Mahmoodi, Bakhtawar K. and Tragante, Vinicius and Kleber, Marcus E. and Holmes, Michael V. and Schmidt, Amand F. and McCubrey, Raymond O. and Howe, Laurence J. and Direk, Kenan and Allayee, Hooman and Baranova, Ekaterina V. and Braund, Peter S. and Delgado, Graciela E. and Eriksson, Niclas and Gijsberts, Crystel M. and Gong, Yan and Hartiala, Jaana and Heydarpour, Mahyar and Pasterkamp, Gerard and Kotti, Salma and Kuukasjarvi, Pekka and Lenzini, Petra A. and Levin, Daniel and Lyytikainen, Leo-Pekka and Muehlschlegel, Jochen D. and Nelson, Christopher P. and Nikus, Kjell and Pilbrow, Anna P. and Wilson Tang, W. H. and van der Laan, Sander W. and van Setten, Jessica and Vilmundarson, Ragnar O. and Deanfield, John and Deloukas, Panos and Dudbridge, Frank and James, Stefan and Mordi, Ify R. and Teren, Andrej and Bergmeijer, Thomas O. and Body, Simon C. and Bots, Michiel and Burkhardt, Ralph and Cooper-DeHoff, Rhonda M. and Cresci, Sharon and Danchin, Nicolas and Doughty, Robert N. and Grobbee, Diederick E. and Hagstrom, Emil and Hazen, Stanley L. and Held, Claes and Hoefer, Imo E. and Hovingh, G. Kees and Johnson, Julie A. and Kaczor, Marcin P. and Kahonen, Mika and Klungel, Olaf H. and Laurikka, Jari O. and Lehtimaki, Terho and van der Zee, Anke H. and McPherson, Ruth and Palmer, Colin N. and Kraaijeveld, Adriaan O. and Pepine, Carl J. and Sanak, Marek and Sattar, Naveed and Scholz, Markus and Simon, Tabassome and Spertus, John A. and Stewart, Alexandre F. R. and Szczeklik, Wojciech and Thiery, Joachim and Visseren, Frank L. J. and Waltenberger, Johannes and Richards, A. Mark and Lang, Chim C. and Cameron, Vicky A. and akerblom, Axel and Pare, Guillaume and Maerz, Winfried and Samani, Nilesh J. and Hingorani, Aroon D. and ten Berg, Jurrien M. and Wallentin, Lars and Asselbergs, Folkert W. and Patel, Riyaz S. (2020) Association of Factor V Leiden With Subsequent Atherothrombotic Events A GENIUS-CHD Study of Individual Participant Data. CIRCULATION, 142 (6). pp. 546-555. ISSN 0009-7322, 1524-4539
Full text not available from this repository. (Request a copy)Abstract
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];I-2=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 were also close to identity. Conclusions: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CARDIOVASCULAR RISK-FACTORS; BASE-LINE CHARACTERISTICS; CORONARY-ARTERY-DISEASE; COAGULATION-FACTOR-V; MYOCARDIAL-INFARCTION; VENOUS THROMBOEMBOLISM; PROTEIN-C; DESIGN; METAANALYSIS; CLOPIDOGREL; coronary artery disease; genetic association studies; thrombosis; prognosis; single nucleotide polymorphism; myocardial infarction; secondary prevention |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Mar 2021 08:36 |
| Last Modified: | 16 Mar 2021 08:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44029 |
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