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5. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.

Author

Franceschini, Nora, Giambartolomei, Claudia, de Vries, Paul S, Finan, Chris, Bis, Joshua C, Huntley, Rachael P, Lovering, Ruth C, Tajuddin, Salman M, Winkler, Thomas W, Graff, Misa, Kavousi, Maryam, Dale, Caroline, Smith, Albert V, Hofer, Edith, van Leeuwen, Elisabeth M, Nolte, Ilja M, Lu, Lingyi, Scholz, Markus, Sargurupremraj, Muralidharan, Pitkänen, Niina, Franzén, Oscar, Joshi, Peter K, Noordam, Raymond, Marioni, Riccardo E, Hwang, Shih-Jen, Musani, Solomon K, Schminke, Ulf, Palmas, Walter, Isaacs, Aaron, Correa, Adolfo, Zonderman, Alan B, Hofman, Albert, Teumer, Alexander, Cox, Amanda J, Uitterlinden, André G, Wong, Andrew, Smit, Andries J, Newman, Anne B, Britton, Annie, Ruusalepp, Arno, Sennblad, Bengt, Hedblad, Bo, Pasaniuc, Bogdan, Penninx, Brenda W, Langefeld, Carl D, Wassel, Christina L, Tzourio, Christophe, Fava, Cristiano, Baldassarre, Damiano, O'Leary, Daniel H, Teupser, Daniel, Kuh, Diana, Tremoli, Elena, Mannarino, Elmo, Grossi, Enzo, Boerwinkle, Eric, Schadt, Eric E, Ingelsson, Erik, Veglia, Fabrizio, Rivadeneira, Fernando, Beutner, Frank, Chauhan, Ganesh, Heiss, Gerardo, Snieder, Harold, Campbell, Harry, Völzke, Henry, Markus, Hugh S, Deary, Ian J, Jukema, J Wouter, de Graaf, Jacqueline, Price, Jacqueline, Pott, Janne, Hopewell, Jemma C, Liang, Jingjing, Thiery, Joachim, Engmann, Jorgen, Gertow, Karl, Rice, Kenneth, Taylor, Kent D, Dhana, Klodian, Kiemeney, Lambertus ALM, Lind, Lars, Raffield, Laura M, Launer, Lenore J, Holdt, Lesca M, Dörr, Marcus, Dichgans, Martin, Traylor, Matthew, Sitzer, Matthias, Kumari, Meena, Kivimaki, Mika, Nalls, Mike A, Melander, Olle, Raitakari, Olli, Franco, Oscar H, Rueda-Ochoa, Oscar L, Roussos, Panos, Whincup, Peter H, Amouyel, Philippe, and Giral, Philippe

Subjects
MEGASTROKE Consortium, Humans, Coronary Disease, Genetic Predisposition to Disease, Amino Acid Oxidoreductases, Protein-Lysine 6-Oxidase, Risk Factors, Lod Score, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study, Plaque, Atherosclerotic, Carotid Intima-Media Thickness, ADAMTS9 Protein, Plaque, Atherosclerotic, Polymorphism, Single Nucleotide
Abstract

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Published
2018

10. Reply

Author

Rueda-Ochoa, Oscar L., Kavousi, Maryam, and Rizopoulos, Dimitris

Published
2019
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13. Thoracic Aortic Diameter and Cardiovascular Events and Mortality among Women and Men

Author

Rueda-Ochoa, Oscar L., primary, Bons, Lidia R., additional, Zhu, Fang, additional, Rohde, Sofie, additional, El Ghoul, Khalid, additional, Budde, Ricardo P. J., additional, Ikram, M. Kamran, additional, Deckers, Jaap W., additional, Vernooij, Meike W., additional, Franco, Oscar H., additional, van der Lugt, Aad, additional, Bos, Daniel, additional, Roos-Hesselink, Jolien W., additional, and Kavousi, Maryam, additional

Published
2022
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19. Echocardiographic parameters, speckle tracking, and brain natriuretic peptide levels as indicators of progression of indeterminate stage to Chagas cardiomyopathy

Author

Echeverría, Luis E., primary, Rojas, Lyda Z., additional, Villamizar, María C., additional, Luengas, Carlos, additional, Chaves, Angel M., additional, Rodríguez, Jaime A., additional, Campo, Rafael, additional, Clavijo, Claudia, additional, Redondo, Adriana M., additional, López, Luis A., additional, Gómez‐Ochoa, Sergio Alejandro, additional, Morillo, Carlos A., additional, Rueda‐Ochoa, Oscar L., additional, and Franco, Oscar H., additional

Published
2020
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20. Epigenetic Link Between Statin Therapy and Type 2 Diabetes

Author

Ochoa-Rosales, Carolina, primary, Portilla-Fernandez, Eliana, additional, Nano, Jana, additional, Wilson, Rory, additional, Lehne, Benjamin, additional, Mishra, Pashupati P., additional, Gao, Xu, additional, Ghanbari, Mohsen, additional, Rueda-Ochoa, Oscar L., additional, Juvinao-Quintero, Diana, additional, Loh, Marie, additional, Zhang, Weihua, additional, Kooner, Jaspal S., additional, Grabe, Hans J., additional, Felix, Stephan B., additional, Schöttker, Ben, additional, Zhang, Yan, additional, Gieger, Christian, additional, Müller-Nurasyid, Martina, additional, Heier, Margit, additional, Peters, Annette, additional, Lehtimäki, Terho, additional, Teumer, Alexander, additional, Brenner, Hermann, additional, Waldenberger, Melanie, additional, Ikram, M. Arfan, additional, van Meurs, Joyce B.J., additional, Franco, Oscar H., additional, Voortman, Trudy, additional, Chambers, John, additional, Stricker, Bruno H., additional, and Muka, Taulant, additional

