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1,247 results on '"van Gilst, Wiek H."'

202. Abstract 14059: High Serum Erythropoietin Levels and the Development of Heart Failure in the General Population

Author

Grote Beverborg, Niels, primary, van der Wal, Haye H, additional, Klip, IJsbrand T, additional, Voors, Adriaan A, additional, de Boer, Rudolph A, additional, van Gilst, Wiek H, additional, van Veldhuisen, Dirk J, additional, Gansevoort, Ron T, additional, Hillege, Hans L, additional, van der Harst, Pim, additional, Bakker, Stephan J, additional, and van der Meer, Peter, additional

Published
2015
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203. Abstract 11958: Predicting Heart Failure With Preserved and Reduced Ejection Fraction: The International Collaboration on Heart Failure Subtypes

Author

Ho, Jennifer E, primary, Brouwers, Frank P, additional, Enserro, Danielle, additional, Shah, Sanjiv J, additional, Psaty, Bruce M, additional, Bartz, Traci M, additional, Santhanakrishnan, Rajalakshmi, additional, Lee, Douglas S, additional, Liu, Kiang, additional, Blaha, Michael J, additional, Hillege, Hans L, additional, van der Harst, Pim, additional, van Gilst, Wiek H, additional, Kop, Willem J, additional, Gansevoort, Ron T, additional, Vasan, Ramachandran S, additional, Gardin, Julius M, additional, Kizer, Jorge R, additional, Levy, Daniel, additional, Gottdiener, John S, additional, de Boer, Rudolf A, additional, and Larson, Martin G, additional

Published
2015
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204. Abstracts of papers clinical pharmacological meeting

Author

Merkus, F. W. H. M., Gribnau, F. W. J., Thien, Th., Louwerenburg, Hans W., Kingma, J. Herre, van Gilst, Wiek H., Six, A. Jacob, de Graeff, Pieter, Wesseling, Harry, BoeLaert, J. R., Schurgers, M. L., Matthys, E. G., Belpaire, F., Daneels, R. F., de Cre, M. J., Boqaert, M. G., D'Haese, P. C., Verpooten, G. A., Lamberts, L. V., Liang, L., de Broe, M. E., de Meijer, P. H. E. M., Russel, F. G. M., Russel, A. J. M., van Ginneken, C. A. M., van Liedekerke, B. M., Lambert, W. E., Yousouf, M. A., de Roose, J. E., de Leenheer, A. P., Lambert, W., de Bersaques, J., Vanneste, L., de Leenheer, A., de Marie, S., Slaghuis, G., Rozing, P. M., Mattie, H., Poelma, F. G. J., Hilbers, H. W., Jansen, A. C. A., Tukker, J. J., Augusti, Jr, P., Verbeke, N., van Peer, A., Snoeck, E., Heykants, J., Bruynseels, J., Peeters, J., Amery, W., Rogiers, V., Vandenberghe, Y., Comet, M., Callaerts, A., Sonck, W., Guillouzo, A., Vercruysse, A., van Rooy, P., Rombaut, N., vanden Bussche, G., Tan, A. C. I. T. L., Jansen, T. L. Th. A., Termond, E. F. S., Kloppenborg, P. W. C., Thien, Th., Benraad, Th. J., van de Velde, V., Woestenbprghs, R., Hermens, W. A. J. J., Romeijn, S. G., Deurloo, M. J. M., Merkus, F. W. H. M., Musch, G., Massart, D. L., van Hengstum, M., Festen, J., van den Broek, W., Corstens, F., Beurskens, C., Hankel, M., de Smet, M., van Belle, S. J. P., de May, J., Storme, G. A., Kuppen, P. J. K., Schuitemaker, H., Veer, L. J. van't, van Oosterom, A. T., Schrier, P. I., de Bruijn, E. A., de Pooter, C. H., Tjaden, U. R., van Slooten, H., Roelevink, H. P., Smit, E., de Vries, E. G. E., Ijmker, J., Uges, D. R. A., Moors, M., Mertens, K., van Hecken, A., de Lepeleire, I., Verbesselt, R., Tjandra-Maga, T. B., de Schepper, P. J., Guelen, P. J. M., Jansen, T. J., Vrijhof, W. P., de Vos, D., Scharpé, S., Verkerk, R., Lsmeire, N., Zijlstra, I. F., Gribnau, F. W. J., Haaijer-Ruskamp, F. M., Post, D., Reddingius, P. F., Wesseling, H., Wollersheim, H. C. H., van den Meiracker, A. H., Veld, A. J. Man in 't, Admiraal, P., Boomsma, F., Derkx, F., Schalekamp, M. A. D. H., Schoors, D. F., Dupont, A. G., Claessen, F., Reljenga, J., Lenders, J. W. M., Thlen, Th., Laekeman, G., Muylle, L., van Hoydonck, A., Herman, A. G., and Peetermans, M. E.

Published
1988
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205. Genome-wide meta-analysis of common variant differences between men and women

Author

Boraska, Vesna Jeroncic, Ana Colonna, Vincenza Southam, Lorraine Nyholt, Dale R. Rayner, Nigel William Perry, John R. B. Toniolo, Daniela Albrecht, Eva Ang, Wei and Bandinelli, Stefania Barbalic, Maja Barroso, Ines Beckmann, Jacques S. Biffar, Reiner Boomsma, Dorret Campbell, Harry and Corre, Tanguy Erdmann, Jeanette Esko, Tonu Fischer, Krista Franceschini, Nora Frayling, Timothy M. Girotto, Giorgia Gonzalez, Juan R. Harris, Tamara B. Heath, Andrew C. and Heid, Iris M. Hoffmann, Wolfgang Hofman, Albert and Horikoshi, Momoko Zhao, Jing Hua Jackson, Anne U. Hottenga, Jouke-Jan Jula, Antti Kahonen, Mika Khaw, Kay-Tee and Kiemeney, Lambertus A. Klopp, Norman Kutalik, Zoltan Lagou, Vasiliki Launer, Lenore J. Lehtimaki, Terho Lemire, Mathieu and Lokki, Marja-Liisa Loley, Christina Luan, Jian'an and Mangino, Massimo Leach, Irene Mateo Medland, Sarah E. and Mihailov, Evelin Montgomery, Grant W. Navis, Gerjan Newnham, John Nieminen, Markku S. Palotie, Aarno Panoutsopoulou, Kalliope Peters, Annette Pirastu, Nicola Polasek, Ozren and Rehnstrom, Karola Ripatti, Samuli Ritchie, Graham R. S. and Rivadeneira, Fernando Robino, Antonietta Samani, Nilesh J. and Shin, So-Youn Sinisalo, Juha Smit, Johannes H. Soranzo, Nicole Stolk, Lisette Swinkels, Dorine W. Tanaka, Toshiko and Teumer, Alexander Tonejes, Anke Traglia, Michela and Tuomilehto, Jaakko Valsesia, Armand van Gilst, Wiek H. van Meurs, Joyce B. J. Smith, Albert Vernon Viikari, Jorma Vink, Jacqueline M. Waeber, Gerard Warrington, Nicole M. Widen, Elisabeth Willemsen, Gonneke Wright, Alan F. Zanke, Brent W. and Zgaga, Lina Boehnke, Michael d'Adamo, Adamo Pio de Geus, Eco Demerath, Ellen W. den Heijer, Martin Eriksson, Johan G. and Ferrucci, Luigi Gieger, Christian Gudnason, Vilmundur and Hayward, Caroline Hengstenberg, Christian Hudson, Thomas J. and Jarvelin, Marjo-Riitta Kogevinas, Manolis Loos, Ruth J. F. and Martin, Nicholas G. Metspalu, Andres Pennell, Craig E. and Penninx, Brenda W. Perola, Markus Raitakari, Olli Salomaa, Veikko Schreiber, Stefan Schunkert, Heribert Spector, Tim D. and Stumvoll, Michael Uitterlinden, Andre G. Ulivi, Sheila and van der Harst, Pim Vollenweider, Peter Volzke, Henry and Wareham, Nicholas J. Wichmann, H-Erich Wilson, James F. and Rudan, Igor Xue, Yali Zeggini, Eleftheria Wellcome Trust Case Control

Abstract

The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency 0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P 5 10(8)) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across approximate to 115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased traits.

Published
2012

206. Galectin-3, Renal Function, and Clinical Outcomes

Author

Drechsler, Christiane, primary, Delgado, Graciela, additional, Wanner, Christoph, additional, Blouin, Katja, additional, Pilz, Stefan, additional, Tomaschitz, Andreas, additional, Kleber, Marcus E., additional, Dressel, Alexander, additional, Willmes, Christoph, additional, Krane, Vera, additional, Krämer, Bernhard K., additional, März, Winfried, additional, Ritz, Eberhard, additional, van Gilst, Wiek H., additional, van der Harst, Pim, additional, and de Boer, Rudolf A., additional

Published
2015
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207. Cardiac LXR α protects against pathological cardiac hypertrophy and dysfunction by enhancing glucose uptake and utilization

Author

Cannon, Megan V, primary, Silljé, Herman HW, additional, Sijbesma, Jürgen WA, additional, Vreeswijk‐Baudoin, Inge, additional, Ciapaite, Jolita, additional, van der Sluis, Bart, additional, van Deursen, Jan, additional, Silva, Gustavo JJ, additional, de Windt, Leon J, additional, Gustafsson, Jan‐Åke, additional, van der Harst, Pim, additional, van Gilst, Wiek H, additional, and de Boer, Rudolf A, additional

Published
2015
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210. Genome-Wide Meta-Analyses of Plasma Renin Activity and Concentration Reveal Association With the Kininogen 1 and Prekallikrein Genes

Author

Lieb, Wolfgang, primary, Chen, Ming-Huei, additional, Teumer, Alexander, additional, de Boer, Rudolf A., additional, Lin, Honghuang, additional, Fox, Ervin R., additional, Musani, Solomon K., additional, Wilson, James G., additional, Wang, Thomas J., additional, Völzke, Henry, additional, Petersen, Ann-Kristin, additional, Meisinger, Christine, additional, Nauck, Matthias, additional, Schlesinger, Sabrina, additional, Li, Yong, additional, Menard, Jöel, additional, Hercberg, Serge, additional, Wichmann, H.-Erich, additional, Völker, Uwe, additional, Rawal, Rajesh, additional, Bidlingmaier, Martin, additional, Hannemann, Anke, additional, Dörr, Marcus, additional, Rettig, Rainer, additional, van Gilst, Wiek H., additional, van Veldhuisen, Dirk J., additional, Bakker, Stephan J.L., additional, Navis, Gerjan, additional, Wallaschofski, Henri, additional, Meneton, Pierre, additional, van der Harst, Pim, additional, Reincke, Martin, additional, and Vasan, Ramachandran S., additional

Published
2015
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211. Variants near TERC are associated with mean telomere length

Author

Codd, Veryan, Mangino, Massimo, van der Harst, Pim, Braund, Peter S, Kaiser, Michael, Beveridge, Alan J, Rafelt, Suzanne, Moore, Jasbir, Nelson, Chris, Soranzo, Nicole, Zhai, Guangju, Valdes, Ana M, Blackburn, Hannah, Leach, Irene Mateo, de Boer, Rudolf A, Goodall, Alison H, Ouwehand, Willem, van Veldhuisen, Dirk J., van Gilst, Wiek H., Navis, Gerjan, Burton, Paul R, Tobin, Martin D, Hall, Alistair S, Thompson, John R, Spector, Tim, and Samani, Nilesh J

Subjects
Aging, Time Factors, Quantitative Trait Loci, Age Factors, Telomere, Polymorphism, Single Nucleotide, Article, Cohort Studies, Gene Frequency, Meta-Analysis as Topic, Humans, RNA, Chromosomes, Human, Pair 3, Telomerase, Genome-Wide Association Study
Abstract

We conducted genome-wide association analyses of mean leukocyte telomere length in 2,917 individuals, with follow-up replication in 9,492 individuals. We identified an association with telomere length on 3q26 (rs12696304, combined P = 3.72 x 10(-14)) at a locus that includes TERC, which encodes the telomerase RNA component. Each copy of the minor allele of rs12696304 was associated with an approximately 75-base-pair reduction in mean telomere length, equivalent to approximately 3.6 years of age-related telomere-length attrition.

Published
2010

213. Fibrosis Marker Syndecan-1 and Outcome in Patients With Heart Failure With Reduced and Preserved Ejection Fraction

Author

Tromp, Jasper, van der Pol, Atze, Klip, IJsbrand T., de Boer, Rudolf A., Jaarsma, Tiny, van Gilst, Wiek H., Voors, Adriaan A., van Veldhuisen, Dirk J., van der Meer, Peter, Tromp, Jasper, van der Pol, Atze, Klip, IJsbrand T., de Boer, Rudolf A., Jaarsma, Tiny, van Gilst, Wiek H., Voors, Adriaan A., van Veldhuisen, Dirk J., and van der Meer, Peter

Abstract

Background-Syndecan-1 is a member of the proteoglycan family involved in cell-matrix interactions. Experimental studies showed that syndecan-1 is associated with inflammation in acute myocardial infarction and remodeling. The goal of this study was to explore the role of syndecan-1 in human heart failure (HF). Methods and Results-We analyzed plasma syndecan-1 levels in 567 patients with chronic HF. Primary end point was a composite of all-cause mortality and rehospitalization for HF at 18 months. Mean age was 71.0 +/- 11.0 years, 38% was women, and mean left ventricular ejection fraction was 32.5 +/- 14.0%. Median syndecan-1 levels were 20.1 ng/mL (interquartile range, 13.9-27.7 ng/mL). Patients with higher syndecan-1 levels were more often men, had higher N-terminal probrain-type natriuretic peptide levels, and worse renal function. Multivariable regression analyses showed a positive correlation between syndecan-1 levels and markers of fibrosis and remodeling but no correlation with inflammation markers. Interaction analysis revealed an interaction between left ventricular ejection fraction and syndecan-1 (P=0.047). A doubling of syndecan-1 was associated with an increased risk of the primary outcome in patients with HF with preserved ejection fraction (hazard ratio, 2.10; 95% confidence interval, 1.14-3.86; P=0.017) but not in patients with HF with reduced ejection fraction (hazard ratio, 0.95; 95% confidence interval, 0.71-1.27; P=0.729). Finally, syndecan-1 enhanced risk classification in patients with HF with preserved ejection fraction when added to a prediction model with established risk factors. Conclusions-In patients with HF, syndecan-1 levels correlate with fibrosis biomarkers pointing toward a role in cardiac remodeling. Syndecan-1 was associated with clinical outcome in patients with HF with preserved ejection fraction but not in patients with HF with reduced ejection fraction.

