Subsequent Event Risk in Individuals With Established Coronary Heart Disease

Riyaz S Patel; Vinicius Tragante; Amand F Schmidt; Raymond O McCubrey; Michael V Holmes; Laurence J Howe; Kenan Direk; Axel Åkerblom; Karin Leander; Salim S Virani; Karol A Kaminski; Jochen D Muehlschlegel; Hooman Allayee; Peter Almgren; Maris Alver; Ekaterina V Baranova; Hassan Behloui; Bram Boeckx; Peter S Braund; Lutz P Breitling; Graciela Delgado; Nubia E Duarte; Marie-Pierre Dubé; Line Dufresne; Niclas Eriksson; Luisa Foco; Markus Scholz; Crystel M Gijsberts; Charlotte Glinge; Yan Gong; Jaana Hartiala; Mahyar Heydarpour; Jaroslav A Hubacek; Marcus Kleber; Daniel Kofink; Salma Kotti; Pekka Kuukasjärvi; Vei-Vei Lee; Andreas Leiherer; Petra A Lenzini; Daniel Levin; Leo-Pekka Lyytikäinen; Nicola Martinelli; Ute Mons; Christopher P Nelson; Kjell Nikus; Anna P Pilbrow; Rafal Ploski; Olaf H Klungel; Anke H Maitland-van der Zee

doi:10.1161/CIRCGEN.119.002470

Subsequent Event Risk in Individuals With Established Coronary Heart Disease

Riyaz S Patel, Vinicius Tragante, Amand F Schmidt, Raymond O McCubrey, Michael V Holmes, Laurence J Howe, Kenan Direk, Axel Åkerblom, Karin Leander, Salim S Virani, Karol A Kaminski, Jochen D Muehlschlegel, Hooman Allayee, Peter Almgren, Maris Alver, Ekaterina V Baranova, Hassan Behloui, Bram Boeckx, Peter S Braund, Lutz P BreitlingGraciela Delgado, Nubia E Duarte, Marie-Pierre Dubé, Line Dufresne, Niclas Eriksson, Luisa Foco, Markus Scholz, Crystel M Gijsberts, Charlotte Glinge, Yan Gong, Jaana Hartiala, Mahyar Heydarpour, Jaroslav A Hubacek, Marcus Kleber, Daniel Kofink, Salma Kotti, Pekka Kuukasjärvi, Vei-Vei Lee, Andreas Leiherer, Petra A Lenzini, Daniel Levin, Leo-Pekka Lyytikäinen, Nicola Martinelli, Ute Mons, Christopher P Nelson, Kjell Nikus, Anna P Pilbrow, Rafal Ploski, Olaf H Klungel, Anke H Maitland-van der Zee

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.

METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.

RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.

CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.

Original language	English
Article number	e002470
Number of pages	16
Journal	Circulation. Genomic and precision medicine
Volume	12
Issue number	4
DOIs	https://doi.org/10.1161/CIRCGEN.119.002470
Publication status	Published - Apr 2019

Keywords

coronary artery disease
genetics
myocardial infarction
prognosis
sedundary preventation

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Patel, R. S., Tragante, V., Schmidt, A. F., McCubrey, R. O., Holmes, M. V., Howe, L. J., Direk, K., Åkerblom, A., Leander, K., Virani, S. S., Kaminski, K. A., Muehlschlegel, J. D., Allayee, H., Almgren, P., Alver, M., Baranova, E. V., Behloui, H., Boeckx, B., Braund, P. S., ... Maitland-van der Zee, A. H. (2019). Subsequent Event Risk in Individuals With Established Coronary Heart Disease. Circulation. Genomic and precision medicine, 12(4), Article e002470. https://doi.org/10.1161/CIRCGEN.119.002470

@article{cd5274349dc3478c9bdafab800473dcb,

title = "Subsequent Event Risk in Individuals With Established Coronary Heart Disease",

abstract = "BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38\%-100\%), mostly male (44\%-91\%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95\% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95\% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95\% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.",

keywords = "coronary artery disease, genetics, myocardial infarction, prognosis, sedundary preventation",

