Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data
| Autor: | Bakhtawar K. Mahmoodi, W.H. Wilson Tang, Frank Dudbridge, Marcus E. Kleber, Ify R. Mordi, Naveed Sattar, Chim C. Lang, Tabassome Simon, Ruth McPherson, Aroon D. Hingorani, Nilesh J. Samani, Imo E. Hoefer, Crystel M. Gijsberts, Winfried März, Michael V. Holmes, Frank L.J. Visseren, Panos Deloukas, Johannes Waltenberger, Claes Held, Alexandre F.R. Stewart, Jaana Hartiala, Anna P. Pilbrow, Kjell Nikus, Guillaume Paré, Ekaterina V Baranova, Nicolas Danchin, Wojciech Szczeklik, Vinicius Tragante, Andrej Teren, Jari Laurikka, Gerard Pasterkamp, Mahyar Heydarpour, Diederick E. Grobbee, Emil Hagström, Kenan Direk, Daniel Levin, Mika Kähönen, Riyaz S. Patel, Hooman Allayee, Yan Gong, A. Mark Richards, Simon C. Body, Michiel L. Bots, Graciela E. Delgado, Rhonda M. Cooper-DeHoff, Thomas O. Bergmeijer, John E. Deanfield, Ragnar O. Vilmundarson, Carl J. Pepine, Julie A. Johnson, Folkert W. Asselbergs, Markus Scholz, Ralph Burkhardt, Pekka Kuukasjärvi, Olaf H. Klungel, Anke H. Maitland-van der Zee, Jochen D. Muehlschlegel, Colin N. A. Palmer, Sander W. van der Laan, Christopher P. Nelson, G. Kees Hovingh, Joachim Thiery, Jessica van Setten, Stefan James, Raymond O McCubrey, Niclas Eriksson, Stanley L. Hazen, Laurence J. Howe, John A. Spertus, Terho Lehtimäki, Salma Kotti, Robert N. Doughty, Vicky A. Cameron, Axel Åkerblom, Marcin P. Kaczor, Peter S. Braund, Petra A. Lenzini, Sharon Cresci, Lars Wallentin, Marek Sanak, Adriaan O. Kraaijeveld, Jurriën M. ten Berg, Amand F. Schmidt, Leo-Pekka Lyytikäinen |
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| Přispěvatelé: | Experimental Vascular Medicine, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Pulmonology, Paediatric Pulmonology, APH - Personalized Medicine |
| Rok vydání: | 2020 |
| Předmět: |
Risk
medicine.medical_specialty Genotype genetic association studies Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] Single-nucleotide polymorphism Coronary Disease 030204 cardiovascular system & hematology Polymorphism Single Nucleotide Article Coronary artery disease 03 medical and health sciences 0302 clinical medicine single nucleotide polymorphism Physiology (medical) Internal medicine medicine Factor V Leiden Humans Genetic Predisposition to Disease 030212 general & internal medicine Myocardial infarction cardiovascular diseases Polymorphism Precision Medicine Factor V/genetics Secondary prevention Clinical Trials as Topic business.industry Individual participant data Coronary Disease/diagnosis Factor V Thrombosis/genetics Thrombosis Single Nucleotide medicine.disease Atherosclerosis Prognosis Coronary heart disease 3. Good health myocardial infarction Cardiology Cardiology and Cardiovascular Medicine business coronary artery disease secondary prevention |
| Zdroj: | Circulation, 142, 6, pp. 546-555 Circulation Circulation, 142(6), 546-555. Lippincott Williams and Wilkins Circulation, 142, 546-555 Circulation, 142(6), 546. Lippincott Williams and Wilkins |
| ISSN: | 0009-7322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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