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101. Bleeding in cardiac patients prescribed antithrombotic drugs: Electronic health record phenotyping algorithms, incidence, trends and prognosis

Author

Pasea, Laura, primary, Chung, Sheng-Chia, additional, Pujades-Rodriguez, Mar, additional, Shah, Anoop D., additional, Alvarez-Madrazo, Samantha, additional, Allan, Victoria, additional, Teo, James T., additional, Bean, Daniel, additional, Sofat, Reecha, additional, Dobson, Richard, additional, Banerjee, Amitava, additional, Patel, Riyaz S., additional, Timmis, Adam, additional, Denaxas, Spiros, additional, and Hemingway, Harry, additional

Published
2019
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102. Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome

Author

Winkelmann Bernhard R, März Winfried, Kleber Marcus E, Quyyumi Arshed A, Waddy Salina P, Eapen Danny J, Patel Riyaz S, Patel Yesha, Hazen Stanley L, Allayee Hooman, Jones Philip, Cresci Sharon, Morgan Thomas M, House John A, Boehm Bernhard O, Krumholz Harlan M, and Spertus John A

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Genome-wide association studies (GWAS) have identified new candidate genes for the occurrence of acute coronary syndrome (ACS), but possible effects of such genes on survival following ACS have yet to be investigated. Methods We examined 95 polymorphisms in 69 distinct gene regions identified in a GWAS for premature myocardial infarction for their association with post-ACS mortality among 811 whites recruited from university-affiliated hospitals in Kansas City, Missouri. We then sought replication of a positive genetic association in a large, racially diverse cohort of myocardial infarction patients (N = 2284) using Kaplan-Meier survival analyses and Cox regression to adjust for relevant covariates. Finally, we investigated the apparent association further in 6086 additional coronary artery disease patients. Results After Cox adjustment for other ACS risk factors, of 95 SNPs tested in 811 whites only the association with the rs6922269 in MTHFD1L was statistically significant, with a 2.6-fold mortality hazard (P = 0.007). The recessive A/A genotype was of borderline significance in an age- and race-adjusted analysis of the entire combined cohort (N = 3095; P = 0.052), but this finding was not confirmed in independent cohorts (N = 6086). Conclusions We found no support for the hypothesis that the GWAS-identified variants in this study substantially alter the probability of post-ACS survival. Large-scale, collaborative, genome-wide studies may be required in order to detect genetic variants that are robustly associated with survival in patients with coronary artery disease.

Published
2011
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103. Druggability of Coronary Artery Disease Risk Loci

Author

Tragante, Vinicius, Hemerich, Daiane, Alshabeeb, Mohammad, Brænne, Ingrid, Lempiäinen, Harri, Patel, Riyaz S, den Ruijter, Hester M, Barnes, Michael R, Moore, Jason H, Schunkert, Heribert, Erdmann, Jeanette, Asselbergs, Folkert W, Tragante, Vinicius, Hemerich, Daiane, Alshabeeb, Mohammad, Brænne, Ingrid, Lempiäinen, Harri, Patel, Riyaz S, den Ruijter, Hester M, Barnes, Michael R, Moore, Jason H, Schunkert, Heribert, Erdmann, Jeanette, and Asselbergs, Folkert W

Published
2018

104. Routinely measured hematological parameters and prediction of recurrent vascular events in patients with clinically manifest vascular disease

Author

Kofink, Daniel, Muller, Steven A., Patel, Riyaz S., Dorresteijn, Jannick A.N., Berkelmans, Gijs F.N., De Groot, Mark C.H., Van Solinge, Wouter W., Haitjema, Saskia, Leiner, Tim, Visseren, Frank L.J., Hoefer, Imo E., Asselbergs, Folkert W., on behalf of the SMART Study Group, Kofink, Daniel, Muller, Steven A., Patel, Riyaz S., Dorresteijn, Jannick A.N., Berkelmans, Gijs F.N., De Groot, Mark C.H., Van Solinge, Wouter W., Haitjema, Saskia, Leiner, Tim, Visseren, Frank L.J., Hoefer, Imo E., Asselbergs, Folkert W., and on behalf of the SMART Study Group

Published
2018

105. An electronic health records cohort study on heart failure following myocardial infarction in England : Incidence and predictors

Author

Gho, Johannes M.I.H., Schmidt, Amand F., Pasea, Laura, Koudstaal, Stefan, Pujades-Rodriguez, Mar, Denaxas, Spiros, Shah, Anoop D., Patel, Riyaz S., Gale, Chris P., Hoes, Arno W., Cleland, John G., Hemingway, Harry, Asselbergs, Folkert W., Gho, Johannes M.I.H., Schmidt, Amand F., Pasea, Laura, Koudstaal, Stefan, Pujades-Rodriguez, Mar, Denaxas, Spiros, Shah, Anoop D., Patel, Riyaz S., Gale, Chris P., Hoes, Arno W., Cleland, John G., Hemingway, Harry, and Asselbergs, Folkert W.

Published
2018

106. Druggability of Coronary Artery Disease Risk Loci

Author

Onderzoek Precision medicine, Circulatory Health, Experimentele Afd. Cardiologie 1, Team Medisch, Tragante, Vinicius, Hemerich, Daiane, Alshabeeb, Mohammad, Brænne, Ingrid, Lempiäinen, Harri, Patel, Riyaz S, den Ruijter, Hester M, Barnes, Michael R, Moore, Jason H, Schunkert, Heribert, Erdmann, Jeanette, Asselbergs, Folkert W, Onderzoek Precision medicine, Circulatory Health, Experimentele Afd. Cardiologie 1, Team Medisch, Tragante, Vinicius, Hemerich, Daiane, Alshabeeb, Mohammad, Brænne, Ingrid, Lempiäinen, Harri, Patel, Riyaz S, den Ruijter, Hester M, Barnes, Michael R, Moore, Jason H, Schunkert, Heribert, Erdmann, Jeanette, and Asselbergs, Folkert W

Published
2018

107. Routinely measured hematological parameters and prediction of recurrent vascular events in patients with clinically manifest vascular disease

Author

Researchbureau DHL, Onderzoek Precision medicine, Circulatory Health, Interne Geneeskunde Vasculaire, Unit Opleiding Aios, CDL Arcadia, Other research (not in main researchprogram), Centraal Diagnostisch Laboratorium, Infection & Immunity, Experimentele Afd. Cardiologie 1, Researchgr. Cardiovasculaire Radiologie, Kofink, Daniel, Muller, Steven A., Patel, Riyaz S., Dorresteijn, Jannick A.N., Berkelmans, Gijs F.N., De Groot, Mark C.H., Van Solinge, Wouter W., Haitjema, Saskia, Leiner, Tim, Visseren, Frank L.J., Hoefer, Imo E., Asselbergs, Folkert W., On behalf of the SMART Study Group, Researchbureau DHL, Onderzoek Precision medicine, Circulatory Health, Interne Geneeskunde Vasculaire, Unit Opleiding Aios, CDL Arcadia, Other research (not in main researchprogram), Centraal Diagnostisch Laboratorium, Infection & Immunity, Experimentele Afd. Cardiologie 1, Researchgr. Cardiovasculaire Radiologie, Kofink, Daniel, Muller, Steven A., Patel, Riyaz S., Dorresteijn, Jannick A.N., Berkelmans, Gijs F.N., De Groot, Mark C.H., Van Solinge, Wouter W., Haitjema, Saskia, Leiner, Tim, Visseren, Frank L.J., Hoefer, Imo E., Asselbergs, Folkert W., and On behalf of the SMART Study Group

Published
2018

108. An electronic health records cohort study on heart failure following myocardial infarction in England: Incidence and predictors

Author

Cardiovasculaire Immunologie, Arts Assistenten Cardiologie, Regenerative Medicine and Stem Cells, Onderzoek Precision medicine, Epidemiology & Health Economics, General Practice & Nursing Science, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, Gho, Johannes M.I.H., Schmidt, Amand F., Pasea, Laura, Koudstaal, Stefan, Pujades-Rodriguez, Mar, Denaxas, Spiros, Shah, Anoop D., Patel, Riyaz S., Gale, Chris P., Hoes, Arno W., Cleland, John G., Hemingway, Harry, Asselbergs, Folkert W., Cardiovasculaire Immunologie, Arts Assistenten Cardiologie, Regenerative Medicine and Stem Cells, Onderzoek Precision medicine, Epidemiology & Health Economics, General Practice & Nursing Science, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, Gho, Johannes M.I.H., Schmidt, Amand F., Pasea, Laura, Koudstaal, Stefan, Pujades-Rodriguez, Mar, Denaxas, Spiros, Shah, Anoop D., Patel, Riyaz S., Gale, Chris P., Hoes, Arno W., Cleland, John G., Hemingway, Harry, and Asselbergs, Folkert W.

