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52. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Author

Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Maegi, R, Randall, JC, Vedantam, S, Winkler, TW, Qi, L, Workalemahu, T, Heid, IM, Steinthorsdottir, V, Stringham, HM, Weedon, MN, Wheeler, E, Wood, AR, Ferreira, T, Weyant, RJ, Segre, AV, Estrada, K, Liang, L, Nemesh, J, Park, J-H, Gustafsson, S, Kilpelaenen, TO, Yang, J, Bouatia-Naji, N, Esko, T, Feitosa, MF, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, AV, Welch, R, Zhao, JH, Aben, KK, Absher, DM, Amin, N, Dixon, AL, Fisher, E, Glazer, NL, Goddard, ME, Heard-Costa, NL, Hoesel, V, Hottenga, J-J, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, MF, Myers, RH, Narisu, N, Perry, JRB, Peters, MJ, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Scott, LJ, Timpson, NJ, Tyrer, JP, van Wingerden, S, Watanabe, RM, White, CC, Wiklund, F, Barlassina, C, Chasman, DI, Cooper, MN, Jansson, J-O, Lawrence, RW, Pellikka, N, Prokopenko, I, Shi, J, Thiering, E, Alavere, H, Alibrandi, MTS, Almgren, P, Arnold, AM, Aspelund, T, Atwood, LD, Balkau, B, Balmforth, AJ, Bennett, AJ, Ben-Shlomo, Y, Bergman, RN, Bergmann, S, Biebermann, H, Blakemore, AIF, Boes, T, Bonnycastle, LL, Bornstein, SR, Brown, MJ, Buchanan, TA, Busonero, F, Campbell, H, Cappuccio, FP, Cavalcanti-Proenca, C, Chen, Y-DI, Chen, C-M, Chines, PS, Clarke, R, Coin, L, Connell, J, Day, INM, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Erdos, MR, Eriksson, JG, Facheris, MF, Felix, SB, Fischer-Posovszky, P, Folsom, AR, Friedrich, N, Freimer, NB, Fu, M, Gaget, S, Gejman, PV, Geus, EJC, Gieger, C, Gjesing, AP, Goel, A, Goyette, P, Grallert, H, Graessler, J, Greenawalt, DM, Groves, CJ, Gudnason, V, Guiducci, C, Hartikainen, A-L, Hassanali, N, Hall, AS, Havulinna, AS, Hayward, C, Heath, AC, Hengstenberg, C, Hicks, AA, Hinney, A, Hofman, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Isomaa, B, Jacobs, KB, Jarick, I, Jewell, E, John, U, Jorgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kajantie, E, Kaplan, LM, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, JW, Kolcic, I, Koenig, IR, Koskinen, S, Kovacs, P, Kuusisto, J, Kraft, P, Kvaloy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, LJ, Lecoeur, C, Lehtimaeki, T, Lettre, G, Liu, J, Lokki, M-L, Lorentzon, M, Luben, RN, Ludwig, B, Manunta, P, Marek, D, Marre, M, Martin, NG, McArdle, WL, McCarthy, A, McKnight, B, Meitinger, T, Melander, O, Meyre, D, Midthjell, K, Montgomery, GW, Morken, MA, Morris, AP, Mulic, R, Ngwa, JS, Nelis, M, Neville, MJ, Nyholt, DR, O'Donnell, CJ, O'Rahilly, S, Ong, KK, Oostra, B, Pare, G, Parker, AN, Perola, M, Pichler, I, Pietilaeinen, KH, Platou, CGP, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, NW, Ridderstrale, M, Rief, W, Ruokonen, A, Robertson, NR, Rzehak, P, Salomaa, V, Sanders, AR, Sandhu, MS, Sanna, S, Saramies, J, Savolainen, MJ, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, DS, Smit, JH, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Swift, AJ, Tammesoo, M-L, Tardif, J-C, Teder-Laving, M, Teslovich, TM, Thompson, JR, Thomson, B, Toenjes, A, Tuomi, T, van Meurs, JBJ, van Ommen, G-J, Vatin, V, Viikari, J, Visvikis-Siest, S, Vitart, V, Vogel, CIG, Voight, BF, Waite, LL, Wallaschofski, H, Walters, GB, Widen, E, Wiegand, S, Wild, SH, Willemsen, G, Witte, DR, Witteman, JC, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, JP, Farooqi, IS, Hebebrand, J, Huikuri, HV, James, AL, Kaehoenen, M, Levinson, DF, Macciardi, F, Nieminen, MS, Ohlsson, C, Palmer, LJ, Ridker, PM, Stumvoll, M, Beckmann, JS, Boeing, H, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Collins, FS, Cupples, LA, Smith, GD, Erdmann, J, Froguel, P, Greonberg, H, Gyllensten, U, Hall, P, Hansen, T, Harris, TB, Hattersley, AT, Hayes, RB, Heinrich, J, Hu, FB, Hveem, K, Illig, T, Jarvelin, M-R, Kaprio, J, Karpe, F, Khaw, K-T, Kiemeney, LA, Krude, H, Laakso, M, Lawlor, DA, Metspalu, A, Munroe, PB, Ouwehand, WH, Pedersen, O, Penninx, BW, Peters, A, Pramstaller, PP, Quertermous, T, Reinehr, T, Rissanen, A, Rudan, I, Samani, NJ, Schwarz, PEH, Shuldiner, AR, Spector, TD, Tuomilehto, J, Uda, M, Uitterlinden, A, Valle, TT, Wabitsch, M, Waeber, G, Wareham, NJ, Watkins, H, Wilson, JF, Wright, AF, Zillikens, MC, Chatterjee, N, McCarroll, SA, Purcell, S, Schadt, EE, Visscher, PM, Assimes, TL, Borecki, IB, Deloukas, P, Fox, CS, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, Mohlke, KL, O'Connell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, van Duijn, CM, Wichmann, H-E, Frayling, TM, Thorsteinsdottir, U, Abecasis, GR, Barroso, I, Boehnke, M, Stefansson, K, North, KE, McCarthy, MI, Hirschhorn, JN, Ingelsson, E, Loos, RJF, Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Maegi, R, Randall, JC, Vedantam, S, Winkler, TW, Qi, L, Workalemahu, T, Heid, IM, Steinthorsdottir, V, Stringham, HM, Weedon, MN, Wheeler, E, Wood, AR, Ferreira, T, Weyant, RJ, Segre, AV, Estrada, K, Liang, L, Nemesh, J, Park, J-H, Gustafsson, S, Kilpelaenen, TO, Yang, J, Bouatia-Naji, N, Esko, T, Feitosa, MF, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, AV, Welch, R, Zhao, JH, Aben, KK, Absher, DM, Amin, N, Dixon, AL, Fisher, E, Glazer, NL, Goddard, ME, Heard-Costa, NL, Hoesel, V, Hottenga, J-J, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, MF, Myers, RH, Narisu, N, Perry, JRB, Peters, MJ, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Scott, LJ, Timpson, NJ, Tyrer, JP, van Wingerden, S, Watanabe, RM, White, CC, Wiklund, F, Barlassina, C, Chasman, DI, Cooper, MN, Jansson, J-O, Lawrence, RW, Pellikka, N, Prokopenko, I, Shi, J, Thiering, E, Alavere, H, Alibrandi, MTS, Almgren, P, Arnold, AM, Aspelund, T, Atwood, LD, Balkau, B, Balmforth, AJ, Bennett, AJ, Ben-Shlomo, Y, Bergman, RN, Bergmann, S, Biebermann, H, Blakemore, AIF, Boes, T, Bonnycastle, LL, Bornstein, SR, Brown, MJ, Buchanan, TA, Busonero, F, Campbell, H, Cappuccio, FP, Cavalcanti-Proenca, C, Chen, Y-DI, Chen, C-M, Chines, PS, Clarke, R, Coin, L, Connell, J, Day, INM, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Erdos, MR, Eriksson, JG, Facheris, MF, Felix, SB, Fischer-Posovszky, P, Folsom, AR, Friedrich, N, Freimer, NB, Fu, M, Gaget, S, Gejman, PV, Geus, EJC, Gieger, C, Gjesing, AP, Goel, A, Goyette, P, Grallert, H, Graessler, J, Greenawalt, DM, Groves, CJ, Gudnason, V, Guiducci, C, Hartikainen, A-L, Hassanali, N, Hall, AS, Havulinna, AS, Hayward, C, Heath, AC, Hengstenberg, C, Hicks, AA, Hinney, A, Hofman, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Isomaa, B, Jacobs, KB, Jarick, I, Jewell, E, John, U, Jorgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kajantie, E, Kaplan, LM, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, JW, Kolcic, I, Koenig, IR, Koskinen, S, Kovacs, P, Kuusisto, J, Kraft, P, Kvaloy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, LJ, Lecoeur, C, Lehtimaeki, T, Lettre, G, Liu, J, Lokki, M-L, Lorentzon, M, Luben, RN, Ludwig, B, Manunta, P, Marek, D, Marre, M, Martin, NG, McArdle, WL, McCarthy, A, McKnight, B, Meitinger, T, Melander, O, Meyre, D, Midthjell, K, Montgomery, GW, Morken, MA, Morris, AP, Mulic, R, Ngwa, JS, Nelis, M, Neville, MJ, Nyholt, DR, O'Donnell, CJ, O'Rahilly, S, Ong, KK, Oostra, B, Pare, G, Parker, AN, Perola, M, Pichler, I, Pietilaeinen, KH, Platou, CGP, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, NW, Ridderstrale, M, Rief, W, Ruokonen, A, Robertson, NR, Rzehak, P, Salomaa, V, Sanders, AR, Sandhu, MS, Sanna, S, Saramies, J, Savolainen, MJ, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, DS, Smit, JH, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Swift, AJ, Tammesoo, M-L, Tardif, J-C, Teder-Laving, M, Teslovich, TM, Thompson, JR, Thomson, B, Toenjes, A, Tuomi, T, van Meurs, JBJ, van Ommen, G-J, Vatin, V, Viikari, J, Visvikis-Siest, S, Vitart, V, Vogel, CIG, Voight, BF, Waite, LL, Wallaschofski, H, Walters, GB, Widen, E, Wiegand, S, Wild, SH, Willemsen, G, Witte, DR, Witteman, JC, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, JP, Farooqi, IS, Hebebrand, J, Huikuri, HV, James, AL, Kaehoenen, M, Levinson, DF, Macciardi, F, Nieminen, MS, Ohlsson, C, Palmer, LJ, Ridker, PM, Stumvoll, M, Beckmann, JS, Boeing, H, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Collins, FS, Cupples, LA, Smith, GD, Erdmann, J, Froguel, P, Greonberg, H, Gyllensten, U, Hall, P, Hansen, T, Harris, TB, Hattersley, AT, Hayes, RB, Heinrich, J, Hu, FB, Hveem, K, Illig, T, Jarvelin, M-R, Kaprio, J, Karpe, F, Khaw, K-T, Kiemeney, LA, Krude, H, Laakso, M, Lawlor, DA, Metspalu, A, Munroe, PB, Ouwehand, WH, Pedersen, O, Penninx, BW, Peters, A, Pramstaller, PP, Quertermous, T, Reinehr, T, Rissanen, A, Rudan, I, Samani, NJ, Schwarz, PEH, Shuldiner, AR, Spector, TD, Tuomilehto, J, Uda, M, Uitterlinden, A, Valle, TT, Wabitsch, M, Waeber, G, Wareham, NJ, Watkins, H, Wilson, JF, Wright, AF, Zillikens, MC, Chatterjee, N, McCarroll, SA, Purcell, S, Schadt, EE, Visscher, PM, Assimes, TL, Borecki, IB, Deloukas, P, Fox, CS, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, Mohlke, KL, O'Connell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, van Duijn, CM, Wichmann, H-E, Frayling, TM, Thorsteinsdottir, U, Abecasis, GR, Barroso, I, Boehnke, M, Stefansson, K, North, KE, McCarthy, MI, Hirschhorn, JN, Ingelsson, E, and Loos, RJF

Abstract

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Published
2010

53. The association of serum testosterone levels and ventricular repolarization

Author

Noord, Charlotte, Dorr, M, Sturkenboom, MCJM, Straus, Sabine, Reffelmann, T, Felix, SB, Hofman, Bert, Kors, Jan, Haring, R, Jong, Frank, Nauck, M, Uitterlinden, André, Wallaschofski, H, Witteman, JCM, Volzke, H, Stricker, Bruno, Noord, Charlotte, Dorr, M, Sturkenboom, MCJM, Straus, Sabine, Reffelmann, T, Felix, SB, Hofman, Bert, Kors, Jan, Haring, R, Jong, Frank, Nauck, M, Uitterlinden, André, Wallaschofski, H, Witteman, JCM, Volzke, H, and Stricker, Bruno

Abstract

It is assumed that testosterone is an important regulator of gender-related differences in ventricular repolarization. Therefore, our aim was to study whether serum levels of testosterone are associated with QTc, QT and RR interval variation. Setting: two independent population-based cohort studies. Participants: 445 male participants (a parts per thousand yen55 years) from the Rotterdam study cohort and 1,428 male participants from the study of health in Pomerania (SHIP) with an electrocardiogram who were randomly sampled for assessment of serum testosterone at baseline, after exclusion of participants with testosterone altering drugs, QTc prolonging drugs or dig(it)oxin, left ventricular hypertrophy and left and right bundle branch block. Endpoints: length of the QTc, QT and RR intervals. Analysis: linear regression model, adjusted for the two individual studies and a pooled analysis of both studies. The pooled analysis of the Rotterdam study and SHIP showed that the QTc interval gradually decreased among the tertiles (P value for trend 0.024). The third tertile of serum testosterone was associated with a lower QTc interval compared to the first tertile [-3.4 ms (-6.5; -0.3)]. However, the third tertile of serum testosterone was not associated with a lower QT interval compared to the first tertile [-0.7 ms (-3.1; 1.8)]. The RR interval gradually increased among the tertiles (P value for trend 0.002) and the third tertile of serum testosterone showed an increased RR interval compared to the first tertile [33.5 ms (12.2; 54.8)]. In the pooled analysis of two population-based studies, serum testosterone levels were not associated with the QT interval, which could be due to a lack of power. Lower QTc intervals in men with higher serum testosterone levels could be due to the association of serum testosterone with prolongation of the RR interval.

