92 results on '"Sijbrands Ejg."'
Search Results
2. Poster session Thursday 12 December - PM: 12/12/2013, 14: 00–18: 00Location: Poster area
- Author
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Van Den Oord, SCH, Akkus, Z, Bosch, JG, Renaud, G, Sijbrands, EJG, Verhagen, HJM, Van Der Lugt, A, Van Der Steen, AFW, and Schinkel, AFL
- Published
- 2013
3. Poster Session: Right ventricular systolic function
- Author
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Van Den Oord, SCH, Akkus, Z, Bosch, JG, Ten Kate, GL, Renaud, G, Sijbrands, EJG, De Jong, N, Van Der Lugt, A, Van Der Steen, AFW, and Schinkel, AFL
- Published
- 2012
4. P339Incremental value of contrast enhanced ultrasound (CEUS) for detection of carotid atherosclerosis.
- Author
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Van Den Oord, SCH, Ten Kate, GL, Akkus, Z, Renaud, G, Sijbrands, EJG, Ten Cate, FJ, De Jong, N, Bosch, JG, Van Der Steen, AFW, and Schinkel, AFL
- Published
- 2011
5. Sex differences in cardiometabolic risk factors, pharmacological treatment and risk factor control in type 2 diabetes: findings from the Dutch Diabetes Pearl cohort
- Author
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Jong, M, Oskam, MJ, Sep, S J S, Ozcan, Behiye, Rutters, F, Sijbrands, EJG, Elders, PJM, Siegelaar, SE, deVries, JH, Tack, CJ, Schroijen, M, de Valk, HW, Abbink, EJW, Stehouwer, CD, Jazet, I, Wolffenbuttel, BH, Peters, SA, Schram, MT (Miranda), Jong, M, Oskam, MJ, Sep, S J S, Ozcan, Behiye, Rutters, F, Sijbrands, EJG, Elders, PJM, Siegelaar, SE, deVries, JH, Tack, CJ, Schroijen, M, de Valk, HW, Abbink, EJW, Stehouwer, CD, Jazet, I, Wolffenbuttel, BH, Peters, SA, and Schram, MT (Miranda)
- Published
- 2020
6. Effects of Alirocumab on Cardiovascular Events After Coronary Bypass Surgery
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Szarek, M, Bhatt, DL, Bittner, VA, Diaz, R, Edelberg, JM, Hanotin, C, Harrington, RA, Jukema, JW, Letierce, A, Moryusef, A, Pordy, R, Lopez, GAR, Roe, MT, White, HD, Zeiher, AM, Steg, PG, Schwartz, GG, Aylward, PE, Drexel, H, Sinnaeve, P, Dilic, M, Goodman, SG, Prieto, JC, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Ostadal, P, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Tse, HF, Xavier, D, Zahger, D, Valgimigli, M, Kimura, T, Kim, HS, Kim, SH, Erglis, A, Laucevicius, A, Kedev, S, Yusoff, K, Alings, M, Halvorsen, S, Flores, RMC, Sy, RG, Budaj, A, Morais, J, Dorobantu, M, Karpov, Y, Ristic, AD, Chua, T, Murin, J, Fras, Z, Tunon, J, de Silva, HA, Muller, C, Ray, KK, Vogel, R, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, JL, Simoons, ML, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, EJG, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, MC, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, Kong, DF, Leonardi, S, Lillis, L, Maron, DJ, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Trotter, C, van Diepen, SFP, Wilson, MD, Yan, ATK, Schiavi, LB, Garrido, M, Alvarisqueta, AF, Sassone, SA, Bordonava, AP, De Lima, AEA, Schmidberg, JM, Duronto, EA, Caruso, OC, Novaretto, LP, Hominal, MA, Montana, OR, Caccavo, A, Vilamajo, OAG, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, AD, Vallejos, JA, Rodolfo, AAG, Novoa, F, Patocchi, CA, Zaidman, CJ, Giuliano, ME, Dran, RD, Vico, ML, Carnero, GS, Guzman, PN, Allende, JCM, Brasca, DFG, Labarta, MHB, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, A, Luciardi, HL, Waisman, GD, Berli, MA, Duran, ROG, Cestari, HG, Luquez, HA, Giordano, JA, Saavedra, SS, Waites, JH, Collins, N, Soward, A, Hii, CLS, Shaw, J, Arstall, MA, Horowitz, J, Rogers, JF, Colquhoun, D, Flores, REO, Roberts-Thomson, P, Raffel, O, Lehman, SJ, Coverdale, SGM, Garrahy, PJ, Starmer, G, Sader, M, Carroll, PA, Zweiker, R, Hoppe, U, Huber, K, Berger, R, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Vrolix, MCM, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Durak-Nalbantic, A, Vulic, D, Muslibegovic, A, Reis, G, Sousa, L, Nicolau, JC, Giorgeto, FE, Silva, RP, Maia, LN, Rech, R, Rossi, PRF, Cerqueira, MJAG, Duda, N, Kalil, R, Kormann, A, Abrantes, JAM, Pimentel, P, Soggia, AP, de Santos, MON, Neuenschwander, F, Bodanese, LC, Michalaros, YL, Eliaschewitz, FG, Vidotti, MH, Leaes, PE, Botelho, RV, Kaiser, S, Manenti, ERFF, Precoma, DB, Jorge, JCM, Silva, PGMD, Silveira, JA, Saporito, W, Marin, JA, Feitosa, GS, Ritt, LEF, de Souza, JA, Costa, F, Souza, WKSB, Reis, HJL, Lopes, RD, Machado, L, Ayoub, JCA, Todorov, GV, Nikolov, FP, Velcheva, ES, Tzekova, ML, Benov, HO, Petranov, SL, Tumbev, HS, Shehova-Yankova, NS, Markov, DT, Raev, DH, Mollov, MN, Kichukov, KN, Ilieva-Pandeva, KA, Gotcheva, NN, Ivanova, R, Mincheva, VM, Lazov, PV, Dimov, BI, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, MacDonald, P, Diaz, A, Michaud, N, Fell, D, Leung, R, Vuurmans, T, Lai, C, Nigro, F, Davies, R, Nogareda, G, Vijayaraghavan, R, Ducas, J, Lepage, S, Mehta, S, Cha, J, Dupuis, R, Fong, P, Rodes-Cabau, J, Fadlallah, H, Cleveland, D, Huynh, T, Bata, I, Hameed, A, Pincetti, C, Potthoff, S, Acevedo, M, Aguirre, A, Vejar, M, Yanez, M, Araneda, G, Fernandez, M, Perez, L, Varleta, P, Florenzano, F, Huidobro, L, Raffo, CA, Olivares, C, Chen, JY, Dong, YG, Huang, WJ, Wang, JZ, Huang, SA, Yao, ZH, Cui, L, Lin, WH, Sun, YM, Wang, JF, Li, JP, Zhang, XL, Zhu, H, Chen, DD, Huang, L, Dong, SH, Su, GH, Xu, B, Su, X, Cheng, XS, Lin, JX, Zong, WX, Li, HM, Feng, Y, Xu, DL, Yang, XC, Ke, YN, Lin, XF, Zhang, Z, Zheng, ZQ, Luo, ZR, Chen, YD, Ding, CH, Zheng, Y, Li, XD, Peng, DQ, Li, Y, Wei, M, Liu, SW, Yu, YH, Qu, BM, Jiang, WH, Zhou, YJ, Zhao, XS, Yuan, ZY, Guo, Y, Xu, XP, Shi, XB, Ge, JB, Fu, GS, Bai, F, Fang, WY, Shou, XL, Yang, XJ, Wang, JA, Jaramillo, N, Vallejo, GS, Botia, DCL, Lopez, RB, De Salazar, DIM, Bonfanti, AJC, Higuera, JD, Silva, SIB, Lozada, HJG, Arroyo, JAC, Mendoza, JLA, Ruiz, RLF, Fernandez, AM, Jatin, FGM, Herazo, AS, Parada, JC, Triana, MAU, Spinar, J, Horak, D, Stasek, J, Alan, D, Machova, V, Linhart, A, Novotny, V, Kaucak, V, Rokyta, R, Naplava, R, Coufal, Z, Adamkova, V, Podpera, I, Zizka, J, Motovska, Z, Marusincova, I, Svab, P, Heinc, P, Kuchar, J, Povolny, P, Raungaard, B, Clemmensen, P, Bang, LE, May, O, Bottcher, M, Hove, JD, Frost, L, Gislason, G, Larsen, J, Johansen, PB, Hald, F, Jeppesen, J, Nielsen, T, Kristensen, KS, Walichiewicz, PM, Lomholdt, JD, Klausen, IC, Nielsen, PK, Davidsen, F, Videbaek, L, Soots, M, Vahula, V, Hedman, A, Soopold, U, Martsin, K, Taskinen, MR, Porthan, K, Airaksinen, JK, Juonala, M, Kiviniemi, T, Vikman, S, Posio, P, Taurio, J, Huikuri, H, Kaikkonen, K, Coste, P, Ferrari, E, Morel, O, Montalescot, G, Barone-Rochette, G, Mansourati, J, Cottin, Y, Leclercq, F, Belhassane, A, Delarche, N, Boccara, F, Paganelli, F, Clerc, J, Schiele, F, Aboyans, V, Probst, V, Berland, J, Lefevre, T, Khintibidze, I, Shaburishvili, T, Pagava, Z, Ghlonti, R, Lominadze, Z, Khabeishvili, G, Hemetsberger, R, Rauch-Krohnert, U, Stratmann, M, Appel, KF, Schmidt, E, Omran, H, Stellbrink, C, Dorsel, T, Lianopoulos, E, Marx, R, Zirlik, A, Schellenberg, D, Heitzer, T, Laufs, U, Marx, N, Gielen, S, Winkelmann, B, Behrens, S, Sydow, K, Simonis, G, Muenzel, T, Werner, N, Leggewie, S, Bocker, D, Braun-Dullaeus, R, Toursarkissian, N, Jeserich, M, Weissbrodt, M, Schaeufele, T, Weil, J, Voller, H, Waltenberger, J, Natour, M, Steiner, S, Heidenreich, L, Gremmler, U, Killat, H, Patsilinakos, S, Kartalis, A, Manolis, A, Sionis, D, Liberopoulos, E, Skoumas, I, Athyros, V, Parthenakis, PIF, Hahalis, PIG, Lekakis, J, Xatzitolios, A, Ovando, SRF, Valdovinos, PCM, Benecke, JLA, De Leon, ERR, Yan, BPY, Siu, DCW, Turi, T, Merkely, B, Kiss, RG, Ungi, I, Lupkovics, G, Nagy, L, Katona, A, Edes, I, Muller, G, Horvath, I, Kapin, T, Falukozy, J, Kumbla, M, Sandhu, M, Annam, S, Proddutur, NR, Premchand, RK, Mahajan, A, Abhyanakar, AD, Kerkar, P, Govinda, RA, Oomman, A, Sinha, D, Patil, SN, Kahali, D, Sawhney, J, Joshi, AB, Chaudhary, S, Harkut, P, Guha, S, Porwal, S, Jujjuru, S, Pothineni, RB, Monteiro, MR, Khan, A, Iyengar, SS, Grewal, JS, Chopda, M, Fulwani, MC, Patange, A, Chopra, VK, Goyal, NK, Shinde, R, Manakshe, GV, Patki, N, Sethi, S, Munusamy, V, Karna, S, Adhyapak, S, Pandurangi, U, Mathur, R, Kalashetti, S, Bhagwat, A, Raghuraman, B, Yerra, SK, Bhansali, P, Borse, R, Das, S, Abdullakutty, J, Saathe, S, Palimkar, P, Atar, S, Shechter, M, Mosseri, M, Arbel, Y, Lotan, C, Rosenschein, U, Katz, A, Henkin, Y, Francis, A, Klutstein, M, Nikolsky, E, Turgeman, Y, Halabi, M, Kornowski, R, Jonas, M, Amir, O, Rozenman, Y, Fuchs, S, Hussein, O, Gavish, D, Vered, Z, Caraco, Y, Elias, M, Tov, N, Piovaccari, G, De Pellegrin, A, Guardigli, G, Licciardello, G, Auguadro, C, Cuccia, C, Salvioni, A, Musumeci, G, Calabro, P, Novo, S, Faggiano, P, De Cesare, NB, Berti, S, Cavallini, C, Puccioni, E, Galvani, M, Tespili, M, Piatti, P, Palvarini, M, De Luca, G, Violini, R, De Leo, A, Filardi, PP, Ferratini, M, Dai, K, Kamiya, H, Ando, K, Takeda, Y, Morino, Y, Hata, Y, Kimura, K, Kishi, K, Michishita, I, Uehara, H, Higashikata, T, Hirayama, A, Hirooka, K, Sakagami, S, Taguchi, S, Koike, A, Fujinaga, H, Koba, S, Kozuma, K, Kawasaki, T, Ono, Y, Shimizu, M, Katsuda, Y, Wada, A, Shinke, T, Ako, J, Fujii, K, Takahashi, T, Sakamoto, T, Furukawa, Y, Sugino, H, Mano, T, Utsu, N, Ito, K, Haraguchi, T, Ueda, Y, Nishibe, A, Fujimoto, K, Yoon, JH, Park, HS, Chae, IH, Kim, MH, Jeong, MH, Rha, S, Kim, C, Hong, T, Busmane, A, Pontaga, N, Strelnieks, A, Mintale, I, Sime, I, Petrulioniene, Z, Kavaliauskiene, R, Jurgaitiene, R, Sakalyte, G, Slapikas, R, Norkiene, S, Misonis, N, Kibarskis, A, Kubilius, R, Bojovski, S, Lozance, N, Kjovkaroski, A, Doncovska, S, Ong, TK, Kasim, S, Maskon, O, Kandasamy, B, Liew, HB, Mohamed, WMIW, Castillo, AG, Calvillo, JC, Campos, PF, Fragoso, JCN, Llamas, EAB, Gamba, MAA, Madrigal, JC, Salas, LGG, Rosas, EL, Diaz, BG, Vazquez, ES, Ackar, AN, Esperon, GAL, Sanchez, CRM, De Leon, MG, Otero, RS, Salmon, GF, Rios, JAP, Ruiz, JAG, Breedveld, RW, Hoogslag, PAM, Suryapranata, H, Oomen, A, Wiersma, JJ, Van Der Wal, RMA, Van Huysduynen-Monraats, PSH, Karalis, I, Verdel, GJE, Brueren, BRG, Troquay, RPT, Viergever, EP, Al-Windy, NYY, Bartels, GL, Cornel, JH, Hermans, WRM, Herrman, JPR, Bos, RJ, Groutars, RGEJ, Van Der Zwaan, CC, Kaplan, R, Ronner, E, Groenemeijer, BE, Bronzwaer, PNA, Liem, AAH, Rensing, BJWM, Bokern, MJJA, Nijmeijer, R, Hersbach, FMRJ, Willems, FF, Gosselink, ATM, Elliott, J, Wilkins, G, Fisher, R, Scott, D, Hart, H, Stewart, R, Harding, S, Ternouth, I, Fisher, N, Aitken, D, Anscombe, R, Tomala, T, Nygard, O, Sparby, JA, Andersen, K, Gullestad, L, Jortveit, J, Munk, PS, Hurtig, U, Ticona, JRC, Velasquez, JRD, Miguel, SAN, Perez, ESS, Chambilla, JMC, Ayala, CAC, Leon, RPC, Gonzales, RJV, Zuniga, JDH, Cosavalente, LAC, Mannucci, JEB, Navarro, NCL, Concha, YMR, Chavez, VER, Hernandez, HAA, Nunez, CAZ, Ferrolino, A, Sy, RAG, Tirador, L, Matiga, G, Coching, RM, Bernan, A, Rogelio, G, Morales, DD, Tan, E, Wlodarczak, A, Jaworska, K, Skonieczny, G, Pawlowicz, L, Wojewoda, P, Busz-Papiez, B, Bednarski, J, Goch, A, Staneta, P, Dulak, E, Saminski, K, Krasowski, W, Sudnik, W, Zurakowski, A, Skorski, M, Lysek, R, Miklaszewicz, B, Kubica, J, Lipko, JA, Kostarska-Srokosz, E, Piepiorka, M, Drzewiecka, A, Sciborski, R, Stasiewski, A, Blicharski, T, Bystryk, L, Szpajer, M, Korol, M, Czerski, T, Mirek-Bryniarska, E, Gniot, J, Lubinski, A, Gorny, J, Franek, E, Monteiro, P, Bastos, JM, Pereira, HH, Martins, D, Seixo, F, Mendonca, C, Botelho, A, Minescu, B, Istratoaie, O, Tesloianu, DN, Cristian, G, Podoleanu, CGC, Constantinescu, MCA, Bengus, CM, Militaru, C, Rosu, D, Parepa, IR, Matei, AV, Alexandru, TM, Shvarts, Y, Orlikova, O, Kobalava, Z, Barbarash, OL, Markov, V, Lyamina, N, Gordienko, A, Zrazhevsky, K, Vishnevsky, AY, Gurevich, V, Stryuk, R, Lomakin, NV, Bokarev, I, Shalaev, S, Khaisheva, L, Chizhov, P, Viktorova, I, Osokina, N, Akatova, E, Chumakova, G, Libov, I, Voevoda, MI, Tretyakova, TV, Baranov, E, Shustov, S, Yakushin, S, Gordeev, I, Khasanov, N, Reshetko, O, Sotnikova, T, Molchanova, O, Nikolaev, K, Gapon, L, Baranova, E, Shogenov, Z, Kosmachova, E, Povzun, A, Egorova, L, Tyrenko, VV, Ivanov, IG, Simic, D, Ivanovic, N, Davidovic, G, Tasic, N, Asanin, MR, Stojic, S, Apostolovic, SR, Ilic, S, Putnikovic, B, Stankovic, A, Arandjelovic, A, Radovanovic, S, Balinovac, J, Dincic, DV, Seferovic, P, Dodic, S, Dimkovic, S, Poh, KK, Ong, HY, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Zuran, I, Oklukar, J, Suligoj, NC, Cevc, M, Lipar, L, Cyster, HP, Ranjith, N, Corbett, C, Bayat, J, Makotoko, EM, Kapp, IE, Basson, MMD, Lottering, H, Van Zyl, LJ, Sebastian, PJ, Pillay, T, Saaiman, JA, Commerford, PJ, Cassimjee, S, Ebrahim, IO, Sarvan, M, Mynhardt, JH, Dalby, AJ, Reuter, H, Moodley, R, Vida, M, Fillat, ARC, Peris, VB, Jimenez, FF, Marin, F, Fernandez, JMC, Gil-Extremera, B, Diz, FW, Garcia-Dorado, D, Iniguez, A, Fernandez, JT, Gonzalez-Juanatey, JR, Portales, JF, Murillo, FC, Pericas, LM, Zamorano, JL, Martin, MD, Cortada, JB, Martin, JJA, Fernandez, JRD, Fernandez, JFD, Lledo, JAG, Sales, JC, Rodriguez, JB, Tragant, GG, Benedicto, A, Gonzalez-Juanatey, C, Potau, MC, Perez, IP, De La Tassa, CM, Rincon, PLO, Recena, JB, Escudier, JM, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Fernando, N, Jayawardena, J, Santharaj, W, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, JI, Amarasena, N, Berglund, S, Rasmanis, G, Hagstrom, E, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Torstensson, I, Jensen, SA, Ahremark, U, Sundelin, T, Moccetti, T, Mach, F, Binder, R, Chiang, CE, Tsai, WC, Ueng, KC, Lai, WT, Liu, ME, Hwang, JJ, Yin, WH, Hsieh, IC, Kuo, JY, Huang, TY, Fang, CY, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Sritara, P, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Camsari, A, Kultursay, H, Guneri, S, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Parkhomenko, A, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, OM, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, RK, Clifford, P, Wong, YK, Iqbal, SMR, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Oliver, R, Mudawi, T, Reynolds, T, Sharman, D, Butler, R, Wilkinson, P, Lip, GYH, Halcox, J, Vardi, G, Baldari, D, Brabham, D, Treasure, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, AE, Ince, C, Flores, E, Wright, S, Cheng, SC, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Lieber, I, Kumar, P, East, C, Krichmar, P, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Suh, D, Arif, I, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Harris, B, Cohen, S, Carter, L, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, SK, Koren, M, Chandna, H, Dodds, G, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Singh, N, Shah, AV, Moriarty, PM, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Keating, F, Kondo, NI, Shetty, S, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Aggarwal, R, Izzo, M, Kumar, A, Hattler, B, Link, C, Bortnick, A, Kinzfogl, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, WW, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, H, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Schifferdecker, B, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, İÜC, and Ege Üniversitesi
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Male ,medicine.medical_specialty ,Acute coronary syndrome ,alirocumab ,030204 cardiovascular system & hematology ,Antibodies, Monoclonal, Humanized ,lipids ,PCSK9 ,03 medical and health sciences ,0302 clinical medicine ,Postoperative Complications ,Double-Blind Method ,coronary artery bypass graft ,Internal medicine ,medicine ,Humans ,Cardiac and Cardiovascular Systems ,030212 general & internal medicine ,Myocardial infarction ,cardiovascular diseases ,Acute Coronary Syndrome ,Coronary Artery Bypass ,Alirocumab ,Aged ,Kardiologi ,business.industry ,Unstable angina ,Hazard ratio ,cholesterol ,Middle Aged ,medicine.disease ,surgical procedures, operative ,Bypass surgery ,Cardiovascular Diseases ,Cardiology ,Drug Therapy, Combination ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,Mace - Abstract
Sherwood, Matthew/0000-0002-4305-5883; Taskinen, Marja-Riitta/0000-0002-6229-3588; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Muenzel, Thomas/0000-0001-5503-4150; Ersanli, Murat/0000-0003-1847-3087; Gislason, Gunnar H/0000-0002-0548-402X; bastos, jose/0000-0002-9526-3123; Abbate, Antonio/0000-0002-1930-785X; Chumakova, Galina A/0000-0002-2810-6531; Nikolaev, Konstantin/0000-0003-4601-6203; Tse, Hung Fat/0000-0002-9578-7808; Keskin, Kudret/0000-0002-9049-1530; Reshetko, Olga/0000-0003-3107-7636; Podoleanu, Cristian/0000-0001-9987-2519; Aylward, Philip/0000-0002-5358-8552; LETIERCE, Alexia/0000-0001-6679-5772, WOS: 000483334800002, PubMed: 31466614, BACKGROUND Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death. OBJECTIVES This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). METHODS Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. the primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003). RESULTS in each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [ 0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [ 0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [-2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [-0.1% to 1.0%], 0.5% [-1.9% to 2.9%], and 3.6% [0.0% to 7.2%]). CONCLUSIONS Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402) (C) 2019 by the American College of Cardiology Foundation., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, The authors thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the manuscript (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.
