المؤلفون: HARTIALA, Jaana A, HAN, Yi, JIA, Qiong, HILSER, James R, HUANG, Pin, GUKASYAN, Janet, SCHWARTZMAN, William S, CAI, Zhiheng, BISWAS, Subarna, TREGOUET, David-Alexandre, SMITH, Nicholas L, SELDIN, Marcus, PAN, Calvin, MEHRABIAN, Margarete, LUSIS, Aldons J, BAZELEY, Peter, SUN, Yan V, LIU, Chang, QUYYUMI, Arshed A, SCHOLZ, Markus, THIERY, Joachim, DELGADO, Graciela E, KLEBER, Marcus E, MÄRZ, Winfried, HOWE, Laurence J, ASSELBERGS, Folkert W, VAN VUGT, Marion, VLACHOJANNIS, Georgios J, PATEL, Riyaz S, LYYTIKÄINEN, Leo-Pekka, KÄHÖNEN, Mika, LEHTIMÄKI, Terho, NIEMINEN, Tuomo V M, KUUKASJÄRVI, Pekka, LAURIKKA, Jari O, CHANG, Xuling, HENG, Chew-Kiat, JIANG, Rong, KRAUS, William E, HAUSER, Elizabeth R, FERGUSON, Jane F, REILLY, Muredach P, ITO, Kaoru, KOYAMA, Satoshi, KAMATANI, Yoichiro, KOMURO, Issei, STOLZE, Lindsey K, ROMANOSKI, Casey E, KHAN, Mohammad Daud, TURNER, Adam W, MILLER, Clint L, AHERRAHROU, Redouane, CIVELEK, Mete, MA, Lijiang, BJÖRKEGREN, Johan L M, KUMAR, S Ram, TANG, W H Wilson, HAZEN, Stanley L, ALLAYEE, Hooman

مصطلحات موضوعية: Myocardial infarction, Genetic factors, Genome-wide association study, Meta-analysis, SLC44A3, Sciences du Vivant [q-bio]/Santé publique et épidémiologie

الوصف: While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation. We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro. A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.

العلاقة: https://oskar-bordeaux.fr/handle/20.500.12278/26843Test

الإتاحة: https://doi.org/20.500.12278/26843Test
https://doi.org/10.1093/eurheartj/ehaa1040Test
https://oskar-bordeaux.fr/handle/20.500.12278/26843Test
https://hdl.handle.net/20.500.12278/26843Test

المؤلفون: Patel, Riyaz S., Schmidt, Amand F., Tragante, Vinicius, McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, 1977, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Dube, Marie-Pierre, Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dufresne, Line, Eriksson, Niclas, 1978, Foco, Luisa, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Fitzpatrick, Natalie, Gigante, Bruna, James, Stefan, 1964, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Cheh, Chris Newton, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Bogaty, Peter, de Borst, Gert J., Brenner, Hermann, Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Hagström, Emil, Hazen, Stanley L., Held, Claes, 1956, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., De Jong, Pim A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, 1952, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, 1982, Mahmoodi, Bakhtawar K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Pepinski, Witold, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Note, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Scholz, Markus, Siegbahn, Agneta, 1947, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, ten Berg, Jurrien M., Thanassoulis, George, Thieiy, Joachim, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Van der Harst, Pim, Tardif, Jean-Claude, Sattar, Naveed, Lang, Chim C., Pare, Guillaume, Brophy, James M., Anderson, Jeffrey L., Maerz, Winfried, Wallentin, Lars, 1943, Cameron, Vicky A., Horne, Benjamin D., Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W.

المصدر: Circulation. 12(4)

مصطلحات موضوعية: chromosome, genetic, variation, myocardial infarction, risk factor, secondary prevention

الوصف: BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-383874Test
https://doi.org/10.1161/CIRCGEN.119.002471Test
https://uu.diva-portal.org/smash/get/diva2:1325068/FULLTEXT01.pdfTest

المؤلفون: Patel, Riyaz S., Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael, V, Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, 1977, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina, V, Behloui, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Gradela, Duarte, Nubia E., Dube, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, 1978, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjarvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikainen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan, V, Tanck, Michael W. T., Tang, W. H. Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Anselmi, Chiara Viviani, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engstrom, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, 1964, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A. M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel L., Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A. A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, 1956, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kahonen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, 1952, Lambrechts, Diether, Laurikka, Jari O., Lehtimaki, Terho, Lindholm, Daniel, 1982, Mahmoodi, B. K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, 1947, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F. R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, ten Berg, Jurrien M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L. J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Pare, Guillaume, Horne, Benjamin D., Marz, Winfried, Wallentin, Lars, 1943, Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W.