Published
2020
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22. Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies

Author

Pennells, Lisa, Kaptoge, Stephen, Wood, Angela, Sweeting, Mike, Zhao, Xiaohui, White, Ian, Burgess, Stephen, Willeit, Peter, Bolton, Thomas, Moons, Karel G M, van der Schouw, Yvonne T, Selmer, Randi, Khaw, Kay-Tee, Gudnason, Vilmundur, Assmann, Gerd, Amouyel, Philippe, Salomaa, Veikko, Kivimaki, Mika, Nordestgaard, Børge G, Blaha, Michael J, Kuller, Lewis H, Brenner, Hermann, Gillum, Richard F, Meisinger, Christa, Ford, Ian, Knuiman, Matthew W, Rosengren, Annika, Lawlor, Debbie A, Völzke, Henry, Cooper, Cyrus, Marín Ibañez, Alejandro, Casiglia, Edoardo, Kauhanen, Jussi, Cooper, Jackie A, Rodriguez, Beatriz, Sundström, Johan, Barrett-Connor, Elizabeth, Dankner, Rachel, Nietert, Paul J, Davidson, Karina W, Wallace, Robert B, Blazer, Dan G, Björkelund, Cecilia, Donfrancesco, Chiara, Krumholz, Harlan M, Nissinen, Aulikki, Davis, Barry R, Coady, Sean, Whincup, Peter H, Jørgensen, Torben, Ducimetiere, Pierre, Trevisan, Maurizio, Engström, Gunnar, Crespo, Carlos J, Meade, Tom W, Visser, Marjolein, Kromhout, Daan, Kiechl, Stefan, Daimon, Makoto, Price, Jackie F, Gómez de la Cámara, Agustin, Wouter Jukema, J, Lamarche, Benoît, Onat, Altan, Simons, Leon A, Kavousi, Maryam, Ben-Shlomo, Yoav, Gallacher, John, Dekker, Jacqueline M, Arima, Hisatomi, Shara, Nawar, Tipping, Robert W, Roussel, Ronan, Brunner, Eric J, Koenig, Wolfgang, Sakurai, Masaru, Pavlovic, Jelena, Gansevoort, Ron T, Nagel, Dorothea, Goldbourt, Uri, Barr, Elizabeth L M, Palmieri, Luigi, Njølstad, Inger, Sato, Shinichi, Monique Verschuren, W M, Varghese, Cherian V, Graham, Ian, Onuma, Oyere, Greenland, Philip, Woodward, Mark, Ezzati, Majid, Psaty, Bruce M, Sattar, Naveed, Jackson, Rod, Ridker, Paul M, Cook, Nancy R, D'Agostino, Ralph B, Thompson, Simon G, Danesh, John, Di Angelantonio, Emanuele, Simpson, Lara M, Pressel, Sara L, Couper, David J, Nambi, Vijay, Matsushita, Kunihiro, Folsom, Aaron R, Shaw, Jonathan E, Magliano, Dianna J, Zimmet, Paul Z, Wannamethee, S Goya, Willeit, Johann, Santer, Peter, Egger, Georg, Casas, Juan Pablo, Amuzu, Antointtte, Tikhonoff, Valérie, Sutherland, Susan E, Cushman, Mary, Søgaard, Anne Johanne, Håheim, Lise Lund, Ariansen, Inger, Tybjærg-Hansen, Anne, Jensen, Gorm B, Schnohr, Peter, Giampaoli, Simona, Vanuzzo, Diego, Panico, Salvatore, Balkau, Beverley, Bonnet, Fabrice, Marre, Michel, de la Cámara, Agustin Gómez, Rubio Herrera, Miguel Angel, Friedlander, Yechiel, McCallum, John, McLachlan, Stela, Guralnik, Jack, Phillips, Caroline L, Wareham, Nick, Schöttker, Ben, Saum, Kai-Uwe, Holleczek, Bernd, Tolonen, Hanna, Vartiainen, Erkki, Jousilahti, Pekka, Harald, Kennet, D’Agostino, Ralph B, Massaro, Joseph M, Pencina, Michael, Vasan, Ramachandran, Kayama, Takamasa, Kato, Takeo, Oizumi, Toshihide, Jespersen, Jørgen, Møller, Lars, Bladbjerg, Else Marie, Chetrit, A, Wilhelmsen, Lars, Lissner, Lauren, Dennison, Elaine, Kiyohara, Yutaka, Ninomiya, Toshiharu, Doi, Yasufumi, Nijpels, Giel, Stehouwer, Coen D A, Kazumasa, Yamagishi, Iso, Hiroyasu, Kurl, Sudhir, Tuomainen, Tomi-Pekka, Salonen, Jukka T, Deeg, Dorly J H, Nilsson, Peter M, Hedblad, Bo, Melander, Olle, De Boer, Ian H, DeFilippis, Andrew Paul, Verschuren, W M Monique, Watt, Graham, Tverdal, Aage, Kirkland, Susan, Shimbo, Daichi, Shaffer, Jonathan, Bakker, Stephan J L, van der Harst, Pim, Hillege, Hans L, Dallongeville, Jean, Schulte, Helmut, Trompet, Stella, Smit, Roelof A J, Stott, David J, Després, Jean-Pierre, Cantin, Bernard, Dagenais, Gilles R, Laughlin, Gail, Wingard, Deborah, Aspelund, Thor, Eiriksdottir, Gudny, Gudmundsson, Elias Freyr, Ikram, Arfan, van Rooij, Frank J A, Franco, Oscar H, Rueda-Ochoa, Oscar L, Muka, Taulant, Glisic, Marija, Tunstall-Pedoe, Hugh, Howard, Barbara V, Zhang, Ying, Jolly, Stacey, Davey-Smith, George, Can, Günay, Yüksel, Hüsniye, Nakagawa, Hideaki, Morikawa, Yuko, Miura, Katsuyuki, Ingelsson, Martin, Giedraitis, Vilmantas, Gaziano, J Michael, Shipley, Martin, Arndt, Volker, Cook, Nancy, Ibañez, Alejandro Marín, Geleijnse, Johanna M, Epidemiology, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Pennells, Lisa [0000-0002-8594-3061], Kaptoge, Stephen [0000-0002-1155-4872], Wood, Angela [0000-0002-7937-304X], Sweeting, Michael [0000-0003-0980-8965], Zhao, Xiaohui [0000-0001-9922-2815], Burgess, Stephen [0000-0001-5365-8760], Danesh, John [0000-0003-1158-6791], Di Angelantonio, Emanuele [0000-0001-8776-6719], Apollo - University of Cambridge Repository, Nutrition and Health, APH - Aging & Later Life, APH - Societal Participation & Health, APH - Health Behaviors & Chronic Diseases, Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Life Course Epidemiology (LCE), AGEM - Endocrinology, metabolism and nutrition, Internal medicine, Epidemiology and Data Science, İÜC, Lisa, Pennell, Stephen, Kaptoge, Angela, Wood, Mike, Sweeting, Xiaohui, Zhao, Ian, White, Stephen, Burge, Peter, Willeit, Thomas, Bolton, Karel G M, Moon, Yvonne T, van der Schouw, Randi, Selmer, Kay-Tee, Khaw, Vilmundur, Gudnason, Gerd, Assmann, Philippe, Amouyel, Veikko, Salomaa, Mika, Kivimaki, Børge G, Nordestgaard, Michael J, Blaha, Lewis H, Kuller, Hermann, Brenner, Richard F, Gillum, Christa, Meisinger, Ian, Ford, Matthew W, Knuiman, Annika, Rosengren, Debbie A, Lawlor, Henry, Völzke, Cyrus, Cooper, Alejandro, Marín Ibañez, Edoardo, Casiglia, Jussi, Kauhanen, Jackie A, Cooper, Beatriz, Rodriguez, Johan, Sundström, Elizabeth, Barrett-Connor, Rachel, Dankner, Paul J, Nietert, Karina W, Davidson, Robert B, Wallace, Dan G, Blazer, Cecilia, Björkelund, Chiara, Donfrancesco, Harlan M, Krumholz, Aulikki, Nissinen, Barry R, Davi, Sean, Coady, Peter H, Whincup, Torben, Jørgensen, Pierre, Ducimetiere, Maurizio, Trevisan, Gunnar, Engström, Carlos J, Crespo, Tom W, Meade, Marjolein, Visser, Daan, Kromhout, Stefan, Kiechl, Makoto, Daimon, Jackie F, Price, Agustin, Gómez de la Cámara, J, Wouter Jukema, Benoît, Lamarche, Altan, Onat, Leon A, Simon, Maryam, Kavousi, Yoav, Ben-Shlomo, John, Gallacher, Jacqueline M, Dekker, Hisatomi, Arima, Nawar, Shara, Robert W, Tipping, Ronan, Roussel, Eric J, Brunner, Wolfgang, Koenig, Masaru, Sakurai, Jelena, Pavlovic, Ron T, Gansevoort, Dorothea, Nagel, Uri, Goldbourt, Elizabeth L M, Barr, Luigi, Palmieri, Inger, Njølstad, Shinichi, Sato, W M, Monique Verschuren, Cherian V, Varghese, Ian, Graham, Oyere, Onuma, Philip, Greenland, Mark, Woodward, Majid, Ezzati, Bruce M, Psaty, Sattar, W Tipping, Naveerobert, M Simpson, Lara, L Pressel, Sara, J Couper, David, Nambi, Vijay, Matsushita, Kunihiro, R Folsom, Aaron, E Shaw, Jonathan, J Magliano, Dianna, Z Zimmet, Paul, W Knuiman, Matthew, H Whincup, Peter, Goya Wannamethee, S, Willeit, Johann, Santer, Peter, Egger, Georg, Pablo Casas, Juan, Amuzu, Antoinette, Ben-Shlomo, Yoav, Gallacher, John, Tikhonoff, Valérie, Casiglia, Edoardo, E Sutherland, Susan, J Nietert, Paul, Cushman, Mary, M Psaty, Bruce, Johanne Søgaard, Anne, Lund Håheim, Lise, Ariansen, Inger, Tybjærg-Hansen, Anne, B Jensen, Gorm, Schnohr, Peter, Giampaoli, Simona, Vanuzzo, Diego, Panico, Salvatore, Palmieri, Luigi, Balkau, Beverley, Bonnet, Fabrice, Marre, Michel, Gómez de la Cámara, Agustin, Angel Rubio Herrera, Miguel, Friedlander, Yechiel, Mccallum, John, Mclachlan, Stela, Guralnik, Jack, L Phillips, Caroline, Khaw, Kay-Tee, Wareham, Nick, Schöttker, Ben, Saum, Kai-Uwe, Holleczek, Bernd, Nissinen, Aulikki, Tolonen, Hanna, Donfrancesco, Chiara, Vartiainen, Erkki, Jousilahti, Pekka, Harald, Kennet, B D’Agostino, Ralph, M Massaro, Joseph, Pencina, Michael, Vasan, Ramachandran, Kayama, Takamasa, Kato, Takeo, Oizumi, Toshihide, Jespersen, Jørgen, Møller, Lar, Marie Bladbjerg, Else, Chetrit, A, Rosengren, Annika, Wilhelmsen, Lar, Björkelund, Cecilia, Lissner, Lauren, Nagel, Dorothea, Dennison, Elaine, Kiyohara, Yutaka, Ninomiya, Toshiharu, Doi, Yasufumi, Rodriguez, Beatriz, Nijpels, Giel, A Stehouwer, Coen D, Sato, Shinichi, Kazumasa, Yamagishi, Iso, Hiroyasu, Goldbourt, Uri, Salomaa, Veikko, Kurl, Sudhir, Tuomainen, Tomi-Pekka, T Salonen, Jukka, Visser, Marjolein, H Deeg, Dorly J, W Meade, Tom, M Nilsson, Peter, Hedblad, Bo, Melander, Olle, H De Boer, Ian, Paul DeFilippis, Andrew, M Monique Verschuren, W, Sattar, Naveed, Watt, Graham, Meisinger, Christa, Koenig, Wolfgang, H Kuller, Lewi, Tverdal, Aage, F Gillum, Richard, A Cooper, Jackie, Kirkland, Susan, Shimbo, Daichi, Shaffer, Jonathan, Ducimetiere, Pierre, L Bakker, Stephan J, van der Harst, Pim, L Hillege, Han, J Crespo, Carlo, Amouyel, Philippe, Dallongeville, Jean, Assmann, Gerd, Schulte, Helmut, Trompet, Stella, J Smit, Roelof A, J Stott, David, T van der Schouw, Yvonne, Després, Jean-Pierre, Cantin, Bernard, R Dagenais, Gille, Laughlin, Gail, Wingard, Deborah, Trevisan, Maurizio, Aspelund, Thor, Eiriksdottir, Gudny, Freyr Gudmundsson, Elia, Ikram, Arfan, A van Rooij, Frank J, H Franco, Oscar, L Rueda-Ochoa, Oscar, Muka, Taulant, Glisic, Marija, Tunstall-Pedoe, Hugh, Völzke, Henry, V Howard, Barbara, Zhang, Ying, Jolly, Stacey, Davey-Smith, George, Can, Günay, Yüksel, Hüsniye, Nakagawa, Hideaki, Morikawa, Yuko, Miura, Katsuyuki, Njølstad, Inger, Ingelsson, Martin, Giedraitis, Vilmanta, M Ridker, Paul, Michael Gaziano, J, Kivimaki, Mika, Shipley, Martin, J Brunner, Eric, Arndt, Volker, Brenner, Hermann, Cook, Nancy, Ford, Ian, Marín Ibañez, Alejandro, M Geleijnsed, Johanna, Rod, Jackson, Paul M, Ridker, Nancy R, Cook, Ralph B, D'Agostino, Simon G, Thompson, John, Danesh, and Emanuele, Di Angelantonio