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- 2019
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7. Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial
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Gonzalez-Juanatey, JR, Fernandez Portales, J, Civeira Murillo, F, Matas Pericas, L, Luis Zamorano, J, De Mora Martin, M, Bruguera Cortada, J, Alonso Martin, JJ, De Berrazueta Fernandez, JR, Diaz Fernandez, JF, Garcia Lledo, JA, Cosin Sales, J, Botas Rodriguez, J, Gusi Tragant, G, Benedicto, A, Gonzalez-Juanatey, C, Camprubi Potau, M, Plaza Perez, I, Moris De La Tassa, C, Loma-Osorio Rincon, P, Balaguer Recena, J, Escudier, JM, Coca Payeras, A, Alonso Orcajo, N, Valdivielso, P, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Fernando, N, Jayawardena, J, Santharaj, W, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, JI, Amarasena, N, Berglund, S, Rasmanis, G, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Jensen, SA, Torstensson, I, Ahremark, U, Sundelin, T, Moccetti, T, Mach, F, Binder, R, Tsai, W-C, Ueng, K-C, Lai, W-T, Liu, M-E, Hwang, J-J, Yin, W-H, Hsieh, I-C, Lin, WH, Kuo, J-Y, Huang, T-Y, Fang, C-Y, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Chotnoparatpat, P, Camsari, A, Kultursay, H, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, OM, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Zheleznyy, V, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, RK, Clifford, P, Wong, Y-K, Iqbal, SMR, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Oliver, R, Mudawi, T, Reynolds, T, Sharman, D, Butler, R, Wilkinson, P, Lip, GYH, Halcox, J, Vardi, G, Baldari, D, Brabham, D, Treasure, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, AE, Ince, C, Flores, E, Wright, S, Cheng, S-C, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Lieber, I, Kumar, P, East, C, Krichmar, P, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Suh, D, Arif, I, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Harris, B, Cohen, S, Carter, L, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, SK, Koren, M, Chandna, H, Dodds, G, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Singh, N, Shah, AV, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Keating, F, Kondo, NI, Shetty, S, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Aggarwal, R, Izzo, M, Kumar, A, Hattler, B, Link, C, Bortnick, A, Kinzfogl, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, W, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, HT, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Schifferdecker, B, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Camp, A, Lopes, R, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Aylward, P, Butters, J, Griffith, L, Shaw, M, Grunberg, L, Islam, S, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Loizeau, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Zhu, C, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, ODYSSEY OUTCOMES Comm, İÜC, Ege Üniversitesi, Rushton-Smith, Sophie, and ODYSSEY OUTCOMES Committees and Investigators
- Subjects
Male ,Cardiac & Cardiovascular Systems ,MONOCLONAL-ANTIBODY ,alirocumab ,Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ,law.invention ,PCSK9 ,chemistry.chemical_compound ,Randomized controlled trial ,law ,Cardiac and Cardiovascular Systems ,1102 Cardiorespiratory Medicine and Haematology ,Hypercholesterolemia/blood ,Kardiologi ,Hazard ratio ,Middle Aged ,Treatment Outcome ,SAFETY ,Cardiology ,Female ,Drug Therapy, Combination ,Cholesterol, LDL/antagonists & inhibitors ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine ,REDUCING LIPIDS ,Akutes Koronarsyndrom ,acute coronary syndrome ,cholesterol ,mortality ,PCSK9 protein ,Antibodies, Monoclonal, Humanized/administration & dosage ,medicine.medical_specialty ,Acute coronary syndrome ,Injections, Subcutaneous ,Hypercholesterolemia ,Placebo ,Antibodies, Monoclonal, Humanized ,1117 Public Health and Health Services ,Sterblichkeit ,Double-Blind Method ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,ddc:610 ,Alirocumab ,Aged ,Science & Technology ,Cholesterol ,business.industry ,EVOLOCUMAB ,1103 Clinical Sciences ,Cholesterol, LDL ,medicine.disease ,EFFICACY ,Increased risk ,chemistry ,Peripheral Vascular Disease ,Cardiovascular System & Hematology ,Cardiovascular System & Cardiology ,Acute Coronary Syndrome/blood ,Cholesterin ,Human medicine ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Follow-Up Studies - Abstract
bastos, jose/0000-0002-9526-3123; Manakshe, Gajendra/0000-0002-4983-4271; Tse, Hung Fat/0000-0002-9578-7808; Gislason, Gunnar H/0000-0002-0548-402X; Taskinen, Marja-Riitta/0000-0002-6229-3588; Racca, Vittorio/0000-0002-4465-3789; Keskin, Kudret/0000-0002-9049-1530; Sherwood, Matthew/0000-0002-4305-5883; Sandhu, Manjinder/0000-0003-2538-2079; Nikolaev, Konstantin/0000-0003-4601-6203; Ersanli, Murat/0000-0003-1847-3087; Raffel, Owen C/0000-0001-5470-7050; Abbate, Antonio/0000-0002-1930-785X; Muenzel, Thomas/0000-0001-5503-4150; Leonardi, Sergio/0000-0002-4800-6132; Chumakova, Galina A/0000-0002-2810-6531; Podoleanu, Cristian/0000-0001-9987-2519; Pereira, Helder/0000-0001-8656-4883; Reshetko, Olga/0000-0003-3107-7636, WOS: 000476768100007, PubMed: 31117810, Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. in a prespecified analysis of 8242 patients eligible for >= 3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P= 100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; P-interaction=0.007). in the alirocumab group, all-cause death declined with achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for >= 3 years, if baseline LDL-C is >= 100 mg/dL, or if achieved LDL-C is low., Sanofi; Regeneron Pharmaceuticals, Inc., The trial was funded by Sanofi and Regeneron Pharmaceuticals, Inc.
- Published
- 2019
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8. Alirocumab Reduces Total Hospitalizations and Increases Days Alive and Out of Hospital in the ODYSSEY OUTCOMES Trial
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MH, Leaes, PE, Botelho, RV, Kaiser, S, Manenti, ERFF, Precoma, DB, Jorge, JCM, Silva, PGMD, Silveira, JA, Saporito, W, Marin, JA, Feitosa, GS, Ritt, LEF, de Souza, JA, Costa, F, Souza, WKSB, Reis, HJL, Machado, L, Ayoub, JCA, Todorov, GV, Nikolov, FP, Velcheva, ES, Tzekova, ML, Benov, HO, Petranov, SL, Tumbev, HS, Shehova-Yankova, NS, Markov, DT, Raev, DH, Mollov, MN, Kichukov, KN, Ilieva-Pandeva, KA, Ivanova, R, Mincheva, VM, Lazov, PV, Dimov, BI, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, MacDonald, P, Diaz, A, Michaud, N, Fell, D, Leung, R, Vuurmans, T, Lai, C, Nigro, F, Davies, R, Nogareda, G, Vijayaraghavan, R, Ducas, J, Lepage, S, Mehta, S, Cha, J, Dupuis, R, Fong, P, Rodes-Cabau, J, Fadlallah, H, Cleveland, D, Huynh, T, Bata, I, Hameed, A, Pincetti, C, Potthoff, S, Acevedo, M, Aguirre, A, Vejar, M, Yanez, M, Araneda, G, Fernandez, 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Dimkovic, S, Poh, KK, Ong, HY, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Olexa, P, Zuran, I, Poklukar, J, Suligoj, NC, Cevc, M, Cyster, HP, Ranjith, N, Corbett, C, Bayat, J, Makotoko, EM, Kapp, IE, Basson, MMD, Lottering, H, Van Zyl, LJ, Sebastian, PJ, Pillay, T, Saaiman, JA, Commerford, PJ, Cassimjee, S, Ebrahim, IO, Sarvan, M, Mynhardt, JH, Reuter, H, Moodley, R, Vida, M, Fillat, ARC, Peris, VB, Jimenez, FF, Marin, F, Fernandez, JMC, Gil-Extremera, B, Diz, FW, Garcia-Dorado, D, Iniguez, A, Fernandez, JT, Gonzalez-Juanatey, JR, Portales, JF, Murillo, FC, Pericas, LM, Zamorano, JL, Martin, MD, Cortada, JB, Martin, JJA, Fernandez, JRD, Fernandez, JFD, Lledo, JAG, Sales, JC, Rodriguez, JB, Tragant, GG, Benedicto, A, Gonzalez-Juanatey, C, Potau, MC, Perez, IP, De La Tassa, CM, Rincon, PLO, Recena, JB, Escudier, JM, Payeras, AC, Orcajo, NA, Valdivielso, P, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Fernando, N, Jayawardena, J, Santharaj, W, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, JI, Amarasena, N, Berglund, S, Rasmanis, G, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Jensen, SA, Torstensson, I, Ahremark, U, Sundelin, T, Moccetti, T, Muller, C, Mach, F, Binder, R, Tsai, WC, Ueng, KC, Lai, WT, Liu, ME, Hwang, JJ, Yin, WH, Hsieh, IC, Kuo, JY, Huang, TY, Fang, CY, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Chotnoparatpat, P, Camsari, A, Kultursay, H, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, OM, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Zheleznyy, V, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, RK, Clifford, P, Wong, YK, Iqbal, SM, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Oliver, R, Mudawi, T, Reynolds, T, Sharman, D, Butler, R, Wilkinson, P, Lip, GYH, Halcox, J, Vardi, G, Baldari, D, Brabham, D, Treasure, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, AE, Ince, C, Flores, E, Wright, S, Cheng, SC, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Lieber, I, Kumar, P, East, C, Krichmar, P, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Suh, D, Arif, I, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Harris, B, Cohen, S, Carter, L, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, SK, Koren, M, Chandna, H, Dodds, G, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Singh, N, Shah, AV, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Keating, F, Kondo, NI, Shetty, S, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Aggarwal, R, Izzo, M, Kumar, A, Hattler, B, Link, C, Bortnick, A, Kinzfogl, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, WW, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, H, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Schifferdecker, B, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Camp, A, Lopes, R, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Aylward, P, Butters, J, Griffith, L, Shaw, M, Hagstrom, E, Grunberg, L, Islam, S, Bregeault, MF, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Tamby, JF, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Loizeau, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Zhu, CY, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, ODYSSEY OUTCOMES Comm Inve, Ege Üniversitesi, Cardiology, and Internal Medicine
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medicine.medical_specialty ,Acute coronary syndrome ,Time Factors ,acute coronary syndrome ,alirocumab ,global burden of disease ,hospitalization ,myocardial infarction ,PCSK9 ,030204 cardiovascular system & hematology ,Antibodies, Monoclonal, Humanized ,Placebo ,Patient Readmission ,Risk Assessment ,03 medical and health sciences ,Patient Admission ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Angina, Unstable ,Hospital Mortality ,030212 general & internal medicine ,Myocardial infarction ,03.02. Klinikai orvostan ,Dyslipidemias ,Alirocumab ,Out of hospital ,business.industry ,Anticholesteremic Agents ,Cholesterol, HDL ,Cholesterol hdl ,Cholesterol, LDL ,medicine.disease ,Treatment Outcome ,Drug Therapy, Combination ,Human medicine ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,Cardiovascular outcomes ,Biomarkers - Abstract
Sherwood, Matthew/0000-0002-4305-5883; Abbate, Antonio/0000-0002-1930-785X; Moris, Cesar/0000-0002-2871-190X; Ersanli, Murat/0000-0003-1847-3087; Taskinen, Marja-Riitta/0000-0002-6229-3588; bastos, jose/0000-0002-9526-3123; Reshetko, Olga/0000-0003-3107-7636; Nikolaev, Konstantin/0000-0003-4601-6203; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Racca, Vittorio/0000-0002-4465-3789; Podoleanu, Cristian/0000-0001-9987-2519; Gislason, Gunnar H/0000-0002-0548-402X; Muenzel, Thomas/0000-0001-5503-4150; Tse, Hung Fat/0000-0002-9578-7808; Chumakova, Galina A/0000-0002-2810-6531, WOS: 000502609000004, PubMed: 31707826, Background: in ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab was compared with placebo, added to high-intensity or maximum tolerated statin treatment after acute coronary syndrome in 18924 patients. Alirocumab reduced first occurrence of the primary composite end point-coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or hospitalization for unstable angina-as well as total nonfatal cardiovascular events and all-cause deaths. the present analysis determined whether alirocumab reduced total (first and subsequent) hospitalizations and death and increased days alive and out of hospital (DAOH) and percent DAOH in ODYSSEY OUTCOMES. Methods and Results: in prespecified analyses, hazard functions for total hospitalizations and death were jointly estimated by a semiparametric model, while in post hoc analyses, DAOH and percent DAOH were compared between treatment groups with Poisson regression and one-inflated beta regression, respectively. With 16629 total hospitalizations and 726 deaths, 331 fewer hospitalizations, and 58 fewer deaths were observed with alirocumab compared with placebo, translating to 15.6 total hospitalizations or deaths avoided with alirocumab per 1000 patient-years of assigned treatment. Alirocumab reduced total hospitalizations (hazard ratio, 0.96 [95% CI, 0.92-1.00]; P=0.04) and increased DAOH relative to placebo (rate ratio, 1.003 [95% CI, 1.000-1.007]; P=0.05), primarily through a reduction in days dead (rate ratio, 0.847 [95% CI, 0.728-0.986]; P=0.03). Patients randomized to alirocumab were also more likely to survive to the end of the study without hospitalization (odds ratio, 1.06 [95% CI, 1.00-1.13]; P=0.03). Conclusions: Alirocumab reduced total hospitalizations with corresponding small increases in DAOH and percent DAOH. These outcomes provide alternative patient-centered metrics to capture the totality of alirocumab clinical efficacy after acute coronary syndrome. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01663402., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, We thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the article (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.
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- 2019
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9. Interactions of Dietary Whole-Grain Intake With Fasting Glucose– and Insulin-Related Genetic Loci in Individuals of European Descent
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Göran Hallmans, Josée Dupuis, Amanda J. Bennett, Ruth J. F. Loos, George Dedoussis, Emily Sonestedt, Rozenn N. Lemaitre, Toshiko Tanaka, Christopher J. Groves, André G. Uitterlinden, Stavroula Kanoni, Nita G. Forouhi, Zheng Ye, Jerome I. Rotter, Jose C. Florez, Ingegerd Johansson, Jose M. Ordovas, Julius S. Ngwa, David S. Siscovick, A. Smith, Luigi Ferrucci, Claudia Langenberg, Ingrid B. Borecki, Jennifer A. Nettleton, Stefania Bandinelli, James S. Pankow, Per Sjögren, M. C. Zillikens, Ulf Risérus, Kenneth J. Mukamal, Stephen B. Kritchevsky, Marju Orho-Melander, Georgia Saylor, van Rooij Fja., Nicholas J. Wareham, C M van Duijn, James B. Meigs, Jack L. Follis, Sijbrands Ejg., Witteman Jcm., Frida Renström, Luc Djoussé, Inga Prokopenko, Laufey Steingrimsdottir, Tamara B. Harris, Olov Rolandsson, L. J. Launer, Mike A. Nalls, Erik Ingelsson, Denise K. Houston, Dariush Mozaffarian, Mary K. Wojczynski, Kenneth Rice, Jennifer S. Anderson, Yongmei Liu, Nicola M. McKeown, Mary F. Feitosa, Melissa E. Garcia, Paul W. Franks, Albert Hofman, Frank B. Hu, Hivert M-F., Constantina Papoutsakis, and L A Cupples
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Single-nucleotide polymorphism ,Type 2 diabetes ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Pancreatic hormone ,030304 developmental biology ,2. Zero hunger ,Advanced and Specialized Nursing ,0303 health sciences ,business.industry ,Insulin ,medicine.disease ,Endocrinology ,L-Glucose ,chemistry ,business ,TCF7L2 ,Body mass index - Abstract
OBJECTIVE Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. RESEARCH DESIGN AND METHODS Via meta-analysis of data from 14 cohorts comprising ∼48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value RESULTS Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: −0.009 mmol/l glucose [−0.013 to −0.005], P < 0.0001 and −0.011 pmol/l [ln] insulin [−0.015 to −0.007], P = 0.0003). No interactions met our multiple testing–adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. CONCLUSIONS Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.
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- 2010
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10. Cardiac computed tomography imaging in familial hypercholesterolaemia: implications for therapy and clinical trials
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Sijbrands, EJG, Nieman, K, Budoff, MJ, and Consortium, FHCTA
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familial hypercholesterolemia ,surrogate endpoint ,coronary atherosclerosis ,cholesterol-lowering ,computed tomographic angiography - Published
- 2015
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11. Pleiotropy among common genetic loci identified for cardiometabolic disorders and C-reactive protein
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Ligthart, S, De Vries, PS, Uitterlinden, AG, Hofman, A, Franco, OH, Chasman, DI, Dehghan, A, Dupuis, J, Barbalic, M, Bis, JC, Eiriksdottir, G, Lu, C, Pellikka, N, Wallaschofski, H, Kettunen, J, Henneman, P, Baumert, J, Strachan, DP, Fuchsberger, C, Vitart, V, Wilson, JF, Paré, G, Naitza, S, Rudock, ME, Surakka, I, De Geus, EJC, Alizadeh, BZ, Guralnik, JMD, Shuldiner, A, Tanaka, T, Zee, RYL, Schnabel, RB, Nambi, V, Kavousi, M, Ripatti, S, Nauck, M, Smith, NL, Smith, AV, Sundvall, J, Scheet, P, Liu, Y, Ruokonen, A, Rose, LM, Larson, MG, Hoogeveen, RC, Freimer, NB, Teumer, A, Tracy, RP, Launer, LJ, Buring, JE, Yamamoto, JF, Folsom, AR, Sijbrands, EJG, Pankow, J, Elliott, P, Keaney, JF, Sun, W, Sarin, AP, Fontes, JD, Badola, S, Astor, BC, Pouta, A, Werda, K, Greiser, KH, Kuss, O, Schwabedissen, HEMZ, Thiery, J, Jamshidi, Y, Nolte, IM, Soranzo, N, Spector, TD, Völzke, H, Parker, AN, Aspelund, T, Bates, D, Young, L, Tsui, K, Siscovick, DS, Guo, X, Rotter, JI, Uda, M, Schlessinger, D, Rudan, I, Hicks, AA, Penninx, BW, Thorand, B, Gieger, C, Coresh, J, Willemsen, G, Harris, TB, Järvelin, MR, Rice, K, Radke, D, Salomaa, V, Van Dijk, KW, Boerwinkle, E, Vasan, RS, Ferrucci, L, and Gibson, QD
- Abstract
© 2015 Ligthart et al. Pleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared genetic background of inflammation and cardiometabolic phenotypes using published genome-wide association studies (GWAS). We also evaluated whether the pleiotropic effects of such loci were biological or mediated in nature. First, we examined whether 283 common variants identified for 10 cardiometabolic phenotypes in GWAS are associated with CRP level. Second, we tested whether 18 variants identified for serum CRP are associated with 10 cardiometabolic phenotypes. We used a Bonferroni corrected p-value of 1.1×10-04 (0.05/463) as a threshold of significance. We evaluated the independent pleiotropic effect on both phenotypes using individual level data from the Women Genome Health Study. Evaluating the genetic overlap between inflammation and cardiometabolic phenotypes, we found 13 pleiotropic regions. Additional analyses showed that 6 regions (APOC1, HNF1A, IL6R, PPP1R3B, HNF4A and IL1F10) appeared to have a pleiotropic effect on CRP independent of the effects on the cardiometabolic phenotypes. These included loci where individuals carrying the risk allele for CRP encounter higher lipid levels and risk of type 2 diabetes. In addition, 5 regions (GCKR, PABPC4, BCL7B, FTO and TMEM18) had an effect on CRP largely mediated through the cardiometabolic phenotypes. In conclusion, our results show genetic pleiotropy among inflammation and cardiometabolic phenotypes. In addition to reverse causation, our data suggests that pleiotropic genetic variants partially underlie the association between CRP and cardiometabolic phenotypes.