المصدر: Circulation. 12(4)

مصطلحات موضوعية: coronary artery disease, genetics, myocardial infarction, prognosis, secondary prevention

الوصف: 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.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-383875Test
https://doi.org/10.1161/CIRCGEN.119.002470Test
https://uu.diva-portal.org/smash/get/diva2:1323765/FULLTEXT01.pdfTest

المؤلفون: Mahmoodi, Bakhtawar K., Tragante, Vinicius, Kleber, Marcus E., Holmes, Michael V., Schmidt, Amand F., McCubrey, Raymond O., Howe, Laurence J., Direk, Kenan, Allayee, Hooman, Baranova, Ekaterina V., Braund, Peter S., Delgado, Graciela E., Eriksson, Niclas, Gijsberts, Crystel M., Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Pasterkamp, Gerard, Kotti, Salma, Kuukasjärvi, Pekka, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo-Pekka, Muehlschlegel, Jochen D., Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Tang, W. H. Wilson, van der Laan, Sander W., van Setten, Jessica, Vilmundarson, Ragnar O., Deanfield, John, Deloukas, Panos, Dudbridge, Frank, James, Stefan, Mordi, Ify R., Teren, Andrej, Bergmeijer, Thomas O., Body, Simon C., Bots, Michiel, Burkhardt, Ralph, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, Doughty, Robert N., Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hoefer, Imo E., Hovingh, G. Kees, Johnson, Julie A., Kaczor, Marcin P., Kähönen, Mika, Klungel, Olaf H., Laurikka, Jari O., Lehtimäki, Terho, Maitland-van der Zee, Anke H., McPherson, Ruth, Palmer, Colin N., Kraaijeveld, Adriaan O., Pepine, Carl J., Sanak, Marek, Sattar, Naveed, Scholz, Markus, Simon, Tabassome, Spertus, John A., Stewart, Alexandre F. R., Szczeklik, Wojciech, Thiery, Joachim, Visseren, Frank L. J., Waltenberger, Johannes, Richards, A. Mark, Lang, Chim C., Cameron, Vicky A., Åkerblom, Axel, Pare, Guillaume, März, Winfried, Samani, Nilesh J., Hingorani, Aroon D., Ten Berg, Jurriën M., Wallentin, Lars, Asselbergs, Folkert W., Patel, Riyaz

المصدر: Mahmoodi , B K , Tragante , V , Kleber , M E , Holmes , M V , Schmidt , A F , McCubrey , R O , Howe , L J , Direk , K , Allayee , H , Baranova , E V , Braund , P S , Delgado , G E , Eriksson , N , Gijsberts , C M , Gong , Y , Hartiala , J , Heydarpour , M , Pasterkamp , G , Kotti , S , Kuukasjärvi , P , Lenzini , P A , Levin , D , ....

مصطلحات موضوعية: coronary artery disease, genetic association studies, myocardial infarction, prognosis, secondary prevention, single nucleotide polymorphism, thrombosis, /dk/atira/pure/subjectarea/asjc/2700/2705, name=Cardiology and Cardiovascular Medicine, /dk/atira/pure/subjectarea/asjc/2700/2737, name=Physiology (medical)

الوصف: Background : Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. Methods : We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. Results : The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I2=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality ...

وصف الملف: application/pdf

العلاقة: https://discovery.dundee.ac.uk/en/publications/c61d1aca-90b9-4537-bf9b-63811cfe9165Test

الإتاحة: https://doi.org/10.1161/CIRCULATIONAHA.119.045526Test
https://discovery.dundee.ac.uk/en/publications/c61d1aca-90b9-4537-bf9b-63811cfe9165Test
https://discovery.dundee.ac.uk/ws/files/49338840/GENIUS_CHD_FVL_and_CHD_death_MI_Circulation_R1_v3_final_clean.pdfTest
http://www.scopus.com/inward/record.url?scp=85089358992&partnerID=8YFLogxKTest

المؤلفون: Wang, Meng, Wang, Zeneng, Lee, Yujin, Lai, Heidi T M, de Oliveira Otto, Marcia C, Lemaitre, Rozenn N, Fretts, Amanda, Sotoodehnia, Nona, Budoff, Matthew, DiDonato, Joseph A, McKnight, Barbara, Tang, W H Wilson, Psaty, Bruce M, Siscovick, David S, Hazen, Stanley L, Mozaffarian, Dariush