Subjects
Male, Cardiac & Cardiovascular Systems, Nutrition and Disease, Prevention and Epidemiology, PREDICTION, Áhættuþættir, 030204 cardiovascular system & hematology, GUIDELINES, 0302 clinical medicine, Risk Factors, Voeding en Ziekte, FRAMINGHAM, Discrimination, Medicine, Cardiac and Cardiovascular Systems, Blóðrásarsjúkdómar, Prospective Studies, Prospective cohort study, Non-U.S. Gov't, 1102 Cardiorespiratory Medicine and Haematology, CALIBRATION, Kardiologi, Framingham Risk Score, Emerging Risk Factors Collaboration, SCORES, Research Support, Non-U.S. Gov't, Incidence (epidemiology), Middle Aged, Cardiovascular disease, Justice and Strong Institutions, Risk prediction, ddc, 3. Good health, Cardiovascular Diseases, Meta-analysis, Cohort, Calibration, Female, Risk assessment, Cardiology and Cardiovascular Medicine, Algorithm, Life Sciences & Biomedicine, Algorithms, SDG 16 - Peace, Risk algorithms, DISEASE PREVENTION, Research Support, Risk Assessment, VALIDATION, 03 medical and health sciences, Clinical Research, Journal Article, Humans, ddc:610, Risk factor, VLAG, Aged, Science & Technology, business.industry, SDG 16 - Peace, Justice and Strong Institutions, 030229 sport sciences, R1, STATIN USE, Cardiovascular System & Hematology, Cardiovascular System & Cardiology, business, PRIMARY PREVENTION, TASK-FORCE
Abstract

Publisher's version (útgefin grein), Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need., The work of the co-ordinating centre was funded by the UK Medical Research Council (G0800270), British Heart Foundation (SP/09/ 002), British Heart Foundation Cambridge Cardiovascular Centre of Excellence, UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (268834), and European Commission Framework Programme 7 (HEALTH-F2-2012-279233). The Emerging Risk Factor Collaboration’s website https://www.phpc.cam.ac.uk/ceu/erfc/list-of-studies/ has compiled a list provided by investigators of some of the funders of the component studies in this analysis. I.W. was supported by the Medical Research Council Unit Programme MC_UU_12023/21. M.K. is supported by the Netherlands Organization for Scientific Research (NWO) Veni grant (Veni, 91616079). J.P. is supported by Erasmus Mundus Western Balkans (ERAWEB), a project funded by the European Commission.