Published
2010

57. Genetic Loci for Retinal Arteriolar Microcirculation

Author

Xueling, Sim, Jensen, Richard A., Kamran Ikram, M., Mary Frances Cotch, Xiaohui, Li, Stuart, Macgregor, Jing, Xie, Albert Vernon Smith, Eric, Boerwinkle, Paul, Mitchell, Ronald, Klein, Klein, Barbara E. K., Glazer, Nicole L., Thomas, Lumley, Barbara, Mcknight, Psaty, Bruce M., de Jong, Paulus T. V. M., Albert, Hofman, Fernando, Rivadeneira, Uitterlinden, Andre G., van Duijn, Cornelia M., Thor, Aspelund, Gudny, Eiriksdottir, Harris, Tamara B., Fridbert, Jonasson, Launer, Lenore J., John, Attia, Baird, Paul N., Stephen, Harrap, Holliday, Elizabeth G., Michael, Inouye, Elena, Rochtchina, Scott, Rodney J., Ananth, Viswanathan, Guo, Li, Smith, Nicholas L., Wiggins, Kerri L., Kuo, Jane Z., Taylor, Kent D., Hewitt, Alex W., Martin, Nicholas G., Montgomery, Grant W., Cong, Sun, Young, Terri L., Mackey, David A., van Zuydam, Natalie R., Doney, Alex S. F., Palmer, Colin N. A., Morris, Andrew D., Rotter, Jerome I., Shyong Tai, E., Vilmundur, Gudnason, Vingerling, Johannes R., Siscovick, David S., Jie Jin Wang, Wong, Tien Y., Donnelly, P, Barroso, I, Blackwell, Jm, Bramon, E, Brown, Ma, Casas, Jp, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, Hs, Mathew, Cg, Palmer, Cn, Plomin, R, Rautanen, A, Sawcer, Sj, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cc, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, Se, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Mathew, C, Mccarthy, Mi, Newton Cheh, C, Johnson, T, Gateva, V, Tobin, Md, Bochud, M, Coin, L, Najjar, Ss, Zhao, Jh, Heath, Sc, Eyheramendy, S, Papadakis, K, Voight, Bf, Scott, Lj, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, Chambers, Jc, Khaw, Kt, Nilsson, P, van der Harst, P, Polidoro, Silvia, Grobbee, De, Onland Moret NC, Bots, Ml, Wain, Lv, Elliott, Ks, Teumer, A, Luan, J, Lucas, G, Kuusisto, J, Burton, Pr, Hadley, D, Mcardle, Wl, Brown, M, Dominiczak, A, Newhouse, Sj, Samani, Nj, Webster, J, Zeggini, E, Beckmann, Js, Bergmann, S, Lim, N, Song, K, Vollenweider, P, Waeber, G, Waterworth, Dm, Yuan, X, Groop, L, Orho Melander, M, Allione, A, Di Gregorio, A, Guarrera, Simonetta, Panico, S, Ricceri, Fulvio, Romanazzi, V, Sacerdote, Carlotta, Vineis, Paolo, Sandhu, Ms, Luben, Rn, Crawford, Gj, Jousilahti, P, Perola, M, Boehnke, M, Bonnycastle, Ll, Collins, Fs, Jackson, Au, Mohlke, Kl, Stringham, Hm, Valle, Tt, Willer, Cj, Bergman, Rn, Morken, Ma, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, Wichmann, He, Kathiresan, S, Marrugat, J, O'Donnell, Cj, Schwartz, Sm, Siscovick, Ds, Subirana, I, Freimer, Nb, Hartikainen, Al, O'Reilly, Pf, Peltonen, L, Pouta, A, de Jong PE, Snieder, H, van Gilst WH, Clarke, R, Goel, A, Hamsten, A, Peden, Jf, Seedorf, U, Syvänen, Ac, Tognoni, G, Lakatta, Eg, Sanna, S, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Ernst, F, Felix, Sb, Homuth, G, Lorbeer, R, Reffelmann, T, Rettig, R, Völker, U, Galan, P, Gut, Ig, Hercberg, S, Lathrop, Gm, Zeleneka, D, Soranzo, N, Williams, Fm, Zhai, G, Salomaa, V, Laakso, M, Elosua, R, Forouhi, Ng, Völzke, H, Uiterwaal, Cs, van der Schouw YT, Numans, Me, Matullo, Giuseppe, Navis, G, Berglund, G, Bingham, Sa, Kooner, Js, Connell, Jm, Bandinelli, S, Ferrucci, L, Watkins, H, Spector, Td, Tuomilehto, J, Altshuler, D, Strachan, Dp, Laan, M, Meneton, P, Wareham, Nj, Uda, M, Jarvelin, Mr, Mooser, V, Melander, O, Loos, Rj, Elliott, P, Abecasis, Gr, Caulfield, M, Munroe, P. B., Inouye, Michael [0000-0001-9413-6520], Apollo - University of Cambridge Repository, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Wellcome Trust Case Control Consortium 2, Global BPGen Consortium, Donnelly, P., Barroso, I., Blackwell, J.M., Bramon, E., Brown, M.A., Casas, J.P., Corvin, A., Deloukas, P., Duncanson, A., Jankowski, J., Markus, H.S., Mathew, C.G., Palmer, C.N., Plomin, R., Rautanen, A., Sawcer, S.J., Trembath, R.C., Viswanathan, A.C., Wood, N.W., Spencer, C.C., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Giannoulatou, E., Pirinen, M., Pearson, R., Strange, A., Su, Z., Vukcevic, D., Langford, C., Hunt, S.E., Edkins, S., Gwilliam, R., Blackburn, H., Bumpstead, S.J., Dronov, S., Gillman, M., Gray, E., Hammond, N., Jayakumar, A., McCann, O.T., Liddle, J., Potter, S.C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Mathew, C., McCarthy, M.I., Newton-Cheh, C., Johnson, T., Gateva, V., Tobin, M.D., Bochud, M., Coin, L., Najjar, S.S., Zhao, J.H., Heath, S.C., Eyheramendy, S., Papadakis, K., Voight, B.F., Scott, L.J., Zhang, F., Farrall, M., Tanaka, T., Wallace, C., Chambers, J.C., Khaw, K.T., Nilsson, P., van der Harst, P., Polidoro, S., Grobbee, D.E., Onland-Moret, N.C., Bots, M.L., Wain, L.V., Elliott, K.S., Teumer, A., Luan, J.J., Lucas, G., Kuusisto, J., Burton, P.R., Hadley, D., McArdle, W.L., Brown, M., Dominiczak, A., Newhouse, S.J., Samani, N.J., Webster, J., Zeggini, E., Beckmann, J.S., Bergmann, S., Lim, N., Song, K., Vollenweider, P., Waeber, G., Waterworth, D.M., Yuan, X., Groop, L., Orho-Melander, M., Allione, A., Di Gregorio, A., Guarrera, S., Panico, S., Ricceri, F., Romanazzi, V., Sacerdote, C., Vineis, P., Sandhu, M.S., Luben, R.N., Crawford, G.J., Jousilahti, P., Perola, M., Boehnke, M., Bonnycastle, L.L., Collins, F.S., Jackson, A.U., Mohlke, K.L., Stringham, H.M., Valle, T.T., Willer, C.J., Bergman, R.N., Morken, M.A., Döring, A., Gieger, C., Illig, T., Meitinger, T., Org, E., Pfeufer, A., Wichmann, H.E., Kathiresan, S., Marrugat, J., O'Donnell, C.J., Schwartz, S.M., Siscovick, D.S., Subirana, I., Freimer, N.B., Hartikainen, A.L., O'Reilly, P.F., Peltonen, L., Pouta, A., de Jong, P.E., Snieder, H., van Gilst, W.H., Clarke, R., Goel, A., Hamsten, A., Peden, J.F., Seedorf, U., Syvänen, A.C., Tognoni, G., Lakatta, E.G., Sanna, S., Scheet, P., Schlessinger, D., Scuteri, A., Dörr, M., Ernst, F., Felix, S.B., Homuth, G., Lorbeer, R., Reffelmann, T., Rettig, R., Völker, U., Galan, P., Gut, I.G., Hercberg, S., Lathrop, G.M., Zeleneka, D., Soranzo, N., Williams, F.M., Zhai, G., Salomaa, V., Laakso, M., Elosua, R., Forouhi, N.G., Völzke, H., Uiterwaal, C.S., van der Schouw, Y.T., Numans, M.E., Matullo, G., Navis, G., Berglund, G., Bingham, S.A., Kooner, J.S., Connell, J.M., Bandinelli, S., Ferrucci, L., Watkins, H., Spector, T.D., Tuomilehto, J., Altshuler, D., Strachan, D.P., Laan, M., Meneton, P., Wareham, N.J., Uda, M., Jarvelin, M.R., Mooser, V., Melander, O., Loos, R.J., Elliott, P., Abecasis, G.R., Caulfield, M., Munroe, P.B., Ophthalmology, Epidemiology, Internal Medicine, Erasmus School of Social and Behavioural Sciences, and Obstetrics & Gynecology

Subjects
Male, Pathology, BLUE MOUNTAINS EYE, VESSEL DIAMETERS, lcsh:Medicine, MICROVASCULAR ABNORMALITIES, Genome-wide association study, Cardiovascular, Coronary artery disease, chemistry.chemical_compound, 0302 clinical medicine, genome-wide association, Microcirculation, Retinal Arteriolar Microcirculation, Myocardial infarction, lcsh:Science, Aged, 80 and over, Medicine(all), 0303 health sciences, Multidisciplinary, Agricultural and Biological Sciences(all), MEF2 Transcription Factors, Genomics, Middle Aged, 3. Good health, Arterioles, medicine.anatomical_structure, Medicine, Chromosomes, Human, Pair 5, Female, INCIDENT SEVERE HYPERTENSION, Research Article, medicine.medical_specialty, Genotype, Clinical Research Design, ANTIHYPERTENSIVE DRUG THERAPIES, Single-nucleotide polymorphism, White People, 03 medical and health sciences, Genome Analysis Tools, Vascular Biology, BEAVER DAM EYE, Genetics, Genome-Wide Association Studies, medicine, Humans, CORONARY-HEART-DISEASE, GENOME-WIDE ASSOCIATION, Biology, Aged, 030304 developmental biology, Retina, Models, Genetic, Biochemistry, Genetics and Molecular Biology(all), Vascular disease, business.industry, lcsh:R, Computational Biology, Retinal Vessels, Human Genetics, Retinal, medicine.disease, Ophthalmology, chemistry, Genetic Loci, VASCULAR CALIBER, 030221 ophthalmology & optometry, lcsh:Q, Meta-Analyses, GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK, business, Genome-Wide Association Study
Abstract

Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value -8. This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11×10-12 in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.

Published
2013
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62. Telemedicine meets epidemiology

Author

Alte, D, Völzke, H, Robinson, DM, Kleine, V, Grabe, HJ, John, U, Felix, SB, Alte, D, Völzke, H, Robinson, DM, Kleine, V, Grabe, HJ, John, U, and Felix, SB

Published
2004

76. Prediction of metabolic syndrome by low serum testosterone levels in men: results from the study of health in Pomerania.