Published
2014
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214. The impact of coronary artery disease risk loci on ischemic heart failure severity and prognosis: association analysis in the COntrolled ROsuvastatin multiNAtional trial in heart failure (CORONA)

Author

Haver, Vincent G, primary, Verweij, Niek, additional, Kjekshus, John, additional, Fox, Jayne C, additional, Wedel, Hans, additional, Wikstrand, John, additional, van Gilst, Wiek H, additional, de Boer, Rudolf A, additional, van Veldhuisen, Dirk J, additional, and van der Harst, Pim, additional

Published
2014
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216. Sex differences in new-onset heart failure

Author

Meyer, Sven, primary, Brouwers, Frank P., additional, Voors, Adriaan A., additional, Hillege, Hans L., additional, de Boer, Rudolf A., additional, Gansevoort, Ron T., additional, van der Harst, Pim, additional, Rienstra, Michiel, additional, van Gelder, Isabelle C., additional, van Veldhuisen, Dirk J., additional, van Gilst, Wiek H., additional, and van der Meer, Peter, additional

Published
2014
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217. Separating the mechanism-based and off-target actions of CETP-inhibitors using CETP gene polymorphisms

Author

Sofat, Reecha, Hingorani, Aroon D, Smeeth, Liam, Humphries, Steve E, Talmud, Philippa J, Cooper, Jackie, Shah, Tina, Sandhu, Manjinder S, Ricketts, Sally L, Boekholdt, S Matthijs, Wareham, Nicholas, Khaw, Kay Tee, Kumari, Meena, Kivimaki, Mika, Marmot, Michael, Asselbergs, Folkert W, van der Harst, Pim, Dullaart, Robin P F, Navis, Gerjan, van Veldhuisen, Dirk J, Van Gilst, Wiek H, Thompson, John F, McCaskie, Pamela, Palmer, Lyle J, Arca, Marcello, Quagliarini, Fabiana, Gaudio, Carlo, Cambien, François, Nicaud, Viviane, Poirer, Odette, Gudnason, Vilmundur, Isaacs, Aaron, Witteman, Jacqueline C M, van Duijn, Cornelia M, Pencina, Michael, Vasan, Ramachandran. S, D'Agostino, Ralph B, Ordovas, Jose, Li, Tricia Y., Kakko, Sakari, Kauma, Heikki, Savolainen, Markku J., Kesäniemi, Y.Antero, Sandhofer, Anton, Paulweber, Bernhard, Sorli, Jose V, Goto, Akimoto, Yokoyama, Shinji, Okumura, Kenji, Horne, Benjamin D, Packard, Chris, Freeman, Dilys, Ford, Ian, Sattar, Naveed, McCormack, Valerie, Lawlor, Debbie A, Ebrahim, Shah, Davey Smith, George, Kastelein, John J P, Deanfield, John, and Casas, Juan P

Subjects
Dose-Response Relationship, Drug, Genotype, Anticholesteremic Agents, Hypercholesterolemia, Blood Pressure, Polymorphism, Single Nucleotide, Article, White People, Cholesterol Ester Transfer Proteins, Electrolytes, Risk Factors, Hypertension, Quinolines, Humans, Lipoproteins, HDL, Biomarkers, Randomized Controlled Trials as Topic
Abstract

Cholesteryl ester transfer protein (CETP) inhibitors raise high-density lipoprotein (HDL) cholesterol, but torcetrapib, the first-in-class inhibitor tested in a large outcome trial, caused an unexpected blood pressure elevation and increased cardiovascular events. Whether the hypertensive effect resulted from CETP inhibition or an off-target action of torcetrapib has been debated. We hypothesized that common single-nucleotide polymorphisms in the CETP gene could help distinguish mechanism-based from off-target actions of CETP inhibitors to inform on the validity of CETP as a therapeutic target.We compared the effect of CETP single-nucleotide polymorphisms and torcetrapib treatment on lipid fractions, blood pressure, and electrolytes in up to 67 687 individuals from genetic studies and 17 911 from randomized trials. CETP single-nucleotide polymorphisms and torcetrapib treatment reduced CETP activity and had a directionally concordant effect on 8 lipid and lipoprotein traits (total, low-density lipoprotein, and HDL cholesterol; HDL2; HDL3; apolipoproteins A-I and B; and triglycerides), with the genetic effect on HDL cholesterol (0.13 mmol/L, 95% confidence interval [CI] 0.11 to 0.14 mmol/L) being consistent with that expected of a 10-mg dose of torcetrapib (0.13 mmol/L, 95% CI 0.10 to 0.15). In trials, 60 mg of torcetrapib elevated systolic and diastolic blood pressure by 4.47 mm Hg (95% CI 4.10 to 4.84 mm Hg) and 2.08 mm Hg (95% CI 1.84 to 2.31 mm Hg), respectively. However, the effect of CETP single-nucleotide polymorphisms on systolic blood pressure (0.16 mm Hg, 95% CI -0.28 to 0.60 mm Hg) and diastolic blood pressure (-0.04 mm Hg, 95% CI -0.36 to 0.28 mm Hg) was null and significantly different from that expected of 10 mg of torcetrapib.Discordance in the effects of CETP single-nucleotide polymorphisms and torcetrapib treatment on blood pressure despite the concordant effects on lipids indicates the hypertensive action of torcetrapib is unlikely to be due to CETP inhibition or shared by chemically dissimilar CETP inhibitors. Genetic studies could find a place in drug-development programs as a new source of randomized evidence for drug-target validation in humans.

Published
2009

218. The gender-specific role of polymorphisms from the fibrinolytic, renin-angiotensin, and bradykinin systems in determining plasma t-PA and PAI-I levels

Author

Asselbergs, Folkert W., Williams, Scott M., Hebert, Patricia R., Coffey, Christopher S., Hillege, Hans L., Navis, Gerjan, Vaughan, Douglas E., van Gilst, Wiek H., Moore, Jason H., Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), and Vascular Ageing Programme (VAP)

Subjects
PROTHROMBOTIC STATE, CARDIOVASCULAR RISK, INSULIN-RESISTANCE SYNDROME, PAI-1-4G/5G POLYMORPHISMS, URINARY ALBUMIN EXCRETION, PLASMINOGEN-ACTIVATOR INHIBITOR-1, MYOCARDIAL-INFARCTION, POSTMENOPAUSAL WOMEN, epidemiological studies, plasminogen, RISK-FACTORS, risk factors, sex, CONVERTING ENZYME-INHIBITION, thrombosis
Abstract

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor I (PAI-I) directly influence thrombus formation and degradation and thus risk for arterial thrombosis. We report here results from a genetic analysis of plasma t-PA and PAI-I levels in a large population-based sample from the PREVEND study in Groningen, the Netherlands (n = 2,527). We measured polymorphisms from genes of the fibrinolytic system, the renin-angiotensin system (RAS), and the bradykinin system. We found that males had higher levels of natural-log transformed t-PA, and PAI-I (P

Published
2006

219. Renal Handling of Galectin‐3 in the General Population, Chronic Heart Failure, and Hemodialysis

Author

Meijers, Wouter C., primary, van der Velde, A. Rogier, additional, Ruifrok, Willem P., additional, Schroten, Nicolas F., additional, Dokter, Martin M., additional, Damman, Kevin, additional, Assa, Solmaz, additional, Franssen, Casper F., additional, Gansevoort, Ron T., additional, van Gilst, Wiek H., additional, Silljé, Herman H., additional, and de Boer, Rudolf A., additional

Published
2014
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221. Clinical Risk Stratification Optimizes Value of Biomarkers to Predict New-Onset Heart Failure in a Community-Based Cohort

Author

Brouwers, Frank P., primary, van Gilst, Wiek H., additional, Damman, Kevin, additional, van den Berg, Maarten P., additional, Gansevoort, Ron T., additional, Bakker, Stephan J.L., additional, Hillege, Hans L., additional, van Veldhuisen, Dirk J., additional, van der Harst, Pim, additional, and de Boer, Rudolf A., additional

Published
2014
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222. Effects of Long-Term Averaging of Quantitative Blood Pressure Traits on the Detection of Genetic Associations

Author

Ganesh, Santhi K., primary, Chasman, Daniel I., additional, Larson, Martin G., additional, Guo, Xiuqing, additional, Verwoert, Germain, additional, Bis, Joshua C., additional, Gu, Xiangjun, additional, Smith, Albert V., additional, Yang, Min-Lee, additional, Zhang, Yan, additional, Ehret, Georg, additional, Rose, Lynda M., additional, Hwang, Shih-Jen, additional, Papanicolau, George J., additional, Sijbrands, Eric J., additional, Rice, Kenneth, additional, Eiriksdottir, Gudny, additional, Pihur, Vasyl, additional, Ridker, Paul M., additional, Vasan, Ramachandran S., additional, Newton-Cheh, Christopher, additional, Raffel, Leslie J., additional, Amin, Najaf, additional, Rotter, Jerome I., additional, Liu, Kiang, additional, Launer, Lenore J., additional, Xu, Ming, additional, Caulfield, Mark, additional, Morrison, Alanna C., additional, Johnson, Andrew D., additional, Vaidya, Dhananjay, additional, Dehghan, Abbas, additional, Li, Guo, additional, Bouchard, Claude, additional, Harris, Tamara B., additional, Zhang, He, additional, Boerwinkle, Eric, additional, Siscovick, David S., additional, Gao, Wei, additional, Uitterlinden, Andre G., additional, Rivadeneira, Fernando, additional, Hofman, Albert, additional, Willer, Cristen J., additional, Franco, Oscar H., additional, Huo, Yong, additional, Witteman, Jacqueline C.M., additional, Munroe, Patricia B., additional, Gudnason, Vilmundur, additional, Palmas, Walter, additional, van Duijn, Cornelia, additional, Fornage, Myriam, additional, Levy, Daniel, additional, Psaty, Bruce M., additional, Chakravarti, Aravinda, additional, Johnson, Toby, additional, Gateva, Vesela, additional, Tobin, Martin D., additional, Bochud, Murielle, additional, Coin, Lachlan, additional, Najjar, Samer S., additional, Zhao, Jing Hua, additional, Heath, Simon C., additional, Eyheramendy, Susana, additional, Papadakis, Konstantinos, additional, Voight, Benjamin F., additional, Scott, Laura J., additional, Zhang, Feng, additional, Farrall, Martin, additional, Tanaka, Toshiko, additional, Wallace, Chris, additional, Chambers, John C., additional, Khaw, Kay-Tee, additional, Nilsson, Peter, additional, van der Harst, Pim, additional, Polidoro, Silvia, additional, Grobbee, Diederick E., additional, Onland-Moret, N. Charlotte, additional, Bots, Michiel L., additional, Wain, Louise V., additional, Elliott, Katherine S., additional, Teumer, Alexander, additional, Luan, Jian’an, additional, Lucas, Gavin, additional, Kuusisto, Johanna, additional, Burton, Paul R., additional, Hadley, David, additional, McArdle, Wendy L., additional, Brown, Morris, additional, Dominiczak, Anna, additional, Newhouse, Stephen J., additional, Samani, Nilesh J., additional, Webster, John, additional, Zeggini, Eleftheria, additional, Beckmann, Jacques S., additional, Bergmann, Sven, additional, Lim, Noha, additional, Song, Kijoung, additional, Vollenweider, Peter, additional, Waeber, Gerard, additional, Waterworth, Dawn M., additional, Yuan, Xin, additional, Groop, Leif, additional, Orho-Melander, Marju, additional, Allione, Alessandra, additional, Di Gregorio, Alessandra, additional, Guarrera, Simonetta, additional, Panico, Salvatore, additional, Ricceri, Fulvio, additional, Romanazzi, Valeria, additional, Sacerdote, Carlotta, additional, Vineis, Paolo, additional, Barroso, Inês, additional, Sandhu, Manjinder S., additional, Luben, Robert N., additional, Crawford, Gabriel J., additional, Jousilahti, Pekka, additional, Perola, Markus, additional, Boehnke, Michael, additional, Bonnycastle, Lori L., additional, Collins, Francis S., additional, Jackson, Anne U., additional, Mohlke, Karen L., additional, Stringham, Heather M., additional, Valle, Timo T., additional, Willer, Cristen J., additional, Bergman, Richard N., additional, Morken, Mario A., additional, Döring, Angela, additional, Gieger, Christian, additional, Illig, Thomas, additional, Meitinger, Thomas, additional, Org, Elin, additional, Pfeufer, Arne, additional, Wichmann, H. Erich, additional, Kathiresan, Sekar, additional, Marrugat, Jaume, additional, O’Donnell, Christopher J., additional, Schwartz, Stephen M., additional, Siscovick, David S., additional, Subirana, Isaac, additional, Freimer, Nelson B., additional, Hartikainen, Anna-Liisa, additional, McCarthy, Mark I., additional, O’Reilly, Paul F., additional, Peltonen, Leena, additional, Pouta, Anneli, additional, de Jong, Paul E., additional, Snieder, Harold, additional, van Gilst, Wiek H., additional, Clarke, Robert, additional, Goel, Anuj, additional, Hamsten, Anders, additional, Peden, John F., additional, Seedorf, Udo, additional, Syvänen, Ann-Christine, additional, Tognoni, Giovanni, additional, Lakatta, Edward G., additional, Sanna, Serena, additional, Scheet, Paul, additional, Schlessinger, David, additional, Scuteri, Angelo, additional, Dörr, Marcus, additional, Ernst, Florian, additional, Felix, Stephan B., additional, Homuth, Georg, additional, Lorbeer, Roberto, additional, Reffelmann, Thorsten, additional, Rettig, Rainer, additional, Völker, Uwe, additional, Galan, Pilar, additional, Gut, Ivo G., additional, Hercberg, Serge, additional, Lathrop, G. Mark, additional, Zeleneka, Diana, additional, Deloukas, Panos, additional, Soranzo, Nicole, additional, Williams, Frances M., additional, Zhai, Guangju, additional, Salomaa, Veikko, additional, Laakso, Markku, additional, Elosua, Roberto, additional, Forouhi, Nita G., additional, Völzke, Henry, additional, Uiterwaal, Cuno S., additional, van der Schouw, Yvonne T, additional, Numans, Mattijs E., additional, Matullo, Giuseppe, additional, Navis, Gerjan, additional, Berglund, Göran, additional, Bingham, Sheila A., additional, Kooner, Jaspal S., additional, Paterson, Andrew D., additional, Connell, John M., additional, Bandinelli, Stefania, additional, Ferrucci, Luigi, additional, Watkins, Hugh, additional, Spector, Tim D., additional, Tuomilehto, Jaakko, additional, Altshuler, David, additional, Strachan, David P., additional, Laan, Maris, additional, Meneton, Pierre, additional, Wareham, Nicholas J., additional, Uda, Manuela, additional, Jarvelin, Marjo-Riitta, additional, Mooser, Vincent, additional, Melander, Olle, additional, Loos, Ruth J.F., additional, Elliott, Paul, additional, Abecasis, Gonçalo R., additional, and Munroe, Patricia B., additional

Published
2014
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224. Genome-Wide Association Study for Circulating Tissue Plasminogen Activator Levels and Functional Follow-Up Implicates Endothelial STXBP5 and STX2