Published
2019

23. Sex-specific distributions and determinants of thoracic aortic diameters in the elderly

Author

Bons, Lidia R, primary, Rueda-Ochoa, Oscar L, additional, El Ghoul, Khalid, additional, Rohde, Sofie, additional, Budde, Ricardo PJ, additional, Leening, Maarten JG, additional, Vernooij, Meike W, additional, Franco, Oscar H, additional, van der Lugt, Aad, additional, Roos-Hesselink, Jolien W, additional, Kavousi, Maryam, additional, and Bos, Daniel, additional

Published
2019
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26. The cardiovascular risk profile of middle age women previously diagnosed with premature ovarian insufficiency: A case-control study.

Author

Gunning, Marlise N., Meun, Cindy, van Rijn, Bas B., Daan, Nadine M. P., Roeters van Lennep, Jeanine E., Appelman, Yolande, Boersma, Eric, Hofstra, Leonard, Fauser, Clemens G. K. M., Rueda-Ochoa, Oscar L., Ikram, Mohammad A., Kavousi, Maryam, Lambalk, Cornelis B., Eijkemans, Marinus J. C., Laven, Joop S. E., and Fauser, Bart C. J. M.

Subjects
PREMATURE ovarian failure, WAIST-hip ratio, MIDDLE age, WAIST circumference, CARDIOVASCULAR diseases risk factors, SYSTOLIC blood pressure, AGE groups, MATERNAL age
Abstract

Background: Cardiovascular disease (CVD) is the leading cause of death in women worldwide. The cardiovascular risk profile deteriorates after women enter menopause. By definition, women diagnosed with premature ovarian insufficiency (POI) experience menopause before 40 years of age, which may render these women even more susceptible to develop CVD later in life. However, prospective long-term follow up data of well phenotyped women with POI are scarce. In the current study we compare the CVD profile and risk of middle aged women previously diagnosed with POI, to a population based reference group matched for age and BMI. Methods and findings: We compared 123 women (age 49.0 (± 4.3) years) and diagnosed with POI 8.1 (IQR: 6.8–9.6) years earlier, with 123 population controls (age 49.4 (± 3.9) years). All women underwent an extensive standardized cardiovascular screening. We assessed CVD risk factors including waist circumference, BMI, blood pressure, lipid profile, pulse wave velocity (PWV), and the prevalence of diabetes mellitus, metabolic syndrome (MetS) and carotid intima media thickness (cIMT), in both women with POI and controls. We calculated the 10-year CVD Framingham Risk Score (FRS) and the American Heart Association's suggested cardiovascular health score (CHS). Waist circumference (90.0 (IQR: 83.0–98.0) versus 80.7 (IQR: 75.1–86.8), p < 0.01), waist-to-hip ratio (0.90 (IQR: 0.85–0.93) versus 0.79 (IQR: 0.75–0.83), p < 0.01), systolic blood pressure (124 (IQR 112–135) versus 120 (IQR109-131), p < 0.04) and diastolic blood pressure (81 (IQR: 76–89) versus 78 (IQR: 71–86), p < 0.01), prevalence of hypertension (45 (37%) versus 21 (17%), p < 0.01) and MetS (19 (16%) versus 4 (3%), p < 0.01) were all significantly increased in women with POI compared to healthy controls. Other risk factors, however, such as lipids, glucose levels and prevalence of diabetes were similar comparing women with POI versus controls. The arterial stiffness assessed by PWV was also similar in both populations (8.1 (IQR: 7.1–9.4) versus 7.9 (IQR: 7.1–8.4), p = 0.21). In addition, cIMT was lower in women with POI compared to controls (550 μm (500–615) versus 684 μm (618–737), p < 0.01). The calculated 10-year CVD risk was 5.9% (IQR: 3.7–10.6) versus 6.0% (IQR: 3.9–9.0) (p = 0.31) and current CHS was 6.1 (1.9) versus 6.5 (1.6) (p = 0.07), respectively in POI versus controls. Conclusions: Middle age women with POI presented with more unfavorable cardiovascular risk factors (increased waist circumference and a higher prevalence of hypertension and MetS) compared to age and BMI matched population controls. In contrast, the current study reveals a lower cIMT and similar 10-year cardiovascular disease risk and cardiovascular health score. In summary, neither signs of premature atherosclerosis nor a worse cardiovascular disease risk or health score were observed among middle age women with POI compared to population controls. Longer-term follow-up studies of women of more advanced age are warranted to establish whether women with POI are truly at increased risk of developing CVD events later in life. Trial registration: ClinicalTrials.gov Identifier: NCT02616510. [ABSTRACT FROM AUTHOR]

Published
2020
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27. Sex-specific distributions and determinants of thoracic aortic diameters in the elderly.

