge
    Int Agcy Res Canc, Lyon, France..
    Hwalla, Nahla
    Amer Univ Beirut, Beirut, Lebanon..
    Iacoviello, Licia
    IRCCS Ist Neurol Mediterraneo Neuromed, Rome, Italy..
    Iannone, Anna G.
    Cardiol Mercato S Severino, Mercato San Severino, Italy..
    Ibrahim, M. Mohsen
    Cairo Univ, Cairo, Egypt..
    Ikram, M. Arfan
    Erasmus MC, Rotterdam, Netherlands..
    Irazola, Vilma E.
    Islam, Muhammad
    Aga Khan Univ, Lahore, Pakistan..
    Iwasaki, Masanori
    Niigata Univ, Niigata 95021, Japan..
    Jackson, Rod T.
    Univ Auckland, Auckland 1, New Zealand..
    Jacobs, Jeremy M.
    Hadassah Univ, Med Ctr, Tel Aviv, Israel..
    Jafar, Tazeen
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Jamil, Kazi M.
    Kuwait Inst Scientifi c Res, Kuwait, Kuwait..
    Jamrozik, Konrad
    Univ Adelaide, Adelaide, SA 5005, Australia..
    Jasienska, Grazyna
    Jiang, Chao Qiang
    Guangzhou 12th Hosp, Guangzhou, Guangdong, Peoples R China..
    Joffres, Michel
    Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada..
    Johansson, Mattias
    Jonas, Jost B.
    Heidelberg Univ, Heidelberg, Germany..
    Jorgensen, Torben
    Joshi, Pradeep
    World Hlth Org Country Off, New Delhi, India..
    Juolevi, Anne
    Natl Inst Hlth & Welf, Espoo, Finland..
    Jurak, Gregor
    Univ Ljubljana, Ljubljana 61000, Slovenia..
    Juresa, Vesna
    Univ Zagreb, Zagreb 41000, Croatia..
    Kaaks, Rudolf
    German Canc Res Ctr, Berlin, Germany..
    Kafatos, Anthony
    Univ Crete, Iraklion, Greece..
    Kalter-Leibovici, Ofra
    Gertner Inst Epidemiol & Hlth Policy Res, Tel Aviv, Israel..
    Kapantais, Efthymios
    Hellen Med Assoc Obes, Iraklion, Greece..
    Kasaeian, Amir
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Katz, Joanne
    Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA..
    Kaur, Prabhdeep
    Natl Inst Epidemiol, Madras, Tamil Nadu, India..
    Kavousi, Maryam
    Erasmus MC, Rotterdam, Netherlands..
    Keil, Ulrich
    Univ Munster, Munster, Germany..
    Boker, Lital Keinan
    Univ Haifa, IL-31999 Haifa, Israel..
    Kelishadi, Roya
    Kemper, Han H. C. G.
    Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Kengne, Andre P.
    South African Med Res Council, Johannesburg, South Africa..
    Kersting, Mathilde
    Res Inst Child Nutr FKE, Munich, Germany..
    Key, Timothy
    Univ Oxford, Oxford OX1 2JD, England..
    Khader, Yousef Saleh
    Jordan Univ Sci & Technol, Amman, Jordan..
    Khalili, Davood
    Shahid Beheshti Univ Med Sci, Tehran, Iran..
    Khaw, Kay-Tee H.
    Univ Cambridge, Cambridge CB2 1TN, England..
    Khouw, Ilse M. S. L.
    FrieslandCampina, Singapore, Singapore..
    Kiechl, Stefan
    Med Univ Innsbruck, A-6020 Innsbruck, Austria..
    Killewo, Japhet
    Univ Hlth & Allied Sci, Tanza, Tanzania..
    Kim, Jeongseon
    Natl Canc Ctr, Seoul, South Korea..
    Kiyohara, Yutaka
    Kyushu Univ, Fukuoka 812, Japan..
    Klimont, Jeannette
    Stat Austria, Vienna, Austria..
    Kolle, Elin
    Norwegian Sch Sport Sci, Oslo, Norway..
    Kolsteren, Patrick
    Inst Trop Med, Brussels, Belgium..
    Korrovits, Paul
    Tartu Univ Clin, Tartu, Estonia..
    Koskinen, Seppo
    Kouda, Katsuyasu
    Kinki Univ, Fac Med, Higashiosaka, Osaka 577, Japan..
    Koziel, Slawomir
    Polish Acad Sci, Anthropol Unit, Wroclaw, Poland..
    Kratzer, Wolfgang
    Univ Hosp Ulm, Ulm, Germany..
    Krokstad, Steinar
    Norwegian Univ Sci & Technol, Oslo, Norway..
    Kromhout, Daan
    Wageningen Univ, NL-6700 AP Wageningen, Netherlands..
    Kruger, Herculina S.
    North West Univ, Johannesburg, South Africa..
    Kula, Krzysztof
    Med Univ Lodz, Lodz, Poland..
    Kulaga, Zbigniew
    Childrens Mem Hlth Inst, Warsaw, Poland..
    Kumar, R. Krishna
    Amrita Inst Med Sci, Kochi, India..
    Kusuma, Yadlapalli S.
    All India Inst Med Sci, New Delhi 110029, India..
    Kuulasmaa, Kari
    Laamiri, Fatima Zahra
    Univ Mohammed V Rabat, Rabat, Morocco..
    Laatikainen, Tiina
    Lachat, Carl
    Univ Ghent, B-9000 Ghent, Belgium..
    Laid, Youcef
    Lam, Tai Hing
    Landrove, Orlando
    Lanska, Vera
    Lappas, Georg
    Sahlgrens Acad, Stockholm, Sweden..
    Laugsand, Lars E.
    Norwegian Univ Sci & Technol, Oslo, Norway..
    Bao, Khanh Le Nguyen
    Le, Tuyen D.
    Natl Inst Nutr, Hanoi, Vietnam..
    Leclercq, Catherine
    Food & Agr Org, Rome, Italy..
    Lee, Jeannette
    Natl Univ Singapore, Singapore 117548, Singapore..
    Lee, Jeonghee
    Natl Canc Ctr, Seoul, South Korea..
    Lehtimaki, Terho
    Tampere Univ Hosp, Tampere, Finland..
    Lekhraj, Rampal
    Univ Putra Malaysia, Serdang 43400, Malaysia..
    Leon-Munoz, Luz M.
    Univ Autonoma Madrid, E-28049 Madrid, Spain..
    Lim, Wei-Yen
    Natl Univ Singapore, Singapore 117548, Singapore..
    Fernanda Lima-Costa, M.
    Fundacao Oswaldo Cruz, Rene Rachou Res Inst, Rio De Janeiro, Brazil..
    Lin, Xu
    Univ Chinese Acad Sci, Beijing, Peoples R China..
    Linneberg, Allan
    Res Ctr Prevent & Hlth, Aalborg, Denmark..
    Lissner, Lauren
    Gothenburg Univ, S-41124 Gothenburg, Sweden..
    Litwin, Mieczyslaw
    Childrens Mem Hlth Inst, Lodz, Poland..
    Liu, Jing
    Capital Med Univ, Beijing Anzhen Hosp, Beijing, Peoples R China..
    Lorbeer, Roberto
    Univ Med Greifswald, Greifswald, Germany..
    Lotufo, Paulo A.
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Eugenio Lozano, Jose
    Consejeria Sanidad Junta Castilla & Leon, Leon, Spain..
    Luksiene, Dalia
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Lundqvist, Annamari
    Natl Inst Hlth & Welf, Tampere, Finland..
    Lunet, Nuno
    Univ Porto, Sch Med, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ma, Guansheng
    Peking Univ, Beijing 100871, Peoples R China..
    Machi, Suka
    Jikei Univ, Sch Med, Tokyo, Japan..
    Maggi, Stefania
    CNR, Pisa, Italy..
    Magliano, Dianna J.
    Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia..
    Makdisse, Marcia
    Hosp Israelita Albert Einstein, Sao Paulo, Brazil..
    Malekzadeh, Reza
    Univ Tehran Med Sci, Tehran, Iran..
    Malhotra, Rahul
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Rao, Kodavanti Mallikharjuna
    Indian Council Med Res, New Delhi, India..
    Manios, Yannis
    Harokopio Univ Athens, Athens, Greece..
    Mann, Jim I.
    Univ Otago, Otaru, Hokkaido, Japan..
    Manzato, Enzo
    Univ Padua, I-35100 Padua, Italy..
    Margozzini, Paula
    Pontificia Univ Catolica Chile, Santiago, Chile..
    Markey, Oonagh
    Univ Reading, Reading RG6 2AH, Berks, England..
    Marques-Vidal, Pedro
    Univ Lausanne Hosp, Lausanne, Switzerland..
    Marrugat, Jaume
    Martin-Prevel, Yves
    Inst Rech Dev, Lyon, France..
    Martorell, Reynaldo
    Emory Univ, Atlanta, GA 30322 USA..
    Masoodi, Shariq R.
    Sherikashmir Inst Med Sci, Jammu, India..
    Matsha, Tandi E.
    Cape Peninsula Univ Technol, Cape Town, South Africa..
    Mazur, Artur
    Univ Rzeszow, Rzeszow, Poland..
    Mbanya, Jean Claude N.
    Univ Yaounde I, Yaounde, Cameroon..
    McFarlane, Shelly R.
    McGarvey, Stephen T.
    Brown Univ, Providence, RI 02912 USA..
    McKee, Martin
    London Sch Hyg & Trop Med, London, England..
    McLachlan, Stela
    Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland..
    McLean, Rachael M.
    McNulty, Breige A.
    Univ Coll Dublin, Dublin, Ireland..
    Yusof, Safiah Md
    Univ Teknol MARA, Serdang, Malaysia..
    Mediene-Benchekor, Sounnia
    Meirhaeghe, Aline
    Meisinger, Christa
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Mendes, Larissa L.
    Univ Fed Juiz de Fora, Juiz De Fora, Brazil..
    Menezes, Ana Maria B.
    Mensink, Gert B. M.
    Robert Koch Inst, Berlin, Germany..
    Meshram, Indrapal I.
    Indian Council Med Res, New Delhi, India..
    Metspalu, Andres
    Univ Tartu, Ulikooli 18, EE-50090 Tartu, Estonia..
    Mi, Jie
    Capital Inst Pediat, Beijing, Peoples R China..
    Michaelsen, Kim F.
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Mikkel, Kairit
    Univ Tartu, Ulikooli 18, EE-50090 Tartu, Estonia..
    Miller, Jody C.
    Francisco Miquel, Juan
    Jaime Miranda, J.
    Univ Peruana Cayetano Heredia, Lima, Peru..
    Misigoj-Durakovic, Marjeta
    Univ Zagreb, Zagreb 41000, Croatia..
    Mohamed, Mostafa K.
    Ain Shams Univ, Cairo, Egypt..
    Mohammad, Kazem
    Univ Tehran Med Sci, Tehran, Iran..
    Mohammadifard, Noushin
    Isfahan Cardiovasc Res Ctr, Esfahan, Iran..
    Mohan, Viswanathan
    Madras Diabet Res Fdn, Madras, Tamil Nadu, India..
    Yusoff, Muhammad Fadhli Mohd
    Minist Hlth, Kuala Lumpur, Malaysia..
    Molbo, Drude
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Moller, Niels C.
    Univ Southern Denmark, Lyngby, Denmark..
    Molnar, Denes
    Univ Pecs, Pecs, Hungary..
    Mondo, Charles K.
    Mulago Hosp, Kampala, Uganda..
    Monterrubio, Eric A.
    Monyeki, Kotsedi Daniel K.
    Univ Limpopo, Limpopo, South Africa..
    Moreira, Leila B.
    Morejon, Alain
    Univ Med Sci, Havana, Cuba..
    Moreno, Luis A.
    Univ Zaragoza, E-50009 Zaragoza, Spain..
    Morgan, Karen
    RCSI Dublin, Dublin, Ireland..
    Mortensen, Erik Lykke
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Moschonis, George
    Harokopio Univ Athens, Athens, Greece..
    Mossakowska, Malgorzata
    Mota, Jorge
    Univ Porto, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Motlagh, Mohammad Esmaeel
    Ahvaz Jundishapur Univ Med Sci, Tehran, Iran..
    Motta, Jorge
    Gorgas Mem Inst Publ Hlth, Panama City, Panama..
    Mu, Thet Thet
    Muiesan, Maria Lorenza
    Univ Brescia, I-25121 Brescia, Italy..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Murphy, Neil
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Mursu, Jaakko
    Univ Eastern Finland, Joensuu, Finland..
    Murtagh, Elaine M.
    Mary Immaculate Coll, Limerick, Ireland..
    Musa, Kamarul Imran
    Univ Sains Malaysia, Kota Baharu, Malaysia..
    Musil, Vera
    Univ Zagreb, Zagreb 41000, Croatia..
    Nagel, Gabriele
    Univ Ulm, D-89069 Ulm, Germany..
    Nakamura, Harunobu
    Namesna, Jana
    Reg Author Publ Hlth, Banska Bystrica, Slovakia..
    Nang, Ei Ei K.
    Nangia, Vinay B.
    Suraj Eye Inst, Nagpur, Maharashtra, India..
    Nankap, Martin
    Helen Keller Int, Yaounde, Cameroon..
    Narake, Sameer
    Maria Navarrete-Munoz, Eva
    Nenko, Ilona
    Neovius, Martin
    Karolinska Inst, S-10401 Stockholm, Sweden..
    Nervi, Flavio
    Neuhauser, Hannelore K.
    Nguyen, Nguyen D.
    Univ Pharm & Med Ho Chi Minh City, Ho Chi Minh City, Vietnam..
    Nguyen, Quang Ngoc
    Nieto-Martinez, Ramfis E.
    Ning, Guang
    Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China..
    Ninomiya, Toshiharu
    Nishtar, Sania
    Heartfile, Karachi, Pakistan..
    Noale, Marianna
    Norat, Teresa
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Noto, Davide
    Univ Palermo, I-90133 Palermo, Italy..
    Al Nsour, Mohannad
    Eastern Mediterranean Publ Hlth Network, Amman, Jordan..
    O'Reilly, Dermot
    Ochoa-Aviles, Angelica M.
    Univ Cuenca, Cuenca, Ecuador..
    Oh, Kyungwon
    Korea Ctr Dis Control & Prevent, Seoul, South Korea..
    Olayan, Iman H.
    Kuwait Inst Sci Res, Kuwait, Kuwait..
    Anselmo Olinto, Maria Teresa
    Univ Vale Rio dos Sinos, Sao Leopoldo, RS, Brazil..
    Oltarzewski, Maciej
    Omar, Mohd A.
    Minist Hlth, Kuala Lumpur, Malaysia..
    Ordunez, Pedro
    Pan Amer Hlth Org, El Paso, TX USA..
    Ortiz, Ana P.
    Univ Puerto Rico, San Juan, PR USA..
    Osler, Merete
    Osmond, Clive
    MRC Lifecourse Epidemiol Unit, Southampton, Hants, England..
    Ostojic, Sergej M.
    Univ Novi Sad, Novi Sad 21000, Serbia..
    Otero, Johanna A.
    Overvad, Kim
    Aarhus Univ, DK-8000 Aarhus C, Denmark..
    Paccaud, Fred Michel
    Padez, Cristina
    Univ Coimbra, P-3000 Coimbra, Portugal..
    Pajak, Andrzej
    Palli, Domenico
    Palloni, Alberto
    Univ Madison Wisconsin, Madison, WI USA..
    Palmieri, Luigi
    Ist Super Sanita, Rome, Italy..
    Panda-Jonas, Songhomitra
    Panza, Francesco
    Univ Bari, I-70121 Bari, Italy..
    Parnell, Winsome R.
    Parsaeian, Mahboubeh
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Pednekar, Mangesh S.
    Peeters, Petra H.
    Univ Med Ctr Utrecht, Utrecht, Netherlands..
    Peixoto, Sergio Viana
    Pereira, Alexandre C.
    Heart Inst InCor, Sao Paulo, Brazil..
    Perez, Cynthia M.
    Peters, Annette
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Peykari, Niloofar
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Pham, Son Thai
    Pigeot, Iris
    Leibniz Inst Prevent Res & Epidemiol BIPS, Leibniz, Germany..
    Pikhart, Hynek
    UCL, London WC1E 6BT, England..
    Pilav, Aida
    Fed Minist Hlth, Sarajevo, Bosnia & Herceg..
    Pilotto, Lorenza
    Pistelli, Francesco
    Univ Hosp Pisa, Pisa, Italy..
    Pitakaka, Freda
    Univ New S Wales, Sydney, NSW 2052, Australia..
    Piwonska, Aleksandra
    Cardinal Wyszynski Inst Cardiol, Warsaw, Poland..
    Piwonski, Jerzy
    Plans-Rubio, Pedro
    Poh, Bee Koon
    Publ Hlth Agcy Catalonia, Catalonia, Spain..
    Porta, Miquel
    Portegies, Marileen L. P.
    Erasmus MC, Rotterdam, Netherlands..
    Poulimeneas, Dimitrios
    Pradeepa, Rajendra
    Madras Diabet Res Fdn, Madras, Tamil Nadu, India..
    Prashant, Mathur
    Indian Council Med Res, New Delhi, India..
    Price, Jacqueline F.
    Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland..
    Puiu, Maria
    Victor Babes Univ Med & Pharm, Cluj Napoca, Romania..
    Punab, Margus