Published
2018

109. Impact of Selection Bias on Estimation of Subsequent Event Risk

Author

Hu, Yi Juan, Schmidt, Amand F., Dudbridge, Frank, Holmes, Michael V, Brophy, James M., Tragante, Vinicius, Li, Ziyi, Liao, Peizhou, Quyyumi, Arshed A., McCubrey, Raymond O., Horne, Benjamin D., Hingorani, Aroon D, Asselbergs, Folkert W, Patel, Riyaz S., Long, Qi, Åkerblom, Axel, Algra, Ale, Allayee, Hooman, Almgren, Peter, Anderson, Jeffrey L., Andreassi, Maria G., Anselmi, Chiara V., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Baranova, Ekaterina V., Behloui, Hassan, Bergmeijer, Thomas O, Bezzina, Connie R, Bjornsson, Eythor, Body, Simon C., Boeckx, Bram, Boersma, Eric H., Boerwinkle, Eric, Bogaty, Peter, Braund, Peter S, Breitling, Lutz P., Brenner, Hermann, Briguori, Carlo, Brugts, Jasper J., Burkhardt, Ralph, Cameron, Vicky A., Carlquist, John F., Carpeggiani, Clara, Carruthers, Kathryn F., Casu, Gavino, Condorelli, Gianluigi, Cresci, Sharon, Klungel, Olaf H., Maitland-Van Der Zee, Anke H., on behalf of the GENIUS-CHD Consortium, Afd Pharmacoepi & Clinical Pharmacology, and Pharmacoepidemiology and Clinical Pharmacology

Subjects
genetic association studies, alleles, Genetics, selection bias, Genetics(clinical), Cardiology and Cardiovascular Medicine, confidence intervals, sample size, risk
Abstract

Background - Studies of recurrent or subsequent disease events may be susceptible to bias caused by selection of subjects who both experience and survive the primary indexing event. Currently, the magnitude of any selection bias, particularly for subsequent time-to-event analysis in genetic association studies, is unknown. Methods and Results - We used empirically inspired simulation studies to explore the impact of selection bias on the marginal hazard ratio for risk of subsequent events among those with established coronary heart disease. The extent of selection bias was determined by the magnitudes of genetic and nongenetic effects on the indexing (first) coronary heart disease event. Unless the genetic hazard ratio was unrealistically large (>1.6 per allele) and assuming the sum of all nongenetic hazard ratios was

Published
2017

110. PCSK9 genetic variants and risk of type 2 diabetes:a mendelian randomisation study

Author

Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik P. A., Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew N., Panayiotou, Andrie G., Onland-Moret, Charlotte N., van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Asselbergs, Folkert W., PharmacoTherapy, -Epidemiology and -Economics, Cardiovascular Centre (CVC), and Life Course Epidemiology (LCE)

Subjects
ARCHITECTURE, INSIGHTS, STATIN THERAPY, CHOLESTEROL, PATHWAYS, HEART-DISEASE, ASSOCIATION, COMMON, HYPERCHOLESTEROLEMIA, METAANALYSIS
Abstract

BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk.METHODS: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores.FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m(2), -0·09 to 0·30).INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins.FUNDING: British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.

Published
2017

111. Pathway-Specific Aggregate Biomarker Risk Score Is Associated With Burden of Coronary Artery Disease and Predicts Near-Term Risk of Myocardial Infarction and Death

Author

Ghasemzadeh, Nima Hayek, Salim S. Ko, Yi-An Eapen, Danny J. and Patel, Riyaz S. Manocha, Pankaj Al Kassem, Hatem and Khayata, Mohamed Veledar, Emir Kremastinos, Dimitrios and Thorball, Christian W. Pielak, Tomasz Sikora, Sergey Zafari, A. Maziar Lerakis, Stamatios Sperling, Laurence Vaccarino, Viola Epstein, Stephen E. Quyyumi, Arshed A.

Abstract

Background-Inflammation, coagulation, and cell stress contribute to atherosclerosis and its adverse events. A biomarker risk score (BRS) based on the circulating levels of biomarkers C-reactive protein, fibrin degradation products, and heat shockprotein-70 representing these 3 pathways was a strong predictor of future outcomes. We investigated whether soluble urokinase plasminogen activator receptor (suPAR), a marker of immune activation, is predictive of outcomes independent of the aforementioned markers and whether its addition to a 3-BRS improves risk reclassification. Methods and Results-C-reactive protein, fibrin degradation product, heat shock protein-70, and suPAR were measured in 3278 patients undergoing coronary angiography. The BRS was calculated by counting the number of biomarkers above a cutoff determined using the Youden’s index. Survival analyses were performed using models adjusted for traditional risk factors. A high suPAR level >= 3.5 ng/mL was associated with all-cause death and myocardial infarction ( hazard ratio, 1.83; 95% confidence interval, 1.43-2.35) after adjustment for risk factors, C-reactive protein, fibrin degradation product, and heat shock protein-70. Addition of suPAR to the 3-BRS significantly improved the C statistic, integrated discrimination improvement, and net reclassification index for the primary outcome. A BRS of 1, 2, 3, or 4 was associated with a 1.81-, 2.59-, 6.17-, and 8.80-fold increase, respectively, in the risk of death and myocardial infarction. The 4-BRS was also associated with severity of coronary artery disease and composite end points. Conclusions-SuPAR is independently predictive of adverse outcomes, and its addition to a 3-BRS comprising C-reactive protein, fibrin degradation product, and heat shock protein-70 improved risk reclassification. The clinical utility of using a 4-BRS for risk prediction and management of patients with coronary artery disease warrants further study.

Published
2017

113. Druggability of Coronary Artery Disease Risk Loci

Author

Tragante, Vinicius, primary, Hemerich, Daiane, additional, Alshabeeb, Mohammad, additional, Brænne, Ingrid, additional, Lempiäinen, Harri, additional, Patel, Riyaz S., additional, den Ruijter, Hester M., additional, Barnes, Michael R., additional, Moore, Jason H., additional, Schunkert, Heribert, additional, Erdmann, Jeanette, additional, and Asselbergs, Folkert W., additional

Published
2018
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114. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author