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- 2015
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12. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure
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Wain, LV, Verwoert, GC, O'Reilly, PF, Shi, G, Johnson, T, Johnson, AD, Bochud, M, Rice, KM, Henneman, P, Smith, AV, Ehret, GB, Amin, N, Larson, MG, Mooser, V, Hadley, D, Dörr, M, Bis, JC, Aspelund, T, Esko, T, Janssens, ACJW, Zhao, JH, Heath, S, Laan, M, Fu, J, Pistis, G, Luan, J, Arora, P, Lucas, G, Pirastu, N, Pichler, I, Jackson, AU, Webster, RJ, Zhang, F, Peden, JF, Schmidt, H, Tanaka, T, Campbell, H, Igl, W, Milaneschi, Y, Hottenga, J-J, Vitart, V, Chasman, DI, Trompet, S, Bragg-Gresham, JL, Alizadeh, BZ, Chambers, JC, Guo, X, Lehtimäki, T, Kühnel, B, Lopez, LM, Polašek, O, Boban, M, Nelson, CP, Morrison, AC, Pihur, V, Ganesh, SK, Hofman, A, Kundu, S, Mattace-Raso, FUS, Rivadeneira, F, Sijbrands, EJG, Uitterlinden, AG, Hwang, S-J, Vasan, RS, Wang, TJ, Bergmann, S, Vollenweider, P, Waeber, G, Laitinen, J, Pouta, A, Zitting, P, McArdle, WL, Kroemer, HK, Völker, U, Völzke, H, Glazer, NL, Taylor, KD, Harris, TB, Alavere, H, Haller, T, Keis, A, Tammesoo, M-L, Aulchenko, Y, Barroso, I, Khaw, K-T, Galan, P, Hercberg, S, Lathrop, M, Eyheramendy, S, Org, E, Sõber, S, Lu, X, Nolte, IM, Penninx, BW, Corre, T, Masciullo, C, Sala, C, Groop, L, Voight, BF, Melander, O, O'Donnell, CJ, Salomaa, V, d'Adamo, AP, Fabretto, A, Faletra, F, Ulivi, S, Del Greco M, F, Facheris, M, Collins, FS, Bergman, RN, Beilby, JP, Hung, J, Musk, AW, Mangino, M, Shin, S-Y, Soranzo, N, Watkins, H, Goel, A, Hamsten, A, Gider, P, Loitfelder, M, Zeginigg, M, Hernandez, D, Najjar, SS, Navarro, P, Wild, SH, Corsi, AM, Singleton, A, de Geus, EJC, Willemsen, G, Parker, AN, Rose, LM, Buckley, B, Stott, D, Orru, M, Uda, M, van der Klauw, MM, Zhang, W, Li, X, Scott, J, Chen, Y-DI, Burke, GL, Kähönen, M, Viikari, J, Döring, A, Meitinger, T, Davies, G, Starr, JM, Emilsson, V, Plump, A, Lindeman, JH, Hoen, PAC', König, IR, Felix, JF, Clarke, R, Hopewell, JC, Ongen, H, Breteler, M, Debette, S, DeStefano, AL, Fornage, M, Mitchell, GF, Smith, NL, Holm, H, Stefansson, K, Thorleifsson, G, Thorsteinsdottir, U, Samani, NJ, Preuss, M, Rudan, I, Hayward, C, Deary, IJ, Wichmann, H-E, Raitakari, OT, Palmas, W, Kooner, JS, Stolk, RP, Jukema, JW, Wright, AF, Boomsma, DI, Bandinelli, S, Gyllensten, UB, Wilson, JF, Ferrucci, L, Schmidt, R, Farrall, M, Spector, TD, Palmer, LJ, Tuomilehto, J, Pfeufer, A, Gasparini, P, Siscovick, D, Altshuler, D, Loos, RJF, Toniolo, D, Snieder, H, Gieger, C, Meneton, P, Wareham, NJ, Oostra, BA, Metspalu, A, Launer, L, Rettig, R, Strachan, DP, Beckmann, JS, Witteman, JCM, Erdmann, J, van Dijk, KW, Boerwinkle, E, Boehnke, M, Ridker, PM, Jarvelin, M-R, Chakravarti, A, Abecasis, GR, Gudnason, V, Newton-Cheh, C, Levy, D, Munroe, PB, Psaty, BM, Caulfield, MJ, Rao, DC, Tobin, MD, Elliott, P, and van Duijn, CM
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- 2011
13. Erratum: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk (Nature Genetics (2010) 42 (105-116))
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Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, AU, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Gloyn, AL, Lindgren, CM, Mägi, R, Morris, AP, Randall, J, Johnson, T, Elliott, P, Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P, Grallert, H, Dehghan, A, Hottenga, JJ, Franklin, CS, Navarro, P, Song, K, Goel, A, Perry, JRB, Egan, JM, Lajunen, T, Grarup, N, Sparsø, T, Doney, A, Voight, BF, Stringham, HM, Li, M, Kanoni, S, Shrader, P, Cavalcanti-Proença, C, Kumari, M, Qi, L, Timpson, NJ, Gieger, C, Zabena, C, Rocheleau, G, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, McCarroll, SA, Payne, F, Roccasecca, RM, Pattou, F, Sethupathy, P, Ardlie, K, Ariyurek, Y, Balkau, B, Barter, P, Beilby, JP, Ben-Shlomo, Y, Benediktsson, R, Bennett, AJ, Bergmann, S, Bochud, M, Boerwinkle, E, Bonnefond, A, Bonnycastle, LL, Borch-Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, SJ, Charpentier, G, Chen, Y-DI, Chines, P, Clarke, R, Coin, LJM, Cooper, MN, Cornelis, M, Crawford, G, Crisponi, L, Day, INM, De Geus, EJC, Delplanque, J, Dina, C, Erdos, MR, Fedson, AC, Fischer-Rosinsky, A, Forouhi, NG, Fox, CS, Frants, R, Franzosi, MG, Galan, P, Goodarzi, MO, Graessler, J, Groves, CJ, Grundy, S, Gwilliam, R, Gyllensten, U, Hadjadj, S, Hallmans, G, Hammond, N, Han, X, Hartikainen, A-L, Hassanali, N, Hayward, C, Heath, SC, Hercberg, S, Herder, C, Hicks, AA, Hillman, DR, Hingorani, AD, Hofman, A, Hui, J, Hung, J, Isomaa, B, Johnson, PRV, Jørgensen, T, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, YA, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, KO, Lathrop, GM, Lawlor, DA, Le Bacquer, O, Lecoeur, C, Li, Y, Lyssenko, V, Mahley, R, Mangino, M, Manning, AK, Martínez-Larrad, MT, McAteer, JB, McCulloch, LJ, McPherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, BD, Morken, MA, Mukherjee, S, Naitza, S, Narisu, N, Neville, MJ, Oostra, BA, Orr, M, Pakyz, R, Palmer, CNA, Paolisso, G, Pattaro, C, Pearson, D, Peden, JF, Pedersen, NL, Perola, M, Pfeiffer, AFH, Pichler, I, Polasek, O, Posthuma, D, Potter, SC, Pouta, A, Province, MA, Psaty, BM, Rathmann, W, Rayner, NW, Rice, K, Ripatti, S, Rivadeneira, F, Roden, M, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, AA, Scheet, P, Scott, LJ, Seedorf, U, Sharp, SJ, Shields, B, Sigursson, G, Sijbrands, EJG, Silveira, A, Simpson, L, Singleton, A, Smith, NL, Sovio, U, Swift, A, Syddall, H, Syvänen, A-C, Tanaka, T, Thorand, B, Tichet, J, Tönjes, A, Tuomi, T, Uitterlinden, AG, Van Dijk, KW, Van Hoek, M, Varma, D, Visvikis-Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, PJ, Walley, A, Walters, GB, Ward, KL, Watkins, H, Weedon, MN, Wild, SH, Willemsen, G, Witteman, JCM, Yarnell, JWG, Zeggini, E, Zelenika, D, Zethelius, B, Zhai, G, Zhao, JH, Zillikens, MC, Consortium, D, Consortium, G, Consortium, GB, Borecki, IB, Loos, RJF, Meneton, P, Magnusson, PKE, Nathan, DM, Williams, GH, Hattersley, AT, Silander, K, Salomaa, V, Smith, GD, Bornstein, SR, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, AR, Cooper, C, Dedoussis, GV, Serrano-Ríos, M, Morris, AD, Lind, L, Palmer, LJ, Hu, FB, Franks, PW, Ebrahim, S, Marmot, M, Kao, WHL, Pankow, JS, Sampson, MJ, Kuusisto, J, Laakso, M, Hansen, T, Pedersen, O, Pramstaller, PP, Wichmann, HE, Illig, T, Rudan, I, Wright, AF, Stumvoll, M, Campbell, H, Wilson, JF, Hamsten, A, Bergman, RN, Buchanan, TA, Collins, FS, Mohlke, KL, Tuomilehto, J, Valle, TT, Altshuler, D, Rotter, JI, Siscovick, DS, Penninx, BWJH, Boomsma, DI, Deloukas, P, Spector, TD, Frayling, TM, Ferrucci, L, Kong, A, Thorsteinsdottir, U, Stefansson, K, Van Duijn, CM, Aulchenko, YS, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, M-R, Waterworth, DM, Vollenweider, P, Peltonen, L, Mooser, V, Abecasis, GR, Wareham, NJ, Sladek, R, Froguel, P, Watanabe, RM, Meigs, JB, Groop, L, Boehnke, M, McCarthy, MI, Florez, JC, and Barroso, I
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- 2010
14. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk (vol 42, pg 105, 2010)
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Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, AU, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Gloyn, AL, Lindgren, CM, Maegi, R, Morris, AP, Randall, J, Johnson, T, Elliott, P, Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P, Grallert, H, Dehghan, A, Hottenga, JJ, Franklin, CS, Navarro, P, Song, K, Goel, A, Perry, JRB, Egan, JM, Lajunen, T, Grarup, N, Sparso, T, Doney, A, Voight, BF, Stringham, HM, Li, M, Kanoni, S, Shrader, P, Cavalcanti-Proenca, C, Kumari, M, Qi, L, Timpson, NJ, Gieger, C, Zabena, C, Rocheleau, G, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, McCarroll, SA, Payne, F, Roccasecca, RM, Pattou, F, Sethupathy, P, Ardlie, K, Ariyurek, Y, Balkau, B, Barter, P, Beilby, JP, Ben-Shlomo, Y, Benediktsson, R, Bennett, AJ, Bergmann, S, Bochud, M, Boerwinkle, E, Bonnefond, A, Bonnycastle, LL, Borch-Johnsen, K, Boettcher, Y, Brunner, E, Bumpstead, SJ, Charpentier, G, Chen, Y-DI, Chines, P, Clarke, R, Coin, LJM, Cooper, MN, Cornelis, M, Crawford, G, Crisponi, L, Day, INM, de Geus, EJC, Delplanque, J, Dina, C, Erdos, MR, Fedson, AC, Fischer-Rosinsky, A, Forouhi, NG, Fox, CS, Frants, R, Franzosi, MG, Galan, P, Goodarzi, MO, Graessler, J, Groves, CJ, Grundy, S, Gwilliam, R, Gyllensten, U, Hadjadj, S, Hallmans, G, Hammond, N, Han, X, Hartikainen, A-L, Hassanali, N, Hayward, C, Heath, SC, Hercberg, S, Herder, C, Hicks, AA, Hillman, DR, Hingorani, AD, Hofman, A, Hui, J, Hung, J, Isomaa, B, Johnson, PRV, Jorgensen, T, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, YA, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, KO, Lathrop, GM, Lawlor, DA, Le Bacquer, O, Lecoeur, C, Li, Y, Lyssenko, V, Mahley, R, Mangino, M, Manning, AK, Martinez-Larrad, MT, McAteer, JB, McCulloch, LJ, McPherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, BD, Morken, MA, Mukherjee, S, Naitza, S, Narisu, N, Neville, MJ, Oostra, BA, Orru, M, Pakyz, R, Palmer, CNA, Paolisso, G, Pattaro, C, Pearson, D, Peden, JF, Pedersen, NL, Perola, M, Pfeiffer, AFH, Pichler, I, Polasek, O, Posthuma, D, Potter, SC, Pouta, A, Province, MA, Psaty, BM, Rathmann, W, Rayner, NW, Rice, K, Ripatti, S, Rivadeneira, F, Roden, M, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, AA, Scheet, P, Scott, LJ, Seedorf, U, Sharp, SJ, Shields, B, Sigurosson, G, Sijbrands, EJG, Silveira, A, Simpson, L, Singleton, A, Smith, NL, Sovio, U, Swift, A, Syddall, H, Syvaenen, A-C, Tanaka, T, Thorand, B, Tichet, J, Toenjes, A, Tuomi, T, Uitterlinden, AG, van Dijk, KW, van Hoek, M, Varma, D, Visvikis-Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, PJ, Walley, A, Walters, GB, Ward, KL, Watkins, H, Weedon, MN, Wild, SH, Willemsen, G, Witteman, JCM, Yarnell, JWG, Zeggini, E, Zelenika, D, Zethelius, B, Zhai, G, Zhao, JH, Zillikens, MC, Borecki, IB, Loos, RJF, Meneton, P, Magnusson, PKE, Nathan, DM, Williams, GH, Hattersley, AT, Silander, K, Salomaa, V, Smith, GD, Bornstein, SR, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, AR, Cooper, C, Dedoussis, GV, Serrano-Rios, M, Morris, AD, Lind, L, Palmer, LJ, Hu, FB, Franks, PW, Ebrahim, S, Marmot, M, Kao, WHL, Pankow, JS, Sampson, MJ, Kuusisto, J, Laakso, M, Hansen, T, Pedersen, O, Pramstaller, PP, Wichmann, HE, Illig, T, Rudan, I, Wright, AF, Stumvoll, M, Campbell, H, Wilson, JF, Hamsten, A, Bergman, RN, Buchanan, TA, Collins, FS, Mohlke, KL, Tuomilehto, J, Valle, TT, Altshuler, D, Rotter, JI, Siscovick, DS, Penninx, BWJH, Boomsma, DI, Deloukas, P, Spector, TD, Frayling, TM, Ferrucci, L, Kong, A, Thorsteinsdottir, U, Stefansson, K, van Duijn, CM, Aulchenko, YS, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, M-R, Waterworth, DM, Vollenweider, P, Peltonen, L, Mooser, V, Abecasis, GR, Wareham, NJ, Sladek, R, Froguel, P, Watanabe, RM, Meigs, JB, Groop, L, Boehnke, M, McCarthy, MI, Florez, JC, Consortium, DIAGRAM, Consortium, GIANT, Consortium, GB, Consortium, P, and Investigators, IBMAGIC
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- 2010
15. Plasma phospholipid transfer protein activity is decreased in type 2diabetes during treatment with atorvastatin - A role for apolipoprotein E?
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Dallinga-Thie, GM, van Tol, A, Hattori, H, Rensen, PCN, Sijbrands, EJG, DALY Study Group, [No Value], Faculteit Medische Wetenschappen/UMCG, and Science in Healthy Ageing & healthcaRE (SHARE)
- Subjects
ALZHEIMERS-DISEASE ,TRANSGENIC MICE ,RISK ,INSULIN-RESISTANCE ,ATHEROSCLEROSIS ,INCREASES ,HIGH-DENSITY-LIPOPROTEINS ,PLTP MASS ,nutritional and metabolic diseases ,lipids (amino acids, peptides, and proteins) ,CORONARY-HEART-DISEASE ,DIABETIC-PATIENTS - Abstract
Plasma phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism. PLTP activity is elevated in patients with diabetes, a condition with strongly elevated risk for coronary heart disease. The aim of this study was to test the hypothesis that statins reduce PLTP activity and to examine the potential role of apolipoprotein E (apoE). PLTP activity and apoE were measured in patients with type 2 diabetes from the DAM (Diabetes Atorvastatin Lipid Intervention) Study, a 30-week randomized double-blind placebo-controlled trial with atorvastatin (10 and 80 mg daily). At baseline, PLTP activity was positively correlated with waist circumference, HbAl. glucose, and apoE (all P
- Published
- 2006
16. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
- Author
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Ehret, GB, Munroe, PB, Rice, KM, Bochud, M, Johnson, AD, Chasman, DI, Smith, AV, Tobin, MD, Verwoert, GC, Hwang, S-J, Pihur, V, Vollenweider, P, O'Reilly, PF, Amin, N, Bragg-Gresham, JL, Teumer, A, Glazer, NL, Launer, L, Zhao, JH, Aulchenko, Y, Heath, S, Sober, S, Parsa, A, Luan, J, Arora, P, Dehghan, A, Zhang, F, Lucas, G, Hicks, AA, Jackson, AU, Peden, JF, Tanaka, T, Wild, SH, Rudan, I, Igl, W, Milaneschi, Y, Parker, AN, Fava, C, Chambers, JC, Fox, ER, Kumari, M, Go, MJ, van der Harst, P, Kao, WHL, Sjogren, M, Vinay, DG, Alexander, M, Tabara, Y, Shaw-Hawkins, S, Whincup, PH, Liu, Y, Shi, G, Kuusisto, J, Tayo, B, Seielstad, M, Sim, X, Khanh-Dung, HN, Lehtimaki, T, Matullo, G, Wu, Y, Gaunt, TR, Onland-Moret, NC, Cooper, MN, Platou, CGP, Org, E, Hardy, R, Dahgam, S, Palmen, J, Vitart, V, Braund, PS, Kuznetsova, T, Uiterwaal, CSPM, Adeyemo, A, Palmas, W, Campbell, H, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, ND, Aspelund, T, Garcia, M, Chang, Y-PC, O'Connell, JR, Steinle, NI, Grobbee, DE, Arking, DE, Kardia, SL, Morrison, AC, Hernandez, D, Najjar, S, McArdle, WL, Hadley, D, Brown, MJ, Connell, JM, Hingorani, AD, Day, INM, Lawlor, DA, Beilby, JP, Lawrence, RW, Clarke, R, Hopewell, JC, Ongen, H, Dreisbach, AW, Li, Y, Young, JH, Bis, JC, Kahonen, M, Viikari, J, Adair, LS, Lee, NR, Chen, M-H, Olden, M, Pattaro, C, Bolton, JAH, Koettgen, A, Bergmann, S, Mooser, V, Chaturvedi, N, Frayling, TM, Islam, M, Jafar, TH, Erdmann, J, Kulkarni, SR, Bornstein, SR, Graessler, J, Groop, L, Voight, BF, Kettunen, J, Howard, P, Taylor, A, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Barroso, IS, Khaw, K-T, Weder, AB, Hunt, SC, Sun, YV, Bergman, RN, Collins, FS, Bonnycastle, LL, Scott, LJ, Stringham, HM, Peltonen, L, Perola, M, Vartiainen, E, Brand, S-M, Staessen, JA, Wang, TJ, Burton, PR, Artigas, MS, Dong, Y, Snieder, H, Wang, X, Zhu, H, Lohman, KK, Rudock, ME, Heckbert, SR, Smith, NL, Wiggins, KL, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, CD, Rosengren, A, Thelle, DS, Corsi, AM, Singleton, A, Forrester, T, Hilton, G, McKenzie, CA, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Wichmann, H-E, Cho, YS, Kim, H-L, Lee, J-Y, Scott, J, Sehmi, JS, Zhang, W, Hedblad, B, Nilsson, P, Smith, GD, Wong, A, Narisu, N, Stancakova, A, Raffel, LJ, Yao, J, Kathiresan, S, O'Donnell, CJ, Schwartz, SM, Ikram, MA, Longstreth, WT, Mosley, TH, Seshadri, S, Shrine, NRG, Wain, LV, Morken, MA, Swift, AJ, Laitinen, J, Prokopenko, I, Zitting, P, Cooper, JA, Humphries, SE, Danesh, J, Rasheed, A, Goel, A, Hamsten, A, Watkins, H, Bakker, SJL, van Gilst, WH, Janipalli, CS, Mani, KR, Yajnik, CS, Hofman, A, Mattace-Raso, FUS, Oostra, BA, Demirkan, A, Isaacs, A, Rivadeneira, F, Lakatta, EG, Orru, M, Scuteri, A, Ala-Korpela, M, Kangas, AJ, Lyytikainen, L-P, Soininen, P, Tukiainen, T, Wurtz, P, Ong, RT-H, Doerr, M, Kroemer, HK, Voelker, U, Voelzke, H, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Deloukas, P, Mangino, M, Spector, TD, Zhai, G, Meschia, JF, Nalls, MA, Sharma, P, Terzic, J, Kumar, MVK, Denniff, M, Zukowska-Szczechowska, E, Wagenknecht, LE, Fowkes, FGR, Charchar, FJ, Schwarz, PEH, Hayward, C, Guo, X, Rotimi, C, Bots, ML, Brand, E, Samani, NJ, Polasek, O, Talmud, PJ, Nyberg, F, Kuh, D, Laan, M, Hveem, K, Palmer, LJ, van der Schouw, YT, Casas, JP, Mohlke, KL, Vineis, P, Raitakari, O, Ganesh, SK, Wong, TY, Tai, ES, Cooper, RS, Laakso, M, Rao, DC, Harris, TB, Morris, RW, Dominiczak, AF, Kivimaki, M, Marmot, MG, Miki, T, Saleheen, D, Chandak, GR, Coresh, J, Navis, G, Salomaa, V, Han, B-G, Zhu, X, Kooner, JS, Melander, O, Ridker, PM, Bandinelli, S, Gyllensten, UB, Wright, AF, Wilson, JF, Ferrucci, L, Farrall, M, Tuomilehto, J, Pramstaller, PP, Elosua, R, Soranzo, N, Sijbrands, EJG, Altshuler, D, Loos, RJF, Shuldiner, AR, Gieger, C, Meneton, P, Uitterlinden, AG, Wareham, NJ, Gudnason, V, Rotter, JI, Rettig, R, Uda, M, Strachan, DP, Witteman, JCM, Hartikainen, A-L, Beckmann, JS, Boerwinkle, E, Vasan, RS, Boehnke, M, Larson, MG, Jarvelin, M-R, Psaty, BM, Abecasis, GR, Chakravarti, A, Elliott, P, van Duijn, CM, Newton-Cheh, C, Levy, D, Caulfield, MJ, Johnson, T, Ehret, GB, Munroe, PB, Rice, KM, Bochud, M, Johnson, AD, Chasman, DI, Smith, AV, Tobin, MD, Verwoert, GC, Hwang, S-J, Pihur, V, Vollenweider, P, O'Reilly, PF, Amin, N, Bragg-Gresham, JL, Teumer, A, Glazer, NL, Launer, L, Zhao, JH, Aulchenko, Y, Heath, S, Sober, S, Parsa, A, Luan, J, Arora, P, Dehghan, A, Zhang, F, Lucas, G, Hicks, AA, Jackson, AU, Peden, JF, Tanaka, T, Wild, SH, Rudan, I, Igl, W, Milaneschi, Y, Parker, AN, Fava, C, Chambers, JC, Fox, ER, Kumari, M, Go, MJ, van der Harst, P, Kao, WHL, Sjogren, M, Vinay, DG, Alexander, M, Tabara, Y, Shaw-Hawkins, S, Whincup, PH, Liu, Y, Shi, G, Kuusisto, J, Tayo, B, Seielstad, M, Sim, X, Khanh-Dung, HN, Lehtimaki, T, Matullo, G, Wu, Y, Gaunt, TR, Onland-Moret, NC, Cooper, MN, Platou, CGP, Org, E, Hardy, R, Dahgam, S, Palmen, J, Vitart, V, Braund, PS, Kuznetsova, T, Uiterwaal, CSPM, Adeyemo, A, Palmas, W, Campbell, H, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, ND, Aspelund, T, Garcia, M, Chang, Y-PC, O'Connell, JR, Steinle, NI, Grobbee, DE, Arking, DE, Kardia, SL, Morrison, AC, Hernandez, D, Najjar, S, McArdle, WL, Hadley, D, Brown, MJ, Connell, JM, Hingorani, AD, Day, INM, Lawlor, DA, Beilby, JP, Lawrence, RW, Clarke, R, Hopewell, JC, Ongen, H, Dreisbach, AW, Li, Y, Young, JH, Bis, JC, Kahonen, M, Viikari, J, Adair, LS, Lee, NR, Chen, M-H, Olden, M, Pattaro, C, Bolton, JAH, Koettgen, A, Bergmann, S, Mooser, V, Chaturvedi, N, Frayling, TM, Islam, M, Jafar, TH, Erdmann, J, Kulkarni, SR, Bornstein, SR, Graessler, J, Groop, L, Voight, BF, Kettunen, J, Howard, P, Taylor, A, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Barroso, IS, Khaw, K-T, Weder, AB, Hunt, SC, Sun, YV, Bergman, RN, Collins, FS, Bonnycastle, LL, Scott, LJ, Stringham, HM, Peltonen, L, Perola, M, Vartiainen, E, Brand, S-M, Staessen, JA, Wang, TJ, Burton, PR, Artigas, MS, Dong, Y, Snieder, H, Wang, X, Zhu, H, Lohman, KK, Rudock, ME, Heckbert, SR, Smith, NL, Wiggins, KL, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, CD, Rosengren, A, Thelle, DS, Corsi, AM, Singleton, A, Forrester, T, Hilton, G, McKenzie, CA, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Wichmann, H-E, Cho, YS, Kim, H-L, Lee, J-Y, Scott, J, Sehmi, JS, Zhang, W, Hedblad, B, Nilsson, P, Smith, GD, Wong, A, Narisu, N, Stancakova, A, Raffel, LJ, Yao, J, Kathiresan, S, O'Donnell, CJ, Schwartz, SM, Ikram, MA, Longstreth, WT, Mosley, TH, Seshadri, S, Shrine, NRG, Wain, LV, Morken, MA, Swift, AJ, Laitinen, J, Prokopenko, I, Zitting, P, Cooper, JA, Humphries, SE, Danesh, J, Rasheed, A, Goel, A, Hamsten, A, Watkins, H, Bakker, SJL, van Gilst, WH, Janipalli, CS, Mani, KR, Yajnik, CS, Hofman, A, Mattace-Raso, FUS, Oostra, BA, Demirkan, A, Isaacs, A, Rivadeneira, F, Lakatta, EG, Orru, M, Scuteri, A, Ala-Korpela, M, Kangas, AJ, Lyytikainen, L-P, Soininen, P, Tukiainen, T, Wurtz, P, Ong, RT-H, Doerr, M, Kroemer, HK, Voelker, U, Voelzke, H, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Deloukas, P, Mangino, M, Spector, TD, Zhai, G, Meschia, JF, Nalls, MA, Sharma, P, Terzic, J, Kumar, MVK, Denniff, M, Zukowska-Szczechowska, E, Wagenknecht, LE, Fowkes, FGR, Charchar, FJ, Schwarz, PEH, Hayward, C, Guo, X, Rotimi, C, Bots, ML, Brand, E, Samani, NJ, Polasek, O, Talmud, PJ, Nyberg, F, Kuh, D, Laan, M, Hveem, K, Palmer, LJ, van der Schouw, YT, Casas, JP, Mohlke, KL, Vineis, P, Raitakari, O, Ganesh, SK, Wong, TY, Tai, ES, Cooper, RS, Laakso, M, Rao, DC, Harris, TB, Morris, RW, Dominiczak, AF, Kivimaki, M, Marmot, MG, Miki, T, Saleheen, D, Chandak, GR, Coresh, J, Navis, G, Salomaa, V, Han, B-G, Zhu, X, Kooner, JS, Melander, O, Ridker, PM, Bandinelli, S, Gyllensten, UB, Wright, AF, Wilson, JF, Ferrucci, L, Farrall, M, Tuomilehto, J, Pramstaller, PP, Elosua, R, Soranzo, N, Sijbrands, EJG, Altshuler, D, Loos, RJF, Shuldiner, AR, Gieger, C, Meneton, P, Uitterlinden, AG, Wareham, NJ, Gudnason, V, Rotter, JI, Rettig, R, Uda, M, Strachan, DP, Witteman, JCM, Hartikainen, A-L, Beckmann, JS, Boerwinkle, E, Vasan, RS, Boehnke, M, Larson, MG, Jarvelin, M-R, Psaty, BM, Abecasis, GR, Chakravarti, A, Elliott, P, van Duijn, CM, Newton-Cheh, C, Levy, D, Caulfield, MJ, and Johnson, T