Author

Haring R, Völzke H, Felix SB, Schipf S, Dörr M, Rosskopf D, Nauck M, Schöfl C, Wallaschofski H, Haring, Robin, Völzke, Henry, Felix, Stephan B, Schipf, Sabine, Dörr, Marcus, Rosskopf, Dieter, Nauck, Matthias, Schöfl, Christof, and Wallaschofski, Henri

Abstract

Objective: The aim of this analysis was to assess the prospective association of serum testosterone and dehydroepiandrosterone sulfate (DHEAS) levels with incident metabolic syndrome (MetS) in men.Research Design and Methods: Data were obtained from the Study of Health in Pomerania (SHIP), a population-based prospective cohort of adults aged 20-79 years. Analyses were conducted in 1,004 men without baseline MetS defined by National Cholesterol Education Program Adult Treatment Panel III guidelines. Testosterone and DHEAS were categorized by age-specific quartiles and Poisson regression models with relative risks (RRs) and 95% CIs were estimated.Results: After a median follow-up time of 5.0 years, 480 men (47.8%) developed MetS. Testosterone levels decreased with increasing number of MetS components. Testosterone in the lowest quartile predicted MetS (RR 1.38 [95% CI 1.13-1.69]), particularly among men aged 20-39 years (2.06 [1.29-3.29]), even after adjustment for age, smoking, alcohol consumption, physical activity, waist circumference, self-related health, and time of blood sampling. DHEAS levels were not related to incident MetS (0.99 [0.83-1.19]).Conclusions: Low testosterone but not DHEAS predicts development of MetS in a population-based cohort of 1,004 men aged 20-79 years. Especially in young men aged 20-39 years, results suggest low testosterone as a strong predictor for incident MetS. Assessment of testosterone in young and middle-age men may allow early interventions in the general population. [ABSTRACT FROM AUTHOR]

Published
2009
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77. Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.

Author

Vasan RS, Glazer NL, Felix JF, Lieb W, Wild PS, Felix SB, Watzinger N, Larson MG, Smith NL, Dehghan A, Grosshennig A, Schillert A, Teumer A, Schmidt R, Kathiresan S, Lumley T, Aulchenko YS, König IR, Zeller T, and Homuth G

Abstract

Context: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease.Objective: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples.Design, Setting, and Participants: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort.Main Outcome Measures: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size.Results: In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance).Conclusions: We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease. [ABSTRACT FROM AUTHOR]

Published
2009
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83. Tele-electrocardiography in the epidemiological 'Study of Health in Pomerania' (SHIP)

Author

Alte D, Völzke H, Robinson DM, Kleine V, Grabe HJ, John U, and Felix SB

Abstract

We have evaluated a portable electrocardiogram (ECG) card in the large population-based epidemiological 'Study of Health in Pomerania' (SHIP). In all, 7008 men and women (20-79 years) were randomly selected from population registries and 4310 subjects participated. Participants used an ECG card for four weeks and recorded two ECGs daily. The participants were also encouraged to record additional ECGs in the case of symptomatic arrhythmias, chest pain or dizziness. The ECGs were sent via telephone. Acrobat (.pdf) files arrived at the study centre via email. Arrhythmias were analysed by visual ECG inspection. Seventy-one per cent of the participants sent at least 80% of the requested ECGs for four weeks. There were few problems (about 70) in the total of 38,162 ECGs transmitted. Overall, 94% of all ECGs were rated as 'good'. Physicians required about 1.5 h to read approximately 100 ECGs daily. The functionality and ergonomics of ECG cards appear to be sufficiently developed for large-scale use in epidemiological studies. [ABSTRACT FROM AUTHOR]

Published
2006
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85. Genome-wide association study identifies eight loci associated with blood pressure

Author

Newton-Cheh, C, Johnson, T, Gateva, V, Tobin, MD, Bochud, M, Coin, L, Najjar, SS, Zhao, JH, Heath, SC, Eyheramendy, S, Papadakis, K, Voight, BF, Scott, LJ, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, Chambers, JC, Khaw, K, Nilsson, P, Van Der Harst, P, Polidoro, S, Grobbee, DE, Onland-Moret, NC, Bots, ML, Wain, LV, Elliot, KS, Teumer, A, Luan, J, Lucas, G, Kuusisto, J, Burton, PR, Hadley, D, McArdle, WL, Brown, M, Dominiczak, A, Newhouse, SJ, Samani, NJ, Webster, J, Zeggini, E, Beckmann, JS, Bergmann, S, Lim, N, Song, K, Vollenweider, P, Waeber, G, Waterworth, DM, Yuan, X, Groop, L, Orho-Melander, M, Allione, A, Di Gregorio, A, Guarrera, S, Panico, S, Ricceri, F, Romanazzi, V, Sacerdote, C, Vineis, P, Barroso, I, Sandhu, MS, Luben, RN, Crawford, GJ, Jousilahti, P, Perola, M, Boehnke, M, Bonnycastle, LL, Collins, FS, Jackson, AU, Mohlke, KL, Stringham, HM, Valle, TT, Willer, CJ, Bergman, RN, Morken, MA, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, Wichmann, HE, Kathiresan, S, Marrugat, J, O'Donnell, CJ, Schwartz, SM, Siscovick, DS, Subirana, I, Freimer, NB, Hartikainen, A, McCarthy, MI, O'Reilly, PF, Peltonen, L, Pouta, A, De Jong, PE, Snieder, H, Van Gilst, WH, Clarke, R, Goel, A, Hamsten, A, Altshuler, D, Jarvelin, M, Elliott, P, Lakatta, EG, Forouhi, N, Wareham, NJ, Loos, RJF, Deloukas, P, Lathrop, GM, Zelenika, D, Strachan, DP, Soranzo, N, Williams, FM, Zhai, G, Spector, TD, Peden, JF, Watkins, H, Ferrucci, L, Caulfield, M, Munroe, PB, Berglund, G, Melander, O, Matullo, G, Uiterwaal, CS, van der Schouw, YT, Numans, ME, Ernst, F, Homuth, G, Völker, U, Elosua, R, Laakso, M, Connell, JM, Mooser, V, Salomaa, V, Tuomilehto, J, Laan, M, Navis, G, Seedorf, U, Syvänen, A, Tognoni, G, Sanna, S, Uda, M, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Felix, SB, Reffelmann, T, Lorbeer, R, Völzke, H, Rettig, R, Galan, P, Hercberg, S, Bingham, SA, Kooner, JS, Bandinelli, S, Meneton, P, Abecasis, G, Thompson, JR, Braga Marcano, CA, Barke, B, Dobson, R, Gungadoo, J, Lee, KL, Onipinla, A, Wallace, I, Xue, M, Clayton, DG, Leung, H, Nutland, S, Walker, NM, Todd, JA, Stevens, HE, Dunger, DB, Widmer, B, Downes, K, Cardon, LR, Kwiatkowski, DP, Barrett, JC, Evans, D, Morris, AP, Lindgren, CM, Rayner, NW, Timpson, NJ, Lyons, E, Vannberg, F, Hill, AVS, Teo, YY, Rockett, KA, Craddock, N, Attwood, AP, Bryan, C, Bumpstead, SJ, Chaney, A, Ghori, J, William, RG, Hunt, SE, Inouye, M, Keniry, E, King, E, McGinnis, R, Potter, S, Ravindrarajan, R, Whittaker, P, Withers, D, Bentley, D, Groves, CJ, Duncanson, A, Ouwehand, WH, Boorman, JP, Cant, B, Jolley, JD, Knight, AS, Koch, K, Taylor, NC, Watkins, NA, Winzer, T, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Donnely, P, Davidson, D, Marchini, JL, Spencer, ICA, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdottir, IB, Howie, BN, Su, Z, Vukcevic, D, Easton, D, Everson, U, Hussey, JM, Meech, E, Prowse, CV, Walters, GR, Jones, RW, Ring, SM, Prembey, M, Breen, G, St Clair, D, Ceasar, S, Gordon-Smith, K, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskovina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGruffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, DT, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Lewis, CM, Onnie, CM, Prescott, NJ, Mathew, CG, Forbes, A, Sanderson, J, Mathew, C, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hider, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DPM, Thomson, W, Worthington, J, Frayling, TM, Freathy, RM, Lango, H, Perry, JRB, Weedon, MN, Hattersley, AT, Shields, BM, Hitman, GA, Walker, M, Newport, M, Sirugo, G, Conway, D, Jallow, M, Bradbury, LA, Pointon, JL, Brown, MA, Farrar, C, Wordsworth, P, Franklyn, JA, Heward, JM, Simmonds, MJ, Cough, SCL, Seal, S, Stratton, MR, Ban, M, Goris, A, Sawcer, SJ, Compston, A, Newton-Cheh, C, Johnson, T, Gateva, V, Tobin, MD, Bochud, M, Coin, L, Najjar, SS, Zhao, JH, Heath, SC, Eyheramendy, S, Papadakis, K, Voight, BF, Scott, LJ, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, Chambers, JC, Khaw, K, Nilsson, P, Van Der Harst, P, Polidoro, S, Grobbee, DE, Onland-Moret, NC, Bots, ML, Wain, LV, Elliot, KS, Teumer, A, Luan, J, Lucas, G, Kuusisto, J, Burton, PR, Hadley, D, McArdle, WL, Brown, M, Dominiczak, A, Newhouse, SJ, Samani, NJ, Webster, J, Zeggini, E, Beckmann, JS, Bergmann, S, Lim, N, Song, K, Vollenweider, P, Waeber, G, Waterworth, DM, Yuan, X, Groop, L, Orho-Melander, M, Allione, A, Di Gregorio, A, Guarrera, S, Panico, S, Ricceri, F, Romanazzi, V, Sacerdote, C, Vineis, P, Barroso, I, Sandhu, MS, Luben, RN, Crawford, GJ, Jousilahti, P, Perola, M, Boehnke, M, Bonnycastle, LL, Collins, FS, Jackson, AU, Mohlke, KL, Stringham, HM, Valle, TT, Willer, CJ, Bergman, RN, Morken, MA, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, Wichmann, HE, Kathiresan, S, Marrugat, J, O'Donnell, CJ, Schwartz, SM, Siscovick, DS, Subirana, I, Freimer, NB, Hartikainen, A, McCarthy, MI, O'Reilly, PF, Peltonen, L, Pouta, A, De Jong, PE, Snieder, H, Van Gilst, WH, Clarke, R, Goel, A, Hamsten, A, Altshuler, D, Jarvelin, M, Elliott, P, Lakatta, EG, Forouhi, N, Wareham, NJ, Loos, RJF, Deloukas, P, Lathrop, GM, Zelenika, D, Strachan, DP, Soranzo, N, Williams, FM, Zhai, G, Spector, TD, Peden, JF, Watkins, H, Ferrucci, L, Caulfield, M, Munroe, PB, Berglund, G, Melander, O, Matullo, G, Uiterwaal, CS, van der Schouw, YT, Numans, ME, Ernst, F, Homuth, G, Völker, U, Elosua, R, Laakso, M, Connell, JM, Mooser, V, Salomaa, V, Tuomilehto, J, Laan, M, Navis, G, Seedorf, U, Syvänen, A, Tognoni, G, Sanna, S, Uda, M, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Felix, SB, Reffelmann, T, Lorbeer, R, Völzke, H, Rettig, R, Galan, P, Hercberg, S, Bingham, SA, Kooner, JS, Bandinelli, S, Meneton, P, Abecasis, G, Thompson, JR, Braga Marcano, CA, Barke, B, Dobson, R, Gungadoo, J, Lee, KL, Onipinla, A, Wallace, I, Xue, M, Clayton, DG, Leung, H, Nutland, S, Walker, NM, Todd, JA, Stevens, HE, Dunger, DB, Widmer, B, Downes, K, Cardon, LR, Kwiatkowski, DP, Barrett, JC, Evans, D, Morris, AP, Lindgren, CM, Rayner, NW, Timpson, NJ, Lyons, E, Vannberg, F, Hill, AVS, Teo, YY, Rockett, KA, Craddock, N, Attwood, AP, Bryan, C, Bumpstead, SJ, Chaney, A, Ghori, J, William, RG, Hunt, SE, Inouye, M, Keniry, E, King, E, McGinnis, R, Potter, S, Ravindrarajan, R, Whittaker, P, Withers, D, Bentley, D, Groves, CJ, Duncanson, A, Ouwehand, WH, Boorman, JP, Cant, B, Jolley, JD, Knight, AS, Koch, K, Taylor, NC, Watkins, NA, Winzer, T, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Donnely, P, Davidson, D, Marchini, JL, Spencer, ICA, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdottir, IB, Howie, BN, Su, Z, Vukcevic, D, Easton, D, Everson, U, Hussey, JM, Meech, E, Prowse, CV, Walters, GR, Jones, RW, Ring, SM, Prembey, M, Breen, G, St Clair, D, Ceasar, S, Gordon-Smith, K, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskovina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGruffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, DT, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Lewis, CM, Onnie, CM, Prescott, NJ, Mathew, CG, Forbes, A, Sanderson, J, Mathew, C, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hider, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DPM, Thomson, W, Worthington, J, Frayling, TM, Freathy, RM, Lango, H, Perry, JRB, Weedon, MN, Hattersley, AT, Shields, BM, Hitman, GA, Walker, M, Newport, M, Sirugo, G, Conway, D, Jallow, M, Bradbury, LA, Pointon, JL, Brown, MA, Farrar, C, Wordsworth, P, Franklyn, JA, Heward, JM, Simmonds, MJ, Cough, SCL, Seal, S, Stratton, MR, Ban, M, Goris, A, Sawcer, SJ, and Compston, A

Abstract

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10−24), CYP1A2 (P = 1 × 10−23), FGF5 (P = 1 × 10−21), SH2B3 (P = 3 × 10−18), MTHFR (P = 2 × 10−13), c10orf107 (P = 1 × 10−9), ZNF652 (P = 5 × 10−9) and PLCD3 (P = 1 × 10−8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

