Family history of venous thromboembolism (VTE) and risk of recurrent hospitalization for VTE: a nationwide family study in Sweden

Zöller, Bengt; Sundquist, Jan; Sundquist, Kristina

doi:10.1111/jth.12499

Cited by 22 publications

(27 citation statements)

References 29 publications

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“…The HR of recurrent VTE hospitalisation in individuals with two affected parents was 1.92 (95 % CI 1.44-2.58). These three studies (72)(73)(74) are in line with studies that have shown Factor V Leiden to be a modest or no risk factor for recurrence in a large number of studies (75). In a study by Lijfering et al even individuals with homozygous FV Leiden and/or homozygous FII G20210A or double heterozygous carriers of FV Leiden and FII G20210A did not have a high risk of recurrent VTE (76).…”

Section: Family History and Recurrent Vtesupporting

confidence: 73%

“…However, two family studies have found no association with FH of VTE and risk for recurrent disease (72,73). A Swedish nationwide study found a significant association (74). The HR was 1.20 (95 % CI 1.10-1.32) for subjects with parent history and 1.30 (95 % CI 1.14-1.49) for VTE patients with sibling history, which is much lower than the familial risk for primary VTE (▶ Table 1 and ▶ Table 2).…”

Section: Family History and Recurrent Vtementioning

confidence: 99%

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Family history of venous thromboembolism as a risk factor and genetic research tool

Zöller

Li²,

Ji³

et al. 2015

Thromb Haemost

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Familial clustering of venous thromboembolism (VTE) was described as far back as 1905 by Briggs. Although Egeberg discovered inherited deficiency of antithrombin in 1965, it was not until Dahlbäck discovered resistance to activated protein C in 1993 that it became clear that genetic factors are common risk factors of VTE. Several genes have been linked to familial aggregation of VTE and genome-wide association studies have found several novel gene loci. Still, it has been estimated that much of the heritability for VTE remains to be discovered. Family history (FH) of VTE is therefore still important to determine whether a patient has an increased genetic risk of VTE. FH has the potential to represent the sum of effects and interactions between environmental and genetic factors. In this article the design, methodology, results, clinical and genetic implications of FH studies of VTE are reviewed. FH in first-degree relatives (siblings and/or parents) is associated with a 2-3 times increased familial relative risk (FRR). However, the FRR is dependent on age, number of affected relatives, and presentation of VTE (provoked/unprovoked). Especially high familial risks are observed in individuals with two or more affected siblings (FFR> 50). However, the familial risk for recurrent VTE is much lower or non-significant. Moreover, FH of VTE appears mainly to be important for venous diseases (i. e. VTE and varicose veins). The familial associations with other diseases are weaker. In conclusion, FH of VTE is an important research tool and a clinically potential useful risk factor for VTE.

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Section: Family History and Recurrent Vtesupporting

confidence: 73%

Section: Family History and Recurrent Vtementioning

confidence: 99%

Family history of venous thromboembolism as a risk factor and genetic research tool

Zöller

Li²,

Ji³

et al. 2015

Thromb Haemost

View full text Add to dashboard Cite

show abstract

“…Family history of VTE has been found to be a risk factor for first VTE, even in the absence of the known thrombophilias (51,52). Heritability has also been found to be a predictor of hospitalization for recurrent VTE in a Swedish study (53). The effect of heritability was strongest in younger patients, suggesting a genetic contribution.…”

Section: Recurrent Vtementioning

confidence: 94%

Cardiovascular disease and mortality after a first episode of venous thromboembolism in young and middle-aged women

Ljungqvist

Holmström

Kieler

et al. 2016

Thrombosis Research

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“…84,85 A Swedish nationwide family study showed a weak but significant association. 86 The HR was 1.2 for VTE patients with parent history and 1.3 for VTE cases with sibling history, which is much lower than the FRR for first event of VTE (►Table 2). 86 The HR of recurrent VTE in patients with two affected parents was 1.9 (i.e., a biological gradient compared with one affected parent).…”

Section: Family History Of Venous Thromboembolism and Spontaneous Venmentioning

confidence: 79%

“…86 The HR was 1.2 for VTE patients with parent history and 1.3 for VTE cases with sibling history, which is much lower than the FRR for first event of VTE (►Table 2). 86 The HR of recurrent VTE in patients with two affected parents was 1.9 (i.e., a biological gradient compared with one affected parent). Two recent studies have confirmed that FH of VTE is an independent risk factor for recurrent VTE even in the presence of established genetic determinants for VTE.…”

Section: Family History Of Venous Thromboembolism and Spontaneous Venmentioning

confidence: 79%

Epidemiology of Familial Aggregation of Venous Thromboembolism

Zöller

et al. 2016

Semin Thromb Hemost

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Familial aggregation (clustering) of venous thromboembolism (VTE) is the clustering of VTE within a family. Though several genes, such as antithrombin, protein C, protein S, factor V, and prothrombin are associated with the familial clustering of VTE, these loci only partially explain the familial aggregation of VTE. The epidemiology of the familial aggregation of VTE exhibits typical characteristics of complex traits. The family history of VTE in first-degree relatives is associated with a two to three times increased familial relative risk (FRR). The FRR of VTE is higher in younger individuals, increases with a number of affected relatives, decreases as the familial relationship becomes more distant, increases with severity (unprovoked), and exhibits slightly stronger male transmission (Carter effect). High FRR is observed in individuals with two or more affected siblings (FRR > 50). Because familial aggregation represents the sum of shared family environmental and genetic factors, one should not assume that evidence of familial aggregation implies genetic effects. However, studies in twins, extended families, adoptees, and spouses indicate a weak involvement of shared environmental factors to the familial aggregation of VTE. Moreover, familial aggregation of VTE fulfills the Hill's criteria for causation. In conclusion, familial aggregation of VTE signals a clinically relevant inherent predisposition for VTE.

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Family history of venous thromboembolism (VTE) and risk of recurrent hospitalization for VTE: a nationwide family study in Sweden

Cited by 22 publications

References 29 publications

Family history of venous thromboembolism as a risk factor and genetic research tool

Family history of venous thromboembolism as a risk factor and genetic research tool

Cardiovascular disease and mortality after a first episode of venous thromboembolism in young and middle-aged women

Epidemiology of Familial Aggregation of Venous Thromboembolism

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