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5. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

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Zhou, Bin, Carrillo-Larco, Rodrigo M, Danaei, Goodarz, Riley, Leanne M, Paciorek, Christopher J, Stevens, Gretchen A, Gregg, Edward W, Bennett, James E, Solomon, Bethlehem, Singleton, Rosie K, Sophiea, Marisa K, Iurilli, Maria LC, Lhoste, Victor PF, Cowan, Melanie J, Savin, Stefan, Woodward, Mark, Balanova, Yulia, Cifkova, Renata, Damasceno, Albertino, Elliott, Paul, Farzadfar, Farshad, He, Jiang, Ikeda, Nayu, Kengne, Andre P, Khang, Young-Ho, Kim, Hyeon Chang, Laxmaiah, Avula, Lin, Hsien-Ho, Margozzini Maira, Paula, Miranda, J Jaime, Neuhauser, Hannelore, Sundström, Johan, Varghese, Cherian, Widyahening, Indah S, Zdrojewski, Tomasz, Abarca-Gómez, Leandra, Abdeen, Ziad A, Abdul Rahim, Hanan F, Abu-Rmeileh, Niveen M, Acosta-Cazares, Benjamin, Adams, Robert J, Aekplakorn, Wichai, Afsana, Kaosar, Afzal, Shoaib, Agdeppa, Imelda A, Aghazadeh-Attari, Javad, Aguilar-Salinas, Carlos A, Agyemang, Charles, Ahmad, Noor Ani, Ahmadi, Ali, Ahmadi, Naser, Ahmadi, Nastaran, Ahmadizar, Fariba, Ahmed, Soheir H, Ahrens, Wolfgang, Ajlouni, Kamel, Al-Raddadi, Rajaa, Alarouj, Monira, AlBuhairan, Fadia, AlDhukair, Shahla, Ali, Mohamed M, Alkandari, Abdullah, Alkerwi, Ala'a, Allin, Kristine, Aly, Eman, Amarapurkar, Deepak N, Amougou, Norbert, Amouyel, Philippe, Andersen, Lars Bo, Anderssen, Sigmund A, Anjana, Ranjit Mohan, Ansari-Moghaddam, Alireza, Ansong, Daniel, Aounallah-Skhiri, Hajer, Araújo, Joana, Ariansen, Inger, Aris, Tahir, Arku, Raphael E, Arlappa, Nimmathota, Aryal, Krishna K, Aspelund, Thor, Assah, Felix K, Assunção, Maria Cecília F, Auvinen, Juha, Avdićová, Mária, Azevedo, Ana, Azimi-Nezhad, Mohsen, Azizi, Fereidoun, Azmin, Mehrdad, Babu, Bontha V, Bahijri, Suhad, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Banadinović, Maja, Bandosz, Piotr, Banegas, José R, Baran, Joanna, Barbagallo, Carlo M, Barceló, Alberto, Barkat, Amina, Barreto, Marta, Barros, Aluisio JD, Barros, Mauro Virgílio Gomes, Bartosiewicz, Anna, Basit, Abdul, Bastos, Joao Luiz D, Bata, Iqbal, Batieha, Anwar M, Batyrbek, Assembekov, Baur, Louise A, Beaglehole, Robert, Belavendra, Antonisamy, Ben Romdhane, Habiba, Benet, Mikhail, Benson, Lowell S, Berkinbayev, Salim, Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloísa, Bezerra, Jorge, Bhagyalaxmi, Aroor, Bhargava, Santosh K, Bia, Daniel, Biasch, Katia, Bika Lele, Elysée Claude, Bikbov, Mukharram M, Bista, Bihungum, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B, Björkelund, Cecilia, Bloch, Katia V, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boeing, Heiner, Boggia, Jose G, Boissonnet, Carlos P, Bojesen, Stig E, Bongard, Vanina, Bonilla-Vargas, Alice, Bopp, Matthias, Borghs, Herman, Bovet, Pascal, Boyer, Christopher B, Braeckman, Lutgart, Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Brenner, Hermann, Brewster, Lizzy M, Briceño, Yajaira, Brito, Miguel, Bruno, Graziella, Bueno-de-Mesquita, H Bas, Bueno, Gloria, Bugge, Anna, Burns, Con, Bursztyn, Michael, Cabrera de León, Antonio, Cacciottolo, Joseph, Cameron, Christine, Can, Günay, Cândido, Ana Paula C, Capanzana, Mario V, Čapková, Naděžda, Capuano, Eduardo, Capuano, Vincenzo, Cardoso, Viviane C, Carlsson, Axel C, Carvalho, Joana, Casanueva, Felipe F, Censi, Laura, Cervantes-Loaiza, Marvin, Chadjigeorgiou, Charalambos A, Chamukuttan, Snehalatha, Chan, Angelique W, Chan, Queenie, Chaturvedi, Himanshu K, Chaturvedi, Nish, Chee, Miao Li, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Chen, Zhengming, Cheng, Ching-Yu, Cheraghian, Bahman, Cherkaoui Dekkaki, Imane, Chetrit, Angela, Chien, Kuo-Liong, Chiolero, Arnaud, Chiou, Shu-Ti, Chirita-Emandi, Adela, Chirlaque, María-Dolores, Cho, Belong, Christensen, Kaare, Christofaro, Diego G, Chudek, Jerzy, Cinteza, Eliza, Claessens, Frank, Clarke, Janine, Clays, Els, Cohen, Emmanuel, Concin, Hans, Cooper, Cyrus, Coppinger, Tara C, Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L, Crampin, Amelia C, Crujeiras, Ana B, Cruz, Juan J, Csilla, Semánová, Cui, Liufu, Cureau, Felipe V, Cuschieri, Sarah, D'Arrigo, Graziella, d'Orsi, Eleonora, Dallongeville, Jean, Dankner, Rachel, Dantoft, Thomas M, Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, De Curtis, Amalia, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Ridder, David, De Smedt, Delphine, Deepa, Mohan, Deev, Alexander D, DeGennaro, Vincent Jr, Delisle, Hélène, Demarest, Stefaan, Dennison, Elaine, Deschamps, Valérie, Dhimal, Meghnath, Di Castelnuovo, Augusto F, Dias-da-Costa, Juvenal Soares, Diaz, Alejandro, Dickerson, Ty T, Dika, Zivka, Djalalinia, Shirin, Do, Ha TP, Dobson, Annette J, Donfrancesco, Chiara, Donoso, Silvana P, Döring, Angela, Dorobantu, Maria, Dörr, Marcus, Doua, Kouamelan, Dragano, Nico, Drygas, Wojciech, Duante, Charmaine A, Duboz, Priscilla, Duda, Rosemary B, Dulskiene, Virginija, Dushpanova, Anar, Džakula, Aleksandar, Dzerve, Vilnis, Dziankowska-Zaborszczyk, Elzbieta, Eddie, Ricky, Eftekhar, Ebrahim, Eggertsen, Robert, Eghtesad, Sareh, Eiben, Gabriele, Ekelund, Ulf, El-Khateeb, Mohammad, El Ati, Jalila, Eldemire-Shearer, Denise, Eliasen, Marie, Elosua, Roberto, Erasmus, Rajiv T, Erbel, Raimund, Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G, Escobedo-de la Peña, Jorge, Eslami, Saeid, Esmaeili, Ali, Evans, Alun, Faeh, David, Fakhretdinova, Albina A, Fall, Caroline H, Faramarzi, Elnaz, Farjam, Mojtaba, Fattahi, Mohammad Reza, Fawwad, Asher, Felix-Redondo, Francisco J, Felix, Stephan B, Ferguson, Trevor S, Fernandes, Romulo A, Fernández-Bergés, Daniel, Ferrante, Daniel, Ferrao, Thomas, Ferrari, Marika, Ferrario, Marco M, Ferreccio, Catterina, Ferreira, Haroldo S, Ferrer, Eldridge, Ferrieres, Jean, Figueiró, Thamara Hubler, Fink, Günther, Fischer, Krista, Foo, Leng Huat, Forsner, Maria, Fouad, Heba M, Francis, Damian K, Franco, Maria do Carmo, Frikke-Schmidt, Ruth, Frontera, Guillermo, Fuchs, Flavio D, Fuchs, Sandra C, Fujita, Yuki, Fumihiko, Matsuda, Furdela, Viktoriya, Furer, Ariel, Furusawa, Takuro, Gaciong, Zbigniew, Galbarczyk, Andrzej, Galenkamp, Henrike, Galvano, Fabio, Gao, Jingli, Gao, Pei, Garcia-de-la-Hera, Manoli, Garcia, Pablo, Gareta, Dickman, Garnett, Sarah P, Gaspoz, Jean-Michel, Gasull, Magda, Gazzinelli, Andrea, Gehring, Ulrike, Geleijnse, Johanna M, George, Ronnie, Ghanbari, Ali, Ghasemi, Erfan, Gheorghe-Fronea, Oana-Florentina, Ghimire, Anup, Gialluisi, Alessandro, Giampaoli, Simona, Gieger, Christian, Gill, Tiffany K, Giovannelli, Jonathan, Gironella, Glen, Giwercman, Aleksander, Gkiouras, Konstantinos, Goldberg, Marcel, Goldsmith, Rebecca A, Gomez, Luis F, Gomula, Aleksandra, Gonçalves, Helen, Gonçalves, Mauer, Gonçalves Cordeiro da Silva, Bruna, Gonzalez-Chica, David A, Gonzalez-Gross, Marcela, González-Rivas, Juan P, González-Villalpando, Clicerio, González-Villalpando, María-Elena, Gonzalez, Angel R, Gorbea, Mariano Bonet, Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dušan, Grajda, Aneta, Grammatikopoulou, Maria G, Gregor, Ronald D, Grodzicki, Tomasz, Grosso, Giuseppe, Gruden, Gabriella, Gu, Dongfeng, Guan, Ong Peng, Gudmundsson, Elias F, Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idris, Guimaraes, Andre L, Gulliford, Martin C, Gunnlaugsdottir, Johanna, Gunter, Marc J, Gupta, Prakash C, Gupta, Rajeev, Gureje, Oye, Gurzkowska, Beata, Gutierrez, Laura, Gutzwiller, Felix, Ha, Seongjun, Hadaegh, Farzad, Haghshenas, Rosa, Hakimi, Hamid, Halkjær, Jytte, Hambleton, Ian R, Hamzeh, Behrooz, Hange, Dominique, Hanif, Abu AM, Hantunen, Sari, Hao, Jie, Hardman, Carla Menêses, Hari Kumar, Rachakulla, Hashemi-Shahri, Seyed Mohammad, Hata, Jun, Haugsgjerd, Teresa, Hayes, Alison J, He, Yuna, Heier, Margit, Hendriks, Marleen Elisabeth, Henrique, Rafael dos Santos, Henriques, Ana, Hernandez Cadena, Leticia, Herqutanto, Herrala, Sauli, Heshmat, Ramin, Hill, Allan G, Ho, Sai Yin, Ho, Suzanne C, Hobbs, Michael, Holdsworth, Michelle, Homayounfar, Reza, Horasan Dinc, Gonul, Horimoto, Andrea RVR, Hormiga, Claudia M, Horta, Bernardo L, Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Htike, Maung Maung Than, Hu, Yonghua, Huerta, José María, Huhtaniemi, Ilpo Tapani, Huiart, Laetitia, Huisman, Martijn, Husseini, Abdullatif S, Huybrechts, Inge, Hwalla, Nahla, Iacoviello, Licia, Iannone, Anna G, Ibrahim, Mohsen M, Ibrahim Wong, Norazizah, Ikram, M Arfan, Iotova, Violeta, Irazola, Vilma E, Ishida, Takafumi, Isiguzo, Godsent C, Islam, Muhammad, Islam, Sheikh Mohammed Shariful, Iwasaki, Masanori, Jackson, Rod T, Jacobs, Jeremy M, Jaddou, Hashem Y, Jafar, Tazeen, James, Kenneth, Jamrozik, Konrad, Janszky, Imre, Janus, Edward, Jarvelin, Marjo-Riitta, Jasienska, Grazyna, Jelaković, Ana, Jelaković, Bojan, Jennings, Garry, Jha, Anjani Kumar, Jiang, Chao Qiang, Jimenez, Ramon O, Jöckel, Karl-Heinz, Joffres, Michel, Johansson, Mattias, Jokelainen, Jari J, Jonas, Jost B, Jørgensen, Torben, Joshi, Pradeep, Joukar, Farahnaz, Jóżwiak, Jacek, Juolevi, Anne, Jurak, Gregor, Jureša, Vesna, Kaaks, Rudolf, Kafatos, Anthony, Kajantie, Eero O, Kalmatayeva, Zhanna, Kalpourtzi, Natasa, Kalter-Leibovici, Ofra, Kampmann, Freja B, Kannan, Srinivasan, Karaglani, Eva, Kårhus, Line L, Karki, Khem B, Katibeh, Marzieh, Katz, Joanne, Kauhanen, Jussi, Kaur, Prabhdeep, Kavousi, Maryam, Kazakbaeva, Gyulli M, Keil, Ulrich, Keinan Boker, Lital, Keinänen-Kiukaanniemi, Sirkka, Kelishadi, Roya, Kemper, Han CG, Keramati, Maryam, Kerimkulova, Alina, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khaw, Kay-Tee, Kheiri, Bahareh, Kheradmand, Motahareh, Khosravi, Alireza, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Dong Wook, Kim, Jeongseon, Klakk, Heidi, Klimek, Magdalena, Klumbiene, Jurate, Knoflach, Michael, Kolle, Elin, Kolsteren, Patrick, Kontto, Jukka P, Korpelainen, Raija, Korrovits, Paul, Kos, Jelena, Koskinen, Seppo, Kouda, Katsuyasu, Kowlessur, Sudhir, Koziel, Slawomir, Kratenova, Jana, Kriaucioniene, Vilma, Kristensen, Peter Lund, Krokstad, Steiner, Kromhout, Daan, Kruger, Herculina S, Kubinova, Ruzena, Kuciene, Renata, Kujala, Urho M, Kulaga, Zbigniew, Kumar, R Krishna, Kurjata, Pawel, Kusuma, Yadlapalli S, Kutsenko, Vladimir, Kuulasmaa, Kari, Kyobutungi, Catherine, Laatikainen, Tiina, Lachat, Carl, Laid, Youcef, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Latt, Tint Swe, Le Coroller, Gwenaëlle, Le Nguyen Bao, Khanh, Le, Tuyen D, Lee, Jeannette, Lee, Jeonghee, Lehmann, Nils, Lehtimäki, Terho, Lemogoum, Daniel, Levitt, Naomi S, Li, Yanping, Lilly, Christa L, Lim, Wei-Yen, Lima-Costa, M Fernanda, Lin, Xu, Lin, Yi-Ting, Lind, Lars, Lingam, Vijaya, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Lo, Wei-Cheng, Loit, Helle-Mai, Lopez-Garcia, Esther, Lopez, Tania, Lotufo, Paulo A, Lozano, José Eugenio, Lukačević Lovrenčić, Iva, Lukrafka, Janice L, Luksiene, Dalia, Lundqvist, Annamari, Lundqvist, Robert, Lunet, Nuno, Lustigová, Michala, Luszczki, Edyta, Ma, Guansheng, Ma, Jun, Machado-Coelho, George LL, Machado-Rodrigues, Aristides M, Macia, Enguerran, Macieira, Luisa M, Madar, Ahmed A, Maggi, Stefania, Magliano, Dianna J, Magriplis, Emmanuella, Mahasampath, Gowri, Maire, Bernard, Majer, Marjeta, Makdisse, Marcia, Malekzadeh, Fatemeh, Malekzadeh, Reza, Malhotra, Rahul, Mallikharjuna Rao, Kodavanti, Malyutina, Sofia K, Maniego, Lynell V, Manios, Yannis, Mann, Jim I, Mansour-Ghanaei, Fariborz, Manzato, Enzo, Marcil, Anie, Mårild, Staffan B, Marinović Glavić, Mihalea, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martorell, Reynaldo, Mascarenhas, Luis P, Matasin, Marija, Mathiesen, Ellisiv B, Mathur, Prashant, Matijasevich, Alicia, Matlosz, Piotr, Matsha, Tandi E, Mavrogianni, Christina, Mbanya, Jean Claude N, Mc Donald Posso, Anselmo J, McFarlane, Shelly R, McGarvey, Stephen T, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, McNulty, Breige A, Mediene Benchekor, Sounnia, Medzioniene, Jurate, Mehdipour, Parinaz, Mehlig, Kirsten, Mehrparvar, Amir Houshang, Meirhaeghe, Aline, Meisinger, Christa, Mendoza Montano, Carlos, Menezes, Ana Maria B, Menon, Geetha R, Mereke, Alibek, Meshram, Indrapal I, Metspalu, Andres, Meyer, Haakon E, Mi, Jie, Michels, Nathalie, Mikkel, Kairit, Milkowska, Karolina, Miller, Jody C, Minderico, Cláudia S, Mini, GK, Mirjalili, Mohammad Reza, Mirrakhimov, Erkin, Mišigoj-Duraković, Marjeta, Modesti, Pietro A, Moghaddam, Sahar Saeedi, Mohajer, Bahram, Mohamed, Mostafa K, Mohamed, Shukri F, Mohammad, Kazem, Mohammadi, Mohammad Reza, Mohammadi, Zahra, Mohammadifard, Noushin, Mohammadpourhodki, Reza, Mohan, Viswanathan, Mohanna, Salim, Mohd Yusoff, Muhammad Fadhli, Mohebbi, Iraj, Mohebi, Farnam, Moitry, Marie, Møllehave, Line T, Molnár, Dénes, Momenan, Amirabbas, Mondo, Charles K, Monterrubio-Flores, Eric, Monyeki, Kotsedi Daniel K, Moon, Jin Soo, Moosazadeh, Mahmood, Moreira, Leila B, Morejon, Alain, Moreno, Luis A, Morgan, Karen, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mostafavi, Seyed-Ali, Mota, Jorge, Motlagh, Mohammad Esmaeel, Motta, Jorge, Moura-dos-Santos, Marcos André, Mridha, Malay K, Msyamboza, Kelias P, Mu, Thet Thet, Muhihi, Alfa J, Muiesan, Maria L, Müller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Musa, Kamarul Imran, Musić Milanović, Sanja, Musil, Vera, Mustafa, Norlaila, Nabipour, Iraj, Naderimagham, Shohreh, Nagel, Gabriele, Naidu, Balkish M, Najafi, Farid, Nakamura, Harunobu, Námešná, Jana, Nang, Ei Ei K, Nangia, Vinay B, Narake, Sameer, Ndiaye, Ndeye Coumba, Neal, William A, Nejatizadeh, Azim, Nenko, Ilona, Neovius, Martin, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang V, Nguyen, Quang Ngoc, Nieto-Martínez, Ramfis E, Niiranen, Teemu J, Nikitin, Yury P, Ninomiya, Toshiharu, Nishtar, Sania, Njelekela, Marina A, Noale, Marianna, Noboa, Oscar A, Noorbala, Ahmad Ali, Norat, Teresa, Nordendahl, Maria, Nordestgaard, Børge G, Noto, Davide, Nowak-Szczepanska, Natalia, Nsour, Mohannad Al, Nunes, Baltazar, O'Neill, Terence W, O'Reilly, Dermot, Ochimana, Caleb, Oda, Eiji, Odili, Augustine N, Oh, Kyungwon, Ohara, Kumiko, Ohtsuka, Ryutaro, Olié, Valérie, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Ortiz, Pedro J, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Ellis, Paccaud, Fred Michel, Padez, Cristina, Pahomova, Elena, Paiva, Karina Mary de, Pająk, Andrzej, Palli, Domenico, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Panza, Francesco, Paoli, Mariela, Papandreou, Dimitrios, Park, Soon-Woo, Park, Suyeon, Parnell, Winsome R, Parsaeian, Mahboubeh, Pasquet, Patrick, Patel, Nikhil D, Pavlyshyn, Halyna, Pećin, Ivan, Pednekar, Mangesh S, Pedro, João M, Peer, Nasheeta, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C, Peres, Karen GDA, Peres, Marco A, Peters, Annette, Petkeviciene, Janina, Peykari, Niloofar, Pham, Son Thai, Pichardo, Rafael N, Pigeot, Iris, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pitakaka, Freda, Piwonska, Aleksandra, Pizarro, Andreia n, Plans-Rubió, Pedro, Polašek, Ozren, Porta, Miquel, Poudyal, Anil, Pourfarzi, Farhad, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Price, Alison J, Price, Jacqueline F, Providencia, Rui, Puhakka, Soile E, Puiu, Maria, Punab, Margus, Qasrawi, Radwan F, Qorbani, Mostafa, Queiroz, Daniel, Quoc Bao, Tran, Radić, Ivana, Radisauskas, Ricardas, Rahimikazerooni, Salar, Rahman, Mahfuzar, Raitakari, Olli, Raj, Manu, Rakhimova, Ellina M, Ramachandra Rao, Sudha, Ramachandran, Ambady, Ramos, Elisabete, Rampal, Lekhraj, Rampal, Sanjay, Rangel Reina, Daniel A, Rarra, Vayia, Rech, Cassiano Ricardo, Redon, Josep, Reganit, Paul Ferdinand M, Regecová, Valéria, Revilla, Luis, Rezaianzadeh, Abbas, Ribeiro, Robespierre, Riboli, Elio, Richter, Adrian, Rigo, Fernando, Rinke de Wit, Tobias F, Ritti-Dias, Raphael M, Robitaille, Cynthia, Rodríguez-Artalejo, Fernando, Rodriguez-Perez, María del Cristo, Rodríguez-Villamizar, Laura A, Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Romaguera, Dora, Romeo, Elisabetta L, Rosengren, Annika, Roy, Joel GR, Rubinstein, Adolfo, Ruidavets, Jean-Bernard, Ruiz-Betancourt, Blanca Sandra, Ruiz-Castell, Maria, Rusakova, Iuliia A, Russo, Paola, Rutkowski, Marcin, Sabanayagam, Charumathi, Sabbaghi, Hamideh, Sachdev, Harshpal S, Sadjadi, Alireza, Safarpour, Ali Reza, Safi, Sare, Safiri, Saeid, Saidi, Olfa, Sakarya, Sibel, Saki, Nader, Salanave, Benoit, Salazar Martinez, Eduardo, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Sánchez-Abanto, Jose, Sans, Susana, Santos, Diana A, Santos, Ina S, Santos, Lèlita C, Santos, Maria Paula, Santos, Rute, Saramies, Jouko L, Sardinha, Luis B, Sarganas, Giselle, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savvas, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D, Schargrodsky, Herman, Schipf, Sabine, Schmidt, Carsten O, Schnohr, Peter, Schöttker, Ben, Schramm, Sara, Schultsz, Constance, Schutte, Aletta E, Sebert, Sylvain, Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Servais, Jennifer, Shalnova, Svetlana A, Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K, Shaw, Jonathan E, Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Silva, Caroline Ramos de Moura, Silva, Diego Augusto Santos, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöström, Michael, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobngwi, Eugène, Söderberg, Stefan, Soemantri, Agustinus, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Sorić, Maroje, Sossa Jérome, Charles, Soumaré, Aïcha, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Staessen, Jan A, Starc, Gregor, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stieber, Jutta, Stöckl, Doris, Stocks, Tanja, Stokwiszewski, Jakub, Stronks, Karien, Strufaldi, Maria Wany, Suka, Machi, Sun, Chien-An, Sung, Yn-Tz, Suriyawongpaisal, Paibul, Sy, Rody G, Syddall, Holly E, Sylva, René Charles, Szklo, Moyses, Tai, E Shyong, Tammesoo, Mari-Liis, Tamosiunas, Abdonas, Tan, Eng Joo, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarqui-Mamani, Carolina B, Taylor, Anne, Taylor, Julie, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thinggaard, Mikael, Thomas, Nihal, Thorand, Barbara, Thuesen, Betina H, Timmermans, Erik J, Tjandrarini, Dwi H, Tjonneland, Anne, Toft, Ulla, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Tormo, María José, Tornaritis, Michael J, Torrent, Maties, Torres-Collado, Laura, Touloumi, Giota, Traissac, Pierre, Triantafyllou, Areti, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ulmer, Hanno, Uusitalo, Hannu MT, Valdivia, Gonzalo, Valvi, Damaskini, van Dam, Rob M, van den Born, Bert-Jan, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, van Zutphen, Elisabeth M, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Vasan, Senthil K, Vega, Tomas, Veidebaum, Toomas, Velasquez-Melendez, Gustavo, Veronesi, Giovanni, Verschuren, WM Monique, Verstraeten, Roosmarijn, Victora, Cesar G, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesus, Virtanen, Jyrki K, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vlasoff, Tiina, Vollenweider, Peter, Voutilainen, Ari, Wade, Alisha N, Walton, Janette, Wambiya, Elvis OA, Wan Bebakar, Wan Mohamad, Wan Mohamud, Wan Nazaimoon, Wanderley Júnior, Rildo de Souza, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nicholas, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Emmanuel A, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Tien Yin, Woo, Jean, Wu, Frederick C, Wu, Shouling, Wyszynska, Justyna, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, San-Lin, Younger-Coleman, Novie O, Yusoff, Ahmad Faudzi, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antonis, Zapata, Maria Elisa, Zaw, Ko Ko, Zejglicova, Kristyna, Zeljkovic Vrkic, Tajana, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhen, Shiqi, Zheng, Yingfeng, Zholdin, Bekbolat, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Zoghlami, Nada, Zuñiga Cisneros, Julio, and Ezzati, Majid