Schmidt, Amand F, primary, Holmes, Michael V, additional, Preiss, David, additional, Swerdlow, Daniel, additional, Denaxas, Spiros, additional, Fatemifar, Ghazaleh, additional, Faraway, Rupert, additional, Finan, Chris, additional, Lumbers, Tom, additional, Henry, Albert, additional, Valentine, Dennis, additional, Fairhurst-Hunter, Zammy, additional, Hartwig, Fernando Pires, additional, Horta, Bernardo Lessa, additional, Hypponen, Elina, additional, Power, Christine, additional, Moldovan, Max, additional, van Iperen, Erik, additional, Hovingh, Kees, additional, Demuth, Ilja, additional, Norman, Kristina, additional, Steinhagen-Thiessen, Elisabeth, additional, Demuth, Juri, additional, Bertram, Lars, additional, Lill, Christina M, additional, Coassin, Stefan, additional, Willeit, Johann, additional, Kiechl, Stefan, additional, Willeit, Karin, additional, Mason, Dan, additional, Wright, John, additional, Morris, Richard, additional, Wanamethee, Goya, additional, Whincup, Peter, additional, Ben-Shlomo, Yoav, additional, McLachlan, Stela, additional, Price, Jackie F., additional, Kivimaki, Mika, additional, Welch, Catherine, additional, Sanchez-Galvez, Adelaida, additional, Marques-Vidal, Pedro, additional, Nicolaides, Andrew, additional, Panayiotou, Andrie G., additional, Onland-Moret, N. Charlotte, additional, van der Schouw, Yvonne T., additional, Matullo, Giuseppe, additional, Fiorito, Giovanni, additional, Guarrera, Simonetta, additional, Sacerdote, Carlotta, additional, Wareham, Nicholas J, additional, Langenberg, Claudia, additional, Scott, Robert A, additional, Luan, Jian’an, additional, Bobak, Martin, additional, Malyutina, Sofia, additional, Pajak, Andrzej, additional, Kubinova, Ruzena, additional, Tamosiunas, Abdonas, additional, Pikhart, Hynek, additional, Grarup, Niels, additional, Pedersen, Oluf, additional, Hansen, Torben, additional, Linneberg, Allan, additional, Jess, Tine, additional, Cooper, Jackie, additional, Humphries, Steve E, additional, Brilliant, Murray, additional, Kitchner, Terrie, additional, Hakonarson, Hakon, additional, Carrell, David S., additional, McCarty, Catherine A., additional, Lester, Kirchner H, additional, Larson, Eric B., additional, Crosslin, David R., additional, Andrade, Mariza de, additional, Roden, Dan M, additional, Denny, Joshua C, additional, Carty, Cara, additional, Hancock, Stephen, additional, Attia, John, additional, Holliday, Elizabeth, additional, Scott, Rodney, additional, Schofield, Peter, additional, O’Donnell, Martin, additional, Yusuf, Salim, additional, Chong, Michael, additional, Pare, Guillaume, additional, van der Harst, Pim, additional, Said, M. Abdullah, additional, Eppinga, Ruben N., additional, Verweij, Niek, additional, Snieder, Harold, additional, Christen, Tim, additional, Mook-Kanamori, D.O., additional, Gustafsson, Stefan, additional, Lind, Lars, additional, Ingelsson, Erik, additional, Pazoki, Raha, additional, Franco, Oscar, additional, Hofman, Albert, additional, Uitterlinden, Andre, additional, Dehghan, Abbas, additional, Teumer, Alexander, additional, Baumeister, Sebastian, additional, Dörr, Marcus, additional, Lerch, Markus M., additional, Völker, Uwe, additional, Völzke, Henry, additional, Ward, Joey, additional, Pell, Jill P, additional, Meade, Tom, additional, Christophersen, Ingrid E., additional, Maitland-van der Zee, Anke H., additional, Baranova, Ekaterina V., additional, Young, Robin, additional, Ford, Ian, additional, Campbell, Archie, additional, Padmanabhan, Sandosh, additional, Bots, Michiel L, additional, Grobbee, Diederick E., additional, Froguel, Philippe, additional, Thuillier, Dorothée, additional, Roussel, Ronan, additional, Bonnefond, Amelie, additional, Cariou, Bertrand, additional, Smart, Melissa, additional, Bao, Yanchun, additional, Kumari, Meena, additional, Mahajan, Anubha, additional, Hopewell, Jemma C., additional, Seshadri, Sudha, additional, Dale, Caroline, additional, Costa, Rui Providencia E, additional, Ridker, Paul M, additional, Chasman, Daniel I., additional, Reiner, Alex P., additional, Ritchie, Marylyn D, additional, Lange, Leslie A, additional, Cornish, Alex J., additional, Dobbins, Sara E., additional, Hemminki, Kari, additional, Kinnersley, Ben, additional, Sanson, Marc, additional, Labreche, Karim, additional, Simon, Matthias, additional, Bondy, Melissa, additional, Law, Philip, additional, Speedy, Helen, additional, Allan, James, additional, Li, Ni, additional, Went, Molly, additional, Weinhold, Niels, additional, Morgan, Gareth, additional, Sonneveld, Pieter, additional, Nilsson, Björn, additional, Goldschmidt, Hartmut, additional, Sud, Amit, additional, Engert, Andreas, additional, Hansson, Markus, additional, Hemingway, Harry, additional, Asselbergs, Folkert W, additional, Patel, Riyaz S, additional, Keating, Brendan J, additional, Sattar, Naveed, additional, Houlston, Richard, additional, Casas, Juan P, additional, and Hingorani, Aroon D, additional

Published
2018
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115. An electronic health records cohort study on heart failure following myocardial infarction in England: incidence and predictors

Author

Gho, Johannes M I H, primary, Schmidt, Amand F, additional, Pasea, Laura, additional, Koudstaal, Stefan, additional, Pujades-Rodriguez, Mar, additional, Denaxas, Spiros, additional, Shah, Anoop D, additional, Patel, Riyaz S, additional, Gale, Chris P, additional, Hoes, Arno W, additional, Cleland, John G, additional, Hemingway, Harry, additional, and Asselbergs, Folkert W, additional

Published
2018
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116. Diagnostic accuracy and prognostic value of simultaneous hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in cardiac sarcoidosis

Author

Wicks, Eleanor C, primary, Menezes, Leon J, additional, Barnes, Anna, additional, Mohiddin, Saidi A, additional, Sekhri, Neha, additional, Porter, Joanna C, additional, Booth, Helen L, additional, Garrett, Emily, additional, Patel, Riyaz S, additional, Pavlou, Menelaos, additional, Groves, Ashley M, additional, and Elliott, Perry M, additional

Published
2018
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117. Association analyses based on false discovery rate implicate new loci for coronary artery disease

Author

Nelson, Christopher P., Goel, Anuj, Butterworth, Adam S., Kanoni, Stavroula, Webb, Tom R., Marouli, Eirini, Zeng, Lingyao, Ntalla, Ioanna, Lai, Florence Y., Hopewell, Jemma C., Giannakopoulou, Olga, Jiang, Tao, Hamby, Stephen E., Di Angelantonio, Emanuele, Assimes, Themistocles L., Bottinger, Erwin P., Chambers, John C., Clarke, Robert, Palmer, Colin N. A., Cubbon, Richard M., Ellinor, Patrick, Ermel, Raili, Evangelou, Evangelos, Franks, Paul W., Grace, Christopher, Gu, Dongfeng, Hingorani, Aroon D., Howson, Joanna M. M., Ingelsson, Erik, Kastrati, Adnan, Kessler, Thorsten, Kyriakou, Theodosios, Lehtimaki, Terho, Lu, Xiangfeng, Lu, Yingchang, Maerz, Winfried, McPherson, Ruth, Metspalu, Andres, Pujades-Rodriguez, Mar, Ruusalepp, Arno, Schadt, Eric E., Schmidt, Amand F., Sweeting, Michael J., Zalloua, Pierre A., AlGhalayini, Kamal, Keavney, Bernard D., Kooner, Jaspal S., Loos, Ruth J. F., Patel, Riyaz S., Rutter, Martin K., Tomaszewski, Maciej, Tzoulaki, Ioanna, Zeggini, Eleftheria, Erdmann, Jeanette, Dedoussis, George, Bjorkegren, Johan L. M., Schunkert, Heribert, Farrall, Martin, Danesh, John, Samani, Nilesh J., Watkins, Hugh, Deloukas, Panos, Nelson, Christopher P., Goel, Anuj, Butterworth, Adam S., Kanoni, Stavroula, Webb, Tom R., Marouli, Eirini, Zeng, Lingyao, Ntalla, Ioanna, Lai, Florence Y., Hopewell, Jemma C., Giannakopoulou, Olga, Jiang, Tao, Hamby, Stephen E., Di Angelantonio, Emanuele, Assimes, Themistocles L., Bottinger, Erwin P., Chambers, John C., Clarke, Robert, Palmer, Colin N. A., Cubbon, Richard M., Ellinor, Patrick, Ermel, Raili, Evangelou, Evangelos, Franks, Paul W., Grace, Christopher, Gu, Dongfeng, Hingorani, Aroon D., Howson, Joanna M. M., Ingelsson, Erik, Kastrati, Adnan, Kessler, Thorsten, Kyriakou, Theodosios, Lehtimaki, Terho, Lu, Xiangfeng, Lu, Yingchang, Maerz, Winfried, McPherson, Ruth, Metspalu, Andres, Pujades-Rodriguez, Mar, Ruusalepp, Arno, Schadt, Eric E., Schmidt, Amand F., Sweeting, Michael J., Zalloua, Pierre A., AlGhalayini, Kamal, Keavney, Bernard D., Kooner, Jaspal S., Loos, Ruth J. F., Patel, Riyaz S., Rutter, Martin K., Tomaszewski, Maciej, Tzoulaki, Ioanna, Zeggini, Eleftheria, Erdmann, Jeanette, Dedoussis, George, Bjorkegren, Johan L. M., Schunkert, Heribert, Farrall, Martin, Danesh, John, Samani, Nilesh J., Watkins, Hugh, and Deloukas, Panos

Abstract

Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 x 10(-8)) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1-4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; n(cases) = 10,801) as well as a stricter definition without angina (HARD; n(cases) = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS(2,3). This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold(2), thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.