86. Prediction of short‐ and long‐term mortality in takotsubo syndrome: the InterTAK Prognostic Score

Author

Thomas Münzel, Yoshio Kobayashi, Wolfgang Koenig, Hugo A. Katus, Paul Bridgman, Christina Chan, Ioana Sorici-Barb, Eduardo Bossone, Gregor Poglajen, Abhiram Prasad, Fabrizio D'Ascenzo, Jelena R. Ghadri, Monika Budnik, Konrad A. Szawan, Fausto J. Pinto, David E. Winchester, Guido Michels, Carlo Di Mario, Thomas Fischer, Matteo Bianco, Jerold S. Shinbane, Burkert Pieske, Alessandro Candreva, Rodolfo Citro, P. Christian Schulze, Annahita Sarcon, Kan Liu, Christian Ukena, Christoph Kaiser, Martin Borggrefe, Florim Cuculi, Stefan Osswald, Behrouz Kherad, Heribert Schunkert, Jeroen J. Bax, Maike Knorr, Ken Kato, Petr Widimský, Alexandra Shilova, Frank Ruschitzka, Martin Kozel, Victoria L. Cammann, Roman Pfister, Olivier Lairez, Michael Neuhaus, Alessandro Cuneo, Wolfgang Rottbauer, Ibrahim Akin, Lucas Jörg, Christian Hauck, L. Christian Napp, Holger Thiele, Manfred Wischnewsky, K.E. Juhani Airaksinen, Hans Rickli, Tuija Vasankari, Carla Paolini, Lars S. Maier, Philippe Meyer, Adrian P. Banning, Richard Kobza, Beatrice Bacchi, Miłosz Jaguszewski, Rafal Dworakowski, Michael Böhm, Claudio Bilato, Mahir Karakas, Philip MacCarthy, Mikhail Gilyarov, Charanjit S. Rihal, Alexander Pott, Claudius Jacobshagen, Clément Delmas, Jose David Arroja, Ibrahim El-Battrawy, Filippo Crea, Carsten Tschöpe, Pedro Carrilho-Ferreira, Ekaterina Gilyarova, Jennifer Franke, Daniel Beug, Ruediger C. Braun-Dullaeus, John D. Horowitz, Thanh H Nguyen, Sebastiano Gili, Christof Burgdorf, Jan Galuszka, Leonarda Galiuto, Grzegorz Opolski, Susanne Heiner, Johann Bauersachs, Christian Templin, Petr Tousek, Michel Noutsias, Lawrence Rajan, Stephan B. Felix, Wolfgang Dichtl, Thomas F. Lüscher, Gerd Hasenfuß, Wischnewsky, Mb, Candreva, A, Bacchi, B, Cammann, Vl, Kato, K, Szawan, Ka, Gili, S, D'Ascenzo, F, Dichtl, W, Citro, R, Bossone, E, Neuhaus, M, Franke, J, Sorici-Barb, I, Jaguszewski, M, Noutsias, M, Knorr, M, Heiner, S, Burgdorf, C, Kherad, B, Tschope, C, Sarcon, A, Shinbane, J, Rajan, L, Michels, G, Pfister, R, Cuneo, A, Jacobshagen, C, Karakas, M, Koenig, W, Pott, A, Meyer, P, Arroja, Jd, Banning, A, Cuculi, F, Kobza, R, Fischer, Ta, Vasankari, T, Airaksinen, Kej, Napp, Lc, Budnik, M, Dworakowski, R, Maccarthy, P, Kaiser, C, Osswald, S, Galiuto, L, Chan, C, Bridgman, P, Beug, D, Delmas, C, Lairez, O, El-Battrawy, I, Akin, I, Gilyarova, E, Shilova, A, Gilyarov, M, Kozel, M, Tousek, P, Winchester, De, Galuszka, J, Ukena, C, Poglajen, G, Carrilho-Ferreira, P, Hauck, C, Paolini, C, Bilato, C, Prasad, A, Rihal, C, Liu, K, Schulze, Pc, Bianco, M, Jorg, L, Rickli, H, Nguyen, Th, Kobayashi, Y, Bohm, M, Maier, L, Pinto, Fj, Widimsky, P, Borggrefe, M, Felix, Sb, Opolski, G, Braun-Dullaeus, Rc, Rottbauer, W, Hasenfuss, G, Pieske, Bm, Schunkert, H, Thiele, H, Bauersachs, J, Katus, Ha, Horowitz, J, Di Mario, C, Munzel, T, Crea, F, Bax, Jj, Luscher, Tf, Ruschitzka, F, Ghadri, Jr, Templin, C, and Repositório da Universidade de Lisboa

Subjects
Male, Research design, medicine.medical_specialty, MEDLINE, 030204 cardiovascular system & hematology, Prognostic score, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Takotsubo Cardiomyopathy, Internal medicine, medicine, Humans, 030212 general & internal medicine, Survival analysis, Aged, Aged, 80 and over, Takotsubo syndrome, business.industry, Stroke Volume, Stroke volume, Middle Aged, Prognosis, medicine.disease, Survival Analysis, 3. Good health, Research Design, Heart failure, Cardiology, Female, Long term mortality, Cardiology and Cardiovascular Medicine, business
Abstract

© 2019 The Authors European Journal of Heart Failure © 2019 European Society of Cardiology, Recent evidence suggests comparable in‐hospital and long‐term outcomes between takotsubo syndrome (TTS) and acute coronary syndrome. Medical scoring systems are practical tools for decision making and prognostic assessment. However, TTS‐specific scoring systems for risk stratification have not yet been established. Recently, classification based on triggering conditions proved useful in predicting adverse outcomes in TTS (InterTAK Classification).1 Since clinical parameters other than triggering conditions can be associated with adverse outcomes in TTS, such as systolic blood pressure and heart rate, the present study aimed to establish a scoring system combining triggering factors with other important but easily‐ obtainable clinical parameters of daily clinical practice., C.T. has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme and the Swiss Heart Foundation. L.S.M. was supported by EU HORIZON 2020 (SILICOFCM ID777204). The InterTAK Registry is supported by the Biss Davies Charitable Trust.

Published
2019
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87. Intraventricular thrombus formation and embolism in Takotsubo syndrome insights from the international Takotsubo registry

Author

Alexandra Shilova, Davide Di Vece, Johann Bauersachs, Wolfgang Koenig, Michael Neuhaus, Rodolfo Citro, Jose David Arroja, Adrian P. Banning, Jennifer Franke, Charanjit S. Rihal, Abhiram Prasad, Carlo Di Mario, Michael Böhm, Carsten Tschöpe, Burkhardt Seifert, Filippo Crea, Christian Templin, David E. Winchester, Hugo A. Katus, Clément Delmas, Pedro Carrilho-Ferreira, Paul Bridgman, Petr Tousek, Guido Michels, Fausto J. Pinto, Sebastiano Gili, Jelena R. Ghadri, Petr Widimský, Burkert Pieske, Jeroen J. Bax, Christian Ukena, Christoph Kaiser, Wolfgang Dichtl, Christof Burgdorf, Philippe Meyer, Christina Chan, Gerd Hasenfuß, Philip MacCarthy, Mikhail Gilyarov, Leonarda Galiuto, Grzegorz Opolski, Susanne Heiner, Ruediger C. Braun-Dullaeus, Alexander Pott, Annahita Sarcon, Ekaterina Gilyarova, Michel Noutsias, Lawrence Rajan, Claudius Jacobshagen, Roman Pfister, Behrouz Kherad, John D. Horowitz, Martin Borggrefe, Mahir Karakas, Stefan Osswald, Victoria L. Cammann, Katharina J. Ding, Jan Galuszka, Wolfgang Rottbauer, Ibrahim El-Battrawy, Stephan B. Felix, Martin Kozel, Ibrahim Akin, Thomas F. Lüscher, Frank Ruschitzka, Thomas Fischer, Fabrizio D'Ascenzo, Rafal Dworakowski, Olivier Lairez, L. Christian Napp, Holger Thiele, Eduardo Bossone, Thomas Münzel, Claudio Bilato, Maike Knorr, K.E. Juhani Airaksinen, Florim Cuculi, Carla Paolini, Konrad A. Szawan, Richard Kobza, Alessandro Cuneo, Barbara E. Stähli, Heribert Schunkert, Miłosz Jaguszewski, Manfred Wischnewsky, Tuija Vasankari, Ding, Kj, Cammann, Vl, Szawan, Ka, Stähli, Be, Wischnewsky, M, Di Vece, D, Citro, R, Jaguszewski, M, Seifert, B, Sarcon, A, Knorr, M, Heiner, S, Gili, S, D'Ascenzo, F, Neuhaus, M, Napp, Lc, Franke, J, Noutsias, M, Burgdorf, C, Koenig, W, Kherad, B, Rajan L, Michels, G, Pfister, R, Cuneo, A, Jacobshagen, C, Karakas, M, Pott, A, Meyer, P, Arroja, Jd, Banning, A, Cuculi, F, Kobza, R, Fischer, Ta, Vasankari, T, Airaksinen, Kej, Paolini, C, Bilato, C, Carrilho-Ferreira, P, Opolski, G, Dworakowski, R, Maccarthy, P, Kaiser, C, Osswald, S, Galiuto, L, Dichtl, W, Chan, C, Bridgman, P, Delmas, C, Lairez, O, El-Battrawy, I, Akin, I, Gilyarova, E, Shilova, A, Gilyarov, M, Kozel, M, Tousek, P, Widimský, P, Winchester, De, Galuszka, J, Ukena, C, Horowitz, Jd, Di Mario, C, Prasad A, Rihal, C, Pinto, Fj, Crea, F, Borggrefe, M, Braun-Dullaeus, Rc, Rottbauer, W, Bauersachs, J, Katus, Ha, Hasenfuß, G, Tschöpe, C, Pieske, Bm, Thiele, H, Schunkert, H, Böhm, M, Felix, Sb, Münzel, T, Bax, Jj, Lüscher, Tf, Ruschitzka, F, Ghadri, Jr, Bossone, E, and Templin, C.

Subjects
Male, Coronary angiography, Time Factors, Radionuclide ventriculography, 030204 cardiovascular system & hematology, Coronary Angiography, Electrocardiography, 0302 clinical medicine, Risk Factors, Registries, 030212 general & internal medicine, Framingham Risk Score, medicine.diagnostic_test, Incidence, Incidence (epidemiology), Magnetic Resonance Imaging, 3. Good health, Europe, Survival Rate, Cine, thrombus, cardiovascular system, Cardiology, outcome, Female, Cardiology and Cardiovascular Medicine, Takotsubo syndrome, medicine.medical_specialty, Heart Diseases, Heart Ventricles, Magnetic Resonance Imaging, Cine, risk score, Risk Assessment, embolism, 03 medical and health sciences, Takotsubo Cardiomyopathy, Internal medicine, medicine, Humans, cardiovascular diseases, Thrombus, Radionuclide Ventriculography, Aged, business.industry, Australia, Thrombosis, medicine.disease, United States, Embolism, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, business, Follow-Up Studies
Abstract

Objective: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0–38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×10 3 cells/μL emerged as independent predictors for thrombus formation or embolism. Conclusions: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01947621.