Published
2021
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6. A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

Author

Scott, Robert A, Freitag, Daniel F, Li, Li, Chu, Audrey Y, Surendran, Praveen, Young, Robin, Grarup, Niels, Stancáková, Alena, Chen, Yuning, Varga, Tibor V, Yaghootkar, Hanieh, Luan, Jian’an, Zhao, Jing Hua, Willems, Sara M, Wessel, Jennifer, Wang, Shuai, Maruthur, Nisa, Michailidou, Kyriaki, Pirie, Ailith, van der Lee, Sven J, Gillson, Christopher, Al Olama, Ali Amin, Amouyel, Philippe, Arriola, Larraitz, Arveiler, Dominique, Aviles-Olmos, Iciar, Balkau, Beverley, Barricarte, Aurelio, Barroso, Inês, Garcia, Sara Benlloch, Bis, Joshua C, Blankenberg, Stefan, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Borecki, Ingrid B, Bork-Jensen, Jette, Bowden, Sarah, Caldas, Carlos, Caslake, Muriel, consortium, The CVD50, Cupples, L Adrienne, Cruchaga, Carlos, Czajkowski, Jacek, Hoed, Marcel den, Dunn, Janet A, Earl, Helena M, Ehret, Georg B, Ferrannini, Ele, Ferrieres, Jean, Foltynie, Thomas, Ford, Ian, Forouhi, Nita G, Gianfagna, Francesco, Gonzalez, Carlos, Grioni, Sara, Hiller, Louise, Jansson, Jan-Håkan, Jørgensen, Marit E, Jukema, J Wouter, Kaaks, Rudolf, Kee, Frank, Kerrison, Nicola D, Key, Timothy J, Kontto, Jukka, Kote-Jarai, Zsofia, Kraja, Aldi T, Kuulasmaa, Kari, Kuusisto, Johanna, Linneberg, Allan, Liu, Chunyu, Marenne, Gaëlle, Mohlke, Karen L, Morris, Andrew P, Muir, Kenneth, Müller-Nurasyid, Martina, Munroe, Patricia B, Navarro, Carmen, Nielsen, Sune F, Nilsson, Peter M, Nordestgaard, Børge G, Packard, Chris J, Palli, Domenico, Panico, Salvatore, Peloso, Gina M, Perola, Markus, Peters, Annette, Poole, Christopher J, Quirós, J Ramón, Rolandsson, Olov, Sacerdote, Carlotta, Salomaa, Veikko, Sánchez, María-José, Sattar, Naveed, Sharp, Stephen J, Sims, Rebecca, Slimani, Nadia, Smith, Jennifer A, Thompson, Deborah J, and Trompet, Stella

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Research, Diabetes, Human Genome, Cardiovascular, Prevention, Obesity, Genetics, Heart Disease, Heart Disease - Coronary Heart Disease, Clinical Trials and Supportive Activities, Aetiology, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Metabolic and endocrine, Good Health and Well Being, Alleles, Coronary Disease, Diabetes Mellitus, Type 2, Dipeptidyl Peptidase 4, Genotype, Glucagon-Like Peptide-1 Receptor, Humans, Receptor, Cannabinoid, CB2, Receptor, Serotonin, 5-HT2C, Receptors, Somatostatin, Sodium-Glucose Transporter 1, CVD50 consortium, GERAD_EC Consortium, Neurology Working Group of the Cohorts for Heart, Aging Research in Genomic Epidemiology, Alzheimer’s Disease Genetics Consortium, Pancreatic Cancer Cohort Consortium, European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease, EPIC-InterAct, CHARGE consortium, CHD Exome+ Consortium, CARDIOGRAM Exome Consortium, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.