Published
2017
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118. PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study

Author

Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofi A., Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O', Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Balkau, Beverley, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan-Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., Sattar, Naveed, Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofi A., Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O', Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Balkau, Beverley, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan-Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., and Sattar, Naveed

Abstract

Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibi

Published
2017
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119. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study

Author

Pharmacoepidemiology and Clinical Pharmacology, Schmidt, Amand F., Swerdlow, Daniel I, Holmes, Michael V, Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik Pa, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard W, Wanamethee, Goya, Whincup, Peter H, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew N., Panayiotou, Andrie G., Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A, Luan, Jian'an, Smith, Daniel J, Maitland-van der Zee, Anke H, Baranova, Ekaterina V, LifeLines Cohort Study Group, Pharmacoepidemiology and Clinical Pharmacology, Schmidt, Amand F., Swerdlow, Daniel I, Holmes, Michael V, Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik Pa, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard W, Wanamethee, Goya, Whincup, Peter H, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew N., Panayiotou, Andrie G., Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A, Luan, Jian'an, Smith, Daniel J, Maitland-van der Zee, Anke H, Baranova, Ekaterina V, and LifeLines Cohort Study Group

Published
2017

120. Impact of Selection Bias on Estimation of Subsequent Event Risk

Author

Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Hu, Yi Juan, Schmidt, Amand F., Dudbridge, Frank, Holmes, Michael V, Brophy, James M., Tragante, Vinicius, Li, Ziyi, Liao, Peizhou, Quyyumi, Arshed A., McCubrey, Raymond O., Horne, Benjamin D., Hingorani, Aroon D, Asselbergs, Folkert W, Patel, Riyaz S., Long, Qi, Åkerblom, Axel, Algra, Ale, Allayee, Hooman, Almgren, Peter, Anderson, Jeffrey L., Andreassi, Maria G., Anselmi, Chiara V., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Baranova, Ekaterina V., Behloui, Hassan, Bergmeijer, Thomas O, Bezzina, Connie R, Bjornsson, Eythor, Body, Simon C., Boeckx, Bram, Boersma, Eric H., Boerwinkle, Eric, Bogaty, Peter, Braund, Peter S, Breitling, Lutz P., Brenner, Hermann, Briguori, Carlo, Brugts, Jasper J., Burkhardt, Ralph, Cameron, Vicky A., Carlquist, John F., Carpeggiani, Clara, Carruthers, Kathryn F., Casu, Gavino, Condorelli, Gianluigi, Cresci, Sharon, Klungel, Olaf H., Maitland-Van Der Zee, Anke H., on behalf of the GENIUS-CHD Consortium, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Hu, Yi Juan, Schmidt, Amand F., Dudbridge, Frank, Holmes, Michael V, Brophy, James M., Tragante, Vinicius, Li, Ziyi, Liao, Peizhou, Quyyumi, Arshed A., McCubrey, Raymond O., Horne, Benjamin D., Hingorani, Aroon D, Asselbergs, Folkert W, Patel, Riyaz S., Long, Qi, Åkerblom, Axel, Algra, Ale, Allayee, Hooman, Almgren, Peter, Anderson, Jeffrey L., Andreassi, Maria G., Anselmi, Chiara V., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Baranova, Ekaterina V., Behloui, Hassan, Bergmeijer, Thomas O, Bezzina, Connie R, Bjornsson, Eythor, Body, Simon C., Boeckx, Bram, Boersma, Eric H., Boerwinkle, Eric, Bogaty, Peter, Braund, Peter S, Breitling, Lutz P., Brenner, Hermann, Briguori, Carlo, Brugts, Jasper J., Burkhardt, Ralph, Cameron, Vicky A., Carlquist, John F., Carpeggiani, Clara, Carruthers, Kathryn F., Casu, Gavino, Condorelli, Gianluigi, Cresci, Sharon, Klungel, Olaf H., Maitland-Van Der Zee, Anke H., and on behalf of the GENIUS-CHD Consortium

Published
2017

121. Prognostic burden of heart failure recorded in primary care, acute hospital admissions, or both: a population-based linked electronic health record cohort study in 2.1 million people

Author

Cardiovasculaire Immunologie, UMC Utrecht, Arts Assistenten Cardiologie, Onderzoek Precision medicine, Regenerative Medicine and Stem Cells, Epidemiology & Health Economics, General Practice & Nursing Science, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, Koudstaal, Stefan, Pujades-Rodriguez, Mar, Denaxas, Spiros C, Gho, Johannes M.I.H., Shah, Anoop D, Yu, Ning, Patel, Riyaz S, Gale, Chris P, Hoes, Arno W., Cleland, John G F, Asselbergs, Folkert W., Hemingway, Harry, Cardiovasculaire Immunologie, UMC Utrecht, Arts Assistenten Cardiologie, Onderzoek Precision medicine, Regenerative Medicine and Stem Cells, Epidemiology & Health Economics, General Practice & Nursing Science, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, Koudstaal, Stefan, Pujades-Rodriguez, Mar, Denaxas, Spiros C, Gho, Johannes M.I.H., Shah, Anoop D, Yu, Ning, Patel, Riyaz S, Gale, Chris P, Hoes, Arno W., Cleland, John G F, Asselbergs, Folkert W., and Hemingway, Harry

Published
2017

122. Impact of Selection Bias on Estimation of Subsequent Event Risk

Author

Circulatory Health, Experimentele Afd. Cardiologie 1, Onderzoek Precision medicine, Team Medisch, Cardiologie, Hu, Yi-Juan, Schmidt, Amand F, Dudbridge, Frank, Holmes, Michael V., Brophy, James M., Tragante, Vinicius, Li, Ziyi, Liao, Peizhou, Quyyumi, Arshed A., McCubrey, Raymond O., Horne, Benjamin D, Hingorani, Aroon D., Asselbergs, Folkert W, Patel, Riyaz S, Long, Qi, Circulatory Health, Experimentele Afd. Cardiologie 1, Onderzoek Precision medicine, Team Medisch, Cardiologie, Hu, Yi-Juan, Schmidt, Amand F, Dudbridge, Frank, Holmes, Michael V., Brophy, James M., Tragante, Vinicius, Li, Ziyi, Liao, Peizhou, Quyyumi, Arshed A., McCubrey, Raymond O., Horne, Benjamin D, Hingorani, Aroon D., Asselbergs, Folkert W, Patel, Riyaz S, and Long, Qi

Published
2017

123. PCSK9 genetic variants and risk of type 2 diabetes: A mendelian randomisation study

Author

UMC Utrecht, Cardiovasculaire Epi Team 3, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Brain, JC onderzoeksprogramma Kanker, Circulatory Health, Cardiovasculaire Epidemiologie, TN groep Adan, Aios en Stafsecr. Cardiologie, Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 9, Cardiologie, Team Medisch, Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O., Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M., Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothée, Balkau, Beverley, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., Sattar, Naveed, UMC Utrecht, Cardiovasculaire Epi Team 3, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Brain, JC onderzoeksprogramma Kanker, Circulatory Health, Cardiovasculaire Epidemiologie, TN groep Adan, Aios en Stafsecr. Cardiologie, Cardiovasculaire Epi Team 5, Cardiovasculaire Epi Team 9, Cardiologie, Team Medisch, Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O., Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Dörr, Marcus, Lerch, Markus M., Völker, Uwe, Völzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothée, Balkau, Beverley, Bonnefond, Amélie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., and Sattar, Naveed

Published
2017

124. PCSK9 genetic variants and risk of type 2 diabetes:a mendelian randomisation study

Author

Schmidt, Amand F, Swerdlow, Daniel I, Holmes, Michael V, Patel, Riyaz S, Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J, Langenberg, Claudia, Scott, Robert, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Schmidt, Amand F, Swerdlow, Daniel I, Holmes, Michael V, Patel, Riyaz S, Fairhurst-Hunter, Zammy, Lyall, Donald M, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hyppönen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F, Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J, Langenberg, Claudia, Scott, Robert, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, and Linneberg, Allan

Abstract

BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk.METHODS: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores.FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m(2), -0·09 to 0·30).INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benef

Published
2017

125. Evaluation of Machine Learning Methods to Predict Coronary Artery Disease Using Metabolomic Data

Author

Forssen, Henrietta, Patel, Riyaz S., Fitzpatrick, Natalie, Hingorani, Aroon, Timmis, Adam, Hemingway, Harry, Denaxas, Spiros C., Forssen, Henrietta, Patel, Riyaz S., Fitzpatrick, Natalie, Hingorani, Aroon, Timmis, Adam, Hemingway, Harry, and Denaxas, Spiros C.