المصدر: Arterioscler Thromb Vasc Biol ; ISSN:1524-4636 ; Volume:42 ; Issue:9

مصطلحات موضوعية: cardiovascular diseases, microbiome, myocardial infarction, red meat, stroke, trimethylamine N-oxide

الوصف: Effects of animal source foods (ASF) on atherosclerotic cardiovascular disease (ASCVD) and underlying mechanisms remain controversial. We investigated prospective associations of different ASF with incident ASCVD and potential mediation by gut microbiota-generated trimethylamine N-oxide, its L-carnitine-derived intermediates γ-butyrobetaine and crotonobetaine, and traditional ASCVD risk pathways.

العلاقة: https://doi.org/10.1161/ATVBAHA.121.316533Test; https://pubmed.ncbi.nlm.nih.gov/35912635Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420768Test/

الإتاحة: https://doi.org/10.1161/ATVBAHA.121.316533Test
https://pubmed.ncbi.nlm.nih.gov/35912635Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420768Test/

المؤلفون: Schillemans, Tessa, Tragante, Vinicius, Maitusong, Buamina, Gigante, Bruna, Cresci, Sharon, Laguzzi, Federica, Vikström, Max, Richards, Mark, Pilbrow, Anna, Cameron, Vicky, Foco, Luisa, Doughty, Robert N., Kuukasjärvi, Pekka, Allayee, Hooman, Hartiala, Jaana A., Tang, W. H. Wilson, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Laurikka, Jari O., Srinivasan, Sundararajan

المصدر: Frontiers in Physiology; 6/23/2022, Vol. 13, p1-14, 14p

مصطلحات موضوعية: CORONARY disease, PEROXISOME proliferator-activated receptors, MYOCARDIAL infarction, PROPORTIONAL hazards models, CARDIOVASCULAR disease diagnosis, ACUTE coronary syndrome

مستخلص: Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98–1.05 and rs7672915, HR: 0.97, 95% CI 0.94–1.00; rs3755863, HR: 1.02, 95% CI 0.99–1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users. Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline. [ABSTRACT FROM AUTHOR]

