Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.
coronary artery disease
genetic association studies
myocardial infarction
prognosis
secondary prevention
single nucleotide polymorphism
thrombosis
Journal
Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763
Informations de publication
Date de publication:
11 08 2020
11 08 2020
Historique:
pubmed:
14
7
2020
medline:
4
9
2021
entrez:
14
7
2020
Statut:
ppublish
Résumé
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. 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. 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]; 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.
Sections du résumé
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];
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.
Identifiants
pubmed: 32654539
doi: 10.1161/CIRCULATIONAHA.119.045526
pmc: PMC7493828
mid: NIHMS1610813
doi:
Substances chimiques
factor V Leiden
0
Factor V
9001-24-5
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
546-555Subventions
Organisme : Medical Research Council
ID : G0601354
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK106000
Pays : United States
Organisme : NIMHD NIH HHS
ID : R01 MD010358
Pays : United States
Organisme : NIGMS NIH HHS
ID : U01 GM074492
Pays : United States
Organisme : Wellcome Trust
ID : 084726/Z/08/Z
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL126827
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL076491
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133169
Pays : United States
Organisme : Wellcome Trust
ID : 084727/Z/08/Z
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : P01 HL098055
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 072960/Z/03/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 085475/Z/08/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K013351/1
Pays : United Kingdom
Organisme : NIEHS NIH HHS
ID : R01 ES021801
Pays : United States
Organisme : Medical Research Council
ID : G0801414
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL103931
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL103866
Pays : United States
Organisme : Medical Research Council
ID : MR/K006584/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 085475/B/08/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0600580
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : P20 HL113452
Pays : United States
Organisme : Medical Research Council
ID : G0902037
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801566
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL074730
Pays : United States
Organisme : NHLBI NIH HHS
ID : P50 HL077113
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL098601
Pays : United States
Organisme : British Heart Foundation
ID : SP/13/6/30554
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/10/12/28456
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/18/50/33837
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL148110
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES025786
Pays : United States
Organisme : NINR NIH HHS
ID : R01 NR013396
Pays : United States
Organisme : Medical Research Council
ID : G0802318
Pays : United Kingdom
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