Dataset Information

Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.

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]; 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 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.

SUBMITTER: Mahmoodi BK

PROVIDER: S-EPMC7493828 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.

Mahmoodi Bakhtawar K BK Tragante Vinicius V Kleber Marcus E ME Holmes Michael V MV Schmidt Amand F AF McCubrey Raymond O RO Howe Laurence J LJ Direk Kenan K Allayee Hooman H Baranova Ekaterina V EV Braund Peter S PS Delgado Graciela E GE Eriksson Niclas N Gijsberts Crystel M CM Gong Yan Y Hartiala Jaana J Heydarpour Mahyar M Pasterkamp Gerard G Kotti Salma S Kuukasjärvi Pekka P Lenzini Petra A PA Levin Daniel D Lyytikäinen Leo-Pekka LP Muehlschlegel Jochen D JD Nelson Christopher P CP Nikus Kjell K Pilbrow Anna P AP Wilson Tang W H WH van der Laan Sander W SW van Setten Jessica J Vilmundarson Ragnar O RO Deanfield John J Deloukas Panos P Dudbridge Frank F James Stefan S Mordi Ify R IR Teren Andrej A Bergmeijer Thomas O TO Body Simon C SC Bots Michiel M Burkhardt Ralph R Cooper-DeHoff Rhonda M RM Cresci Sharon S Danchin Nicolas N Doughty Robert N RN Grobbee Diederick E DE Hagström Emil E Hazen Stanley L SL Held Claes C Hoefer Imo E IE Hovingh G Kees GK Johnson Julie A JA Kaczor Marcin P MP Kähönen Mika M Klungel Olaf H OH Laurikka Jari O JO Lehtimäki Terho T Maitland-van der Zee Anke H AH McPherson Ruth R Palmer Colin N CN Kraaijeveld Adriaan O AO Pepine Carl J CJ Sanak Marek M Sattar Naveed N Scholz Markus M Simon Tabassome T Spertus John A JA Stewart Alexandre F R AFR Szczeklik Wojciech W Thiery Joachim J Visseren Frank L J FLJ Waltenberger Johannes J Richards A Mark AM Lang Chim C CC Cameron Vicky A VA Åkerblom Axel A Pare Guillaume G März Winfried W Samani Nilesh J NJ Hingorani Aroon D AD Ten Berg Jurriën M JM Wallentin Lars L Asselbergs Folkert W FW Patel Riyaz S RS

Circulation 20200713 6

<h4>Background</h4>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.<h4>Methods</h4>We performed an individual-level meta-analysis including ...[more]

PMID: 32654539

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Project description:BACKGROUND:Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. METHODS:We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. FINDINGS:30,214 (15%) of 197,473 participants reported job strain. In 1·49 million person-years at risk (mean follow-up 7·5 years [SD 1·7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1·23 (95% CI 1·10-1·37). This effect estimate was higher in published (1·43, 1·15-1·77) than unpublished (1·16, 1·02-1·32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1·31, 1·15-1·48) and 5 years (1·30, 1·13-1·50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3·4%. INTERPRETATION:Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. FUNDING:Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.

Dataset Information

Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.

Background

Methods

Results

Conclusions

Publications

Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.

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