- Abstract
Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
- Published
- 2011
17. Biological, clinical and population relevance of 95 loci for blood lipids
- Author
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Teslovich, TM, Musunuru, K, Smith, AV, Edmondson, AC, Stylianou, IM, Koseki, M, Pirruccello, JP, Ripatti, S, Chasman, DI, Willer, CJ, Johansen, CT, Fouchier, SW, Isaacs, A, Peloso, GM, Barbalic, M, Ricketts, SL, Bis, JC, Aulchenko, YS, Thorleifsson, G, Feitosa, MF, Chambers, J, Orho-Melander, M, Melander, O, Johnson, T, Li, X, Guo, X, Li, M, Cho, YS, Go, MJ, Kim, YJ, Lee, J-Y, Park, T, Kim, K, Sim, X, Ong, RT-H, Croteau-Chonka, DC, Lange, LA, Smith, JD, Song, K, Zhao, JH, Yuan, X, Luan, J, Lamina, C, Ziegler, A, Zhang, W, Zee, RYL, Wright, AF, Witteman, JCM, Wilson, JF, Willemsen, G, Wichmann, H-E, Whitfield, JB, Waterworth, DM, Wareham, NJ, Waeber, G, Vollenweider, P, Voight, BF, Vitart, V, Uitterlinden, AG, Uda, M, Tuomilehto, J, Thompson, JR, Tanaka, T, Surakka, I, Stringham, HM, Spector, TD, Soranzo, N, Smit, JH, Sinisalo, J, Silander, K, Sijbrands, EJG, Scuteri, A, Scott, J, Schlessinger, D, Sanna, S, Salomaa, V, Saharinen, J, Sabatti, C, Ruokonen, A, Rudan, I, Rose, LM, Roberts, R, Rieder, M, Psaty, BM, Pramstaller, PP, Pichler, I, Perola, M, Penninx, BWJH, Pedersen, NL, Pattaro, C, Parker, AN, Pare, G, Oostra, BA, O'Donnell, CJ, Nieminen, MS, Nickerson, DA, Montgomery, GW, Meitinger, T, McPherson, R, McCarthy, MI, McArdle, W, Masson, D, Martin, NG, Marroni, F, Mangino, M, Magnusson, PKE, Lucas, G, Luben, R, Loos, RJF, Lokki, M-L, Lettre, G, Langenberg, C, Launer, LJ, Lakatta, EG, Laaksonen, R, Kyvik, KO, Kronenberg, F, Koenig, IR, Khaw, K-T, Kaprio, J, Kaplan, LM, Johansson, A, Jarvelin, M-R, Janssens, ACJW, Ingelsson, E, Igi, W, Hovingh, GK, Hottenga, J-J, Hofman, A, Hicks, AA, Hengstenberg, C, Heid, IM, Hayward, C, Havulinna, AS, Hastie, ND, Harris, TB, Haritunians, T, Hall, AS, Gyllensten, U, Guiducci, C, Groop, LC, Gonzalez, E, Gieger, C, Freimer, NB, Ferrucci, L, Erdmann, J, Elliott, P, Ejebe, KG, Doering, A, Dominiczak, AF, Demissie, S, Deloukas, P, de Geus, EJC, de Faire, U, Crawford, G, Collins, FS, Chen, Y-DI, Caulfield, MJ, Campbell, H, Burtt, NP, Bonnycastle, LL, Boomsma, DI, Boekholdt, SM, Bergman, RN, Barroso, I, Bandinelli, S, Ballantyne, CM, Assimes, TL, Quertermous, T, Altshuler, D, Seielstad, M, Wong, TY, Tai, E-S, Feranil, AB, Kuzawa, CW, Adair, LS, Taylor, HA, Borecki, IB, Gabriel, SB, Wilson, JG, Holm, H, Thorsteinsdottir, U, Gudnason, V, Krauss, RM, Mohlke, KL, Ordovas, JM, Munroe, PB, Kooner, JS, Tall, AR, Hegele, RA, Kastelein, JJP, Schadt, EE, Rotter, JI, Boerwinkle, E, Strachan, DP, Mooser, V, Stefansson, K, Reilly, MP, Samani, NJ, Schunkert, H, Cupples, LA, Sandhu, MS, Ridker, PM, Rader, DJ, van Duijn, CM, Peltonen, L, Abecasis, GR, Boehnke, M, Kathiresan, S, Teslovich, TM, Musunuru, K, Smith, AV, Edmondson, AC, Stylianou, IM, Koseki, M, Pirruccello, JP, Ripatti, S, Chasman, DI, Willer, CJ, Johansen, CT, Fouchier, SW, Isaacs, A, Peloso, GM, Barbalic, M, Ricketts, SL, Bis, JC, Aulchenko, YS, Thorleifsson, G, Feitosa, MF, Chambers, J, Orho-Melander, M, Melander, O, Johnson, T, Li, X, Guo, X, Li, M, Cho, YS, Go, MJ, Kim, YJ, Lee, J-Y, Park, T, Kim, K, Sim, X, Ong, RT-H, Croteau-Chonka, DC, Lange, LA, Smith, JD, Song, K, Zhao, JH, Yuan, X, Luan, J, Lamina, C, Ziegler, A, Zhang, W, Zee, RYL, Wright, AF, Witteman, JCM, Wilson, JF, Willemsen, G, Wichmann, H-E, Whitfield, JB, Waterworth, DM, Wareham, NJ, Waeber, G, Vollenweider, P, Voight, BF, Vitart, V, Uitterlinden, AG, Uda, M, Tuomilehto, J, Thompson, JR, Tanaka, T, Surakka, I, Stringham, HM, Spector, TD, Soranzo, N, Smit, JH, Sinisalo, J, Silander, K, Sijbrands, EJG, Scuteri, A, Scott, J, Schlessinger, D, Sanna, S, Salomaa, V, Saharinen, J, Sabatti, C, Ruokonen, A, Rudan, I, Rose, LM, Roberts, R, Rieder, M, Psaty, BM, Pramstaller, PP, Pichler, I, Perola, M, Penninx, BWJH, Pedersen, NL, Pattaro, C, Parker, AN, Pare, G, Oostra, BA, O'Donnell, CJ, Nieminen, MS, Nickerson, DA, Montgomery, GW, Meitinger, T, McPherson, R, McCarthy, MI, McArdle, W, Masson, D, Martin, NG, Marroni, F, Mangino, M, Magnusson, PKE, Lucas, G, Luben, R, Loos, RJF, Lokki, M-L, Lettre, G, Langenberg, C, Launer, LJ, Lakatta, EG, Laaksonen, R, Kyvik, KO, Kronenberg, F, Koenig, IR, Khaw, K-T, Kaprio, J, Kaplan, LM, Johansson, A, Jarvelin, M-R, Janssens, ACJW, Ingelsson, E, Igi, W, Hovingh, GK, Hottenga, J-J, Hofman, A, Hicks, AA, Hengstenberg, C, Heid, IM, Hayward, C, Havulinna, AS, Hastie, ND, Harris, TB, Haritunians, T, Hall, AS, Gyllensten, U, Guiducci, C, Groop, LC, Gonzalez, E, Gieger, C, Freimer, NB, Ferrucci, L, Erdmann, J, Elliott, P, Ejebe, KG, Doering, A, Dominiczak, AF, Demissie, S, Deloukas, P, de Geus, EJC, de Faire, U, Crawford, G, Collins, FS, Chen, Y-DI, Caulfield, MJ, Campbell, H, Burtt, NP, Bonnycastle, LL, Boomsma, DI, Boekholdt, SM, Bergman, RN, Barroso, I, Bandinelli, S, Ballantyne, CM, Assimes, TL, Quertermous, T, Altshuler, D, Seielstad, M, Wong, TY, Tai, E-S, Feranil, AB, Kuzawa, CW, Adair, LS, Taylor, HA, Borecki, IB, Gabriel, SB, Wilson, JG, Holm, H, Thorsteinsdottir, U, Gudnason, V, Krauss, RM, Mohlke, KL, Ordovas, JM, Munroe, PB, Kooner, JS, Tall, AR, Hegele, RA, Kastelein, JJP, Schadt, EE, Rotter, JI, Boerwinkle, E, Strachan, DP, Mooser, V, Stefansson, K, Reilly, MP, Samani, NJ, Schunkert, H, Cupples, LA, Sandhu, MS, Ridker, PM, Rader, DJ, van Duijn, CM, Peltonen, L, Abecasis, GR, Boehnke, M, and Kathiresan, S
- Abstract
Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
- Published
- 2010
18. Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals
- Author
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Seppo Koskinen, Christian Herder, Daniel I. Chasman, Andrew R. Wood, Jonna L. Grimsby, J.F. Wilson, Day Inm., Massimo Mangino, Gonneke Willemsen, Robert W. Mahley, Cristian Pattaro, Nicole L. Glazer, T.B. Harris, Irene Pichler, M S Sandhu, D. van Heemst, Christine Proença, Martha Ganser, Robert A. Hegele, Richa Saxena, Eleftheria Zeggini, Markku Laakso, Peter Kraft, Judith B. Borja, Karen L. Mohlke, J B Richards, de Geus Ejc., Robert Sladek, Cristen J. Willer, Samy Hadjadj, S.M. Boekholdt, Gina M. Peloso, Kijoung Song, Sutapa Mukherjee, Gudmar Thorleifsson, Winston Hide, Mark I. McCarthy, Ruth E. Pakyz, Marian Beekman, Ayellet V. Segrè, Inga Prokopenko, Ping An, George Dedoussis, Danielle Posthuma, Jeanette Erdmann, Simon J. Griffin, Nilesh J. Samani, Inke R. König, Frank B. Hu, Lokki M-L., David M. Evans, Xiaohui Li, Valgerdur Steinthorsdottir, Aimo Ruokonen, A Pouta, Kerrin S. Small, Cecilia M. Lindgren, O Le Bacquer, Xijing Han, Florian Kronenberg, E Katsareli, Christian Dina, S. Gabriel, Jochen Spranger, James S. Pankow, M. Kloppenburg, Penninx Bwjh., Torben Hansen, Josh Smith, Jennie Hui, Gordon H. Williams, Mark Seielstad, Ingrid B. Borecki, Weihua Zhang, Peter P. Pramstaller, Stephen J. Sharp, Neil R. Robertson, Zee Ryl., Mike Sampson, Angela Silveira, C.M. van Duijn, Anders Hamsten, Peter Shrader, Denis Rybin, Chen Y-Di., Gunnar Sigurdsson, Michael Stumvoll, Russel Tracy, Mark O. Goodarzi, Göran Hallmans, Michael R. Erdos, Valeriya Lyssenko, Juha Saharinen, Sven Bergmann, Jeffrey R. O'Connell, Debbie A Lawlor, Thomas Meitinger, Yvonne Böttcher, Jérôme Delplanque, Sarah G. Buxbaum, Silvia Naitza, Shah Ebrahim, Graham A. Hitman, Angelo Scuteri, Aroon D. Hingorani, Heribert Schunkert, François Pattou, Claudia Lamina, A L Elliott, Sekar Kathiresan, Dawn M. Waterworth, Jennifer A. Brody, Thomas Quertermous, Leena Peltonen, Josephine M. Egan, Daniel J. Rader, J F Peden, Yarnell Jwg., Daniel S. 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S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, Pj, Walley, A, Ward, Kl, Watkins, H, Wild, Sh, Willemsen, G, Witteman, Jc, Yarnell, Jw, Zelenika, D, Zethelius, B, Zhai, G, Zhao, Jh, Zillikens, Mc, Diagram, Consortium, Giant, Consortium, Global B., Pgen Consortium, Borecki, Ib, Meneton, P, Magnusson, Pk, Nathan, Dm, Williams, Gh, Silander, K, Bornstein, Sr, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, Ar, Cooper, C, Serrano Ríos, M, Lind, L, Palmer, Lj, Hu FB, 1st, Franks, Pw, Ebrahim, S, Marmot, M, Wright, Af, Stumvoll, M, Hamsten, A, Procardis, Consortium, Buchanan, Ta, Valle, Tt, Rotter, Ji, Penninx, Bw, Boomsma, Di, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, Mr, Peltonen, L, Mooser, V, Magic, Investigator, Glgc, Consortium, Musunuru, K, Smith, Av, Edmondson, Ac, Stylianou, Im, Koseki, M, Pirruccello, Jp, Chasman, Di, Johansen, Ct, Fouchier, Sw, Peloso, Gm, Barbalic, M, Ricketts, Sl, Bis, Jc, Feitosa, Mf, Orho Melander, M, Melander, O, Li, X, Cho, Y, Go, Mj, Kim, Yj, Lee, Jy, Park, T, Kim, K, Sim, X, Ong, Rt, Croteau Chonka, Dc, Lange, La, Smith, Jd, Ziegler, A, Zhang, W, Zee, Ry, Whitfield, Jb, Thompson, Jr, Surakka, I, Smit, Jh, Sinisalo, J, Scott, J, Saharinen, J, Sabatti, C, Rose, Lm, Roberts, R, Rieder, M, Parker, An, Pare, G, O'Donnell, Cj, Nieminen, M, Nickerson, Da, Montgomery, Gw, Mcardle, W, Masson, D, Martin, Ng, Marroni, F, Lucas, G, Luben, R, Lokki, Ml, Lettre, G, Launer, Lj, Lakatta, Eg, Laaksonen, R, König, Ir, Khaw, Kt, Kaplan, Lm, Johansson, Å, Janssens, Ac, Igl, W, Hovingh, Gk, Hengstenberg, C, Havulinna, A, Hastie, Nd, Harris, Tb, Haritunians, T, Hall, A, Groop, Lc, Gonzalez, E, Freimer, Nb, Erdmann, J, Ejebe, Kg, Döring, A, Dominiczak, Af, Demissie, S, de Faire, U, Caulfield, Mj, Boekholdt, Sm, Assimes, Tl, Quertermous, T, Seielstad, M, Wong, Ty, Tai, E, Feranil, Ab, Kuzawa, Cw, Taylor HA, Jr, Gabriel, Sb, Holm, H, Gudnason, V, Krauss, Rm, Ordovas, Jm, Munroe, Pb, Tall, Ar, Hegele, Ra, Kastelein, Jj, Schadt, Ee, Strachan, Dp, Reilly, Mp, Samani, Nj, Schunkert, H, Cupples, La, Ridker, Pm, Rader, Dj, Kathiresan, S., Medical Research Council (MRC), Perry, John [0000-0001-6483-3771], Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], Semple, Robert [0000-0001-6539-3069], Griffin, Simon [0000-0002-2157-4797], Barroso, Ines [0000-0001-5800-4520], Soranzo, Nicole [0000-0003-1095-3852], Wheeler, Eleanor [0000-0002-8616-6444], Luan, Jian'an [0000-0003-3137-6337], Forouhi, Nita [0000-0002-5041-248X], Sharp, Stephen [0000-0003-2375-1440], Sovio, Ulla [0000-0002-0799-1105], Zhao, Jing Hua [0000-0003-4930-3582], Luben, Robert [0000-0002-5088-6343], Khaw, Kay-Tee [0000-0002-8802-2903], Sandhu, Manjinder [0000-0002-2725-142X], Apollo - University of Cambridge Repository, Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Attention & Cognition, EMGO+ - Lifestyle, Overweight and Diabetes, Other departments, Experimental Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Cardiology, Human genetics, Psychiatry, NCA - Attention & Cognition, EMGO - Lifestyle, overweight and diabetes, Lääketieteen yksikkö - School of Medicine, University of Tampere, Institute for Molecular Medicine Finland, Hjelt Institute (-2014), Clinicum, Department of General Practice and Primary Health Care, Department of Public Health, Haartman Institute (-2014), Transplantation Laboratory, Biostatistics Helsinki, Quantitative Genetics, Complex Disease Genetics, Genetic Epidemiology, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., and O'Leary, DH.
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Netherlands Twin Register (NTR) ,Male ,Insulin Resistance/genetics ,VARIANTS ,0302 clinical medicine ,POPULATION ,African Americans ,blood/genetics ,0303 health sciences ,education.field_of_study ,Adiponectin/blood ,Adiponectin/genetics ,Asian Continental Ancestry Group ,Cholesterol, HDL/genetics ,Diabetes Mellitus, Type 2/genetics ,European Continental Ancestry Group ,Female ,Gene Expression ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Glucose Tolerance Test ,Humans ,Metabolic Networks and Pathways ,Polymorphism, Single Nucleotide ,Waist-Hip Ratio ,Global B Pgen Consortium ,MAGIC investigators ,3. Good health ,Cholesterol ,Medicine ,Adiponectin ,Type 2 ,medicine.medical_specialty ,HDL ,Biolääketieteet - Biomedicine ,Single-nucleotide polymorphism ,DIAGRAM Consortium ,White People ,Molecular Genetics ,GLGC Consortium ,03 medical and health sciences ,Asian People ,SDG 3 - Good Health and Well-being ,GIANT Consortium ,Diabetes Mellitus ,Genetics ,DIAGRAM+ Consortium ,GENOME-WIDE ASSOCIATION ,Polymorphism ,education ,Biology ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,0604 Genetics ,Science & Technology ,GLGC Investigators ,nutritional and metabolic diseases ,ta3121 ,medicine.disease ,Obesity ,Black or African American ,blood/genetics, African Americans, Asian Continental Ancestry Group, Cholesterol ,genetics, Diabetes Mellitus ,genetics, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Insulin Resistance ,genetics, Male, Metabolic Networks and Pathways, Polymorphism ,Single Nucleotide, Waist-Hip Ratio ,Endocrinology ,Diabetes Mellitus, Type 2 ,Developmental Biology ,Type 2/genetics ,Cancer Research ,Type 2 diabetes ,QH426-470 ,030204 cardiovascular system & hematology ,LIPID CONCENTRATIONS ,GENETICS & HEREDITY ,Genetics (clinical) ,RISK ,2. Zero hunger ,INSULIN-RESISTANCE ,Glucose tolerance test ,medicine.diagnostic_test ,MAGIC Consortium ,Single Nucleotide ,ADIPOSE-TISSUE ,CORONARY-ARTERY-DISEASE ,Life Sciences & Biomedicine ,Research Article ,Clinical Research Design ,GENETIC-BASIS ,Population ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,medicine ,ddc:610 ,030304 developmental biology ,RECEPTOR ,Cholesterol, HDL ,Human Genetics ,HDL/genetics ,3121 General medicine, internal medicine and other clinical medicine ,MuTHER Consortium ,3111 Biomedicine ,Procardis Consortium ,Insulin Resistance - Abstract
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8–1.2×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p, Author Summary Serum adiponectin levels are highly heritable and are inversely correlated with the risk of type 2 diabetes (T2D), coronary artery disease, stroke, and several metabolic traits. To identify common genetic variants associated with adiponectin levels and risk of T2D and metabolic traits, we conducted a meta-analysis of genome-wide association studies of 45,891 multi-ethnic individuals. In addition to confirming that variants at the ADIPOQ and CDH13 loci influence adiponectin levels, our analyses revealed that 10 new loci also affecting circulating adiponectin levels. We demonstrated that expression levels of several genes in these candidate regions are associated with serum adiponectin levels. Using a powerful novel method to assess the contribution of the identified variants with other traits using summary-level results from large-scale GWAS consortia, we provide evidence that the risk alleles for adiponectin are associated with deleterious changes in T2D risk and metabolic syndrome traits (triglycerides, HDL, post-prandial glucose, insulin, and waist-to-hip ratio), demonstrating that the identified loci, taken together, impact upon metabolic disease.
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- 2012
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19. DAILY RED WINE CONSUMPTION IMPROVES VASCULAR FUNCTION IN YOUNG HEALTHY WOMEN, PROPABLY BY AN ENDOTHELIUM-DEPENDENT NITRIC OXIDE-SOLUBLE GUANYLYL CYCLASE - MEDIATED PATHWAY: PP.6.236
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Botden, I, primary, Langendonk, JG, additional, Danser, AHJ, additional, and Sijbrands, EJG, additional
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- 2010
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20. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study.
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Versmissen J, Oosterveer DM, Yazdanpanah M, Defesche JC, Basart DCG, Liem AH, Heeringa J, Witteman JC, Lansberg PJ, Kastelein JJP, and Sijbrands EJG
- Published
- 2009
21. Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study.