Author

Bons, Lidia R., Rueda-Ochoa, Oscar L., El Ghoul, Khalid, Rohde, Sofie, Budde, Ricardo P. J., Leening, Maarten J. G., Vernooij, Meike W., Franco, Oscar H., van der Lugt, Aad, Roos-Hesselink, Jolien W., Kavousi, Maryam, Bos, Daniel, Budde, Ricardo Pj, and Leening, Maarten Jg

Subjects
BODY surface area, DIAMETER, CARDIOVASCULAR diseases risk factors, THORACIC aneurysms
Abstract

Objective: To provide population-based distributions of thoracic aortic diameters in men and women aged 55 years or older and to identify determinants of thoracic aortic diameters.Methods: From 2003 to 2006, 2505 participants (1208 men, mean age 69.1±6.8 years) from the prospective population-based Rotterdam Study underwent non-enhanced cardiac CT. The diameter of the ascending (AA) and descending aorta (DA) was measured at the level of the pulmonary bifurcation.Results: The mean diameter of the ascending and descending aorta was substantially larger in men (38±4 mm and 30±2 mm) than in women (35±3 mm and 27±2 mm). An ascending aortic diameter of larger than 40 mm was found in 228 (18.9%) men and 76 (5.9%) women and a descending aortic diameter larger than 40 mm was found in two men and no women. Male sex was found to be independently associated with larger DA diameter (standardised β 0.24, 95% CI 0.19 to 0.30), while a statistically non-significant trend was found for the AA diameter (standardised β 0.06, 95% CI 0.00 to 0.12). Age, height, weight and traditional cardiovascular risk factors were also associated with larger AA and/or DA diameters. Diabetes was associated with smaller AA and DA diameters. We found no evidence for effect modification by sex.Conclusions: In persons aged 55 years or older, an ascending aortic diameter of 40 mm or larger was found in 18.9% of men and 5.9% of women. Given the importance of sex, sex-specific distribution values may prove useful in clinical practice, even when correcting for body surface area or height. [ABSTRACT FROM AUTHOR]

Published
2020
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28. Epigenetic Link between Statin Use and Diabetes

Author

OCHOA-ROSALES, CAROLINA, primary, PORTILLA-FERNANDEZ, ELIANA, additional, WILSON, RORY, additional, NANO, JANA, additional, GHANBARI, MOHSEN, additional, RUEDA-OCHOA, OSCAR L., additional, LEHTIMÄKI, TERHO, additional, GAO, XU, additional, LEHNE, BENJAMIN, additional, VOORTMAN, TRUDY, additional, FRANCO, OSCAR, additional, and MUKA, TAULANT, additional

Published
2018
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29. Electrocardiographic abnormalities in Chagas disease in the general population: A systematic review and meta-analysis

Author

Rojas, Lyda Z., primary, Glisic, Marija, additional, Pletsch-Borba, Laura, additional, Echeverría, Luis E., additional, Bramer, Wichor M., additional, Bano, Arjola, additional, Stringa, Najada, additional, Zaciragic, Asija, additional, Kraja, Bledar, additional, Asllanaj, Eralda, additional, Chowdhury, Rajiv, additional, Morillo, Carlos A., additional, Rueda-Ochoa, Oscar L., additional, Franco, Oscar H., additional, and Muka, Taulant, additional

Published
2018
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30. Associations of endogenous estradiol and testosterone levels with plaque composition and risk of stroke in subjects with carotid atherosclerosis

Author

Glisic, Marija, primary, Mujaj, Blerim, additional, Rueda-Ochoa, Oscar L., additional, Asllanaj, Eralda, additional, Laven, Joop S.E., additional, Kavousi, Maryam, additional, Ikram, M. Kamran, additional, Vernooij, Meike W., additional, Ikram, M. Arfan, additional, Franco, Oscar H., additional, Bos, Daniel, additional, and Muka, Taulant, additional

Published
2017
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33. Factor de crecimiento similar a la insulina

Author

Cadena Ortiz, Lina María, Cornejo Martínez, Silvia J, Quiroz Pinto, Martin F, and Rueda Ochoa, Oscar L

Subjects
Ciencias biomédicas, Medical Sciences, Medicina, Innovations in health, Research, Investigaciones, Biomedical Sciences, Life Sciences, Ciencias de la salud, Health Sciences, Medicine, Ciencias de la vida, Ciencias médicas, Innovaciones en salud
Abstract

ResumenEl factor de crecimiento I Similar a la Insulina (IGF-1, del término en inglés insuline Like Growth Factor) forma parte de una familia de factores de crecimiento cuyas acciones están encaminadas a la proliferación y diferenciación de múltiples tejidos en el organismo. Su efecto fisiológico se alcanza por su interacción con receptores especÍficos ubicados en toda la economÍa del cuerpo.Palabras clave: Hormona de crecimiento, Factor de crecimiento 1 similar a la insulina, Proliferación celular, Enzimas tirosinkinasas, Diabetes mellitus.

Published
1998

34. Abstract 15083: Impact of Cumulative Systolic Blood Pressure and Serious Adverse Events on Efficacy of Intensive Blood Pressure Treatment: A Randomized Clinical Trial.