Author

Huang, Jie, primary, Huffman, Jennifer E., additional, Yamakuchi, Munekazu, additional, Trompet, Stella, additional, Asselbergs, Folkert W., additional, Sabater-Lleal, Maria, additional, Trégouët, David-Alexandre, additional, Chen, Wei-Min, additional, Smith, Nicholas L., additional, Kleber, Marcus E., additional, Shin, So-Youn, additional, Becker, Diane M., additional, Tang, Weihong, additional, Dehghan, Abbas, additional, Johnson, Andrew D., additional, Truong, Vinh, additional, Folkersen, Lasse, additional, Yang, Qiong, additional, Oudot-Mellkah, Tiphaine, additional, Buckley, Brendan M., additional, Moore, Jason H., additional, Williams, Frances M.K., additional, Campbell, Harry, additional, Silbernagel, Günther, additional, Vitart, Veronique, additional, Rudan, Igor, additional, Tofler, Geoffrey H., additional, Navis, Gerjan J., additional, DeStefano, Anita, additional, Wright, Alan F., additional, Chen, Ming-Huei, additional, de Craen, Anton J.M., additional, Worrall, Bradford B., additional, Rudnicka, Alicja R., additional, Rumley, Ann, additional, Bookman, Ebony B., additional, Psaty, Bruce M., additional, Chen, Fang, additional, Keene, Keith L., additional, Franco, Oscar H., additional, Böhm, Bernhard O., additional, Uitterlinden, Andre G., additional, Carter, Angela M., additional, Jukema, J. Wouter, additional, Sattar, Naveed, additional, Bis, Joshua C., additional, Ikram, Mohammad A., additional, Sale, Michèle M., additional, McKnight, Barbara, additional, Fornage, Myriam, additional, Ford, Ian, additional, Taylor, Kent, additional, Slagboom, P. Eline, additional, McArdle, Wendy L., additional, Hsu, Fang-Chi, additional, Franco-Cereceda, Anders, additional, Goodall, Alison H., additional, Yanek, Lisa R., additional, Furie, Karen L., additional, Cushman, Mary, additional, Hofman, Albert, additional, Witteman, Jacqueline C.M., additional, Folsom, Aaron R., additional, Basu, Saonli, additional, Matijevic, Nena, additional, van Gilst, Wiek H., additional, Wilson, James F., additional, Westendorp, Rudi G.J., additional, Kathiresan, Sekar, additional, Reilly, Muredach P., additional, Tracy, Russell P., additional, Polasek, Ozren, additional, Winkelmann, Bernhard R., additional, Grant, Peter J., additional, Hillege, Hans L., additional, Cambien, Francois, additional, Stott, David J., additional, Lowe, Gordon D., additional, Spector, Timothy D., additional, Meigs, James B., additional, Marz, Winfried, additional, Eriksson, Per, additional, Becker, Lewis C., additional, Morange, Pierre-Emmanuel, additional, Soranzo, Nicole, additional, Williams, Scott M., additional, Hayward, Caroline, additional, van der Harst, Pim, additional, Hamsten, Anders, additional, Lowenstein, Charles J., additional, Strachan, David P., additional, and O’Donnell, Christopher J., additional

Published
2014
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227. HEMOGLOBIN LEVELS AND THE RISK OF NEW ONSET HEART FAILURE IN A COMMUNITY-BASED COHORT: DATA FROM PREVEND

Author

Klip, IJsbrand Thomas, primary, Postmus, Douwe, additional, Voors, Adriaan, additional, Brouwers, Frank P.J., additional, Gansevoort, Ron T., additional, Bakker, Stephan J.L., additional, Hillege, Hans, additional, de Boer, Rudolf A., additional, van der Harst, Pim, additional, van Gilst, Wiek H., additional, van Veldhuisen, Dirk, additional, and Vandermeer, Peter, additional

Published
2014
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228. Cardiac Function and Architecture Are Maintained in a Model of Cardiorestricted Overexpression of the Prorenin-Renin Receptor

Author

Mahmud, Hasan, primary, Candido, Wellington Mardoqueu, additional, van Genne, Linda, additional, Vreeswijk-Baudoin, Inge, additional, Yu, Hongjuan, additional, van de Sluis, Bart, additional, van Deursen, Jan, additional, van Gilst, Wiek H., additional, Silljé, Herman H. W., additional, and de Boer, Rudolf A., additional

Published
2014
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229. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders

Author

den Hoed, Marcel, Eijgelsheim, Mark, Esko, Tonu, Brundel, Bianca J. J. M., Peal, David S., Evans, David M., Nolte, Ilja M., Segre, Ayellet V., Holm, Hilma, Handsaker, Robert E., Westra, Harm-Jan, Johnson, Toby, Isaacs, Aaron, Yang, Jian, Lundby, Alicia, Zhao, Jing Hua, Kim, Young Jin, Go, Min Jin, Almgren, Peter, Bochud, Murielle, Boucher, Gabrielle, Cornelis, Marilyn C., Gudbjartsson, Daniel, Hadley, David, van der Harst, Pim, Hayward, Caroline, den Heijer, Martin, Igl, Wilmar, Jackson, Anne U., Kutalik, Zoltan, Luan, Jian'an, Kemp, John P., Kristiansson, Kati, Ladenvall, Claes, Lorentzon, Mattias, Montasser, May E., Njajou, Omer T., O'Reilly, Paul F., Padmanabhan, Sandosh, Pourcain, Beate St., Rankinen, Tuomo, Salo, Perttu, Tanaka, Toshiko, Timpson, Nicholas J., Vitart, Veronique, Waite, Lindsay, Wheeler, William, Zhang, Weihua, Draisma, Harmen H. M., Feitosa, Mary F., Kerr, Kathleen F., Lind, Penelope A., Mihailov, Evelin, Onland-Moret, N. Charlotte, Song, Ci, Weedon, Michael N., Xie, Weijia, Yengo, Loic, Absher, Devin, Albert, Christine M., Alonso, Alvaro, Arking, Dan E., de Bakker, Paul I. W., Balkau, Beverley, Barlassina, Cristina, Benaglio, Paola, Bis, Joshua C., Bouatia-Naji, Nabila, Brage, Soren, Chanock, Stephen J., Chines, Peter S., Chung, Mina, Darbar, Dawood, Dina, Christian, Doerr, Marcus, Elliott, Paul, Felix, Stephan B., Fischer, Krista, Fuchsberger, Christian, de Geus, Eco J. C., Goyette, Philippe, Gudnason, Vilmundur, Harris, Tamara B., Hartikainen, Anna-Liisa, Havulinna, Aki S., Heckbert, Susan R., Hicks, Andrew A., Hofman, Albert, Holewijn, Suzanne, Hoogstra-Berends, Femke, Hottenga, Jouke-Jan, Jensen, Majken K., Johansson, Asa, Junttila, Juhani, Kaeaeb, Stefan, Kanon, Bart, Ketkar, Shamika, Khaw, Kay-Tee, Knowles, Joshua W., Kooner, Angrad S., Kors, Jan A., Kumari, Meena, Milani, Lili, Laiho, Paeivi, Lakatta, Edward G., Langenberg, Claudia, Leusink, Maarten, Liu, Yongmei, Luben, Robert N., Lunetta, Kathryn L., Lynch, Stacey N., Markus, Marcello R. P., Marques-Vidal, Pedro, Leach, Irene Mateo, McArdle, Wendy L., McCarroll, Steven A., Medland, Sarah E., Miller, Kathryn A., Montgomery, Grant W., Morrison, Alanna C., Mueller-Nurasyid, Martina, Navarro, Pau, Nelis, Mari, O'Connell, Jeffrey R., O'Donnell, Christopher J., Ong, Ken K., Newman, Anne B., Peters, Annette, Polasek, Ozren, Pouta, Anneli, Pramstaller, Peter P., Psaty, Bruce M., Rao, Dabeeru C., Ring, Susan M., Rossin, Elizabeth J., Rudan, Diana, Sanna, Serena, Scott, Robert A., Sehmi, Jaban S., Sharp, Stephen, Shin, Jordan T., Singleton, Andrew B., Smith, Albert V., Soranzo, Nicole, Spector, Tim D., Stewart, Chip, Stringham, Heather M., Tarasov, Kirill V., Uitterlinden, Andre G., Vandenput, Liesbeth, Hwang, Shih-Jen, Whitfield, John B., Wijmenga, Cisca, Wild, Sarah H., Willemsen, Gonneke, Wilson, James F., Witteman, Jacqueline C. M., Wong, Andrew, Wong, Quenna, Jamshidi, Yalda, Zitting, Paavo, Boer, Jolanda M. A., Boomsma, Dorret I., Borecki, Ingrid B., van Duijn, Cornelia M., Ekelund, Ulf, Forouhi, Nita G., Froguel, Philippe, Hingorani, Aroon, Ingelsson, Erik, Kivimaki, Mika, Kronmal, Richard A., Kuh, Diana, Lind, Lars, Martin, Nicholas G., Oostra, Ben A., Pedersen, Nancy L., Quertermous, Thomas, Rotter, Jerome I., van der Schouw, Yvonne T., Verschuren, W. M. Monique, Walker, Mark, Albanes, Demetrius, Arnar, David O., Assimes, Themistocles L., Bandinelli, Stefania, Boehnke, Michael, de Boer, Rudolf A., Bouchard, Claude, Caulfield, W. L. Mark, Chambers, John C., Curhan, Gary, Cusi, Daniele, Eriksson, Johan, Ferrucci, Luigi, van Gilst, Wiek H., Glorioso, Nicola, de Graaf, Jacqueline, Groop, Leif, Gyllensten, Ulf, Hsueh, Wen-Chi, Hu, Frank B., Huikuri, Heikki V., Hunter, David J., Iribarren, Carlos, Isomaa, Bo, Jarvelin, Marjo-Riitta, Jula, Antti, Kahonen, Mika, Kiemeney, Lambertus A., van der Klauw, Melanie M., Kooner, Jaspal S., Kraft, Peter, Iacoviello, Licia, Lehtimaki, Terho, Lokki, Marja-Liisa L., Mitchell, Braxton D., Navis, Gerjan, Nieminen, Markku S., Ohlsson, Claes, Poulter, Neil R., Qi, Lu, Raitakari, Olli T., Rimm, Eric B., Rioux, John D., Rizzi, Federica, Rudan, Igor, Salomaa, Veikko, Sever, Peter S., Shields, Denis C., Shuldiner, Alan R., Sinisalo, Juha, Stanton, Alice V., Stolk, Ronald P., Strachan, David P., Tardif, Jean-Claude, Thorsteinsdottir, Unnur, Tuomilehto, Jaako, van Veldhuisen, Dirk J., Virtamo, Jarmo, Viikari, Jorma, Vollenweider, Peter, Waeber, Gerard, Widen, Elisabeth, Cho, Yoon Shin, Olsen, Jesper V., Visscher, Peter M., Willer, Cristen, Franke, Lude, Erdmann, Jeanette, Thompson, John R., Pfeufer, Arne, Sotoodehnia, Nona, Newton-Cheh, Christopher, Ellinor, Patrick T., Stricker, Bruno H. Ch, Metspalu, Andres, Perola, Markus, Beckmann, Jacques S., Smith, George Davey, Stefansson, Kari, Wareham, Nicholas J., Munroe, Patricia B., Sibon, Ody C. M., Milan, David J., Snieder, Harold, Samani, Nilesh J., Loos, Ruth J. F., den Hoed, Marcel, Eijgelsheim, Mark, Esko, Tonu, Brundel, Bianca J. J. M., Peal, David S., Evans, David M., Nolte, Ilja M., Segre, Ayellet V., Holm, Hilma, Handsaker, Robert E., Westra, Harm-Jan, Johnson, Toby, Isaacs, Aaron, Yang, Jian, Lundby, Alicia, Zhao, Jing Hua, Kim, Young Jin, Go, Min Jin, Almgren, Peter, Bochud, Murielle, Boucher, Gabrielle, Cornelis, Marilyn C., Gudbjartsson, Daniel, Hadley, David, van der Harst, Pim, Hayward, Caroline, den Heijer, Martin, Igl, Wilmar, Jackson, Anne U., Kutalik, Zoltan, Luan, Jian'an, Kemp, John P., Kristiansson, Kati, Ladenvall, Claes, Lorentzon, Mattias, Montasser, May E., Njajou, Omer T., O'Reilly, Paul F., Padmanabhan, Sandosh, Pourcain, Beate St., Rankinen, Tuomo, Salo, Perttu, Tanaka, Toshiko, Timpson, Nicholas J., Vitart, Veronique, Waite, Lindsay, Wheeler, William, Zhang, Weihua, Draisma, Harmen H. M., Feitosa, Mary F., Kerr, Kathleen F., Lind, Penelope A., Mihailov, Evelin, Onland-Moret, N. Charlotte, Song, Ci, Weedon, Michael N., Xie, Weijia, Yengo, Loic, Absher, Devin, Albert, Christine M., Alonso, Alvaro, Arking, Dan E., de Bakker, Paul I. W., Balkau, Beverley, Barlassina, Cristina, Benaglio, Paola, Bis, Joshua C., Bouatia-Naji, Nabila, Brage, Soren, Chanock, Stephen J., Chines, Peter S., Chung, Mina, Darbar, Dawood, Dina, Christian, Doerr, Marcus, Elliott, Paul, Felix, Stephan B., Fischer, Krista, Fuchsberger, Christian, de Geus, Eco J. C., Goyette, Philippe, Gudnason, Vilmundur, Harris, Tamara B., Hartikainen, Anna-Liisa, Havulinna, Aki S., Heckbert, Susan R., Hicks, Andrew A., Hofman, Albert, Holewijn, Suzanne, Hoogstra-Berends, Femke, Hottenga, Jouke-Jan, Jensen, Majken K., Johansson, Asa, Junttila, Juhani, Kaeaeb, Stefan, Kanon, Bart, Ketkar, Shamika, Khaw, Kay-Tee, Knowles, Joshua W., Kooner, Angrad S., Kors, Jan A., Kumari, Meena, Milani, Lili, Laiho, Paeivi, Lakatta, Edward G., Langenberg, Claudia, Leusink, Maarten, Liu, Yongmei, Luben, Robert N., Lunetta, Kathryn L., Lynch, Stacey N., Markus, Marcello R. P., Marques-Vidal, Pedro, Leach, Irene Mateo, McArdle, Wendy L., McCarroll, Steven A., Medland, Sarah E., Miller, Kathryn A., Montgomery, Grant W., Morrison, Alanna C., Mueller-Nurasyid, Martina, Navarro, Pau, Nelis, Mari, O'Connell, Jeffrey R., O'Donnell, Christopher J., Ong, Ken K., Newman, Anne B., Peters, Annette, Polasek, Ozren, Pouta, Anneli, Pramstaller, Peter P., Psaty, Bruce M., Rao, Dabeeru C., Ring, Susan M., Rossin, Elizabeth J., Rudan, Diana, Sanna, Serena, Scott, Robert A., Sehmi, Jaban S., Sharp, Stephen, Shin, Jordan T., Singleton, Andrew B., Smith, Albert V., Soranzo, Nicole, Spector, Tim D., Stewart, Chip, Stringham, Heather M., Tarasov, Kirill V., Uitterlinden, Andre G., Vandenput, Liesbeth, Hwang, Shih-Jen, Whitfield, John B., Wijmenga, Cisca, Wild, Sarah H., Willemsen, Gonneke, Wilson, James F., Witteman, Jacqueline C. M., Wong, Andrew, Wong, Quenna, Jamshidi, Yalda, Zitting, Paavo, Boer, Jolanda M. A., Boomsma, Dorret I., Borecki, Ingrid B., van Duijn, Cornelia M., Ekelund, Ulf, Forouhi, Nita G., Froguel, Philippe, Hingorani, Aroon, Ingelsson, Erik, Kivimaki, Mika, Kronmal, Richard A., Kuh, Diana, Lind, Lars, Martin, Nicholas G., Oostra, Ben A., Pedersen, Nancy L., Quertermous, Thomas, Rotter, Jerome I., van der Schouw, Yvonne T., Verschuren, W. M. Monique, Walker, Mark, Albanes, Demetrius, Arnar, David O., Assimes, Themistocles L., Bandinelli, Stefania, Boehnke, Michael, de Boer, Rudolf A., Bouchard, Claude, Caulfield, W. L. Mark, Chambers, John C., Curhan, Gary, Cusi, Daniele, Eriksson, Johan, Ferrucci, Luigi, van Gilst, Wiek H., Glorioso, Nicola, de Graaf, Jacqueline, Groop, Leif, Gyllensten, Ulf, Hsueh, Wen-Chi, Hu, Frank B., Huikuri, Heikki V., Hunter, David J., Iribarren, Carlos, Isomaa, Bo, Jarvelin, Marjo-Riitta, Jula, Antti, Kahonen, Mika, Kiemeney, Lambertus A., van der Klauw, Melanie M., Kooner, Jaspal S., Kraft, Peter, Iacoviello, Licia, Lehtimaki, Terho, Lokki, Marja-Liisa L., Mitchell, Braxton D., Navis, Gerjan, Nieminen, Markku S., Ohlsson, Claes, Poulter, Neil R., Qi, Lu, Raitakari, Olli T., Rimm, Eric B., Rioux, John D., Rizzi, Federica, Rudan, Igor, Salomaa, Veikko, Sever, Peter S., Shields, Denis C., Shuldiner, Alan R., Sinisalo, Juha, Stanton, Alice V., Stolk, Ronald P., Strachan, David P., Tardif, Jean-Claude, Thorsteinsdottir, Unnur, Tuomilehto, Jaako, van Veldhuisen, Dirk J., Virtamo, Jarmo, Viikari, Jorma, Vollenweider, Peter, Waeber, Gerard, Widen, Elisabeth, Cho, Yoon Shin, Olsen, Jesper V., Visscher, Peter M., Willer, Cristen, Franke, Lude, Erdmann, Jeanette, Thompson, John R., Pfeufer, Arne, Sotoodehnia, Nona, Newton-Cheh, Christopher, Ellinor, Patrick T., Stricker, Bruno H. Ch, Metspalu, Andres, Perola, Markus, Beckmann, Jacques S., Smith, George Davey, Stefansson, Kari, Wareham, Nicholas J., Munroe, Patricia B., Sibon, Ody C. M., Milan, David J., Snieder, Harold, Samani, Nilesh J., and Loos, Ruth J. F.