    Tartu Univ Clin, Tartu, Estonia..
    Qasrawi, Radwan F.
    Al Quds Univ, Jerusalem, Israel..
    Qorbani, Mostafa
    Alborz Univ Med Sci, Golestan, Iran..
    Bao, Tran Quoc
    Radic, Ivana
    Inst Publ Hlth Vojvodina, Vojvodina, Serbia..
    Radisauskas, Ricardas
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Rahman, Mahmudur
    Inst Epidemiol Dis Control & Res, Dhaka, Bangladesh..
    Raitakari, Olli
    Turku Univ Hosp, FIN-20520 Turku, Finland..
    Raj, Manu
    Rao, Sudha Ramachandra
    Ramachandran, Ambady
    India Diabet Res Fdn, New Delhi, India..
    Ramke, Jacqueline
    Univ New S Wales, Sydney, NSW 2052, Australia..
    Ramos, Rafel
    Rampal, Sanjay
    Univ Malaya, Serdang, Malaysia..
    Rasmussen, Finn
    Redon, Josep
    Univ Valencia, E-46003 Valencia, Spain..
    Reganit, Paul Ferdinand M.
    Univ Philippines, Quezon City 1101, Philippines..
    Ribeiro, Robespierre
    Riboli, Elio
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Rigo, Fernando
    Hlth Ctr San Agustin, Madrid, Spain..
    de Wit, Tobias Floris Rinke
    PharmAccess Fdn, Groningen, Netherlands..
    Ritti-Dias, Raphael M.
    Rivera, Juan A.
    Robinson, Sian M.
    Univ Southampton, Southampton SO9 5NH, Hants, England..
    Robitaille, Cynthia
    Publ Hlth Agcy Canada, Montreal, PQ, Canada..
    Rodriguez-Artalejo, Fernando
    Univ Autonoma Madrid, E-28049 Madrid, Spain..
    del Cristo Rodriguez-Perez, Maria
    Canarian Hlth Serv, Madrid, Spain..
    Rodriguez-Villamizar, Laura A.
    Univ Ind Santander, Santander, Colombia..
    Rojas-Martinez, Rosalba
    Rojroongwasinkul, Nipa
    Mahidol Univ, Bangkok 10700, Thailand..
    Romaguera, Dora
    CIBEROBN, Madrid, Spain..
    Ronkainen, Kimmo
    Rosengren, Annika
    Gothenburg Univ, S-41124 Gothenburg, Sweden..
    Rouse, Ian
    Fiji Natl Univ, Nasinu, Fiji..
    Rubinstein, Adolfo
    Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina..
    Ruehli, Frank J.
    Univ Zurich, CH-8006 Zurich, Switzerland..
    Rui, Ornelas
    Univ Madeira, Funchal, Portugal..
    Sandra Ruiz-Betancourt, Blanca
    Inst Mexicano Seguro Social, Rio Grande, Mexico..
    Russo Horimoto, Andrea R. V.
    Rutkowski, Marcin
    Med Univ Gdansk, Gdansk, Poland..
    Sabanayagam, Charumathi
    Singapore Eye Res Inst, Singapore, Singapore..
    Sachdev, Harshpal S.
    Sitaram Bhartia Inst Sci & Res, New Delhi, India..
    Saidi, Olfa
    Fac Med Tunis, Tunis, Tunisia..
    Salanave, Benoit
    French Inst Hlth Surveillance, Lyon, France..
    Salazar Martinez, Eduardo
    Salomaa, Veikko
    Salonen, Jukka T.
    Univ Helsinki, FIN-00014 Helsinki, Finland..
    Salvetti, Massimo
    Univ Brescia, I-25121 Brescia, Italy..
    Sanchez-Abanto, Jose
    Natl Inst Hlth, Lima, Peru..
    Sandjaja,
    Sans, Susana
    Catalan Dept Hlth, Madrid, Spain..
    Santos, Diana A.
    Univ Lisbon, P-1699 Lisbon, Portugal..
    Santos, Osvaldo
    dos Santos, Renata Nunes
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Santos, Rute
    Univ Porto, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Sardinha, Luis B.
    Univ Lisbon, P-1699 Lisbon, Portugal..
    Sarrafzadegan, Nizal
    Saum, Kai-Uwe
    German Canc Res Ctr, Berlin, Germany..
    Savva, Savvas C.
    Res & Educ Inst Child Hlth, Nicosia, Cyprus..
    Scazufca, Marcia
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Rosario, Angelika Schaffrath
    Schargrodsky, Herman
    Hosp Italiano Buenos Aires, Buenos Aires, DF, Argentina..
    Schienkiewitz, Anja
    Schmidt, Ida Maria
    Rigshosp, Copenhagen, Denmark..
    Schneider, Ione J.
    Univ Fed Santa Catarina, BR-88040900 Florianopolis, SC, Brazil..
    Schultsz, Constance
    Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands..
    Schutte, Aletta E.
    MRC North West Univ, Johannesburg, South Africa..
    Sein, Aye Aye
    Minist Hlth, Bangkok, Thailand..
    Senbanjo, Idowu O.
    Lagos State Univ, Coll Med, Lagos, Nigeria..
    Sepanlou, Sadaf G.
    Digest Dis Res Inst, Tehran, Iran..
    Shalnova, Svetlana A.
    Natl Res Ctr Prevent Med, Moscow, Russia..
    Shaw, Jonathan E.
    Shibuya, Kenji
    Univ Tokyo, Tokyo 1138654, Japan..
    Shin, Youchan
    Shiri, Rahman
    Finnish Inst Occupat Hlth, Espoo, Finland..
    Siantar, Rosalynn
    Sibai, Abla M.
    Silva, Antonio M.
    Univ Fed Maranhao, Sao Luis, Brazil.;Univ Fed Santa Catarina, BR-88040900 Florianopolis, SC, Brazil..
    Santos Silva, Diego Augusto
    Simon, Mary
    India Diabet Res Fdn, New Delhi, India..
    Simons, Judith
    St Vincents Hosp, Melbourne, Vic, Australia..
    Simons, Leon A.
    Sjostrom, Michael
    Slowikowska-Hilczer, Jolanta
    Med Univ Lodz, Lodz, Poland..
    Slusarczyk, Przemyslaw
    Smeeth, Liam
    London Sch Hyg & Trop Med, London, England..
    Smith, Margaret C.
    Univ Oxford, Oxford OX1 2JD, England..
    Snijder, Marieke B.
    So, Hung-Kwan
    Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Sobngwi, Eugene
    Univ Yaounde I, Yaounde, Cameroon..
    Soderberg, Stefan
    Umea Univ, S-90187 Umea, Sweden..
    Soekatri, Moesijanti Y. E.
    Hlth Polytech Inst, Bandung, Indonesia..
    Solfrizzi, Vincenzo
    Univ Bari, I-70121 Bari, Italy..
    Sonestedt, Emily
    Lund Univ, S-22100 Lund, Sweden..
    Sorensen, Thorkild I. A.
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Soric, Maroje
    Univ Zagreb, Zagreb 41000, Croatia..
    Jerome, Charles Sossa
    Soumare, Aicha
    Univ Bordeaux, Bordeaux, France..
    Staessen, Jan A.
    Univ Leuven, Leuven, Belgium..
    Starc, Gregor
    Stathopoulou, Maria G.
    INSERM, F-75654 Paris 13, France..
    Staub, Kaspar
    Univ Zurich, CH-8006 Zurich, Switzerland..
    Stavreski, Bill
    Heart Fdn, Sydney, NSW, Australia..
    Steene-Johannessen, Jostein
    Norwegian Sch Sport Sci, Oslo, Norway..
    Stehle, Peter
    Univ Bonn, Bonn, Germany..
    Stein, Aryeh D.
    Emory Univ, Atlanta, GA 30322 USA..
    Stergiou, George S.
    Sotiria Hosp, Athina, Greece..
    Stessman, Jochanan
    Stieber, Jutta
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Stoeckl, Doris
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Stocks, Tanja
    Stokwiszewski, Jakub
    Natl Inst Hyg, Natl Inst Publ Hlth, Warsaw, Poland..
    Stratton, Gareth
    Swansea Univ, Swansea, W Glam, Wales..
    Strufaldi, Maria Wany
    Sun, Chien-An
    Fu Jen Catholic Univ, Taipei, Taiwan..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sung, Yn-Tz
    Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Sunyer, Jordi
    Ctr Res Environm Epidemiol, Madrid, Spain..
    Suriyawongpaisal, Paibul
    Mahidol Univ, Bangkok 10700, Thailand..
    Swinburn, Boyd A.
    Univ Auckland, Auckland 1, New Zealand..
    Sy, Rody G.
    Univ Philippines, Quezon City 1101, Philippines..
    Szponar, Lucjan
    Natl Food & Nutr Inst, Warsaw, Poland..
    Tai, E. Shyong
    Natl Univ Singapore, Singapore 117548, Singapore..
    Tammesoo, Mari-Liis
    Univ Tartu, Ulikooli 18, EE-50090 Tartu, Estonia..
    Tamosiunas, Abdonas
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Tang, Line
    Res Ctr Prevent & Hlth, Odense, Denmark..
    Tang, Xun
    Peking Univ, Hlth Sci Ctr, Beijing 100871, Peoples R China..
    Tanser, Frank
    Univ KwaZulu Natal, Durban, South Africa..
    Tao, Yong
    Peking Univ, Beijing 100871, Peoples R China..
    Tarp, Jakob
    Univ Southern Denmark, Lyngby, Denmark..
    Tarqui-Mamani, Carolina B.
    Natl Inst Hlth, Lima, Peru..
    Taylor, Anne
    Univ Adelaide, Adelaide, SA 5005, Australia..
    Tchibindat, Felicite
    UNICEF, Yaounde, Cameroon..
    Thijs, Lutgarde
    Thuesen, Betina H.
    Tjonneland, Anne
    Danish Canc Soc Res Ctr, Odense, Denmark..
    Tolonen, Hanna K.
    Tolstrup, Janne S.
    Univ Southern Denmark, Lyngby, Denmark..
    Topbas, Murat
    Karadeniz Tech Univ, Ankara, Turkey..
    Topor-Madry, Roman
    Jagiellonian Univ, Coll Med, PL-31007 Krakow, Poland..
    Torrent, Maties
    Traissac, Pierre
    Inst Rech Dev, Lyon, France..
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.;Alexander Technol Educ Inst, Athens, Greece..
    Trinh, Oanh T. H.
    Trivedi, Atul
    Govt Med Coll, New Delhi, India..
    Tshepo, Lechaba
    Sefako Makgatho Hlth Sci Univ, Johannesburg, South Africa..
    Tulloch-Reid, Marshall K.
    Tuomainen, Tomi-Pekka
    Tuomilehto, Jaakko
    Dasman Diabet Inst, Kuwait, Kuwait. Minist Hlth, Hamilton, New Zealand..
    Tynelius, Per
    Karolinska Inst, S-10401 Stockholm, Sweden..
    Tzotzas, Themistoklis
    Hellen Med Assoc Obes, Athens, Greece..
    Tzourio, Christophe
    Univ Bordeaux, Bordeaux, France..
    Ueda, Peter
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Ukoli, Flora A. M.
    Meharry Med Coll, Nashville, TN USA..
    Ulmer, Hanno
    Med Univ Innsbruck, A-6020 Innsbruck, Austria..
    Unal, Belgin
    Dokuz Eylul Univ, TR-35210 Alsancak, Turkey..
    Valdivia, Gonzalo
    Vale, Susana
    Univ Porto, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Valvi, Damaskini
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Utrecht, Netherlands..
    Van Herck, Koen
    Univ Ghent, B-9000 Ghent, Belgium..
    Minh, Hoang Van
    van Valkengoed, Irene G. M.
    Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands..
    Vanderschueren, Dirk
    Katholieke Univ Leuven, Louvain, Belgium..
    Vanuzzo, Diego
    Ctr Prevenz Cardiovasc Udine, Udine, Italy..
    Vatten, Lars
    Vega, Tomas
    Velasquez-Melendez, Gustavo
    Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil..
    Veronesi, Giovanni
    Univ Insubria, Varese, Italy..
    Verschuren, W. M. Monique
    Natl Inst Publ Hlth & Environm, Amsterdam, Netherlands..
    Viegi, Giovanni
    Viet, Lucie
    Natl Inst Publ Hlth & Environm, Amsterdam, Netherlands..
    Viikari-Juntura, Eira
    Finnish Inst Occupat Hlth, Helsinki, Finland..
    Vineis, Paolo
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Vioque, Jesus
    Univ Miguel Hernandez, Madrid, Spain..
    Virtanen, Jyrki K.
    Visvikis-Siest, Sophie
    INSERM, F-75654 Paris 13, France..
    Viswanathan, Bharathi
    Minist Hlth, Victoria, Seychelles..
    Vollenweider, Peter
    Univ Lausanne Hosp, Lausanne, Switzerland..
    Voutilainen, Sari
    Vrijheid, Martine
    Ctr Res Environm Epidemiol, Madrid, Spain..
    Wade, Alisha N.
    Univ Witwatersrand, ZA-2050 Johannesburg, South Africa..
    Wagner, Aline
    Univ Strasbourg, Strasbourg, France..
    Walton, Janette
    Univ Coll Cork, Cork, Ireland..
    Mohamud, Wan Nazaimoon Wan
    Inst Med Res, Serdang, Malaysia..
    Wang, Ming-Dong
    Wang, Qian
    Xinjiang Med Univ, Xinjiang, Peoples R China..
    Wang, Ya Xing
    Beijing Tongren Hosp, Beijing, Peoples R China..
    Wannamethee, S. Goya
    UCL, London WC1E 6BT, England..
    Wareham, Nicholas
    Univ Cambridge, Cambridge CB2 1TN, England..
    Weerasekera, Deepa
    Minist Hlth, Hamilton, New Zealand..
    Whincup, Peter H.
    Univ London, London WC1E 7HU, England..
    Widhalm, Kurt
    Med Univ Vienna, Vienna, Austria..
    Widyahening, Indah S.
    Univ Indonesia, Bandung, Indonesia..
    Wiecek, Andrzej
    Med Univ Silesia, Katowice, Poland..
    Wilks, Rainford J.
    Willeit, Johann
    Med Univ Innsbruck, A-6020 Innsbruck, Austria..
    Wojtyniak, Bogdan
    Wong, Jyh Eiin
    Univ Kebangsaan Malaysia, Bangi 43600, Malaysia..
    Wong, Tien Yin
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Woo, Jean
    Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Woodward, Mark
    Univ Sydney, Sydney, NSW 2006, Australia.;Univ Oxford, Oxford OX1 2JD, England..
    Wu, Frederick C.
    Univ Manchester, Manchester M13 9PL, Lancs, England..
    Wu, JianFeng
    Shandong Univ Tradit Chinese Med, Jinan, Peoples R China..
    Wu, Shou Ling
    Kailuan Gen Hosp, Beijing, Peoples R China..
    Xu, Haiquan
    Minist Agr, Inst Food & Nutr Dev, Beijing, Peoples R China..
    Xu, Liang
    Capital Med Univ, Beijing, Peoples R China..
    Yamborisut, Uruwan
    Mahidol Univ, Bangkok 10700, Thailand..
    Yan, Weili
    Fudan Univ, Shanghai, Peoples R China..
    Yang, Xiaoguang
    Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China..
    Yardim, Nazan
    Minist Hlth, Ankara, Turkey..
    Ye, Xingwang
    Univ Chinese Acad Sci, Beijing, Peoples R China..
    Yiallouros, Panayiotis K.
    Cyprus Univ Technol, Limassol, Cyprus..
    Yoshihara, Akihiro
    Niigata Univ, Niigata 95021, Japan..
    You, Qi Sheng
    Younger-Coleman, Novie O.
    Yusoff, Ahmad F.
    Minist Hlth, Kuala Lumpur, Malaysia..
    Zainuddin, Ahmad A.
    Univ Teknol MARA, Serdang, Malaysia..
    Zambon, Sabina
    Univ Padua, I-35100 Padua, Italy..
    Zdrojewski, Tomasz
    Med Univ Gdansk, Gdansk, Poland..
    Zeng, Yi
    Duke Univ, Durham, NC 27706 USA.;Peking Univ, Beijing 100871, Peoples R China..
    Zhao, Dong
    Capital Med Univ, Beijing Anzhen Hosp, Beijing, Peoples R China..
    Zhao, Wenhua
    Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China..
    Zheng, Yingfeng
    Singapore Eye Res Inst, Singapore, Singapore..
    Zhou, Maigeng
    Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China..
    Zhu, Dan
    Inner Mongolia Med Univ, Inner Mongolia, Peoples R China..
    Zimmermann, Esther
    Bispebjerg Hosp, Copenhagen, Denmark.;Frederiksberg Univ Hosp, Frederiksberg, Denmark..
    Zuniga Cisneros, Julio
    Gorgas Mem Inst Publ Hlth, Panama City, Panama..
    Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants2016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, no 10026, p. 1377-1396Article in journal (Refereed)
    Abstract [en]