Published
2020

88. Long-Term Prognosis of Patients With Takotsubo Syndrome

Author

John D. Horowitz, Thomas Münzel, David E. Winchester, Guido Michels, Katharina J. Ding, Wolfgang Koenig, Jeroen J. Bax, Burkert Pieske, Mahir Karakas, Christian Ukena, K.E. Juhani Airaksinen, Christoph Kaiser, Sebastiano Gili, Stephan B. Felix, Rafal Dworakowski, Christian Templin, Claudius Jacobshagen, Abhiram Prasad, Fabrizio D'Ascenzo, Lawrence Rajan, Martin Borggrefe, Rena A. Levinson, Christof Burgdorf, Florim Cuculi, Petr Tousek, Thomas F. Lüscher, Alexandra Shilova, Mikhail Gilyarov, Victoria L. Cammann, Roman Pfister, Frank Ruschitzka, Alessandro Candreva, Filippo Crea, Davide Di Vece, Wolfgang Rottbauer, Ruediger C. Braun-Dullaeus, Heribert Schunkert, Carsten Tschöpe, Stefan Osswald, Rodolfo Citro, Burkhardt Seifert, Annahita Sarcon, Ibrahim Akin, Gerd Hasenfuß, Leonarda Galiuto, L. Christian Napp, Holger Thiele, Ekaterina Gilyarova, Grzegorz Opolski, Susanne Heiner, Michel Noutsias, Johann Bauersachs, Miłosz Jaguszewski, Alessandro Cuneo, Hugo A. Katus, Olivier Lairez, Ibrahim El-Battrawy, Wolfgang Dichtl, Jozef Micek, Philip MacCarthy, Rahel Bianchi, Maike Knorr, Ken Kato, Adrian P. Banning, Jelena-R. Ghadri, Martin Kozel, Michael Böhm, Konrad A. Szawan, Jennifer Franke, Manfred Wischnewsky, Klaus Empen, Tuija Vasankari, Eduardo Bossone, Richard Kobza, Beatrice Bacchi, Susanne A. Schlossbauer, Petr Widimský, Stjepan Jurisic, Samir M. Said, Thomas Fischer, Clément Delmas, Ghadri, Jr, Kato, K, Cammann, Vl, Gili, S, Jurisic, S, Di Vece, D, Candreva, A, Ding, Kj, Micek, J, Szawan, Ka, Bacchi, B, Bianchi, R, Levinson, Ra, Wischnewsky, M, Seifert, B, Schlossbauer, Sa, Citro, R, Bossone, E, Munzel, T, Knorr, M, Heiner, S, D'Ascenzo, F, Franke, J, Sarcon, A, Napp, Lc, Jaguszewski, M, Noutsias, M, Katus, Ha, Burgdorf, C, Schunkert, H, Thiele, H, Bauersachs, J, Tschope, C, Pieske, Bm, Rajan, L, Michels, G, Pfister, R, Cuneo, A, Jacobshagen, C, Hasenfuss, G, Karakas, M, Koenig, W, Rottbauer, W, Said, Sm, Braun-Dullaeus, Rc, Banning, A, Cuculi, F, Kobza, R, Fischer, Ta, Vasankari, T, Airaksinen, Kej, Opolski, G, Dworakowski, R, Maccarthy, P, Kaiser, C, Osswald, S, Galiuto, L, Crea, F, Dichtl, W, Empen, K, Felix, Sb, Delmas, C, Lairez, O, El-Battrawy, I, Akin, I, Borggrefe, M, Horowitz, J, Kozel, M, Tousek, P, Widimsky, P, Gilyarova, E, Shilova, A, Gilyarov, M, Winchester, De, Ukena, C, Bax, Jj, Prasad, A, Bohm, M, Luscher, Tf, Ruschitzka, F, and Templin, C

Subjects
Male, Acute coronary syndrome, medicine.medical_specialty, Time Factors, 030204 cardiovascular system & hematology, tako tsubo syndrome, acute coronary syndrome, broken heart syndrome, classification, outcome, stress factor, Broken heart syndrome, 03 medical and health sciences, 0302 clinical medicine, Takotsubo Cardiomyopathy, Internal medicine, medicine, Humans, Registries, 030212 general & internal medicine, Mortality, Aged, Aged, 80 and over, Takotsubo syndrome, business.industry, Mortality rate, Electroencephalography, Emotional stress, Middle Aged, ta3121, Prognosis, Stress factor, medicine.disease, 3. Good health, Physical stress, Cardiology and Cardiovascular Medicine, Cohort, Female, Nervous System Diseases, business, Stress, Psychological, Follow-Up Studies
Abstract

Background Prognosis of Takotsubo syndrome (TTS) remains controversial due to scarcity of available data. Additionally, the effect of the triggering factors remains elusive. Objectives This study compared prognosis between TTS and acute coronary syndrome (ACS) patients and investigated short- and long-term outcomes in TTS based on different triggers. Methods Patients with TTS were enrolled from the International Takotsubo Registry. Long-term mortality of patients with TTS was compared to an age- and sex-matched cohort of patients with ACS. In addition, short- and long-term outcomes were compared between different groups according to triggering conditions. Results Overall, TTS patients had a comparable long-term mortality risk with ACS patients. Of 1,613 TTS patients, an emotional trigger was detected in 485 patients (30%). Of 630 patients (39%) related to physical triggers, 98 patients (6%) had acute neurologic disorders, while in the other 532 patients (33%), physical activities, medical conditions, or procedures were the triggering conditions. The remaining 498 patients (31%) had no identifiable trigger. TTS patients related to physical stress showed higher mortality rates than ACS patients during long-term follow-up, whereas patients related to emotional stress had better outcomes compared with ACS patients. Conclusions Overall, TTS patients had long-term outcomes comparable to age- and sex-matched ACS patients. Also, we demonstrated that TTS can either be benign or a life-threating condition depending on the inciting stress factor. We propose a new classification based on triggers, which can serve as a clinical tool to predict short- and long-term outcomes of TTS. (International Takotsubo Registry [InterTAK Registry]; NCT01947621)

Published
2018

92. Clinical Predictors and Prognostic Impact of Recovery of Wall Motion Abnormalities in Takotsubo Syndrome: Results From the International Takotsubo Registry

Author

Alessandro Cuneo, Rodolfo Citro, Sebastiano Gili, Victoria L. Cammann, L. Christian Napp, Wolfgang Rottbauer, Heribert Schunkert, Alexandra Shilova, Roman Pfister, Holger Thiele, Ibrahim Akin, Annahita Sarcon, Christof Burgdorf, Wolfgang Dichtl, Wolfgang Koenig, Petr Widimský, Pedro Carrilho-Ferreira, Mikhail Gilyarov, Philip MacCarthy, Fabrizio D'Ascenzo, Jeroen J. Bax, Hugo A. Katus, Paul Bridgman, K.E. Juhani Airaksinen, Eduardo Bossone, Stefan Osswald, Yoshio Kobayashi, Jan Galuszka, Gregor Poglajen, John D. Horowitz, Thomas Fischer, Ruediger C. Braun-Dullaeus, Konrad A. Szawan, Abhiram Prasad, Carlo Di Mario, Fausto J. Pinto, Thomas Münzel, Jennifer Franke, Carla Paolini, Richard Kobza, Christina Chan, Daniel Beug, Olivier Lairez, Claudio Bilato, Mahir Karakas, Florim Cuculi, Gerd Hasenfuß, Lawrence Rajan, Tuija Vasankari, Philippe Meyer, David E. Winchester, Jelena R. Ghadri, Adrian P. Banning, Leonarda Galiuto, Guido Michels, Stjepan Jurisic, Michel Noutsias, Rafal Dworakowski, Grzegorz Opolski, Maike Knorr, Susanne Heiner, Behrouz Kherad, Christian Templin, Johann Bauersachs, Stephan B. Felix, Burkert Pieske, Frank Ruschitzka, Martin Borggrefe, Petr Tousek, Thomas F. Lüscher, Michael Böhm, Christian Ukena, Ken Kato, Christoph Kaiser, Martin Kozel, Filippo Crea, Ekaterina Gilyarova, Ibrahim El-Battrawy, Charanjit S. Rihal, Clément Delmas, Alexander Pott, Claudius Jacobshagen, Jose David Arroja, Carsten Tschöpe, Miłosz Jaguszewski, Repositório da Universidade de Lisboa, Jurisic, S, Gili, S, Cammann, Vl, Kato, K, Szawan, Ka, D'Ascenzo, F, Jaguszewski, M, Bossone, E, Citro, R, Sarcon, A, Napp, Lc, Franke, J, Noutsias, M, Knorr, M, Heiner, S, Burgdorf, C, Koenig, W, Pott, A, Kherad, B, Rajan, L, Michels, G, Pfister, R, Cuneo, A, Jacobshagen, C, Karakas, M, Meyer, P, Arroja, Jd, Banning, A, Cuculi, F, Kobza, R, Fischer, Ta, Vasankari, T, Airaksinen, Kej, Dworakowski, R, Kaiser, C, Osswald, S, Galiuto, L, Dichtl, W, Chan, C, Bridgman, P, Beug, D, Delmas, C, Lairez, O, Kozel, M, Tousek, P, Winchester, De, Gilyarova, E, Shilova, A, Gilyarov, M, El-Battrawy, I, Akin, I, Galuszka, J, Ukena, C, Poglajen, G, Paolini, C, Bilato, C, Carrilho-Ferreira, P, Pinto, Fj, Opolski, G, Maccarthy, P, Kobayashi, Y, Prasad, A, Rihal, C, Widimsky, P, Horowitz, Jd, Di Mario, C, Crea, F, Tschope, C, Pieske, Bm, Hasenfuss, G, Rottbauer, W, Braun-Dullaeus, Rc, Felix, Sb, Borggrefe, M, Thiele, H, Bauersachs, J, Katus, Ha, Schunkert, H, Munzel, T, Bohm, M, Bax, Jj, Luscher, Tf, Ruschitzka, F, Ghadri, Jr, and Templin, C

Subjects
Male, medicine.medical_specialty, Time Factors, outcome, recovery, takotsubo syndrome, wall motion abnormalities, MEDLINE, 030204 cardiovascular system & hematology, Wall motion abnormalities, 03 medical and health sciences, 0302 clinical medicine, Takotsubo Cardiomyopathy, Recovery, Medicine, Humans, 030212 general & internal medicine, Wall motion, Prospective Studies, Registries, Intensive care medicine, Aged, Retrospective Studies, Original Research, Outcome, Heart Failure, Takotsubo syndrome, business.industry, Creative commons, Recovery of Function, Middle Aged, Prognosis, 3. Good health, ddc, Female, Cardiology and Cardiovascular Medicine, business, Switzerland
Abstract

© 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes., Background: Left ventricular (LV) recovery in takotsubo syndrome (TTS) occurs over a wide‐ranging interval, varying from hours to weeks. We sought to investigate the clinical predictors and prognostic impact of recovery time for TTS patients. Methods and Results: TTS patients from the International Takotsubo Registry were included in this study. Cut‐off for early LV recovery was determined to be 10 days after the acute event. Multivariable logistic regression was used to assess factors associated with the absence of early recovery. In‐hospital outcomes and 1‐year mortality were compared for patients with versus without early recovery. We analyzed 406 patients with comprehensive and serial imaging data regarding time to recovery. Of these, 191 (47.0%) had early LV recovery and 215 (53.0%) demonstrated late LV improvement. Patients without early recovery were more often male (12.6% versus 5.2%; P=0.011) and presented more frequently with typical TTS (76.3% versus 67.0%, P=0.040). Cardiac and inflammatory markers were higher in patients without early recovery than in those with early recovery. Patients without early recovery showed unfavorable 1‐year outcome compared with patients with early recovery (P=0.003). On multiple logistic regression, male sex, LV ejection fraction, Christian Templin was supported by the H.H. Sheikh Khalifa bin Hamad Al‐Thani Research Programme and the Swiss Heart Foundation. The InterTAK Registry is supported by the Biss Davies Charitable Trust.

Published
2019

93. Clinical Features and Outcomes of Patients With Malignancy and Takotsubo Syndrome: Observations From the International Takotsubo Registry

Author

Petr Widimský, Katharina J. Ding, Sebastiano Gili, L. Christian Napp, Holger Thiele, Stephan B. Felix, Christof Burgdorf, Thomas F. Lüscher, Johann Bauersachs, Mahir Karakas, Alexandra Shilova, Davide Di Vece, Gerd Hasenfuß, Miłosz Jaguszewski, Roman Pfister, Thomas Münzel, Hugo A. Katus, David E. Winchester, Stefan Osswald, Thomas Fischer, Guido Michels, Ruediger C. Braun-Dullaeus, Adrian P. Banning, Philip MacCarthy, Stjepan Jurisic, Burkert Pieske, Christian Ukena, Fabrizio D'Ascenzo, Christoph Kaiser, Michael Böhm, Olivier Lairez, Rodolfo Citro, Richard Kobza, Antonio H. Frangieh, John D. Horowitz, Leonarda Galiuto, Grzegorz Opolski, Susanne Heiner, Filippo Crea, Beatrice Bacchi, Annahita Sarcon, Jeroen J. Bax, Wolfgang Dichtl, Victoria L. Cammann, Jelena R. Ghadri, Ekaterina Gilyarova, Wolfgang Rottbauer, Frank Ruschitzka, Ibrahim Akin, Ibrahim El-Battrawy, Martin Borggrefe, Jozef Micek, Clément Delmas, Lawrence Rajan, Rafal Dworakowski, Mikhail Gilyarov, Christian Templin, Petr Tousek, Jerold S. Shinbane, Tuija Vasankari, Michel Noutsias, Heribert Schunkert, Wolfgang Koenig, Eduardo Bossone, Abhiram Prasad, Carlo Di Mario, Alessandro Cuneo, Ken Kato, Martin Kozel, Konrad A. Szawan, Florim Cuculi, Maike Knorr, K.E. Juhani Airaksinen, Jennifer Franke, Carsten Tschöpe, Burkhardt Seifert, Claudius Jacobshagen, Cammann, Vl, Sarcon, A, Ding, Kj, Seifert, B, Kato, K, Di Vece, D, Szawan, Ka, Gili, S, Jurisic, S, Bacchi, B, Micek, J, Frangieh, Ah, Napp, Lc, Jaguszewski, M, Bossone, E, Citro, R, D'Ascenzo, F, Franke, J, Noutsias, M, Knorr, M, Heiner, S, Burgdorf, C, Koenig, W, Thiele, H, Tschope, C, Rajan, L, Michels, G, Pfister, R, Cuneo, A, Jacobshagen, C, Karakas, M, Banning, A, Cuculi, F, Kobza, R, Fischer, Ta, Vasankari, T, Airaksinen, Kej, Dworakowski, R, Kaiser, C, Osswald, S, Galiuto, L, Dichtl, W, Delmas, C, Lairez, O, Horowitz, Jd, Kozel, M, Widimsky, P, Tousek, P, Winchester, De, Gilyarova, E, Shilova, A, Gilyarov, M, El-Battrawy, I, Akin, I, Ukena, C, Bauersachs, J, Pieske, Bm, Hasenfuss, G, Rottbauer, W, Braun-Dullaeus, Rc, Opolski, G, Maccarthy, P, Felix, Sb, Borggrefe, M, Di Mario, C, Crea, F, Katus, Ha, Schunkert, H, Munzel, T, Bohm, M, Bax, Jj, Prasad, A, Shinbane, J, Luscher, Tf, Ruschitzka, F, Ghadri, Jr, and Templin, C