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المؤلفون: Patel, Riyaz, Tragante, Vinicius, Schmidt, Amand F., McCubrey, Raymond O., Holmes, Michael V., Howe, Laurence J., Direk, Kenan, Åkerblom, Axel, Leander, Karin, Virani, Salim S., Kaminski, Karol A., Muehlschlegel, Jochen D., Allayee, Hooman, Almgren, Peter, Alver, Maris, Baranova, Ekaterina V., Behlouli, Hassan, Boeckx, Bram, Braund, Peter S., Breitling, Lutz P., Delgado, Graciela, Duarte, Nubia E., Dubé, Marie-Pierre, Dufresne, Line, Eriksson, Niclas, Foco, Luisa, Scholz, Markus, Gijsberts, Crystel M., Glinge, Charlotte, Gong, Yan, Hartiala, Jaana, Heydarpour, Mahyar, Hubacek, Jaroslav A., Kleber, Marcus, Kofink, Daniel, Kotti, Salma, Kuukasjärvi, Pekka, Lee, Vei-Vei, Leiherer, Andreas, Lenzini, Petra A., Levin, Daniel, Lyytikäinen, Leo-Pekka, Martinelli, Nicola, Mons, Ute, Nelson, Christopher P., Nikus, Kjell, Pilbrow, Anna P., Ploski, Rafal, Sun, Yan V., Tanck, Michael W.T., Tang, W H Wilson, Trompet, Stella, van der Laan, Sander W., Van Setten, Jessica, Vilmundarson, Ragnar O., Viviani Anselmi, Chiara, Vlachopoulou, Efthymia, Al Ali, Lawien, Boerwinkle, Eric, Briguori, Carlo, Carlquist, John F., Carruthers, Kathryn F., Casu, Gavino, Deanfield, John, Deloukas, Panos, Dudbridge, Frank, Engström, Thomas, Fitzpatrick, Natalie, Fox, Kim, Gigante, Bruna, James, Stefan, Lokki, Marja-Liisa, Lotufo, Paulo A., Marziliano, Nicola, Mordi, Ify R., Muhlestein, Joseph B., Newton-Cheh, Christopher, Pitha, Jan, Saely, Christoph H., Samman-Tahhan, Ayman, Sandesara, Pratik B., Teren, Andrej, Timmis, Adam, Van de Werf, Frans, Wauters, Els, Wilde, Arthur A.M., Ford, Ian, Stott, David J., Algra, Ale, Andreassi, Maria G., Ardissino, Diego, Arsenault, Benoit J., Ballantyne, Christie M., Bergmeijer, Thomas O., Bezzina, Connie R., Body, Simon C., Boersma, Eric H., Bogaty, Peter, Bots, Michiel, Brenner, Hermann, Brugts, Jasper J., Burkhardt, Ralph, Carpeggiani, Clara, Condorelli, Gianluigi, Cooper-DeHoff, Rhonda M., Cresci, Sharon, Danchin, Nicolas, de Faire, Ulf, Doughty, Robert N., Drexel, Heinz, Engert, James C., Fox, Keith A.A., Girelli, Domenico, Grobbee, Diederick E., Hagström, Emil, Hazen, Stanley L., Held, Claes, Hemingway, Harry, Hoefer, Imo E., Hovingh, G. Kees, Jabbari, Reza, Johnson, Julie A., Jukema, J. Wouter, Kaczor, Marcin P., Kähönen, Mika, Kettner, Jiri, Kiliszek, Marek, Klungel, Olaf H., Lagerqvist, Bo, Lambrechts, Diether, Laurikka, Jari O., Lehtimäki, Terho, Lindholm, Daniel, Mahmoodi, B.K., Maitland-van der Zee, Anke H., McPherson, Ruth, Melander, Olle, Metspalu, Andres, Niemcunowicz-Janica, Anna, Olivieri, Oliviero, Opolski, Grzegorz, Palmer, Colin N., Pasterkamp, Gerard, Pepine, Carl J., Pereira, Alexandre C., Pilote, Louise, Quyyumi, Arshed A., Richards, A. Mark, Sanak, Marek, Siegbahn, Agneta, Simon, Tabassome, Sinisalo, Juha, Smith, J. Gustav, Spertus, John A., Stender, Steen, Stewart, Alexandre F.R., Szczeklik, Wojciech, Szpakowicz, Anna, Tardif, Jean-Claude, Ten Berg, Jurriën M., Tfelt-Hansen, Jacob, Thanassoulis, George, Thiery, Joachim, Torp-Pedersen, Christian, van der Graaf, Yolanda, Visseren, Frank L.J., Waltenberger, Johannes, Weeke, Peter E., Van der Harst, Pim, Lang, Chim C., Sattar, Naveed, Cameron, Vicky A., Anderson, Jeffrey L., Brophy, James M., Paré, Guillaume, Horne, Benjamin D., März, Winfried, Wallentin, Lars, Samani, Nilesh J., Hingorani, Aroon D., Asselbergs, Folkert W.

المساهمون: Cardiovascular Centre (CVC)