Abstract

Metabolomic data can potentially enable accurate, non-invasive and low-cost prediction of coronary artery disease. Regression-based analytical approaches however might fail to fully account for interactions between metabolites, rely on a priori selected input features and thus might suffer from poorer accuracy. Supervised machine learning methods can potentially be used in order to fully exploit the dimensionality and richness of the data. In this paper, we systematically implement and evaluate a set of supervised learning methods (L1 regression, random forest classifier) and compare them to traditional regression-based approaches for disease prediction using metabolomic data., Comment: Medical Informatics Europe (MIE2017)

Published
2017

126. Online self-assessment of cardiovascular risk using the Joint British Societies (JBS3)-derived heart age tool: a descriptive study

Author

Patel, Riyaz S, Lagord, Catherine, Waterall, Jamie, Moth, Martin, Knapton, Mike, and Deanfield, John E

Subjects
Risk factors, Self Assessment, Research, Cardiovascular Medicine, Digital health, Cardiovascular Risk, Cardiovascular Prevention
Abstract

Objective A modified version of the Joint British Societies (JBS3) ‘heart age’ tool was introduced online to broaden access to personalised risk assessment to the general population and encourage participation in the National Health Service (NHS) Health Check programme. This study reports on its early uptake and the profiles of those who used the self-assessment tool to determine their own cardiovascular risk. Design Observational, retrospective analysis of online tool use. Setting Between February and July 2015, user data collected from the NHS Choices website, where the tool was hosted, were analysed anonymously using standard analytic packages. Results The online tool landing page was viewed 1.4 million times in the first 5 months, with increased activity following limited media coverage. Of the 575 782 users completing the data journey with a valid ‘heart age’ result, their demographic and risk factor profiles broadly resembled the population of England, although both younger users and males (60%) were over-represented. Almost 50% and 79% did not know or enter their blood pressure or total cholesterol values, respectively. Estimated heart age was higher than chronological age for 79% of all users, and also for 69% of younger users under 40 years who are at low 10-year risk and not invited for NHS Health Checks. Conclusions These data suggest a high level of public interest in self-assessment of cardiovascular risk when an easily understood metric is used, although a large number of users lack awareness of their own risk factors. The heart age tool was accessed by a group not easily reached by conventional approaches yet is at high cardiovascular risk and would benefit most from early and sustained risk reduction. These are both important opportunities for interventions to educate and empower the public to manage better their cardiovascular risk and promote population-level prevention.

Published
2016

127. Cystatin C and cardiovascular disease: a Mendelian randomization study

Author

van der Laan, Sander W., Fall, Tove, Soumaré, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E., Arpegård, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Dörr, Marcus, Magnusson, Patrik K., Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P., Felix, Janine F., Morrison, Alanna C., Franceschini, Nora, Bis, Joshua C, Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B., Malik, Rainer, Dichgans, Martin, Worrall, Bradford B., Erdmann, Jeanette, Nelson, Christopher P., Samani, Nilesh J., Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S., Hingorani, Aroon D., Lind, Lars, Pedersen, Nancy L., de Graaf, Jacqueline, Kiemeney, Lambertus A.L.M., Baumeister, Sebastian E., Franco, Oscar H., Hofman, Albert, Uitterlinden, André G., Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J. Wouter, Eriksen, Bjørn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Debette, Stéphanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J., Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P., Ingelsson, Erik, den Ruijter, Hester M., de Bakker, Paul I.W., Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V., Asselbergs, Folkert W., Academic Medical Center, Isotope Research, Cardiovascular Centre (CVC), Epidemiology, and Internal Medicine

Subjects
CHRONIC KIDNEY-DISEASE, Cardiac & Cardiovascular Systems, SUSCEPTIBILITY LOCI, Genotype, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Coronary, heart failure, Heart disease, Global Health, urologic and male genital diseases, Polymorphism, Single Nucleotide, 1102 Cardiovascular Medicine And Haematology, SDG 3 - Good Health and Well-being, Risk Factors, Journal Article, ischemic stroke, Humans, Cardiac and Cardiovascular Systems, genetics, Prospective Studies, GENOME-WIDE ASSOCIATION, Cystatin C, coronary heart disease, Alleles, Aged, RISK, Kardiologi, Science & Technology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, INCIDENT HEART-FAILURE, Incidence, COMMON VARIANTS, Mendelian Randomization Analysis, Middle Aged, female genital diseases and pregnancy complications, CHARGE CONSORTIUM, Multicenter Study, BODY-MASS INDEX, ISCHEMIC-STROKE, 1117 Public Health And Health Services, Cardiovascular System & Hematology, Cardiovascular Diseases, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Cardiovascular System & Cardiology, CORONARY-ARTERY-DISEASE, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Life Sciences & Biomedicine
Abstract

Source: doi: 10.1016/j.jacc.2016.05.092 BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVESThe aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n ¼ 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n ¼ 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p ¼ 2.12 10 14). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p ¼ 5.95 10 211), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p ¼ 0.994), which was statistically different from the observational estimate (p ¼ 1.6 10 5). A causal effect of cystatin C was not detected for any individual component of CVD.CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD. (J Am Coll Cardiol 2016;68:934–45) © 2016 The Authors. Published by Elsevier Inc. on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Published
2016

128. Variation in Interleukin 6 Receptor Gene Associates With Risk of Crohn’s Disease and Ulcerative Colitis

Author

Parisinos, Constantinos A., Serghiou, Stylianos, Katsoulis, Michail, George, Marc Jonathan, Patel, Riyaz S., Hemingway, Harry, and Hingorani, Aroon D.

Subjects
IBD, inflammatory bowel disease, IL6, interleukin 6, MR, Mendelian randomization, SNP, SNP, single nucleotide polymorphism, Article, CI, confidence interval, OR, odds ratio, UC, ulcerative colitis, IL6R, IL6 receptor, Mendelian Randomization, Genetics, CD, Crohn’s disease, RCT, randomized controlled trial, Drug Target Validation, s-IL6R, soluble IL6R, gp130, glycoprotein 130
Abstract

Interleukin 6 (IL6) is an inflammatory cytokine; signaling via its receptor (IL6R) is believed to contribute to development of inflammatory bowel diseases (IBD). The single nucleotide polymorphism rs2228145 in IL6R associates with increased levels of soluble IL6R (s-IL6R), as well as reduced IL6R signaling and risk of inflammatory disorders; its effects are similar to those of a therapeutic monoclonal antibody that blocks IL6R signaling. We used the effect of rs2228145 on s-IL6R level as an indirect marker to investigate whether reduced IL6R signaling associates with risk of ulcerative colitis (UC) or Crohn’s disease (CD). In a genome-wide meta-analysis of 20,550 patients with CD, 17,647 patients with UC, and more than 40,000 individuals without IBD (controls), we found that rs2228145 (scaled to a 2-fold increase in s-IL6R) was associated with reduced risk of CD (odds ratio 0.876; 95% confidence interval 0.822–0.933; P = .00003) or UC (odds ratio 0.932; 95% confidence interval 0.875–0.996; P = .036). These findings indicate that therapeutics designed to block IL6R signaling might be effective in treatment of IBD.

Published
2018

131. Prognostic burden of heart failure recorded in primary care, acute hospital admissions, or both: a population‐based linked electronic health record cohort study in 2.1 million people

Author

Koudstaal, Stefan, primary, Pujades‐Rodriguez, Mar, additional, Denaxas, Spiros, additional, Gho, Johannes M.I.H., additional, Shah, Anoop D., additional, Yu, Ning, additional, Patel, Riyaz S., additional, Gale, Chris P., additional, Hoes, Arno W., additional, Cleland, John G., additional, Asselbergs, Folkert W., additional, and Hemingway, Harry, additional

Published
2016
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132. Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres.

Author

Kaura, Amit, Panoulas, Vasileios, Glampson, Benjamin, Davies, Jim, Mulla, Abdulrahim, Woods, Kerrie, Omigie, Joe, Shah, Anoop D., Channon, Keith M., Weber, Jonathan N., Thursz, Mark R., Elliott, Paul, Hemingway, Harry, Williams, Bryan, Asselbergs, Folkert, O'Sullivan, Michael, Kharbanda, Rajesh, Lord, Graham M., Melikian, Narbeh, and Patel, Riyaz S.