    Background Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries.

    Methods We analysed, with use of a consistent protocol, population-based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (<18.5 kg/m(2) [underweight], 18.5 kg/m(2) to <20 kg/m(2), 20 kg/m(2) to <25 kg/m(2), 25 kg/m(2) to <30 kg/m(2), 30 kg/m(2) to <35 kg/m(2), 35 kg/m(2) to <40 kg/m(2), = 40 kg/m(2) [morbid obesity]), by sex in 200 countries and territories, organised in 21 regions. We calculated the posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue.

    Findings We used 1698 population-based data sources, with more than 19.2 million adult participants (9.9 million men and 9.3 million women) in 186 of 200 countries for which estimates were made. Global age-standardised mean BMI increased from 21.7 kg/m(2) (95% credible interval 21.3-22.1) in 1975 to 24.2 kg/m(2) (24.0-24.4) in 2014 in men, and from 22.1 kg/m(2) (21.7-22.5) in 1975 to 24.4 kg/m(2) (24.2-24.6) in 2014 in women. Regional mean BMIs in 2014 for men ranged from 21.4 kg/m(2) in central Africa and south Asia to 29.2 kg/m(2) (28.6-29.8) in Polynesia and Micronesia; for women the range was from 21.8 kg/m(2) (21.4-22.3) in south Asia to 32.2 kg/m(2) (31.5-32.8) in Polynesia and Micronesia. Over these four decades, age-standardised global prevalence of underweight decreased from 13.8% (10.5-17.4) to 8.8% (7.4-10.3) in men and from 14.6% (11.6-17.9) to 9.7% (8.3-11.1) in women. South Asia had the highest prevalence of underweight in 2014, 23.4% (17.8-29.2) in men and 24.0% (18.9-29.3) in women. Age-standardised prevalence of obesity increased from 3.2% (2.4-4.1) in 1975 to 10.8% (9.7-12.0) in 2014 in men, and from 6.4% (5.1-7.8) to 14.9% (13.6-16.1) in women. 2.3% (2.0-2.7) of the world's men and 5.0% (4.4-5.6) of women were severely obese (ie, have BMI = 35 kg/m(2)). Globally, prevalence of morbid obesity was 0.64% (0.46-0.86) in men and 1.6% (1.3-1.9) in women.

    Interpretation If post-2000 trends continue, the probability of meeting the global obesity target is virtually zero. Rather, if these trends continue, by 2025, global obesity prevalence will reach 18% in men and surpass 21% in women; severe obesity will surpass 6% in men and 9% in women. Nonetheless, underweight remains prevalent in the world's poorest regions, especially in south Asia.

  • 308. Di Mario, C.
    et al.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Dudek, D.
    Sabate, M.
    Degertekin, M.
    Commentary: The risk of over-regulation2011In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 342, p. d3021-Article in journal (Other academic)
  • 309. Di Mario, Carlo
    et al.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Ludman, Peter
    Windecker, Stephan
    Sabate, Manel
    Scientific societies and clinical trials2010In: EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, ISSN 1969-6213, Vol. 6, no 2, p. 185-188Article in journal (Refereed)
  • 310. Diener, H. C.
    et al.
    Marijon, E.
    Le Heuzey, J. -Y
    Connolly, S.
    Noack, H.
    Brueckmann, M.
    Eikelboom, J.
    Ezekowitz, M.
    Clemens, A.
    Reilly, P.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Yusuf, S.
    Recurrent Events and Mortality Among Atrial Fibrillation Patients Treated with Dabigatran or Warfarin in the RE-LY Trial2013In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 35, p. 165-165Article in journal (Other academic)
  • 311. Diener, H. -C
    et al.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Brueckmann, M.
    Noack, H.
    Eikelboom, J.
    Ezekowitz, M.
    Clemens, A.
    Reilly, P.
    Yusuf, S.
    Connolly, S.
    Clinical Outcomes of Patients with Previous Transient Ischaemic Attack or Stroke - a Subgroup Analysis of the Long-Term Extension of Dabigatran in Patients with Atrial Fibrillation (RELY-ABLE) Study2013In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 35, p. 121-121Article in journal (Other academic)
  • 312. Diener, Hans Christoph
    et al.
    Connolly, Stuart J.
    Ezekowitz, Michael D.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Reilly, Paul A.
    Yang, Sean
    Xavier, Denis
    Di Pasquale, Giuseppe
    Yusuf, Salim
    Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial2010In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 9, no 12, p. 1157-1163Article in journal (Refereed)
    Abstract [en]

    Background In the Randomised Evaluation of Long Term Anticoagulation Therapy (RE LY) trial dabigatran reduced occurrence of both stroke and haemorrhage compared with warfarin in patients who had atrial fibrillation and were at increased risk of stroke We aimed to assess the effects of dabigatran compared with warfarin in the subgroup of patients with previous stroke or transient ischaemic attack

    Methods In the RE LY trial 18113 patients from 967 centres in 44 countries were randomly assigned to 110 mg or 150 mg dabigatran twice daily or to warfarin dose adjusted to international normalised ratio 2 0 to 3 0 Median follow up was 2 0 years (IQR 1 14-2 86) and the primary outcome was stroke or systemic embolism The primary safety outcome was major haemorrhage Patients and investigators were aware of whether patients received warfarin or dabigatran but not of dabigatran dose and event adjudicators were masked to treatment In a predefined analysis we investigated the outcomes of the RE LY trial in subgroups of patients with or without previous stroke or transient ischaemic attack RE LY is registered with ClimcalTriaLs gov NCT00262600

    Findings Within the subgroup of patients with previous stroke or transient ischaemic attack, 1195 patients were from the 110 mg dabigatran group 1233 from the 150 mg dabigatran group and 1195 from the warfarin group Stroke or systemic embolism occurred m 65 patients (2 78% per year) on warfarin compared with 55 (2 32% per year) on 110 mg dabigatran (relative risk 0 84, 95% CI 0 58-1 20) and 51 (2 07% per year) on 150 mg dabigatran (0 75 0 52-1 08) The rate of major bleeding was significantly lower in patients on 110 mg dabigatran (RR 0 66 95% CI 0 48-0 90) and similar in those on 150 mg dabigatran (RR 1 01 95% CI 0 77-1 34) compared with those on warfarin The effects of both doses of dabigatran compared with warfarin were not significantly different between patients with previous stroke or transient ischaemic attack and those without for any of the outcomes from RE LY apart from vascular death (110 mg group compared with warfaric group mteraction p=0 038)

    Interpretation In patients with previous stroke or transient ischaemic attack, the effects of 110 mg dabigatran and 150 mg dabigatran on stroke or systemic embolism were similar to those of warfarin Most effects of both dabigatran doses were consistent in patients with versus those without previous stroke or transient ischaemic attack.

