Association of Factor V Leiden With Subsequent Atherothrombotic Events-Reference-Cited by-同舟云学术

Association of Factor V Leiden With Subsequent Atherothrombotic Events

Published:2020-08-11 Issue:6 Volume:142 Page:546-555
ISSN:0009-7322
Container-title:Circulation
language:en
Short-container-title:Circulation

Author:

Mahmoodi Bakhtawar K.¹²,Tragante Vinicius³,Kleber Marcus E.⁴,Holmes Michael V.⁵⁶,Schmidt Amand F.³⁷,McCubrey Raymond O.⁸,Howe Laurence J.⁷,Direk Kenan⁷,Allayee Hooman⁹,Baranova Ekaterina V.¹⁰,Braund Peter S.¹¹¹²,Delgado Graciela E.⁴,Eriksson Niclas¹³,Gijsberts Crystel M.¹⁴,Gong Yan¹⁵,Hartiala Jaana⁹¹⁶^ORCID,Heydarpour Mahyar¹⁷¹⁸,Pasterkamp Gerard¹⁹,Kotti Salma²⁰,Kuukasjärvi Pekka²¹,Lenzini Petra A.²²,Levin Daniel²³,Lyytikäinen Leo-Pekka²⁴²⁵,Muehlschlegel Jochen D.¹⁷¹⁸^ORCID,Nelson Christopher P.¹⁴¹¹,Nikus Kjell²⁶²⁷^ORCID,Pilbrow Anna P.²⁸^ORCID,Wilson Tang W.H.²⁹³⁰^ORCID,van der Laan Sander W.³¹^ORCID,van Setten Jessica³,Vilmundarson Ragnar O.³²,Deanfield John⁷,Deloukas Panos³³^ORCID,Dudbridge Frank³⁴,James Stefan¹³³⁵,Mordi Ify R²³^ORCID,Teren Andrej³⁶³⁷,Bergmeijer Thomas O.¹,Body Simon C.³⁸,Bots Michiel³⁹⁴⁰,Burkhardt Ralph³⁷,Cooper-DeHoff Rhonda M.¹⁵⁴¹,Cresci Sharon²²⁴²,Danchin Nicolas⁴³^ORCID,Doughty Robert N.⁴⁴,Grobbee Diederick E.³⁹,Hagström Emil³⁵⁴⁵,Hazen Stanley L.²⁹⁴⁶^ORCID,Held Claes¹³³⁵,Hoefer Imo E.⁴⁷,Hovingh G. Kees⁴⁸,Johnson Julie A.¹⁵⁴¹,Kaczor Marcin P.⁴⁹,Kähönen Mika⁵⁰⁵¹,Klungel Olaf H.¹⁰,Laurikka Jari O.²¹⁵²,Lehtimäki Terho²⁴²⁵,Maitland-van der Zee Anke H.¹⁰⁵³,McPherson Ruth⁵⁴^ORCID,Palmer Colin N.⁵⁵^ORCID,Kraaijeveld Adriaan O.³,Pepine Carl J.⁴¹^ORCID,Sanak Marek⁴⁹,Sattar Naveed⁵⁶^ORCID,Scholz Markus³⁷⁵⁷,Simon Tabassome⁵⁸⁵⁹,Spertus John A.⁶⁰⁶¹,Stewart Alexandre F.R.³²⁵⁴^ORCID,Szczeklik Wojciech⁴⁹,Thiery Joachim³⁷⁶²,Visseren Frank L.J.⁶³,Waltenberger Johannes⁶⁴^ORCID,Richards A. Mark²⁸⁶⁵,Lang Chim C.²³,Cameron Vicky A.²⁸,Åkerblom Axel¹³³⁵,Pare Guillaume⁶⁶⁶⁷^ORCID,März Winfried⁴⁶⁸⁶⁹,Samani Nilesh J.¹¹¹²^ORCID,Hingorani Aroon D.⁷,ten Berg Jurriën M.¹,Wallentin Lars¹³,Asselbergs Folkert W.³⁷⁷⁰^ORCID,Patel Riyaz S.⁷⁷¹

Affiliation:

1. St. Antonius Hospital, Department of Cardiology, Nieuwegein, the Netherlands (B.K.M., T.O.B., J.M.t.B.).

2. Division of Hemostasis and Thrombosis, Department of Hematology, UMC Groningen, University of Groningen, The Netherlands (B.K.M.).