author = "Patel, \{Riyaz S\} and Vinicius Tragante and Schmidt, \{Amand F\} and McCubrey, \{Raymond O\} and Holmes, \{Michael V\} and Howe, \{Laurence J\} and Kenan Direk and Axel {\AA}kerblom and Karin Leander and Virani, \{Salim S\} and Kaminski, \{Karol A\} and Muehlschlegel, \{Jochen D\} and Hooman Allayee and Peter Almgren and Maris Alver and Baranova, \{Ekaterina V\} and Hassan Behloui and Bram Boeckx and Braund, \{Peter S\} and Breitling, \{Lutz P\} and Graciela Delgado and Duarte, \{Nubia E\} and Marie-Pierre Dub{\'e} and Line Dufresne and Niclas Eriksson and Luisa Foco and Markus Scholz and Gijsberts, \{Crystel M\} and Charlotte Glinge and Yan Gong and Jaana Hartiala and Mahyar Heydarpour and Hubacek, \{Jaroslav A\} and Marcus Kleber and Daniel Kofink and Salma Kotti and Pekka Kuukasj{\"a}rvi and Vei-Vei Lee and Andreas Leiherer and Lenzini, \{Petra A\} and Daniel Levin and Leo-Pekka Lyytik{\"a}inen and Nicola Martinelli and Ute Mons and Nelson, \{Christopher P\} and Kjell Nikus and Pilbrow, \{Anna P\} and Rafal Ploski and Klungel, \{Olaf H\} and \{Maitland-van der Zee\}, \{Anke H\}",

year = "2019",

month = apr,

doi = "10.1161/CIRCGEN.119.002470",

language = "English",

volume = "12",

journal = "Circulation. Genomic and precision medicine",

issn = "2574-8300",

publisher = "Lippincott Williams and Wilkins",

number = "4",

}

Patel, RS, Tragante, V, Schmidt, AF, McCubrey, RO, Holmes, MV, Howe, LJ, Direk, K, Åkerblom, A, Leander, K, Virani, SS, Kaminski, KA, Muehlschlegel, JD, Allayee, H, Almgren, P, Alver, M, Baranova, EV, Behloui, H, Boeckx, B, Braund, PS, Breitling, LP, Delgado, G, Duarte, NE, Dubé, M-P, Dufresne, L, Eriksson, N, Foco, L, Scholz, M, Gijsberts, CM, Glinge, C, Gong, Y, Hartiala, J, Heydarpour, M, Hubacek, JA, Kleber, M, Kofink, D, Kotti, S, Kuukasjärvi, P, Lee, V-V, Leiherer, A, Lenzini, PA, Levin, D, Lyytikäinen, L-P, Martinelli, N, Mons, U, Nelson, CP, Nikus, K, Pilbrow, AP, Ploski, R, Klungel, OH & Maitland-van der Zee, AH 2019, 'Subsequent Event Risk in Individuals With Established Coronary Heart Disease', Circulation. Genomic and precision medicine, vol. 12, no. 4, e002470. https://doi.org/10.1161/CIRCGEN.119.002470

TY - JOUR

T1 - Subsequent Event Risk in Individuals With Established Coronary Heart Disease

AU - Patel, Riyaz S

AU - Tragante, Vinicius

AU - Schmidt, Amand F

AU - McCubrey, Raymond O

AU - Holmes, Michael V

AU - Howe, Laurence J

AU - Direk, Kenan

AU - Åkerblom, Axel

AU - Leander, Karin

AU - Virani, Salim S

AU - Kaminski, Karol A

AU - Muehlschlegel, Jochen D

AU - Allayee, Hooman

AU - Almgren, Peter

AU - Alver, Maris

AU - Baranova, Ekaterina V

AU - Behloui, Hassan

AU - Boeckx, Bram

AU - Braund, Peter S

AU - Breitling, Lutz P

AU - Delgado, Graciela

AU - Duarte, Nubia E

AU - Dubé, Marie-Pierre

AU - Dufresne, Line

AU - Eriksson, Niclas

AU - Foco, Luisa

AU - Scholz, Markus

AU - Gijsberts, Crystel M

AU - Glinge, Charlotte

AU - Gong, Yan

AU - Hartiala, Jaana

AU - Heydarpour, Mahyar

AU - Hubacek, Jaroslav A

AU - Kleber, Marcus

AU - Kofink, Daniel

AU - Kotti, Salma

AU - Kuukasjärvi, Pekka

AU - Lee, Vei-Vei

AU - Leiherer, Andreas

AU - Lenzini, Petra A

AU - Levin, Daniel

AU - Lyytikäinen, Leo-Pekka

AU - Martinelli, Nicola

AU - Mons, Ute

AU - Nelson, Christopher P

AU - Nikus, Kjell

AU - Pilbrow, Anna P

AU - Ploski, Rafal

AU - Klungel, Olaf H

AU - Maitland-van der Zee, Anke H

PY - 2019/4

Y1 - 2019/4

N2 - BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.

AB - BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.

KW - coronary artery disease

KW - genetics

KW - myocardial infarction

KW - prognosis

KW - sedundary preventation

U2 - 10.1161/CIRCGEN.119.002470

DO - 10.1161/CIRCGEN.119.002470

M3 - Article

C2 - 30896328

SN - 2574-8300

VL - 12

JO - Circulation. Genomic and precision medicine

JF - Circulation. Genomic and precision medicine

IS - 4

M1 - e002470

ER -

Subsequent Event Risk in Individuals With Established Coronary Heart Disease

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