Cardiovascular implications of the factor V Leiden mutation

Major, David A.; Sane, David C.; Herrington, David M.

doi:10.1067/mhj.2000.108241

Cited by 18 publications

(13 citation statements)

References 65 publications

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“…The 6.4% prevalence of the mutation in this study population and the 3-to 6-fold relative increase in the risk of VTE in women with the mutation are consistent with earlier reports from studies of largely healthy normal subjects. 27,28 However, because of the substantially higher baseline risk of VTE in this group of women with coronary disease, the absolute increase in risk associated with factor V Leiden (Ϸ0.5% per year) was much higher than that in healthier cohorts. Use of HRT in factor V Leiden-positive women further increased the risk to Ͼ1.5% per year.…”

Section: Discussionmentioning

confidence: 96%

“…The prevalence of the Leiden mutation is highest in northern Europeans and is almost nonexistent in most Asian populations. 27 It is also important to emphasize that the observations in the present study are limited to women with established coronary disease. The joint effects of HRT and factor V Leiden in healthy women are not yet determined.…”

Section: Discussionmentioning

confidence: 97%

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Factor V Leiden, Hormone Replacement Therapy, and Risk of Venous Thromboembolic Events in Women With Coronary Disease

Herrington

Vittinghoff

Howard

et al. 2002

ATVB

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Abstract-Oral contraceptive use in women with factor V Leiden is associated with increased rates of venous thromboembolic events (VTEs). However, the effects of hormone replacement therapy (HRT) in postmenopausal women with factor V Leiden are not known. A nested case-control study was conducted among women with established coronary disease enrolled in 2 randomized clinical trials of HRT, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Estrogen Replacement and Atherosclerosis (ERA) trial. The Leiden mutation was present in 8 (16.7%) of 48 cases with VTE compared with only 7 (6.3%) of 112 controls (odds ratio [OR] Leiden 3.3, 95% CI 1.1 to 9.8; Pϭ0.03). In women without the factor V Leiden mutation, risk associated with HRT use was significantly increased (OR HRT 3.7, 95% CI 1.4 to 9.4; PϽ0.01). On the other hand, in women with the factor V Leiden mutation, the estimated risk associated with HRT was increased nearly 6-fold, although the CIs were wide and included unity (OR HRT 5.7, 95% CI 0.6 to 53.9; Pϭ0.13). The OR for women with the Leiden mutation who were also assigned to HRT compared with wild-type women assigned to placebo was 14.1 (95% CI 2.7 to 72.4, Pϭ0.0015). In women with the factor V Leiden mutation who were treated with HRT, the estimated absolute incidence of VTE was 15.4 of 1000 per year compared with 2.0 of 1000 per year in women without the mutation who were taking a placebo (Pϭ0.0015). On the basis of these data, in women with coronary disease, the estimated number needed to screen for factor V Leiden to avoid an HRT-associated VTE during 5 years of treatment is 376. If factor V Leiden genotyping becomes less expensive, it could be cost effective to screen for the presence of the mutation before instituting HRT in women with coronary disease. Key Words: cardiology Ⅲ risk factors for stroke Ⅲ genetics Ⅲ thrombosis risk factors I n 1994, Bertina et al 1 described a single point mutation in the gene coding for factor V. This mutation, referred to as the factor V Leiden mutation, renders factor Va relatively resistant to degradation by the natural anticoagulant, activated protein C (APC). 2,3 The presence of this mutation or its functional consequence, APC resistance, is associated with an increased risk of venous thromboembolic events (VTEs). 1,4 -6 Risk for VTE appears to be even higher in women with APC resistance or the factor V Leiden mutation who are also pregnant 7-11 or who use oral contraceptives. 7,[12][13][14][15] The effect of hormone replacement therapy (HRT) on the risk of VTE in women with APC resistance is not well established. One observational study found a multiplicative relationship between the effects of HRT and APC resistance on VTE risk, 16 whereas a small randomized clinical trial of oral HRT in women with previously verified VTE failed to confirm such a relationship. 17 Determining the relative and absolute impact of HRT and factor V Leiden on VTE risk is especially important for older women or for women with coronary disease, whose baseline risk of VTE i...

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 97%

Factor V Leiden, Hormone Replacement Therapy, and Risk of Venous Thromboembolic Events in Women With Coronary Disease

Herrington

Vittinghoff

Howard

et al. 2002

ATVB

Self Cite

144

100

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“…This defect was identified in 52%-64% of undiagnosed thrombophilic patients [5]. In 1994 Bertina reported that the phenotype of APC resistance was associated in 95% of cases with heterozygosity or homozygosity for a single point mutation in the factor V gene: a G→A transition in position 1691, in exon 10 [4,6,7,8,9,10]. This mutation converts codon 506 from CGA encoding arginine to CAA encoding glutamine (Arg506Gln) and has come to be a factor V Leiden (FVL) mutation [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…This mutation is at the site of cleavage by APC [11,12]. Activated factor V with glutamine at position 506 is not cleaved by APC at this posi-tion [10,13], resulting in an increased thrombin potential and risk of thrombosis.…”

Section: Introductionmentioning

confidence: 99%

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Genetic analysis of factor V Leiden in a family with history of thrombosis and venous leg ulcers

Procopciuc

Has

Drugan

et al. 2000

J Cellular Molecular Medi

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Inherited resistance to activated protein C has been recognized as a major risk factor for thrombosis. The factor V Leiden mutation, which is detectable by molecular DNA techniques, is responsible for 95% of cases of activated protein C resistance. In our study one patient with venous leg ulcers from a family with a history of thrombosis showed factor V Leiden mutation. Genotypic analysis demonstrated that the patient was homozygous for factor V Leiden. All family members of the index subject showed the same abnormalities. Two were homozygous and 3 were heterozygous for factor V Leiden mutation. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by enzymatic digestion with MnlI for mutation detection. Patients with a family history of thrombosis and factor V Leiden have an increased risk of venous leg ulcers. Screening for factor V Leiden may be indicated in patients with venous leg ulcers and their family members.

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Genpolymorphismen der Hämostase und Koronarrisiko

et al. 2001

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Hemostatic disorders are substantially involved in the pathogenesis of coronary heart disease and acute coronary syndromes. In addition to biochemical markers, gene polymorphisms of hemostasis have been intensively studied in terms of their association with coronary risk. These include polymorphisms of the genes of platelet glycoproteins, fibrinogen, prothrombin, factors V, VIII and XIII, plasminogen activator inhibitor-1 and tissue-type plasminogen activator. An association of a certain gene polymorphism with an increased coronary risk has usually been demonstrated in retrospective case-control studies. However, numerous clinical studies have not yet been able to identify any of these polymorphisms as unequivocal risk factors of coronary heart disease or acute coronary syndromes. These inconsistencies are mainly due to the complexity of the pathogenesis of coronary heart disease and the minor contribution of a single polymorphism to total coronary risk. This review reports on essential requirements of future studies as a prerequisite to improve our understanding of the genetic basis of coronary heart disease.

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Cardiovascular implications of the factor V Leiden mutation

Cited by 18 publications

References 65 publications

Factor V Leiden, Hormone Replacement Therapy, and Risk of Venous Thromboembolic Events in Women With Coronary Disease

Factor V Leiden, Hormone Replacement Therapy, and Risk of Venous Thromboembolic Events in Women With Coronary Disease

Genetic analysis of factor V Leiden in a family with history of thrombosis and venous leg ulcers

Genpolymorphismen der Hämostase und Koronarrisiko

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