Subjects
medicine.medical_specialty, Acute coronary syndrome, acute coronary syndrome, broken heart syndrome, cancer, malignancy, outcome, takotsubo syndrome, 030204 cardiovascular system & hematology, Malignancy, Broken heart syndrome, 03 medical and health sciences, 0302 clinical medicine, Takotsubo Cardiomyopathy, Neoplasms, Internal medicine, medicine, Humans, In patient, Registries, 030212 general & internal medicine, Original Research, Heart Failure, Takotsubo syndrome, business.industry, Cancer, medicine.disease, ddc, 3. Good health, Clinical trial, Cohort, Cardiology and Cardiovascular Medicine, business
Abstract

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short‐ and long‐term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short‐ and long‐term mortality. A subanalysis was performed comparing long‐term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long‐term mortality was higher in patients with malignancy (P, See Editorial Angelini and Uribe

Published
2019

94. Cardiac arrest in takotsubo syndrome: results from the InterTAK Registry

Author

David E. Winchester, Philip MacCarthy, Leonarda Galiuto, Guido Michels, Hugo A. Katus, Grzegorz Opolski, Susanne Heiner, Burkert Pieske, Christian Ukena, Wolfgang Koenig, Richard Kobza, Sebastiano Gili, Christoph Kaiser, Eduardo Bossone, Beatrice Bacchi, Johann Bauersachs, Filippo Crea, K.E. Juhani Airaksinen, Konrad A. Szawan, Heribert Schunkert, Abhiram Prasad, Carlo Di Mario, John D. Horowitz, L. Christian Napp, Holger Thiele, Gerd Hasenfuß, Rafal Dworakowski, Ekaterina Gilyarova, Roman Pfister, Christof Burgdorf, Christian Templin, Flurina Famos, Stjepan Jurisic, Victoria L. Cammann, Stefan Osswald, Miłosz Jaguszewski, Maike Knorr, Wolfgang Rottbauer, Alexandra Shilova, Ibrahim Akin, Petr Tousek, Jeroen J. Bax, Adrian P. Banning, Lawrence Rajan, Alessandro Cuneo, Davide Di Vece, Claudius Jacobshagen, Katharina J. Ding, Susanne A. Schlossbauer, Jennifer Franke, Ruediger C. Braun-Dullaeus, Manfred Wischnewsky, Klaus Empen, Michael Böhm, Carsten Tschöpe, Petr Widimský, Stephan B. Felix, Olivier Lairez, Burkhardt Seifert, Thomas Münzel, Michel Noutsias, Tuija Vasankari, Thomas F. Lüscher, Ibrahim El-Battrawy, Slayman Obeid, Fabrizio D'Ascenzo, Florim Cuculi, Mikhail Gilyarov, Rodolfo Citro, Mahir Karakas, Ken Kato, Jozef Micek, Fiorenzo Gaita, Martin Kozel, Wolfgang Dichtl, Clément Delmas, Rena A. Levinson, Samir M. Said, Olivia Lenoir, Annahita Sarcon, Thomas Fischer, Jelena R. Ghadri, Martin Borggrefe, Frank Ruschitzka, Gili, S, Cammann, Vl, Schlossbauer, Sa, Kato, K, D'Ascenzo, F, Di Vece, D, Jurisic, S, Micek, J, Obeid, S, Bacchi, B, Szawan, Ka, Famos, F, Sarcon, A, Levinson, R, Ding, Kj, Seifert, B, Lenoir, O, Bossone, E, Citro, R, Franke, J, Napp, Lc, Jaguszewski, M, Noutsias, M, Munzel, T, Knorr, M, Heiner, S, Katus, Ha, Burgdorf, C, Schunkert, H, Thiele, H, Bauersachs, J, Tschope, C, Pieske, Bm, Rajan, L, Michels, G, Pfister, R, Cuneo, A, Jacobshagen, C, Hasenfuss, G, Karakas, M, Koenig, W, Rottbauer, W, Said, Sm, Braun-Dullaeus, Rc, Banning, A, Cuculi, F, Kobza, R, Fischer, Ta, Vasankari, T, Airaksinen, Kej, Opolski, G, Dworakowski, R, Maccarthy, P, Kaiser, C, Osswald, S, Galiuto, L, Crea, F, Dichtl, W, Empen, K, Felix, Sb, Delmas, C, Lairez, O, El-Battrawy, I, Akin, I, Borggrefe, M, Gilyarova, E, Shilova, A, Gilyarov, M, Horowitz, Jd, Kozel, M, Tousek, P, Widimsky, P, Winchester, De, Ukena, C, Gaita, F, Di Mario, C, Wischnewsky, Mb, Bax, Jj, Prasad, A, Bohm, M, Ruschitzka, F, Luscher, Tf, Ghadri, Jr, and Templin, C

Subjects
Male, Tachycardia, Acute heart failure, Broken heart syndrome, Cardiac arrest, Outcome, Takotsubo syndrome, medicine.medical_specialty, Cardiomyopathy, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Takotsubo Cardiomyopathy, Internal medicine, Humans, Medicine, Registries, 030212 general & internal medicine, Asystole, Retrospective Studies, Ejection fraction, business.industry, Atrial fibrillation, Middle Aged, Prognosis, medicine.disease, Survival Analysis, ddc, Heart Arrest, 3. Good health, Editor's Choice, Editorial, Pulseless electrical activity, Ventricular fibrillation, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract

Aims We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS). Methods and results We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P Conclusions Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.

Published
2019

95. Outcomes Associated With Cardiogenic Shock in Takotsubo Syndrome: Results From the International Takotsubo Registry

Author

Roman Pfister, Florim Cuculi, Stefan Osswald, Michel Noutsias, Klaus Empen, Annahita Sarcon, Philip MacCarthy, Alessandro Cuneo, Tuija Vasankari, Ruediger C. Braun-Dullaeus, Alessandro Candreva, Rodolfo Citro, Mahir Karakas, Katharina J. Ding, Christian Templin, Wolfgang Koenig, Petr Tousek, L. Christian Napp, Fabrizio D'Ascenzo, Petr Widimský, Samir M. Said, Richard Kobza, Olivier Lairez, Holger Thiele, K.E. Juhani Airaksinen, Beatrice Bacchi, Abhiram Prasad, Carlo Di Mario, David E. Winchester, Eduardo Bossone, Filippo Crea, Claudius Jacobshagen, Heribert Schunkert, Guido Michels, Alexandra Shilova, Sebastiano Gili, Jozef Micek, Ekaterina Gilyarova, Konrad A. Szawan, Davide Di Vece, Burkert Pieske, Carsten Tschöpe, Thomas Fischer, Thomas Münzel, Christian Ukena, Christoph Kaiser, Adrian P. Banning, Stephan B. Felix, Jennifer Franke, John D. Horowitz, Thomas F. Lüscher, Hugo A. Katus, Jelena-R. Ghadri, Christof Burgdorf, Ken Kato, Martin Borggrefe, Michael Böhm, Miłosz Jaguszewski, Martin Kozel, Frank Ruschitzka, Maike Knorr, Victoria L. Cammann, Ibrahim El-Battrawy, Wolfgang Rottbauer, Moritz Schwyzer, Stjepan Jurisic, Ibrahim Akin, Clément Delmas, Mikhail Gilyarov, Jeroen J. Bax, Leonarda Galiuto, Grzegorz Opolski, Susanne Heiner, Johann Bauersachs, Gerd Hasenfuβ, Rafal Dworakowski, Lawrence Rajan, Wolfgang Dichtl, Di Vece, D, Citro, R, Cammann, Vl, Kato, K, Gili, S, Szawan, Ka, Micek, J, Jurisic, S, Ding, Kj, Bacchi, B, Schwyzer, M, Candreva, A, Bossone, E, D'Ascenzo, F, Sarcon, A, Franke, J, Napp, Lc, Jaguszewski, M, Noutsias, M, Munzel, T, Knorr, M, Heiner, S, Katus, Ha, Burgdorf, C, Schunkert, H, Thiele, H, Bauersachs, J, Tschope, C, Pieske, Bm, Rajan, L, Michels, G, Pfister, R, Cuneo, A, Jacobshagen, C, Hasenfuss, G, Karakas, M, Koenig, W, Rottbauer, W, Said, Sm, Braun-Dullaeus, Rc, Banning, A, Cuculi, F, Kobza, R, Fischer, Ta, Vasankari, T, Airaksinen, Kj, Opolski, G, Dworakowski, R, Maccarthy, P, Kaiser, C, Osswald, S, Galiuto, L, Crea, F, Dichtl, W, Empen, K, Felix, Sb, Delmas, C, Lairez, O, El-Battrawy, I, Akin, I, Borggrefe, M, Gilyarova, E, Shilova, A, Gilyarov, M, Horowitz, J, Kozel, M, Tousek, P, Widimsky, P, Winchester, De, Ukena, C, Di Mario, C, Prasad, A, Bohm, M, Bax, Jj, Luscher, Tf, Ruschitzka, F, Ghadri, Jr, and Templin, C

Subjects
Male, medicine.medical_specialty, Time Factors, Comorbidity, 030204 cardiovascular system & hematology, Risk Assessment, Broken heart syndrome, 03 medical and health sciences, 0302 clinical medicine, Informed consent, Risk Factors, Takotsubo Cardiomyopathy, Physiology (medical), cardiac mechanical support, Medicine, Humans, takotsubo syndrome, 030212 general & internal medicine, Hospital Mortality, Prospective Studies, Registries, broken heart syndrome, cardiogenic shock, outcome, Aged, Female, Middle Aged, Prognosis, Retrospective Studies, Shock, Cardiogenic, Takotsubo syndrome, business.industry, Cardiogenic shock, Incidence (epidemiology), Medical record, Ethics committee, Shock, ta3121, medicine.disease, Cardiogenic, 3. Good health, Emergency medicine, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Observational study, Cardiology and Cardiovascular Medicine, business
Abstract

The clinical course of takotsubo syndrome (TTS) can be complicated by several life-threatening conditions. In particular, cardiogenic shock (CS) represents one of the leading causes of mortality in the acute phase and occurs in a considerable number of patients with TTS, with an incidence of ≈10%. At present, no established guidelines are available to support specific treatment recommendations,and the conventional therapy for CS leads to uncertain results in TTS cases. The International Takotsubo Registry (www.takotsubo-registry.com) is an observational, prospective, and retrospective registry established at the University Hospital Zurich in 2011, with the largest TTS database worldwide. Patients were included in the registry between 2011 and 2017 based on modified Mayo Clinic Diagnostic criteria. Hospitalization data were recorded through standardized forms on admission or during revision of clinical charts; follow-up data were obtained from medical records, telephone follow-up, or clinical visits. The study population was categorized into 2 groups: patients with TTS with and without CS. The study protocol was reviewed by the respective local ethics committees or investigational review boards at each collaboration site. Where informed consent was required, formal written consent was obtained from patients.