Published
2016

9. Overweight duration in older adults and cancer risk: a study of cohorts in Europe and the United States

Author

Arnold, Melina, Freisling, Heinz, Stolzenberg-Solomon, Rachael, Kee, Frank, O’Doherty, Mark George, Ordóñez-Mena, José Manuel, Wilsgaard, Tom, May, Anne Maria, Bueno-de-Mesquita, Hendrik Bas, Tjønneland, Anne, Orfanos, Philippos, Trichopoulou, Antonia, Boffetta, Paolo, Bray, Freddie, Jenab, Mazda, Soerjomataram, Isabelle, Baceviciene, Migle, Boer, Jolanda M. A., Drygas, Wojciech, Eriksson, Sture, Feskens, Edith, Gafarov, Valeriy, Gardiner, Julian, Hakansson, Niclas, Jansson, Jan-Hakan, Jousilahti, Pekka, Kampman, Ellen, Kontto, Jukka, Kubinova, Ruzena, Leenders, Max, Linneberg, Allan, Lochen, Maja-Lisa, Lorbeer, Roberto, Malyutina, Sofia, Mathiesen, Ellisiv B., Melhus, Hakan, Michaëlsson, Karl, Njolstad, Inger, Orsini, Nicola, Pająk, Andrzej, Pikhart, Hynek, Pisinger, Charlotta, Salomaa, Veikko, Sánchez, María-José, Sans, Susana, Schaan, Barbara, Schneider, Andrea, Siganos, Galatios, Söderberg, Stefan, Streppel, Martinette, Tamošiūnas, Abdonas, Veronesi, Giovanni, Veronesi, Giovanni, Wennberg, Patrik, and on behalf of the CHANCES consortium

Published
2016
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10. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Author