المصدر: Circulation: Genomic and Precision Medicine, 12(4). LIPPINCOTT WILLIAMS & WILKINS
Circulation. Genomic and precision medicine, 12(4):002470. LIPPINCOTT WILLIAMS & WILKINS
Patel, R, 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, Behlouli, H, Boeckx, B, Braund, P S, Breitling, L P, Delgado, G, Duarte, N E, Dubé, M-P, Dufresne, L, Eriksson, N, Foco, L, Scholz, M, Gijsberts, C M, Glinge, C, Gong, Y, Hartiala, J, Heydarpour, M, Hubacek, J A, Kleber, M, Kofink, D, Kotti, S, Kuukasjärvi, P, Lee, V-V, Leiherer, A, Lenzini, P A, Levin, D, Lyytikäinen, L-P, Martinelli, N, Mons, U, Nelson, C P, Nikus, K, Pilbrow, A P, Ploski, R, Sun, Y V, Tanck, M W T, Tang, W H W, Trompet, S, van der Laan, S W, Van Setten, J, Vilmundarson, R O, Viviani Anselmi, C, Vlachopoulou, E, Al Ali, L, Boerwinkle, E, Briguori, C, Carlquist, J F, Carruthers, K F, Casu, G, Deanfield, J, Deloukas, P, Dudbridge, F, Engström, T, Fitzpatrick, N, Fox, K, Gigante, B, James, S, Lokki, M-L, Lotufo, P A, Marziliano, N, Mordi, I R, Muhlestein, J B, Newton-Cheh, C, Pitha, J, Saely, C H, Samman-Tahhan, A, Sandesara, P B, Teren, A, Timmis, A, Van de Werf, F, Wauters, E, Wilde, A A M, Ford, I, Stott, D J, Algra, A, Andreassi, M G, Ardissino, D, Arsenault, B J, Ballantyne, C M, Bergmeijer, T O, Bezzina, C R, Body, S C, Boersma, E H, Bogaty, P, Bots, M, Brenner, H, Brugts, J J, Burkhardt, R, Carpeggiani, C, Condorelli, G, Cooper-DeHoff, R M, Cresci, S, Danchin, N, de Faire, U, Doughty, R N, Drexel, H, Engert, J C, Fox, K A A, Girelli, D, Grobbee, D E, Hagström, E, Hazen, S L, Held, C, Hemingway, H, Hoefer, I E, Hovingh, G K, Jabbari, R, Johnson, J A, Jukema, J W, Kaczor, M P, Kähönen, M, Kettner, J, Kiliszek, M, Klungel, O H, Lagerqvist, B, Lambrechts, D, Laurikka, J O, Lehtimäki, T, Lindholm, D, Mahmoodi, B K, Maitland-van der Zee, A H, McPherson, R, Melander, O, Metspalu, A, Niemcunowicz-Janica, A, Olivieri, O, Opolski, G, Palmer, C N, Pasterkamp, G, Pepine, C J, Pereira, A C, Pilote, L, Quyyumi, A A, Richards, A M, Sanak, M, Siegbahn, A, Simon, T, Sinisalo, J, Smith, J G, Spertus, J A, Stender, S, Stewart, A F R, Szczeklik, W, Szpakowicz, A, Tardif, J-C, Ten Berg, J M, Tfelt-Hansen, J, Thanassoulis, G, Thiery, J, Torp-Pedersen, C, van der Graaf, Y, Visseren, F L J, Waltenberger, J, Weeke, P E, Van der Harst, P, Lang, C C, Sattar, N, Cameron, V A, Anderson, J L, Brophy, J M, Paré, G, Horne, B D, März, W, Wallentin, L, Samani, N J, Hingorani, A D & Asselbergs, F W 2019, ' Subsequent Event Risk in Individuals with Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium ', Circulation. Genomic and precision medicine, vol. 12, no. 4, e002470, pp. 145-160 . https://doi.org/10.1161/CIRCGEN.119.002470Test
Patel, R, 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, Behlouli, H, Boeckx, B, Braund, P S, Breitling, L P, Delgado, G, Duarte, N E, Dubé, M-P, Dufresne, L, Eriksson, N, Foco, L, Scholz, M, Gijsberts, C M, Glinge, C, Gong, Y, Hartiala, J, Heydarpour, M, Hubacek, J A, Kleber, M, Kofink, D, Kotti, S, Kuukasjärvi, P, Lee, V-V, Leiherer, A, Lenzini, P A, Levin, D, Lyytikäinen, L-P, Martinelli, N, Mons, U, Nelson, C P, Nikus, K, Pilbrow, A P, Ploski, R, Sun, Y V, Tanck, M W T, Tang, W H W, Trompet, S, van der Laan, S W, Van Setten, J, Vilmundarson, R O, Viviani Anselmi, C, Vlachopoulou, E, Al Ali, L, Boerwinkle, E, Briguori, C, Carlquist, J F, Carruthers, K F, Casu, G, Deanfield, J, Deloukas, P, Dudbridge, F, Engström, T, Fitzpatrick, N, Fox, K, Gigante, B, James, S, Lokki, M-L, Lotufo, P A, Marziliano, N, Mordi, I R, Muhlestein, J B, Newton-Cheh, C, Pitha, J, Saely, C H, Samman-Tahhan, A, Sandesara, P B, Teren, A, Timmis, A, Van de Werf, F, Wauters, E, Wilde, A A M, Ford, I, Stott, D J, Algra, A, Andreassi, M G, Ardissino, D, Arsenault, B J, Ballantyne, C M, Bergmeijer, T O, Bezzina, C R, Body, S C, Boersma, E H, Bogaty, P, Bots, M, Brenner, H, Brugts, J J, Burkhardt, R, Carpeggiani, C, Condorelli, G, Cooper-DeHoff, R M, Cresci, S, Danchin, N, de Faire, U, Doughty, R N, Drexel, H, Engert, J C, Fox, K A A, Girelli, D, Grobbee, D E, Hagström, E, Hazen, S L, Held, C, Hemingway, H, Hoefer, I E, Hovingh, G K, Jabbari, R, Johnson, J A, Jukema, J W, Kaczor, M P, Kähönen, M, Kettner, J, Kiliszek, M, Klungel, O H, Lagerqvist, B, Lambrechts, D, Laurikka, J O, Lehtimäki, T, Lindholm, D, Mahmoodi, B K, Maitland-van der Zee, A H, McPherson, R, Melander, O, Metspalu, A, Niemcunowicz-Janica, A, Olivieri, O, Opolski, G, Palmer, C N, Pasterkamp, G, Pepine, C J, Pereira, A C, Pilote, L, Quyyumi, A A, Richards, A M, Sanak, M, Siegbahn, A, Simon, T, Sinisalo, J, Smith, J G, Spertus, J A, Stender, S, Stewart, A F R, Szczeklik, W, Szpakowicz, A, Tardif, J-C, Ten Berg, J M, Tfelt-Hansen, J, Thanassoulis, G, Thiery, J, Torp-Pedersen, C, van der Graaf, Y, Visseren, F L J, Waltenberger, J, Weeke, P E, Van der Harst, P, Lang, C C, Sattar, N, Cameron, V A, Anderson, J L, Brophy, J M, Paré, G, Horne, B D, März, W, Wallentin, L, Samani, N J, Hingorani, A D & Asselbergs, F W 2019, ' Subsequent Event Risk in Individuals with Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium ', CIRCULATION-GENOMIC AND PRECISION MEDICINE, vol. 12, no. 4, pp. 145-160 . https://doi.org/10.1161/CIRCGEN.119.002470Test
Circulation. Genomic and precision medicine, 12(4). Lippincott Williams and Wilkins Ltd.