Published
2019

96. The Cardiomyopathy Registry of the EURObservational Research Programme of the European Society of Cardiology: baseline data and contemporary management of adult patients with cardiomyopathies

Author

Charron, Philippe, Elliott, Perry M, Gimeno, Juan R, Caforio, Alida L P, Kaski, Juan Pablo, Tavazzi, Luigi, Tendera, Michal, Maupain, Carole, Laroche, Cécile, Rubis, Pawel, Jurcut, Ruxandra, Calò, Leonardo, Heliö, Tiina M, Sinagra, Gianfranco, Zdravkovic, Marija, Kavoliūnienė, Aušra, Felix, Stephan B, Grzybowski, Jacek, Losi, Maria-Angela, Asselbergs, Folkert W, García-Pinilla, José Manuel, Salazar-Mendiguchia, Joel, Mizia-Stec, Katarzyna, Maggioni, Aldo P, Anastasakis, Aris, Biagini, Elena, Bilinska, Zofia, Castro, Francisco Jose, Celutkiene, Jelena, Chakova, Natalija, Chmielewski, Przemyslaw, Drago, Fabrizio, Frigy, Attila, Frustaci, Andrea, Garcia-Pavia, Pablo, Hinic, Sasa, Kindermann, Ingrid, Limongelli, Giuseppe, Medrano, Constancio, Monserrat, Lorenzo, Olusegun-Joseph, Akinsanya, Ripoll-Vera, Tomas, Rocha Lopes, Luis, Saad, Aly, Sala, Simone, Seferovic, Petar M, Sepp, Robert, Urbano-Moral, Jose Angel, Villacorta, Eduardo, Wybraniec, Maciej, Yotti, Raquel, Zachara, Elisabetta, Zorio, Esther, Charron, P., Elliott, P. M., Gimeno, J. R., Caforio, A. L. P., Kaski, J. P., Tavazzi, L., Tendera, M., Maupain, C., Laroche, C., Rubis, P., Jurcut, R., Calo, L., Helio, T. M., Sinagra, G., Zdravkovic, M., Kavoliuniene, A., Felix, S. B., Grzybowski, J., Losi, M. A., Asselbergs, F. W., Garcia-Pinilla, J. M., Salazar-Mendiguchia, J., Mizia-Stec, K., Maggioni, A. P., Anastasakis, A., Biagini, E., Bilinska, Z., Castro, F. J., Celutkiene, J., Chakova, N., Chmielewski, P., Drago, F., Frigy, A., Frustaci, A., Garcia-Pavia, P., Hinic, S., Kindermann, I., Limongelli, G., Medrano, C., Monserrat, L., Olusegun-Joseph, A., Ripoll-Vera, T., Lopes, L. R., Saad, A., Sala, S., Seferovic, P. M., Sepp, R., Urbano-Moral, J. A., Villacorta, E., Wybraniec, M., Yotti, R., Zachara, E., Zorio, E., Charron, Philippe, Elliott, Perry M., Gimeno, Juan R., Caforio, Alida L. P., Kaski, Juan Pablo, Tavazzi, Luigi, Tendera, Michal, Maupain, Carole, Laroche, Cécile, Rubis, Pawel, Jurcut, Ruxandra, Calò, Leonardo, Heliö, Tiina M., Sinagra, Gianfranco, Zdravkovic, Marija, Kavoliuniene, Aušra, Felix, Stephan B., Grzybowski, Jacek, Losi, Maria-Angela, Asselbergs, Folkert W., García-Pinilla, José Manuel, Salazar-Mendiguchia, Joel, Mizia-Stec, Katarzyna, Maggioni, Aldo P., Anastasakis, Ari, Biagini, Elena, Bilinska, Zofia, Castro, Francisco Jose, Celutkiene, Jelena, Chakova, Natalija, Chmielewski, Przemyslaw, Drago, Fabrizio, Frigy, Attila, Frustaci, Andrea, Garcia-Pavia, Pablo, Hinic, Sasa, Kindermann, Ingrid, Limongelli, Giuseppe, Medrano, Constancio, Monserrat, Lorenzo, Olusegun-Joseph, Akinsanya, Ripoll-Vera, Toma, Lopes, Luis Rocha, Saad, Aly, Sala, Simone, Seferovic, Petar M., Sepp, Robert, Urbano-Moral, Jose Angel, Villacorta, Eduardo, Wybraniec, Maciej, Yotti, Raquel, Zachara, Elisabetta, Zorio, Esther, Charron, P, Elliott, Pm, Gimeno, Jr, Caforio, Alp, Kaski, Jp, Tavazzi, L, Tendera, M, Maupain, C, Laroche, C, Rubis, P, Jurcut, R, Calò, L, Heliö, Tm, Sinagra, G, Zdravkovic, M, Kavoliuniene, A, Felix, Sb, Grzybowski, J, Losi, Ma, Asselbergs, Fw, García-Pinilla, Jm, Salazar-Mendiguchia, J, Mizia-Stec, K, and Maggioni, Ap

Subjects
Male, Cardiomyopathy, 030204 cardiovascular system & hematology, Defibrillator, 0302 clinical medicine, Dilated, Age Factor, 030212 general & internal medicine, Prospective Studies, Registries, Prospective cohort study, Arrhythmogenic Right Ventricular Dysplasia, Cardiomyopathy, Restrictive, adult, Hypertrophic cardiomyopathy, Age Factors, Disease Management, Dilated cardiomyopathy, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Arrhythmogenic right ventricular dysplasia, Europe, Arrhythmogenic right ventricular, Female, Cardiology and Cardiovascular Medicine, Cardiomyopathies, Human, Adult, Cardiomyopathy, Dilated, Registry, medicine.medical_specialty, Cardiomyopathies, adult, Restrictive, Context (language use), Right ventricular cardiomyopathy, 03 medical and health sciences, Internal medicine, medicine, Humans, Cardiomyopathie, business.industry, Restrictive cardiomyopathy, Cardiomyopathy, Hypertrophic, medicine.disease, Prospective Studie, Hypertrophic, business, Defibrillators
Abstract

Aims The Cardiomyopathy Registry of the EURObservational Research Programme is a prospective, observational, and multinational registry of consecutive patients with four cardiomyopathy subtypes: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). We report the baseline characteristics and management of adults enrolled in the registry. ................................................................................................................................................................................................... Methods and results A total of 3208 patients were enrolled by 69 centres in 18 countries [HCM (n = 1739); DCM (n = 1260); ARVC (n = 143); and RCM (n = 66)]. Differences between cardiomyopathy subtypes (P < 0.001) were observed for age at diagnosis, history of familial disease, history of sustained ventricular arrhythmia, use of magnetic resonance imaging or genetic testing, and implantation of defibrillators. When compared with probands, relatives had a lower age at diagnosis (P < 0.001), but a similar rate of symptoms and defibrillators. When compared with the Long-Term phase, patients of the Pilot phase (enrolled in more expert centres) had a more frequent rate of familial disease (P < 0.001), were more frequently diagnosed with a rare underlying disease (P < 0.001), and more frequently implanted with a defibrillator (P = 0.023). Comparing four geographical areas, patients from Southern Europe had a familial disease more frequently (P < 0.001), were more frequently diagnosed in the context of a family screening (P < 0.001), and more frequently diagnosed with a rare underlying disease (P < 0.001). ................................................................................................................................................................................................... Conclusion By providing contemporary observational data on characteristics and management of patients with cardiomyopathies, the registry provides a platform for the evaluation of guideline implementation. Potential gaps with existing recommendations are discussed as well as some suggestions for improvement of health care provision in Europe.

Published
2018

97. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Author

Fredrik Karpe, Ivonne Jarick, Julius S. Ngwa, Alan F. Wright, Robert Luben, Aaron R. Folsom, Sailaja Vedantam, Veikko Salomaa, Markku J. Savolainen, Robert Clarke, Shah Ebrahim, Thomas A. Buchanan, Mao Fu, Albert Hofman, Philippe Goyette, Camilla H. Sandholt, Fabio Macciardi, Elizabeth K. Speliotes, Barbara McKnight, Anne McCarthy, Mika Kaehoenen, Christian Gieger, Jorma S. A. Viikari, Nicholas J. Timpson, Kirsti Kvaløy, Douglas F. Levinson, Toby Johnson, Cornelia M. van Duijn, Samuli Ripatti, Andrew A. Hicks, Niina Pellikka, Charles C. White, Leena Peltonen, Reedik Maegi, John-Olov Jansson, Qunyuan Zhang, Claudia Lamina, Robert C. Kaplan, Peter M. Visscher, Laura J. Scott, Claes Ohlsson, Brian Thomson, Jubao Duan, Heikki V. Huikuri, Stephen O'Rahilly, Anette P. Gjesing, David P. Strachan, Caroline S. Fox, Sekar Kathiresan, Anna-Liisa Hartikainen, Johannes Kettunen, Maris Teder-Laving, Erik Ingelsson, Mario A. Morken, Peter Kovacs, Elisabeth Widen, Caroline Hayward, Eleanor Wheeler, Jing Hua Zhao, Vilmundur Gudnason, Panos Deloukas, Jacqueline C. M. Witteman, Gert-Jan B. van Ommen, Eric Boerwinkle, Martin Wabitsch, Christian Hengstenberg, Beverley Balkau, Thor Aspelund, Neelam Hassanali, Paul M. Ridker, Nicole L. Glazer, Joyce B. J. van Meurs, Michel Marre, Alan James, Ben A. Oostra, David Meyre, Ida Surakka, Stefan Schreiber, Nigel W. Rayner, Heribert Schunkert, Thomas Quertermous, Stefan Gustafsson, Peter Kraft, Benjamin F. Voight, Irene Pichler, Olle Melander, Ozren Polasek, Antti Jula, Alan R. Sanders, Andrew R. Wood, Yoav Ben-Shlomo, Thomas Illig, Jianjun Liu, Gerard Waeber, André G. Uitterlinden, Torben Hansen, Helene Alavere, André Scherag, Paolo Manunta, Johannes Hebebrand, Themistocles L. Assimes, Stefan R. Bornstein, Jaakko Tuomilehto, Morris Brown, Jianfeng Xu, Yii-Der Ida Chen, Nancy L. Heard-Costa, Cristen J. Willer, Henrik Greonberg, Guillaume Lettre, John R. Thompson, Inês Barroso, John R. B. Perry, Andreas Ziegler, James F. Wilson, Christopher J. O'Donnell, Maurizio F. Facheris, Robert Lawrence, Jan Smit, Lyle J. Palmer, Ulf Gyllensten, Richard B. Hayes, Shengxu Li, Barbara Ludwig, Larry D. Atwood, Valgerdur Steinthorsdottir, Sabine Schipf, Jouko Saramies, Tanja Boes, Martin Ridderstråle, Jennie Hui, Lina Zgaga, Susann Scherag, Alexandra I. F. Blakemore, Marjolein Peters, Timo T. Valle, Nelson B. Freimer, Kay-Tee Khaw, Amy J. Swift, Michael Stumvoll, Miriam F. Moffatt, Cecilia M. Lindgren, Ayellet V. Segrè, Neil Robertson, Richard N. Bergman, Francis S. Collins, Ryan P. Welch, Mari-Liis Tammesoo, Devin Absher, Tamara B. Harris, Kari E. North, Manuela Uda, Karen L. Mohlke, Inga Prokopenko, Per Hall, Gudmar Thorleifsson, Marjo-Riitta Järvelin, Guillaume Paré, Stefan Gaget, G. Bragi Walters, Michael N. Weedon, Jean-Claude Tardif, Mary F. Feitosa, Anke Toenjes, Ken K. Ong, Cécile Lecoeur, Paavo Zitting, David S. Siscovick, Chih-Mei Chen, Peter Almgren, Anneli Pouta, Philippe Froguel, Pekka Jousilahti, Jaakko Kaprio, Maria Teresa Sciarrone Alibrandi, Sophie van Wingerden, Steven A. McCarroll, Oluf Pedersen, Shaun Purcell, Veronique Vitart, Leena Kinnunen, Markus Perola, Jacques S. Beckmann, Vincent Vatin, Christopher J. Groves, Zoltán Kutalik, Lu Qi, Volker Hoesel, Seppo Koskinen, Suzanne Rafelt, Anke Hinney, Annette Peters, David Schlessinger, Eero Kajantie, Jian Yang, Nicholas G. Martin, Joshua W. Knowles, Kristian Midthjell, Olivier Lantieri, Dorret I. Boomsma, Harry Campbell, Ulrich John, Kirsi H. Pietilaeinen, George Davey Smith, Carl G. P. Platou, Sarah H. Wild, Patricia B. Munroe, Iris M. Heid, Diana Marek, Michael Boehnke, Andres Metspalu, Hana Lango Allen, Peter Rzehak, Christine Cavalcanti-Proença, M. Carola Zillikens, Åsa Johansson, Anuj Goel, Andrew T. Hattersley, Massimo Mangino, Michael E. Goddard, Tim D. Spector, Winfried Rief, Jonathan Tyrer, Lachlan J. M. Coin, Peter P. Pramstaller, Narisu Narisu, John Beilby, Jonathan Stephens, Christina Barlassina, Pamela Fischer-Posovszky, Brenda W.J.H. Penninx, Kaisa Silander, Richard H. Myers, Jouke-Jan Hottenga, Eric E. Schadt, Francesco P. Cappuccio, Martin den Heijer, Fernando Rivadeneira, Lindsay L. Waite, Wilmar Igl, Igor Rudan, Manjinder S. Sandhu, Debbie A Lawlor, Kristian Hveem, Susanna Wiegand, Mari Nelis, Thomas Reinehr, Elisabeth Thiering, Inke R. Koenig, Stephan B. Felix, Fredrik Wiklund, Ian N. M. Day, Willem H. Ouwehand, Peter Schwarz, Richard M. Watanabe, Keri L. Monda, Kari Stefansson, Gudny Eiriksdottir, H-Erich Wichmann, Jianxin Shi, Najaf Amin, Carlos Iribarren, Heiko Krude, Dale R. Nyholt, Lenore J. Launer, Stephen J. Chanock, Harald Grallert, Hugh Watkins, Juergen Graessler, Tsegaselassie Workalemahu, Jeanette Erdmann, Mattias Lorentzon, Leif Groop, Teresa Ferreira, Chiara Lanzani, Johanna Kuusisto, Johan G. Eriksson, Tõnu Esko, Torben Jørgensen, Robert J. Weyant, Michael Preuss, Lambertus A. Kiemeney, Daniel I. Chasman, Daniel R. Witte, Kevin B. Jacobs, Nicole Soranzo, John M. C. Connell, Soumya Raychaudhuri, Jian'an Luan, Joshua C. Randall, Joachim Heinrich, Anthony J. Balmforth, Eva Fisher, Elizabeth S. Jewell, Alice M. Arnold, Nele Friedrich, Olli T. Raitakari, Henri Wallaschofski, Jeffrey R. O'Connell, Terho Lehtimaeki, Marika Kaakinen, Heather M. Stringham, Bo Isomaa, I. Sadaf Farooqi, Anna L. Dixon, Anne U. Jackson, Mark I. McCarthy, Lori L. Bonnycastle, Aila Rissanen, Joel N. Hirschhorn, Nilesh J. Samani, Aimo Ruokonen, Frank B. Hu, L. Adrienne Cupples, Amanda J. Bennett, Shamika Ketkar, Ruth J. F. Loos, Nicholas J. Wareham, Tiinamaija Tuomi, Timothy M. Frayling, Ulla Sovio, Georg Homuth, Liming Liang, Heiner Boeing, Unnur Thorsteinsdottir, Ingrid B. Borecki, Danielle M. Greenawalt, Rosanda Mulić, Ivana Kolcic, Talin Haritunians, Mark J. Caulfield, Marja-Liisa Lokki, Tanya M. Teslovich, Paul Elliott, Matt Neville, Nilanjan Chatterjee, Albert V. Smith, Andrew P. Morris, Fabio Busonero, Gonçalo R. Abecasis, Jaana Laitinen, Michael R. Erdos, Candace Guiducci, Lee M. Kaplan, Aki S. Havulinna, Pablo V. Gejman, Alan R. Shuldiner, Serena Sanna, David J. Hunter, Sonja I. Berndt, Carla I. G. Vogel, Alistair S. Hall, Karol Estrada, Sven Bergmann, Thomas Meitinger, Gonneke Willemsen, Andrew C. Heath, Katja K.H. Aben, Markku Laakso, Juha Sinisalo, Tuomas O. Kilpelaenen, Mark E. Cooper, Heike Biebermann, Eco J. C. de Geus, Grant W. Montgomery, Sophie Visvikis-Siest, Thomas W. Winkler, Ju-Hyun Park, Alex N. Parker, Peter S. Chines, James Nemesh, Nabila Bouatia-Naji, Wendy L. McArdle, Roberto Elosua, Markku S. Nieminen, Psychiatry, NCA - Anxiety & Depression, EMGO - Mental health, Epidemiology, Internal Medicine, Clinical Genetics, Radiology & Nuclear Medicine, Erasmus MC other, Public Health, Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, EMGO+ - Mental Health, MAGIC, Procardis Consortium, Medical Research Council (MRC), Speliotes, Ek, Willer, Cj, Berndt, Si, Monda, Kl, Thorleifsson, G, Jackson, Au, Allen, Hl, Lindgren, Cm, Luan, J, Mägi, R, Randall, Jc, Vedantam, S, Winkler, Tw, Qi, L, Workalemahu, T, Heid, Im, Steinthorsdottir, V, Stringham, Hm, Weedon, Mn, Wheeler, E, Wood, Ar, Ferreira, T, Weyant, Rj, Segrè, Av, Estrada, K, Liang, L, Nemesh, J, Park, Jh, Gustafsson, S, Kilpeläinen, To, Yang, J, BOUATIA NAJI, N, Esko, T, Feitosa, Mf, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, Av, Welch, R, Zhao, Jh, Aben, Kk, Absher, Dm, Amin, N, Dixon, Al, Fisher, E, Glazer, Nl, Goddard, Me, HEARD COSTA, Nl, Hoesel, V, Hottenga, Jj, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, Mf, Myers, Rh, Narisu, N, Perry, Jr, Peters, Mj, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Scott, Lj, Timpson, Nj, Tyrer, Jp, VAN WINGERDEN, S, Watanabe, Rm, White, Cc, Wiklund, F, Barlassina, C, Chasman, Di, Cooper, Mn, Jansson, Jo, Lawrence, Rw, Pellikka, N, Prokopenko, I, Shi, J, Thiering, E, Alavere, H, Alibrandi, Mt, Almgren, P, Arnold, Am, Aspelund, T, Atwood, Ld, Balkau, B, Balmforth, Aj, Bennett, Aj, BEN SHLOMO, Y, Bergman, Rn, Bergmann, S, Biebermann, H, Blakemore, Ai, Boes, T, Bonnycastle, Ll, Bornstein, Sr, Brown, Mj, Buchanan, Ta, Busonero, F, Campbell, H, Cappuccio, Fp, CAVALCANTI PROENÇA, C, Chen, Yd, Chen, Cm, Chines, P, Clarke, R, Coin, L, Connell, J, Day, In, DEN HEIJER, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Erdos, Mr, Eriksson, Jg, Facheris, Mf, Felix, Sb, FISCHER POSOVSZKY, P, Folsom, Ar, Friedrich, N, Freimer, Nb, Fu, M, Gaget, S, Gejman, Pv, Geus, Ej, Gieger, C, Gjesing, Ap, Goel, A, 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Pietiläinen, Kh, Platou, Cg, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, Nw, Ridderstråle, M, Rief, W, Ruokonen, A, Robertson, Nr, Rzehak, P, Salomaa, V, Sanders, Ar, Sandhu, M, Sanna, S, Saramies, J, Savolainen, Mj, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, D, Smit, Jh, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Swift, Aj, Tammesoo, Ml, Tardif, Jc, TEDER LAVING, M, Teslovich, Tm, Thompson, Jr, Thomson, B, Tönjes, A, Tuomi, T, VAN MEURS, Jb, VAN OMMEN, Gj, Vatin, V, Viikari, J, VISVIKIS SIEST, S, Vitart, V, Vogel, Ci, Voight, Bf, Waite, Ll, Wallaschofski, H, Walters, Gb, Widen, E, Wiegand, S, Wild, Sh, Willemsen, G, Witte, Dr, Witteman, Jc, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, Jp, Farooqi, I, Hebebrand, J, Huikuri, Hv, James, Al, Kähönen, M, Levinson, Df, Macciardi, F, Nieminen, M, Ohlsson, C, Palmer, Lj, Ridker, Pm, Stumvoll, M, Beckmann, J, Boeing, H, Boerwinkle, E, Boomsma, Di, Caulfield, Mj, Chanock, 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North, Ke, Mccarthy, Mi, Hirschhorn, Jn, Ingelsson, E, and Loos, Rj