Zhou, Bin Carrillo-Larco, Rodrigo M. Danaei, Goodarz Riley, Leanne M. Paciorek, Christopher J. Stevens, Gretchen A. and Gregg, Edward W. Bennett, James E. Solomon, Bethlehem and Singleton, Rosie K. Sophiea, Marisa K. Iurilli, Maria L. C. and Lhoste, Victor P. F. Cowan, Melanie J. Savin, Stefan and Woodward, Mark Balanova, Yulia Cifkova, Renata Damasceno, Albertino Elliott, Paul Farzadfar, Farshad He, Jiang and Ikeda, Nayu Kengne, Andre P. Khang, Young-Ho Kim, Hyeon Chang Laxmaiah, Avula Lin, Hsien-Ho Margozzini Maira, Paula and Miranda, J. Jaime Neuhauser, Hannelore Sundstrom, Johan and Varghese, Cherian Widyahening, Indah S. Zdrojewski, Tomasz and Ezzati, Majid Abarca-Gomez, Leandra Abdeen, Ziad A. Rahim, Hanan F. Abdul Abu-Rmeileh, Niveen M. Acosta-Cazares, Benjamin and Adams, Robert J. Aekplakorn, Wichai Afsana, Kaosar and Afzal, Shoaib Agdeppa, Imelda A. Aghazadeh-Attari, Javad and Aguilar-Salinas, Carlos A. Agyemang, Charles Ahmad, Noor Ani and Ahmadi, Ali Ahmadi, Naser Ahmadi, Nastaran Ahmadizar, Fariba and Ahmed, Soheir H. Ahrens, Wolfgang Ajlouni, Kamel and Al-Raddadi, Rajaa Alarouj, Monira AlBuhairan, Fadia and AlDhukair, Shahla Ali, Mohamed M. Alkandari, Abdullah and Alkerwi, Ala'a Allin, Kristine Aly, Eman Amarapurkar, Deepak N. Amougou, Norbert Amouyel, Philippe Andersen, Lars Bo and Anderssen, Sigmund A. Anjana, Ranjit Mohan Ansari-Moghaddam, Alireza Ansong, Daniel Aounallah-Skhiri, Hajer Araujo, Joana and Ariansen, Inger Aris, Tahir Arku, Raphael E. Arlappa, Nimmathota Aryal, Krishna K. Aspelund, Thor Assah, Felix K. and Assuncao, Maria Cecilia F. Auvinen, Juha Avdicova, Maria and Azevedo, Ana Azimi-Nezhad, Mohsen Azizi, Fereidoun Azmin, Mehrdad Babu, Bontha V. Bahijri, Suhad Balakrishna, Nagalla and Balanova, Yulia Bamoshmoosh, Mohamed Banach, Maciej and Banadinovic, Maja Bandosz, Piotr Banegas, Jose R. Baran, Joanna Barbagallo, Carlo M. Barcelo, Alberto Barkat, Amina and Barreto, Marta Barros, Aluisio J. D. Gomes Barros, Mauro Virgilio Bartosiewicz, Anna Basit, Abdul Bastos, Joao Luiz D. Bata, Iqbal Batieha, Anwar M. Batyrbek, Assembekov and Baur, Louise A. Beaglehole, Robert Belavendra, Antonisamy and Ben Romdhane, Habiba Benet, Mikhail Bennett, James E. and Benson, Lowell S. Berkinbayev, Salim Bernabe-Ortiz, Antonio and Bettiol, Heloisa Bezerra, Jorge Bhagyalaxmi, Aroor Bhargava, Santosh K. Bia, Daniel Biasch, Katia Lele, Elysee Claude Bika Bikbov, Mukharram M. Bista, Bihungum Bjerregaard, Peter and Bjertness, Espen Bjertness, Marius B. Bjorkelund, Cecilia and Bloch, Katia V. Blokstra, Anneke Bo, Simona Bobak, Martin Boeing, Heiner Boggia, Jose G. Boissonnet, Carlos P. and Bojesen, Stig E. Bongard, Vanina Bonilla-Vargas, Alice and Bopp, Matthias Borghs, Herman Bovet, Pascal Boyer, Christopher B. Braeckman, Lutgart Brajkovich, Imperia and Branca, Francesco Breckenkamp, Juergen Brenner, Hermann and Brewster, Lizzy M. Briceno, Yajaira Brito, Miguel Bruno, Graziella Bueno-de-Mesquita, H. Bas Bueno, Gloria Bugge, Anna Burns, Con Bursztyn, Michael Cabrera de Leon, Antonio and Cacciottolo, Joseph Cameron, Christine Can, Gunay and Candido, Ana Paula C. Capanzana, Mario V. Capkova, Nadezda and Capuano, Eduardo Capuano, Vincenzo Cardoso, Viviane C. and Carlsson, Axel C. Carvalho, Joana Casanueva, Felipe F. and Censi, Laura Cervantes-Loaiza, Marvin Chadjigeorgiou, Charalambos A. Chamukuttan, Snehalatha Chan, Angelique W. and Chan, Queenie Chaturvedi, Himanshu K. Chaturvedi, Nish Chee, Miao Li Chen, Chien-Jen Chen, Fangfang Chen, Huashuai and Chen, Shuohua Chen, Zhengming Cheng, Ching-Yu Cheraghian, Bahman Dekkaki, Imane Cherkaoui Chetrit, Angela Chien, Kuo-Liong Chiolero, Arnaud Chiou, Shu-Ti Chirita-Emandi, Adela Chirlaque, Maria-Dolores Cho, Belong Christensen, Kaare Christofaro, Diego G. Chudek, Jerzy Cifkova, Renata and Cinteza, Eliza Claessens, Frank Clarke, Janine Clays, Els Cohen, Emmanuel Concin, Hans Cooper, Cyrus and Coppinger, Tara C. Costanzo, Simona Cottel, Dominique and Cowell, Chris Craig, Cora L. Crampin, Amelia C. Crujeiras, Ana B. Cruz, Juan J. Csilla, Semanova Cui, Liufu Cureau, Felipe V. Cuschieri, Sarah D'Arrigo, Graziella d'Orsi, Eleonora Dallongeville, Jean Damasceno, Albertino Danaei, Goodarz Dankner, Rachel Dantoft, Thomas M. Dauchet, Luc and Davletov, Kairat De Backer, Guy De Bacquer, Dirk De Curtis, Amalia de Gaetano, Giovanni De Henauw, Stefaan de Oliveira, Paula Duarte De Ridder, David De Smedt, Delphine Deepa, Mohan Deev, Alexander D. DeGennaro, Vincent Jr Delisle, Helene Demarest, Stefaan Dennison, Elaine Deschamps, Valerie and Dhimal, Meghnath Di Castelnuovo, Augusto F. Dias-da-Costa, Juvenal Soares Diaz, Alejandro Dickerson, Ty T. Dika, Zivka and Djalalinia, Shirin Do, Ha T. P. Dobson, Annette J. and Donfrancesco, Chiara Donoso, Silvana P. Doering, Angela and Dorobantu, Maria Doerr, Marcus Doua, Kouamelan Dragano, Nico and Drygas, Wojciech Duante, Charmaine A. Duboz, Priscilla and Duda, Rosemary B. Dulskiene, Virginija Dushpanova, Anar and Dzakula, Aleksandar Dzerve, Vilnis Dziankowska-Zaborszczyk, Elzbieta Eddie, Ricky Eftekhar, Ebrahim Eggertsen, Robert and Eghtesad, Sareh Eiben, Gabriele Ekelund, Ulf El-Khateeb, Mohammad El Ati, Jalila Eldemire-Shearer, Denise Eliasen, Marie Elliott, Paul Elosua, Roberto Erasmus, Rajiv T. and Erbel, Raimund Erem, Cihangir Eriksen, Louise Eriksson, Johan G. Escobedo-de la Pena, Jorge Eslami, Saeid Esmaeili, Ali Evans, Alun Faeh, David Fakhretdinova, Albina A. and Fall, Caroline H. Faramarzi, Elnaz Farjam, Mojtaba and Farzadfar, Farshad Fattahi, Mohammad Reza Fawwad, Asher and Felix-Redondo, Francisco J. Felix, Stephan B. Ferguson, Trevor S. Fernandes, Romulo A. Fernandez-Berges, Daniel Ferrante, Daniel Ferrao, Thomas Ferrari, Marika Ferrario, Marco M. and Ferreccio, Catterina Ferreira, Haroldo S. Ferrer, Eldridge and Ferrieres, Jean Figueiro, Thamara Hubler Fink, Gunther and Fischer, Krista Foo, Leng Huat Forsner, Maria Fouad, Heba M. and Francis, Damian K. Franco, Maria do Carmo Frikke-Schmidt, Ruth Frontera, Guillermo Fuchs, Flavio D. Fuchs, Sandra C. and Fujita, Yuki Fumihiko, Matsuda Furdela, Viktoriya Furer, Ariel Furusawa, Takuro Gaciong, Zbigniew Galbarczyk, Andrzej and Galenkamp, Henrike Galvano, Fabio Gao, Jingli Gao, Pei and Garcia-de-la-Hera, Manoli Garcia, Pablo Gareta, Dickman and Garnett, Sarah P. Gaspoz, Jean-Michel Gasull, Magda and Gazzinelli, Andrea Gehring, Ulrike Geleijnse, Johanna M. and George, Ronnie Ghanbari, Ali Ghasemi, Erfan Gheorghe-Fronea, Oana-Florentina Ghimire, Anup Gialluisi, Alessandro and Giampaoli, Simona Gieger, Christian Gill, Tiffany K. and Giovannelli, Jonathan Gironella, Glen Giwercman, Aleksander and Gkiouras, Konstantinos Goldberg, Marcel Goldsmith, Rebecca A. and Gomez, Luis F. Gomula, Aleksandra Cordeiro da Silva, Bruna Goncalves Goncalves, Helen Goncalves, Mauer Gonzalez-Chica, David A. Gonzalez-Gross, Marcela Gonzalez-Rivas, Juan P. and Gonzalez-Villalpando, Clicerio Gonzalez-Villalpando, Maria-Elena and Gonzalez, Angel R. Bonet Gorbea, Mariano Gottrand, Frederic and Graff-Iversen, Sidsel Grafnetter, Dusan Grajda, Aneta and Grammatikopoulou, Maria G. Gregor, Ronald D. Grodzicki, Tomasz and Grosso, Giuseppe Gruden, Gabriella Gu, Dongfeng Guan, Ong Peng Gudmundsson, Elias F. Gudnason, Vilmundur Guerrero, Ramiro Guessous, Idris Guimaraes, Andre L. Gulliford, Martin C. Gunnlaugsdottir, Johanna Gunter, Marc J. Gupta, Prakash C. Gupta, Rajeev Gureje, Oye Gurzkowska, Beata and Gutierrez, Laura Gutzwiller, Felix Ha, Seongjun Hadaegh, Farzad Haghshenas, Rosa Hakimi, Hamid Halkjaer, Jytte and Hambleton, Ian R. Hamzeh, Behrooz Hange, Dominique Hanif, Abu A. M. Hantunen, Sari Hao, Jie Hardman, Carla Meneses and Kumar, Rachakulla Hari Hashemi-Shahri, Seyed Mohammad Hata, Jun and Haugsgjerd, Teresa Hayes, Alison J. He, Jiang He, Yuna and Heier, Margit Hendriks, Marleen Elisabeth Henrique, Rafael dos Santos Henriques, Ana Cadena, Leticia Hernandez Herrala, Sauli Heshmat, Ramin Hill, Allan G. Ho, Sai Yin Ho, Suzanne C. Hobbs, Michael Holdsworth, Michelle Homayounfar, Reza Dinc, Gonul Horasan Horimoto, Andrea R. V. R. Hormiga, Claudia M. Horta, Bernardo L. Houti, Leila Howitt, Christina and Htay, Thein Thein Htet, Aung Soe Htike, Maung Maung Than and Hu, Yonghua Huerta, Jose Maria Huhtaniemi, Ilpo Tapani and Huiart, Laetitia Huisman, Martijn Husseini, Abdullatif S. and Huybrechts, Inge Hwalla, Nahla Iacoviello, Licia Iannone, Anna G. Ibrahim, Mohsen M. Wong, Norazizah Ibrahim Ikeda, Nayu Ikram, M. Arfan Iotova, Violeta Irazola, Vilma E. and Ishida, Takafumi Isiguzo, Godsent C. Islam, Muhammad Islam, Sheikh Mohammed Shariful Iwasaki, Masanori Jackson, Rod T. and Jacobs, Jeremy M. Jaddou, Hashem Y. Jafar, Tazeen James, Kenneth Jamrozik, Konrad Janszky, Imre Janus, Edward and Jarvelin, Marjo-Riitta Jasienska, Grazyna Jelakovic, Ana and Jelakovic, Bojan Jennings, Garry Jha, Anjani Kumar Jiang, Chao Qiang Jimenez, Ramon O. Joeckel, Karl-Heinz Joffres, Michel Johansson, Mattias Jokelainen, Jari J. Jonas, Jost B. and Jorgensen, Torben Joshi, Pradeep Joukar, Farahnaz and Jozwiak, Jacek Juolevi, Anne Jurak, Gregor Juresa, Vesna and Kaaks, Rudolf Kafatos, Anthony Kajantie, Eero O. and Kalmatayeva, Zhanna Kalpourtzi, Natasa Kalter-Leibovici, Ofra and Kampmann, Freja B. Kannan, Srinivasan Karaglani, Eva and Karhus, Line L. Karki, Khem B. Katibeh, Marzieh Katz, Joanne and Kauhanen, Jussi Kaur, Prabhdeep Kavousi, Maryam and Kazakbaeva, Gyulli M. Keil, Ulrich Boker, Lital Keinan and Keinanen-Kiukaanniemi, Sirkka Kelishadi, Roya Kemper, Han C. G. and Kengne, Andre P. Keramati, Maryam Kerimkulova, Alina and Kersting, Mathilde Key, Timothy Khader, Yousef Saleh and Khalili, Davood Khang, Young-Ho Khaw, Kay-Tee Kheiri, Bahareh Kheradmand, Motahareh Khosravi, Alireza and Kiechl-Kohlendorfer, Ursula Kiechl, Stefan Killewo, Japhet and Kim, Dong Wook Kim, Hyeon Chang Kim, Jeongseon Klakk, Heidi and Klimek, Magdalena Klumbiene, Jurate Knoflach, Michael and Kolle, Elin Kolsteren, Patrick Kontto, Jukka P. Korpelainen, Raija Korrovits, Paul Kos, Jelena Koskinen, Seppo Kouda, Katsuyasu Kowlessur, Sudhir Koziel, Slawomir Kratenova, Jana and Kriaucioniene, Vilma Kristensen, Peter Lund Krokstad, Steiner Kromhout, Daan Kruger, Herculina S. Kubinova, Ruzena and Kuciene, Renata Kujala, Urho M. Kulaga, Zbigniew Kumar, R. Krishna Kurjata, Pawel Kusuma, Yadlapalli S. Kutsenko, Vladimir Kuulasmaa, Kari Kyobutungi, Catherine Laatikainen, Tiina Lachat, Carl Laid, Youcef Lam, Tai Hing Landrove, Orlando Lanska, Vera Lappas, Georg Larijani, Bagher and Latt, Tint Swe Laxmaiah, Avula Le Coroller, Gwenaelle Khanh Le Nguyen Bao Le, Tuyen D. Lee, Jeannette Lee, Jeonghee and Lehmann, Nils Lehtimaki, Terho Lemogoum, Daniel Levitt, Naomi S. Li, Yanping Lilly, Christa L. Lim, Wei-Yen and Lima-Costa, M. Fernanda Lin, Hsien-Ho Lin, Xu Lin, Yi-Ting and Lind, Lars Lingam, Vijaya Linneberg, Allan Lissner, Lauren Litwin, Mieczyslaw Lo, Wei-Cheng Loit, Helle-Mai and Lopez-Garcia, Esther Lopez, Tania Lotufo, Paulo A. Lozano, Jose Eugenio Lovrencic, Iva Lukacevic Lukrafka, Janice L. and Luksiene, Dalia Lundqvist, Annamari Lundqvist, Robert Lunet, Nuno Lustigova, Michala Luszczki, Edyta Ma, Guansheng and Ma, Jun Machado-Coelho, George L. L. Machado-Rodrigues, Aristides M. Macia, Enguerran Macieira, Luisa M. Madar, Ahmed A. Maggi, Stefania Magliano, Dianna J. Magriplis, Emmanuella Mahasampath, Gowri Maire, Bernard Majer, Marjeta and Makdisse, Marcia Malekzadeh, Fatemeh Malekzadeh, Reza and Malhotra, Rahul Mallikharjuna, Kodavanti Malyutina, Sofia K. and Maniego, Lynell V. Manios, Yannis Mann, Jim I. and Mansour-Ghanaei, Fariborz Manzato, Enzo Marcil, Anie and Margozzini, Paula Marild, Staffan B. Glavic, Mihalea Marinovic and Marques-Vidal, Pedro Marques, Larissa Pruner Marrugat, Jaume and Martorell, Reynaldo Mascarenhas, Luis P. Matasin, Marija and Mathiesen, Ellisiv B. Mathur, Prashant Matijasevich, Alicia and Matlosz, Piotr Matsha, Tandi E. Mavrogianni, Christina and Mbanya, Jean Claude N. Mc Donald Posso, Anselmo J. McFarlane, Shelly R. McGarvey, Stephen T. McLachlan, Stela McLean, Rachael M. McLean, Scott B. McNulty, Breige A. Benchekor, Sounnia Mediene Medzioniene, Jurate Mehdipour, Parinaz and Mehlig, Kirsten Mehrparvar, Amir Houshang Meirhaeghe, Aline and Meisinger, Christa Mendoza Montano, Carlos Menezes, Ana Maria B. and Menon, Geetha R. Mereke, Alibek Meshram, Indrapal I. and Metspalu, Andres Meyer, Haakon E. Mi, Jie Michels, Nathalie and Mikkel, Kairit Milkowska, Karolina Miller, Jody C. and Minderico, Claudia S. Mini, G. K. Miranda, J. Jaime and Mirjalili, Mohammad Reza Mirrakhimov, Erkin Misigoj-Durakovic, Marjeta Modesti, Pietro A. Moghaddam, Sahar Saeedi Mohajer, Bahram Mohamed, Mostafa K. Mohamed, Shukri F. Mohammad, Kazem Mohammadi, Mohammad Reza Mohammadi, Zahra and Mohammadifard, Noushin Mohammadpourhodki, Reza Mohan, Viswanathan Mohanna, Salim Yusoff, Muhammad Fadhli Mohd and Mohebbi, Iraj Mohebi, Farnam Moitry, Marie Mollehave, Line T. Molnar, Denes Momenan, Amirabbas Mondo, Charles K. and Monterrubio-Flores, Eric Monyeki, Kotsedi Daniel K. Moon, Jin Soo Moosazadeh, Mahmood Moreira, Leila B. Morejon, Alain and Moreno, Luis A. Morgan, Karen Moschonis, George Mossakowska, Malgorzata Mostafa, Aya Mostafavi, Seyed-Ali Mota, Jorge and Motlagh, Mohammad Esmaeel Motta, Jorge Andre Moura-dos-Santos, Marcos Mridha, Malay K. Msyamboza, Kelias P. Mu, Thet Thet and Muhihi, Alfa J. Muiesan, Maria L. Muller-Nurasyid, Martina and Murphy, Neil Mursu, Jaakko Musa, Kamarul Imran and Milanovic, Sanja Music Musil, Vera Mustafa, Norlaila and Nabipour, Iraj Naderimagham, Shohreh Nagel, Gabriele Naidu, Balkish M. Najafi, Farid Nakamura, Harunobu Namesna, Jana and Nang, Ei Ei K. Nangia, Vinay B. Narake, Sameer Ndiaye, Ndeye Coumba Neal, William A. Nejatizadeh, Azim Nenko, Ilona and Neovius, Martin Neuhauser, Hannelore K. Nguyen, Chung T. and Nguyen, Nguyen D. Nguyen, Quang V. Quang Ngoc Nguyen and Nieto-Martinez, Ramfis E. Niiranen, Teemu J. Nikitin, Yury P. and Ninomiya, Toshiharu Nishtar, Sania Njelekela, Marina A. and Noale, Marianna Noboa, Oscar A. Noorbala, Ahmad Ali Norat, Teresa Nordendahl, Maria Nordestgaard, Borge G. Noto, Davide and Nowak-Szczepanska, Natalia Al Nsour, Mohannad Nunes, Baltazar O'Neill, Terence W. O'Reilly, Dermot Ochimana, Caleb Oda, Eiji Odili, Augustine N. Oh, Kyungwon Ohara, Kumiko Ohtsuka, Ryutaro Olie, Valerie Olinto, Maria Teresa A. Oliveira, Isabel O. Omar, Mohd Azahadi Onat, Altan and Ong, Sok King Ono, Lariane M. Ordunez, Pedro Ornelas, Rui and Ortiz, Pedro J. Osmond, Clive Ostojic, Sergej M. and Ostovar, Afshin Otero, Johanna A. Overvad, Kim Owusu-Dabo, Ellis Paccaud, Fred Michel Padez, Cristina Pahomova, Elena and de Paiva, Karina Mary Pajak, Andrzej Palli, Domenico and Palmieri, Luigi Pan, Wen-Harn Panda-Jonas, Songhomitra and Panza, Francesco Paoli, Mariela Papandreou, Dimitrios Park, Soon-Woo Park, Suyeon Parnell, Winsome R. Parsaeian, Mahboubeh Pasquet, Patrick Patel, Nikhil D. Pavlyshyn, Halyna Pecin, Ivan Pednekar, Mangesh S. Pedro, Joao M. and Peer, Nasheeta Peixoto, Sergio Viana Peltonen, Markku and Pereira, Alexandre C. Peres, Karen G. D. A. Peres, Marco A. and Peters, Annette Petkeviciene, Janina Peykari, Niloofar Son Thai Pham Pichardo, Rafael N. Pigeot, Iris Pikhart, Hynek and Pilav, Aida Pilotto, Lorenza Pitakaka, Freda Piwonska, Aleksandra Pizarro, Andreia N. Plans-Rubio, Pedro Polasek, Ozren Porta, Miquel Poudyal, Anil Pourfarzi, Farhad and Pourshams, Akram Poustchi, Hossein Pradeepa, Rajendra Price, Alison J. Price, Jacqueline F. Providencia, Rui Puhakka, Soile E. Puiu, Maria Punab, Margus Qasrawi, Radwan F. and Qorbani, Mostafa Queiroz, Daniel Tran Quoc Bao Radic, Ivana and Radisauskas, Ricardas Rahimikazerooni, Salar Rahman, Mahfuzar Raitakari, Olli Raj, Manu Rakhimova, Ellina M. and Rao, Sudha Ramachandra Ramachandran, Ambady Ramos, Elisabete and Rampal, Lekhraj Rampal, Sanjay Rangel Reina, Daniel A. and Rarra, Vayia Rech, Cassiano Ricardo Redon, Josep Reganit, Paul Ferdinand M. Regecova, Valeria Revilla, Luis and Rezaianzadeh, Abbas Ribeiro, Robespierre Riboli, Elio and Richter, Adrian Rigo, Fernando de Wit, Tobias F. Rinke and Ritti-Dias, Raphael M. Robitaille, Cynthia Rodriguez-Artalejo, Fernando del Cristo Rodriguez-Perez, Maria Rodriguez-Villamizar, Laura A. Roggenbuck, Ulla Rojas-Martinez, Rosalba Romaguera, Dora Romeo, Elisabetta L. Rosengren, Annika Roy, Joel G. R. and Rubinstein, Adolfo Ruidavets, Jean-Bernard Sandra Ruiz-Betancourt, Blanca Ruiz-Castell, Maria Rusakova, Iuliia A. and Russo, Paola Rutkowski, Marcin Sabanayagam, Charumathi and Sabbaghi, Hamideh Sachdev, Harshpal S. Sadjadi, Alireza and Safarpour, Ali Reza Safi, Sare Safiri, Saeid Saidi, Olfa and Sakarya, Sibel Saki, Nader Salanave, Benoit Salazar Martinez, Eduardo Salmeron, Diego Salomaa, Veikko Salonen, Jukka T. Salvetti, Massimo Sanchez-Abanto, Jose Sans, Susana and Santos, Diana A. Santos, Ina S. Santos, Lelita C. and Santos, Maria Paula Santos, Rute Saramies, Jouko L. and Sardinha, Luis B. Sarganas, Giselle Sarrafzadegan, Nizal and Sathish, Thirunavukkarasu Saum, Kai-Uwe Savva, Savvas and Sawada, Norie Sbaraini, Mariana Scazufca, Marcia Schaan, Beatriz D. Schargrodsky, Herman Schipf, Sabine Schmidt, Carsten O. Schnohr, Peter Schoettker, Ben Schramm, Sara and Schultsz, Constance Schutte, Aletta E. Sebert, Sylvain Sein, Aye Aye Sen, Abhijit Senbanjo, Idowu O. Sepanlou, Sadaf G. and Servais, Jennifer Shalnova, Svetlana A. Shamah-Levy, Teresa and Shamshirgaran, Morteza Shanthirani, Coimbatore Subramaniam and Sharafkhah, Maryam Sharma, Sanjib K. Shaw, Jonathan E. and Shayanrad, Amaneh Shayesteh, Ali Akbar Shi, Zumin Shibuya, Kenji Shimizu-Furusawa, Hana Shin, Dong Wook Shirani, Majid and Shiri, Rahman Shrestha, Namuna Si-Ramlee, Khairil Siani, Alfonso Siantar, Rosalynn Sibai, Abla M. de Moura Silva, Caroline Ramos Santos Silva, Diego Augusto Simon, Mary and Simons, Judith Simons, Leon A. Sjostrom, Michael and Slowikowska-Hilczer, Jolanta Slusarczyk, Przemyslaw Smeeth, Liam and So, Hung-Kwan Soares, Fernanda Cunha Sobngwi, Eugene and Soderberg, Stefan Soemantri, Agustinus Sofat, Reecha and Solfrizzi, Vincenzo Somi, Mohammad Hossein Sonestedt, Emily and Song, Yi Sorensen, Thorkild I. A. Sorgjerd, Elin P. Soric, Maroje Jerome, Charles Sossa Soumare, Aicha Sparboe-Nilsen, Bente Sparrenberger, Karen Staessen, Jan A. Starc, Gregor and Stavreski, Bill Steene-Johannessen, Jostein Stehle, Peter and Stein, Aryeh D. Stergiou, George S. Stessman, Jochanan and Stieber, Jutta Stoeckl, Doris Stocks, Tanja Stokwiszewski, Jakub Stronks, Karien Strufaldi, Maria Wany Suka, Machi and Sun, Chien-An Sundstrom, Johan Sung, Yn-Tz Suriyawongpaisal, Paibul Sy, Rody G. Syddall, Holly E. Sylva, Rene Charles and Szklo, Moyses Tai, E. Shyong Tammesoo, Mari-Liis Tamosiunas, Abdonas Tan, Eng Joo Tang, Xun Tanser, Frank Tao, Yong and Tarawneh, Mohammed Rasoul Tarqui-Mamani, Carolina B. Taylor, Anne Taylor, Julie Tebar, William R. Tell, Grethe S. and Tello, Tania Tham, Yih Chung Thankappan, K. R. Theobald, Holger Theodoridis, Xenophon Thijs, Lutgarde Thinggaard, Mikael Thomas, Nihal Thorand, Barbara Thuesen, Betina H. and Timmermans, Erik J. Tjandrarini, Dwi H. Tjonneland, Anne and Toft, Ulla Tolonen, Hanna K. Tolstrup, Janne S. Topbas, Murat Topor-Madry, Roman Jose Tormo, Maria Tornaritis, Michael J. Torrent, Maties Torres-Collado, Laura Touloumi, Giota Traissac, Pierre Triantafyllou, Areti Trichopoulos, Dimitrios Trichopoulou, Antonia Trinh, Oanh T. H. Trivedi, Atul Tshepo, Lechaba Tsugane, Shoichiro Tuliakova, Azaliia M. Tulloch-Reid, Marshall K. Tullu, Fikru Tuomainen, Tomi-Pekka Tuomilehto, Jaakko Turley, Maria L. Twig, Gilad and Tynelius, Per Tzourio, Christophe Ueda, Peter Ugel, Eunice Ulmer, Hanno Uusitalo, Hannu M. T. Valdivia, Gonzalo and Valvi, Damaskini van Dam, Rob M. van den Born, Bert-Jan and Van der Heyden, Johan van der Schouw, Yvonne T. Van Herck, Koen and Hoang Van Minh Van Schoor, Natasja M. van Valkengoed, Irene G. M. van Zutphen, Elisabeth M. Vanderschueren, Dirk and Vanuzzo, Diego Varbo, Anette Vasan, Senthil K. Vega, Tomas and Veidebaum, Toomas Velasquez-Melendez, Gustavo Veronesi, Giovanni Verschuren, W. M. Monique Verstraeten, Roosmarijn and Victora, Cesar G. Viet, Lucie Villalpando, Salvador Vineis, Paolo Vioque, Jesus Virtanen, Jyrki K. Visvikis-Siest, Sophie Viswanathan, Bharathi Vlasoff, Tiina Vollenweider, Peter Voutilainen, Ari Wade, Alisha N. Walton, Janette and Wambiya, Elvis O. A. Bebakar, Wan Mohamad Wan Mohamud, Wan Nazaimoon Wan Wanderley Junior, Rildo de Souza Wang, Ming-Dong and Wang, Ningli Wang, Qian Wang, Xiangjun Wang, Ya Xing and Wang, Ying-Wei Wannamethee, S. Goya Wareham, Nicholas Wei, Wenbin Weres, Aneta Werner, Bo Whincup, Peter H. and Widhalm, Kurt Widyahening, Indah S. Wiecek, Andrzej Wilks, Rainford J. Willeit, Johann Willeit, Peter Williams, Emmanuel A. Wilsgaard, Tom Wojtyniak, Bogdan Wong-McClure, Roy A. Wong, Andrew Wong, Tien Yin Woo, Jean Woodward, Mark Wu, Frederick C. Wu, Shouling Wyszynska, Justyna and Xu, Haiquan Xu, Liang Yaacob, Nor Azwany Yan, Weili and Yang, Ling Yang, Xiaoguang Yang, Yang Yasuharu, Tabara and Ye, Xingwang Yiallouros, Panayiotis K. Yoosefi, Moein and Yoshihara, Akihiro You, San-Lin Younger-Coleman, Novie O. and Yusoff, Ahmad Faudzi Zainuddin, Ahmad A. Zakavi, Seyed Rasoul and Zamani, Farhad Zambon, Sabina Zampelas, Antonis Elisa Zapata, Maria Zaw, Ko Ko Zdrojewski, Tomasz Zejglicova, Kristyna Vrkic, Tajana Zeljkovic Zeng, Yi Zhang, Luxia and Zhang, Zhen-Yu Zhao, Dong Zhao, Ming-Hui Zhen, Shiqi and Zheng, Yingfeng Zholdin, Bekbolat Zhu, Dan Zins, Marie and Zitt, Emanuel Zocalo, Yanina Zoghlami, Nada Zuniga Cisneros, Julio NCD Risk Factor Collaboration

Abstract

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings. Copyright (C) 2021 World Health Organization; licensee Elsevier.