Author

Rueda-Ochoa, Oscar L, Rojas Sanchez, Lyda Z, Ahmad, Shahzad, van Duijn, Cornelia M, Ikram, M. Arfan, Deckers, Jaap W, Franco, Oscar H, Rizopoulos, Dimitris, and Kavousi, Maryam

Subjects
*SYSTOLIC blood pressure, *BLOOD pressure, *CLINICAL trials, *ADVERSE health care events, *HYPERTENSION, *HEART failure, *STROKE
Abstract

Background: Intensive blood pressure lowering is increasingly gaining attention. Besides higher baseline blood pressure, cumulative systolic blood pressure (SBP), visit-to-visit variability and treatment-induced serious adverse events (SAEs) could impact treatment efficacy over time. Objective: To assess the impact of cumulative SBP, SBP variability and SAEs on intensive hypertension treatment in the SPRINT population during follow-up. Design: Secondary analysis of The SPRINT, randomized, controlled, open-label trial. Setting: 102 clinical sites in the United States. Participants: We included 9065 SPRINT participants with 129487 repeated systolic blood pressure (SBP) measurements. Interventions: Participants were randomly assigned to intensive (target SBP <120 mmHg) vs standard treatment (target SBP between 130-139 mmHg). We used cumulative joint models (cJM) for longitudinal and survival data analysis. Measurements: Composite outcome of myocardial infarction, other acute coronary syndromes, acute decompensated heart failure, stroke, and cardiovascular mortality. Results: While intensive treatment decreased the risk for the primary SPRINT outcome at the start of follow-up, its effect lost significance after 3.4 years of follow-up in the total SPRINT population and after 1.3, 1.3, 1.1, 1.8, 2.1, 1.8, and 3.4 years among participants with prevalent chronic kidney disease, prevalent cardiovascular disease, women, black individuals, subjects <75 years, those with baseline SBP >132 mmHg, and individuals who suffered SAEs during follow-up respectively. These subgroups also showed large SBP variability over time. Limitations: Despite the observed increasing tendency in the HRs over time, as the SPRINT trial terminated after median 3.26 years of follow-up (range 0 to 4.5 years), our findings are only applicable to this time-window. Conclusions: The initial beneficial impact of intensive hypertension treatment might be offset by cumulative SBP, SBP variability and development of SAEs during follow-up. Trial Registration: clinicaltrials.gov Identifier: NCT01206062 [ABSTRACT FROM AUTHOR]

Published
2018

35. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author

Franceschini, Nora, Giambartolomei, Claudia, De Vries, Paul S, Finan, Chris, Bis, Joshua C, Huntley, Rachael P, Lovering, Ruth C, Tajuddin, Salman M, Winkler, Thomas W, Graff, Misa, Kavousi, Maryam, Dale, Caroline, Smith, Albert V, Hofer, Edith, Van Leeuwen, Elisabeth M, Nolte, Ilja M, Lu, Lingyi, Scholz, Markus, Sargurupremraj, Muralidharan, Pitkänen, Niina, Franzén, Oscar, Joshi, Peter K, Noordam, Raymond, Marioni, Riccardo E, Hwang, Shih-Jen, Musani, Solomon K, Schminke, Ulf, Palmas, Walter, Isaacs, Aaron, Correa, Adolfo, Zonderman, Alan B, Hofman, Albert, Teumer, Alexander, Cox, Amanda J, Uitterlinden, André G, Wong, Andrew, Smit, Andries J, Newman, Anne B, Britton, Annie, Ruusalepp, Arno, Sennblad, Bengt, Hedblad, Bo, Pasaniuc, Bogdan, Penninx, Brenda W, Langefeld, Carl D, Wassel, Christina L, Tzourio, Christophe, Fava, Cristiano, Baldassarre, Damiano, O'Leary, Daniel H, Teupser, Daniel, Kuh, Diana, Tremoli, Elena, Mannarino, Elmo, Grossi, Enzo, Boerwinkle, Eric, Schadt, Eric E, Ingelsson, Erik, Veglia, Fabrizio, Rivadeneira, Fernando, Beutner, Frank, Chauhan, Ganesh, Heiss, Gerardo, Snieder, Harold, Campbell, Harry, Völzke, Henry, Markus, Hugh S, Deary, Ian J, Jukema, J Wouter, De Graaf, Jacqueline, Price, Jacqueline, Pott, Janne, Hopewell, Jemma C, Liang, Jingjing, Thiery, Joachim, Engmann, Jorgen, Gertow, Karl, Rice, Kenneth, Taylor, Kent D, Dhana, Klodian, Kiemeney, Lambertus ALM, Lind, Lars, Raffield, Laura M, Launer, Lenore J, Holdt, Lesca M, Dörr, Marcus, Dichgans, Martin, Traylor, Matthew, Sitzer, Matthias, Kumari, Meena, Kivimaki, Mika, Nalls, Mike A, Melander, Olle, Raitakari, Olli, Franco, Oscar H, Rueda-Ochoa, Oscar L, Roussos, Panos, Whincup, Peter H, Amouyel, Philippe, Giral, Philippe, Anugu, Pramod, Wong, Quenna, Malik, Rainer, Rauramaa, Rainer, Burkhardt, Ralph, Hardy, Rebecca, Schmidt, Reinhold, De Mutsert, Renée, Morris, Richard W, Strawbridge, Rona J, Wannamethee, S Goya, Hägg, Sara, Shah, Sonia, McLachlan, Stela, Trompet, Stella, Seshadri, Sudha, Kurl, Sudhir, Heckbert, Susan R, Ring, Susan, Harris, Tamara B, Lehtimäki, Terho, Galesloot, Tessel E, Shah, Tina, De Faire, Ulf, Plagnol, Vincent, Rosamond, Wayne D, Post, Wendy, Zhu, Xiaofeng, Zhang, Xiaoling, Guo, Xiuqing, Saba, Yasaman, MEGASTROKE Consortium, Dehghan, Abbas, Seldenrijk, Adrie, Morrison, Alanna C, Hamsten, Anders, Psaty, Bruce M, Van Duijn, Cornelia M, Lawlor, Deborah A, Mook-Kanamori, Dennis O, Bowden, Donald W, Schmidt, Helena, Wilson, James F, Wilson, James G, Rotter, Jerome I, Wardlaw, Joanna M, Deanfield, John, Halcox, Julian, Lyytikäinen, Leo-Pekka, Loeffler, Markus, Evans, Michele K, Debette, Stéphanie, Humphries, Steve E, Völker, Uwe, Gudnason, Vilmundur, Hingorani, Aroon D, Björkegren, Johan LM, Casas, Juan P, and O'Donnell, Christopher J