3. Department of Cardiology, Division Heart and Lungs (V.T., A.F.S., J.v.S., A.O.K., F.W.A.), UMC Utrecht, Utrecht University, the Netherlands.

4. Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Germany (M.E.K., G.E.D., W.M.).

5. Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health and Medical Research Council Population Health Research Unit, University of Oxford, United Kingdom (M.V.H.).

6. National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital, United Kingdom (M.V.H.).

7. Institute of Cardiovascular Science and UCL BHF Research Accelerator, Faculty of Population Health Science, University College London, United Kingdom (A.F.S., L.J.H., K.D., J.D., A.D.H., F.W.A., R.S.P.).

8. Intermountain Heart Institute, Intermountain Medical Center, Salt Lake City, UT (R.O.McC.).

9. Departments of Preventive Medicine and Biochemistry and Molecular Medicine (H.A., J.H.), Keck School of Medicine of University of Southern California, Los Angeles.

10. Division of Pharmacoepidemiology and Clinical Pharmacology (E.V.B., O.H.K., A.H.M.-v.d.Z.), UMC Utrecht, Utrecht University, the Netherlands.

11. Department of Cardiovascular Sciences, University of Leicester, BHF Cardiovascular Research Centre, Glenfield Hospital, United Kingdom (P.S.B., C.P.N., N.J.S.).

12. NIHR Leicester Biomedical Research Centre, Glenfield Hospital, United Kingdom (P.S.B., C.P.N., N.J.S.).

13. Uppsala Clinical Research Center, Sweden (N.E., S.J., C.H., A.Å., L.W.).

14. Laboratory of Experimental Cardiology (C.M.G.), UMC Utrecht, Utrecht University, the Netherlands.

15. Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., R.M.C.-D.H., J.A.J.), University of Florida, Gainesville.

16. Institute for Genetic Medicine (J.H.), Keck School of Medicine of University of Southern California, Los Angeles.

17. Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA (M.H., J.D.M.).

18. Harvard Medical School, Harvard University, Boston, MA (M.H., J.D.M.).

19. Department of Clinical Chemistry (G.Pasterkamp), UMC Utrecht, Utrecht University, the Netherlands.

20. Assistance Publique-Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, Platform of Clinical Research of East Paris (URCEST-CRCEST-CRB HUEP-UPMC), France (S.K.).

21. Departments of Cardio-Thoracic Surgery (P.K., J.O.L.), Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Techonology, Tampere University, Finland.

22. Department of Genetics, Statistical Genomics Division (P.A.L., S.C.), Washington University School of Medicine, Saint Louis, MO.

23. Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Scotland, United Kingdom (D.L., I.R.M., C.C.L.).

24. Clinical Chemistry (L.-P.L., T.L.), Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Techonology, Tampere University, Finland.

25. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland (L.-P.L., T.L.).

26. Cardiology (K.N.), Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Techonology, Tampere University, Finland.

27. Department of Cardiology (K.N.), Heart Center, Tampere University Hospital, Finland.

28. The Christchurch Heart Institute, University of Otago Christchurch, New Zealand (A.P.P., A.M.R., V.A.C.).

29. Department of Cardiovascular and Metabolic Sciences, Lerner Research institute (W.H.W.T., S.L.H.), Cleveland Clinic, OH.

30. Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T.), Cleveland Clinic, OH.

31. Central Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics (S.W.v.d.L.), UMC Utrecht, Utrecht University, the Netherlands.

32. Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ontario, Canada (R.O.V., A.F.R.S.).

33. William Harvey Research Institute, Barts and the London Medical School, and the Centre for Genomic Health, Queen Mary University of London, United Kingdom (P.D.).