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van Hoek M, Dehghan A, Witteman JCM, van Duijn CM, Uitterlinden AG, Oostra BA, Hofman A, Sijbrands EJG, Janssens ACJ, van Hoek, Mandy, Dehghan, Abbas, Witteman, Jacqueline C M, van Duijn, Cornelia M, Uitterlinden, André G, Oostra, Ben A, Hofman, Albert, Sijbrands, Eric J G, and Janssens, A Cecile J W
- Abstract
Objective: Prediction of type 2 diabetes based on genetic testing might improve identification of high-risk subjects. Genome-wide association (GWA) studies identified multiple new genetic variants that associate with type 2 diabetes. The predictive value of genetic testing for prediction of type 2 diabetes in the general population is unclear.Research Design and Methods: We investigated 18 polymorphisms from recent GWA studies on type 2 diabetes in the Rotterdam Study, a prospective, population-based study among homogeneous Caucasian individuals of 55 years and older (genotyped subjects, n = 6,544; prevalent cases, n = 686; incident cases during follow-up, n = 601; mean follow-up 10.6 years). The predictive value of these polymorphisms was examined alone and in addition to clinical characteristics using logistic and Cox regression analyses. The discriminative accuracy of the prediction models was assessed by the area under the receiver operating characteristic curves (AUCs).Results: Of the 18 polymorphisms, the ADAMTS9, CDKAL1, CDKN2A/B-rs1412829, FTO, IGF2BP2, JAZF1, SLC30A8, TCF7L2, and WFS1 variants were associated with type 2 diabetes risk in our population. The AUC was 0.60 (95% CI 0.57-0.63) for prediction based on the genetic polymorphisms; 0.66 (0.63-0.68) for age, sex, and BMI; and 0.68 (0.66-0.71) for the genetic polymorphisms and clinical characteristics combined.Conclusions: We showed that 9 of 18 well-established genetic risk variants were associated with type 2 diabetes in a population-based study. Combining genetic variants has low predictive value for future type 2 diabetes at a population-based level. The genetic polymorphisms only marginally improved the prediction of type 2 diabetes beyond clinical characteristics. [ABSTRACT FROM AUTHOR]- Published
- 2008
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22. Plasma phospholipid transfer protein activity is decreased in type 2 diabetes during treatment with atorvastatin: a role for apolipoprotein E?
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Dallinga-Thie GM, van Tol A, Hattori H, Rensen PCN, Sijbrands EJG, Dallinga-Thie, Geesje M, van Tol, Arie, Hattori, Hiroaki, Rensen, Patrick C N, and Sijbrands, Eric J G
- Abstract
Plasma phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism. PLTP activity is elevated in patients with diabetes, a condition with strongly elevated risk for coronary heart disease. The aim of this study was to test the hypothesis that statins reduce PLTP activity and to examine the potential role of apolipoprotein E (apoE). PLTP activity and apoE were measured in patients with type 2 diabetes from the DALI (Diabetes Atorvastatin Lipid Intervention) Study, a 30-week randomized double-blind placebo-controlled trial with atorvastatin (10 and 80 mg daily). At baseline, PLTP activity was positively correlated with waist circumference, HbA(1c), glucose, and apoE (all P < 0.05). Atorvastatin treatment resulted in decreased PLTP activity (10 mg atorvastatin: -8.3%, P < 0.05; 80 mg atorvastatin: -12.1%, P < 0.002). Plasma apoE decreased by 28 and 36%, respectively (P < 0.001). The decrease in apoE was strongly related to the decrease in PLTP activity (r = 0.565, P < 0.001). The change in apoE remained the sole determinant of the change in PLTP activity in a multivariate model. The activity of PLTP in type 2 diabetes is decreased by atorvastatin. The association between the decrease in PLTP activity and apoE during statin treatment supports the hypothesis that apoE may prevent PLTP inactivation. [ABSTRACT FROM AUTHOR]
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- 2006
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23. Family history and cardiovascular risk in familial hypercholesterolemia: data in more than 1000 children.
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Wiegman A, Rodenburg J, de Jongh S, Defesche JC, Bakker HD, Kastelein JJP, Sijbrands EJG, Wiegman, Albert, Rodenburg, Jessica, de Jongh, Saskia, Defesche, Joep C, Bakker, Henk D, Kastelein, John J P, and Sijbrands, Eric J G
- Published
- 2003
24. Poster session Thursday 12 December - PM: 12/12/2013, 14:00-18:00 * Location: Poster area
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Garcia Martin, A, Fernandez Golfin, C, Salido Tahoces, L, Fernandez Santos, S, Jimenez Nacher, JJ, Moya Mur, JL, Velasco Valdazo, E, Hernandez Antolin, R, Zamorano Gomez, JL, Veronesi, F, Corsi, C, Caiani, EG, Lamberti, C, Tsang, W, Holmgren, C, Guo, X, Bateman, M, Iaizzo, P, Vannier, M, Lang, RM, Patel, AR, Adamayn, KG, Tumasyan, L R, Chilingaryan, AL, Nasr, G, Eleraki, A, Farouk, N, Axelsson, A, Langhoff, L, Jensen, MK, Vejlstrup, N, Iversen, K, Bundgaard, H, Watanabe, T, Iwai-Takano, M, Attenhofer Jost, C H, Pfyffer, M, Seifert, B, Scharf, C, Candinas, R, Medeiros-Domingo, A, Chin, J-Y, Yoon, HJ, Vollbon, W, Singbal, Y, Rhodes, K, Wahi, S, Katova, T M, Simova, I I, Hristova, K, Kostova, V, Pauncheva, B, Bircan, A, Sade, LE, Eroglu, S, Pirat, B, Okyay, K, Bal, U, Muderrisoglu, H, Heggemann, F, Buggisch, H, Welzel, G, Doesch, C, Hansmann, J, Schoenberg, S, Borggrefe, M, Wenz, F, Papavassiliu, T, Lohr, F, Roussin, I, Drakopoulou, M, Rosen, S, Sharma, R, Prasad, S, Lyon, AR, Carpenter, JP, Senior, R, Breithardt, O-A, Razavi, H, Arya, A, Nabutovsky, Y, Ryu, K, Gaspar, T, Kosiuk, J, Eitel, C, Hindricks, G, Piorkowski, C, Pires, S, Nunes, A, Cortez-Dias, N, Belo, A, Zimbarra Cabrita, I, Sousa, C, Pinto, F, Baron, T, Johansson, K, Flachskampf, FA, Christersson, C, Pires, S, Cortez-Dias, N, Nunes, A, Belo, A, Zimbarra Cabrita, I, Sousa, C, Pinto, F, Santoro, A, Federico Alvino, FA, Giovanni Antonelli, GA, Raffaella De Vito, RDV, Roberta Molle, RM, Sergio Mondillo, SM, Gustafsson, M, Alehagen, U, Johansson, P, Tsukishiro, Y, Onishi, T, Chimura, M, Yamada, S, Taniguchi, Y, Yasaka, Y, Kawai, H, Souza, J R M, Zacharias, L G T, Pithon, K R, Ozahata, T M, Cliquet, A JR, Blotta, M H, Nadruz, W JR, Fabiani, I, Conte, L, Cuono, C, Liga, R, Giannini, C, Barletta, V, Nardi, C, Delle Donne, MG, Palagi, C, Di Bello, V, Glaveckaite, S, Valeviciene, N, Palionis, D, Laucevicius, A, Hristova, K, Bogdanova, V, Ferferieva, V, Shiue, I, Castellon, X, Boles, U, Rakhit, R, Shiu, M F, Gilbert, T, Papachristidis, A, Henein, M Y, Westholm, C, Johnson, J, Jernberg, T, Winter, R, Ghosh Dastidar, A, Augustine, D, Cengarle, M, Mcalindon, E, Bucciarelli-Ducci, C, Nightingale, A, Onishi, T, Watanabe, T, Fujita, M, Mizukami, Y, Sakata, Y, Nakatani, S, Nanto, S, Uematsu, M, Saraste, A, Luotolahti, M, Varis, A, Vasankari, T, Tunturi, S, Taittonen, M, Rautakorpi, P, Airaksinen, J, Ukkonen, H, Knuuti, J, Boshchenko, A, Vrublevsky, A, Karpov, R, Yoshikawa, H, Suzuki, M, Hashimoto, G, Kusunose, Y, Otsuka, T, Nakamura, M, Sugi, K, Rosner, SJ, Orban, M, Lesevic, H, Karl, M, Hadamitzky, M, Sonne, C, Panaro, A, Martinez, F, Huguet, M, Moral, S, Palet, J, Oller, G, Cuso, I, Jornet, A, Rodriguez Palomares, J, Evangelista, A, Stoebe, S, Tarr, A, Pfeiffer, D, Hagendorff, A, Gilmanov, DSH, Baroni, MB, Cerone, EC, Galli, EG, Berti, SB, Glauber, MG, Soesanto, A, Yuniadi, Y, Mansyur, M, Kusmana, D, Venkateshvaran, A, Dash, P K, Sola, S, Govind, S C, Shahgaldi, K, Winter, R, Brodin, L A, Manouras, A, Dokainish, H, Sadreddini, M, Nieuwlaat, R, Lonn, E, Healey, J, Nguyen, V, Cimadevilla, C, Dreyfus, J, Codogno, I, Vahanian, A, Messika-Zeitoun, D, Lim, Y-J, Kawamura, A, Kawano, S, Polte, CL, Gao, S, Lagerstrand, KM, Cederbom, U, Bech-Hanssen, O, Baum, J, Beeres, F, Van Hall, S, Boering, YC, Zeus, T, Kehmeier, ES, Kelm, M, Balzer, JC, Della Mattia, A, Pinamonti, B, Abate, E, Nicolosi, GL, Proclemer, A, Bassetti, M, Luzzati, R, Sinagra, G, Hlubocka, Z, Jiratova, K, Dostalova, G, Hlubocky, J, Dohnalova, A, Linhart, A, Palecek, T, Sonne, C, Lesevic, H, Karl, M, Rosner, S, Hadamitzky, M, Ott, I, Malev, E, Reeva, S, Zemtsovsky, E, Igual Munoz, B, Alonso Fernandez Pau, PAF, Miro Palau Vicente, VMP, Maceira Gonzalez Alicia, AMG, Estornell Erill, JEE, Andres La Huerta, AALH, Donate Bertolin, LDB, Valera Martinez, FVM, Salvador Sanz Antonio, ASS, Montero Argudo Anastasio, AMA, Nemes, A, Kalapos, A, Domsik, P, Chadaide, S, Sepp, R, Forster, T, Onaindia, JJ, Arana, X, Cacicedo, A, Velasco, S, Rodriguez, I, Capelastegui, A, Sadaba, M, Gonzalez, J, Salcedo, A, Laraudogoitia, E, Archontakis, S, Gatzoulis, K, Vlasseros, I, Arsenos, P, Tsiachris, D, Vouliotis, A, Sideris, S, Karistinos, G, Kalikazaros, I, Stefanadis, C, Ancona, R, Comenale Pinto, S, Caso, P, Coppola, MG, Arenga, F, Cavallaro, C, Vecchione, F, Donofrio, A, Calabro, R, Correia, C E, Moreira, D, Cabral, C, Santos, JO, Cardoso, JS, Igual Munoz, B, Maceira Gonzalez, AMG, Estornell Erill Jordi, JEE, Jimenez Carreno, RJC, Arnau Vives, MAV, Monmeneu Menadas, JVMM, Domingo-Valero, DDV, Sanchez Fernandez, ESF, Montero Argudo Anastasio, AMA, Zorio Grima, EZG, Cincin, A, Tigen, K, Karaahmet, T, Dundar, C, Sunbul, M, Guler, A, Bulut, M, Basaran, Y, Mordi, I, Carrick, D, Berry, C, Tzemos, N, Cruz, I, Ferreira, A, Rocha Lopes, L, Joao, I, Almeida, AR, Fazendas, P, Cotrim, C, Pereira, H, Ochoa, J P, Fernandez, A, Filipuzzi, JM, Casabe, JH, Salmo, JF, Vaisbuj, F, Ganum, G, Di Nunzio, HJ, Veron, LF, Guevara, E, Salemi, VMC, Nerbass, FB, Portilho, N, Ferreira Filho, JCA, Pedrosa, RP, Arteaga-Fernandez, E, Mady, C, Drager, LF, Lorenzi-Filho, G, Marques, JS, Almeida, A M G, Menezes, M, Silva, GL, Placido, R, Amaro, C, Brito, D, Diogo, AN, Lourenco, M R, Azevedo, O, Moutinho, J, Nogueira, I, Machado, I, Portugues, J, Quelhas, I, Lourenco, A, Calore, C, Muraru, D, Melacini, P, Badano, LP, Mihaila, S, Puma, L, Peluso, D, Casablanca, S, Ortile, A, Iliceto, S, Kang, M-K, Yu, SH, Park, JJ, Kim, SH, Park, TY, Mun, H-S, C, S, Cho, S-R, Han, SW, Lee, N, Khalifa, E A, Hamodraka, E, Kallistratos, M, Zacharopoulou, I, Kouremenos, N, Mavropoulos, D, Tsoukas, A, Kontogiannis, N, Papanikolaou, N, Tsoukanas, K, Manolis, A, Villagraz Tecedor, L, Jimenez Lopez Guarch, C, Alonso Chaterina, S, Blazquez Arrollo, L, Lopez Melgar, B, Veitia Sarmiento, AL, Mayordomo Gomez, S, Escribano Subias, MP, Lichodziejewska, B, Kurnicka, K, Goliszek, S, Dzikowska Diduch, O, Kostrubiec, M, Krupa, M, Grudzka, K, Ciurzynski, M, Palczewski, P, Pruszczyk, P, Sakata, K, Ishiguro, M, Kimura, G, Uesugo, Y, Takemoto, K, Minamishima, T, Futuya, M, Matsue, S, Satoh, T, Yoshino, H, Signorello, MC, Gianturco, L, Colombo, C, Stella, D, Atzeni, F, Boccassini, L, Sarzi-Puttini, PC, Turiel, M, Kinova, E, Deliiska, B, Krivoshiev, S, Goudev, A, De Stefano, F, Santoro, C, Buonauro, A, Schiano-Lomoriello, V, Muscariello, R, De Palma, D, Galderisi, M, Ranganadha Babu, B, Chidambaram, SUNDAR, Sangareddi, V, Dhandapani, VE, Ravi, MS, Meenakshi, K, Muthukumar, D, Swaminathan, N, Ravishankar, G, Bruno, R M, Giardini, G, Catizzo, B, Brustia, R, Malacrida, S, Armenia, S, Cauchy, E, Pratali, L, Resamont2, Cesana, F, Alloni, M, Vallerio, P, De Chiara, B, Musca, F, Belli, O, Ricotta, R, Siena, S, Moreo, A, Giannattasio, C, Magnino, C, Omede, P, Avenatti, E, Presutti, D, Sabia, L, Moretti, C, Bucca, C, Gaita, F, Veglio, F, Milan, A, Eichhorn, JG, Springer, W, Helling, A, Alarajab, A, Loukanov, T, Ikeda, M, Kijima, Y, Akagi, T, Toh, N, Oe, H, Nakagawa, K, Tanabe, Y, Watanabe, N, Ito, H, Hascoet, S, Hadeed, K, Marchal, P, Bennadji, A, Peyre, M, Dulac, Y, Heitz, F, Alacoque, X, Chausseray, G, Acar, P, Kong, WILL, Ling, LH, Yip, JAMES, Poh, KK, Vassiliou, V, Rekhraj, S, Hoole, SP, Watkinson, O, Kydd, A, Boyd, J, Mcnab, D, Densem, C, Shapiro, LM, Rana, BS, Potpara, TS, Djikic, D, Polovina, M, Marcetic, Z, Peric, V, Lip, GYH, Gaudron, P, Niemann, M, Herrmann, S, Hu, K, Strotmann, J, Beer, M, Bijnens, B, Liu, D, Ertl, G, Weidemann, F, Peric, V, Jovanovic, A, Djikic, D, Otasevic, P, Kochanowski, J, Piatkowski, R, Scislo, P, Grabowski, M, Marchel, M, Opolski, G, Bandera, F, Guazzi, M, Arena, R, Corra, U, Ghio, S, Forfia, P, Rossi, A, Dini, F, Cahalin, LP, Temporelli, L, Rallidis, L, Tsangaris, I, Makavos, G, Anthi, A, Pappas, A, Orfanos, S, Lekakis, J, Anastasiou-Nana, M, Kuznetsov, V A, Krinochkin, D V, Yaroslavskaya, E I, Zaharova, E H, Pushkarev, G S, Mizia-Stec, K, Wita, K, Mizia, M, Loboz-Grudzien, K, Szwed, H, Kowalik, I, Kukulski, T, Gosciniak, P, Kasprzak, J, Plonska-Gosciniak, E, Cimino, S, Pedrizzetti, G, Tonti, G, Cicogna, F, Petronilli, V, De Luca, L, Iacoboni, C, Agati, L, Hoffmann, R, Barletta, G, Von Bardeleben, S, Kasprzak, J, Greis, C, Vanoverschelde, J, Becher, H, Galrinho, A, Moura Branco, L, Fiarresga, A, Cacela, D, Ramos, R, Cruz Ferreira, R, Van Den Oord, SCH, Akkus, Z, Bosch, JG, Renaud, G, Sijbrands, EJG, Verhagen, HJM, Van Der Lugt, A, Van Der Steen, AFW, Schinkel, AFL, Mordi, I, Tzemos, N, Stanton, T, Delgado, D, Yu, E, Drakopoulou, M, Gonzalez-Gonzalez, AM, Karonis, T, Roussin, I, Babu-Narayan, S, Swan, L, Senior, R, Li, W, Parisi, V, Pagano, G, Pellegrino, T, Femminella, GD, De Lucia, C, Formisano, R, Cuocolo, A, Perrone Filardi, P, Leosco, D, Rengo, G, Unlu, S, Farsalinos, K, Amelot, K, Daraban, A, Ciarka, A, Delcroix, M, Voigt, JU, Miskovic, A, Poerner, TD, Goebel, B, Stiller, CH, Moritz, A, Sakata, K, Uesugo, Y, Kimura, G, Ishiguro, M, Takemoto, K, Minamishima, T, Futuya, M, Satoh, T, Yoshino, H, Miyoshi, T, Tanaka, H, Kaneko, A, Matsumoto, K, Imanishi, J, Motoji, Y, Mochizuki, Y, Minami, H, Kawai, H, Hirata, K, Wutthimanop, A, See, O, Vathesathokit, P, Yamwong, S, Sritara, P, Rosner, A, Kildal, AB, Stenberg, TA, Myrmel, T, How, OJ, Capriolo, M, Frea, S, Giustetto, C, Scrocco, C, Benedetto, S, Grosso Marra, W, Morello, M, Gaita, F, Garcia-Gonzalez, P, Cozar-Santiago, P, Chacon-Hernandez, N, Ferrando-Beltran, M, Fabregat-Andres, O, De La Espriella-Juan, R, Fontane-Martinez, C, Jurado-Sanchez, R, Morell-Cabedo, S, Ridocci-Soriano, F, Mihaila, S, Piasentini, E, Muraru, D, Peluso, D, Casablanca, S, Puma, L, Naso, P, Iliceto, S, Vinereanu, D, Badano, LP, Tarzia, P, Villano, A, Figliozzi, S, Russo, G, Parrinello, R, Lamendola, P, Sestito, A, Lanza, GA, Crea, F, Sulemane, S, Panoulas, VF, Bratsas, A, Frankel, AH, Nihoyannopoulos, P, Dores, H, Andrade, MJ, Almeida, MS, Goncalves, PA, Branco, P, Gaspar, A, Gomes, A, Horta, E, Carvalho, MS, Mendes, M, Yue, WS, Li, XY, Chen, Y, Luo, Y, Gu, P, Yiu, KH, Siu, CW, Tse, HF, Cho, EJ, Lee, SH, Hwang, BH, Kim, DB, Jang, SW, Jeon, HK, Youn, HJ, and Kim, JH
- Abstract
Background: Progress in the technique of TAVR requires good knowledge of the aortic root. With this aim new specialized software appears, with the ability of automated quantitative modeling of the AV and root from 3D TEE.The purpose of this study was to validate this model with the measurements made manually. Methods: Eight patients undergoing TAVR in our center where included. The diameters of the aortic annulus, sinotubular union (STU) and sinus of valsalva (SV) were measured by 2D TEE; diameters and areas of aortic annulus, STU and SV as well as anatomic aortic valve area were measured by 3D TEE. Afterwards, the images were analyzed using the new software (Figure 1). Results. We showed good correlation with aortic annulus diameter measured by 2D TEE (r:,832 p:,01) and excellent correlation with one of the aortic annulus diameter measured by 3D TEE (r:,941 p:,00). The same happened with the area (r:,720 p:,04). Regarding the measurements at SV level, the correlations between the diameters by 2D TEE and 3D TEE with the measurements obtained with the new model were the following (r:,771;p:,025) and (r:,797;p:,018). The correlation of the area was also good (r:,812 p:,014).An excellent correlation was found between the measurements at UST level. UST diameter by 2D TEE (r:,818;P:,013), by ETE3D (r:,800;p:,017) and area (r:,844;p:,008).Finally, the anatomic aortic valve area measured by the new model showed significant correlation with the 3D TTE (r:,830 p:,011). Conclusions. There is a proper correlation between manual and automated measurements analyzed by the new model. The feasibility of determine the TAVR results with geometric models based on image, prior to procedure, is one of the possibilities of this new software. Prospective studies are necessary to define its applicability.