مصطلحات موضوعية: Adult, Male, Cardiac & Cardiovascular Systems, CARDIOVASCULAR MORTALITY, Coronary Disease, BIOBANK, Article, Sex Factors, Risk Factors, Journal Article, Humans, ARTERY-DISEASE, Cardiac and Cardiovascular Systems, genetics, Aged, Proportional Hazards Models, Genetics & Heredity, Kardiologi, Science & Technology, Smoking, Age Factors, Middle Aged, BODY-MASS INDEX, myocardial infarction, MYOCARDIAL-INFARCTION, PUBLIC-HEALTH, Cardiovascular System & Cardiology, Female, prognosis, Life Sciences & Biomedicine, coronary artery disease, secondary prevention

الوصف: 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. ispartof: CIRCULATION-GENOMIC AND PRECISION MEDICINE vol:12 issue:4 ispartof: location:United States status: published

وصف الملف: Print-Electronic; image/pdf; application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::9b2445bbb0c14f93c127d62c7bc86af0Test
https://lirias.kuleuven.be/handle/123456789/654755Test

المؤلفون: Do, Ron, Stitziel, Nathan O, Won, Hong Hee, Jørgensen, Anders Berg, Duga, Stefano, Angelica Merlini, Pier, Kiezun, Adam, Farrall, Martin, Goel, Anuj, Zuk, Or, Guella, Illaria, Asselta, Rosanna, Lange, Leslie A, Peloso, Gina M, Auer, Paul L, Farlow, Deborah N, Depristo, Mark A, Roberts, Robert, Stewart, Alexander F. R, Saleheen, Danish, Danesh, John, Epstein, Stephen E, Sivapalaratnam, Suthesh, Hovingh, G. Kees, Kastelein, John J, Samani, Nilesh J, Schunkert, Heribert, Erdmann, Jeanette, Shah, Svati H, Kraus, William E, Davies, Robert, Nikpay, Majid, Johansen, Christopher T, Wang, Jian, Hegele, Robert A, Hechter, Eliana, Marz, Winfried, Kleber, Marcus E, Huang, Jie, Johnson, Andrew D, Li, Mingyao, Burke, Greg L, Gross, Myron, Liu, Yongmei, Assimes, Themistocles L, Heiss, Gerardo, Lange, Ethan M, Folsom, Aaron R, Taylor, Herman A, Hamsten, Anders, Clarke, Robert, Reilly, Dermot F, Yin, Wu, Rivas, Manuel A, Donnelly, Peter, Rossouw, Jacques E, Psaty, Bruce M, Herrington, David M, Wilson, James G, Rich, Stephen S, Bamshad, Michael J, Tracy, Russell P, Cupples, L. Adrienne, Rader, Daniel J, Reilly, Muredach P, Spertus, John A, Cresci, Sharon, Hartiala, Jaana, Tang, W. H. Wilson, Hazen, Stanley L, Allayee, Hooman, Reiner, Alex P, Carlson, Christopher S, Kooperberg, Charles, Jackson, Rebecca D, Boerwinkle, Eric, Lander, Eric S, Schwartz, Stephen M, Siscovick, David S, Mcpherson, Ruth, Tybjaerg Hansen, Anne, Abecasis, Goncalo R, Watkins, Hugh, Nickerson, Deborah A, Ardissino, Diego, Sunyaev, Shamil R, O'Donnell, Christopher J, Altshuler, David, Gabriel, Stacey, Kathiresan, Sekar, GIRELLI, Domenico, MARTINELLI, Nicola, OLIVIERI, Oliviero