  • 313.
    Dimopoulou, Angeliki
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Dual Energy CT in patients with complicated renal calculi undergoing Percutaneous Nephrolithotomy: virtual nonenhanced images vs. true nonenhanced images; correlation on calculi number, volume, size and attenuationManuscript (preprint) (Other academic)
  • 314.
    Djureinovic, Dijana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Dodig-Crnkovic, Tea
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden.
    Hellström, Cecilia
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden.
    Holgersson, Georg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Bergqvist, Michael
    Department of Oncology, Gavle Hospital, Gavle, Sweden..
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Schwenk, Jochen M.
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer2018In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 125, p. 157-163Article in journal (Refereed)
    Abstract [en]

    Cancer testis antigens (CTAs) are defined as proteins that are specifically expressed in testis or placenta and their expression is frequently activated in cancer. Due to their ability to induce an immune response, CTAs may serve as suitable targets for immunotherapy. The aim of this study was to evaluate if there is reactivity against CTAs in the plasma of non-small cell lung cancer (NSCLC) patients through the detection of circulating antibodies. 

    To comprehensively analyse auto-antibodies against CTAs the multiplexing capacities of suspension bead array technology was used. Bead arrays were created with 120 protein fragments, representing 112 CTAs. Reactivity profiles were measured in plasma samples from 133 NSCLC patients and 57 cases with benign lung diseases. Altogether reactivity against 69 antigens, representing 81 CTAs, was demonstrated in at least one of the analysed samples. Twenty-nine of the antigens (45 CTAs) demonstrated exclusive reactivity in NSCLC samples. Reactivity against CT47A genes, PAGE3, VCX, MAGEB1, LIN28B and C12orf54 were only found in NSCLC patients at a frequency of 1%-4%. The presence of autoantibodies towards these six antigens was confirmed in an independent group of 34 NSCLC patients.

    In conclusion, we identified autoantibodies against CTAs in the plasma of lung cancer patients. The reactivity pattern of autoantibodies was higher in cancer patients compared to the benign group, stable over time, but low in frequency of occurrence. The findings suggest that some CTAs are immunogenic and that these properties can be utilized as immune targets.

  • 315.
    Djureinovic, Dijana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Hallström, Bjorn M.
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Horie, Masafumi
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan..
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    La Fleur, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Fagerberg, Linn
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Brunnström, Hans
    Reg Labs Reg Skane, Dept Pathol, Lund, Sweden..
    Lindskog, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Madjar, Katrin
    Tech Univ Dortmund, Dept Stat, Dortmund, Germany..
    Rahnenfuehrer, Joerg
    Tech Univ Dortmund, Dept Stat, Dortmund, Germany..
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Koyi, Hirsh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Brandén, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Edlund, Karolina
    Tech Univ Dortmund, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany..
    Hengstler, Jan G.
    Tech Univ Dortmund, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany..
    Lambe, Mats
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Saito, Akira
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan..
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Uhlen, Mathias
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Profiling cancer testis antigens in non-small-cell lung cancer2016In: JCI INSIGHT, ISSN 2379-3708, Vol. 1, no 10, article id e86837Article in journal (Refereed)
    Abstract [en]

    Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies.

  • 316.
    Djureinovic, Dijana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Hallström, Björn
    Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    La Fleur, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Fagerberg, Linn
    Brunnström, Hans
    Lund Univ, Div Pathol, Lund, Sweden..
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Koyi, Hirsh
    Gavle Cent Hosp, Dept Pneumol, S-80187 Gavle, Sweden..
    Lambe, Mats
    Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden..
    Branden, Eva
    Gavle Cent Hosp, Dept Pneumol, S-80187 Gavle, Sweden..
    Lindskog, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Uhlen, Mathias
    Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    The Identification of Therapeutic Targets in Lung Cancer Based on Transcriptomic and Proteomic Characterization of Cancer-Testis Antigens2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, p. S256-S256Article in journal (Other academic)
  • 317. Do, Ron
    et al.
    Willer, Cristen J.
    Schmidt, Ellen M.
    Sengupta, Sebanti
    Gao, Chi
    Peloso, Gina M.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kanoni, Stavroula
    Ganna, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Chen, Jin
    Buchkovich, Martin L.
    Mora, Samia
    Beckmann, Jacques S.
    Bragg-Gresham, Jennifer L.
    Chang, Hsing-Yi
    Demirkan, Ayse
    Den Hertog, Heleen M.
    Donnelly, Louise A.
    Ehret, Georg B.
    Esko, Tonu
    Feitosa, Mary F.
    Ferreira, Teresa
    Fischer, Krista
    Fontanillas, Pierre
    Fraser, Ross M.
    Freitag, Daniel F.
    Gurdasani, Deepti
    Heikkila, Kauko
    Hyppoenen, Elina
    Isaacs, Aaron
    Jackson, Anne U.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnson, Toby
    Kaakinen, Marika
    Kettunen, Johannes
    Kleber, Marcus E.
    Li, Xiaohui
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Magnusson, Patrik K. E.
    Mangino, Massimo
    Mihailov, Evelin
    Montasser, May E.
    Mueller-Nurasyid, Martina
    Nolte, Ilja M.
    O'Connell, Jeffrey R.
    Palmer, Cameron D.
    Perola, Markus
    Petersen, Ann-Kristin
    Sanna, Serena
    Saxena, Richa
    Service, Susan K.
    Shah, Sonia
    Shungin, Dmitry
    Sidore, Carlo
    Song, Ci
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Strawbridge, Rona J.
    Surakka, Ida
    Tanaka, Toshiko
    Teslovich, Tanya M.
    Thorleifsson, Gudmar
    Van den Herik, Evita G.
    Voight, Benjamin F.
    Volcik, Kelly A.
    Waite, Lindsay L.
    Wong, Andrew
    Wu, Ying
    Zhang, Weihua
    Absher, Devin
    Asiki, Gershim
    Barroso, Ines
    Been, Latonya F.
    Bolton, Jennifer L.
    Bonnycastle, Lori L.
    Brambilla, Paolo
    Burnett, Mary S.
    Cesana, Giancarlo
    Dimitriou, Maria
    Doney, Alex S. F.
    Doering, Angela
    Elliott, Paul
    Epstein, Stephen E.
    Eyjolfsson, Gudmundur Ingi
    Gigante, Bruna
    Goodarzi, Mark O.
    Grallert, Harald
    Gravito, Martha L.
    Groves, Christopher J.
    Hallmans, Goran
    Hartikainen, Anna-Liisa
    Hayward, Caroline
    Hernandez, Dena
    Hicks, Andrew A.
    Holm, Hilma
    Hung, Yi-Jen
    Illig, Thomas
    Jones, Michelle R.
    Kaleebu, Pontiano
    Kastelein, John J. P.
    Khaw, Kay-Tee
    Kim, Eric
    Klopp, Norman
    Komulainen, Pirjo
    Kumari, Meena
    Langenberg, Claudia
    Lehtimaki, Terho
    Lin, Shih-Yi
    Lindstrom, Jaana
    Loos, Ruth J. F.
    Mach, Francois
    McArdle, Wendy L.
    Meisinger, Christa
    Mitchell, Braxton D.
    Mueller, Gabrielle
    Nagaraja, Ramaiah
    Narisu, Narisu
    Nieminen, Tuomo V. M.
    Nsubuga, Rebecca N.
    Olafsson, Isleifur
    Ong, Ken K.
    Palotie, Aarno
    Papamarkou, Theodore
    Pomilla, Cristina
    Pouta, Anneli
    Rader, Daniel J.
    Reilly, Muredach P.
    Ridker, Paul M.
    Rivadeneira, Fernando
    Rudan, Igor
    Ruokonen, Aimo
    Samani, Nilesh
    Scharnagl, Hubert
    Seeley, Janet
    Silander, Kaisa
    Stancakova, Alena
    Stirrups, Kathleen
    Swift, Amy J.
    Tiret, Laurence
    Uitterlinden, Andre G.
    van Pelt, L. Joost
    Vedantam, Sailaja
    Wainwright, Nicholas
    Wijmenga, Cisca
    Wild, Sarah H.
    Willemsen, Gonneke
    Wilsgaard, Tom
    Wilson, James F.
    Young, Elizabeth H.
    Zhao, Jing Hua
    Adair, Linda S.
    Arveiler, Dominique
    Assimes, Themistocles L.
    Bandinelli, Stefania
    Bennett, Franklyn
    Bochud, Murielle
    Boehm, Bernhard O.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    Bornstein, Stefan R.
    Bovet, Pascal
    Burnier, Michel
    Campbell, Harry
    Chakravarti, Aravinda
    Chambers, John C.
    Chen, Yii-Der Ida
    Collins, Francis S.
    Cooper, Richard S.
    Danesh, John
    Dedoussis, George
    de Faire, Ulf
    Feranil, Alan B.
    Ferrieres, Jean
    Ferrucci, Luigi
    Freimer, Nelson B.
    Gieger, Christian
    Groop, Leif C.
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hamsten, Anders
    Harris, Tamara B.
    Hingorani, Aroon
    Hirschhorn, Joel N.
    Hofman, Albert
    Hovingh, G. Kees
    Hsiung, Chao Agnes
    Humphries, Steve E.
    Hunt, Steven C.
    Hveem, Kristian
    Iribarren, Carlos
    Jarvelin, Marjo-Riitta
    Jula, Antti
    Kahonen, Mika
    Kaprio, Jaakko
    Kesaniemi, Antero
    Kivimaki, Mika
    Kooner, Jaspal S.
    Koudstaal, Peter J.
    Krauss, Ronald M.
    Kuh, Diana
    Kuusisto, Johanna
    Kyvik, Kirsten O.
    Laakso, Markku
    Lakka, Timo A.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, Cecilia M.
    Martin, Nicholas G.
    Maerz, Winfried
    McCarthy, Mark I.
    McKenzie, Colin A.
    Meneton, Pierre
    Metspalu, Andres
    Moilanen, Leena
    Morris, Andrew D.
    Munroe, Patricia B.
    Njolstad, Inger
    Pedersen, Nancy L.
    Power, Chris
    Pramstaller, Peter P.
    Price, Jackie F.
    Psaty, Bruce M.
    Quertermous, Thomas
    Rauramaa, Rainer
    Saleheen, Danish
    Salomaa, Veikko
    Sanghera, Dharambir K.
    Saramies, Jouko
    Schwarz, Peter E. H.
    Sheu, Wayne H-H
    Shuldiner, Alan R.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Spector, Tim D.
    Stefansson, Kari
    Strachan, David P.
    Tayo, Bamidele O.
    Tremoli, Elena
    Tuomilehto, Jaakko
    Uusitupa, Matti
    van Duijn, Cornelia M.
    Vollenweider, Peter
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wareham, Nicholas J.
    Whitfield, John B.
    Wolffenbuttel, Bruce H. R.
    Altshuler, David
    Ordovas, Jose M.
    Boerwinkle, Eric
    Palmer, Colin N. A.
    Thorsteinsdottir, Unnur
    Chasman, Daniel I.
    Rotter, Jerome I.
    Franks, Paul W.
    Ripatti, Samuli
    Cupples, L. Adrienne
    Sandhu, Manjinder S.
    Rich, Stephen S.
    Boehnke, Michael
    Deloukas, Panos
    Mohlke, Karen L.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Abecasis, Goncalo R.
    Daly, Mark J.
    Neale, Benjamin M.
    Kathiresan, Sekar
    Common variants associated with plasma triglycerides and risk for coronary artery disease2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 11, p. 1345-+Article in journal (Refereed)
    Abstract [en]