Figure 1 - Published
- 2013
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- View/download PDF
25. Poster session Friday 13 December - AM: 13/12/2013, 08:30-12:30 * Location: Poster area
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Gertsen, M, Nemes, A, Szolnoky, G, Altmayer, A, Gavaller, H, Kemeny, L, Forster, T, Park, J R, Jo, SY, Kim, KH, Kho, JS, Kwack, CH, Hwang, JY, Popovic, D, Ostojic, MC, Petrovic, M, Vujisic-Tesic, B, Arandjelovic, A, Banovic, M, Vukcevic, V, Petrovic, I, Popovic, B, Damjanovic, S, Placido, R, Marta, L, Ramalho, AR, Nobre Menezes, M, Cortez-Dias, N, Martins, S, Goncalves, S, Almeida, AG, Silva-Marques, J, Nunes-Diogo, A, Germanakis, I, Kakouri, P, Karachaliou, M, Vassilaki, M, Chatzi, L, Roumeliotaki, T, Kogevinas, M, Horst, J-P, Kelter-Kloepping, A, Koerperich, H, Barth, P, Haas, NA, Kececioglu, D, Laser, KT, Laser, KT, Horst, J-P, Kelter-Kloepping, A, Barth, P, Haas, NA, Kececioglu, D, Koerperich, H, Samiei, N, Nabati, M, Azari-Jafari, M, Vakili-Zarch, A, Parsaee, M, Haghjoo, M, Ahmed, A J, Val-Mejias, J E, Von Bulow, F M, Baltussen, E J M, Darban, AM, Claus, P, Voigt, JU, Rodriguez Munoz, DA, Moya Mur, JL, Gonzalez, A, Garcia Martin, A, Becker Filho, D, Fernandez Santos, S, Lazaro Rivera, C, Recio Vazquez, M, Fernandez Golfin, C, Zamorano Gomez, JL, Bandera, F, Pellegrino, M, Generati, G, Alfonzetti, E, Donghi, V, Castelvecchio, S, Garatti, A, Menicanti, L, Guazzi, M, Kowalik, E, Klisiewicz, A, Hoffman, P, Kim, EJ, Cho, I J, Oh, J, Chang, HJ, Park, J, Shin, S, Shim, CY, Hong, GR, Ha, JW, Chung, N, Park, JH, Lee, HS, Kim, HS, Ahn, KT, Kim, JH, Lee, JH, Choi, SW, Jeong, JO, Seong, IW, Holzendorf, V, Gelbrich, G, Wachter, R, Loeffler, M, Pieske, BM, Broda, A, Edelmann, F, Failure, German Competence Network for Heart, Kim, YH, Kim, DH, Kim, SH, Ahn, JC, Song, WH, Hashimoto, G, Suzuki, M, Yoshikawa, H, Otsuka, T, Kusunose, Y, Nakamura, M, Sugi, K, De Knegt, M C, Biering-Sorensen, T, Sogaard, P, Sivertsen, J, Jensen, JS, Mogelvang, R, Murbraech, K, Smeland, KH, Holte, H, Loge, JH, Kiserud, CE, Aakhus, S, Peteiro, J, Gargallo-Fernandez, P, Garcia-Guimaraes, M, Bouzas-Mosquera, A, Yanez-Wronenburger, JC, Martinez-Ruiz, D, Castro-Beiras, A, Trzcinski, PT, Jaskowski, MJ, Nowak, JN, Pawlus, MP, Figiel, LF, Kasprzak, JDK, Lipiec, PL, Zhong, L, Su, Y, Teo, SK, Le, TT, Tan, RS, Tesic, M, Djordjevic-Dikic, A, Giga, V, Jovanovic, I, Paunovic, I, Petrovic, MT, Trifunovic, D, Beleslin, B, Stepanovic, J, Vujisic-Tesic, B, Parato, V M, Partemi, M, Nardini, E, Pasanisi, E, Park, T-H, Lee, J-E, Lee, D-H, Park, J-S, Park, K, Kim, M-H, Kim, Y-D, Vegsundvag, J, Holte, E, Wiseth, R, Hegbom, K, Hole, T, Fusini, L, Tamborini, G, Ghulam Ali, S, Muratori, M, Gripari, P, Cefalu, C, Maffessanti, F, Celeste, F, Alamanni, F, Pepi, M, Negrea, SL, Alexandrescu, C, Rossi, P, Iacuzio, L, Dreyfus, G, Moatemri, F, Mahdhaoui, A, Bouraoui, H, Ernez, S, Jeridi, G, Yuan, L, Feng, JL, Jin, X Y, Seoane Garcia, T, Delgado Ortega, M, Mesa Rubio, D, Ruiz Ortiz, M, Martin Hidalgo, M, Carrasco Avalos, F, Casares Mediavilla, J, Alados, P, Lopez Granados, A, Suarez De Lezo Cruz Conde, J, Mutuberria Urdaniz, M, Rodriguez-Palomares, JF, Baneras-Rius, JF, Acosta-Velez, JG, Buera-Surribas, I, 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Jensen, MT, Rossing, P, Sogaard, P, Andersen, HU, Bech, J, Hansen, TF, Gustafsson, I, Galatius, S, Jensen, JS, Shang, Q, Zhang, Q, Sanderson, JE, Tam, LS, Lee, A PW, Fang, F, Li, E KM, Yu, CM, Bruin De- Bon, HACM, Tan, HL, Hardziyenka, M, Symersky, P, Bonta, PI, Brink Van Den, RBA, Bouma, BJ, Bader, RS, Punn, R, Silverman, N, Cruz, C, Pinho, T, Lebreiro, A, Dias, CC, Silva Cardoso, J, Julia Maciel, M, Melao, F, Ribeiro, V, Cruz, C, Maciel, MJ, Attenhofer Jost, C H, Schmidt, D, Pfyffer, M, Biaggi, P, Seifert, B, Weber, R, De Pasquale, G, Kretschmar, O, Seeliger, T, Greutmann, M, Johansson, M C, Mirzada, N, Ladenvall, P, Besiroglu, F, Samadov, F, Atas, H, Sari, I, Tufekcioglu, O, Birincioglu, CL, Acar, B, Duman, I, Colak, A, Zagatina, A, Krylova, L, Zhuravskaya, N, Vareldzhyan, Y, Tyurina, TV, Clitsenko, O, Castro, M, Dores, H, Carvalho, MS, Reis, C, Horta, E, Trabulo, MS, Andrade, MJ, Mendes, M, Gasior, Z, Plonska-Gosciniak, E, Wita, K, Mizia-Stec, K, Kulach, A, Szwed, H, Chrzanowski, L, Tomaszewski, A, Sinkiewicz, W, Wojciechowska, C, Aggeli, C, Felekos, I, Stergiou, P, Roussakis, G, Kakiouzi, V, Kastellanos, S, Koutagiar, I, Stefanadis, C, Bouzas Mosquera, A, Peteiro, J, Alvarez-Garcia, N, Broullon, FJ, Garcia-Guimaraes, MM, Martinez-Ruiz, D, Yanez-Wonenburger, JC, Bouzas-Zubeldia, B, Fabregas, R, Castro-Beiras, A, Brugger, N, Huerzeler, M, Wustmann, K, Wahl, A, Steck, H, Seiler, C, Sarwar, R, Malhotra, A, Wong, KC, Betts, TR, Bashir, Y, Rajappan, K, Newton, JD, Casanova Rodriguez, C, Cano Carrizal, R, Iglesias Del Valle, D, Martin Penato Molina, A, Garcia Garcia, A, Prieto Moriche, E, Alvarez Rubio, J, Paredes Gonzalez, B, De Juan Baguda, J, Plaza Perez, I, Van Den Oord, SCH, Akkus, Z, Roeters Van Lennep, JE, Bosch, JG, Van Der Steen, AFW, Sijbrands, EJG, Schinkel, AFL, Muraru, D, Calore, C, Badano, LP, Melacini, C, Mihaila, S, Peluso, D, Puma, L, Kocabay, G, Rizzon, G, Iliceto, S, Bochard Villanueva, B, Paya-Serrano, R, Garcia-Gonzalez, P, Fabregat-Andres, O, Perez-Bosca, JL, Cubillos-Arango, A, Ferrando-Beltran, M, Chacon-Hernandez, N, Albiach-Montanana, C, Ridocci-Soriano, F, Ancona, R, Comenale Pinto, S, Caso, P, Arenga, F, Coppola, MG, Calabro, R, Tarr, A, Stoebe, S, Pfeiffer, D, Hagendorff, A, Hollekim, SM, Bjorgaas, MR, Tjonna, AE, Wisloff, U, Ingul, CB, (CERG), Cardiac Exercise Research Group, Oreto, L, Zito, C, Cusma-Piccione, M, Calabro, MP, Todaro, MC, Vita, GL, Messina, S, Vita, G, Sframeli, M, Carerj, S, Remoli, R, Lamberti, F, Bellini, C, Mercurio, M, Dottori, S, Bellusci, F, Mazzuca, V, Gaspardone, A, Rimbas, RC, Enescu, OA, Mihaila, S, Ciobanu, A, Vinereanu, D, Henri, C, Magne, J, Dulgheru, R, Laaraibi, S, Voilliot, D, Kou, S, Pierard, L, Lancellotti, P, Wellnhofer, E, Kriatselis, C, Gerds-Li, H, Furundzija, VESNA, Thanabalasingam, U, Fleck, E, Graefe, M, Kouris, N, Keramida, K, Karidas, V, Kostopoulos, V, Kostakou, P, Mprempos, G, Olympios, CD, Duchateau, N, Giraldeau, G, Gabrielli, L, Penela, D, Evertz, R, Mont, L, Brugada, J, Berruezo, A, Bijnens, BH, Sitges, M, Bernard, A, Donal, E, Reynaud, A, Schnell, F, Daubert, JC, Leclercq, C, Hernandez, A, Keramida, K, Kouris, N, Kostopoulos, V, Karidas, V, Dagre, A, Ntarladimas, I, Damaskos, D, Stamatelatou, M, Olympios, CD, Panetta, G L, Peraldo Neja, C, Urbano Moral, JA, Evangelista, A, Azzolini, P, Gaudio, C, Pandian, NG, Barbier, P, Mirea, O, Savioli, G, Cefalu, C, Guglielmo, M, Fusini, L, Maltagliati, A, Hamdy, AM, Fereig, HM, Nabih, MA, Abdel-Aziz, A, Ali, AA, Buccheri, S, Mangiafico, S, Leggio, S, B, VE, Tropea, L, Tamburino, C, Monte, I P, Garcia-Gonzalez, P, Chacon-Hernandez, N, Cozar-Santiago, P, Fabregat-Andres, O, Sanchez-Jurado, R, Higueras-Ortega, L, Albiach-Motanana, C, Perez-Bosca, JL, Paya-Serrano, R, Ridocci-Soriano, F, Flori, M, Valette, F, Guijarro, D, Pallardy, A, Le Tourneau, T, Kraeber-Bodere, F, Piriou, N, Saxena, A, Ramakrishnan, S, Tulunay Kaya, C, Ongun, A, Kilickap, M, Candemir, B, Altin, AT, Gerede, M, Ozcan, OU, Erol, C, Yue, WS, Yang, F, Huang, D, Gu, P, Luo, Y, Lv, Z, Siu, CW, Tse, HF, Yiu, KH, Saura Espin, D, Lopez Cuenca, A, Espinosa Garcia, MD, Oliva Sandoval, MJ, Lopez Ruiz, M, Gonzalez Carrillo, J, Garcia Navarro, MJ, Valdes Chavarri, M, De La Morena Valenzuela, G, Gustafsson, U, Spuhler, JH, Hoffman, J, Brodin, LÅ, Kisko, A, Dernarova, L, Hudakova, A, Santova, T, Jakubikova, M, Mikulak, M, Horlenko, O, Kishko, N, Svystak, V, Shyp, A, Faden, G, Gaibazzi, N, Rigo, F, Mureddu, GF, Moreo, A, Bussadori, G, Facchetti, R, Cesana, F, Giannattasio, C, Faggiano, P, and group, APRES collaborative
- Abstract
Pulmonary vascular dysfunction is claimed to be a contributor to the development of pulmonary hypertension (PH). Impaired systemic vascular reactivity is one of the essential factors in the pathogenesis of cardiovascular disease. The aim of the investigation was to study whether there is any association between systemic vascular function and pulmonary artery pressure (PAP) in patients who have associated causes for PH development, such as coronary heart disease (CHD) and chronic obstructive pulmonary disease (COPD). Methods: The brachial artery vasodilator responses were measured by the ultrasound technique in twenty patients with mild to moderate COPD (group I) and twenty age–matched and COPD stage-matched patients who had past history of myocardial infarction (NYHA II) (group II).Conventional echocardiographic variables were measured in the said patients too. Results: Both flow-mediated dilatation (FMD) and nitrate-mediated dilatation (NMD) were significantly lower, and PAP was significantly higher in the group II patients compared to the same parameters of group I patients. NMD was inversely correlated with PAP (r=-0.7, p=0.02) in group I patients. There was no interrelation between FMD and PAP in patients from group I. Neither FMD nor NMD were correlated with PAP in group II patients. A significant positive correlation between PAP and left ventricular mass index (r=0.8, p=0.003) was revealed in the said patients as well. Conclusions: Attenuated vasodilator response of brachial artery to nitroglycerine is associated with PAP elevation in COPD patients. PH is closely related to cardiac remodeling in COPD patients in whom CHD developed. These data suggest different "stages" of vascular and cardiac remodeling in patients with COPD alone and in coexistence with CHD. The obtained data can be useful in the selection of treatment as regards these patient categories.
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- 2013
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26. Review of first 5 years of screening for familial hypercholesterolaemia in the Netherlands.
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Umans-Eckenhausen MAW, Defesche JC, Sijbrands EJG, Scheerder RLJ, and Kastelein JJP
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- 2001
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27. Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach
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Anho H Liem, Albert Hofman, Adriana C. Blommesteijn-Touw, Iris Kindt, Jeanette Erdman, Mojgan Yazdanpanah, Fátima Almagro, Frans van der Ouderaa, Ranitha Vongpromek, Fernando Civeira, Jose M. Ordovas, Peter W. de Leeuw, Keith J. Johnson, Hrobjartur D. Karlsson, Monique T. Mulder, Daniëlla M. Oosterveer, Tony Dadd, Martin R. Green, Joep C. Defesche, Roeland Huijgen, Abbas Dehghan, Maarten L. Simoons, Hilma Holm, Leonie C. van Vark-van der Zee, Leiv Ose, Aeilko H. Zwinderman, Cornelia M. van Duijn, Gisle Langslet, Luis Masana, Maurizio Averna, Gudmar Thorleifsson, Jorie Versmissen, A F L Schinkel, Jaap Kwekkeboom, Yurii S. Aulchenko, Jacqueline C. M. Witteman, John J.P. Kastelein, Heribert Schunkert, Steve E. Humphries, Arne S. Schaefer, Stefano Bertolini, Emilio Ros, Xavier Pintó, Andrew Neil, André G. Uitterlinden, Eric J.G. Sijbrands, Amelia Jarman, Sebastiano Calandra, Other departments, Amsterdam Cardiovascular Sciences, Experimental Vascular Medicine, Amsterdam Public Health, Epidemiology and Data Science, Vascular Medicine, Psychiatrie & Neuropsychologie, MUMC+: MA Alg Interne Geneeskunde (9), RS: CARIM - R3 - Vascular biology, Interne Geneeskunde, Family Medicine, Versmissen, J, Oosterveer, DM, Yazdanpanah, M, Dehghan, A, Hólm, H, Erdman, J, Aulchenko, YS, Thorleifsson, G, Schunkert, H, Huijgen, R, Vongpromek, R, Uitterlinden, AG, Defesche, JC, van Duijn, CM, Mulder, M, Dadd, T, Karlsson, HD, Ordovas, J, Kindt, I, Jarman, A, Hofman, A, van Vark-van der Zee, L, Blommesteijn-Touw, AC, Kwekkeboom, J, Liem, AH, van der Ouderaa, FJ, Calandra, S, Bertolini, S, Averna, M, Langslet, G, Ose, L, Ros, E, Almagro, F, de Leeuw, PW, Civeira, F, Masana, L, Pintó, X, Simoons, ML, Schinkel, AFL, Green, MR, Zwinderman, AH, Johnson, KJ, Schaefer, A, Neil, A, Witteman, JCM, Humphries, SE, Kastelein, JJP, Sijbrands, EJG, Internal Medicine, Epidemiology, Gastroenterology & Hepatology, and Cardiology
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Adult ,Male ,Risk ,Settore MED/09 - Medicina Interna ,Genotype ,Population ,Coronary Disease ,Single-nucleotide polymorphism ,Genome-wide association study ,Comorbidity ,Familial hypercholesterolemia ,Quantitative trait locus ,Biology ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Article ,Hyperlipoproteinemia Type II ,Young Adult ,symbols.namesake ,Gene Frequency ,Risk Factors ,Odds Ratio ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,education ,Alleles ,Genetics (clinical) ,Aged ,Aged, 80 and over ,Mutation ,education.field_of_study ,familial hypercholesterolemia ,PCSK9 ,genetic risk factor ,Genetic Variation ,Middle Aged ,medicine.disease ,Bonferroni correction ,Receptors, LDL ,Case-Control Studies ,symbols ,Female ,Genome-Wide Association Study - Abstract
Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Illumina HumanHap550K chip. In the next stage, two independent samples (one from the Netherlands and one from Italy, Norway, Spain, and the United Kingdom) of FH patients were used as replication samples. In the initial GWA analysis, we identified 29 independent single nucleotide polymorphisms (SNPs) with suggestive associations with premature CHD (P
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- 2015
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28. Arterial intima-media thickness in children heterozygous for familial hypercholesterolaemia.
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Wiegman A, de Groot E, Hutten BA, Rodenburg J, Gort J, Bakker HD, Sijbrands EJG, and Kastelein JJP
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- 2004
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29. The effects of APOE4 and familial Alzheimer's disease mutations on free fatty acid profiles in mouse brain are age- and sex-dependent.
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den Hoedt S, Crivelli SM, Dorst-Lagerwerf KY, Leijten FPJ, Losen M, de Vries HE, Sijbrands EJG, Verhoeven AJM, Martinez-Martinez P, and Mulder MT
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- Animals, Female, Humans, Male, Mice, Age Factors, Aging genetics, Aging metabolism, Mice, Inbred C57BL, Mice, Transgenic, Sex Characteristics, Alzheimer Disease metabolism, Alzheimer Disease genetics, Apolipoprotein E4 genetics, Brain metabolism, Fatty Acids, Nonesterified metabolism, Mutation genetics
- Abstract
APOE4 encoding apolipoprotein (Apo)E4 is the strongest genetic risk factor for Alzheimer's disease (AD). ApoE is key in intercellular lipid trafficking. Fatty acids are essential for brain integrity and cognitive performance and are implicated in neurodegeneration. We determined the sex- and age-dependent effect of AD and APOE4 on brain free fatty acid (FFA) profiles. FFA profiles were determined by LC-MS/MS in hippocampus, cortex, and cerebellum of female and male, young (≤3 months) and older (>5 months), transgenic APOE3 and APOE4 mice with and without five familial AD (FAD) mutations (16 groups; n = 7-10 each). In the different brain regions, females had higher levels than males of either saturated or polyunsaturated FFAs or both. In the hippocampus of young males, but not of older males, APOE4 and FAD each induced 1.3-fold higher levels of almost all FFAs. In young and older females, FAD and to a less extent APOE4-induced shifts among saturated, monounsaturated, and polyunsaturated FFAs without affecting total FFA levels. In cortex and cerebellum, APOE4 and FAD had only minor effects on individual FFAs. The effects of APOE4 and FAD on FFA levels and FFA profiles in the three brain regions were strongly dependent of sex and age, particularly in the hippocampus. Here, most FFAs that are affected by FAD are similarly affected by APOE4. Since APOE4 and FAD affected hippocampal FFA profiles already at young age, these APOE4-induced alterations may modulate the pathogenesis of AD., (© 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)
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- 2024
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30. Quantification of the effect of GLP-1R agonists on body weight using in vitro efficacy information: An extension of the Hall body composition model.
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Bosch R, Sijbrands EJG, and Snelder N
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- Humans, Weight Loss drug effects, Energy Intake drug effects, Anti-Obesity Agents pharmacology, Anti-Obesity Agents administration & dosage, Male, Liraglutide pharmacology, Liraglutide administration & dosage, Glucagon-Like Peptides pharmacology, Glucagon-Like Peptides administration & dosage, Body Composition drug effects, Body Weight drug effects, Obesity drug therapy, Models, Biological, Glucagon-Like Peptide-1 Receptor Agonists
- Abstract
Obesity has become a major public health concern worldwide. Pharmacological interventions with the glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promising results in facilitating weight loss and improving metabolic outcomes in individuals with obesity. Quantifying drug effects of GLP-1RAs on energy intake (EI) and body weight (BW) using a QSP modeling approach can further increase the mechanistic understanding of these effects, and support obesity drug development. An extensive literature-based dataset was created, including data from several diet, liraglutide and semaglutide studies and their effects on BW and related parameters. The Hall body composition model was used to quantify and predict effects on EI. The model was extended with (1) a lifestyle change/placebo effect on EI, (2) a weight loss effect on activity for the studies that included weight management support, and (3) a GLP-1R agonistic effect using in vitro potency efficacy information. The estimated reduction in EI of clinically relevant dosages of semaglutide (2.4 mg) and liraglutide (3.0 mg) was 34.5% and 13.0%, respectively. The model adequately described the resulting change in BW over time. At 20 weeks the change in BW was estimated to be -17% for 2.4 mg semaglutide and -8% for 3 mg liraglutide, respectively. External validation showed the model was able to predict the effect of semaglutide on BW in the STEP 1 study. The GLP-1RA body composition model can be used to quantify and predict the effect of novel GLP-1R agonists on BW and changes in underlying processes using early in vitro efficacy information., (© 2024 The Author(s). CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
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- 2024
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31. Characterisation of cotadutide's dual GLP-1/glucagon receptor agonistic effects on glycaemic control using an in vivo human glucose regulation quantitative systems pharmacology model.
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Bosch R, Petrone M, Arends R, Vicini P, Sijbrands EJG, Hoefman S, and Snelder N
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- Humans, Male, Glycemic Control, Middle Aged, Female, Adult, Glucagon pharmacology, Glucagon metabolism, Insulin metabolism, Insulin pharmacology, Obesity drug therapy, Obesity metabolism, Glucagon-Like Peptide 1 agonists, Glucagon-Like Peptide 1 pharmacology, Dose-Response Relationship, Drug, Peptides, Receptors, Glucagon agonists, Receptors, Glucagon metabolism, Glucagon-Like Peptide-1 Receptor metabolism, Hypoglycemic Agents pharmacology, Blood Glucose drug effects, Blood Glucose metabolism, Models, Biological, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 metabolism, Glucagon-Like Peptide-1 Receptor Agonists
- Abstract
Background and Purpose: Cotadutide is a dual GLP-1 and glucagon receptor agonist with balanced agonistic activity at each receptor designed to harness the advantages on promoting liver health, weight loss and glycaemic control. We characterised the effects of cotadutide on glucose, insulin, GLP-1, GIP, and glucagon over time in a quantitative manner using our glucose dynamics systems model (4GI systems model), in combination with clinical data from a multiple ascending dose/Phase 2a (MAD/Ph2a) study in overweight and obese subjects with a history of Type 2 diabetes mellitus (NCT02548585)., Experimental Approach: The cotadutide PK-4GI systems model was calibrated to clinical data by re-estimating only food related parameters. In vivo cotadutide efficacy was scaled based on in vitro potency. The model was used to explore the effect of weight loss on insulin sensitivity and predict the relative contribution of the GLP-1 and glucagon receptor agonistic effects on glucose., Key Results: Cotadutide MAD/Ph2a clinical endpoints were successfully predicted. The 4GI model captured a positive effect of weight loss on insulin sensitivity and showed that the stimulating effect of glucagon on glucose production counteracts the GLP-1 receptor-mediated decrease in glucose, resulting in a plateau for glucose decrease around a 200-μg cotadutide dose., Conclusion and Implications: The 4GI quantitative systems pharmacology model was able to predict the clinical effects of cotadutide on glucose, insulin, GLP-1, glucagon and GIP given known in vitro potency. The analyses demonstrated that the quantitative systems pharmacology model, and its successive refinements, will be a valuable tool to support the clinical development of cotadutide and related compounds., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
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- 2024
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32. Apolipoprotein-CIII O-Glycosylation Is Associated with Micro- and Macrovascular Complications of Type 2 Diabetes.