34. Department of Health Sciences, University of Leicester, United Kingdom (F.D.).

35. Department of Medical Sciences, Cardiology, Uppsala University, Sweden (S.J., E.H., C.H., A.Å., L.W.).

36. Heart Center Leipzig, Germany (A.T.).

37. LIFE Research Center for Civilization Diseases (A.T., R.B., M.Scholz, J.T.), University of Leipzig, Germany.

38. Department of Anesthesiology, Boston University School of Medicine, MA (S.C.B.).

39. Julius Center for Health Sciences and Primary Care (M.B., D.E.G.), UMC Utrecht, Utrecht University, the Netherlands.

40. Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Germany (R.B.).

41. College of Medicine, Division of Cardiovascular Medicine (R.M.C.-D.H., J.A.J., C.J.P.), University of Florida, Gainesville.

42. Department of Medicine, Cardiovascular Division (S.C.), Washington University School of Medicine, Saint Louis, MO.

43. Assistance Publique-Hôpitaux de Paris (APHP), Department of Cardiology, Hôpital Européen Georges Pompidou; FACT (french Alliance for cardiovascular trials); and Université Paris Descartes, France (N.D.).

44. Heart Health Research Group, University of Auckland, New Zealand (R.N.D.).

45. Department of Cardiology, Uppsala University, and Uppsala Clinical Research Center, Sweden (E.H.).

46. Center for Microbiome and Human Health (S.L.H.), Cleveland Clinic, OH.

47. Department of Clinical Chemistry and Hematology (I.E.H.), UMC Utrecht, Utrecht University, the Netherlands.

48. Department of Vascular Medicine (G.K.H.), Academic Medical Center, University of Amsterdam, The Netherlands.

49. Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland (M.P.K., M.Sanak, W.S.).

50. Clinical Physiology (M.K.), Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Techonology, Tampere University, Finland.

51. Department of Clinical Physiology, Tampere University Hospital, Finland (M.K.).

52. Department of Cardio-Thoracic Surgery (J.O.L.), Heart Center, Tampere University Hospital, Finland.

53. Department of Respiratory Medicine (A.H.M.-v.d.Z.), Academic Medical Center, University of Amsterdam, The Netherlands.

54. Departments of Medicine and Biochemistry, Microbiology, and Immunology, University of Ottawa, Ontario, Canada (R.McP. R.O.V., A.F.R.S.).

55. Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, Dundee, United Kingdom (C.N.P.).

56. Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (N.S.).

57. Institute for Medical Informatics, Statistics, and Epidemiology (M.Scholz), University of Leipzig, Germany.

58. Assistance Publique-Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, Platform of Clinical Research of East Paris (URCEST-CRCEST-CRB HUEP-UPMC), FACT (French Alliance for Cardiovascular trials); Sorbonne Université, Paris-06, France (T.S.).

59. Paris-Sorbonne University, UPMC-Site St Antoine, France (T.S.).

60. University of Missouri-Kansas City (J.A.S.).

61. Saint Luke’s Mid America Heart Institute, Kansas City, MO (J.A.S.).

62. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital, Leipzig, Germany (J.T.).

63. Department of Vascular Medicine (F.L.J.V.), UMC Utrecht, Utrecht University, the Netherlands.

64. Department of Cardiovascular Medicine, University of Münster, Germany (J.W.).

65. Cardiovascular Research Institute, National University of Singapore (A.M.R.).

66. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada (G.Pare).

67. Population Health Research Institute, Hamilton, Ontario, Canada (G.Pare).

68. Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany (W.M.).

69. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria (W.M.).

70. Health Data Research UK and Institute of Health Informatics, University College London, United Kingdom (F.W.A.).

71. Bart’s Heart Centre, St Bartholomew’s Hospital, London, United Kingdom (R.S.P.).

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

Reference51 articles.

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2. Ethnic Distribution of Factor V Leiden in 4047 Men and Women

3. Risk of venous thromboembolism associated with single and combined effects of Factor V Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls

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