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

  • 318.
    Dondo, T. B.
    et al.
    Univ Leeds, Div Epidemiol & Biostat, LICAMM, Leeds, W Yorkshire, England..
    Hall, M.
    Univ Leeds, Div Epidemiol & Biostat, LICAMM, Leeds, W Yorkshire, England..
    West, R.
    Univ Leeds, Leeds Inst Hlth Sci, Leeds, W Yorkshire, England..
    Jernberg, T.
    Karolinska Univ Hosp, Cardiol Sect, Dept Med, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bueno, H.
    Univ Hosp 12 Octubre, Inst Invest I 12, Madrid, Spain.;Univ Hosp 12 Octubre, Dept Cardiol, Madrid, Spain..
    Deanfield, J. E.
    UCL, Natl Inst Cardiovasc Outcomes Res, London, England..
    Hemingway, H.
    UCL, Farr Inst, London, England..
    Timmis, A. D.
    Barts Hlth NHS Trust, Natl Inst Hlth Biomed Res Unit, London, England..
    Gale, C. P.
    Univ Leeds, Div Epidemiol & Biostat, LICAMM, Leeds, W Yorkshire, England..
    Beta blocker use and mortality in hospital survivors of acute myocardial infarction without heart failure2016In: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, p. 1253-1253Article in journal (Other academic)
  • 319.
    Dondo, Tatendashe B.
    et al.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, MRC, Bioinformat Ctr, Level 11,Worsley Bldg, Leeds LS2 9JT, W Yorkshire, England..
    Hall, Marlous
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, MRC, Bioinformat Ctr, Level 11,Worsley Bldg, Leeds LS2 9JT, W Yorkshire, England..
    West, Robert M.
    Univ Leeds, Leeds Inst Hlth Sci, Leeds, W Yorkshire, England..
    Jernberg, Tomas
    Karolinska Univ Hosp, Karolinska Inst, Dept Cardiol, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bueno, Hector
    Ctr Nacl Invest Cardiovasc, Madrid, Spain.;Hosp Univ 12 Octubre, Inst Invest i 12, Madrid, Spain.;Hosp Univ 12 Octubre, Cardiol Dept, Madrid, Spain.;Univ Complutense Madrid, Fac Med, Madrid, Spain..
    Danchin, Nicolas
    Hop Europeen Georges Pompidou, Dept Cardiol, Paris, France.;AP HP, Paris, France.;Univ Paris 05, Paris, France..
    Deanfield, John E.
    UCL, Natl Inst Cardiovasc Outcomes Res, London, England..
    Hemingway, Harry
    UCL, London, England.;Farr Inst Hlth Informat Res, London, England..
    Fox, Keith A. A.
    Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland..
    Timmis, Adam D.
    Barts Heart Ctr, Biomed Res Unit, Natl Inst Hlth, London, England..
    Gale, Chris P.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, MRC, Bioinformat Ctr, Level 11,Worsley Bldg, Leeds LS2 9JT, W Yorkshire, England.;York Teaching Hosp NHS Fdn Trust, Dept Cardiol, York, N Yorkshire, England..
    beta-Blockers and Mortality After Acute Myocardial Infarction in Patients Without Heart Failure or Ventricular Dysfunction2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 69, no 22, p. 2710-2720Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if beta-blockers are associated with reduced mortality.

    OBJECTIVES: The goal of this study was to determine the association between beta-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD).

    METHODS: This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of beta-blockers and 1-year mortality.

    RESULTS: Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non-ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received beta-blockers, respectively. For the entire cohort, with> 163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received beta-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without beta-blocker use (average treatment effect [ATE] coefficient: 0.07; 95% confidence interval [CI]: -0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: -0.98 to 1.58; p = 0.637) and non-ST-segment elevation myocardial infarction (ATE coefficient: -0.07; 95% CI: -0.68 to 0.54; p = 0.819).

    CONCLUSIONS: Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of beta-blockers was not associated with a lower risk of death at any time point up to 1 year.

  • 320. Douketis, J.
    et al.
    Healey, J. S.
    Brueckmann, M.
    Fraessdorf, M.
    Spyropoulos, A.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Oldgren, J.
    Reilly, P.
    Ezekowitz, M.
    Connolly, S.
    Yusuf, S.
    Bleeding and thromboembolic outcomes in warfarin-and dabigatran-treated patients in the RE-LY trial who required an urgent surgery or procedure2015In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, no S2, p. 393-394, article id PO362-MONArticle in journal (Other academic)
  • 321.
    Douketis, James D.
    et al.
    McMaster Univ, Dept Med, Hamilton, ON, Canada..
    Healey, Jeff S.
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Brueckmann, Martina
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.;Mannheim Univ Heidelberg, Fac Med, Heidelberg, Germany..
    Fraessdorf, Mandy
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany..
    Spyropoulos, Alex C.
    Hofstra North Shore Long Isl Jewish Sch Med, Manhasset, NY USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Reilly, Paul
    Boehringer Ingelheim Pharmaceut, Ridgefield, CT USA..
    Ezekowitz, Michael D.
    Jefferson Med Coll, Wynnewood, PA USA..
    Connolly, Stuart J.
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Yusuf, Salim
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Eikelboom, John W.
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Urgent surgery or procedures in patients taking dabigatran or warfarin: Analysis of perioperative outcomes from the RE-LY trial2016In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 139, p. 77-81Article, review/survey (Refereed)
    Abstract [en]

    Background: There is concern about the management of anticoagulated patients with atrial fibrillation (AF) who require an urgent surgery/procedure, especially in those who are receiving a direct oral anticoagulant such as dabigatran. Methods: We accessed the database from RE-LY, a randomized trial comparing dabigatran (110 mg and 150 mg twice daily) with warfarin for stroke prevention in AF, to assess patients who had an urgent and elective surgery/procedure. We compared the risk for thromboembolism, major bleeding and mortality according to treatment allocation (dabigatran 110 mg or 150 mg, or warfarin) or surgery/procedure type (urgent or elective). Outcomes were assessed from day-7 to day 30 after a surgery/procedure. Results: 353 patients (2.0% of study population) had an urgent surgery/procedure and 4168 patients (23.1% of study population) had an elective surgery/procedure. In patients on dabigatran 110 mg, dabigatran 150 mg and warfarin who had an urgent surgery/procedure: rates of thromboembolism were 16.1%, 7.4%, and 10.5%; rates of major bleeding were 17.0%, 17.6%, and 22.9%; rates of mortality were 6.3%, 1.5%, and 2.9%, respectively (P > 0.50 for all comparisons). Rates of these outcomes were multi-fold higher in patients having an urgent rather than an elective surgery/procedure (P < 0.5 for all comparisons). Conclusion: In anticoagulated patients with atrial fibrillation who require an urgent surgery/procedure, the risks for thromboembolism, major bleeding and mortality did not differ depending on treatment with dabigatran or warfarin, but rates of these outcomes were multi-fold higher than in patients having an elective surgery/procedure.

  • 322.
    Ducrocq, G.
    et al.
    Hop Bichat Claude Bernard, AP HP, F-75877 Paris 18, France..
    Schulte, P. J.
    Duke Clin Res Inst, Durham, NC USA..
    Budaj, A.
    Grochowski Hosp, Warsaw, Poland..
    Cornel, J. H.
    Med Ctr Alkmaar, Alkmaar, Netherlands..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Himmelmann, A.
    AstraZeneca Res & Dev, Molndal, Sweden..
    Husted, S.
    Holstebro Hosp, Holstebro, Denmark..
    Storey, R. F.
    Univ Sheffield, Sheffield, S Yorkshire, England..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Steg, P. G.
    Hop Bichat Claude Bernard, F-75877 Paris 18, France..
    Balancing the risk of ischaemic and bleeding events in ACS2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 860-861Article in journal (Other academic)
  • 323. Ducrocq, G.
    et al.
    Schulte, P. J.
    Cannon, C. P.
    Becker, R. C.
    Harrington, R. A.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Himmelmann, A.
    Sorbets, E.
    Wallentin, L.
    Steg, P. G.
    Prognostic implications of major bleeding on mortality in ACS patients: An analysis of the PLATO trial2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 724-724Article in journal (Refereed)
  • 324.
    Ducrocq, Gregory
    et al.
    FACT, Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.;INSERM, Unite 1148, Paris, France..
    Schulte, Phillip J.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.;Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA..
    Budaj, Andrzej
    Grochowski Hosp, Postgrad Med Sch, Warsaw, Poland..
    Cornel, Jan H.
    Noordwest Ziekenhuisgrp, Dept Cardiol, Alkmaar, Netherlands..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Himmelmann, Anders
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    Hunted, Steen
    Hosp Unit Wwst, Med Dept, Herning Holstebro, Denmark..
    Storey, Robert F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England..
    Cannon, Christopher P.
    Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.;Baim Inst Clin Res Boston, Boston, MA USA..
    Becker, Richard C.
    Univ Cincinnati, Coll Med, Heart Lung & Vasc Inst, Div Cardiovasc Hlth & Dis, Cincinnati, OH USA..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Katus, Hugo A.
    Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany..
    Lopes, Renato D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Sorbets, Enunanuel
    FACT, Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Paris, France.;INSERM, Unite 1148, Paris, France.;Hop Avicenne, AP HP, Bobigny, France.;Univ Paris 13, Bobigny, France..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Steg, Philippe Gabriel
    FACT, Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.;INSERM, Unite 1148, Paris, France.;NHLI Imperial Coll, Royal Brampton Hosp, ICMS, London, England..
    Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 186, p. 91-99Article in journal (Refereed)
    Abstract [en]

    Background: Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality.

    Methods: In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events.

    Results: A total of 822 patients (4.4%) had >= 1 spontaneous ischemic event; 485 patients (2.6%), >= 1 spontaneous PLATO major bleed, 282 (1.5%), >= 1 spontaneous TIMI major bleed; and 207 (1.1%), >= 1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% Cls) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P > 0.05)

    Conclusions: In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem "prognostically equivalent" to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.

  • 325. Dudas, Kerstin
    et al.
    Björck, Lena
    Jernberg, Tomas
    Lappas, Georgios
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Rosengren, Annika
    Differences between acute myocardial infarction and unstable angina: a longitudinal cohort study reporting findings from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA)2013In: BMJ open, ISSN 2044-6055, Vol. 3, no 1, p. e002155-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    The aim of this study was to compare risk factors and comorbidities in patients with a first episode of acute coronary syndrome (ACS), being either acute myocardial infarction (AMI) or unstable angina pectoris (UAP).

    DESIGN:

    Cross-sectional and prospective.

    SETTING:

    The Swedish population.

    PARTICIPANTS:

    A total of 145 346 consecutive patients aged 25-105 years included in the Swedish Register of Cardiac Intensive Care Admission (Register of Information and Knowledge about Swedish Heart Intensive Care) and admitted to hospital between 1 January 1996 and 30 June 2009 with a first episode of either AMI or UAP. PRIMARY AND SECONDARY OUTCOME MEASURES: Type of ACS and 1-year outcome.

    RESULTS:

    Compared with patients with UAP, AMI patients were more likely to be older; men; and former or current smokers; they were also more likely to have had diabetes and peripheral artery disease, but had lower rates of prior heart failure (HF) and fewer cardioprotective medications on admission. Among patients aged <65 years, 1.4% of men and 1.6% of women with UAP died within 1 year in 2003-2006 compared with 4.2% of men and 3.1% of women AMI patients (multiple-adjusted OR 3.54 (99% CI 2.29 to 5.48) in women and 2.65 (99% CI 2.11 to 3.34) in men). Corresponding proportions in patients aged ≥65 years was 7.5% in men and 7.6% in women with UAP and 21.5% in men and 17.8% in women with AMI.

    CONCLUSIONS:

    In patients with a first-time ACS episode, male sex, slightly older age, smoking, diabetes and peripheral arterial disease (PAD), but fewer cardioprotective medications, were major determinants for presenting with AMI. Despite increasingly active treatment in AMI and more inclusive diagnostic criteria in recent years, persistently worse prognosis was observed in AMI patients.

  • 326.
    Dunder, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lithell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Evaluation of a scoring scheme, including proinsulin and the apolipoprotein B/apolipoprotein A1 ratio, for the risk of acute coronary events in middle-aged men: Uppsala Longitudinal Study of Adult Men (ULSAM)2004In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 148, no 4, p. 596-601Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In recent years, the importance of circulating levels of proinsulin and apolipoproteins as risk factors for myocardial infarction (MI) has been highlighted. The aims of the current study were to investigate whether introduction of these new markers of coronary risk could improve the performance of a risk prediction score and to compare this new score with traditional scoring schemes, such as the Framingham Study and the Prospective Cardiovascular Munster (PROCAM) Study schemes.

    METHODS: From 1970 to 1973 all 50-year-old men in Uppsala, Sweden, were invited to participate in a health survey aimed at identifying risk factors for cardiovascular disease (the Uppsala Longitudinal Study of Adult Men [ULSAM] cohort). The current study investigated metabolic characteristics at baseline and the incidence of fatal and nonfatal MI (n = 251) during 28.7 years of follow-up in 1108 men who were free of coronary heart disease at baseline.

    RESULTS: The risk prediction score was derived from one half of the population sample from the ULSAM cohort and included systolic blood pressure, smoking, family history of MI, serum proinsulin, and the ratio between apolipoprotein B and apolipoprotein A1. The score was highly predictive for future MI (hazard ratio, 1.77 for a 1 SD increase; 95% CI, 1.49 to 2.10, P <.0001) in the other half of the population that was not used for generating the score. The ULSAM score performed slightly better than the Framingham and PROCAM scores (evaluated as areas under the receiver operating curves; Framingham, 61%; PROCAM, 63%; ULSAM, 66%; P =.08).

    CONCLUSIONS: A risk prediction score for MI including proinsulin and the ratio between apolipoprotein B and apolipoprotein A1 was developed in middle-aged men. This score was highly predictive for future fatal and nonfatal MI and proved to be at least as good as the Framingham and the PROCAM scores, being based on traditional risk factors.