Published
2021

13. Does Estimated Pulse Wave Velocity Add Prognostic Information?: MORGAM Prospective Cohort Project.

Author

Vishram-Nielsen, Julie K.K., Laurent, Stephane, Nilsson, Peter M., Linneberg, Allan, Sehested, Thomas S.G., Greve, Sara V., Pareek, Manan, Palmieri, Luigi, Giampaoli, Simona, Donfrancesco, Chiara, Kee, Frank, Mancia, Giuseppe, Cesana, Giancarlo, Veronesi, Giovanni, Kuulasmaa, Kari, Salomaa, Veikko, Kontto, Jukka, Palosaari, Tarja, Sans, Susana, and Ferrieres, Jean

Abstract

The Reference Values for Arterial Stiffness Collaboration has derived an equation using age and mean blood pressure to estimated pulse wave velocity (ePWV), which predicted cardiovascular events independently of Systematic COoronary Risk Evaluation (SCORE) and Framingham Risk Score. The study aim was to investigate the independent association between ePWV and clinical outcomes in 107 599 apparently healthy subjects (53% men) aged 19 to 97 years from the MORGAM Project who were included between 1982 and 2002 in 38 cohorts from 11 countries. Using multiple Cox-regression analyses, the predictive value of ePWV was calculated adjusting for country of inclusion and either SCORE, Framingham Risk Score, or traditional cardiovascular risk factors (age, sex, smoking, systolic blood pressure, body mass index [BMI], total and high-density lipoprotein cholesterol). Cardiovascular mortality consisted of fatal stroke, fatal myocardial infarction, or coronary death, and the composite cardiovascular end point consisted of stroke, myocardial infarction, or coronary death. Model discrimination was assessed using Harrell's C-statistic. Adjusting for country and logSCORE or Framingham Risk Score, ePWV was associated with all-cause mortality (hazard ratio, 1.23 [95% CI 1.20-1.25] per m/s or 1.32 [1.29-1.34]), cardiovascular mortality (1.26 [1.21-1.32] or 1.35 [1.31-1.40]), and composite cardiovascular end point (1.19 [1.16-1.22] or 1.23 [1.20-1.25]; all P<0.001). However, after adjusting for traditional cardiovascular risk factors, ePWV was only associated with all-cause mortality (1.15 [1.08-1.22], P<0.001) and not with cardiovascular mortality (0.97 [0.91-1.03]) nor composite cardiovascular end point (1.10 [0.97-1.26]). The areas under the last 3 receiver operator characteristic curves remained unchanged when adding ePWV. Elevated ePWV was associated with subsequent mortality and cardiovascular morbidity independently of systematic coronary risk evaluation and Framingham Risk Score but not independently of traditional cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Published
2020
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14. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Author

Surendran, Praveen, Feofanova, Elena V., Lahrouchi, Najim, Ntalla, Ioanna, Karthikeyan, Savita, Cook, James, Chen, Lingyan, Mifsud, Borbala, Yao, Chen, Kraja, Aldi T., Cartwright, James H., Hellwege, Jacklyn N., Giri, Ayush, Tragante, Vinicius, Thorleifsson, Gudmar, Liu, Dajiang J., Prins, Bram P., Stewart, Isobel D., Cabrera, Claudia P., Eales, James M., Akbarov, Artur, Auer, Paul L., Bielak, Lawrence F., Bis, Joshua C., Braithwaite, Vickie S., Brody, Jennifer A., Daw, E. Warwick, Warren, Helen R., Drenos, Fotios, Nielsen, Sune Fallgaard, Faul, Jessica D., Fauman, Eric B., Fava, Cristiano, Ferreira, Teresa, Foley, Christopher N., Franceschini, Nora, Gao, He, Giannakopoulou, Olga, Giulianini, Franco, Gudbjartsson, Daniel F., Guo, Xiuqing, Harris, Sarah E., Havulinna, Aki S., Helgadottir, Anna, Huffman, Jennifer E., Hwang, Shih-Jen, Kanoni, Stavroula, Kontto, Jukka, Larson, Martin G., Li-Gao, Ruifang, Lindström, Jaana, Lotta, Luca A., Lu, Yingchang, Luan, Jian’an, Mahajan, Anubha, Malerba, Giovanni, Masca, Nicholas G. D., Mei, Hao, Menni, Cristina, Mook-Kanamori, Dennis O., Mosen-Ansorena, David, Müller-Nurasyid, Martina, Paré, Guillaume, Paul, Dirk S., Perola, Markus, Poveda, Alaitz, Rauramaa, Rainer, Richard, Melissa, Richardson, Tom G., Sepúlveda, Nuno, Sim, Xueling, Smith, Albert V., Smith, Jennifer A., Staley, James R., Stanáková, Alena, Sulem, Patrick, Thériault, Sébastien, Thorsteinsdottir, Unnur, Trompet, Stella, Varga, Tibor V., Velez Edwards, Digna R., Veronesi, Giovanni, Weiss, Stefan, Willems, Sara M., Yao, Jie, Young, Robin, Yu, Bing, Zhang, Weihua, Zhao, Jing-Hua, Zhao, Wei, Zhao, Wei, Evangelou, Evangelos, Aeschbacher, Stefanie, Asllanaj, Eralda, Blankenberg, Stefan, Bonnycastle, Lori L., Bork-Jensen, Jette, Brandslund, Ivan, Braund, Peter S., Burgess, Stephen, Cho, Kelly, Christensen, Cramer, Connell, John, Mutsert, Renée de, Dominiczak, Anna F., Dörr, Marcus, Eiriksdottir, Gudny, Farmaki, Aliki-Eleni, Gaziano, J. Michael, Grarup, Niels, Grove, Megan L., Hallmans, Göran, Hansen, Torben, Have, Christian T., Heiss, Gerardo, Jørgensen, Marit E., Jousilahti, Pekka, Kajantie, Eero, Kamat, Mihir, Käräjämäki, AnneMari, Karpe, Fredrik, Koistinen, Heikki A., Kovesdy, Csaba P., Kuulasmaa, Kari, Laatikainen, Tiina, Lannfelt, Lars, Lee, I-Te, Lee, Wen-Jane, Linneberg, Allan, Martin, Lisa W., Moitry, Marie, Nadkarni, Girish, Neville, Matt J., Palmer, Colin N. A., Papanicolaou, George J., Pedersen, Oluf, Peters, James, Poulter, Neil, Rasheed, Asif, Rasmussen, Katrine L., Rayner, N. William, Mägi, Reedik, Renström, Frida, Rettig, Rainer, Rossouw, Jacques, Schreiner, Pamela J., Sever, Peter S., Sigurdsson, Emil L., Skaaby, Tea, Sun, Yan V., Sundstrom, Johan, Thorgeirsson, Gudmundur, Esko, Tõnu, Trabetti, Elisabetta, Tsao, Philip S., Tuomi, Tiinamaija, Turner, Stephen T., Tzoulaki, Ioanna, Vaartjes, Ilonca, Vergnaud, Anne-Claire, Willer, Cristen J., Wilson, Peter W. F., Witte, Daniel R., Yonova-Doing, Ekaterina, Zhang, He, Aliya, Naheed, Almgren, Peter, Amouyel, Philippe, Asselbergs, Folkert W., Barnes, Michael R., Blakemore, Alexandra I., Boehnke, Michael, Bots, Michiel L., Bottinger, Erwin P., Buring, Julie E., Chambers, John C., Chen, Yii-Der Ida, Chowdhury, Rajiv, Conen, David, Correa, Adolfo, Davey Smith, George, Boer, Rudolf A. de, Deary, Ian J., Dedoussis, George, Deloukas, Panos, Di Angelantonio, Emanuele, Elliott, Paul, Felix, Stephan B., Ferrières, Jean, Ford, Ian, Fornage, Myriam, Franks, Paul W., Franks, Stephen, Frossard, Philippe, Gambaro, Giovanni, Gaunt, Tom R., Groop, Leif, Gudnason, Vilmundur, Harris, Tamara B., Hayward, Caroline, Hennig, Branwen J., Herzig, Karl-Heinz, Ingelsson, Erik, Tuomilehto, Jaakko, Järvelin, Marjo-Riitta, Jukema, J. Wouter, Kardia, Sharon L. R., Kee, Frank, Kooner, Jaspal S., Kooperberg, Charles, Launer, Lenore J., Lind, Lars, Loos, Ruth J. F., Majumder, Abdulla al Shafi., Laakso, Markku, McCarthy, Mark I., Melander, Olle, Mohlke, Karen L., Murray, Alison D., Nordestgaard, Børge Grønne, Orho-Melander, Marju, Packard, Chris J., Padmanabhan, Sandosh, Palmas, Walter, Polasek, Ozren, Porteous, David J., Prentice, Andrew M., Province, Michael A., Relton, Caroline L., Rice, Kenneth, Ridker, Paul M., Rolandsson, Olov, Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Sattar, Naveed, Sheu, Wayne H.-H., Smith, Blair H., Soranzo, Nicole, Spector, Timothy D., Starr, John M., Sebert, Sylvain, Taylor, Kent D., Lakka, Timo A., Timpson, Nicholas J., Tobin, Martin D., van der Harst, Pim, van der Meer, Peter, Ramachandran, Vasan S., Verweij, Niek, Virtamo, Jarmo, Völker, Uwe, Weir, David R., Zeggini, Eleftheria, Charchar, Fadi J., Wareham, Nicholas J., Langenberg, Claudia, Tomaszewski, Maciej, Butterworth, Adam S., Caulfield, Mark J., Danesh, John, Edwards, Todd L., Holm, Hilma, Hung, Adriana M., Lindgren, Cecilia M., Liu, Chunyu, Manning, Alisa K., Morris, Andrew P., Morrison, Alanna C., O’Donnell, Christopher J., Psaty, Bruce M., Saleheen, Danish, Stefansson, Kari, Boerwinkle, Eric, Chasman, Daniel I., Levy, Daniel, Newton-Cheh, Christopher, Munroe, Patricia B., and Howson, Joanna M. M.

Abstract

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency?>?0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency?=?0.01) variant BP associations (P?

Published
2020
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15. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Author

Erzurumluoglu, A. Mesut, Liu, Mengzhen, Jackson, Victoria E., Barnes, Daniel R., Datta, Gargi, Melbourne, Carl A., Young, Robin, Batini, Chiara, Surendran, Praveen, Jiang, Tao, Adnan, Sheikh Daud, Afaq, Saima, Agrawal, Arpana, Altmaier, Elisabeth, Antoniou, Antonis C., Asselbergs, Folkert W., Baumbach, Clemens, Bierut, Laura, Bertelsen, Sarah, Boehnke, Michael, Bots, Michiel L., Brazel, David M, Chambers, John C., Chang-Claude, Jenny, Chen, Chu, Corley, Janie, Chou, Yi-Ling, David, Sean P., de Boer, Rudolf A., de Leeuw, Christiaan A., Dennis, Joe G., Dominiczak, Anna F., Dunning, Alison M., Easton, Douglas F., Eaton, Charles, Elliott, Paul, Evangelou, Evangelos, Faul, Jessica D., Foroud, Tatiana, Goate, Alison, Gong, Jian, Grabe, Hans J., Haessler, Jeff, Haiman, Christopher, Hallmans, Göran, Hammerschlag, Anke R., Harris, Sarah E., Hattersley, Andrew, Heath, Andrew, Hsu, Chris, Iacono, William G., Kanoni, Stavroula, Kapoor, Manav, Kaprio, Jaakko, Kardia, Sharon L., Karpe, Fredrik, Kontto, Jukka, Kooner, Jaspal S., Kooperberg, Charles, Kuulasmaa, Kari, Laakso, Markku, Lai, Dongbing, Langenberg, Claudia, Le, Nhung, Lettre, Guillaume, Loukola, Anu, Luan, Jian’an, Madden, Pamela A. F., Mangino, Massimo, Marioni, Riccardo E., Marouli, Eirini, Marten, Jonathan, Martin, Nicholas G., McGue, Matt, Michailidou, Kyriaki, Mihailov, Evelin, Moayyeri, Alireza, Moitry, Marie, Müller-Nurasyid, Martina, Naheed, Aliya, Nauck, Matthias, Neville, Matthew J., Nielsen, Sune Fallgaard, North, Kari, Perola, Markus, Pharoah, Paul D. P., Pistis, Giorgio, Polderman, Tinca J., Posthuma, Danielle, Poulter, Neil, Qaiser, Beenish, Rasheed, Asif, Reiner, Alex, Renström, Frida, Rice, John, Rohde, Rebecca, Rolandsson, Olov, Samani, Nilesh J., Samuel, Maria, Schlessinger, David, Scholte, Steven H, Scott, Robert A., Sever, Peter, Shao, Yaming, Shrine, Nick, Smith, Jennifer A., Starr, John M., Stirrups, Kathleen, Stram, Danielle, Stringham, Heather M., Tachmazidou, Ioanna, Tardif, Jean-Claude, Thompson, Deborah J., Tindle, Hilary A., Tragante, Vinicius, Trompet, Stella, Turcot, Valerie, Tyrrell, Jessica, Vaartjes, Ilonca, van der Leij, Andries R, van der Meer, Peter, Varga, Tibor V., Verweij, Niek, Völzke, Henry, Wareham, Nicholas J., Warren, Helen R., Weir, David R., Weiss, Stefan, Wetherill, Leah, Yaghootkar, Hanieh, Yavas, Ersin, Jiang, Yu, Chen, Fang, Zhan, Xiaowei, Zhang, Weihua, Zhao, Wei, Zhao, Wei, Zhou, Kaixin, Amouyel, Philippe, Blankenberg, Stefan, Caulfield, Mark J., Chowdhury, Rajiv, Cucca, Francesco, Deary, Ian J., Deloukas, Panos, Di Angelantonio, Emanuele, Ferrario, Marco, Ferrières, Jean, Franks, Paul W., Frayling, Tim M., Frossard, Philippe, Hall, Ian P., Hayward, Caroline, Jansson, Jan-Håkan, Jukema, J. Wouter, Kee, Frank, Männistö, Satu, Metspalu, Andres, Munroe, Patricia B., Nordestgaard, Børge Grønne, Palmer, Colin N. A., Salomaa, Veikko, Sattar, Naveed, Spector, Timothy, Strachan, David Peter, van der Harst, Pim, Zeggini, Eleftheria, Saleheen, Danish, Butterworth, Adam S., Wain, Louise V., Abecasis, Goncalo R., Danesh, John, Tobin, Martin D., Vrieze, Scott, Liu, Dajiang J., and Howson, Joanna M. M.