Subjects
Netherlands Twin Register (NTR), Medizin, Genome-wide association study, Aetiology, screening and detection [ONCOL 5], FTO gene, Body Mass Index, 0302 clinical medicine, SH2B1, GASTRIC-INHIBITORY POLYPEPTIDE, ADULT OBESITY, Glucose homeostasis, Body Size, GENETICS & HEREDITY, 2. Zero hunger, Genetics, Genetics & Heredity, RISK, 0303 health sciences, Neuronal growth regulator 1, Genetics of obesity, COMMON VARIANTS, Chromosome Mapping, 11 Medical And Health Sciences, Body Height/genetics, Body Size/genetics, Body Weight/genetics, European Continental Ancestry Group/genetics, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Humans, Obesity/genetics, Polymorphism, Single Nucleotide, FAT MASS, Body Height/*genetics *Body Mass Index Body Size/genetics Body Weight/*genetics *Chromosome Mapping European Continental Ancestry Group/genetics Genetic Predisposition to Disease/genetics Genome-Wide Association Study Humans Obesity/genetics Polymorphism, Single Nucleotide, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, MELANOCORTIN-4 RECEPTOR GENE, Life Sciences & Biomedicine, European Continental Ancestry Group, EARLY-ONSET, 030209 endocrinology & metabolism, Locus (genetics), Biology, Article, White People, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, SDG 3 - Good Health and Well-being, body mass index, genome-wide association, meta-analysis, Genetic Predisposition to Disease, Obesity, GENOME-WIDE ASSOCIATION, FTO GENE, 030304 developmental biology, Science & Technology, genome-wide association gastric-inhibitory polypeptide melanocortin-4 receptor gene glucose-homeostasis common variants adult obesity early-onset fat mass risk metaanalysis, Body Weight, 06 Biological Sciences, MAGIC, Body Height, GLUCOSE-HOMEOSTASIS, Procardis Consortium, Body mass index, Developmental Biology
Abstract

Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS index (P < 5-10-8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly aSociated loci may provide new insights into human body weight regulation. © 2010 Nature America, Inc. All rights reserved.

Published
2010
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98. Research update for articles published in EJCI in 2008

Author

Anderwald, C., Ankersmit, H. J., Badaoui, A., Beneduce, L., Buko, V. U., Calo, L. A., Carrero, J. J., Chang, C. Y., Chang, K. C., Chen, Y. J., Cnotliwy, M., Costelli, Paola, Crujeiras, A. B., Cuocolo, A., Davis, P. A., de Boer, O. J., Ebenbichler, C. F., Erridge, C., Fassina, G., Felix, S. B., García Gómez, M. C., Guerrero Romero, F., Haider, D. G., Heinemann, A., Herda, L. R., Hoogeveen, E. K., Hörl, W. H., Iglseder, B., Huang, K. C., Kaser, S., Kastrati, A., Kuzniatsova, N., Latella, G., Lichtenauer, M., Lin, Y. K., Lip, G. Y., N. H., Lu, Lukivskaya, O., Luschnig, P., Maniscalco, M., Martinez, J. A., Müller Krebs, S., Ndrepepa, G., Nicolaou, G., Peck Radosavljevic, M., Penna, Fabio, Pintó, X., Reiberger, T., Rodriguez Moran, M., Schmidt, A., Schwenger, V., Spinelli, L., Starkel, P., Stehouwer, C. D., Stenvinkel, P., Strasser, P., Suzuki, H., Tschoner, A., van der Wal, A. C., Vesely, D. L., Wen, C. J., Wiernicki, I., Zanninelli, G., Zhu, Y., Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), RS: CARIM School for Cardiovascular Diseases, Anderwald, C, Ankersmit, Hj, Badaoui, A, Beneduce, L, Buko, Vu, Calo, La, Carrero, Jj, Chang, C, Chang, K, Chen, Y, Cnotliwy, M, Costelli, P, Crujeiras, Ab, Cuocolo, Alberto, Davis, Pa, De Boer, Oj, Ebenbichler, Cf, Erridge, C, Fassina, G, Felix, Sb, García Gómez, Mc, Guerrero Romero, F, Haider, Dg, Heinemann, A, Herda, Lr, Hoogeveen, Ek, Hörl, Wh, Iglseder, B, Huang, K, Kaser, S, Kastrati, A, Kuzniatsova, N, Latella, G, Lichtenauer, M, Lin, Y, Lip, Gyh, Lu, N, Lukivskaya, O, Luschnig, P, Maniscalco, M, Martinez, Ja, Müller Krebs, S, Ndrepepa, G, Nicolaou, G, Peck Radosavljevic, M, Penna, F, Pintó, X, Reiberger, T, Rodriguez Moran, M, Schmidt, A, Schwenger, V, Spinelli, Letizia, Starkel, P, Stehouwer, Cda, Stenvinkel, P, Strasser, P, Suzuki, H, Tschoner, A, Van Der Wal, Ac, Vesely, Dl, Wen, C, Wiernicki, I, Zanninelli, G, and Zhu, Y.

Abstract

Eur J Clin Invest 2010; 40 (9): 770-789.

Published
2010

100. Multicentre, randomized, double-blind, prospective study on the effects of ImmunoAdSorptiOn on cardiac function in patients with Dilated CardioMyopathy (IASO-DCM): Rationale and design.

Author

Dörr M, Böhm M, Erdmann E, Groß S, Mahabadi AA, Nauck M, Nickening G, Schultheiss HP, Staudt A, Werdan K, Waagstein F, Hjalmarson Å, and Felix SB

Abstract

Aims: Pilot studies indicate that immunoadsorption with subsequent IgG substitution (IA/IgG) induces beneficial effects in patients with dilated cardiomyopathy (DCM) and heart failure. This placebo-controlled study investigates whether IA/IgG treatment enhances left ventricular (LV) systolic function as compared to a control group receiving pseudo-treatment., Methods: This multicentre, randomized, double-blind, parallel-group trial aims to include 200 patients with heart failure due to DCM (LV ejection fraction [LVEF] <40%) on optimized guideline-directed heart failure medication. Participants are randomly assigned in a 1:1 ratio to IA/IgG using protein-A columns, or to pseudo-immunoadsorption followed by an intravenous infusion without IgG. Follow-up visits take place by telephone after 1 and 3 months and at the study centres after 6, 12 and 24 months. The primary efficacy endpoint is the change in LVEF from baseline to 6 months determined by contrast echocardiography, analysed at a core lab. In addition, LV end-diastolic and end-systolic volumes will be analysed as secondary endpoints over the entire study period to assess whether IA/IgG affects LV remodelling. As main secondary outcome, a composite of all-cause death, cardiac resuscitation, hospitalization for heart failure, and need for cardiac surgery to improve myocardial pump function will be evaluated after 24 months. In addition, exploratory outcomes as well as safety endpoints related to the treatment will be assessed throughout the whole study period., Conclusion: IASO-DCM is a randomized study which will provide comprehensive insights into the effects of immunoadsorption with subsequent IgG substitution in patients with DCM., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Published
2024
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