  • 327.
    Durheim, Michael T.
    et al.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC USA..
    Cyr, Derek D.
    Duke Clin Res Inst, Durham, NC USA..
    Lopes, Renato D.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA..
    Thomas, Laine E.
    Duke Clin Res Inst, Durham, NC USA..
    Tsuang, Wayne M.
    Cleveland Clin, Dept Pulm Med, Cleveland, OH 44106 USA..
    Gersh, Bernard J.
    Coll Med, Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Granger, Christopher B.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA..
    Palmer, Scott M.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC USA..
    Al-Khatib, Sana M.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA..
    Chronic obstructive pulmonary disease in patients with atrial fibrillation: Insights from the ARISTOTLE trial2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 202, p. 589-594Article in journal (Refereed)
    Abstract [en]

    Background: Comorbid chronic obstructive pulmonary disease (COPD) is associated with poor outcomes among patients with cardiovascular disease. The risks of stroke and mortality associated with COPD among patients with atrial fibrillation are not well understood. Methods: We analyzed patients from ARISTOTLE, a randomized trial of 18,201 patients with atrial fibrillation comparing the effects of apixaban versus warfarin on the risk of stroke or systemic embolism. Using Cox proportional hazards models, we assessed the associations between comorbid COPD and risk of stroke or systemic embolism and of mortality, adjusting for treatment allocation, smoking history and other risk factors. Results: COPD was present in 1950 (10.8%) of 18,134 patients with data on pulmonary disease history. After multivariable adjustment, COPD was not associated with risk of stroke or systemic embolism (adjusted HR 0.85 [95% CI 0.60, 1.21], p = 0.356). However, COPD was associated with a higher risk of all-cause mortality (adjusted HR 1.60 [95% CI 1.36, 1.88], p < 0.001) and both cardiovascular and non-cardiovascular mortality. The benefit of apixaban over warfarin on stroke or systemic embolism was consistent among patients with and without COPD (HR 0.92 [95% CI 0.52, 1.63] versus 0.78 [95% CI 0.65, 0.95], interaction p = 0.617). Conclusions: COPD was independently associated with increased risk of cardiovascular and non-cardiovascular mortality among patients with atrial fibrillation, but was not associated with risk of stroke or systemic embolism. The effect of apixaban on stroke or systemic embolism in COPD patients was consistent with its effect in the overall trial population.

  • 328. Déry, Jean-Pierre
    et al.
    Mahaffey, Kenneth W
    Tricoci, Pierluigi
    White, Harvey D
    Podder, Mohua
    Westerhout, Cynthia M
    Moliterno, David J
    Harrington, Robert A
    Chen, Edmond
    Strony, John
    Van de Werf, Frans
    Ziada, Khaled M
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Aylward, Philip E
    Armstrong, Paul W
    Rao, Sunil V
    Arterial access site and outcomes in patients undergoing percutaneous coronary intervention with and without vorapaxar2016In: Catheterization and cardiovascular interventions, ISSN 1522-1946, E-ISSN 1522-726X, Vol. 88, no 2, p. 163-173Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: We evaluated outcomes associated with transradial vs. transfemoral approaches and vorapaxar in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) in the TRACER trial.

    BACKGROUND: Vorapaxar reduces ischemic events but increases the risk of major bleeding.

    METHODS: We compared 30-day and 2-year major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization) and noncoronary artery bypass graft (CABG)-related bleedings in 2,192 transradial and 4,880 transfemoral patients undergoing PCI after adjusting for confounding variables, including propensity for transradial access.

    RESULTS: Overall, 30-day GUSTO moderate/severe and non-CABG TIMI major/minor bleeding occurred less frequently in transradial (0.9% vs. 2.0%, P = 0.001) vs. transfemoral (1.1% vs. 2.5%, P = 0.005) patients. A similar reduction was seen at 2 years (3.3% vs. 4.7%, P = 0.008; 3.3% vs. 4.9%, P < 0.001, respectively). Transradial was associated with an increased risk of ischemic events at 30 days (OR 1.38, 95% CI 1.11-1.72; P = 0.004), driven primarily by increased periprocedural myocardial infarctions. At 2 years, rates of MACE were comparable (HR 1.14, 95% CI 0.98-1.33; P = 0.096). Although bleeding rates were higher with vorapaxar in transfemoral vs. transradial patients, there was no significant treatment interaction. Also, the access site did not modulate the association between vorapaxar and MACE.

    CONCLUSIONS: Transradial access was associated with lower bleeding rates and similar long-term ischemic outcomes, suggesting transradial access is safer than transfemoral access among ACS patients receiving potent antiplatelet therapies. Because of the nonrandomized allocation of arterial access, these results should be considered exploratory. © 2015 Wiley Periodicals, Inc.

  • 329.
    Eaker, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Halmin, Märit
    Bellocco, Rino
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Ahlgren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lambe, Mats
    Social differences in breast cancer survival in relation to patient management within a National Health Care System (Sweden)2009In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 124, no 1, p. 180-187Article in journal (Refereed)
    Abstract [en]

    Epidemiologic studies have shown that cancer survival is poorer in low compared with high socioeconomic groups. We investigated whether these differences were associated with disparities in tumour characteristics and management. This cohort study was based on 9,908 women aged 20-79 years at diagnosis with primary breast cancer identified in a Swedish population-based clinical register. Information on socioeconomic standing was obtained from a social database. The 5-year cause-specific survival (CSS) and mortality hazard ratios (HR) were estimated by Cox proportional hazard models to assess differences in survival between socioeconomic groups while adjusting for diagnostic intensity, tumour characteristics and treatment. Following adjustment for age, year and stage at diagnosis, the risk of dying of breast cancer was 35% lower among women with high education compared with that of low education (HR = 0.65, 95% CI 0.53-0.80). When compared with women with high education, a lower percentage of women with low education had been investigated for proliferation (84 vs. 76%) or hormone receptor status (89 vs. 81%), had tumours <or=20 mm (68 vs. 64%), were treated at a main hospital (75 vs. 68%) and had received radiation treatment (80 vs. 67%) or chemotherapy (31 vs. 18%). However, these proportional differences could not explain the observed social gradient in survival. To minimize social differences in breast cancer survival, further research should address not only factors leading to inequities in management but also focus on patient factors such as health awareness, comorbidity burden and compliance to adjuvant treatment.

  • 330. Easton, J. Donald
    et al.
    Lopes, Renato D.
    Bahit, M. Cecilia
    Wojdyla, Daniel M.
    Granger, Christopher B.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alings, Marco
    Goto, Shinya
    Lewis, Basil S.
    Rosenqvist, Marten
    Hanna, Michael
    Mohan, Puneet
    Alexander, John H.
    Diener, Hans-Christoph
    Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial2012In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 11, no 6, p. 503-511Article in journal (Refereed)
    Abstract [en]

    Background

    In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA.

    Methods

    Between Dec 19,2006, and April 2,2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18 201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2.0-3.0). The median duration of follow-up was 1.8 years (IQR 1.4-2.3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984.

    Findings

    Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2.46 per 100 patient-years of follow-up in the apixaban group and 3.24 in the warfarin group (hazard ratio [HR] 0.76, 95% CI 0.56 to 1.03); in the subgroup of patients without previous stroke or TLA, the rate of stroke or systemic embolism was 1.01 per 100 patient-years of follow-up with apixaban and 1.23 with warfarin (HR 0.82, 95% CI 0.65 to 1.03; p for interaction=0.71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0.77 per 100 patient-years of follow-up (95% CI -0.08 to 1.63) in patients with and 0.22 (-0.03 to 0.47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1.07 per 100 patient-years (95% CI 0.09-2.04) in patients with and 0.93 (0.54-1.32) in those without previous stroke or TIA.

    Interpretation

    The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population.

    Funding

    Bristol-Myers Squibb and Pfizer.

  • 331.
    Ebeling Barbier, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lundin, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Melki, Vilyam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Percutaneous Closure in Transfemoral Aortic Valve Implantation: A Single-Centre Experience2015In: Cardiovascular and Interventional Radiology, ISSN 0174-1551, E-ISSN 1432-086X, Vol. 38, no 6, p. 1438-1443Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To report the experience of a percutaneous closure device used for transfemoral transcatheter aortic valve implantation (TAVI) in an unselected patient and operator population.

    MATERIALS AND METHODS: Eighty-two consecutive patients (32 women, 50 men) who underwent transfemoral TAVI between September 2009 and February 2014 at our hospital were retrospectively reviewed for percutaneous closure device (PCD) failure, vascular complications, and bleeding. The diameter and calcification of the common femoral artery (CFA) and the thickness of the subcutaneous fat layer in the groin were assessed on computed tomography images.

    RESULTS: The incidences of PCD failure and minor and major vascular complications were 19.5 % (n = 16/82), 19.5 % (n = 16/82), and 7 % (n = 6/82) respectively. 8.5 % (n = 7/82) had a minor perioperative bleeding, 6 % (n = 5/82) had a major bleeding, and none had any life-threatening bleeding. When PCD failed, haemostasis was obtained with fascia suturing, covered stent placement, or with surgical cutdown. Thirty-day mortality and 1-year all-cause mortality were 8.5 % (n = 7/82) and 19.5 % (n = 16/82), respectively. In a multiple regression analysis, the CFA diameter and the presence of severe calcification were independently related to PCD failure (correlation coefficient = -0.24, p = 0.027 and correlation coefficient = 0.23, p = 0.036, respectively).

    CONCLUSION: PCD failure was related to a small CFA diameter and to a severely calcified CFA. Failure could largely be managed with minimally invasive techniques such as covered stents or fascia suturing.

  • 332.
    Edfors, Robert
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden.
    Sahlen, Anders
    Karolinska Inst, Dept Med, Stockholm, Sweden;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden;Natl Heart Ctr, Singapore, Singapore.
    Szummer, Karolina
    Karolinska Inst, Dept Med, Stockholm, Sweden;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Evans, Marie
    Karolinska Inst, Ctr Mol Med, Stockholm, Sweden;Karolinska Inst, Div Renal Med, Stockholm, Sweden.
    Carrero, Juan-Jesus
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Spaak, Jonas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Stockholm, Sweden.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Stockholm, Sweden.
    Outcomes in patients treated with ticagrelor versus clopidogrel after acute myocardial infarction stratified by renal function2018In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 104, no 19, p. 1575-1582Article in journal (Refereed)
    Abstract [en]

    Objectives We aimed to analyse outcomes of ticagrelor and clopidogrel stratified by estimated glomerular filtration rate (eGFR) in a large unselected cohort of patients with acute myocardial infarction (MI). Methods We used follow-up data in MI survivors discharged on ticagrelor or clopidogrel enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry. The association between ticagrelor versus clopidogrel and the primary composite outcome of death, MI or stroke and the secondary outcome rehospitalisation with bleeding diagnosis at 1year, was studied using adjusted Cox proportional hazards models, stratifying after eGFR levels. Results In total, 45 206 patients with MI discharged on clopidogrel (n=33472) or ticagrelor (n=11734) were included. The unadjusted 1-year event rate for the composite endpoint of death, MI or stroke was 7.0%, 18.0% and 48.0% for ticagrelor treatment and 11.0%, 33.0% and 64.0% for clopidogrel treatment in patients with eGFR(>60) (n=33668), eGFR(30-60) (n=9803) and eGFR(<30) (n=1735), respectively. After adjustment, ticagrelor as compared with clopidogrel was associated with a lower 1-year risk of the composite outcome (eGFR(>60): HR 0.87, 95%CI 0.76 to 99, eGFR(30-60): 0.82 (0.70 to 0.97), eGFR(<30): 0.95 (0.69 to 1.29), P for interaction=0.55) and a higher risk of bleeding (eGFR(>60): HR 1.10, 95%CI 0.90 to 1.35, eGFR(30-60): 1.13 (0.84 to 1.51), eGFR(<30): 1.79 (1.00 to 3.21), P for interaction=0.30) across the eGFR strata. Conclusions Treatment with ticagrelor as compared with clopidogrel in patients with MI was associated with lower risk for the composite of death, MI or stroke and a higher bleeding risk across all strata of eGFR. Of caution, bleeding events were more abundant in patients with eGFR(<30).

  • 333.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Auner, U
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Enlund, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Post-operative atelectasis: a randomised trial investigating a ventilatory strategy and low oxygen fraction during recovery2014In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, no 6, p. 681-688Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy with a combination of 1) continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) and 2) a reduced end-expiratory oxygen concentration during recovery would reduce post-operative atelectasis.

    METHODS: Sixty patients were randomized into two groups. During anaesthesia induction, inspiratory oxygen fraction (FI O2 ) was 1.0, and depending on weight, CPAP 6, 7 or 8 cmH2 O was applied in both groups via facemask. During maintenance of anaesthesia, a laryngeal mask airway (LMA) was used, and PEEP was 6-8 cmH2 O in both groups. Before removal of the LMA, FI O2 was set to 0.3 in the intervention group and 1.0 in the control group. Atelectasis was studied by computed tomography (CT) approximately 14 min post-operatively.

    RESULTS: In one patient in the group given an FI O2 of 0.3 before removal of the LMA a CT scan could not be performed so the patient was excluded. The area of atelectasis was 5.5, 0-16.9 cm(2) (median and range), and 6.8, 0-27.5 cm(2) in the groups given FI O2 0.3 or FI O2 1.0 before removal of the LMA, a difference that was not statistically significant (P = 0.48). Post-hoc analysis showed dependence of atelectasis on smoking (despite all were clinically lung healthy) and American Society of Anesthesiologists class (P = 0.038 and 0.015, respectively).