Abstract

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

Published
2013
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230. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

Author

Koettgen, Anna, Albrecht, Eva, Teumer, Alexander, Vitart, Veronique, Krumsiek, Jan, Hundertmark, Claudia, Pistis, Giorgio, Ruggiero, Daniela, O'Seaghdha, Conall M., Haller, Toomas, Yang, Qiong, Tanaka, Toshiko, Johnson, Andrew D., Kutalik, Zoltan, Smith, Albert V., Shi, Julia, Struchalin, Maksim, Middelberg, Rita P. S., Brown, Morris J., Gaffo, Angelo L., Pirastu, Nicola, Li, Guo, Hayward, Caroline, Zemunik, Tatijana, Huffman, Jennifer, Yengo, Loic, Zhao, Jing Hua, Demirkan, Ayse, Feitosa, Mary F., Liu, Xuan, Malerba, Giovanni, Lopez, Lorna M., van der Harst, Pim, Li, Xinzhong, Kleber, Marcus E., Hicks, Andrew A., Nolte, Ilja M., Johansson, Åsa, Murgia, Federico, Wild, Sarah H., Bakker, Stephan J. L., Peden, John F., Dehghan, Abbas, Steri, Maristella, Tenesa, Albert, Lagou, Vasiliki, Salo, Perttu, Mangino, Massimo, Rose, Lynda M., Lehtimaki, Terho, Woodward, Owen M., Okada, Yukinori, Tin, Adrienne, Mueller, Christian, Oldmeadow, Christopher, Putku, Margus, Czamara, Darina, Kraft, Peter, Frogheri, Laura, Thun, Gian Andri, Grotevendt, Anne, Gislason, Gauti Kjartan, Harris, Tamara B., Launer, Lenore J., McArdle, Patrick, Shuldiner, Alan R., Boerwinkle, Eric, Coresh, Josef, Schmidt, Helena, Schallert, Michael, Martin, Nicholas G., Montgomery, Grant W., Kubo, Michiaki, Nakamura, Yusuke, Tanaka, Toshihiro, Munroe, Patricia B., Samani, Nilesh J., Jacobs, David R., Jr., Liu, Kiang, D'Adamo, Pio, Ulivi, Sheila, Rotter, Jerome I., Psaty, Bruce M., Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Devuyst, Olivier, Navarro, Pau, Kolcic, Ivana, Hastie, Nicholas, Balkau, Beverley, Froguel, Philippe, Esko, Tonu, Salumets, Andres, Khaw, Kay Tee, Langenberg, Claudia, Wareham, Nicholas J., Isaacs, Aaron, Kraja, Aldi, Zhang, Qunyuan, Wild, Philipp S., Scott, Rodney J., Holliday, Elizabeth G., Org, Elin, Viigimaa, Margus, Bandinelli, Stefania, Metter, Jeffrey E., Lupo, Antonio, Trabetti, Elisabetta, Sorice, Rossella, Doering, Angela, Lattka, Eva, Strauch, Konstantin, Theis, Fabian, Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J., Bruinenberg, Marcel, Stolk, Ronald P., Kooner, Jaspal S., Zhang, Weihua, Winkelmann, Bernhard R., Boehm, Bernhard O., Lucae, Susanne, Penninx, Brenda W., Smit, Johannes H., Curhan, Gary, Mudgal, Poorva, Plenge, Robert M., Portas, Laura, Persico, Ivana, Kirin, Mirna, Wilson, James F., Leach, Irene Mateo, van Gilst, Wiek H., Goel, Anuj, Ongen, Halit, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Imboden, Medea, von Eckardstein, Arnold, Cucca, Francesco, Nagaraja, Ramaiah, Piras, Maria Grazia, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Ernst, Florian, Farrington, Susan M., Theodoratou, Evropi, Prokopenko, Inga, Stumvoll, Michael, Jula, Antti, Perola, Markus, Salomaa, Veikko, Shin, So-Youn, Spector, Tim D., Sala, Cinzia, Ridker, Paul M., Kaehoenen, Mika, Viikari, Jorma, Hengstenberg, Christian, Nelson, Christopher P., Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Singleton, Andrew B., Kamatani, Naoyuki, Zeller, Tanja, Burnier, Michel, Attia, John, Laan, Maris, Klopp, Norman, Hillege, Hans L., Kloiber, Stefan, Choi, Hyon, Pirastu, Mario, Tore, Silvia, Probst-Hensch, Nicole M., Voelzke, Henry, Gudnason, Vilmundur, Parsa, Afshin, Schmidt, Reinhold, Whitfield, John B., Fornage, Myriam, Gasparini, Paolo, Siscovick, David S., Polasek, Ozren, Campbell, Harry, Rudan, Igor, Bouatia-Naji, Nabila, Metspalu, Andres, Loos, Ruth J. F., van Duijn, Cornelia M., Borecki, Ingrid B., Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J., Wolffenbuttel, Bruce H. R., Chambers, John C., Maerz, Winfried, Pramstaller, Peter P., Snieder, Harold, Gyllensten, Ulf, Wright, Alan F., Navis, Gerjan, Watkins, Hugh, Witteman, Jacqueline C. M., Sanna, Serena, Schipf, Sabine, Dunlop, Malcolm G., Toenjes, Anke, Ripatti, Samuli, Soranzo, Nicole, Toniolo, Daniela, Chasman, Daniel I., Raitakari, Olli, Kao, W. H. Linda, Ciullo, Marina, Fox, Caroline S., Caulfield, Mark, Bochud, Murielle, Gieger, Christian, Koettgen, Anna, Albrecht, Eva, Teumer, Alexander, Vitart, Veronique, Krumsiek, Jan, Hundertmark, Claudia, Pistis, Giorgio, Ruggiero, Daniela, O'Seaghdha, Conall M., Haller, Toomas, Yang, Qiong, Tanaka, Toshiko, Johnson, Andrew D., Kutalik, Zoltan, Smith, Albert V., Shi, Julia, Struchalin, Maksim, Middelberg, Rita P. S., Brown, Morris J., Gaffo, Angelo L., Pirastu, Nicola, Li, Guo, Hayward, Caroline, Zemunik, Tatijana, Huffman, Jennifer, Yengo, Loic, Zhao, Jing Hua, Demirkan, Ayse, Feitosa, Mary F., Liu, Xuan, Malerba, Giovanni, Lopez, Lorna M., van der Harst, Pim, Li, Xinzhong, Kleber, Marcus E., Hicks, Andrew A., Nolte, Ilja M., Johansson, Åsa, Murgia, Federico, Wild, Sarah H., Bakker, Stephan J. L., Peden, John F., Dehghan, Abbas, Steri, Maristella, Tenesa, Albert, Lagou, Vasiliki, Salo, Perttu, Mangino, Massimo, Rose, Lynda M., Lehtimaki, Terho, Woodward, Owen M., Okada, Yukinori, Tin, Adrienne, Mueller, Christian, Oldmeadow, Christopher, Putku, Margus, Czamara, Darina, Kraft, Peter, Frogheri, Laura, Thun, Gian Andri, Grotevendt, Anne, Gislason, Gauti Kjartan, Harris, Tamara B., Launer, Lenore J., McArdle, Patrick, Shuldiner, Alan R., Boerwinkle, Eric, Coresh, Josef, Schmidt, Helena, Schallert, Michael, Martin, Nicholas G., Montgomery, Grant W., Kubo, Michiaki, Nakamura, Yusuke, Tanaka, Toshihiro, Munroe, Patricia B., Samani, Nilesh J., Jacobs, David R., Jr., Liu, Kiang, D'Adamo, Pio, Ulivi, Sheila, Rotter, Jerome I., Psaty, Bruce M., Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Devuyst, Olivier, Navarro, Pau, Kolcic, Ivana, Hastie, Nicholas, Balkau, Beverley, Froguel, Philippe, Esko, Tonu, Salumets, Andres, Khaw, Kay Tee, Langenberg, Claudia, Wareham, Nicholas J., Isaacs, Aaron, Kraja, Aldi, Zhang, Qunyuan, Wild, Philipp S., Scott, Rodney J., Holliday, Elizabeth G., Org, Elin, Viigimaa, Margus, Bandinelli, Stefania, Metter, Jeffrey E., Lupo, Antonio, Trabetti, Elisabetta, Sorice, Rossella, Doering, Angela, Lattka, Eva, Strauch, Konstantin, Theis, Fabian, Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J., Bruinenberg, Marcel, Stolk, Ronald P., Kooner, Jaspal S., Zhang, Weihua, Winkelmann, Bernhard R., Boehm, Bernhard O., Lucae, Susanne, Penninx, Brenda W., Smit, Johannes H., Curhan, Gary, Mudgal, Poorva, Plenge, Robert M., Portas, Laura, Persico, Ivana, Kirin, Mirna, Wilson, James F., Leach, Irene Mateo, van Gilst, Wiek H., Goel, Anuj, Ongen, Halit, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Imboden, Medea, von Eckardstein, Arnold, Cucca, Francesco, Nagaraja, Ramaiah, Piras, Maria Grazia, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Ernst, Florian, Farrington, Susan M., Theodoratou, Evropi, Prokopenko, Inga, Stumvoll, Michael, Jula, Antti, Perola, Markus, Salomaa, Veikko, Shin, So-Youn, Spector, Tim D., Sala, Cinzia, Ridker, Paul M., Kaehoenen, Mika, Viikari, Jorma, Hengstenberg, Christian, Nelson, Christopher P., Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Singleton, Andrew B., Kamatani, Naoyuki, Zeller, Tanja, Burnier, Michel, Attia, John, Laan, Maris, Klopp, Norman, Hillege, Hans L., Kloiber, Stefan, Choi, Hyon, Pirastu, Mario, Tore, Silvia, Probst-Hensch, Nicole M., Voelzke, Henry, Gudnason, Vilmundur, Parsa, Afshin, Schmidt, Reinhold, Whitfield, John B., Fornage, Myriam, Gasparini, Paolo, Siscovick, David S., Polasek, Ozren, Campbell, Harry, Rudan, Igor, Bouatia-Naji, Nabila, Metspalu, Andres, Loos, Ruth J. F., van Duijn, Cornelia M., Borecki, Ingrid B., Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J., Wolffenbuttel, Bruce H. R., Chambers, John C., Maerz, Winfried, Pramstaller, Peter P., Snieder, Harold, Gyllensten, Ulf, Wright, Alan F., Navis, Gerjan, Watkins, Hugh, Witteman, Jacqueline C. M., Sanna, Serena, Schipf, Sabine, Dunlop, Malcolm G., Toenjes, Anke, Ripatti, Samuli, Soranzo, Nicole, Toniolo, Daniela, Chasman, Daniel I., Raitakari, Olli, Kao, W. H. Linda, Ciullo, Marina, Fox, Caroline S., Caulfield, Mark, Bochud, Murielle, and Gieger, Christian

Abstract

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.