Abstract

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P< 5 × 10−8in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P< 5 × 10−8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P< 4.5 × 10−3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141and two low-frequency SNVs in CEP350and HDGFRP2. Functional follow-up implied that decreased expression of REV3Lmay lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

Published
2020
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16. High-Sensitivity Cardiac Troponin I Levels and Prediction of Heart Failure

Author

Yan, Isabell, Börschel, Christin S., Neumann, Johannes T., Sprünker, Ngoc A., Makarova, Nataliya, Kontto, Jukka, Kuulasmaa, Kari, Salomaa, Veikko, Magnussen, Christina, Iacoviello, Licia, Di Castelnuovo, Augusto, Costanzo, Simona, Linneberg, Allan, Söderberg, Stefan, Zeller, Tanja, Ojeda-Echevarria, Francisco M., Blankenberg, Stefan, and Westermann, Dirk

Abstract

The aims of this study were to characterize the association of high-sensitivity cardiac troponin I (hs-cTnI) with heart failure (HF), to determine its predictive value beyond classical cardiovascular risk factors (CVRFs) and N-terminal pro–B-type natriuretic peptide, and to derive a relevant cutoff for potential clinical application.

Published
2020
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17. Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium

Author

Brunner, Fabian J, Waldeyer, Christoph, Ojeda, Francisco, Salomaa, Veikko, Kee, Frank, Sans, Susana, Thorand, Barbara, Giampaoli, Simona, Brambilla, Paolo, Tunstall-Pedoe, Hugh, Moitry, Marie, Iacoviello, Licia, Veronesi, Giovanni, Grassi, Guido, Mathiesen, Ellisiv B, Söderberg, Stefan, Linneberg, Allan, Brenner, Hermann, Amouyel, Philippe, Ferrières, Jean, Tamosiunas, Abdonas, Nikitin, Yuriy P, Drygas, Wojciech, Melander, Olle, Jöckel, Karl-Heinz, Leistner, David M, Shaw, Jonathan E, Panagiotakos, Demosthenes B, Simons, Leon A, Kavousi, Maryam, Vasan, Ramachandran S, Dullaart, Robin P F, Wannamethee, S Goya, Risérus, Ulf, Shea, Steven, de Lemos, James A, Omland, Torbjørn, Kuulasmaa, Kari, Landmesser, Ulf, Blankenberg, Stefan, Zeller, Tanja, Kontto, Jukka, Männistö, Satu, Metspalu, Andres, Lackner, Karl, Wild, Philipp, Peters, Annette, Meisinger, Christa, Donfrancesco, Chiara, Signorini, Stefano G., Alver, Maris, Woodward, Mark, Gianfagna, Francesco, Costanzo, Simona, Wilsgaard, Tom, Eliasson, Mats, Jørgensen, Torben, Völzke, Henry, Dörr, Marcus, Nauck, Matthias, Schöttker, Ben, Lorenz, Thiess, Makarova, Nataliya, Twerenbold, Raphael, Dallongeville, Jean, Dobson, Annette, Malyutina, Sofia, Pajak, Andrzej, Engström, Gunnar, Bobak, Martin, Schmidt, Börge, Jääskeläinen, Tuija, Niiranen, Teemu, Jousilahti, Pekka, Giles, Graham, Hodge, Allison, Klotsche, Jens, Magliano, Dianna J., Lyngbakken, Magnus N., Hveem, Kristian, Pitsavos, Christos, Benjamin, Emelia J., Bakker, Stephan J.L., Whincup, Peter, Ikram, M. Kamran, Ingelsson, Martin, and Koenig, Wolfgang

Abstract

The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment.

Published
2019
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18. Association of Circulating Metabolites With Risk of Coronary Heart Disease in a European Population: Results From the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium

Author

Cavus, Ersin, Karakas, Mahir, Ojeda, Francisco M., Kontto, Jukka, Veronesi, Giovanni, Ferrario, Marco Mario, Linneberg, Allan, Jørgensen, Torben, Meisinger, Christa, Thorand, Barbara, Iacoviello, Licia, Börnigen, Daniela, Woodward, Mark, Schnabel, Renate, Costanzo, Simona, Tunstall-Pedoe, Hugh, Koenig, Wolfgang, Kuulasmaa, Kari, Salomaa, Veikko, Blankenberg, Stefan, and Zeller, Tanja

Abstract

IMPORTANCE: Risk stratification for coronary heart disease (CHD) remains challenging because of the complex causative mechanism of the disease. Metabolomic profiling offers the potential to detect new biomarkers and improve CHD risk assessment. OBJECTIVE: To evaluate the association between circulating metabolites and incident CHD in a large European cohort. DESIGN, SETTING, AND PARTICIPANTS: This population-based study used the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) case-cohort to measure circulating metabolites using a targeted approach in serum samples from 10 741 individuals without prevalent CHD. The cohort consisted of a weighted, random subcohort of the original cohort of more than 70 000 individuals. The case-cohort design was applied to 6 European cohorts: FINRISK97 (Finland), Monitoring of Trends and Determinants in Cardiovascular Diseases/Cooperative Health Research in the Region of Augsburg (MONICA/KORA; Germany), MONICA-Brianza and Moli-sani (Italy), DanMONICA (Denmark), and the Scottish Heart Health Extended Cohort (United Kingdom). MAIN OUTCOMES AND MEASURES: Associations with time to CHD onset were assessed individually by applying weighted and adjusted Cox proportional hazard models. The association of metabolites with CHD onset was examined by C indices. RESULTS: In 10 741 individuals (4157 women [38.7%]; median [interquartile range] age, 56.5 [49.2-62.2] years), 2166 incident CHD events (20.2%) occurred over a median (interquartile range) follow-up time of 9.2 (4.5-15.0) years. Among the 141 metabolites analyzed, 24 were significantly associated with incident CHD at a nominal P value of .05, including phosphatidylcholines (PCs), lysoPCs, amino acids, and sphingolipids. Five PCs remained significant after correction for multiple testing: acyl-alkyl-PC C40:6 (hazard ratio [HR], 1.13 [95% CI, 1.07-1.18]), diacyl-PC C40:6 (HR, 1.10 [95% CI, 1.04-1.15]), acyl-alkyl-PC C38:6 (HR, 1.11 [95% CI, 1.05-1.16]), diacyl-PC C38:6 (HR, 1.09 [95% CI, 1.04-1.14]) and diacyl-PC C38:5 (HR, 1.10 [95% CI, 1.05-1.16]). Lower levels of these metabolites were associated with increased risk of incident CHD. The strength of the associations competes with those of classic risk factors (C statistics: acyl-alkyl-PC C40:6, 0.756 [95% CI, 0.738-0.774], diacyl-PC C40:6, 0.754 [95% CI, 0.736-0.772], acyl-alkyl-PC C38:6, 0.755 [95% CI, 0.736-0.773], diacyl-PC C38:6, 0.754 [95% CI, 0.736-0.772]), diacyl-PC C38:5, 0.754 [95% CI, 0.736-0.772]). Adding metabolites to a base risk model including classic risk factors high-sensitivity C-reactive protein and high-sensitivity troponin I did not improve discrimination by C statistics. CONCLUSIONS AND RELEVANCE: Five PCs were significantly associated with increased risk of incident CHD and showed comparable discrimination with individual classic risk factors. Although these metabolites do not improve CHD risk assessment beyond that of classic risk factors, these findings hold promise for an improved understanding of the pathophysiology of CHD.

Published
2019
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20. Suomalaisten rahapelikulutus -- keneltä rahapeliyhtiöiden tuotot tulevat?

Author

SALONEN, ANNE H., KONTTO, JUKKA, ALHO, HANNU, and CASTRÉN, SARI

Abstract

Copyright of Yhteiskuntapolitiikka is the property of University of Helsinki, Faculty of Political Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2017

21. Genetic invalidation of Lp-PLA2as a therapeutic target: Large-scale study of five functional Lp-PLA2-lowering alleles

Author

Gregson, John M, Freitag, Daniel F, Surendran, Praveen, Stitziel, Nathan O, Chowdhury, Rajiv, Burgess, Stephen, Kaptoge, Stephen, Gao, Pei, Staley, James R, Willeit, Peter, Nielsen, Sune F, Caslake, Muriel, Trompet, Stella, Polfus, Linda M, Kuulasmaa, Kari, Kontto, Jukka, Perola, Markus, Blankenberg, Stefan, Veronesi, Giovanni, Gianfagna, Francesco, Männistö, Satu, Kimura, Akinori, Lin, Honghuang, Reilly, Dermot F, Gorski, Mathias, Mijatovic, Vladan, Munroe, Patricia B, Ehret, Georg B, Thompson, Alex, Uria-Nickelsen, Maria, Malarstig, Anders, Dehghan, Abbas, Vogt, Thomas F, Sasaoka, Taishi, Takeuchi, Fumihiko, Kato, Norihiro, Yamada, Yoshiji, Kee, Frank, Müller-Nurasyid, Martina, Ferrières, Jean, Arveiler, Dominique, Amouyel, Philippe, Salomaa, Veikko, Boerwinkle, Eric, Thompson, Simon G, Ford, Ian, Wouter Jukema, J, Sattar, Naveed, Packard, Chris J, Shafi Majumder, Abdulla al, Alam, Dewan S, Deloukas, Panos, Schunkert, Heribert, Samani, Nilesh J, Kathiresan, Sekar, Nordestgaard, Børge G, Saleheen, Danish, Howson, Joanna MM, Di Angelantonio, Emanuele, Butterworth, Adam S, and Danesh, John

Abstract

Aims Darapladib, a potent inhibitor of lipoprotein-associated phospholipase A2(Lp-PLA2), has not reduced risk of cardiovascular disease outcomes in recent randomized trials. We aimed to test whether Lp-PLA2enzyme activity is causally relevant to coronary heart disease.Methods In 72,657 patients with coronary heart disease and 110,218 controls in 23 epidemiological studies, we genotyped five functional variants: four rare loss-of-function mutations (c.109+2T > C (rs142974898), Arg82His (rs144983904), Val279Phe (rs76863441), Gln287Ter (rs140020965)) and one common modest-impact variant (Val379Ala (rs1051931)) in PLA2G7,the gene encoding Lp-PLA2. We supplemented de-novo genotyping with information on a further 45,823 coronary heart disease patients and 88,680 controls in publicly available databases and other previous studies. We conducted a systematic review of randomized trials to compare effects of darapladib treatment on soluble Lp-PLA2activity, conventional cardiovascular risk factors, and coronary heart disease risk with corresponding effects of Lp-PLA2-lowering alleles.Results Lp-PLA2activity was decreased by 64% (p= 2.4 × 10–25) with carriage of any of the four loss-of-function variants, by 45% (p< 10–300) for every allele inherited at Val279Phe, and by 2.7% (p= 1.9 × 10–12) for every allele inherited at Val379Ala. Darapladib 160 mg once-daily reduced Lp-PLA2activity by 65% (p< 10–300). Causal risk ratios for coronary heart disease per 65% lower Lp-PLA2activity were: 0.95 (0.88–1.03) with Val279Phe; 0.92 (0.74–1.16) with carriage of any loss-of-function variant; 1.01 (0.68–1.51) with Val379Ala; and 0.95 (0.89–1.02) with darapladib treatment.Conclusions In a large-scale human genetic study, none of a series of Lp-PLA2-lowering alleles was related to coronary heart disease risk, suggesting that Lp-PLA2is unlikely to be a causal risk factor.

Published
2017
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22. Rare and low-frequency coding variants alter human adult height

Author

Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R., Kjaer, Troels R., Fine, Rebecca S., Lu, Yingchang, Schurmann, Claudia, Highland, Heather M., Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E., Lamparter, David, Stirrups, Kathleen E., Turcot, Valérie, Young, Kristin L., Winkler, Thomas W., Esko, Tõnu, Karaderi, Tugce, Locke, Adam E., Masca, Nicholas G. D., Ng, Maggie C. Y., Mudgal, Poorva, Rivas, Manuel A., Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K., Adair, Linda S., Alam, Dewan S., Albrecht, Eva, Allin, Kristine H., Allison, Matthew, Amouyel, Philippe, Appel, Emil V., Arveiler, Dominique, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Banas, Bernhard, Bang, Lia E., Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bonnycastle, Lori L., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Burt, Amber A., Butterworth, Adam S., Carey, David J., Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Cuellar-Partida, Gabriel, Danesh, John, Davies, Gail, de Bakker, Paul I. W., de Borst, Gert J., de Denus, Simon, de Groot, Mark C. H., de Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., den Hollander, Anneke I., Dennis, Joe G., Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dunning, Alison M., Easton, Douglas F., Ebeling, Tapani, Edwards, Todd L., Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Faul, Jessica D., Feitosa, Mary F., Feng, Shuang, Ferrannini, Ele, Ferrario, Marco M., Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franks, Paul W., Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Giri, Ayush, Girotto, Giorgia, Gordon, Scott D., Gordon-Larsen, Penny, Gorski, Mathias, Grarup, Niels, Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Hayward, Caroline, He, Liang, Heid, Iris M., Heikkilä, Kauko, Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Hocking, Lynne J., Hollensted, Mette, Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hoyng, Carel B., Huang, Paul L., Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jhun, Min A., Jia, Yucheng, Jiang, Xuejuan, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jousilahti, Pekka, Jukema, J. Wouter, Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Keeman, Renske, Kiemeney, Lambertus A., Kitajima, Hidetoshi, Kluivers, Kirsten B., Kocher, Thomas, Komulainen, Pirjo, Kontto, Jukka, Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kriebel, Jennifer, Kuivaniemi, Helena, Küry, Sébastien, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lakka, Timo A., Lange, Ethan M., Lange, Leslie A., Langefeld, Carl D., Langenberg, Claudia, Larson, Eric B., Lee, I-Te, Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Yeheng, Liu, Yongmei, Lophatananon, Artitaya, Luan, Jian'an, Lubitz, Steven A., Lyytikäinen, Leo-Pekka, Mackey, David A., Madden, Pamela A. F., Manning, Alisa K., Männistö, Satu, Marenne, Gaëlle, Marten, Jonathan, Martin, Nicholas G., Mazul, Angela L., Meidtner, Karina, Metspalu, Andres, Mitchell, Paul, Mohlke, Karen L., Mook-Kanamori, Dennis O., Morgan, Anna, Morris, Andrew D., Morris, Andrew P., Müller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Ntalla, Ioanna, O'Connel, Jeffrey R., Oksa, Heikki, Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Person, Thomas N., Pirie, Ailith, Polasek, Ozren, Posthuma, Danielle, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Renström, Frida, Ridker, Paul M., Rioux, John D., Robertson, Neil, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sandow, Kevin, Sapkota, Yadav, Sattar, Naveed, Schmidt, Marjanka K., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S., Smith, Albert Vernon, Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Steinthorsdottir, Valgerdur, Stringham, Heather M., Stumvoll, Michael, Surendran, Praveen, ‘t Hart, Leen M., Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Ulivi, Sheila, van der Laan, Sander W., Van Der Leij, Andries R., van Duijn, Cornelia M., van Schoor, Natasja M., van Setten, Jessica, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vozzi, Diego, Walker, Mark, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Wareham, Nicholas J., Warren, Helen R., Wessel, Jennifer, Willems, Sara M., Wilson, James G., Witte, Daniel R., Woods, Michael O., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhao, Wei, Zheng, He, Zhou, Wei, Rotter, Jerome I, Boehnke, Michael, Kathiresan, Sekar, McCarthy, Mark I., Willer, Cristen J., Stefansson, Kari, Borecki, Ingrid B., Liu, Dajiang J., North, Kari E., Heard-Costa, Nancy L., Pers, Tune H., Lindgren, Cecilia M., Oxvig, Claus, Kutalik, Zoltán, Rivadeneira, Fernando, Loos, Ruth J. F., Frayling, Timothy M., Hirschhorn, Joel N., Deloukas, Panos, and Lettre, Guillaume

Abstract

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1–4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, ARand CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2(giving an increase of 1–2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RAand NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