    CONCLUSION: Inducing anaesthesia with CPAP/PEEP and FI O2 1.0 and deliberately reducing FI O2 during recovery before removal of the LMA did not reduce post-operative atelectasis compared with FI O2 1.0 before removal of the LMA.

  • 334.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Auner, Udo
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Enlund, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Atelectasis after anaesthesia: a randomised trial of positive airway pressure and low oxygen2013Article in journal (Other academic)
    Abstract [en]

    Background:

    Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy with a combination of 1) continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) and 2) a reduced end-expiratory oxygen fraction (FETO2) before extubation would reduce postoperative atelectasis.

    Methods:

    Sixty patients were randomized into two groups. During anaesthesia induction, inspiratory oxygen fractions (FIO2) were 1.0, and depending on weight, CPAP 6–8 cm H2O was applied in both groups via face mask. During maintenance of anaesthesia, a laryngeal mask airway was used, and depending on weight, PEEP was 6–8 cm H2O in both groups. Before extubation, FIO2 was set to 0.3 in the intervention groups and 1.0 in the control group. Atelectasis was studied by computed tomography approximately 13 min postoperatively.

    Results:

    The area of atelectasis was 5.5, 0–16.9 cm2 (median and range), and 6.8, 0–27.5 cm2 in the groups given FIO2 0.3 or FIO2 1.0 before extubation, a difference that was not statistically significant.

    Conclusion:

    Inducing anaesthesia with CPAP/PEEP and FIO2 1.0 and deliberately reducing FIO2 before extubation did not reduce postoperative atelectasis compared with FIO2 1.0 before extubation.

  • 335. Edström Plüss, Cathrine
    et al.
    Billing, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Henriksson, Peter
    Kiessling, Anna
    Rydell Karlsson, Monica
    Wallén, Håkan N.
    Long-term effects of an expanded cardiac rehabilitation programme after myocardial infarction or coronary artery bypass surgery: a five-year follow-up of a randomized controlled study2011In: Clinical Rehabilitation, ISSN 0269-2155, E-ISSN 1477-0873, Vol. 25, no 1, p. 79-87Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the long-term effect of expanded cardiac rehabilitation on a composite end-point, consisting of cardiovascular death, myocardial infarction or readmission for cardiovascular disease, in patients with coronary artery disease.Design: Single-centre prospective randomized controlled trial.Setting: University hospital.Subjects: Two hundred and twenty-four patients with acute myocardial infarction or undergoing coronary artery by-pass grafting.Intervention: Patients were randomized to expanded cardiac rehabilitation (a one-year stress management programme, increased physical training, staying at a 'patient hotel' for five days after the event, and cooking sessions), or to standard cardiac rehabilitation. MAIN MEASURES: Data on cardiovascular death, myocardial infarction, readmission for cardiovascular disease and days at hospital for cardiovascular reasons were obtained from national registries of the Swedish National Board of Health and Welfare.Results: The primary end-point occurred in 121 patients altogether (54%). The number of cardiovascular events were reduced in the expanded rehabilitation group compared with the standard cardiac rehabilitation (53 patients (47.7%) versus 68 patients (60.2%); hazard ratio 0.69; P = 0.049). This was mainly because of a reduction of myocardial infarctions in the expanded rehabilitation group. During the five years 12 patients (10.8%) versus 23 patients (20.3%); hazard ratio 0.47; P = 0.047 had a myocardial infarction. Days at hospital for cardiovascular reasons were significantly reduced in patients who received expanded cardiac rehabilitation (median 6 days) compared with standard cardiac rehabilitation (median 10 days; P = 0.02).Conclusion: Expanded cardiac rehabilitation after acute myocardial infarction or coronary artery bypass grafting reduces cardiovascular morbidity and days at hospital for cardiovascular reasons.

  • 336.
    Eggers, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Apple, Fred S.
    Hennepin Cty Med Ctr, Dept Lab Med & Pathol, Minneapolis, MN 55415 USA;Abbott NW Hosp, Minneapolis Heart Inst, Minneapolis, MN USA .
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    The applied statistical approach highly influences the 99th percentile of cardiac troponin I2016In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 49, no 15, p. 1109-1112Article in journal (Refereed)
    Abstract [en]

    Background

    Cardiac troponin (cTn) is the biomarker of choice for assessment of patients with acute coronary syndromes. Guidelines recommend the cTn 99th percentile derived from a cardiovascular healthy reference population as decision threshold. The importance of standardized criteria for the composition of such a reference population is well acknowledged. In this analysis, we investigated to which extent different statistical methods might have bearing on the calculated cTnI 99th percentile.

    Methods

    cTnI (Abbott) 99th percentiles were determined in 521 cardiovascular healthy community-dwelling subjects using the nonparametric method, the Harrell-Davis bootstrap method and the robust method together with different tests to identify potential outliers (Dixon, Tukey, Reed) and different statistical softwares.

    Results

    The cTnI 99th percentiles (nonparametric method) were 37 ng/L (total population), 42 ng/L (men) and 25 ng/L (women). These estimates differed by − 7.4% to + 5.7% using the Harrell-Davis bootstrap method and were up to 64.1% lower using the robust method. For the robust method, cTnI 99th percentiles varied by 44.2% depending on the applied software. The method of Tukey classified nine subjects as outliers while no outlier was detected using the other methods. Excluding these nine subjects resulted in up to 60.2% lower cTnI 99th percentiles.

    Conclusions

    Our results emphasize the need of a standardized statistical approach to calculate cTnI 99th percentiles. Our findings support the use of the nonparametric method and a conservative approach to detect outliers. This requires that the assessed population is sufficiently large and well selected on the basis of stringently applied clinical criteria.

  • 337.
    Eggers, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hammarsten, Ola
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bedömning av patienter med bröstsmärta:: Kan vi nöja oss med mätning av troponin enbart vid ankomst?2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 25-26, p. 1132-1133Article in journal (Other (popular science, discussion, etc.))
  • 338.
    Eggers, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, Tomas
    Karolinska Univ Hosp, Karolinska Inst, Cardiol Sect, Dept Med, Huddinge, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Prognostic Importance of Sex-Specific Cardiac Troponin T 99(th) Percentiles in Suspected Acute Coronary Syndrome2016In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 129, no 8, article id 880.e1Article in journal (Refereed)
    Abstract [en]

    Objective

    Cardiac troponin levels differ between the sexes, with higher values commonly seen in men. The use of sex-specific troponin thresholds is, thus, subject of an ongoing debate. We assessed whether sex-specific cardiac troponin T (cTnT) 99th percentiles would improve risk prediction in patients admitted to Swedish coronary care units due to suspected acute coronary syndrome.

    Methods

    In this retrospective register-based study (48,250 patients), we investigated the prediction of all-cause mortality and the composite of cardiovascular death or nonfatal myocardial infarction within 1 year using the single 99th cTnT percentile (>14 ng/L) or sex-specific cTnT 99th percentiles (>16/9 ng/L).

    Results

    A total of 1078 men (3.0%) with cTnT 15-16 ng/L and 1854 women (8.4%) with cTnT 10-14 ng/L would have been reclassified regarding their cTnT status by the means of sex-specific 99th percentiles. The prevalence of cardiovascular risk factors and crude event rates increased across higher cTnT strata in both men and women. Multivariable-adjusted Cox models, however, did not demonstrate better risk prediction by sex-specific 99th percentiles. Assessing cTnT as a continuous variable demonstrated an increase in multivariable-adjusted risk starting at levels around 10-12 ng/L in both men and women.

    Conclusions

    We found no evidence supporting the use of sex-specific cTnT 99th percentiles in men and women admitted because of suspected acute coronary syndrome. This likely depends on sex-specific differences in disease mechanisms associated with small cTnT elevations. From a pragmatic perspective, a single cTnT cutoff slightly below 14 ng/L seems to be preferable as a threshold for medical decision-making.

  • 339.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Serial Measurement of Biomarkers after Acute Coronary Syndrome: Which One to Choose?2017In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 7, p. 1181-1183Article in journal (Other academic)
  • 340.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Aldous, Sally
    Greenslade, Jaimi H.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Parsonage, William A.
    Pickering, John W.
    Than, Martin
    Cullen, Louise
    Two-hour diagnostic algorithms for early assessment of patients with acute chest pain - Implications of lowering the cardiac troponin I cut-off to the 97.5th percentile2015In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 445, p. 19-24Article in journal (Refereed)
    Abstract [en]

    Aims: Assessment of patients with suspected non-ST elevation myocardial infarction (NSTEMI) is based on cardiac troponin (cTn) levels with the 99th percentile as cut-off. However, cardiovascular risk starts already at lower troponin concentrations. We therefore, aimed to investigate the utility of 2-hour algorithms using the high-sensitivity cardiac troponin I (hs-cTnI) 97.5th percentile as cut-off which corresponds to the standard URL for most biomarkers. Methods: Hs-cTnI was measured at presentation and 2 h in 1624 chest pain patients. Diagnostic algorithms were developed applying hs-cTnI levels dichotomized at the 99th and 97.5th percentiles combined with hs-cTnI changes and/or ECG findings. Results: The prevalence of NSTEMI was 13.9%. The adjusted odds ratios for 1-year mortality were 2.7(95% CI 1.4-5.1) for the 99th percentile and 3.1 (95% CI 1.6-5.9) for the 97.5th percentile. The best-performing 99th percentile-based algorithms provided a positive predictive value (PPV) of 863% and a negative predictive value (NPV) of 993%. Using 97.5th percentile-based algorithms to define NSTEMI resulted in few reclassifications and yielded similar diagnostic estimates (PPV 85.4%, NPV 99.4%). Conclusion: The hs-cTnI 97.5th percentile integrated into 2-hour algorithms provided high diagnostic estimates and could, due to better prognostic properties serve as an alternative to the 99th percentile.

  • 341.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Al-Shakarchi, Jinan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    High-sensitive cardiac troponin T and its relations to cardiovascular risk factors, morbidity, and mortality in elderly men2013In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 166, no 3, p. 541-+Article in journal (Refereed)
    Abstract [en]

    Background Cardiac troponin is emerging as risk indicator in community-dwelling populations. In this study, we investigated the associations of cardiac troponin T (cTnT) to cardiovascular (CV) disease and outcome in elderly men. Methods Cardiac troponin T was measured using a high-sensitive assay in 940 men aged 71 years participating in the Uppsala Longitudinal Study of Adult Men. We assessed both the cross-sectional associations of cTnT to CV risk factors and morbidities including cancer and the longitudinal associations to outcomes over 10 years of follow-up. Results Cardiac troponin T levels were measurable in 872 subjects (92.8%). In the cross-sectional analyses, cTnT was associated to CV risk factors (diabetes, smoking, and obesity), renal dysfunction, CV disease including atrial fibrillation and coronary artery disease, and biomarkers of inflammation and left ventricular dysfunction. In the longitudinal analyses, cTnT independently predicted total mortality and CV events including stroke. The standardized adjusted hazard ratio regarding the composite CV end point was 1.5 (95% CI 1.3-1.8), P < .001, for men with prevalent CV disease and 1.2 (95% CI 1.0-1.4), P = .02, for men without. Cardiac troponin T improved discrimination metrics for all outcomes in the total population. This was mainly driven by the prognostic value of cTnT in subjects with prevalent CV disease. Conclusions In community-dwelling men, cTnT levels are associated to CV risk factors and morbidities and predict both fatal and nonfatal CV events. The relations to outcome are mainly seen in men with prevalent CV disease indicating that the prognostic value of cTnT in subjects free from CV disease is limited.

  • 342.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Armstrong, Paul W.
    Califf, Robert M.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Simoons, Maarten L.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Clinical and prognostic implications of circulating pentraxin 3 levels in non ST-elevation acute coronary syndrome2013In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 46, no 16-17, p. 1655-1659Article in journal (Refereed)
    Abstract [en]

    Objectives: Pentraxin 3 (PTX3) is the prototype of the long pentraxin family. PTX3 is involved in inflammatory processes affecting the cardiovascular system, and PTX3 levels have been shown to be elevated and independently prognostic in ST-elevation myocardial infarction. Data on PTX3 levels in non-ST-elevation acute coronary syndrome (NSTE-ACS), in contrast, are limited. The aim of the present analysis was to investigate the implications of PTX3 levels in a fairly large sample of NSTE-ACS patients and in comparison to levels of C-reactive protein (CRP). Design and methods: We measured levels of PTX3 and CRP in both 82 healthy controls and 401 NSTE-ACS patients from the GUSTO IV study, and studied the associations of these biomarkers to clinical data and 1-year mortality. Results: NSTE-ACS patients had significantly higher median PTX3 levels compared to healthy controls (3.8 vs. 1.9 mu g/L; p < 0.001). PTX3 levels in patients with NSTE-ACS were independently related to female sex and cardiac troponin T levels, but not to age or cardiovascular risk factors. PTX3 levels were higher in patients who died within 1 year but did not emerge as an independent predictor of 1-year mortality (adjusted OR 1,2 [95% Cl 0.6-2.31). This was in contrast to CRP (adjusted OR 1.5 [95% Cl 1.1-2.3]). Neither PTX3 nor CRP yielded significant discriminative value regarding mortality prediction. Conclusions: PTX3 levels are elevated in NSTE-ACS. However, the prognostic information provided by PTX3 levels is limited and inferior compared to CRP. Our data, thus, do not support the measurement of PTX3 in patients with NSTE-ACS.