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Naber A, Demus D, Slieker RC, Nicolardi S, Beulens JWJ, Elders PJM, Lieverse AG, Sijbrands EJG, 't Hart LM, Wuhrer M, and van Hoek M
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Diabetic Angiopathies metabolism, Diabetic Angiopathies genetics, Diabetic Angiopathies etiology, Diabetic Retinopathy metabolism, Diabetic Retinopathy genetics, Diabetic Retinopathy etiology, Glycosylation, Polymorphism, Single Nucleotide, Apolipoprotein C-III genetics, Apolipoprotein C-III metabolism, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 genetics
- Abstract
Apolipoprotein-CIII (apo-CIII) inhibits the clearance of triglycerides from circulation and is associated with an increased risk of diabetes complications. It exists in four main proteoforms: O-glycosylated variants containing either zero, one, or two sialic acids and a non-glycosylated variant. O-glycosylation may affect the metabolic functions of apo-CIII. We investigated the associations of apo-CIII glycosylation in blood plasma, measured by mass spectrometry of the intact protein, and genetic variants with micro- and macrovascular complications (retinopathy, nephropathy, neuropathy, cardiovascular disease) of type 2 diabetes in a DiaGene study ( n = 1571) and the Hoorn DCS cohort ( n = 5409). Mono-sialylated apolipoprotein-CIII (apo-CIII
1 ) was associated with a reduced risk of retinopathy (β = -7.215, 95% CI -11.137 to -3.294) whereas disialylated apolipoprotein-CIII (apo-CIII2 ) was associated with an increased risk (β = 5.309, 95% CI 2.279 to 8.339). A variant of the GALNT2 -gene (rs4846913), previously linked to lower apo-CIII0a , was associated with a decreased prevalence of retinopathy (OR = 0.739, 95% CI 0.575 to 0.951). Higher apo-CIII1 levels were associated with neuropathy (β = 7.706, 95% CI 2.317 to 13.095) and lower apo-CIII0a with macrovascular complications (β = -9.195, 95% CI -15.847 to -2.543). In conclusion, apo-CIII glycosylation was associated with the prevalence of micro- and macrovascular complications of diabetes. Moreover, a variant in the GALNT2 -gene was associated with apo-CIII glycosylation and retinopathy, suggesting a causal effect. The findings facilitate a molecular understanding of the pathophysiology of diabetes complications and warrant consideration of apo-CIII glycosylation as a potential target in the prevention of diabetes complications.- Published
- 2024
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33. Defining type 2 diabetes polygenic risk scores through colocalization and network-based clustering of metabolic trait genetic associations.
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Ghatan S, van Rooij J, van Hoek M, Boer CG, Felix JF, Kavousi M, Jaddoe VW, Sijbrands EJG, Medina-Gomez C, Rivadeneira F, and Oei L
- Subjects
- Humans, Child, Genetic Risk Score, Cluster Analysis, Obesity genetics, Diabetes Mellitus, Type 2 genetics, Insulin Resistance genetics
- Abstract
Background: Type 2 diabetes (T2D) is a heterogeneous and polygenic disease. Previous studies have leveraged the highly polygenic and pleiotropic nature of T2D variants to partition the heterogeneity of T2D, in order to stratify patient risk and gain mechanistic insight. We expanded on these approaches by performing colocalization across GWAS traits while assessing the causality and directionality of genetic associations., Methods: We applied colocalization between T2D and 20 related metabolic traits, across 243 loci, to obtain inferences of shared casual variants. Network-based unsupervised hierarchical clustering was performed on variant-trait associations. Partitioned polygenic risk scores (PRSs) were generated for each cluster using T2D summary statistics and validated in 21,742 individuals with T2D from 3 cohorts. Inferences of directionality and causality were obtained by applying Mendelian randomization Steiger's Z-test and further validated in a pediatric cohort without diabetes (aged 9-12 years old, n = 3866)., Results: We identified 146 T2D loci that colocalized with at least one metabolic trait locus. T2D variants within these loci were grouped into 5 clusters. The clusters corresponded to the following pathways: obesity, lipodystrophic insulin resistance, liver and lipid metabolism, hepatic glucose metabolism, and beta-cell dysfunction. We observed heterogeneity in associations between PRSs and metabolic measures across clusters. For instance, the lipodystrophic insulin resistance (Beta - 0.08 SD, 95% CI [- 0.10-0.07], p = 6.50 × 10
-32 ) and beta-cell dysfunction (Beta - 0.10 SD, 95% CI [- 0.12, - 0.08], p = 1.46 × 10-47 ) PRSs were associated to lower BMI. Mendelian randomization Steiger analysis indicated that increased T2D risk in these pathways was causally associated to lower BMI. However, the obesity PRS was conversely associated with increased BMI (Beta 0.08 SD, 95% CI 0.06-0.10, p = 8.0 × 10-33 ). Analyses within a pediatric cohort supported this finding. Additionally, the lipodystrophic insulin resistance PRS was associated with a higher odds of chronic kidney disease (OR 1.29, 95% CI 1.02-1.62, p = 0.03)., Conclusions: We successfully partitioned T2D genetic variants into phenotypic pathways using a colocalization first approach. Partitioned PRSs were associated to unique metabolic and clinical outcomes indicating successful partitioning of disease heterogeneity. Our work expands on previous approaches by providing stronger inferences of shared causal variants, causality, and directionality of GWAS variant-trait associations., (© 2024. The Author(s).)- Published
- 2024
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34. Age- and sex-based heterogeneity in coronary artery plaque presence and burden in familial hypercholesterolemia: A multi-national study.
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Nasir K, Mszar R, Cainzos-Achirica M, Grandhi GR, Tromp TR, Alonso R, Bittencourt MS, Bruckert E, Díaz-Díaz JL, Gallo A, Hovingh GK, Miname MH, Muñiz-Grijalvo O, Pang J, de Isla LP, Sijbrands EJG, Watts GF, Mata P, and Santos RD
- Abstract
Objectives: Individuals with familial hypercholesterolemia (FH) are at an increased risk for coronary artery disease (CAD). While prior research has shown variability in coronary artery calcification (CAC) among those with FH, studies with small sample sizes and single-center recruitment have been limited in their ability to characterize CAC and plaque burden in subgroups based on age and sex. Understanding the spectrum of atherosclerosis may result in personalized risk assessment and tailored allocation of costly add-on, non-statin lipid-lowering therapies. We aimed to characterize the presence and burden of CAC and coronary plaque on computed tomography angiography (CTA) across age- and sex-stratified subgroups of individuals with FH who were without CAD at baseline., Methods: We pooled 1,011 patients from six cohorts across Brazil, France, the Netherlands, Spain, and Australia. Our main measures of subclinical atherosclerosis included CAC ranges (i.e., 0, 1-100, 101-400, >400) and CTA-derived plaque burden (i.e., no plaque, non-obstructive CAD, obstructive CAD)., Results: Ninety-five percent of individuals with FH (mean age: 48 years; 54% female; treated LDL-C: 154 mg/dL) had a molecular diagnosis and 899 (89%) were on statin therapy. Overall, 423 (42%) had CAC=0, 329 (33%) had CAC 1-100, 160 (16%) had CAC 101-400, and 99 (10%) had CAC >400. Compared to males, female patients were more likely to have CAC=0 (48% [ n = 262] vs 35% [ n = 161]) and no plaque on CTA (39% [ n = 215] vs 26% [ n = 120]). Among patients with CAC=0, 85 (20%) had non-obstructive CAD. Females also had a lower prevalence of obstructive CAD in CAC 1-100 (8% [ n = 15] vs 18% [ n = 26]), CAC 101-400 (32% [ n = 22] vs 40% [ n = 36]), and CAC >400 (52% [ n = 16] vs 65% [ n = 44]). Female patients aged 50-59 years were less likely to have obstructive CAD in CAC >400 (55% [ n = 6] vs 70% [ n = 19])., Conclusion: In this large, multi-national study, we found substantial age- and sex-based heterogeneity in CAC and plaque burden in a cohort of predominantly statin-treated individuals with FH, with evidence for a less pronounced increase in atherosclerosis among female patients. Future studies should examine the predictors of resilience to and long-term implications of the differential burden of subclinical coronary atherosclerosis in this higher risk population., Competing Interests: Dr. Nasir is supported by the Katz Academy for Translational Research. Dr. Santos received honoraria for consulting, speaker activities and research from Abbott, Ache, Amgen, Astra Zeneca, EMS, Hypera, Libbs, Esperion, Kowa, Getz pharma, PTC therapeutics, Novo-Nordisk, Novartis, Merck, MSD, Pfizer, and Sanofi, he also receives a research scholarship from Conselho Nacional de Pesquisa e Desenvolvimento Tecnológico, Brazil, (CNPq) #303734/2018-3. Dr. Watts has received honoraria related to consulting, research and/or speaker activities from: Amgen, Arrowhead, AstraZeneca, Esperion, Kowa, Novartis, and Sanofi/Regeneron. Dr. Hovingh reports research grants from the Netherlands Organization for Scientific Research (vidi 016.156.445), CardioVascular Research Initiative, European Union and the Klinkerpad fonds, institutional research support from Aegerion, Amgen, AstraZeneca, Eli Lilly, Genzyme, Ionis, Kowa, Pfizer, Regeneron, Roche, Sanofi, and The Medicines Company; speaker's bureau and consulting fees from Amgen, Aegerion, Sanofi, and Regeneron until April 2019 (fees paid to the academic institution); and part-time employment at Novo-Nordisk A/S, Denmark since April 2019. Dr. Gallo has received grants and personal fees from Amgen, Sanofi and Regeneron, Mylan Viatris, MSD, Akcea Therapeutics, Amryt, Novartis, Servier, Eli Lilly, Ultragenyx. Dr. Sijbrands has received a research grants from Amgen and the European Union. Dr. Bruckert has received honoraria from Amgen, Genfit, MSD, Sanofi-Regeneron, Novartis, Danone, Amarin, Akcea, Servier, MYLAN, Silence Therapeutic. Dr. Miname has received honoraria for speaker activities from Amgen. Other authors report no disclosures., (© 2023 The Author(s).)
- Published
- 2023
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35. Identifying lipid traces of atherogenic mechanisms in human carotid plaque.
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Slijkhuis N, Towers M, Mirzaian M, Korteland SA, Heijs B, van Gaalen K, Nieuwenhuizen I, Nigg A, van der Heiden K, de Rijke YB, van der Lugt A, Sijbrands EJG, Claude E, and van Soest G
- Subjects
- Animals, Humans, Mass Spectrometry, Carotid Arteries, Phospholipids, Spectrometry, Mass, Electrospray Ionization methods, Atherosclerosis, Plaque, Atherosclerotic chemistry
- Abstract
Background and Aims: Lipids play an important role in atherosclerotic plaque development and are interesting candidate predictive biomarkers. However, the link between circulating lipids, accumulating lipids in the vessel wall, and plaque destabilization processes in humans remains largely unknown. This study aims to provide new insights into the role of lipids in atherosclerosis using lipidomics and mass spectrometry imaging to investigate lipid signatures in advanced human carotid plaque and plasma samples., Methods: We used lipidomics and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to investigate lipid signatures of advanced human carotid plaque and plasma obtained from patients who underwent carotid endarterectomy (n = 14 out of 17 whose plaque samples were analyzed by DESI-MSI). Multivariate data analysis and unsupervised clustering were applied to identify lipids that were the most discriminative species between different patterns in plaque and plasma. These patterns were interpreted by quantitative comparison with conventional histology., Results: Lipidomics detected more than 300 lipid species in plasma and plaque, with markedly different relative abundances. DESI-MSI visualized the spatial distribution of 611 lipid-related m/z features in plaques, of which 330 m/z features could be assigned based on exact mass, comparison to the lipidomic data, and high mass resolution MSI. Matching spatial lipid patterns to histological areas of interest revealed several molecular species that were colocalized with pertinent disease processes in plaque including specific sphingomyelin and ceramide species with calcification, phospholipids and free fatty acids with inflammation, and triacylglycerols and phosphatidylinositols with fibrin-rich areas., Conclusions: By comparing lipid species in plaque and plasma, we identified those circulating species that were also prominently present in plaque. Quantitative comparison of lipid spectral patterns with histology revealed the presence of specific lipid species in destabilized plaque areas, corroborating previous in vitro and animal studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mark Towers and Emmanuelle Claude are employees of Waters Corporation. The other authors have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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36. Apolipoprotein-CIII O -Glycosylation, a Link between GALNT2 and Plasma Lipids.
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Naber A, Demus D, Slieker R, Nicolardi S, Beulens JWJ, Elders PJM, Lieverse AG, Sijbrands EJG, 't Hart LM, Wuhrer M, and van Hoek M
- Subjects
- Humans, Apolipoprotein C-III genetics, Apolipoproteins C genetics, Glycosylation, Genome-Wide Association Study, Triglycerides, Cholesterol, HDL, Receptors, Cytoplasmic and Nuclear genetics, Vesicular Transport Proteins genetics, Cytoskeletal Proteins genetics, Adaptor Proteins, Signal Transducing genetics, Diabetes Mellitus, Type 2 genetics, Hypertriglyceridemia, Hyperlipidemias
- Abstract
Apolipoprotein-CIII (apo-CIII) is involved in triglyceride-rich lipoprotein metabolism and linked to beta-cell damage, insulin resistance, and cardiovascular disease. Apo-CIII exists in four main proteoforms: non-glycosylated (apo-CIII
0a ), and glycosylated apo-CIII with zero, one, or two sialic acids (apo-CIII0c , apo-CIII1 and apo-CIII2 ). Our objective is to determine how apo-CIII glycosylation affects lipid traits and type 2 diabetes prevalence, and to investigate the genetic basis of these relations with a genome-wide association study (GWAS) on apo-CIII glycosylation. We conducted GWAS on the four apo-CIII proteoforms in the DiaGene study in people with and without type 2 diabetes ( n = 2318). We investigated the relations of the identified genetic loci and apo-CIII glycosylation with lipids and type 2 diabetes. The associations of the genetic variants with lipids were replicated in the Diabetes Care System ( n = 5409). Rs4846913-A, in the GALNT2 -gene, was associated with decreased apo-CIII0a . This variant was associated with increased high-density lipoprotein cholesterol and decreased triglycerides, while high apo-CIII0a was associated with raised high-density lipoprotein-cholesterol and triglycerides. Rs67086575-G, located in the IFT172 -gene, was associated with decreased apo-CIII2 and with hypertriglyceridemia. In line, apo-CIII2 was associated with low triglycerides. On a genome-wide scale, we confirmed that the GALNT2 -gene plays a major role i O -glycosylation of apolipoprotein-CIII, with subsequent associations with lipid parameters. We newly identified the IFT172 / NRBP1 region, in the literature previously associated with hypertriglyceridemia, as involved in apolipoprotein-CIII sialylation and hypertriglyceridemia. These results link genomics, glycosylation, and lipid metabolism, and represent a key step towards unravelling the importance of O -glycosylation in health and disease.- Published
- 2023
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37. Heart Rate Variability and Incident Type 2 Diabetes in General Population.
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Wang K, Ahmadizar F, Geurts S, Arshi B, Kors JA, Rizopoulos D, Sijbrands EJG, Ikram MA, and Kavousi M
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- Humans, Female, Middle Aged, Male, Heart Rate physiology, Risk Factors, Diabetes Mellitus, Type 2 complications, Atrial Fibrillation etiology, Atrial Fibrillation complications, Autonomic Nervous System Diseases complications
- Abstract
Context: Hyperglycemia and autonomic dysfunction are bidirectionally related., Objective: We investigated the association of longitudinal evolution of heart rate variability (HRV) with incident type 2 diabetes (T2D) among the general population., Methods: We included 7630 participants (mean age 63.7 years, 58% women) from the population-based Rotterdam Study who had no history of T2D and atrial fibrillation at baseline and had repeated HRV assessments at baseline and during follow-up. We used joint models to assess the association between longitudinal evolution of heart rate and different HRV metrics (including the heart rate-corrected SD of the normal-to-normal RR intervals [SDNNc], and root mean square of successive RR-interval differences [RMSSDc]) with incident T2D. Models were adjusted for cardiovascular risk factors. Bidirectional Mendelian randomization (MR) using summary-level data was also performed., Results: During a median follow-up of 8.6 years, 871 individuals developed incident T2D. One SD increase in heart rate (hazard ratio [HR] 1.20; 95% CI, 1.09-1.33), and log(RMSSDc) (HR 1.16; 95% CI, 1.01-1.33) were independently associated with incident T2D. The HRs were 1.54 (95% CI, 1.08-2.06) for participants younger than 62 years and 1.15 (95% CI, 1.01-1.31) for those older than 62 years for heart rate (P for interaction <.001). Results from bidirectional MR analyses suggested that HRV and T2D were not significantly related to each other., Conclusion: Autonomic dysfunction precedes development of T2D, especially among younger individuals, while MR analysis suggests no causal relationship. More studies are needed to further validate our findings., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)
- Published
- 2023
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38. Lipoprotein(a) is associated with a larger systemic burden of arterial calcification.
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Singh SS, van der Toorn JE, Sijbrands EJG, de Rijke YB, Kavousi M, and Bos D
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- Male, Humans, Female, Aged, Lipoprotein(a), Risk Factors, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease epidemiology, Carotid Artery Diseases, Calcinosis, Vascular Calcification diagnostic imaging, Vascular Calcification epidemiology
- Abstract
Aims: Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for cardiovascular disease. However, population-based evidence on the link between Lp(a) and subclinical arteriosclerosis is lacking. We assessed associations of Lp(a) concentrations with arteriosclerosis in multiple arteries., Methods and Results: From the population-based Rotterdam study, 2354 participants (mean age: 69.5 years, 52.3% women) underwent non-contrast computed tomography to assess arterial calcification as a hallmark of arteriosclerosis. We quantified the volume of coronary artery calcification (CAC), aortic arch calcification (AAC), extracranial (ECAC), and intracranial carotid artery calcification (ICAC). All participants underwent blood sampling, from which plasma Lp(a) concentrations were derived. The association of plasma Lp(a) levels was assessed with calcification volumes and with severe calcification (upper quartile of calcification volume) using sex-stratified multivariable linear and logistic regression models. Higher Lp(a) levels were associated with larger ln-transformed volumes of CAC [fully adjusted beta 95% confidence interval (CI) per 1 standard deviation (SD) in women: 0.09, 95% CI 0.04-0.14, men: 0.09, 95% CI 0.03-0.14], AAC (women: 0.06, 95% CI 0.01-0.11, men: 0.09, 95% CI 0.03-0.14), ECAC (women: 0.07, 95% CI 0.02-0.13, men: 0.08, 95% CI 0.03-0.14), and ICAC (women: 0.09, 95% CI 0.03-0.14, men: 0.05, 95% CI -0.02 to 0.11]. In the highest Lp(a) percentile, severe ICAC was most prevalent in women [fully adjusted odds ratio (OR) 2.41, 95% CI 1.25-4.63] and severe AAC in men (fully adjusted OR 3.29, 95% CI 1.67-6.49)., Conclusion: Higher Lp(a) was consistently associated with a larger calcification burden in all major arteries. The findings of this study indicate that Lp(a) is a systemic risk factor for arteriosclerosis and thus potentially an effective target for treatment. Lp(a)-reducing therapies may reduce the burden from arteriosclerotic events throughout the arterial system., Translational Perspective: In 2354 participants from the Rotterdam study, we assessed the link between Lp(a) concentrations and arterial calcifications, as proxy for arteriosclerosis, in major arteries. We found that higher Lp(a) levels were consistently associated with larger volumes of calcification in the coronary arteries, aortic arch, extracranial carotid arteries, and intracranial carotid arteries. The findings of our study indicate that Lp(a) is a systemic risk factor for arteriosclerosis, suggesting that the systemic burden of arteriosclerosis throughout the arterial system could be reduced by targeting Lp(a)., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)
- Published
- 2023
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39. Sphingolipids in Cerebrospinal Fluid and Plasma Lipoproteins of APOE4 Homozygotes and Non- APOE4 Carriers with Mild Cognitive Impairment versus Subjective Cognitive Decline.
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den Hoedt S, Dorst-Lagerwerf KY, de Vries HE, Rozemuller AJM, Scheltens P, Walter J, Sijbrands EJG, Martinez-Martinez P, Verhoeven AJM, Teunissen CE, and Mulder MT
- Abstract
Background: Alzheimer's disease (AD) patients display alterations in cerebrospinal fluid (CSF) and plasma sphingolipids. The APOE4 genotype increases the risk of developing AD., Objective: To test the hypothesis that the APOE4 genotype affects common sphingolipids in CSF and in plasma of patients with early stages of AD., Methods: Patients homozygous for APOE4 and non- APOE4 carriers with mild cognitive impairment (MCI; n = 20 versus 20) were compared to patients with subjective cognitive decline (SCD; n = 18 versus 20). Sphingolipids in CSF and plasma lipoproteins were determined by liquid-chromatography-tandem mass spectrometry. Aβ
42 levels in CSF were determined by immunoassay., Results: APOE4 homozygotes displayed lower levels of sphingomyelin (SM; p = 0.042), SM(d18:1/18:0) ( p = 0.026), and Aβ42 ( p < 0.001) in CSF than non- APOE4 carriers. CSF-Aβ42 correlated with Cer(d18:1/18:0), SM(d18:1/18:0), and SM(d18:1/18:1) levels in APOE4 homozygotes ( r > 0.49; p < 0.032) and with Cer(d18:1/24:1) in non- APOE4 carriers ( r = 0.50; p = 0.025). CSF-Aβ42 correlated positively with Cer(d18:1/24:0) in MCI ( p = 0.028), but negatively in SCD patients ( p = 0.019). Levels of Cer(d18:1/22:0) and long-chain SMs were inversely correlated with Mini-Mental State Examination score among MCI patients, independent of APOE4 genotype ( r < -0.47; p < 0.039). Nevertheless, age and sex are stronger determinants of individual sphingolipid levels in CSF than either the APOE genotype or the cognitive state. In HDL, ratios of Cer(d18:1/18:0) and Cer(d18:1/22:0) to cholesterol were higher in APOE4 homozygotes than in non- APOE4 carriers ( p = 0.048 and 0.047, respectively)., Conclusion: The APOE4 genotype affects sphingolipid profiles of CSF and plasma lipoproteins already at early stages of AD. ApoE4 may contribute to the early development of AD through modulation of sphingolipid metabolism., Competing Interests: The authors have no conflict of interest to report., (© 2023 – The authors. Published by IOS Press.)- Published
- 2023
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40. Associations of baseline glycemic status and its transitions with cognitive and physical functioning decline.