Published
2013
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231. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

Author

UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Köttgen, Anna, Albrecht, Eva, Teumer, Alexander, Vitart, Veronique, Krumsiek, Jan, Hundertmark, Claudia, Pistis, Giorgio, Ruggiero, Daniela, O'Seaghdha, Conall M, Haller, Toomas, Yang, Qiong, Tanaka, Toshiko, Johnson, Andrew D, Kutalik, Zoltán, Smith, Albert V, Shi, Julia, Struchalin, Maksim, Middelberg, Rita P S, Brown, Morris J, Gaffo, Angelo L, Pirastu, Nicola, Li, Guo, Hayward, Caroline, Zemunik, Tatijana, Huffman, Jennifer, Yengo, Loic, Zhao, Jing Hua, Demirkan, Ayse, Feitosa, Mary F, Liu, Xuan, Malerba, Giovanni, Lopez, Lorna M, van der Harst, Pim, Li, Xinzhong, Kleber, Marcus E, Hicks, Andrew A, Nolte, Ilja M, Johansson, Asa, Murgia, Federico, Wild, Sarah H, Bakker, Stephan J L, Peden, John F, Dehghan, Abbas, Steri, Maristella, Tenesa, Albert, Lagou, Vasiliki, Salo, Perttu, Mangino, Massimo, Rose, Lynda M, Lehtimäki, Terho, Woodward, Owen M, Okada, Yukinori, Tin, Adrienne, Müller, Christian, Oldmeadow, Christopher, Putku, Margus, Czamara, Darina, Kraft, Peter, Frogheri, Laura, Thun, Gian Andri, Grotevendt, Anne, Gislason, Gauti Kjartan, Harris, Tamara B, Launer, Lenore J, McArdle, Patrick, Shuldiner, Alan R, Boerwinkle, Eric, Coresh, Josef, Schmidt, Helena, Schallert, Michael, Martin, Nicholas G, Montgomery, Grant W, Kubo, Michiaki, Nakamura, Yusuke, Tanaka, Toshihiro, Munroe, Patricia B, Samani, Nilesh J, Jacobs, David R, Liu, Kiang, D'Adamo, Pio, Ulivi, Sheila, Rotter, Jerome I, Psaty, Bruce M, Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Devuyst, Olivier, Navarro, Pau, Kolcic, Ivana, Hastie, Nicholas, Balkau, Beverley, Froguel, Philippe, Esko, Tõnu, Salumets, Andres, Khaw, Kay Tee, Langenberg, Claudia, Wareham, Nicholas J, Isaacs, Aaron, Kraja, Aldi, Zhang, Qunyuan, Wild, Philipp S, Scott, Rodney J, Holliday, Elizabeth G, Org, Elin, Viigimaa, Margus, Bandinelli, Stefania, Metter, Jeffrey E, Lupo, Antonio, Trabetti, Elisabetta, Sorice, Rossella, Döring, Angela, Lattka, Eva, Strauch, Konstantin, Theis, Fabian, Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J, Bruinenberg, Marcel, Stolk, Ronald P, Kooner, Jaspal S, Zhang, Weihua, Winkelmann, Bernhard R, Boehm, Bernhard O, Lucae, Susanne, Penninx, Brenda W, Smit, Johannes H, Curhan, Gary, Mudgal, Poorva, Plenge, Robert M, Portas, Laura, Persico, Ivana, Kirin, Mirna, Wilson, James F, Leach, Irene Mateo, van Gilst, Wiek H, Goel, Anuj, Ongen, Halit, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G, Imboden, Medea, von Eckardstein, Arnold, Cucca, Francesco, Nagaraja, Ramaiah, Piras, Maria Grazia, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Ernst, Florian, Farrington, Susan M, Theodoratou, Evropi, Prokopenko, Inga, Stumvoll, Michael, Jula, Antti, Perola, Markus, Salomaa, Veikko, Shin, So-Youn, Spector, Tim D, Sala, Cinzia, Ridker, Paul M, Kähönen, Mika, Viikari, Jorma, Hengstenberg, Christian, Nelson, Christopher P, Meschia, James F, Nalls, Michael A, Sharma, Pankaj, Singleton, Andrew B, Kamatani, Naoyuki, Zeller, Tanja, Burnier, Michel, Attia, John, Laan, Maris, Klopp, Norman, Hillege, Hans L, Kloiber, Stefan, Choi, Hyon, Pirastu, Mario, Tore, Silvia, Probst-Hensch, Nicole M, Völzke, Henry, Gudnason, Vilmundur, Parsa, Afshin, Schmidt, Reinhold, Whitfield, John B, Fornage, Myriam, Gasparini, Paolo, Siscovick, David S, Polašek, Ozren, Campbell, Harry, Rudan, Igor, Bouatia-Naji, Nabila, Metspalu, Andres, Loos, Ruth J F, van Duijn, Cornelia M, Borecki, Ingrid B, Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J, Wolffenbuttel, Bruce H R, Chambers, John C, März, Winfried, Pramstaller, Peter P, Snieder, Harold, Gyllensten, Ulf, Wright, Alan F, Navis, Gerjan, Watkins, Hugh, Witteman, Jacqueline C M, Sanna, Serena, Schipf, Sabine, Dunlop, Malcolm G, Tönjes, Anke, Ripatti, Samuli, Soranzo, Nicole, Toniolo, Daniela, Chasman, Daniel I, Raitakari, Olli, Kao, W H Linda, Ciullo, Marina, Fox, Caroline S, Caulfield, Mark, Bochud, Murielle, Gieger, Christian, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Köttgen, Anna, Albrecht, Eva, Teumer, Alexander, Vitart, Veronique, Krumsiek, Jan, Hundertmark, Claudia, Pistis, Giorgio, Ruggiero, Daniela, O'Seaghdha, Conall M, Haller, Toomas, Yang, Qiong, Tanaka, Toshiko, Johnson, Andrew D, Kutalik, Zoltán, Smith, Albert V, Shi, Julia, Struchalin, Maksim, Middelberg, Rita P S, Brown, Morris J, Gaffo, Angelo L, Pirastu, Nicola, Li, Guo, Hayward, Caroline, Zemunik, Tatijana, Huffman, Jennifer, Yengo, Loic, Zhao, Jing Hua, Demirkan, Ayse, Feitosa, Mary F, Liu, Xuan, Malerba, Giovanni, Lopez, Lorna M, van der Harst, Pim, Li, Xinzhong, Kleber, Marcus E, Hicks, Andrew A, Nolte, Ilja M, Johansson, Asa, Murgia, Federico, Wild, Sarah H, Bakker, Stephan J L, Peden, John F, Dehghan, Abbas, Steri, Maristella, Tenesa, Albert, Lagou, Vasiliki, Salo, Perttu, Mangino, Massimo, Rose, Lynda M, Lehtimäki, Terho, Woodward, Owen M, Okada, Yukinori, Tin, Adrienne, Müller, Christian, Oldmeadow, Christopher, Putku, Margus, Czamara, Darina, Kraft, Peter, Frogheri, Laura, Thun, Gian Andri, Grotevendt, Anne, Gislason, Gauti Kjartan, Harris, Tamara B, Launer, Lenore J, McArdle, Patrick, Shuldiner, Alan R, Boerwinkle, Eric, Coresh, Josef, Schmidt, Helena, Schallert, Michael, Martin, Nicholas G, Montgomery, Grant W, Kubo, Michiaki, Nakamura, Yusuke, Tanaka, Toshihiro, Munroe, Patricia B, Samani, Nilesh J, Jacobs, David R, Liu, Kiang, D'Adamo, Pio, Ulivi, Sheila, Rotter, Jerome I, Psaty, Bruce M, Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Devuyst, Olivier, Navarro, Pau, Kolcic, Ivana, Hastie, Nicholas, Balkau, Beverley, Froguel, Philippe, Esko, Tõnu, Salumets, Andres, Khaw, Kay Tee, Langenberg, Claudia, Wareham, Nicholas J, Isaacs, Aaron, Kraja, Aldi, Zhang, Qunyuan, Wild, Philipp S, Scott, Rodney J, Holliday, Elizabeth G, Org, Elin, Viigimaa, Margus, Bandinelli, Stefania, Metter, Jeffrey E, Lupo, Antonio, Trabetti, Elisabetta, Sorice, Rossella, Döring, Angela, Lattka, Eva, Strauch, Konstantin, Theis, Fabian, Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J, Bruinenberg, Marcel, Stolk, Ronald P, Kooner, Jaspal S, Zhang, Weihua, Winkelmann, Bernhard R, Boehm, Bernhard O, Lucae, Susanne, Penninx, Brenda W, Smit, Johannes H, Curhan, Gary, Mudgal, Poorva, Plenge, Robert M, Portas, Laura, Persico, Ivana, Kirin, Mirna, Wilson, James F, Leach, Irene Mateo, van Gilst, Wiek H, Goel, Anuj, Ongen, Halit, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G, Imboden, Medea, von Eckardstein, Arnold, Cucca, Francesco, Nagaraja, Ramaiah, Piras, Maria Grazia, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Ernst, Florian, Farrington, Susan M, Theodoratou, Evropi, Prokopenko, Inga, Stumvoll, Michael, Jula, Antti, Perola, Markus, Salomaa, Veikko, Shin, So-Youn, Spector, Tim D, Sala, Cinzia, Ridker, Paul M, Kähönen, Mika, Viikari, Jorma, Hengstenberg, Christian, Nelson, Christopher P, Meschia, James F, Nalls, Michael A, Sharma, Pankaj, Singleton, Andrew B, Kamatani, Naoyuki, Zeller, Tanja, Burnier, Michel, Attia, John, Laan, Maris, Klopp, Norman, Hillege, Hans L, Kloiber, Stefan, Choi, Hyon, Pirastu, Mario, Tore, Silvia, Probst-Hensch, Nicole M, Völzke, Henry, Gudnason, Vilmundur, Parsa, Afshin, Schmidt, Reinhold, Whitfield, John B, Fornage, Myriam, Gasparini, Paolo, Siscovick, David S, Polašek, Ozren, Campbell, Harry, Rudan, Igor, Bouatia-Naji, Nabila, Metspalu, Andres, Loos, Ruth J F, van Duijn, Cornelia M, Borecki, Ingrid B, Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J, Wolffenbuttel, Bruce H R, Chambers, John C, März, Winfried, Pramstaller, Peter P, Snieder, Harold, Gyllensten, Ulf, Wright, Alan F, Navis, Gerjan, Watkins, Hugh, Witteman, Jacqueline C M, Sanna, Serena, Schipf, Sabine, Dunlop, Malcolm G, Tönjes, Anke, Ripatti, Samuli, Soranzo, Nicole, Toniolo, Daniela, Chasman, Daniel I, Raitakari, Olli, Kao, W H Linda, Ciullo, Marina, Fox, Caroline S, Caulfield, Mark, Bochud, Murielle, and Gieger, Christian