Published
2017
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25. Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease

Author

Webb, Thomas R., Erdmann, Jeanette, Stirrups, Kathleen E., Stitziel, Nathan O., Masca, Nicholas G.D., Jansen, Henning, Kanoni, Stavroula, Nelson, Christopher P., Ferrario, Paola G., König, Inke R., Eicher, John D., Johnson, Andrew D., Hamby, Stephen E., Betsholtz, Christer, Ruusalepp, Arno, Franzén, Oscar, Schadt, Eric E., Björkegren, Johan L.M., Weeke, Peter E., Auer, Paul L., Schick, Ursula M., Lu, Yingchang, Zhang, He, Dube, Marie-Pierre, Goel, Anuj, Farrall, Martin, Peloso, Gina M., Won, Hong-Hee, Do, Ron, van Iperen, Erik, Kruppa, Jochen, Mahajan, Anubha, Scott, Robert A., Willenborg, Christina, Braund, Peter S., van Capelleveen, Julian C., Doney, Alex S.F., Donnelly, Louise A., Asselta, Rosanna, Merlini, Pier A., Duga, Stefano, Marziliano, Nicola, Denny, Josh C., Shaffer, Christian, El-Mokhtari, Nour Eddine, Franke, Andre, Heilmann, Stefanie, Hengstenberg, Christian, Hoffmann, Per, Holmen, Oddgeir L., Hveem, Kristian, Jansson, Jan-Håkan, Jöckel, Karl-Heinz, Kessler, Thorsten, Kriebel, Jennifer, Laugwitz, Karl L., Marouli, Eirini, Martinelli, Nicola, McCarthy, Mark I., Van Zuydam, Natalie R., Meisinger, Christa, Esko, Tõnu, Mihailov, Evelin, Escher, Stefan A., Alver, Maris, Moebus, Susanne, Morris, Andrew D., Virtamo, Jarma, Nikpay, Majid, Olivieri, Oliviero, Provost, Sylvie, AlQarawi, Alaa, Robertson, Neil R., Akinsansya, Karen O., Reilly, Dermot F., Vogt, Thomas F., Yin, Wu, Asselbergs, Folkert W., Kooperberg, Charles, Jackson, Rebecca D., Stahl, Eli, Müller-Nurasyid, Martina, Strauch, Konstantin, Varga, Tibor V., Waldenberger, Melanie, Zeng, Lingyao, Chowdhury, Rajiv, Salomaa, Veikko, Ford, Ian, Jukema, J. Wouter, Amouyel, Philippe, Kontto, Jukka, Nordestgaard, Børge G., Ferrières, Jean, Saleheen, Danish, Sattar, Naveed, Surendran, Praveen, Wagner, Aline, Young, Robin, Howson, Joanna M.M., Butterworth, Adam S., Danesh, John, Ardissino, Diego, Bottinger, Erwin P., Erbel, Raimund, Franks, Paul W., Girelli, Domenico, Hall, Alistair S., Hovingh, G. Kees, Kastrati, Adnan, Lieb, Wolfgang, Meitinger, Thomas, Kraus, William E., Shah, Svati H., McPherson, Ruth, Orho-Melander, Marju, Melander, Olle, Metspalu, Andres, Palmer, Colin N.A., Peters, Annette, Rader, Daniel J., Reilly, Muredach P., Loos, Ruth J.F., Reiner, Alex P., Roden, Dan M., Tardif, Jean-Claude, Thompson, John R., Wareham, Nicholas J., Watkins, Hugh, Willer, Cristen J., Samani, Nilesh J., Schunkert, Heribert, Deloukas, Panos, and Kathiresan, Sekar

Subjects
cholesteryl ester transfer protein, expression quantitative trait loci, genetics, genome-wide association, single nucleotide polymorphism, BMI, body mass index, CAD, coronary artery disease, CETP, eQTL, expression quantitative trait locus, GWAS, genome-wide association study, HDL, high-density lipoprotein, LD, linkage disequilibrium, LDL, low-density lipoprotein, SNP
Abstract

Background: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits. Objectives: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci. Methods: In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs. Results: We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10−4 with a range of other diseases/traits. Conclusions: We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.

Published
2017
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26. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Author

Surendran, Praveen, Drenos, Fotios, Young, Robin, Warren, Helen, Cook, James P, Manning, Alisa K, Grarup, Niels, Sim, Xueling, Barnes, Daniel R, Witkowska, Kate, Staley, James R, Tragante, Vinicius, Tukiainen, Taru, Yaghootkar, Hanieh, Masca, Nicholas, Freitag, Daniel F, Ferreira, Teresa, Giannakopoulou, Olga, Tinker, Andrew, Harakalova, Magdalena, Mihailov, Evelin, Liu, Chunyu, Kraja, Aldi T, Nielsen, Sune Fallgaard, Rasheed, Asif, Samuel, Maria, Zhao, Wei, Bonnycastle, Lori L, Jackson, Anne U, Narisu, Narisu, Swift, Amy J, Southam, Lorraine, Marten, Jonathan, Huyghe, Jeroen R, Stančáková, Alena, Fava, Cristiano, Ohlsson, Therese, Matchan, Angela, Stirrups, Kathleen E, Bork-Jensen, Jette, Gjesing, Anette P, Kontto, Jukka, Perola, Markus, Shaw-Hawkins, Susan, Havulinna, Aki S, Zhang, He, Donnelly, Louise A, Groves, Christopher J, Rayner, N William, Neville, Matt J, Robertson, Neil R, Yiorkas, Andrianos M, Herzig, Karl-Heinz, Kajantie, Eero, Zhang, Weihua, Willems, Sara M, Lannfelt, Lars, Malerba, Giovanni, Soranzo, Nicole, Trabetti, Elisabetta, Verweij, Niek, Evangelou, Evangelos, Moayyeri, Alireza, Vergnaud, Anne-Claire, Nelson, Christopher P, Poveda, Alaitz, Varga, Tibor V, Caslake, Muriel, de Craen, Anton J M, Trompet, Stella, Luan, Jian’an, Scott, Robert A, Harris, Sarah E, Liewald, David C M, Marioni, Riccardo, Menni, Cristina, Farmaki, Aliki-Eleni, Hallmans, Göran, Renström, Frida, Huffman, Jennifer E, Hassinen, Maija, Burgess, Stephen, Vasan, Ramachandran S, Felix, Janine F, Uria-Nickelsen, Maria, Malarstig, Anders, Reilly, Dermot F, Hoek, Maarten, Vogt, Thomas F, Lin, Honghuang, Lieb, Wolfgang, Traylor, Matthew, Markus, Hugh S, Highland, Heather M, Justice, Anne E, Marouli, Eirini, Lindström, Jaana, Uusitupa, Matti, Komulainen, Pirjo, Lakka, Timo A, Rauramaa, Rainer, Polasek, Ozren, Rudan, Igor, Rolandsson, Olov, Franks, Paul W, Dedoussis, George, Spector, Timothy D, Jousilahti, Pekka, Männistö, Satu, Deary, Ian J, Starr, John M, Langenberg, Claudia, Wareham, Nick J, Brown, Morris J, Dominiczak, Anna F, Connell, John M, Jukema, J Wouter, Sattar, Naveed, Ford, Ian, Packard, Chris J, Esko, Tõnu, Mägi, Reedik, Metspalu, Andres, de Boer, Rudolf A, van der Meer, Peter, van der Harst, Pim, Gambaro, Giovanni, Ingelsson, Erik, Lind, Lars, de Bakker, Paul I W, Numans, Mattijs E, Brandslund, Ivan, Christensen, Cramer, Petersen, Eva R B, Korpi-Hyövälti, Eeva, Oksa, Heikki, Chambers, John C, Kooner, Jaspal S, Blakemore, Alexandra I F, Franks, Steve, Jarvelin, Marjo-Riitta, Husemoen, Lise L, Linneberg, Allan, Skaaby, Tea, Thuesen, Betina, Karpe, Fredrik, Tuomilehto, Jaakko, Doney, Alex S F, Morris, Andrew D, Palmer, Colin N A, Holmen, Oddgeir Lingaas, Hveem, Kristian, Willer, Cristen J, Tuomi, Tiinamaija, Groop, Leif, Käräjämäki, AnneMari, Palotie, Aarno, Ripatti, Samuli, Salomaa, Veikko, Alam, Dewan S, Majumder, Abdulla al Shafi, Di Angelantonio, Emanuele, Chowdhury, Rajiv, McCarthy, Mark I, Poulter, Neil, Stanton, Alice V, Sever, Peter, Amouyel, Philippe, Arveiler, Dominique, Blankenberg, Stefan, Ferrières, Jean, Kee, Frank, Kuulasmaa, Kari, Müller-Nurasyid, Martina, Veronesi, Giovanni, Virtamo, Jarmo, Deloukas, Panos, Elliott, Paul, Zeggini, Eleftheria, Kathiresan, Sekar, Melander, Olle, Kuusisto, Johanna, Laakso, Markku, Padmanabhan, Sandosh, Porteous, David J, Hayward, Caroline, Scotland, Generation, Collins, Francis S, Mohlke, Karen L, Hansen, Torben, Pedersen, Oluf, Boehnke, Michael, Stringham, Heather M, Frossard, Philippe, Newton-Cheh, Christopher, Tobin, Martin D, Nordestgaard, Børge Grønne, Caulfield, Mark J, Mahajan, Anubha, Morris, Andrew P, Tomaszewski, Maciej, Samani, Nilesh J, Saleheen, Danish, Asselbergs, Folkert W, Lindgren, Cecilia M, Danesh, John, Wain, Louise V, Butterworth, Adam S, Howson, Joanna M M, and Munroe, Patricia B

Abstract

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure– or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.

Published
2016
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27. Rare and low-frequency coding variants alter human adult height

Author

Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valérie, Young, Kristin L, Winkler, Thomas W, Esko, Tõnu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas GD, Ng, Maggie CY, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bonnycastle, Lori L, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Burt, Amber A, Butterworth, Adam S, Carey, David J, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J, Cuellar-Partida, Gabriel, Danesh, John, Davies, Gail, de Bakker, Paul IW, de Borst, Gert J., de Denus, Simon, de Groot, Mark CH, de Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, den Hollander, Anneke I, Dennis, Joe G, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dunning, Alison M, Easton, Douglas F, Ebeling, Tapani, Edwards, Todd L, Ellinor, Patrick T, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Faul, Jessica D, Feitosa, Mary F, Feng, Shuang, Ferrannini, Ele, Ferrario, Marco M, Ferrieres, Jean, Florez, Jose C, Ford, Ian, Fornage, Myriam, Franks, Paul W, Frikke-Schmidt, Ruth, Galesloot, Tessel E, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Giri, Ayush, Girotto, Giorgia, Gordon, Scott D, Gordon-Larsen, Penny, Gorski, Mathias, Grarup, Niels, Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B, Hattersley, Andrew T, Hayward, Caroline, He, Liang, Heid, Iris M, Heikkilä, Kauko, Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Hovingh, G. Kees, Howson, Joanna MM, Hoyng, Carel B, Huang, Paul L, Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U, Jansson, Jan-Håkan, Jarvik, Gail P, Jensen, Gorm B, Jhun, Min A, Jia, Yucheng, Jiang, Xuejuan, Johansson, Stefan, Jørgensen, Marit E, Jørgensen, Torben, Jousilahti, Pekka, Jukema, J Wouter, Kahali, Bratati, Kahn, René S, Kähönen, Mika, Kamstrup, Pia R, Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon LR, Karpe, Fredrik, Kee, Frank, Keeman, Renske, Kiemeney, Lambertus A, Kitajima, Hidetoshi, Kluivers, Kirsten B, Kocher, Thomas, Komulainen, Pirjo, Kontto, Jukka, Kooner, Jaspal S, Kooperberg, Charles, Kovacs, Peter, Kriebel, Jennifer, Kuivaniemi, Helena, Küry, Sébastien, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lakka, Timo A, Lange, Ethan M, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Larson, Eric B, Lee, I-Te, Lehtimäki, Terho, Lewis, Cora E, Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Yeheng, Liu, Yongmei, Lophatananon, Artitaya, Luan, Jian'an, Lubitz, Steven A, Lyytikäinen, Leo-Pekka, Mackey, David A, Madden, Pamela AF, Manning, Alisa K, Männistö, Satu, Marenne, Gaëlle, Marten, Jonathan, Martin, Nicholas G, Mazul, Angela L, Meidtner, Karina, Metspalu, Andres, Mitchell, Paul, Mohlke, Karen L, Mook-Kanamori, Dennis O, Morgan, Anna, Morris, Andrew D, Morris, Andrew P, Müller-Nurasyid, Martina, Munroe, Patricia B, Nalls, Mike A, Nauck, Matthias, Nelson, Christopher P, Neville, Matt, Nielsen, Sune F, Nikus, Kjell, Njølstad, Pål R, Nordestgaard, Børge G, Ntalla, Ioanna, O'Connel, Jeffrey R, Oksa, Heikki, Loohuis, Loes M Olde, Ophoff, Roel A, Owen, Katharine R, Packard, Chris J, Padmanabhan, Sandosh, Palmer, Colin NA, Pasterkamp, Gerard, Patel, Aniruddh P, Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L, Peloso, Gina M, Pennell, Craig E, Perola, Markus, Perry, James A, Perry, John R.B., Person, Thomas N, Pirie, Ailith, Polasek, Ozren, Posthuma, Danielle, Raitakari, Olli T, Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F, Reiner, Alex P, Renström, Frida, Ridker, Paul M, Rioux, John D, Robertson, Neil, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J, Sandow, Kevin, Sapkota, Yadav, Sattar, Naveed, Schmidt, Marjanka K, Schreiner, Pamela J, Schulze, Matthias B, Scott, Robert A, Segura-Lepe, Marcelo P, Shah, Svati, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S, Smith, Albert Vernon, Smith, Jennifer A, Southam, Lorraine, Spector, Timothy D, Speliotes, Elizabeth K, Starr, John M, Steinthorsdottir, Valgerdur, Stringham, Heather M, Stumvoll, Michael, Surendran, Praveen, Hart, Leen M ‘t, Tansey, Katherine E, Tardif, Jean-Claude, Taylor, Kent D, Teumer, Alexander, Thompson, Deborah J, Thorsteinsdottir, Unnur, Thuesen, Betina H, Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P, Uher, Rudolf, Uitterlinden, André G, Ulivi, Sheila, van der Laan, Sander W, Van Der Leij, Andries R, van Duijn, Cornelia M, van Schoor, Natasja M, van Setten, Jessica, Varbo, Anette, Varga, Tibor V, Varma, Rohit, Edwards, Digna R Velez, Vermeulen, Sita H, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F, Vozzi, Diego, Walker, Mark, Wang, Feijie, Wang, Carol A, Wang, Shuai, Wang, Yiqin, Wareham, Nicholas J, Warren, Helen R, Wessel, Jennifer, Willems, Sara M, Wilson, James G, Witte, Daniel R, Woods, Michael O, Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M, Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Rotter, Jerome I, Boehnke, Michael, Kathiresan, Sekar, McCarthy, Mark I, Willer, Cristen J, Stefansson, Kari, Borecki, Ingrid B, Liu, Dajiang J, North, Kari E, Heard-Costa, Nancy L, Pers, Tune H, Lindgren, Cecilia M, Oxvig, Claus, Kutalik, Zoltán, Rivadeneira, Fernando, Loos, Ruth JF, Frayling, Timothy M, Hirschhorn, Joel N, Deloukas, Panos, and Lettre, Guillaume

Abstract

Summary Height is a highly heritable, classic polygenic trait with ∼700 common associated variants identified so far through genome-wide association studies. Here, we report 83 height-associated coding variants with lower minor allele frequencies (range of 0.1-4.8%) and effects of up to 2 cm/allele (e.g. in IHH, STC2, AR and CRISPLD2), >10 times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (+1-2 cm/allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates (e.g. ADAMTS3, IL11RA, NOX4) and pathways (e.g. proteoglycan/glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate to large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

Published
2016
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29. Dairy foods and risk of stroke.