Subjects
Quantitative Trait Loci, ADAMTS9 Protein, Coronary Disease, Carotid Intima-Media Thickness, Polymorphism, Single Nucleotide, Plaque, Atherosclerotic, 3. Good health, Protein-Lysine 6-Oxidase, Risk Factors, cardiovascular system, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Amino Acid Oxidoreductases, Lod Score, Genome-Wide Association Study
Abstract

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

36. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author

Franceschini, Nora, Giambartolomei, Claudia, De Vries, Paul S, Finan, Chris, Bis, Joshua C, Huntley, Rachael P, Lovering, Ruth C, Tajuddin, Salman M, Winkler, Thomas W, Graff, Misa, Kavousi, Maryam, Dale, Caroline, Smith, Albert V, Hofer, Edith, Van Leeuwen, Elisabeth M, Nolte, Ilja M, Lu, Lingyi, Scholz, Markus, Sargurupremraj, Muralidharan, Pitkänen, Niina, Franzén, Oscar, Joshi, Peter K, Noordam, Raymond, Marioni, Riccardo E, Hwang, Shih-Jen, Musani, Solomon K, Schminke, Ulf, Palmas, Walter, Isaacs, Aaron, Correa, Adolfo, Zonderman, Alan B, Hofman, Albert, Teumer, Alexander, Cox, Amanda J, Uitterlinden, André G, Wong, Andrew, Smit, Andries J, Newman, Anne B, Britton, Annie, Ruusalepp, Arno, Sennblad, Bengt, Hedblad, Bo, Pasaniuc, Bogdan, Penninx, Brenda W, Langefeld, Carl D, Wassel, Christina L, Tzourio, Christophe, Fava, Cristiano, Baldassarre, Damiano, O'Leary, Daniel H, Teupser, Daniel, Kuh, Diana, Tremoli, Elena, Mannarino, Elmo, Grossi, Enzo, Boerwinkle, Eric, Schadt, Eric E, Ingelsson, Erik, Veglia, Fabrizio, Rivadeneira, Fernando, Beutner, Frank, Chauhan, Ganesh, Heiss, Gerardo, Snieder, Harold, Campbell, Harry, Völzke, Henry, Markus, Hugh S, Deary, Ian J, Jukema, J Wouter, De Graaf, Jacqueline, Price, Jacqueline, Pott, Janne, Hopewell, Jemma C, Liang, Jingjing, Thiery, Joachim, Engmann, Jorgen, Gertow, Karl, Rice, Kenneth, Taylor, Kent D, Dhana, Klodian, Kiemeney, Lambertus A L M, Lind, Lars, Raffield, Laura M, Launer, Lenore J, Holdt, Lesca M, Dörr, Marcus, Dichgans, Martin, Traylor, Matthew, Sitzer, Matthias, Kumari, Meena, Kivimaki, Mika, Nalls, Mike A, Melander, Olle, Raitakari, Olli, Franco, Oscar H, Rueda-Ochoa, Oscar L, Roussos, Panos, Whincup, Peter H, Amouyel, Philippe, Giral, Philippe, Anugu, Pramod, Wong, Quenna, Malik, Rainer, Rauramaa, Rainer, Burkhardt, Ralph, Hardy, Rebecca, Schmidt, Reinhold, De Mutsert, Renée, Morris, Richard W, Strawbridge, Rona J, Wannamethee, S Goya, Hägg, Sara, Shah, Sonia, McLachlan, Stela, Trompet, Stella, Seshadri, Sudha, Kurl, Sudhir, Heckbert, Susan R, Ring, Susan, Harris, Tamara B, Lehtimäki, Terho, Galesloot, Tessel E, Shah, Tina, De Faire, Ulf, Plagnol, Vincent, Rosamond, Wayne D, Post, Wendy, Zhu, Xiaofeng, Zhang, Xiaoling, Guo, Xiuqing, Saba, Yasaman, Dehghan, Abbas, Seldenrijk, Adrie, Morrison, Alanna C, Hamsten, Anders, Psaty, Bruce M, Van Duijn, Cornelia M, Lawlor, Deborah A, Mook-Kanamori, Dennis O, Bowden, Donald W, Schmidt, Helena, Wilson, James F, Wilson, James G, Rotter, Jerome I, Wardlaw, Joanna M, Deanfield, John, Halcox, Julian, Lyytikäinen, Leo-Pekka, Loeffler, Markus, Evans, Michele K, Debette, Stéphanie, Humphries, Steve E, Völker, Uwe, Gudnason, Vilmundur, Hingorani, Aroon D, Björkegren, Johan L M, Casas, Juan P, and O'Donnell, Christopher J

Subjects
cardiovascular system, cardiovascular diseases, 610 Medicine & health, 360 Social problems & social services, 3. Good health
Abstract

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

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