Subjects
MORTALITY risk factors, AGE distribution, BIOMARKERS, CONFIDENCE intervals, CAUSES of death, LONGITUDINAL method, RISK assessment, PROPORTIONAL hazards models, RETROSPECTIVE studies, ACUTE coronary syndrome, TROPONIN, DESCRIPTIVE statistics
Published
2019
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134. Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study

Author

van der Laan, Sander W, Fall, Tove, Soumaré, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E, Arpegård, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Dörr, Marcus, Magnusson, Patrik K, Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P, Felix, Janine F, Morrison, Alanna C, Franceschini, Nora, Bis, Joshua C, Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B, Malik, Rainer, Dichgans, Martin, Worrall, Bradford B, Erdmann, Jeanette, Nelson, Christopher P, Samani, Nilesh J, Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S, Hingorani, Aroon D, Lind, Lars, Pedersen, Nancy L, de Graaf, Jacqueline, Kiemeney, Lambertus A L M, Baumeister, Sebastian E, Franco, Oscar H, Hofman, Albert, Uitterlinden, André G, Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J Wouter, Eriksen, Bjørn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Debette, Stéphanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J, Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P, Ingelsson, Erik, den Ruijter, Hester M, de Bakker, Paul I W, Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V, Asselbergs, Folkert W, van der Laan, Sander W, Fall, Tove, Soumaré, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E, Arpegård, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Dörr, Marcus, Magnusson, Patrik K, Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P, Felix, Janine F, Morrison, Alanna C, Franceschini, Nora, Bis, Joshua C, Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B, Malik, Rainer, Dichgans, Martin, Worrall, Bradford B, Erdmann, Jeanette, Nelson, Christopher P, Samani, Nilesh J, Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S, Hingorani, Aroon D, Lind, Lars, Pedersen, Nancy L, de Graaf, Jacqueline, Kiemeney, Lambertus A L M, Baumeister, Sebastian E, Franco, Oscar H, Hofman, Albert, Uitterlinden, André G, Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J Wouter, Eriksen, Bjørn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Debette, Stéphanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J, Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P, Ingelsson, Erik, den Ruijter, Hester M, de Bakker, Paul I W, Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V, and Asselbergs, Folkert W

Published
2016

135. Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study

Author

Experimentele Afd. Cardiologie 1, Beeldverwerking ISI, Circulatory Health, Brain, Cardiovasculaire Epi Team 3, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Cardiovasculaire Epidemiologie, Onderzoek Vrouw Hart & Vaatziekten, CMM Groep Kaaij, Infection & Immunity, CDL Cluster Onderzoek en Onderwijs, Cardiologie, van der Laan, Sander W, Fall, Tove, Soumaré, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E, Arpegård, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Dörr, Marcus, Magnusson, Patrik K, Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P, Felix, Janine F, Morrison, Alanna C, Franceschini, Nora, Bis, Joshua C, Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B, Malik, Rainer, Dichgans, Martin, Worrall, Bradford B, Erdmann, Jeanette, Nelson, Christopher P, Samani, Nilesh J, Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S, Hingorani, Aroon D, Lind, Lars, Pedersen, Nancy L, de Graaf, Jacqueline, Kiemeney, Lambertus A L M, Baumeister, Sebastian E, Franco, Oscar H, Hofman, Albert, Uitterlinden, André G, Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J Wouter, Eriksen, Bjørn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Debette, Stéphanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J, Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P, Ingelsson, Erik, den Ruijter, Hester M, de Bakker, Paul I W, Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V, Asselbergs, Folkert W, Experimentele Afd. Cardiologie 1, Beeldverwerking ISI, Circulatory Health, Brain, Cardiovasculaire Epi Team 3, Cancer, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, JC onderzoeksprogramma Kanker, Cardiovasculaire Epidemiologie, Onderzoek Vrouw Hart & Vaatziekten, CMM Groep Kaaij, Infection & Immunity, CDL Cluster Onderzoek en Onderwijs, Cardiologie, van der Laan, Sander W, Fall, Tove, Soumaré, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E, Arpegård, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Dörr, Marcus, Magnusson, Patrik K, Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P, Felix, Janine F, Morrison, Alanna C, Franceschini, Nora, Bis, Joshua C, Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B, Malik, Rainer, Dichgans, Martin, Worrall, Bradford B, Erdmann, Jeanette, Nelson, Christopher P, Samani, Nilesh J, Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S, Hingorani, Aroon D, Lind, Lars, Pedersen, Nancy L, de Graaf, Jacqueline, Kiemeney, Lambertus A L M, Baumeister, Sebastian E, Franco, Oscar H, Hofman, Albert, Uitterlinden, André G, Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J Wouter, Eriksen, Bjørn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Debette, Stéphanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J, Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P, Ingelsson, Erik, den Ruijter, Hester M, de Bakker, Paul I W, Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V, and Asselbergs, Folkert W

Published
2016

136. Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

Author

Eapen, Danny J. Manocha, Pankaj Ghasemzadeh, Nima Patel, Riyaz S. Al Kassem, Hatem Hammadah, Muhammad Veledar, Emir and Le, Ngoc-Anh Pielak, Tomasz Thorball, Christian W. and Velegraki, Aristea Kremastinos, Dimitrios T. Lerakis, Stamatios and Sperling, Laurence Quyyumi, Arshed A.

Abstract

Introduction-Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown. Methods and Results-We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1 +/- 1.1 years. Presence of angiographic CAD (>= 50% stenosis in >= 1 coronary artery) and its severity were quantitated using the Gensini score. Cox’s proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C-reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P= 3.5 ng/mL (cutoff by Youden’s index) predicted future risk of MI (hazard ratio [HR] =3.2; P

Published
2014

137. VariantASGR1Associated with a Reduced Risk of Coronary Artery Disease

Author

Nioi, Paul, primary, Sigurdsson, Asgeir, additional, Thorleifsson, Gudmar, additional, Helgason, Hannes, additional, Agustsdottir, Arna B., additional, Norddahl, Gudmundur L., additional, Helgadottir, Anna, additional, Magnusdottir, Audur, additional, Jonasdottir, Aslaug, additional, Gretarsdottir, Solveig, additional, Jonsdottir, Ingileif, additional, Steinthorsdottir, Valgerdur, additional, Rafnar, Thorunn, additional, Swinkels, Dorine W., additional, Galesloot, Tessel E., additional, Grarup, Niels, additional, Jørgensen, Torben, additional, Vestergaard, Henrik, additional, Hansen, Torben, additional, Lauritzen, Torsten, additional, Linneberg, Allan, additional, Friedrich, Nele, additional, Krarup, Nikolaj T., additional, Fenger, Mogens, additional, Abildgaard, Ulrik, additional, Hansen, Peter R., additional, Galløe, Anders M., additional, Braund, Peter S., additional, Nelson, Christopher P., additional, Hall, Alistair S., additional, Williams, Michael J.A., additional, van Rij, Andre M., additional, Jones, Gregory T., additional, Patel, Riyaz S., additional, Levey, Allan I., additional, Hayek, Salim, additional, Shah, Svati H., additional, Reilly, Muredach, additional, Eyjolfsson, Gudmundur I., additional, Sigurdardottir, Olof, additional, Olafsson, Isleifur, additional, Kiemeney, Lambertus A., additional, Quyyumi, Arshed A., additional, Rader, Daniel J., additional, Kraus, William E., additional, Samani, Nilesh J., additional, Pedersen, Oluf, additional, Thorgeirsson, Gudmundur, additional, Masson, Gisli, additional, Holm, Hilma, additional, Gudbjartsson, Daniel, additional, Sulem, Patrick, additional, Thorsteinsdottir, Unnur, additional, and Stefansson, Kari, additional

Published
2016
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138. Response to Letter Regarding Article “Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease”

Author

Patel, Riyaz S., primary, Ghasemzadeh, Nima, additional, Eapen, Danny J., additional, Sher, Salman, additional, Arshad, Shawn, additional, Ko, Yi-an, additional, Veledar, Emir, additional, Samady, Habib, additional, Zafari, A. Maziar, additional, Sperling, Laurence, additional, Vaccarino, Viola, additional, Jones, Dean P., additional, and Quyyumi, Arshed A., additional

Published
2016
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139. Variants with large effects on blood lipids and the role of cholesterol and triglycerides in coronary disease

Author

Helgadottir, Anna, primary, Gretarsdottir, Solveig, additional, Thorleifsson, Gudmar, additional, Hjartarson, Eirikur, additional, Sigurdsson, Asgeir, additional, Magnusdottir, Audur, additional, Jonasdottir, Aslaug, additional, Kristjansson, Helgi, additional, Sulem, Patrick, additional, Oddsson, Asmundur, additional, Sveinbjornsson, Gardar, additional, Steinthorsdottir, Valgerdur, additional, Rafnar, Thorunn, additional, Masson, Gisli, additional, Jonsdottir, Ingileif, additional, Olafsson, Isleifur, additional, Eyjolfsson, Gudmundur I, additional, Sigurdardottir, Olof, additional, Daneshpour, Maryam S, additional, Khalili, Davood, additional, Azizi, Fereidoun, additional, Swinkels, Dorine W, additional, Kiemeney, Lambertus, additional, Quyyumi, Arshed A, additional, Levey, Allan I, additional, Patel, Riyaz S, additional, Hayek, Salim S, additional, Gudmundsdottir, Ingibjorg J, additional, Thorgeirsson, Gudmundur, additional, Thorsteinsdottir, Unnur, additional, Gudbjartsson, Daniel F, additional, Holm, Hilma, additional, and Stefansson, Kari, additional