Published
2013

232. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

Author

Köttgen, Anna, Albrecht, Eva, Teumer, Alexander, Vitart, Veronique, Krumsiek, Jan, Hundertmark, Claudia, Pistis, Giorgio, Ruggiero, Daniela, O'Seaghdha, Conall M, Haller, Toomas, Yang, Qiong, Tanaka, Toshiko, Johnson, Andrew D, Kutalik, Zoltán, Smith, Albert V, Shi, Julia, Struchalin, Maksim, Middelberg, Rita P S, Brown, Morris J, Gaffo, Angelo L, Pirastu, Nicola, Li, Guo, Hayward, Caroline, Zemunik, Tatijana, Huffman, Jennifer, Yengo, Loic, Zhao, Jing Hua, Demirkan, Ayse, Feitosa, Mary F, Liu, Xuan, Malerba, Giovanni, Lopez, Lorna M., van der Harst, Pim, Li, Xinzhong, Kleber, Marcus E, Hicks, Andrew A, Nolte, Ilja M, Johansson, Asa, Murgia, Federico, Wild, Sarah H, Bakker, Stephan J L, Peden, John F, Dehghan, Abbas, Steri, Maristella, Tenesa, Albert, Lagou, Vasiliki, Salo, Perttu, Mangino, Massimo, Rose, Lynda M, Lehtimäki, Terho, Woodward, Owen M, Okada, Yukinori, Tin, Adrienne, Müller, Christian, Oldmeadow, Christopher, Putku, Margus, Czamara, Darina, Kraft, Peter, Frogheri, Laura, Thun, Gian Andri, Grotevendt, Anne, Gislason, Gauti Kjartan, Harris, Tamara B, Launer, Lenore J, McArdle, Patrick, Shuldiner, Alan R, Boerwinkle, Eric, Coresh, Josef, Schmidt, Helena, Schallert, Michael, Martin, Nicholas G, Montgomery, Grant W, Kubo, Michiaki, Nakamura, Yusuke, Tanaka, Toshihiro, Munroe, Patricia B, Samani, Nilesh J, Jacobs, David R, Liu, Kiang, D'Adamo, Pio, Ulivi, Sheila, Rotter, Jerome I, Psaty, Bruce M, Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Devuyst, Olivier, Navarro, Pau, Kolcic, Ivana, Hastie, Nicholas, Balkau, Beverley, Froguel, Philippe, Esko, Tõnu, Salumets, Andres, Khaw, Kay Tee, Langenberg, Claudia, Wareham, Nicholas J, Isaacs, Aaron, Kraja, Aldi, Zhang, Qunyuan, Wild, Philipp S, Scott, Rodney J, Holliday, Elizabeth G, Org, Elin, Viigimaa, Margus, Bandinelli, Stefania, Metter, Jeffrey E, Lupo, Antonio, Trabetti, Elisabetta, Sorice, Rossella, Döring, Angela, Lattka, Eva, Strauch, Konstantin, Theis, Fabian, Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J, Bruinenberg, Marcel, Stolk, Ronald P, Kooner, Jaspal S, Zhang, Weihua, Winkelmann, Bernhard R, Boehm, Bernhard O, Lucae, Susanne, Penninx, Brenda W, Smit, Johannes H, Curhan, Gary, Mudgal, Poorva, Plenge, Robert M, Portas, Laura, Persico, Ivana, Kirin, Mirna, Wilson, James F, Leach, Irene Mateo, van Gilst, Wiek H, Goel, Anuj, Ongen, Halit, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G, Imboden, Medea, von Eckardstein, Arnold, Cucca, Francesco, Nagaraja, Ramaiah, Piras, Maria Grazia, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Ernst, Florian, Farrington, Susan M, Theodoratou, Evropi, Prokopenko, Inga, Stumvoll, Michael, Jula, Antti, Perola, Markus, Salomaa, Veikko, Shin, So-Youn, Spector, Tim D, Sala, Cinzia, Ridker, Paul M, Kähönen, Mika, Viikari, Jorma, Hengstenberg, Christian, Nelson, Christopher P, Meschia, James F, Nalls, Michael A, Sharma, Pankaj, Singleton, Andrew B, Kamatani, Naoyuki, Zeller, Tanja, Burnier, Michel, Attia, John, Laan, Maris, Klopp, Norman, Hillege, Hans L, Kloiber, Stefan, Choi, Hyon, Pirastu, Mario, Tore, Silvia, Probst-Hensch, Nicole M, Völzke, Henry, Gudnason, Vilmundur, Parsa, Afshin, Schmidt, Reinhold, Whitfield, John B, Fornage, Myriam, Gasparini, Paolo, Siscovick, David S, Polašek, Ozren, Campbell, Harry, Rudan, Igor, Bouatia-Naji, Nabila, Metspalu, Andres, Loos, Ruth J F, van Duijn, Cornelia M, Borecki, Ingrid B, Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J, Wolffenbuttel, Bruce H R, Chambers, John C, März, Winfried, Pramstaller, Peter P, Snieder, Harold, Gyllensten, Ulf, Wright, Alan F, Navis, Gerjan, Watkins, Hugh, Witteman, Jacqueline C M, Sanna, Serena, Schipf, Sabine, Dunlop, Malcolm G, Tönjes, Anke, Ripatti, Samuli, Soranzo, Nicole, Toniolo, Daniela, Chasman, Daniel I, Raitakari, Olli, Kao, W H Linda, Ciullo, Marina, Fox, Caroline S, Caulfield, Mark, Bochud, Murielle, Gieger, Christian, Köttgen, Anna, Albrecht, Eva, Teumer, Alexander, Vitart, Veronique, Krumsiek, Jan, Hundertmark, Claudia, Pistis, Giorgio, Ruggiero, Daniela, O'Seaghdha, Conall M, Haller, Toomas, Yang, Qiong, Tanaka, Toshiko, Johnson, Andrew D, Kutalik, Zoltán, Smith, Albert V, Shi, Julia, Struchalin, Maksim, Middelberg, Rita P S, Brown, Morris J, Gaffo, Angelo L, Pirastu, Nicola, Li, Guo, Hayward, Caroline, Zemunik, Tatijana, Huffman, Jennifer, Yengo, Loic, Zhao, Jing Hua, Demirkan, Ayse, Feitosa, Mary F, Liu, Xuan, Malerba, Giovanni, Lopez, Lorna M., van der Harst, Pim, Li, Xinzhong, Kleber, Marcus E, Hicks, Andrew A, Nolte, Ilja M, Johansson, Asa, Murgia, Federico, Wild, Sarah H, Bakker, Stephan J L, Peden, John F, Dehghan, Abbas, Steri, Maristella, Tenesa, Albert, Lagou, Vasiliki, Salo, Perttu, Mangino, Massimo, Rose, Lynda M, Lehtimäki, Terho, Woodward, Owen M, Okada, Yukinori, Tin, Adrienne, Müller, Christian, Oldmeadow, Christopher, Putku, Margus, Czamara, Darina, Kraft, Peter, Frogheri, Laura, Thun, Gian Andri, Grotevendt, Anne, Gislason, Gauti Kjartan, Harris, Tamara B, Launer, Lenore J, McArdle, Patrick, Shuldiner, Alan R, Boerwinkle, Eric, Coresh, Josef, Schmidt, Helena, Schallert, Michael, Martin, Nicholas G, Montgomery, Grant W, Kubo, Michiaki, Nakamura, Yusuke, Tanaka, Toshihiro, Munroe, Patricia B, Samani, Nilesh J, Jacobs, David R, Liu, Kiang, D'Adamo, Pio, Ulivi, Sheila, Rotter, Jerome I, Psaty, Bruce M, Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Devuyst, Olivier, Navarro, Pau, Kolcic, Ivana, Hastie, Nicholas, Balkau, Beverley, Froguel, Philippe, Esko, Tõnu, Salumets, Andres, Khaw, Kay Tee, Langenberg, Claudia, Wareham, Nicholas J, Isaacs, Aaron, Kraja, Aldi, Zhang, Qunyuan, Wild, Philipp S, Scott, Rodney J, Holliday, Elizabeth G, Org, Elin, Viigimaa, Margus, Bandinelli, Stefania, Metter, Jeffrey E, Lupo, Antonio, Trabetti, Elisabetta, Sorice, Rossella, Döring, Angela, Lattka, Eva, Strauch, Konstantin, Theis, Fabian, Waldenberger, Melanie, Wichmann, H-Erich, Davies, Gail, Gow, Alan J, Bruinenberg, Marcel, Stolk, Ronald P, Kooner, Jaspal S, Zhang, Weihua, Winkelmann, Bernhard R, Boehm, Bernhard O, Lucae, Susanne, Penninx, Brenda W, Smit, Johannes H, Curhan, Gary, Mudgal, Poorva, Plenge, Robert M, Portas, Laura, Persico, Ivana, Kirin, Mirna, Wilson, James F, Leach, Irene Mateo, van Gilst, Wiek H, Goel, Anuj, Ongen, Halit, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G, Imboden, Medea, von Eckardstein, Arnold, Cucca, Francesco, Nagaraja, Ramaiah, Piras, Maria Grazia, Nauck, Matthias, Schurmann, Claudia, Budde, Kathrin, Ernst, Florian, Farrington, Susan M, Theodoratou, Evropi, Prokopenko, Inga, Stumvoll, Michael, Jula, Antti, Perola, Markus, Salomaa, Veikko, Shin, So-Youn, Spector, Tim D, Sala, Cinzia, Ridker, Paul M, Kähönen, Mika, Viikari, Jorma, Hengstenberg, Christian, Nelson, Christopher P, Meschia, James F, Nalls, Michael A, Sharma, Pankaj, Singleton, Andrew B, Kamatani, Naoyuki, Zeller, Tanja, Burnier, Michel, Attia, John, Laan, Maris, Klopp, Norman, Hillege, Hans L, Kloiber, Stefan, Choi, Hyon, Pirastu, Mario, Tore, Silvia, Probst-Hensch, Nicole M, Völzke, Henry, Gudnason, Vilmundur, Parsa, Afshin, Schmidt, Reinhold, Whitfield, John B, Fornage, Myriam, Gasparini, Paolo, Siscovick, David S, Polašek, Ozren, Campbell, Harry, Rudan, Igor, Bouatia-Naji, Nabila, Metspalu, Andres, Loos, Ruth J F, van Duijn, Cornelia M, Borecki, Ingrid B, Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J, Wolffenbuttel, Bruce H R, Chambers, John C, März, Winfried, Pramstaller, Peter P, Snieder, Harold, Gyllensten, Ulf, Wright, Alan F, Navis, Gerjan, Watkins, Hugh, Witteman, Jacqueline C M, Sanna, Serena, Schipf, Sabine, Dunlop, Malcolm G, Tönjes, Anke, Ripatti, Samuli, Soranzo, Nicole, Toniolo, Daniela, Chasman, Daniel I, Raitakari, Olli, Kao, W H Linda, Ciullo, Marina, Fox, Caroline S, Caulfield, Mark, Bochud, Murielle, and Gieger, Christian

Abstract

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.

Published
2013

233. B-Type Natriuretic Peptide and Prognosis in Heart Failure Patients With Preserved and Reduced Ejection Fraction

Author

van Veldhuisen, Dirk J., Linssen, Gerard C M, Jaarsma, Tiny, van Gilst, Wiek H, Hoes, Arno W, Tijssen, Jan G P, Paulus, Walter J., Voors, Adriaan A., Hillege, Hans L., van Veldhuisen, Dirk J., Linssen, Gerard C M, Jaarsma, Tiny, van Gilst, Wiek H, Hoes, Arno W, Tijssen, Jan G P, Paulus, Walter J., Voors, Adriaan A., and Hillege, Hans L.

Abstract

Objectives This study sought to determine the prognostic value of B-type natriuretic peptide (BNP) in patients with heart failure with preserved ejection fraction (HFPEF), in comparison to data in HF patients with reduced left ventricular (LV) EF (andlt;= 40%). less thanbrgreater than less thanbrgreater thanBackground Management of patients with HFPEF is difficult. BNP is a useful biomarker in patients with reduced LVEF, but data in HFPEF are scarce. less thanbrgreater than less thanbrgreater thanMethods In this study, 615 patients with mild to moderate HF (mean age 70 years, LVEF 33%) were followed for 18 months. BNP concentrations were measured at baseline and were related to the primary outcome, that is, a composite of all-cause mortality and HF hospitalization, and to mortality alone. The population was divided in quintiles, according to LVEF, and patients with reduced LVEF were compared with those with HFPEF. less thanbrgreater than less thanbrgreater thanResults There were 257 patients (42%) who had a primary endpoint and 171 (28%) who died. BNP levels were significantly higher in patients with reduced LVEF than in those with HFPEF (p andlt; 0.001). BNP was a strong predictor of outcome, but LVEF was not. Importantly, if similar levels of BNP were compared across the whole spectrum of LVEF, and for different cutoff levels of LVEF, the associated risk of adverse outcome was similar in HFPEF patients as in those with reduced LVEF. less thanbrgreater than less thanbrgreater thanConclusions BNP levels are lower in patients with HFPEF than in patients with HF with reduced LVEF, but for a given BNP level, the prognosis in patients with HFPEF is as poor as in those with reduced LVEF. (J Am Coll Cardiol 2013;61:1498-506), Funding Agencies|Netherlands Heart Foundation|2000Z003|Biosite Europe, France||Amgen, Johnson Johnson||Novartis||Sorbent||Vifor||BG Medicine||BioControl||Alere||Bayer||Cardio3 Biosciences||Celladon||Ceva||European Commission||Dutch Heart Foundation||Servier||Torrent

Published
2013
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235. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

Author

Murabito, Joanne M, White, Charles C, Kavousi, Maryam, Sun, Hong Yan, Feitosa, Mary F, Nambi, Vijay, Lamina, Claudia, Schillert, Arne, Coassin, Stefan, Bis, Joshua C, Broer, Linda, Crawford, Dana C, Franceschini, Nora, Frikke-Schmidt, Ruth, Haun, Margot, Holewijn, Suzanne, Huffman, Jennifer E, Hwang, Shih-Jen, Kiechl, Stefan, Kollerits, Barbara, Montasser, May E, Nolte, Ilja M, Rudock, Megan E, Senft, Andrea, Teumer, Alexander, van der Harst, Pim, Vitart, Veronique, Waite, Lindsay L, Wood, Andrew R, Wassel, Christina L, Absher, Devin M, Allison, Matthew A, Amin, Najaf, Arnold, Alice, Asselbergs, Folkert W, Aulchenko, Yurii, Bandinelli, Stefania, Barbalic, Maja, Boban, Mladen, Brown-Gentry, Kristin, Couper, David J, Criqui, Michael H, Dehghan, Abbas, den Heijer, Martin, Dieplinger, Benjamin, Ding, Jingzhong, Dörr, Marcus, Espinola-Klein, Christine, Felix, Stephan B, Ferrucci, Luigi, Folsom, Aaron R, Fraedrich, Gustav, Gibson, Quince, Goodloe, Robert, Gunjaca, Grgo, Haltmayer, Meinhard, Heiss, Gerardo, Hofman, Albert, Kieback, Arne, Kiemeney, Lambertus A, Kolcic, Ivana, Kullo, Iftikhar J, Kritchevsky, Stephen B, Lackner, Karl J, Li, Xiaohui, Lieb, Wolfgang, Lohman, Kurt, Meisinger, Christa, Melzer, David, Mohler, Emile R, Mudnic, Ivana, Mueller, Thomas, Navis, Gerjan, Oberhollenzer, Friedrich, Olin, Jeffrey W, O'Connell, Jeff, O'Donnell, Christopher J, Palmas, Walter, Penninx, Brenda W, Petersmann, Astrid, Polasek, Ozren, Psaty, Bruce M, Rantner, Barbara, Rice, Ken, Rivadeneira, Fernando, Rotter, Jerome I, Seldenrijk, Adrie, Stadler, Marietta, Summerer, Monika, Tanaka, Toshiko, Tybjærg-Hansen, Anne, Uitterlinden, Andre G, van Gilst, Wiek H, Vermeulen, Sita H, Wild, Sarah H, Wild, Philipp S, Willeit, Johann, Zeller, Tanja, Zemunik, Tatijana, Zgaga, Lina, Assimes, Themistocles L, Blankenberg, Stefan, Boerwinkle, Eric, Campbell, Harry, Cooke, John P, de Graaf, Jaqueline, Herrington, David, Kardia, Sharon L R, Mitchell, Braxton D, Murray, Anna, Münzel, Thomas, Newman, Anne, Oostra, Ben A, Rudan, Igor, Shuldiner, Alan R, Snieder, Harold, van Duijn, Cornelia M, Völker, Uwe, Wright, Alan F, Wichmann, H-Erich, Wilson, James, Witteman, Jacqueline C M, Liu, Yongmei, Hayward, Caroline, Borecki, Ingrid B, Ziegler, Andreas, North, Kari E, Cupples, L Adrienne, Kronenberg, Florian, Murabito, Joanne M, White, Charles C, Kavousi, Maryam, Sun, Hong Yan, Feitosa, Mary F, Nambi, Vijay, Lamina, Claudia, Schillert, Arne, Coassin, Stefan, Bis, Joshua C, Broer, Linda, Crawford, Dana C, Franceschini, Nora, Frikke-Schmidt, Ruth, Haun, Margot, Holewijn, Suzanne, Huffman, Jennifer E, Hwang, Shih-Jen, Kiechl, Stefan, Kollerits, Barbara, Montasser, May E, Nolte, Ilja M, Rudock, Megan E, Senft, Andrea, Teumer, Alexander, van der Harst, Pim, Vitart, Veronique, Waite, Lindsay L, Wood, Andrew R, Wassel, Christina L, Absher, Devin M, Allison, Matthew A, Amin, Najaf, Arnold, Alice, Asselbergs, Folkert W, Aulchenko, Yurii, Bandinelli, Stefania, Barbalic, Maja, Boban, Mladen, Brown-Gentry, Kristin, Couper, David J, Criqui, Michael H, Dehghan, Abbas, den Heijer, Martin, Dieplinger, Benjamin, Ding, Jingzhong, Dörr, Marcus, Espinola-Klein, Christine, Felix, Stephan B, Ferrucci, Luigi, Folsom, Aaron R, Fraedrich, Gustav, Gibson, Quince, Goodloe, Robert, Gunjaca, Grgo, Haltmayer, Meinhard, Heiss, Gerardo, Hofman, Albert, Kieback, Arne, Kiemeney, Lambertus A, Kolcic, Ivana, Kullo, Iftikhar J, Kritchevsky, Stephen B, Lackner, Karl J, Li, Xiaohui, Lieb, Wolfgang, Lohman, Kurt, Meisinger, Christa, Melzer, David, Mohler, Emile R, Mudnic, Ivana, Mueller, Thomas, Navis, Gerjan, Oberhollenzer, Friedrich, Olin, Jeffrey W, O'Connell, Jeff, O'Donnell, Christopher J, Palmas, Walter, Penninx, Brenda W, Petersmann, Astrid, Polasek, Ozren, Psaty, Bruce M, Rantner, Barbara, Rice, Ken, Rivadeneira, Fernando, Rotter, Jerome I, Seldenrijk, Adrie, Stadler, Marietta, Summerer, Monika, Tanaka, Toshiko, Tybjærg-Hansen, Anne, Uitterlinden, Andre G, van Gilst, Wiek H, Vermeulen, Sita H, Wild, Sarah H, Wild, Philipp S, Willeit, Johann, Zeller, Tanja, Zemunik, Tatijana, Zgaga, Lina, Assimes, Themistocles L, Blankenberg, Stefan, Boerwinkle, Eric, Campbell, Harry, Cooke, John P, de Graaf, Jaqueline, Herrington, David, Kardia, Sharon L R, Mitchell, Braxton D, Murray, Anna, Münzel, Thomas, Newman, Anne, Oostra, Ben A, Rudan, Igor, Shuldiner, Alan R, Snieder, Harold, van Duijn, Cornelia M, Völker, Uwe, Wright, Alan F, Wichmann, H-Erich, Wilson, James, Witteman, Jacqueline C M, Liu, Yongmei, Hayward, Caroline, Borecki, Ingrid B, Ziegler, Andreas, North, Kari E, Cupples, L Adrienne, and Kronenberg, Florian

Abstract

BACKGROUND: -Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. METHODS AND RESULTS: -Continuous ABI and PAD (ABI=0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ~2.5 million SNPs in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed-effects inverse variance weighted meta-analyses. There were a total of 41,692 participants of European ancestry (~60% women, mean ABI 1.02 to 1.19), including 3,409 participants with PAD and with GWAS data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (ß= -0.006, p=2.46x10(-8)). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16,717). The association for rs10757269 strengthened in the combined discovery and replication analysis (p=2.65x10(-9)). No other SNP associations for ABI or PAD achieved genome-wide significance. However, two previously reported candidate genes for PAD and one SNP associated with coronary artery disease (CAD) were associated with ABI: DAB21P (rs13290547, p=3.6x10(-5)); CYBA (rs3794624, p=6.3x10(-5)); and rs1122608 (LDLR, p=0.0026). CONCLUSIONS: -GWAS in more than 40,000 individuals identified one genome-wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for CAD are associated with ABI.