المساهمون: Do, Ron, Stitziel, Nathan O, Won, Hong Hee, Jørgensen, Anders Berg, Duga, Stefano, Angelica Merlini, Pier, Kiezun, Adam, Farrall, Martin, Goel, Anuj, Zuk, Or, Guella, Illaria, Asselta, Rosanna, Lange, Leslie A, Peloso, Gina M, Auer, Paul L, Girelli, Domenico, Martinelli, Nicola, Farlow, Deborah N, Depristo, Mark A, Roberts, Robert, Stewart, Alexander F. R, Saleheen, Danish, Danesh, John, Epstein, Stephen E, Sivapalaratnam, Suthesh, Hovingh, G. Kee, Kastelein, John J, Samani, Nilesh J, Schunkert, Heribert, Erdmann, Jeanette, Shah, Svati H, Kraus, William E, Davies, Robert, Nikpay, Majid, Johansen, Christopher T, Wang, Jian, Hegele, Robert A, Hechter, Eliana, Marz, Winfried, Kleber, Marcus E, Huang, Jie, Johnson, Andrew D, Li, Mingyao, Burke, Greg L, Gross, Myron, Liu, Yongmei, Assimes, Themistocles L, Heiss, Gerardo, Lange, Ethan M, Folsom, Aaron R, Taylor, Herman A, Olivieri, Oliviero, Hamsten, Ander, Clarke, Robert, Reilly, Dermot F, Yin, Wu, Rivas, Manuel A, Donnelly, Peter, Rossouw, Jacques E, Psaty, Bruce M, Herrington, David M, Wilson, James G, Rich, Stephen S, Bamshad, Michael J, Tracy, Russell P, Cupples, L. Adrienne, Rader, Daniel J, Reilly, Muredach P, Spertus, John A, Cresci, Sharon, Hartiala, Jaana, Tang, W. H. Wilson, Hazen, Stanley L, Allayee, Hooman, Reiner, Alex P, Carlson, Christopher S, Kooperberg, Charle, Jackson, Rebecca D, Boerwinkle, Eric, Lander, Eric S, Schwartz, Stephen M, Siscovick, David S, Mcpherson, Ruth, Tybjaerg Hansen, Anne, Abecasis, Goncalo R, Watkins, Hugh, Nickerson, Deborah A, Ardissino, Diego, Sunyaev, Shamil R, O'Donnell, Christopher J, Altshuler, David, Gabriel, Stacey, Kathiresan, Sekar

مصطلحات موضوعية: exome sequencing, LDL receptor, apolipoprotein A5, myocardial infarction

الوصف: Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (≤50 years in males and ≤60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl(-1). At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/25487149; info:eu-repo/semantics/altIdentifier/wos/WOS:000349098000040; volume:518; issue:7537; firstpage:102-6; lastpage:106; numberofpages:5; journal:NATURE; http://hdl.handle.net/11562/951638Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84923082408

الإتاحة: https://doi.org/10.1038/nature13917Test
http://hdl.handle.net/11562/951638Test

المؤلفون: Gurm, Hitinder S, Lincoff, A Michael, Lee, David, Tang, W H Wilson, Jia, Gang, Booth, Joan E, Califf, Robert M, Ohman, E M, Van de Werf, Frans, Armstrong, Paul W, Guetta, Victor, Wilcox, Robert, Topol, Eric J

مصطلحات موضوعية: Antibodies, Monoclonal, Case-Control Studies, Diabetes Complications, Drug Therapy, Combination, Electrocardiography, Female, Fibrinolytic Agents, Humans, Immunoglobulin Fab Fragments, Male, Middle Aged, Myocardial Infarction, Platelet Aggregation Inhibitors, Platelet Glycoprotein GPIIb-IIIa Complex, Recombinant Proteins, Retrospective Studies, Tissue Plasminogen Activator