Published
2016
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140. Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease

Author

Patel, Riyaz S., primary, Ghasemzadeh, Nima, additional, Eapen, Danny J., additional, Sher, Salman, additional, Arshad, Shawn, additional, Ko, Yi-an, additional, Veledar, Emir, additional, Samady, Habib, additional, Zafari, A. Maziar, additional, Sperling, Laurence, additional, Vaccarino, Viola, additional, Jones, Dean P., additional, and Quyyumi, Arshed A., additional

Published
2016
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141. Association Between the Chromosome 9p21 Locus and Angiographic Coronary Artery Disease Burden: A Collaborative Meta-Analysis

Author

Chan, Kenneth, MPharm, Patel, Riyaz S., Newcombe, Paul, Nelson, Christopher P., Qasim, Atif, Epstein, Stephen E., Burnett, Susan, Vaccarino, Viola L., Zafari, A. Maziar, Shah, Svati H., Anderson, Jeffrey L., Carlquist, John F., Hartiala, Jaana, Allayee, Hooman, Hinohara, Kunihiko, Lee, Bok-Soo, Erl, Anna, Ellis, Katrina L., Goel, Anuj, Schaefer, Arne S., El Mokhtari, Nour Eddine, Goldstein, Benjamin A., Hlatky, Mark A., Go, Alan S., Shen, Gong-Qing, Gong, Yan, Pepine, Carl, Laxton, Ross C., Whittaker, John C., Tang, W.H. Wilson, Johnson, Julie A., Wang, Qing K., Assimes, Themistocles L., Nöthlings, Ute, Farrall, Martin, Watkins, Hugh, Richards, A. Mark, Cameron, Vicky A., Muendlein, Axel, Drexel, Heinz, Koch, Werner, Park, Jeong Euy, Kimura, Akinori, Shen, Wei-feng, Simpson, Iain A., Hazen, Stanley L., Horne, Benjamin D., Hauser, Elizabeth R., Quyyumi, Arshed A., Reilly, Muredach P., Samani, Nilesh J., and Ye, Shu

Subjects
Genetic Loci, Myocardial Infarction, Humans, Coronary Artery Disease, Chromosomes, Human, Pair 9, Coronary Angiography, Polymorphism, Single Nucleotide, Article
Abstract

This study sought to ascertain the relationship of 9p21 locus with: 1) angiographic coronary artery disease (CAD) burden; and 2) myocardial infarction (MI) in individuals with underlying CAD.Chromosome 9p21 variants have been robustly associated with coronary heart disease, but questions remain on the mechanism of risk, specifically whether the locus contributes to coronary atheroma burden or plaque instability.We established a collaboration of 21 studies consisting of 33,673 subjects with information on both CAD (clinical or angiographic) and MI status along with 9p21 genotype. Tabular data are provided for each cohort on the presence and burden of angiographic CAD, MI cases with underlying CAD, and the diabetic status of all subjects.We first confirmed an association between 9p21 and CAD with angiographically defined cases and control subjects (pooled odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.20 to 1.43). Among subjects with angiographic CAD (n = 20,987), random-effects model identified an association with multivessel CAD, compared with those with single-vessel disease (OR: 1.10, 95% CI: 1.04 to 1.17)/copy of risk allele). Genotypic models showed an OR of 1.15, 95% CI: 1.04 to 1.26 for heterozygous carrier and OR: 1.23, 95% CI: 1.08 to 1.39 for homozygous carrier. Finally, there was no significant association between 9p21 and prevalent MI when both cases (n = 17,791) and control subjects (n = 15,882) had underlying CAD (OR: 0.99, 95% CI: 0.95 to 1.03)/risk allele.The 9p21 locus shows convincing association with greater burden of CAD but not with MI in the presence of underlying CAD. This adds further weight to the hypothesis that 9p21 locus primarily mediates an atherosclerotic phenotype.

Published
2013

142. Diagnostic accuracy and prognostic value of simultaneous hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in cardiac sarcoidosis.

Author

Wicks, Eleanor C., Menezes, Leon J., Barnes, Anna, Mohiddin, Saidi A., Sekhri, Neha, Porter, Joanna C., Booth, Helen L., Garrett, Emily, Patel, Riyaz S., Pavlou, Menelaos, Groves, Ashley M., and Elliott, Perry M.

Subjects
SARCOIDOSIS diagnosis, SARCOIDOSIS, CARDIAC arrest, DEOXY sugars, FASTING, CARBOHYDRATE content of food, HEART, HEART block, HEART failure, HOSPITAL admission & discharge, MAGNETIC resonance imaging, MATHEMATICAL models, MEDICAL protocols, PATIENTS, RADIOPHARMACEUTICALS, RESEARCH evaluation, POSITRON emission tomography, VENTRICULAR tachycardia, THEORY, DISEASE prevalence, VENTRICULAR arrhythmia, VENTRICULAR ejection fraction, PROGNOSIS
Abstract

Aims Cardiac death is the leading cause of mortality in patients with sarcoidosis, yet cardiac involvement often remains undetected. Cardiovascular magnetic resonance imaging (CMR) and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) have been used to diagnose cardiac sarcoidosis (CS) yet never simultaneously in a cohort. This study sought to assess the diagnostic and prognostic utility of simultaneous hybrid cardiac PET/MR. Methods and Results Fifty-one consecutive patients with suspected CS (age 50 ± 13 years, 31 males) underwent simultaneous PET/MR following a high-fat/low-carbohydrate diet and 12-h fast. Blinded image analysis of FDG uptake and late gadolinium enhancement (LGE) was performed using the American Heart Association (AHA) 16-segment model. The sensitivity and specificity of PET/MR for diagnosing CS was estimated using the Japanese Ministry of Health and Welfare guidelines. The primary endpoint was a composite of death, aborted sudden cardiac death, sustained ventricular arrhythmia, complete heart block, and hospital admission with decompensated heart failure. The secondary endpoints were a fall in left ventricular ejection fraction (LVEF) >10%, non-sustained ventricular tachycardia and other cardiac-related hospital admission. The prevalence of CS was 65% (n = 33). The sensitivity of PET and CMR alone for detecting CS was 0.85 and 0.82, respectively. Hybrid PET/MR was superior for detecting CS with sensitivity, specificity, positive, and negative predictive values of 0.94, 0.44, 0.76, and 0.80, respectively. There was poor inter-modality agreement for the location of cardiac abnormalities (k = 0.02). Over the median follow-up of 2.2 years, there were 18 (35%) adverse events. Cardiac RV PET abnormalities and presence of LGE were independent predictors of adverse events. Abnormalities found on both PET and magnetic resonance imaging was the strongest predictor of major adverse cardiac events. Conclusion Simultaneous PET/MR is an accurate method for diagnosing CS. FDG-PET and CMR combined offers complementary information on disease pathophysiology. The presence of LGE and FDG uptake on PET/MR identifies patients at higher risk of adverse events. PET and CMR should therefore be considered in the assessment of disease presence, stage, and prognosis in CS. [ABSTRACT FROM AUTHOR]

Published
2018
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143. Common Sequence Variants Associated With Coronary Artery Disease Correlate With the Extent of Coronary Atherosclerosis

Author

Bjornsson, Eythor, primary, Gudbjartsson, Daniel F., additional, Helgadottir, Anna, additional, Gudnason, Thorarinn, additional, Gudbjartsson, Tomas, additional, Eyjolfsson, Kristjan, additional, Patel, Riyaz S., additional, Ghasemzadeh, Nima, additional, Thorleifsson, Gudmar, additional, Quyyumi, Arshed A., additional, Thorsteinsdottir, Unnur, additional, Thorgeirsson, Gudmundur, additional, and Stefansson, Kari, additional

Published
2015
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144. Circulating CD34 + Progenitor Cells and Risk of Mortality in a Population With Coronary Artery Disease