Published
2012

236. Vitamin D status and outcomes in heart failure patients

Author

Liu, Licette C Y, Voors, Adriaan A, van Veldhuisen, Dirk J, van der Veer, Eveline, Belonje, Anne M, Szymanski, Mariusz K, Silljé, Herman H W, van Gilst, Wiek H, Jaarsma, Tiny, de Boer, Rudolf A, Liu, Licette C Y, Voors, Adriaan A, van Veldhuisen, Dirk J, van der Veer, Eveline, Belonje, Anne M, Szymanski, Mariusz K, Silljé, Herman H W, van Gilst, Wiek H, Jaarsma, Tiny, and de Boer, Rudolf A

Abstract

AIMS: Vitamin D status has been implicated in the pathophysiology of heart failure (HF). The aims of this study were to determine whether a low vitamin D status is associated with prognosis in HF and whether activation of the renin-angiotensin system (RAS) and inflammatory markers could explain this potential association. METHODS AND RESULTS: We measured 25-hydroxy-vitamin D (25(OH)D), plasma renin activity (PRA), interleukin-6 (IL-6), C-reactive protein (CRP), and the incidence of death or HF rehospitalization in 548 patients with HF. Median age was 74 (64-80) years, left ventricular ejection fraction was 30% (23-42), and mean follow-up was 18 months. Low 25(OH)D levels were associated with female gender (P< 0.001), higher age (P= 0.002), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (P< 0.001). Multivariable linear regression analysis showed that PRA (P= 0.048), and CRP levels (P= 0.006) were independent predictors of 25(OH)D levels. During follow-up, 155 patients died and 142 patients were rehospitalized. Kaplan-Meier analysis showed that lower 25(OH)D concentration was associated with an increased risk for the combined endpoint (all-cause mortality and HF rehospitalization; log rank test P= 0.045) and increased risk for all-cause mortality (log rank test P= 0.014). After adjustment in a multivariable Cox regression analysis, low 25(OH)D concentration remained independently associated with an increased risk for the combined endpoint [hazard ratio (HR) 1.09 per 10 nmol/L decrease; 95% confidence interval (CI) 1.00-1.16; P= 0.040] and all-cause mortality (HR 1.10 per 10 nmol/L decrease; 95% CI 1.00-1.22; P= 0.049). CONCLUSION: A low 25(OH)D concentration is associated with a poor prognosis in HF patients. Activation of the RAS and inflammation may confer the adverse effects of low vitamin D levels.

Published
2011
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237. Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction

Author

Sotoodehnia, Nona., Sotoodehnia, Nona, Isaacs, Aaron, de Bakker, Paul IW, Dörr, Marcus, Newton-Cheh, Christopher, Nolte, Ilja M, van der Harst, Pim, Müller, Martina, Eijgelsheim, Mark, Alonso, Alvaro, Hicks, Andrew A, Padmanabhan, Sandosh, Hayward, Caroline, Smith, Albert Vernon, Polasek, Ozren, Giovannone, Steven, Fu, Jingyuan, Magnani, Jared W, Marciante, Kristin D, Pfeufer, Arne, Gharib, Sina A, Teumer, Alexander, Li, Man, Bis, Joshua C, Rivadeneira, Fernando, Aspelund, Thor, Köttgen, Anna, Johnson, Toby, Rice, Kenneth, Sie, Mark PS, Wang, Ying A, Klopp, Norman, Fuchsberger, Christian, Wild, Sarah H, Mateo Leach, Irene, Estrada, Karol, Völker, Uwe, Wright, Alan F, Asselbergs, Folkert W, Qu, Jiaxiang, Chakravarti, Aravinda, Sinner, Moritz F, Kors, Jan A, Petersmann, Astrid, Harris, Tamara B, Soliman, Elsayed Z, Munroe, Patricia B, Psaty, Bruce M, Oostra, Ben A, Cupples, L Adrienne, Perz, Siegfried, de Boer, Rudolf A, Uitterlinden, André G, Völzke, Henry, Spector, Timothy D, Liu, Fang-Yu, Boerwinkle, Eric, Dominiczak, Anna F, Rotter, Jerome I, van Herpen, Gé, Levy, Daniel, Wichmann, H-Erich, van Gilst, Wiek H, Witteman, Jacqueline CM, Kroemer, Heyo K, Kao, WH Linda, Heckbert, Susan R, Meitinger, Thomas, Hofman, Albert, Campbell, Harry, Folsom, Aaron R, van Veldhuisen, Dirk J, Schwienbacher, Christine, O'Donnell, Christopher J, Volpato, Claudia Beu, Caulfield, Mark J, Connell, John M, Launer, Lenore, Lu, Xiaowen, Franke, Lude, Fehrmann, Rudolf SN, te Meerman, Gerard, Groen, Harry JM, Weersma, Rinse K, van den Berg, Leonard H, Wijmenga, Cisca, Ophoff, Roel A, Navis, Gerjan, Rudan, Igor, Snieder, Harold, Wilson, James F, Pramstaller, Peter P, Siscovick, David S, Wang, Thomas J, Gudnason, Vilmundur, van Duijn, Cornelia M, Felix, Stephan B, Fishman, Glenn I, Jamshidi, Yalda, Stricker, Bruno H Ch, Sotoodehnia, Nona., Sotoodehnia, Nona, Isaacs, Aaron, de Bakker, Paul IW, Dörr, Marcus, Newton-Cheh, Christopher, Nolte, Ilja M, van der Harst, Pim, Müller, Martina, Eijgelsheim, Mark, Alonso, Alvaro, Hicks, Andrew A, Padmanabhan, Sandosh, Hayward, Caroline, Smith, Albert Vernon, Polasek, Ozren, Giovannone, Steven, Fu, Jingyuan, Magnani, Jared W, Marciante, Kristin D, Pfeufer, Arne, Gharib, Sina A, Teumer, Alexander, Li, Man, Bis, Joshua C, Rivadeneira, Fernando, Aspelund, Thor, Köttgen, Anna, Johnson, Toby, Rice, Kenneth, Sie, Mark PS, Wang, Ying A, Klopp, Norman, Fuchsberger, Christian, Wild, Sarah H, Mateo Leach, Irene, Estrada, Karol, Völker, Uwe, Wright, Alan F, Asselbergs, Folkert W, Qu, Jiaxiang, Chakravarti, Aravinda, Sinner, Moritz F, Kors, Jan A, Petersmann, Astrid, Harris, Tamara B, Soliman, Elsayed Z, Munroe, Patricia B, Psaty, Bruce M, Oostra, Ben A, Cupples, L Adrienne, Perz, Siegfried, de Boer, Rudolf A, Uitterlinden, André G, Völzke, Henry, Spector, Timothy D, Liu, Fang-Yu, Boerwinkle, Eric, Dominiczak, Anna F, Rotter, Jerome I, van Herpen, Gé, Levy, Daniel, Wichmann, H-Erich, van Gilst, Wiek H, Witteman, Jacqueline CM, Kroemer, Heyo K, Kao, WH Linda, Heckbert, Susan R, Meitinger, Thomas, Hofman, Albert, Campbell, Harry, Folsom, Aaron R, van Veldhuisen, Dirk J, Schwienbacher, Christine, O'Donnell, Christopher J, Volpato, Claudia Beu, Caulfield, Mark J, Connell, John M, Launer, Lenore, Lu, Xiaowen, Franke, Lude, Fehrmann, Rudolf SN, te Meerman, Gerard, Groen, Harry JM, Weersma, Rinse K, van den Berg, Leonard H, Wijmenga, Cisca, Ophoff, Roel A, Navis, Gerjan, Rudan, Igor, Snieder, Harold, Wilson, James F, Pramstaller, Peter P, Siscovick, David S, Wang, Thomas J, Gudnason, Vilmundur, van Duijn, Cornelia M, Felix, Stephan B, Fishman, Glenn I, Jamshidi, Yalda, and Stricker, Bruno H Ch

Abstract

The QRS interval, from the beginning of the Q wave to the end of the S wave on an electrocardiogram, reflects ventricular depolarization and conduction time and is a risk factor for mortality, sudden death and heart failure. We performed a genome-wide association meta-analysis in 40,407 individuals of European descent from 14 studies, with further genotyping in 7,170 additional Europeans, and we identified 22 loci associated with QRS duration (P < 5 × 10(-8)). These loci map in or near genes in pathways with established roles in ventricular conduction such as sodium channels, transcription factors and calcium-handling proteins, but also point to previously unidentified biologic processes, such as kinase inhibitors and genes related to tumorigenesis. We demonstrate that SCN10A, a candidate gene at the most significantly associated locus in this study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN10A blocker prolongs QRS duration. These findings extend our current knowledge of ventricular depolarization and conduction.

Published
2010

238. Anaemia is associated with shorter leucocyte telomere length in patients with chronic heart failure.

Author

Wong, Liza S M, Huzen, Jardi, van der Harst, Pim, de Boer, Rudolf A, Codd, Veryan, Westenbrink, B Daan, Benus, Germaine F J D, Voors, Adriaan A, van Gilst, Wiek H, Samani, Nilesh J, Jaarsma, Tiny, van Veldhuisen, Dirk J, Wong, Liza S M, Huzen, Jardi, van der Harst, Pim, de Boer, Rudolf A, Codd, Veryan, Westenbrink, B Daan, Benus, Germaine F J D, Voors, Adriaan A, van Gilst, Wiek H, Samani, Nilesh J, Jaarsma, Tiny, and van Veldhuisen, Dirk J

Abstract

AIMS: Anaemia is highly prevalent and associated with poor prognosis in patients with chronic heart failure (CHF). Reduced erythroid proliferation capacity of haematopoietic progenitor cells is associated with reduced telomere length, a marker of cellular ageing. We hypothesize that short telomere length contributes to the susceptibility to develop anaemia in patients with CHF. METHODS AND RESULTS: We studied 875 CHF patients, of whom 254 (29%) fulfilled the WHO criteria of anaemia. Telomere length in DNA from peripheral leucocytes was measured with real-time quantitative polymerase chain reaction. Age, gender, and baseline differences adjusted telomere length was correlated with haemoglobin levels (partial r = 0.130; P = 0.011). One standard deviation shorter telomere length was associated with an increased risk of having anaemia [odds ratio (OR), 1.31; 95% confidence interval (CI), 1.12-1.53; P = 0.001]. This observation was not affected by adjustment for potential confounders (OR, 1.38; 95% CI, 1.05-1.81; P = 0.021 after adjustment for age, gender, erythropoietin levels, renal function, left ventricular ejection fraction, age of CHF onset, blood pressure, history of stroke, diabetes, and B-type natriuretic peptide levels). CONCLUSION: Shorter telomere length increases the odds of having anaemia in CHF patients. This finding supports the hypothesis that cellular ageing in CHF contributes to the susceptibility to develop anaemia.

Published
2010
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239. Endogenous erythropoietin and outcome in heart failure.

Author

Belonje, Anne M S, Voors, Adriaan A, van der Meer, Peter, van Gilst, Wiek H, Jaarsma, Tiny, van Veldhuisen, Dirk J, Belonje, Anne M S, Voors, Adriaan A, van der Meer, Peter, van Gilst, Wiek H, Jaarsma, Tiny, and van Veldhuisen, Dirk J

Abstract

BACKGROUND: Endogenous erythropoietin is increased in patients with heart failure (HF). Previous small-scale data suggest that these erythropoietin levels are related to prognosis. This study aims to analyze the clinical and prognostic value of erythropoietin levels in relation to hemoglobin in a large cohort of HF patients. METHODS AND RESULTS: In patients hospitalized for HF, endogenous erythropoietin levels were measured at discharge and after 6 months. In anemic patients, the relation between erythropoietin and hemoglobin levels was determined by calculating the observed/predicted ratio of erythropoietin levels. We studied data from 605 patients with HF. Mean age was 71+/-11 years; 62% were male; and mean left ventricular ejection fraction was 0.33+/-0.14. Median erythropoietin levels were 9.6 U/L at baseline and 10.5 U/L at 6 months. Higher erythropoietin levels at baseline were independently related to an increased mortality at 18 months (hazard ratio, 2.06; 95% confidence interval, 1.40 to 3.04; P<0.01). In addition, persistently elevated erythropoietin levels (higher than median at baseline and at 6 months) were related to an increased mortality risk (hazard ratio, 2.24; 95% confidence interval, 1.02 to 4.90; P=0.044). The observed/predicted ratio was determined in a subset of anemic patients, 79% of whom had erythropoietin levels lower than expected and 9% had levels higher than expected on the basis of their hemoglobin. Multivariate Cox regression analysis revealed that a higher observed/predicted ratio was related to an increased mortality risk (hazard ratio, 3.52; 95% confidence interval, 1.53 to 8.12; P=0.003). CONCLUSIONS: Erythropoietin levels predict mortality in HF patients, and persistently elevated levels have an independent prognostic value. In anemic HF patients, the majority had a low observed/predicted ratio. However, a higher observed/predicted ratio may be related to an independent increased mortality risk.

Published
2010
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240. Qualitative examination of compliance in heart failure patients in The Netherlands.