الوصف: OBJECTIVES: We studied the outcome of diabetics enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) V trial to assess whether the combination of half-dose reteplase and abciximab provides any propitious benefits over standard fibrinolytic therapy in diabetic patients. BACKGROUND: Diabetics with acute ST-segment elevation myocardial infarction (MI) have a worse outcome compared with nondiabetics. Higher-risk patients are usually more likely to benefit from advances in medical therapy. METHODS: We analyzed diabetic patients enrolled in the GUSTO V trial to assess the outcome of those randomized to the combination of half-dose reteplase and abciximab versus those randomized to reteplase. We also evaluated whether any differences existed in presentation and outcome of MI among the diabetics versus the nondiabetics enrolled in the study. RESULTS: The trial enrolled 13782 nondiabetics and 2633 diabetics. Compared to nondiabetics, diabetics had a significantly higher mortality at 30 days (8.5% vs. 5.1%, p < 0.001) and at 1 year (12.7% vs. 7.5%, p < 0.001). Among the diabetic subset, no significant difference existed in the incidence of 30-day (8.8% vs. 8.2%, p = 0.52) or 1-year mortality (13.0% vs. 12.4%, p = 0.62) among patients randomized to reteplase compared to those receiving combination of abciximab and reteplase. The incidence of reinfarction (2.5% vs. 4.3%, p = 0.013), recurrent ischemia (11.8% vs. 14.9%, p = 0.017), and urgent revascularization (10.9% vs. 13.3%, p = 0.055) at seven days was lower in diabetics treated with the combination therapy. CONCLUSIONS: Compared to nondiabetics, diabetics continue to have a worse outcome with MI. Although combination therapy did not provide a survival benefit, nonfatal ischemic outcomes, including reinfarction, recurrent ischemia, and urgent revascularization, were substantially reduced. ; status: published

العلاقة: Journal of the American College of Cardiology vol:43 issue:4 pages:542-8; https://lirias.kuleuven.be/handle/123456789/24380Test; http://linkinghub.elsevier.com/retrieve/pii/S0735109703015365Test

الإتاحة: https://lirias.kuleuven.be/handle/123456789/24380Test
http://linkinghub.elsevier.com/retrieve/pii/S0735109703015365Test

المؤلفون: Wang, Zeneng, Tang, W. H. Wilson, Buffa, Jennifer A., Fu, Xiaoming, Britt, Earl B., Koeth, Robert A., Levison, Bruce S., Fan, Yiying, Wu, Yuping, Hazen, Stanley L.

المصدر: European Heart Journal; Apr2014, Vol. 35 Issue 14, p904-910, 7p, 2 Charts, 6 Graphs

مستخلص: Aims Recent metabolomics and animal model studies show trimethylamine-N-oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietary trimethylamine-containing nutrients such as phosphatidylcholine (PC), choline, and carnitine, is linked to coronary artery disease pathogenesis. Our aim was to examine the prognostic value of systemic choline and betaine levels in stable cardiac patients. Methods and results We examined the relationship between fasting plasma choline and betaine levels and risk of major adverse cardiac events (MACE = death, myocardial infraction, stroke) in relation to TMAO over 3 years of follow-up in 3903 sequential stable subjects undergoing elective diagnostic coronary angiography. In our study cohort, median (IQR) TMAO, choline, and betaine levels were 3.7 (2.4–6.2)μM, 9.8 (7.9–12.2)μM, and 41.1 (32.5–52.1)μM, respectively. Modest but statistically significant correlations were noted between TMAO and choline (r = 0.33, P < 0.001) and less between TMAO and betaine (r = 0.09, P < 0.001). Higher plasma choline and betaine levels were associated with a 1.9-fold and 1.4-fold increased risk of MACE, respectively (Quartiles 4 vs. 1; P < 0.01, each). Following adjustments for traditional cardiovascular risk factors and high-sensitivity C-reactive protein, elevated choline [1.34 (1.03–1.74), P < 0.05], and betaine levels [1.33 (1.03–1.73), P < 0.05] each predicted increased MACE risk. Neither choline nor betaine predicted MACE risk when TMAO was added to the adjustment model, and choline and betaine predicted future risk for MACE only when TMAO was elevated. Conclusion Elevated plasma levels of choline and betaine are each associated with incident MACE risk independent of traditional risk factors. However, high choline and betaine levels are only associated with higher risk of future MACE with concomitant increase in TMAO. [ABSTRACT FROM PUBLISHER]

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