Author

Patel, Riyaz S., primary, Li, Qunna, additional, Ghasemzadeh, Nima, additional, Eapen, Danny J., additional, Moss, Lauren D., additional, Janjua, A. Umair, additional, Manocha, Pankaj, additional, Al Kassem, Hatem, additional, Veledar, Emir, additional, Samady, Habib, additional, Taylor, W. Robert, additional, Zafari, A. Maziar, additional, Sperling, Laurence, additional, Vaccarino, Viola, additional, Waller, Edmund K., additional, and Quyyumi, Arshed A., additional

Published
2015
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145. Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm

Author

Gretarsdottir, Solveig, Baas, Annette F., Thorleifsson, Gudmar, Holm, Hilma, den Heijer, Martin, de Vries, Jean-Paul P. M., Kranendonk, Steef E., Zeebregts, Clark J. A. M., van Sterkenburg, Steven M., Geelkerken, Robert H., van Rij, Andre M., Williams, Michael J. A., Boll, Albert P. M., Kostic, Jelena P., Jonasdottir, Adalbjorg, Jonasdottir, Aslaug, Walters, G. Bragi, Masson, Gisli, Sulem, Patrick, Saemundsdottir, Jona, Mouy, Magali, Magnusson, Kristinn P., Tromp, Gerard, Elmore, James R., Sakalihasan, Natzi, Limet, Raymond, Defraigne, Jean-Olivier, Ferrell, Robert E., Ronkainen, Antti, Ruigrok, Ynte M., Wijmenga, Cisca, Grobbee, Diederick E., Shah, Svati H., Granger, Christopher B., Quyyumi, Arshed A., Vaccarino, Viola, Patel, Riyaz S., Zafari, A. Maziar, Levey, Allan I., Austin, Harland, Girelli, Domenico, Pignatti, Pier Franco, Olivieri, Oliviero, Martinelli, Nicola, Malerba, Giovanni, Trabetti, Elisabetta, Becker, Lewis C., Becker, Diane M., Reilly, Muredach P., Rader, Daniel J., Mueller, Thomas, Dieplinger, Benjamin, Haltmayer, Meinhard, Urbonavicius, Sigitas, Lindblad, Bengt, Gottsater, Anders, Gaetani, Eleonora, Pola, Roberto, Wells, Philip, Rodger, Marc, Forgie, Melissa, Langlois, Nicole, Corral, Javier, Vicente, Vicente, Fontcuberta, Jordi, Espana, Francisco, Grarup, Niels, Jorgensen, Torben, Witte, Daniel R., Hansen, Torben, Pedersen, Oluf, Aben, Katja K., de Graaf, Jacqueline, Holewijn, Suzanne, Folkersen, Lasse, Franco-Cereceda, Anders, Eriksson, Per, Collier, David A., Stefansson, Hreinn, Steinthorsdottir, Valgerdur, Rafnar, Thorunn, Valdimarsson, Einar M., Magnadottir, Hulda B., Sveinbjornsdottir, Sigurlaug, Olafsson, Isleifur, Magnusson, Magnus Karl, Palmason, Robert, Haraldsdottir, Vilhelmina, Andersen, Karl, Onundarson, Pall T., Thorgeirsson, Gudmundur, Kiemeney, Lambertus A., Powell, Janet T., Carey, David J., Kuivaniemi, Helena, Lindholt, Jes S., Jones, Gregory T., Kong, Augustine, Blankensteijn, Jan D., Matthiasson, Stefan E., Thorsteinsdottir, Unnur, and Stefansson, Kari

Published
2010

146. Genetic variants at chromosome 9p21 and risk of first versus subsequent coronary heart disease events:a systematic review and meta-analysis

Author

Patel, Riyaz S., Asselbergs, Folkert W., Quyyumi, Arshed A., Palmer, Tom M., Finan, Chris I., Tragante, Vinicius, Deanfield, John, Hemingway, Harry, Hingorani, Aroon D., Holmes, Michael V., Patel, Riyaz S., Asselbergs, Folkert W., Quyyumi, Arshed A., Palmer, Tom M., Finan, Chris I., Tragante, Vinicius, Deanfield, John, Hemingway, Harry, Hingorani, Aroon D., and Holmes, Michael V.

Abstract

OBJECTIVES: The purpose of this analysis was to compare the association between variants at the chromosome 9p21 locus (Ch9p21) and risk of first versus subsequent coronary heart disease (CHD) events through systematic review and meta-analysis. BACKGROUND: Ch9p21 is a recognized risk factor for a first CHD event. However, its association with risk of subsequent events in patients with established CHD is less clear. METHODS: We searched PubMed and EMBASE for prospective studies reporting association of Ch9p21 with incident CHD events and extracted information on cohort type (individuals without prior CHD or individuals with established CHD) and effect estimates for risk of events. RESULTS: We identified 31 cohorts reporting on 193,372 individuals. Among the 16 cohorts of individuals without prior CHD (n = 168,209), there were 15,664 first CHD events. Ch9p21 was associated with a pooled hazard ratio (HR) of a first event of 1.19 (95% confidence interval: 1.17 to 1.22) per risk allele. In individuals with established CHD (n = 25,163), there were 4,436 subsequent events providing >99% and 91% power to detect a per-allele HR of 1.19 or 1.10, respectively. The pooled HR for subsequent events was 1.01 (95% confidence interval: 0.97 to 1.06) per risk allele. There was strong evidence of heterogeneity between the effect estimates for first and subsequent events (p value for heterogeneity = 5.6 × 10(-11)). We found no evidence for biases to account for these findings. CONCLUSIONS: Ch9p21 shows differential association with risk of first versus subsequent CHD events. This has implications for genetic risk prediction in patients with established CHD and for mechanistic understanding of how Ch9p21 influences risk of CHD.

Published
2014

148. Impact of Selection Bias on Estimation of Subsequent Event Risk.

Author

Yi-Juan Hu, Schmidt, Amand F., Dudbridge, Frank, Holmes, Michael V., Brophy, James M., Tragante, Vinicius, Ziyi Li, Peizhou Liao, Quyyumi, Arshed A., McCubrey, Raymond O., Horne, Benjamin D., Hingorani, Aroon D., Asselbergs, Folkert W., Patel, Riyaz S., and Qi Long

Abstract

Background--Studies of recurrent or subsequent disease events may be susceptible to bias caused by selection of subjects who both experience and survive the primary indexing event. Currently, the magnitude of any selection bias, particularly for subsequent time-to-event analysis in genetic association studies, is unknown. Methods and Results--We used empirically inspired simulation studies to explore the impact of selection bias on the marginal hazard ratio for risk of subsequent events among those with established coronary heart disease. The extent of selection bias was determined by the magnitudes of genetic and nongenetic effects on the indexing (first) coronary heart disease event. Unless the genetic hazard ratio was unrealistically large (>1.6 per allele) and assuming the sum of all nongenetic hazard ratios was <10, bias was usually <10% (downward toward the null). Despite the low bias, the probability that a confidence interval included the true effect decreased (undercoverage) with increasing sample size because of increasing precision. Importantly, false-positive rates were not affected by selection bias. Conclusions--In most empirical settings, selection bias is expected to have a limited impact on genetic effect estimates of subsequent event risk. Nevertheless, because of undercoverage increasing with sample size, most confidence intervals will be over precise (not wide enough). When there is no effect modification by history of coronary heart disease, the false-positive rates of association tests will be close to nominal. [ABSTRACT FROM AUTHOR]

Published
2017
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149. Abstract 11661: A Family History of Premature Coronary Artery Disease is Associated With Location and Severity of Angiographically Defined Coronary Artery Stenosis

Author

Hammadah, Muhammad, primary, Patel, Riyaz S, additional, Eapen, Danny J, additional, Samman Tahhan, Ayman, additional, Ghasemzadeh, Nima, additional, Al Kassem, Hatem, additional, Khayata, Mohamed, additional, Manocha, Pankaj, additional, Awad, Mosaab, additional, Kassas, Ibrahim, additional, Alkhoder, Ayman, additional, Veledar, Emir, additional, and Quyyumi, Arshed A, additional

Published
2014
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150. Abstract 13916: A Novel Biomarker of Oxidative Stress is Predictive of Incident Death and Myocardial Infarction in Patients with Coronary Artery Disease

Author

Patel, Riyaz S, primary, Ghasemzadeh, Nima, additional, Eapen, Danny J, additional, Sher, Salman, additional, Arshad, Shawn, additional, Veledar, Emir, additional, Samady, Habib, additional, Zafari, A. Maziar, additional, Sperling, Laurence, additional, Vaccarino, Viola, additional, Jones, Dean P, additional, and Quyyumi, Arshed A, additional

Published
2014
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