Author

van der Wal, Martje H L, Jaarsma, Tiny, Moser, Debra K, van Gilst, Wiek H, van Veldhuisen, Dirk J, van der Wal, Martje H L, Jaarsma, Tiny, Moser, Debra K, van Gilst, Wiek H, and van Veldhuisen, Dirk J

Abstract

BACKGROUND: Noncompliance with pharmacological and nonpharmacological recommendations is a problem in many heart failure (HF) patients, leading to worse symptoms and readmission. Although knowledge is available regarding factors related to compliance with HF regimens, little is known about patients' perspectives. We investigated patients' reasons and motivations for compliance with HF regimens from their perspective, and we studied how patients manage these recommendations in daily life. The health belief model was used as a framework for this study. METHODS: A qualitative descriptive study was used, and 15 HF patients were interviewed about reasons for compliance, barriers to compliance, interventions that helped them comply with medications, sodium restriction, fluid restriction, and daily weighing. RESULTS: The most commonly reported reasons for compliance included fear of hospitalization and HF symptoms. Barriers to compliance were mainly related to the negative aspects of a regimen, e.g., taste of the food and thirst. Most patients tried to make their lifestyle changes part of the daily routine. Several problems and misunderstandings with the regimen were evident. Patients themselves offered many tips that helped them comply with the regimen. CONCLUSIONS: To improve compliance in HF patients, patient-tailored interventions must be targeted at specific problems and patients' beliefs regarding the regimen, and aim at implementing the regimen into daily life. Healthcare providers need to emphasize the benefits of compliance, motivate patients to comply, and focus on individual barriers to compliance, knowledge deficits, and misunderstandings regarding the regimen. More specific advice about medications and diet is needed. Group interventions, including tips patients themselves provide, might also be useful in helping patients implement the HF regimen in their daily lives.

Published
2010
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241. Telomere length and outcome in heart failure.

Author

van der Harst, Pim, de Boer, Rudolf A, Samani, Nilesh J, Wong, Liza S M, Huzen, Jardi, Codd, Veryan, Hillege, Hans L, Voors, Adriaan A, van Gilst, Wiek H, Jaarsma, Tiny, van Veldhuisen, Dirk J, van der Harst, Pim, de Boer, Rudolf A, Samani, Nilesh J, Wong, Liza S M, Huzen, Jardi, Codd, Veryan, Hillege, Hans L, Voors, Adriaan A, van Gilst, Wiek H, Jaarsma, Tiny, and van Veldhuisen, Dirk J

Abstract

BACKGROUND: Telomeres are causally involved in senescence. Senescence is a potential factor in the pathogenesis and progression of heart failure. In heart failure telomeres are shorter, but the prognostic value associated with telomere length has not been defined. METHODS: Telomere length was prospectively determined by quantitative polymerase chain reaction in 890 patients with New York Heart Association (NYHA) functional class II to IV heart failure. After 18 months, we examined the association between telomere length and the predefined primary end-point: time to death or hospitalization for heart failure. RESULTS: Mean age of the patients was 71 years, 39% were women, 51% were in NYHA class II, and 49% were in class III/IV. A total of 344 patients reached the primary end-point (130 deaths and 214 hospitalizations). Patients with shorter telomeres were at an increased risk of reaching the primary end-point (hazard ratio 1.79; 95% confidence interval (CI) 1.21-2.63). In multivariate analysis shorter telomere length remained associated with a higher risk for death or hospitalization (hazard ratio, 1.74; 95% CI 1.07-2.95) after adjustment for age of heart failure onset, gender, hemoglobin, renal function, and N-terminal pro-B-type natriuretic peptide level, a history of stroke, atrial fibrillation, and diabetes. CONCLUSIONS: Shorter length of telomeres predicts the occurrence of death or hospitalization in patients with chronic heart failure.

Published
2010
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242. Genome-wide association study identifies eight loci associated with blood pressure.

Author

Newton-Cheh, Christopher, Newton-Cheh, Christopher, Johnson, Toby, Gateva, Vesela, Tobin, Martin D, Bochud, Murielle, Coin, Lachlan, Najjar, Samer S, Zhao, Jing Hua, Heath, Simon C, Eyheramendy, Susana, Papadakis, Konstantinos, Voight, Benjamin F, Scott, Laura J, Zhang, Feng, Farrall, Martin, Tanaka, Toshiko, Wallace, Chris, Chambers, John C, Khaw, Kay-Tee, Nilsson, Peter, van der Harst, Pim, Polidoro, Silvia, Grobbee, Diederick E, Onland-Moret, N Charlotte, Bots, Michiel L, Wain, Louise V, Elliott, Katherine S, Teumer, Alexander, Luan, Jian'an, Lucas, Gavin, Kuusisto, Johanna, Burton, Paul R, Hadley, David, McArdle, Wendy L, Wellcome Trust Case Control Consortium, Brown, Morris, Dominiczak, Anna, Newhouse, Stephen J, Samani, Nilesh J, Webster, John, Zeggini, Eleftheria, Beckmann, Jacques S, Bergmann, Sven, Lim, Noha, Song, Kijoung, Vollenweider, Peter, Waeber, Gerard, Waterworth, Dawn M, Yuan, Xin, Groop, Leif, Orho-Melander, Marju, Allione, Alessandra, Di Gregorio, Alessandra, Guarrera, Simonetta, Panico, Salvatore, Ricceri, Fulvio, Romanazzi, Valeria, Sacerdote, Carlotta, Vineis, Paolo, Barroso, Inês, Sandhu, Manjinder S, Luben, Robert N, Crawford, Gabriel J, Jousilahti, Pekka, Perola, Markus, Boehnke, Michael, Bonnycastle, Lori L, Collins, Francis S, Jackson, Anne U, Mohlke, Karen L, Stringham, Heather M, Valle, Timo T, Willer, Cristen J, Bergman, Richard N, Morken, Mario A, Döring, Angela, Gieger, Christian, Illig, Thomas, Meitinger, Thomas, Org, Elin, Pfeufer, Arne, Wichmann, H Erich, Kathiresan, Sekar, Marrugat, Jaume, O'Donnell, Christopher J, Schwartz, Stephen M, Siscovick, David S, Subirana, Isaac, Freimer, Nelson B, Hartikainen, Anna-Liisa, McCarthy, Mark I, O'Reilly, Paul F, Peltonen, Leena, Pouta, Anneli, de Jong, Paul E, Snieder, Harold, van Gilst, Wiek H, Clarke, Robert, Goel, Anuj, Newton-Cheh, Christopher, Newton-Cheh, Christopher, Johnson, Toby, Gateva, Vesela, Tobin, Martin D, Bochud, Murielle, Coin, Lachlan, Najjar, Samer S, Zhao, Jing Hua, Heath, Simon C, Eyheramendy, Susana, Papadakis, Konstantinos, Voight, Benjamin F, Scott, Laura J, Zhang, Feng, Farrall, Martin, Tanaka, Toshiko, Wallace, Chris, Chambers, John C, Khaw, Kay-Tee, Nilsson, Peter, van der Harst, Pim, Polidoro, Silvia, Grobbee, Diederick E, Onland-Moret, N Charlotte, Bots, Michiel L, Wain, Louise V, Elliott, Katherine S, Teumer, Alexander, Luan, Jian'an, Lucas, Gavin, Kuusisto, Johanna, Burton, Paul R, Hadley, David, McArdle, Wendy L, Wellcome Trust Case Control Consortium, Brown, Morris, Dominiczak, Anna, Newhouse, Stephen J, Samani, Nilesh J, Webster, John, Zeggini, Eleftheria, Beckmann, Jacques S, Bergmann, Sven, Lim, Noha, Song, Kijoung, Vollenweider, Peter, Waeber, Gerard, Waterworth, Dawn M, Yuan, Xin, Groop, Leif, Orho-Melander, Marju, Allione, Alessandra, Di Gregorio, Alessandra, Guarrera, Simonetta, Panico, Salvatore, Ricceri, Fulvio, Romanazzi, Valeria, Sacerdote, Carlotta, Vineis, Paolo, Barroso, Inês, Sandhu, Manjinder S, Luben, Robert N, Crawford, Gabriel J, Jousilahti, Pekka, Perola, Markus, Boehnke, Michael, Bonnycastle, Lori L, Collins, Francis S, Jackson, Anne U, Mohlke, Karen L, Stringham, Heather M, Valle, Timo T, Willer, Cristen J, Bergman, Richard N, Morken, Mario A, Döring, Angela, Gieger, Christian, Illig, Thomas, Meitinger, Thomas, Org, Elin, Pfeufer, Arne, Wichmann, H Erich, Kathiresan, Sekar, Marrugat, Jaume, O'Donnell, Christopher J, Schwartz, Stephen M, Siscovick, David S, Subirana, Isaac, Freimer, Nelson B, Hartikainen, Anna-Liisa, McCarthy, Mark I, O'Reilly, Paul F, Peltonen, Leena, Pouta, Anneli, de Jong, Paul E, Snieder, Harold, van Gilst, Wiek H, Clarke, Robert, and Goel, Anuj

Abstract

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

Published
2009

243. Renal dysfunction is associated with shorter telomere length in heart failure.

Author

Wong, Liza S M, van der Harst, Pim, de Boer, Rudolf A, Codd, Veryan, Huzen, Jardi, Samani, Nilesh J, Hillege, Hans L, Voors, Adriaan A, van Gilst, Wiek H, Jaarsma, Tiny, van Veldhuisen, Dirk J, Wong, Liza S M, van der Harst, Pim, de Boer, Rudolf A, Codd, Veryan, Huzen, Jardi, Samani, Nilesh J, Hillege, Hans L, Voors, Adriaan A, van Gilst, Wiek H, Jaarsma, Tiny, and van Veldhuisen, Dirk J

Abstract

BACKGROUND: Renal dysfunction is a frequent comorbidity associated with high mortality in patients with chronic heart failure (CHF). The intrinsic biological age might affect the ability of the kidney to cope with the challenging environment caused by CHF. We explored the association between leukocyte telomere length, a marker for biological age, and renal function in patients with CHF. METHODS AND RESULTS: Telomere length was determined by a real-time quantitative polymerase chain reaction in 866 CHF patients. Renal function was estimated with the simplified Modification of Diet in Renal Disease equation. The median age was 74 (interquartile range 64-79) years, 61% male, left ventricular ejection fraction of 30 (23-44)%, and the estimated glomerular filtration rate was 53 (40-68) ml/min/1.73 m(2). Telomere length was associated with renal function (correlation coefficient 0.123, P < 0.001). This relationship remained significant after adjustment for age, gender, age of CHF onset (standardized-beta 0.091, P = 0.007). Also additionally adjusting for the severity of CHF and baseline differences did not change our findings. CONCLUSION: The association between shorter leukocyte telomere length and reduced renal function in heart failure suggests that intrinsic biological aging affects the ability of the kidney to cope with the systemic changes evoked by heart failure.

Published
2009
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244. Effect of moderate or intensive disease management program on outcome in patients with heart failure : Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH).

Author

Jaarsma, Tiny, van der Wal, Martje H L, Lesman-Leegte, Ivonne, Luttik, Marie-Louise, Hogenhuis, Jochem, Veeger, Nic J, Sanderman, Robbert, Hoes, Arno W, van Gilst, Wiek H, Lok, Dirk J A, Dunselman, Peter H J M, Tijssen, Jan G P, Hillege, Hans L, van Veldhuisen, Dirk J, Jaarsma, Tiny, van der Wal, Martje H L, Lesman-Leegte, Ivonne, Luttik, Marie-Louise, Hogenhuis, Jochem, Veeger, Nic J, Sanderman, Robbert, Hoes, Arno W, van Gilst, Wiek H, Lok, Dirk J A, Dunselman, Peter H J M, Tijssen, Jan G P, Hillege, Hans L, and van Veldhuisen, Dirk J

Abstract

BACKGROUND: Heart failure (HF) disease management programs are widely implemented, but data about their effect on outcome have been inconsistent. METHODS: The Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH) was a multicenter, randomized, controlled trial in which 1023 patients were enrolled after hospitalization because of HF. Patients were assigned to 1 of 3 groups: a control group (follow-up by a cardiologist) and 2 intervention groups with additional basic or intensive support by a nurse specializing in management of patients with HF. Patients were studied for 18 months. Primary end points were time to death or rehospitalization because of HF and the number of days lost to death or hospitalization. RESULTS: Mean patient age was 71 years; 38% were women; and 50% of patients had mild HF and 50% had moderate to severe HF. During the study, 411 patients (40%) were readmitted because of HF or died from any cause: 42% in the control group, and 41% and 38% in the basic and intensive support groups, respectively (hazard ratio, 0.96 and 0.93, respectively; P = .73 and P = .52, respectively). The number of days lost to death or hospitalization was 39 960 in the control group, 33 731 days for the basic intervention group (P = .81), and 34 268 for the intensive support group (P = .49). All-cause mortality occurred in 29% of patients in the control group, and there was a trend toward lower mortality in the intervention groups combined (hazard ratio, 0.85; 95% confidence interval, 0.66-1.08; P = .18). There were slightly more hospitalizations in the 2 intervention groups (basic intervention group, P = .89; and intensive support group, P = .60). CONCLUSIONS: Neither moderate nor intensive disease management by a nurse specializing in management of patients with HF reduced the combined end points of death and hospitalization because of HF compared with standard follow-up. There was a nonsignificant, potentially relevant reduction in mor

Published
2008
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247. Short-term vitamin D3 supplementation lowers plasma renin activity in patients with stable chronic heart failure: An open-label, blinded end point, randomized prospective trial (VitD-CHF trial)

Author

Schroten, Nicolas F., primary, Ruifrok, Willem P.T., additional, Kleijn, Lennaert, additional, Dokter, Martin M., additional, Silljé, Herman H., additional, Lambers Heerspink, Hiddo J., additional, Bakker, Stephan J.L., additional, Kema, Ido P., additional, van Gilst, Wiek H., additional, van Veldhuisen, Dirk J., additional, Hillege, Hans L., additional, and de Boer, Rudolf A., additional

Published
2013
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248. Long Term Effects of Epoetin Alfa in Patients with ST- Elevation Myocardial Infarction

Author

Fokkema, Marieke L., primary, Kleijn, Lennaert, additional, van der Meer, Peter, additional, Belonje, Anne M., additional, Achterhof, Sandra K., additional, Hillege, Hans L., additional, van ’t Hof, Arnoud, additional, Jukema, J. Wouter, additional, Peels, Hans O., additional, Henriques, José P., additional, ten Berg, Jurriën M., additional, Vos, Jeroen, additional, van Gilst, Wiek H., additional, van Veldhuisen, Dirk J., additional, and Voors, Adriaan A., additional

Published
2013
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249. A Simple and Computationally Efficient Approach to Multifactor Dimensionality Reduction Analysis of Gene-Gene Interactions for Quantitative Traits

Author

Gui, Jiang, primary, Moore, Jason H., additional, Williams, Scott M., additional, Andrews, Peter, additional, Hillege, Hans L., additional, van der Harst, Pim, additional, Navis, Gerjan, additional, Van Gilst, Wiek H., additional, Asselbergs, Folkert W., additional, and Gilbert-Diamond, Diane, additional

Published
2013
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