Author

Larsson, Susanna C., Männistö, Satu, Virtanen, Mikko J., Kontto, Jukka, Albanes, Demetrius, and Virtamo, Jarmo

Subjects
COMPARATIVE studies, DAIRY products, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, QUESTIONNAIRES, RESEARCH, RESEARCH funding, RISK assessment, STROKE, EVALUATION research
Abstract

Background: Consumption of milk and other dairy foods has been associated with reduced risk of stroke, although not all studies have shown this consistently.Methods: We examined the association between dairy food intake and risk of stroke subtypes within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Between 1985 and 1988, 26,556 Finnish male smokers aged 50-69 years who had no history of stroke completed a food frequency questionnaire. We used Cox proportional hazards models to estimate relative risks (RRs) and 95% confidence intervals (CIs), adjusted for potential confounders.Results: During a mean follow-up of 13.6 years, 2702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages were ascertained. We observed positive associations between whole milk intake and risk of intracerebral hemorrhage (RR = 1.41 for the highest vs. lowest quintile of intake; 95% CI = 1.02-1.96) and between yogurt intake and subarachnoid hemorrhage (RR = 1.83 for the highest vs. lowest quintile of intake; 95% CI = 1.20-2.80). Men in the highest quintile of cream intake had a moderate decreased risk of cerebral infarction (0.81; 0.72-0.92) and intracerebral hemorrhage (0.72; 0.52-1.00). There were no strong associations between intakes of total dairy, low-fat milk, sour milk, cheese, ice cream, or butter and risk of any stroke subtype.Conclusions: These findings suggest that intake of certain dairy foods may be associated with risk of stroke. [ABSTRACT FROM AUTHOR]

Published
2009
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31. Publisher Correction: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Author

Surendran, Praveen, Feofanova, Elena V., Lahrouchi, Najim, Ntalla, Ioanna, Karthikeyan, Savita, Cook, James, Chen, Lingyan, Mifsud, Borbala, Yao, Chen, Kraja, Aldi T., Cartwright, James H., Hellwege, Jacklyn N., Giri, Ayush, Tragante, Vinicius, Thorleifsson, Gudmar, Liu, Dajiang J., Prins, Bram P., Stewart, Isobel D., Cabrera, Claudia P., Eales, James M., Akbarov, Artur, Auer, Paul L., Bielak, Lawrence F., Bis, Joshua C., Braithwaite, Vickie S., Brody, Jennifer A., Daw, E. Warwick, Warren, Helen R., Drenos, Fotios, Nielsen, Sune Fallgaard, Faul, Jessica D., Fauman, Eric B., Fava, Cristiano, Ferreira, Teresa, Foley, Christopher N., Franceschini, Nora, Gao, He, Giannakopoulou, Olga, Giulianini, Franco, Gudbjartsson, Daniel F., Guo, Xiuqing, Harris, Sarah E., Havulinna, Aki S., Helgadottir, Anna, Huffman, Jennifer E., Hwang, Shih-Jen, Kanoni, Stavroula, Kontto, Jukka, Larson, Martin G., Li-Gao, Ruifang, Lindström, Jaana, Lotta, Luca A., Lu, Yingchang, Luan, Jian’an, Mahajan, Anubha, Malerba, Giovanni, Masca, Nicholas G. D., Mei, Hao, Menni, Cristina, Mook-Kanamori, Dennis O., Mosen-Ansorena, David, Müller-Nurasyid, Martina, Paré, Guillaume, Paul, Dirk S., Perola, Markus, Poveda, Alaitz, Rauramaa, Rainer, Richard, Melissa, Richardson, Tom G., Sepúlveda, Nuno, Sim, Xueling, Smith, Albert V., Smith, Jennifer A., Staley, James R., Stanáková, Alena, Sulem, Patrick, Thériault, Sébastien, Thorsteinsdottir, Unnur, Trompet, Stella, Varga, Tibor V., Velez Edwards, Digna R., Veronesi, Giovanni, Weiss, Stefan, Willems, Sara M., Yao, Jie, Young, Robin, Yu, Bing, Zhang, Weihua, Zhao, Jing-Hua, Zhao, Wei, Zhao, Wei, Evangelou, Evangelos, Aeschbacher, Stefanie, Asllanaj, Eralda, Blankenberg, Stefan, Bonnycastle, Lori L., Bork-Jensen, Jette, Brandslund, Ivan, Braund, Peter S., Burgess, Stephen, Cho, Kelly, Christensen, Cramer, Connell, John, Mutsert, Renée de, Dominiczak, Anna F., Dörr, Marcus, Eiriksdottir, Gudny, Farmaki, Aliki-Eleni, Gaziano, J. Michael, Grarup, Niels, Grove, Megan L., Hallmans, Göran, Hansen, Torben, Have, Christian T., Heiss, Gerardo, Jørgensen, Marit E., Jousilahti, Pekka, Kajantie, Eero, Kamat, Mihir, Käräjämäki, AnneMari, Karpe, Fredrik, Koistinen, Heikki A., Kovesdy, Csaba P., Kuulasmaa, Kari, Laatikainen, Tiina, Lannfelt, Lars, Lee, I-Te, Lee, Wen-Jane, Linneberg, Allan, Martin, Lisa W., Moitry, Marie, Nadkarni, Girish, Neville, Matt J., Palmer, Colin N. A., Papanicolaou, George J., Pedersen, Oluf, Peters, James, Poulter, Neil, Rasheed, Asif, Rasmussen, Katrine L., Rayner, N. William, Mägi, Reedik, Renström, Frida, Rettig, Rainer, Rossouw, Jacques, Schreiner, Pamela J., Sever, Peter S., Sigurdsson, Emil L., Skaaby, Tea, Sun, Yan V., Sundstrom, Johan, Thorgeirsson, Gudmundur, Esko, Tõnu, Trabetti, Elisabetta, Tsao, Philip S., Tuomi, Tiinamaija, Turner, Stephen T., Tzoulaki, Ioanna, Vaartjes, Ilonca, Vergnaud, Anne-Claire, Willer, Cristen J., Wilson, Peter W. F., Witte, Daniel R., Yonova-Doing, Ekaterina, Zhang, He, Aliya, Naheed, Almgren, Peter, Amouyel, Philippe, Asselbergs, Folkert W., Barnes, Michael R., Blakemore, Alexandra I., Boehnke, Michael, Bots, Michiel L., Bottinger, Erwin P., Buring, Julie E., Chambers, John C., Chen, Yii-Der Ida, Chowdhury, Rajiv, Conen, David, Correa, Adolfo, Davey Smith, George, Boer, Rudolf A. de, Deary, Ian J., Dedoussis, George, Deloukas, Panos, Di Angelantonio, Emanuele, Elliott, Paul, Felix, Stephan B., Ferrières, Jean, Ford, Ian, Fornage, Myriam, Franks, Paul W., Franks, Stephen, Frossard, Philippe, Gambaro, Giovanni, Gaunt, Tom R., Groop, Leif, Gudnason, Vilmundur, Harris, Tamara B., Hayward, Caroline, Hennig, Branwen J., Herzig, Karl-Heinz, Ingelsson, Erik, Tuomilehto, Jaakko, Järvelin, Marjo-Riitta, Jukema, J. Wouter, Kardia, Sharon L. R., Kee, Frank, Kooner, Jaspal S., Kooperberg, Charles, Launer, Lenore J., Lind, Lars, Loos, Ruth J. 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Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41588-021-00832-z.

Published
2021
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32. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Author

Zhou, Bin, Carrillo-Larco, Rodrigo M, Danaei, Goodarz, Riley, Leanne M, Paciorek, Christopher J, Stevens, Gretchen A, Gregg, Edward W, Bennett, James E, Solomon, Bethlehem, Singleton, Rosie K, Sophiea, Marisa K, Iurilli, Maria LC, Lhoste, Victor PF, Cowan, Melanie J, Savin, Stefan, Woodward, Mark, Balanova, Yulia, Cifkova, Renata, Damasceno, Albertino, Elliott, Paul, Farzadfar, Farshad, He, Jiang, Ikeda, Nayu, Kengne, Andre P, Khang, Young-Ho, Kim, Hyeon Chang, Laxmaiah, Avula, Lin, Hsien-Ho, Margozzini Maira, Paula, Miranda, J Jaime, Neuhauser, Hannelore, Sundström, Johan, Varghese, Cherian, Widyahening, Indah S, Zdrojewski, Tomasz, Abarca-Gómez, Leandra, Abdeen, Ziad A, Abdul Rahim, Hanan F, Abu-Rmeileh, Niveen M, Acosta-Cazares, Benjamin, Adams, Robert J, Aekplakorn, Wichai, Afsana, Kaosar, Afzal, Shoaib, Agdeppa, Imelda A, Aghazadeh-Attari, Javad, Aguilar-Salinas, Carlos A, Agyemang, Charles, Ahmad, Noor Ani, Ahmadi, Ali, Ahmadi, Naser, Ahmadi, Nastaran, Ahmadizar, Fariba, Ahmed, Soheir H, Ahrens, Wolfgang, Ajlouni, Kamel, Al-Raddadi, Rajaa, Alarouj, Monira, AlBuhairan, Fadia, AlDhukair, Shahla, Ali, Mohamed M, Alkandari, Abdullah, Alkerwi, Ala'a, Allin, Kristine, Aly, Eman, Amarapurkar, Deepak N, Amougou, Norbert, Amouyel, Philippe, Andersen, Lars Bo, Anderssen, Sigmund A, Anjana, Ranjit Mohan, Ansari-Moghaddam, Alireza, Ansong, Daniel, Aounallah-Skhiri, Hajer, Araújo, Joana, Ariansen, Inger, Aris, Tahir, Arku, Raphael E, Arlappa, Nimmathota, Aryal, Krishna K, Aspelund, Thor, Assah, Felix K, Assunção, Maria Cecília F, Auvinen, Juha, Avdićová, Mária, Azevedo, Ana, Azimi-Nezhad, Mohsen, Azizi, Fereidoun, Azmin, Mehrdad, Babu, Bontha V, Bahijri, Suhad, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Banadinović, Maja, Bandosz, Piotr, Banegas, José R, Baran, Joanna, Barbagallo, Carlo M, Barceló, Alberto, Barkat, Amina, Barreto, Marta, Barros, Aluisio JD, Barros, Mauro Virgílio Gomes, Bartosiewicz, Anna, Basit, Abdul, Bastos, Joao Luiz D, Bata, Iqbal, 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Woo, Jean, Wu, Frederick C, Wu, Shouling, Wyszynska, Justyna, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, San-Lin, Younger-Coleman, Novie O, Yusoff, Ahmad Faudzi, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antonis, Zapata, Maria Elisa, Zaw, Ko Ko, Zejglicova, Kristyna, Zeljkovic Vrkic, Tajana, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhen, Shiqi, Zheng, Yingfeng, Zholdin, Bekbolat, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Zoghlami, Nada, Zuñiga Cisneros, Julio, and Ezzati, Majid

Abstract

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30–79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30–79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306–359) million women and 317 (292–344) million men in 1990 to 626 (584–668) million women and 652 (604–698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55–62) of women and 49% (46–52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43–51) of women and 38% (35–41) of

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33. A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1Rvariant protective for coronary heart disease

Author

Scott, Robert A., Freitag, Daniel F., Li, Li, Chu, Audrey Y., Surendran, Praveen, Young, Robin, Grarup, Niels, Stancáková, Alena, Chen, Yuning, Varga, Tibor V., Yaghootkar, Hanieh, Luan, Jian’an, Zhao, Jing Hua, Willems, Sara M., Wessel, Jennifer, Wang, Shuai, Maruthur, Nisa, Michailidou, Kyriaki, Pirie, Ailith, van der Lee, Sven J., Gillson, Christopher, Al Olama, Ali Amin, Amouyel, Philippe, Arriola, Larraitz, Arveiler, Dominique, Aviles-Olmos, Iciar, Balkau, Beverley, Barricarte, Aurelio, Barroso, Inês, Garcia, Sara Benlloch, Bis, Joshua C., Blankenberg, Stefan, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Borecki, Ingrid B., Bork-Jensen, Jette, Bowden, Sarah, Caldas, Carlos, Caslake, Muriel, Cupples, L. Adrienne, Cruchaga, Carlos, Czajkowski, Jacek, den Hoed, Marcel, Dunn, Janet A., Earl, Helena M., Ehret, Georg B., Ferrannini, Ele, Ferrieres, Jean, Foltynie, Thomas, Ford, Ian, Forouhi, Nita G., Gianfagna, Francesco, Gonzalez, Carlos, Grioni, Sara, Hiller, Louise, Jansson, Jan-Håkan, Jørgensen, Marit E., Jukema, J. Wouter, Kaaks, Rudolf, Kee, Frank, Kerrison, Nicola D., Key, Timothy J., Kontto, Jukka, Kote-Jarai, Zsofia, Kraja, Aldi T., Kuulasmaa, Kari, Kuusisto, Johanna, Linneberg, Allan, Liu, Chunyu, Marenne, Gaëlle, Mohlke, Karen L., Morris, Andrew P., Muir, Kenneth, Müller-Nurasyid, Martina, Munroe, Patricia B., Navarro, Carmen, Nielsen, Sune F., Nilsson, Peter M., Nordestgaard, Børge G., Packard, Chris J., Palli, Domenico, Panico, Salvatore, Peloso, Gina M., Perola, Markus, Peters, Annette, Poole, Christopher J., Quirós, J. Ramón, Rolandsson, Olov, Sacerdote, Carlotta, Salomaa, Veikko, Sánchez, María-José, Sattar, Naveed, Sharp, Stephen J., Sims, Rebecca, Slimani, Nadia, Smith, Jennifer A., Thompson, Deborah J., Trompet, Stella, Tumino, Rosario, van der A, Daphne L., van der Schouw, Yvonne T., Virtamo, Jarmo, Walker, Mark, Walter, Klaudia, Abraham, Jean E., Amundadottir, Laufey T., Aponte, Jennifer L., Butterworth, Adam S., Dupuis, Josée, Easton, Douglas F., Eeles, Rosalind A., Erdmann, Jeanette, Franks, Paul W., Frayling, Timothy M., Hansen, Torben, Howson, Joanna M. M., Jørgensen, Torben, Kooner, Jaspal, Laakso, Markku, Langenberg, Claudia, McCarthy, Mark I., Pankow, James S., Pedersen, Oluf, Riboli, Elio, Rotter, Jerome I., Saleheen, Danish, Samani, Nilesh J., Schunkert, Heribert, Vollenweider, Peter, O’Rahilly, Stephen, Deloukas, Panos, Danesh, John, Goodarzi, Mark O., Kathiresan, Sekar, Meigs, James B., Ehm, Margaret G., Wareham, Nicholas J., and Waterworth, Dawn M.

Abstract

A missense variant in GLP1R associated with lower fasting glucose levels and protective against T2D is associated with lower risk of coronary heart disease, suggesting that GLP1R agonists are not associated with an unacceptable increase in cardiovascular risk.

Published
2016
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