  • 343.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Armstrong, Paul W.
    Califf, Robert M.
    Simoons, Maarten L.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    ST2 and mortality in non-ST-segment elevation acute coronary syndrome2010In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 159, no 5, p. 788-794Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: ST2 is a member of the interleukin-1 receptor family that is up-regulated in conditions associated with increased myocardial strain. ST2 has been shown to be independently predictive of adverse outcome in heart failure and ST-segment elevation myocardial infarction, but its prognostic value in non-ST-elevation acute coronary syndrome (NSTE-ACS) has not been established. METHODS: We measured ST2 at randomization and after 24, 48, and 72 hours in 403 NSTE-ACS patients from the GUSTO IV study, and studied its kinetics and its associations to clinical baseline factors and 1-year mortality. RESULTS: Median ST2 levels decreased from 28.4 U/mL at randomization to 21.8 U/mL at 72 hours (P < .001). Peak levels were noted 6 to 17 hours after symptom onset. Randomization ST2 levels were independently associated to N-terminal pro-B-type natriuretic peptide but otherwise exhibited only weak relations to cardiovascular risk factors and comorbidities, and biomarkers of myocardial necrosis or inflammation. ST2 was related to 1-year mortality independently of clinical risk indicators (odds ratio 2.3 [95% CI 1.1-4.6], P = .03) but lost its predictive value after additional adjustment for prognostic biomarkers, in particular N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: ST2 levels are elevated early in NSTE-ACS and predict 1-year mortality. Our data indicate that ST2 represents an interesting novel pathophysiologic pathway in the setting of ischemia-related myocardial dysfunction. However, future prospective evaluations in larger populations are needed before the clinical utility of ST2 can be determined.

  • 344.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Baron, Tomasz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hambraeus, Kristina
    Department of Cardiology, Falun Hospital, Falun, Sweden.
    Jernberg, Tomas
    Department of Clinical Sciences, Cardiology, Danderyd Hospital, Karolinska Institute, Danderyd, Sweden.
    Nordenskjöld, Anna
    Faculty of Health, Department of Cardiology, Örebro University, Örebro, Sweden.
    Tornvall, Per
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Myocardial Infarction with Nonobstructive Coronary Arteries: The Importance of Achieving Secondary Prevention Targets2018In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 131, no 5, p. 524-531.e6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Approximately 5% to 10% of all patients with myocardial infarction have nonobstructive coronary arteries. Studies investigating the importance of follow-up and achievement of conventional secondary prevention targets in these patients are lacking.

    METHODS:

    In this analysis from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, we investigated 5830 patients with myocardial infarction with nonobstructive coronary arteries (group 1) and 54,637 patients with myocardial infarction with significant coronary artery disease (≥50% stenosis; group 2). Multivariable- and propensity score-adjusted statistics were used to assess the reduction in the 1-year risk of major adverse events associated with prespecified secondary preventive measures: participation in follow-up at 6 to 10 weeks after the hospitalization and achievement of secondary prevention targets (blood pressure and low-density lipoprotein cholesterol levels in the target ranges, nonsmoking, and participation in exercise training).

    RESULTS:

    Patients in group 1 were less often followed up compared with patients in group 2 and less often achieved any of the secondary prevention targets. Participation in the 6- to 10-week follow-up was associated with a 3% to 20% risk reduction in group 1, similar as for group 2 according to interaction analysis. The improvement in outcome in group 1 was mainly mediated by achieving target range low-density lipoprotein cholesterol levels (24%-32% risk reduction) and, to a smaller extent, by participation in exercise training (10%-23% risk reduction).

    CONCLUSIONS:

    Selected secondary preventive measures are associated with prognostic benefit in patients with myocardial infarction with nonobstructive coronary arteries, in particular achieving target range low-density lipoprotein cholesterol levels. Our results indicate that these patients should receive similar follow-up as myocardial infarction patients with significant coronary stenoses.

  • 345.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hjort, Marcus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Baron, Tomasz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, T.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Cardiol, Stockholm, Sweden.
    Nordenskjold, A. M.
    Orebro Univ, Dept Cardiol, Fac Hlth, Orebro, Sweden.
    Tornvall, P.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Morbidity and cause-specific mortality in first-time myocardial infarction with nonobstructive coronary arteries2019In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 285, no 4, p. 419-428Article in journal (Refereed)
    Abstract [en]

    Background

    Myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is receiving increasing interest as a prognostically adverse entity distinct from myocardial infarction with significant coronary artery disease (MI-CAD). However, data are still limited regarding long-term cardiovascular morbidity and cause-specific mortality in MINOCA.

    Methods

    This is a registry-based cohort study using data from patients admitted to Swedish coronary care units. We investigated various nonfatal outcomes (recurrent MI, hospitalization for heart failure or stroke) and fatal outcomes (cardiovascular, respiratory or cancer-related mortality) in 4069 patients without apparent acute cardiovascular disease, used as non-MI controls, 7266 patients with first-time MINOCA and 69267 patients with first-time MI-CAD.

    Results

    Almost all event rates (median follow-up 3.8years) increased in a stepwise fashion across the three cohorts [rates of major adverse events (MAE; composite of all-cause mortality, recurrent MI, hospitalization for heart failure or stroke): n=268 (6.6%), n=1563 (21.5%), n=17777 (25.7%), respectively]. Compared to non-MI controls, MINOCA patients had an adjusted hazard ratio (HR) of 2.12 (95% confidence interval 1.84-2.43) regarding MAE. MINOCA patients had a substantial risk of cardiovascular mortality and the highest numerical risks of respiratory and cancer-related mortality. Male sex, previous heart failure and chronic obstructive pulmonary disease had a stronger prognostic impact in MINOCA than in MI-CAD. Female MINOCA patients with atrial fibrillation were at particular risk.

    Conclusions

    Patients with first-time MINOCA have a considerable risk of adverse events. This stresses the need for a comprehensive search of the cause of MINOCA, thorough treatment of underlying disease triggers and close follow-up.

  • 346.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jaffe, Allan S
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    A novel approach to cardiac troponins to improve the diagnostic work-up in chest pain patients2012In: Critical Pathways in Cardiology, ISSN 1535-282X, E-ISSN 1535-2811, Vol. 11, no 4, p. 199-205Article in journal (Refereed)
    Abstract [en]

    In patients with acute chest pain, current guidelines recommend serial measurements of cardiac troponins at predefined and partly late time points. Consequently, diagnostic assessment in these patients tends to be lengthy and often results in unnecessary admissions. We, therefore, evaluated whether an approach integrating troponin results into the clinical context provided by the individual patient's presentation might facilitate the early diagnostic work-up. In 197 chest pain patients, cardiac troponin I (cTnI; Stratus CS) was measured serially within 12 hours after hospital admission. In patient cohorts with different chances of having myocardial infarction (MI) according to clinical data, electrocardiographic findings, and admission biomarker results, pretest probabilities for MI were calculated and compared with posttest probabilities derived from subsequent cTnI results after admission. Elevated cTnI levels at 1 to 2 hours after admission revealed ≥95.0% posttest probabilities for MI in cohorts with intermediate or high chances of having MI. The posttest probabilities for the absence of MI were 94.7% to 98.2% in cohorts with low or intermediate chances of having MI when cTnI was negative at 2 hours. Troponin testing considering the individual patient's pretest probability of MI seems, in conclusion, to provide clinically useful information already 1 to 2 hours after admission. Such an approach has the potential to identify both patient cohorts in whom early discharge or admittance for further evaluation would be appropriate. This could facilitate the early diagnostic work-up of chest pain patients, thereby improving patient flow and reducing overcrowding in healthcare facilities.

  • 347.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jaffe, Allan S.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Clinical implications of the change of cardiac troponin I levels in patients with acute chest pain - An evaluation with respect to the Universal Definition of Myocardial Infarction2011In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 412, no 1-2, p. 91-97Article in journal (Refereed)
    Abstract [en]

    Background: The Universal Definition of Myocardial Infarction incorporates elevated cardiac troponin levels (>99th percentile) together with a significant rise/fall of troponins as biochemical criterion. We sought to evaluate the clinical implications of the relative change of cardiac troponin I (cTnI) levels with respect to the Universal Definition in patients with acute chest pain. Methods: cTnI (Stratus CS) was measured serially in 454 patients within 24 h from admission. Acute myocardial infarction (AMI) was defined using the criteria adapted to the ESC/ACC consensus document, or corresponding to the Universal Definition together with prespecified cTnI changes of >= 20%, >= 50% and >= 100%. Follow-up was completed after 5.8 years. Results: A peak cTnI level above the 99th percentile together with a cTnI change of >= 20% was found in 160 patients of whom 25 did not have AMI according to the ESC/ACC criteria. These 160 patients had a significantly raised mortality (HR 2.5[95% CI 1.7-3.8]). Higher cTnI deltas were not associated with higher mortalities but identified smaller patient cohorts at risk. Conclusions: The Universal Definition of AMI together with a >= 20% cTnI change appears to improve the discrimination of acute from chronic causes of cTnI release, and allows a reliable identification of patients at risk.

  • 348.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Prognostic implications of changes in cardiac troponin I levels in patients with non-ST elevation acute coronary syndrome2013In: Biomarkers, ISSN 1354-750X, E-ISSN 1366-5804, Vol. 18, no 8, p. 668-672Article in journal (Refereed)
    Abstract [en]

    Objective: Information is limited on the prognostic implications of cardiac troponin I (cTnI) changes during the first days of non-ST elevation acute coronary syndrome (NSTE-ACS). Methods: High-sensitivity cTnI levels were measured at study inclusion and after 48 h in 1615 conservatively managed NSTE-ACS patients from the Global Use of Strategies To Open Occluded Coronary Arteries (GUSTO) IV trial. Results: Patients with moderately increased cTnI levels and without a relevant decrease over time had a significantly raised mortality at 30 days and 1 year. No relevant associations between cTnI changes and recurrent myocardial infarction were seen. Conclusion: The cTnI change is predictive for subsequent mortality in selected conservatively managed NSTE-ACS patients.

  • 349.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, T.
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    High-sensitivity cardiac troponin T, left ventricular function, and outcome in non-ST elevation acute coronary syndrome2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 197, p. 70-76Article in journal (Refereed)
    Abstract [en]

    Background Cardiac troponin (cTn) levels reflect infarct size and depressed left ventricular ejection fraction (LVEF) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). However, there is very limited information on whether cTn measured with a high-sensitivity (hs) assay would provide incremental prognostic information to the LVEF in NSTE-ACS patients. Methods This was a registry-based study (SWEDEHEART registry) investigating 20,652 NSTE-ACS patients with available information on hs-cTnT (highest level recorded during the hospitalization) and the LVEF estimated using echocardiography. All patients had been followed for 1 year. Results Hs-cTnT levels independently predicted major cardiovascular events (MACE) in cohorts with normal, slightly depressed, moderately depressed, and severely depressed LVEF. The adjusted hazard ratios in these cohorts were 1.18 (95% CI 1.13-1.23), 1.12 (95% CI 1.06-1.18), 1.12 (95% CI 1.06-1.19), and 1.21 (95% CI 1.13-1.30), respectively. Hs-cTnT levels were particularly predictive for cardiovascular mortality and readmission for heart failure. Excluding patients with previous cardiac disease did not affect the overall interrelations of hs-cTnT and LVEF with MACE. Conclusions Hs-cTnT levels provide incremental prognostic value independent of the LVEF in patients with NSTE-ACS. Hs-cTnT is particularly predictive for MACE in patients with severely depressed LVEF but also in those with a normal LVEF. Accordingly, a normal LVEF should not be used as an argument not to target patients to thorough workup.

  • 350.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cardiac Troponin Elevation in Patients Without a Specific Diagnosis2019In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 73, no 1, p. 1-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Cardiac troponin (cTn) elevation is a common finding in acutely admitted patients, even in the absence of acute coronary syndrome. In some of these patients, no etiology of cTn elevation can be identified. The term troponinemia is sometimes used to describe this scenario.

    OBJECTIVES This study aimed to investigate the associations of cTn levels with clinical findings and long-term outcome in acutely admitted patients with suspected acute coronary syndrome who had been discharged without a specified diagnosis.

    METHODS Retrospective registry-based cohort study investigating 48,872 patients (SWEDEHEART [Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies] registry). Patients were stratified into cohorts with cTn levels less than or equal to the assay-specific 99th percentile and separated by assay-specific cTn tertiles in case of higher levels.

    RESULTS A cTn level >99th percentile was noted in 9,800 (20.1%) patients. The prevalence of cardiovascular risk factors as well as cardiovascular and noncardiovascular comorbidities increased across higher cTn strata. In total, 7,529 (15.4%) patients had a major adverse event (MAE), defined as the composite of all-cause mortality, myocardial infarction, readmission for heart failure, or stroke (median follow-up 4.9 years). MAE risk was associated with higher cTn strata (hazard ratio for highest assay-specific cTn tertile: 2.59; 95% confidence interval: 2.39 to 2.80; hazard ratio in patients without cardiovascular comorbidities, renal dysfunction, left ventricular dysfunction, or significant coronary stenosis: 3.57; 95% confidence interval: 2.30 to 5.54).

    CONCLUSIONS cTn elevation is associated with cardiovascular and noncardiovascular comorbidities and predicts major adverse events in acutely admitted patients, in whom no definite diagnosis could have been established. The term troponinemia is trivializing and should be avoided. Instead, careful work-up is required in these patients.

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