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Wang K, Gao H, Sijbrands EJG, Kavousi M, and Ahmadizar F
- Subjects
- Humans, Female, Male, Blood Glucose, Longitudinal Studies, Glycated Hemoglobin, Cohort Studies, Activities of Daily Living, Cognition, Prediabetic State diagnosis, Diabetes Mellitus
- Abstract
Objective: Evidence about the decline of cognition and physical function across glycemic status (normoglycemia, prediabetes, and diabetes) is inconsistent. We evaluated longitudinal changes in cognition and physical function according to glycemic status and also different glycemic transitions., Study Design: Population-based cohort study., Methods: 9307 participants (mean age 59.7 years, 53.7 % women) were included from the China Health and Retirement Longitudinal Study (2011-2018). Global cognition (assessed by orientation, memory, and executive function) and physical function (calculated as the sum of impaired basic and instrumental activities of daily living) were assessed in each wave. The glycemic status was assessed in waves 2011 and 2015. Diabetes was defined as fasting blood glucose ≥7.0 mmol/L, HbA1c ≥6.5 %, self-reported diabetes, or glucose-lowering medication use. Prediabetes was defined as fasting blood glucose 5.6-6.9 mmol/L or an HbA1c of 5.7-6.4 %., Results: Compared with normoglycemia, baseline diabetes was associated with a faster decline in orientation (-0.018 SD/year, 95%CI -0.032, -0.004) and a faster increase in physical function score (0.082 /year, 95%CI 0.038, 0.126). We did not observe any effect of prediabetes on the changing rate of cognition and physical function. Progression from normoglycemia to diabetes between waves 2011 and 2015 was associated with a significantly faster decline in global cognition, memory, executive function, and physical function compared with stable normoglycemia., Conclusions: Baseline diabetes was associated with accelerated decline of cognition and physical function. Associations with prediabetes were not observed, suggesting an important short diagnostic window when diabetes presents de novo., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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41. Lipoprotein(a) is associated with the onset but not the progression of aortic valve calcification.
- Author
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Kaiser Y, van der Toorn JE, Singh SS, Zheng KH, Kavousi M, Sijbrands EJG, Stroes ESG, Vernooij MW, de Rijke YB, Boekholdt SM, and Bos D
- Subjects
- Aged, Calcinosis, Calcium, Creatinine, Female, Humans, Lipoprotein(a), Male, Middle Aged, Aortic Valve diagnostic imaging, Aortic Valve pathology, Aortic Valve Stenosis epidemiology, Aortic Valve Stenosis etiology
- Abstract
Aim: Lipoprotein(a) [Lp(a)] is a potential causal factor in the pathogenesis of aortic valve disease. However, the relationship of Lp(a) with new onset and progression of aortic valve calcium (AVC) has not been studied. The purpose of the study was to assess whether high serum levels of Lp(a) are associated with AVC incidence and progression., Methods and Results: A total of 922 individuals from the population-based Rotterdam Study (mean age 66.0±4.2 years, 47.7% men), whose Lp(a) measurements were available, underwent non-enhanced cardiac computed tomography imaging at baseline and after a median follow-up of 14.0 [interquartile range (IQR) 13.9-14.2] years. New-onset AVC was defined as an AVC score >0 on the follow-up scan in the absence of AVC on the first scan. Progression was defined as the absolute difference in AVC score between the baseline and follow-up scan. Logistic and linear regression analyses were performed to evaluate the relationship of Lp(a) with baseline, new onset, and progression of AVC. All analyses were corrected for age, sex, body mass index, smoking, hypertension, dyslipidaemia, and creatinine. AVC progression was analysed conditional on baseline AVC score expressed as restricted cubic splines. Of the 702 individuals without AVC at baseline, 415 (59.1%) developed new-onset AVC on the follow-up scan. In those with baseline AVC, median annual progression was 13.5 (IQR = 5.2-37.8) Agatston units (AU). Lipoprotein(a) concentration was independently associated with baseline AVC [odds ratio (OR) 1.43 for each 50 mg/dL higher Lp(a); 95% confidence interval (CI) 1.15-1.79] and new-onset AVC (OR 1.30 for each 50 mg/dL higher Lp(a); 95% CI 1.02-1.65), but not with AVC progression (β: -71 AU for each 50 mg/dL higher Lp(a); 95% CI -117; 35). Only baseline AVC score was significantly associated with AVC progression (P < 0.001)., Conclusion: In the population-based Rotterdam Study, Lp(a) is robustly associated with baseline and new-onset AVC but not with AVC progression, suggesting that Lp(a)-lowering interventions may be most effective in pre-calcific stages of aortic valve disease., Competing Interests: Conflict of interest: S.S.S., Y.B.R., and E.J.G.S. received funding for the Lp(a) Ahead Study from Amgen Netherlands BV. E.S.G.S. has received research grants/support to his institution from Amgen, Sanofi, Resverlogix, and Athera, and has served as a consultant for Amgen, Sanofi, Esperion, Novartis, and Ionis Pharmaceuticals. All other authors report no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2022
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42. A novel integrated QSP model of in vivo human glucose regulation to support the development of a glucagon/GLP-1 dual agonist.
- Author
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Bosch R, Petrone M, Arends R, Vicini P, Sijbrands EJG, Hoefman S, and Snelder N
- Subjects
- Blood Glucose, Glucagon, Glucose metabolism, Humans, Insulin, Glucagon-Like Peptide-1 Receptor Agonists, Diabetes Mellitus, Type 2 drug therapy, Glucagon-Like Peptide 1
- Abstract
Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) and dual GLP-1/glucagon receptor agonists improve glycaemic control and cause significant weight loss in patients with type 2 diabetes.
1 These effects are driven in part by augmenting glucose-stimulated insulin release (incretin effect), reducing caloric intake and delayed gastric emptying. We developed and externally validated a novel integrated quantitative systems pharmacology (QSP) model to gain quantitative insight into the relative contributions and mechanisms of drugs modulating glucose regulatory pathways. This model (4GI model) incorporates known feedback mechanisms among glucose, GLP-1, glucagon, glucose-dependent insulinotropic peptide (GIP), and insulin after glucose provocation (i.e., food intake) and drug intervention utilizing published nonpharmacological and pharmacological (liraglutide, a GLP-1RA) data. The resulting model accurately describes the aforementioned mechanisms and independently predicts the effects of the GLP-1RAs (dulaglutide and semaglutide) on system dynamics. Therefore, the validated 4GI model represents a quantitative decision-making tool to support the advancement of novel therapeutics and combination strategies modulating these pathways., (© 2021 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)- Published
- 2022
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43. Cross-Laboratory Standardization of Preclinical Lipidomics Using Differential Mobility Spectrometry and Multiple Reaction Monitoring.
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Ghorasaini M, Mohammed Y, Adamski J, Bettcher L, Bowden JA, Cabruja M, Contrepois K, Ellenberger M, Gajera B, Haid M, Hornburg D, Hunter C, Jones CM, Klein T, Mayboroda O, Mirzaian M, Moaddel R, Ferrucci L, Lovett J, Nazir K, Pearson M, Ubhi BK, Raftery D, Riols F, Sayers R, Sijbrands EJG, Snyder MP, Su B, Velagapudi V, Williams KJ, de Rijke YB, and Giera M
- Subjects
- Cohort Studies, Humans, Reference Standards, Spectrum Analysis, Laboratories, Lipidomics
- Abstract
Modern biomarker and translational research as well as personalized health care studies rely heavily on powerful omics' technologies, including metabolomics and lipidomics. However, to translate metabolomics and lipidomics discoveries into a high-throughput clinical setting, standardization is of utmost importance. Here, we compared and benchmarked a quantitative lipidomics platform. The employed Lipidyzer platform is based on lipid class separation by means of differential mobility spectrometry with subsequent multiple reaction monitoring. Quantitation is achieved by the use of 54 deuterated internal standards and an automated informatics approach. We investigated the platform performance across nine laboratories using NIST SRM 1950-Metabolites in Frozen Human Plasma, and three NIST Candidate Reference Materials 8231-Frozen Human Plasma Suite for Metabolomics (high triglyceride, diabetic, and African-American plasma). In addition, we comparatively analyzed 59 plasma samples from individuals with familial hypercholesterolemia from a clinical cohort study. We provide evidence that the more practical methyl-tert-butyl ether extraction outperforms the classic Bligh and Dyer approach and compare our results with two previously published ring trials. In summary, we present standardized lipidomics protocols, allowing for the highly reproducible analysis of several hundred human plasma lipids, and present detailed molecular information for potentially disease relevant and ethnicity-related materials.
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- 2021
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44. The effect of monomeric and oligomeric FLAVAnols in patients with type 2 diabetes and microalbuminuria (FLAVA-trial): A double-blind randomized controlled trial.
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Rashid M, Verhoeven AJM, Mulder MT, Timman R, Ozcan B, van Beek-Nieuwland Y, Chow LM, van de Laar RJJM, Dik WA, Sijbrands EJG, and Berk KA
- Subjects
- Aged, Albuminuria complications, Albuminuria physiopathology, Biomarkers blood, Biomarkers urine, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 physiopathology, Double-Blind Method, Female, Flavonols chemistry, Humans, Male, Middle Aged, Treatment Outcome, Albuminuria therapy, Diabetes Mellitus, Type 2 therapy, Dietary Supplements, Endothelium, Vascular drug effects, Flavonols administration & dosage
- Abstract
Background & Aims: Microalbuminuria is an early sign of vascular complications of type 2 diabetes and predicts cardiovascular disease and mortality. Monomeric and oligomeric flavanols (MOFs) are linked to improved vascular health. The aim of this study was to assess the effect of 3 months MOFs on albuminuria and endothelial function markers in patients with type 2 diabetes and microalbuminuria., Methods: We conducted a double-blind, placebo-controlled trial among patients with type 2 diabetes and microalbuminuria. Patients with type 2 diabetes received either 200 mg MOFs or placebo daily on top of their habitual diet and medication. The primary endpoint was the between-group difference of the change in 24-h Albumin Excretion Rate (AER) over three months. Secondary endpoints were the between-group differences of the change in plasma levels of different markers of endothelial dysfunction. Mixed-modelling was applied for the longitudinal analyses., Results: Participants (n = 97) were 63.0 ± 9.5 years old; diabetes-duration was 15.7 ± 8.5 years. Median baseline AER was 60 (IQR 20-120) mg/24 h. There was no within-group difference in median change of AER from baseline to 3 months in the intervention (0 (-35-21) mg/24 h, p = 0.41) or the control group (0 (-20-10) mg/24 h, p = 0.91). There was no between-group difference in the course of AER over three months (log-transformed data: β = -0.02 (95%CI -0.23-0.20), p = 0.88), nor in the plasma levels of the endothelial dysfunction markers., Conclusion: Daily 200 mg MOFs for three months on top of habitual diet and usual care did not reduce AER and plasma markers of endothelial dysfunction compared to placebo, in patients with long-term type 2 diabetes and microalbuminuria., Clinical Trials Registration: NTR4669, www.trialregister.nl., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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45. Effects of Sex, Age, and Apolipoprotein E Genotype on Brain Ceramides and Sphingosine-1-Phosphate in Alzheimer's Disease and Control Mice.
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den Hoedt S, Crivelli SM, Leijten FPJ, Losen M, Stevens JAA, Mané-Damas M, de Vries HE, Walter J, Mirzaian M, Sijbrands EJG, Aerts JMFG, Verhoeven AJM, Martinez-Martinez P, and Mulder MT
- Abstract
Apolipoprotein ε4 ( APOE )4 is a strong risk factor for the development of Alzheimer's disease (AD) and aberrant sphingolipid levels have been implicated in AD. We tested the hypothesis that the APOE4 genotype affects brain sphingolipid levels in AD. Seven ceramides and sphingosine-1-phosphate (S1P) were quantified by LC-MSMS in hippocampus, cortex, cerebellum, and plasma of <3 months and >5 months old human APOE3 and APOE4- targeted replacement mice with or without the familial AD (FAD) background of both sexes (145 animals). APOE4 mice had higher Cer(d18:1/24:0) levels in the cortex (1.7-fold, p = 0.002) than APOE3 mice. Mice with AD background showed higher levels of Cer(d18:1/24:1) in the cortex than mice without (1.4-fold, p = 0.003). S1P levels were higher in all three brain regions of older mice than of young mice (1.7-1.8-fold, all p ≤ 0.001). In female mice, S1P levels in hippocampus ( r = -0.54 [-0.70, -0.35], p < 0.001) and in cortex correlated with those in plasma ( r = -0.53 [-0.71, -0.32], p < 0.001). Ceramide levels were lower in the hippocampus (3.7-10.7-fold, all p < 0.001), but higher in the cortex (2.3-12.8-fold, p < 0.001) of female than male mice. In cerebellum and plasma, sex effects on individual ceramides depended on acyl chain length (9.5-fold lower to 11.5-fold higher, p ≤ 0.001). In conclusion, sex is a stronger determinant of brain ceramide levels in mice than APOE genotype, AD background, or age. Whether these differences impact AD neuropathology in men and women remains to be investigated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 den Hoedt, Crivelli, Leijten, Losen, Stevens, Mané-Damas, de Vries, Walter, Mirzaian, Sijbrands, Aerts, Verhoeven, Martinez-Martinez and Mulder.)
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- 2021
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46. Genetic susceptibility, obesity and lifetime risk of type 2 diabetes: The ARIC study and Rotterdam Study.
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Ligthart S, Hasbani NR, Ahmadizar F, van Herpt TTW, Leening MJG, Uitterlinden AG, Sijbrands EJG, Morrison AC, Boerwinkle E, Pankow JS, Selvin E, Ikram MA, Kavousi M, de Vries PS, and Dehghan A
- Subjects
- Aged, Diabetes Mellitus, Type 2 epidemiology, Female, Genetic Variation, Humans, Male, Middle Aged, Multifactorial Inheritance, Risk, White People, Diabetes Mellitus, Type 2 etiology, Diabetes Mellitus, Type 2 genetics, Genetic Predisposition to Disease genetics, Life Style, Obesity complications
- Abstract
Aims: Both lifestyle factors and genetic background contribute to the development of type 2 diabetes. Estimation of the lifetime risk of diabetes based on genetic information has not been presented, and the extent to which a normal body weight can offset a high lifetime genetic risk is unknown., Methods: We used data from 15,671 diabetes-free participants of European ancestry aged 45 years and older from the prospective population-based ARIC study and Rotterdam Study (RS). We quantified the remaining lifetime risk of diabetes stratified by genetic risk and quantified the effect of normal weight in terms of relative and lifetime risks in low, intermediate and high genetic risk., Results: At age 45 years, the lifetime risk of type 2 diabetes in ARIC in the low, intermediate and high genetic risk category was 33.2%, 41.3% and 47.2%, and in RS 22.8%, 30.6% and 35.5% respectively. The absolute lifetime risk for individuals with normal weight compared to individuals with obesity was 24% lower in ARIC and 8.6% lower in RS in the low genetic risk group, 36.3% lower in ARIC and 31.3% lower in RS in the intermediate genetic risk group, and 25.0% lower in ARIC and 29.4% lower in RS in the high genetic risk group., Conclusions: Genetic variants for type 2 diabetes have value in estimating the lifetime risk of type 2 diabetes. Normal weight mitigates partly the deleterious effect of high genetic risk., (© 2021 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)
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- 2021
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47. Plasma protein N- glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes.
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Memarian E, 't Hart LM, Slieker RC, Lemmers RFL, van der Heijden AA, Rutters F, Nijpels G, Schoep E, Lieverse AG, Sijbrands EJG, Wuhrer M, van Hoek M, and Dotz V
- Subjects
- Blood Proteins, Glycosylation, Humans, Plasma, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, Diabetes Mellitus, Type 2 complications, Retinal Diseases
- Abstract
Introduction: Although associations of total plasma N- glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality. Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System)., Research Design and Methods: Blood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner. Peptide:N-glycosidase F (PNGase F) was used to release N- glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation. After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation. Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed., Results: Our results demonstrated similarities between incident and prevalent complications. The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10
-11 ), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6 ). Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes., Conclusions: These findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms., Competing Interests: Competing interests: MW is inventor on a patent application on sialic acid derivatization by ethyl esterification. EM is employed by Genos. VD currently works at BioTherapeutics Analytical Development, Janssen Biologics BV. No other potential conflicts of interest relevant to this article were reported., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)- Published
- 2021
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48. HDL associates with insulin resistance and beta-cell dysfunction in South Asian families at risk of type 2 diabetes.
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Yahya R, Jainandunsing S, Rashid M, van der Zee L, Touw A, de Rooij FWM, Sijbrands EJG, Verhoeven AJM, and Mulder MT
- Subjects
- Asian People, Blood Glucose, Humans, Insulin, Cholesterol, HDL blood, Diabetes Mellitus, Type 2 epidemiology, Glucose Intolerance epidemiology, Insulin Resistance, Insulin-Secreting Cells pathology
- Abstract
Objective: Dyslipidemia precedes type 2 diabetes (T2D) and worsens with increasing glucose intolerance. First degree relatives of T2D patients have an increased risk to develop dyslipidemia and glucose intolerance. The aim of the present study was to assess the relation between the development of dyslipidemia and glucose intolerance in first-degree relatives of T2D patients., Research Design and Methods: Fasting lipoprotein profiles were determined by density gradient ultracentrifugation in T2D patients and their first-degree relatives (42 Caucasians and 33 South Asians), and in 29 normoglycemic controls from non-T2D families. Glucose tolerance, insulin sensitivity index (ISI) and insulin disposition index (DI) were assessed by an extended, frequently sampled oral glucose tolerance test (OGTT), and fractional insulin synthesis rate (FSR) was measured by
13 C-leucine enrichment in urinary C-peptide during the OGTT., Results: Of the first-degree relatives, 40, 16 and 19 had NGT, prediabetes and T2D, respectively. NGT family members had lower plasma HDL-cholesterol (HDLC) (1.34 ± 0.07 vs 1.58 ± 0.06 mmol/L; p = 0.015), HDL2 -C (0.41 ± 0.05 vs 0.57 ± 0.05 mmol/L; p = 0.021) and HDL3 -C (0.62 ± 0.03 vs 0.72 ± 0.02 mmol/L; p = 0.043) than controls. HDL2 -C levels tended to decrease with increasing glucose intolerance state. In South Asians, buoyant LDL-C levels decreased with increasing glucose intolerance state (p = 0.006). In South Asian families, HDL-C correlated with both ISI and DI (β 0.42; p = 0.04 and β 0.53; p = 0.01, respectively), whereas HDL2 -C and HDL3 -C levels correlated with DI (β 0.64; p = 0.002 and β 0.57; p = 0.005, respectively). HDL2 -C and plasma triglyceride correlated with FSR (β 0.48; p = 0.033 and β -0.50; p = 0.029, respectively)., Conclusions: Low HDL2 -C and HDL3 -C levels are present in NGT first-degree relatives of T2D patients, and HDL2 -C tend to decrease further with increasing glucose intolerance. In South Asian families HDL2 -C and HDL3 -C levels linked predominantly to deteriorating beta cell function., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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49. Lipoprotein(a) is robustly associated with aortic valve calcium.
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Kaiser Y, Singh SS, Zheng KH, Verbeek R, Kavousi M, Pinto SJ, Vernooij MW, Sijbrands EJG, Boekholdt SM, de Rijke YB, Stroes ESG, and Bos D
- Subjects
- Aged, Aortic Valve diagnostic imaging, Cohort Studies, Correlation of Data, Disease Progression, Female, Heart Disease Risk Factors, Humans, Male, Middle Aged, Multidetector Computed Tomography methods, Multidetector Computed Tomography statistics & numerical data, Netherlands epidemiology, Prevalence, Time-to-Treatment, Aortic Valve pathology, Aortic Valve Stenosis blood, Aortic Valve Stenosis diagnostic imaging, Aortic Valve Stenosis epidemiology, Aortic Valve Stenosis prevention & control, Calcinosis blood, Calcinosis diagnostic imaging, Calcinosis epidemiology, Calcinosis prevention & control, Hyperlipoproteinemias blood, Hyperlipoproteinemias drug therapy, Hyperlipoproteinemias epidemiology, Lipid Regulating Agents therapeutic use, Lipoprotein(a) blood, Lipoprotein(a) metabolism
- Abstract
Objectives: To investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC., Methods: We included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC., Results: The prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (β 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase)., Conclusions: Lp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis., Competing Interests: Competing interests: SSS, YBdR and ES were supported by Amgen: Lp(a) Ahead Study. ESGS has received research grants/support to his institution from Amgen, Sanofi, Resverlogix and Athera, and has served as a consultant for Amgen, Sanofi, Esperion, Novartis and Ionis Pharmaceuticals., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2021
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50. Breakfast partly restores the anti-inflammatory function of high-density lipoproteins from patients with type 2 diabetes mellitus.
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Lemmers RFH, Martens NEMA, Maas AH, van Vark-van der Zee LC, Leijten FPJ, Groot-van Ruijven CM, van Hoek M, Lieverse AG, Sijbrands EJG, Haak HR, Leenen PJM, Verhoeven AJM, Dik WA, and Mulder MT
- Abstract
Background and Aims: High-density lipoproteins (HDL) of patients with type 2 diabetes mellitus (T2DM) have impaired anti-inflammatory activities. The anti-inflammatory activity of HDL has been determined ex vivo after isolation by different methods from blood mostly obtained after overnight fasting. We first determined the effect of the HDL isolation method, and subsequently the effect of food intake on the anti-inflammatory function of HDL from T2DM patients., Methods: Blood was collected from healthy controls and T2DM patients after an overnight fast, and from T2DM patients 3 h after breakfast ( n = 17 each). HDL was isolated by a two-step density gradient ultracentrifugation in iodixanol (HDL
DGUC2 ), by sequential salt density flotation (HDLSEQ ) or by PEG precipitation (HDLPEG ). The anti-inflammatory function of HDL was determined by the reduction of the TNFα-induced expression of VCAM-1 in human coronary artery endothelial cells (HCAEC) and retinal endothelial cells (REC)., Results: HDL isolated by the three different methods from healthy controls inhibited TNFα-induced VCAM-1 expression in HCAEC. With apoA-I at 0.7 μM, HDLDGUC2 and HDLSEQ were similarly effective (16% versus 14% reduction; n = 3; p > 0.05) but less effective than HDLPEG (28%, p < 0.05). Since ultracentrifugation removes most of the unbound plasma proteins, we used HDLDGUC2 for further experiments. With apoA-I at 3.2 μM, HDL from fasting healthy controls and T2DM patients reduced TNFα-induced VCAM-1 expression in HCAEC by 58 ± 13% and 51 ± 20%, respectively ( p = 0.35), and in REC by 42 ± 13% and 25 ± 18%, respectively ( p < 0.05). Compared to preprandial HDL, postprandial HDL from T2DM patients reduced VCAM-1 expression by 56 ± 16% (paired test: p < 0.001) in HCAEC and by 34 ± 13% (paired test: p < 0.05) in REC., Conclusions: The ex vivo anti-inflammatory activity of HDL is affected by the HDL isolation method. Two-step ultracentrifugation in an iodixanol gradient is a suitable method for HDL isolation when testing HDL anti-inflammatory function. The anti-inflammatory activity of HDL from overnight fasted T2DM patients is significantly impaired in REC but not in HCAEC. The anti-inflammatory function of HDL is partly restored by food intake., Competing Interests: The authors declare that they have no conflict of interest., (© 2021 The Authors.)- Published
- 2021
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