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Thromb Haemost 2011; 106(01): 102-112
DOI: 10.1160/TH10-10-0655
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Determination of age-specific and sex-specific familial risks for the different manifestations of venous thromboembolism: A nationwide family study in Sweden

Bengt Zöller
1   Center for Primary Health Care Research, Lund University, Malmö, Sweden
,
Xinjun Li
1   Center for Primary Health Care Research, Lund University, Malmö, Sweden
,
Jan Sundquist
1   Center for Primary Health Care Research, Lund University, Malmö, Sweden
2   Stanford Prevention Research Centre, Stanford University School of Medicine, Palo Alto, California, USA
,
Kristina Sundquist
1   Center for Primary Health Care Research, Lund University, Malmö, Sweden
› Author Affiliations Financial support: This work was supported by grants to Drs. Kristina and Jan Sundquist from the Swedish Research Council (2008–3110 and 2008–2638), the Swedish Council for Working Life and Social Research (2006–0386, 2007–1754 and 2007–1962), and the Swedish Research Council Formas (2006–4255–6596–99 and 2007–1352).
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Publication History

Received: 14 October 2010

Accepted after major revision: 01 April 2010

Publication Date:
24 November 2017 (online)

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Summary

This nationwide study aimed to determine whether differences exist in age-specific and sex-specific familial risks for pulmonary embolism (PE), venous thrombosis of the lower limbs (VT) and other forms of venous thromboembolism (OVTE) among offspring, siblings and spouses of affected individuals. The Swedish Multi-Generation Register was linked to the Hospital Discharge Register data for the period 1987–2007. Standardised incidence ratios (SIRs) were calculated for individuals whose relatives were hospitalised for venous thromboembolism (VTE), as determined by the International Classification of Diseases (ICD), and those whose relatives were unaffected by VTE. The total number of hospitalised VTE patients was 45,362. All VTE patients were categorised as PE, VT or OVTE according to ICD at first hospitalisation. For example, the parental SIRs for PE, VT and OVTE in offspring at age 10–19 years were 2.89 (95% CI 1.48–5.06), 4.99 (95% CI 3.22–6.10) and 3.89 (95% CI 2.51–5.75), respectively. The low spousal risks of PE (1.08; 95% CI 1.02–1.13), VT (1.06; 95% CI 1.011.12) and OVTE (1.07; 95% CI 1.00–1.15) suggest the familial risks to be largely genetic. In both men and women, familial relative risks were increased for all the different manifestations of VTE with the exception of those older than 70 years. Familial history is a risk indicator in both sexes, and is potentially useful for clinical risk assessment for the different manifestations of VTE.

Keywords

Venous thrombosis - epidemiology - pulmonary embolism - risk factors - familial thrombosis
 

  • References

  • 1 Silverstein MD, Heit JA, Mohr DN. et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158: 585-593.
    CrossrefPubMedGoogle Scholar
  • 2 Heit JA, Silverstein MD, Mohr DN. et al. The epidemiology of venous thromboembolism in the community. Thromb Haemost 2001; 86: 452-463.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Andersson FA, Jr. Wheeler HB, Goldberg RJ. et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991; 151: 933-938.
    CrossrefPubMedGoogle Scholar
  • 4 Kniffin WD, Jr Baron JA, Barett J. et al. The epidemiology of diagnosed pulmonary embolism and deep venous thrombosis in the elderly. Arch Intern Med 1994; 154: 861-866.
    CrossrefPubMedGoogle Scholar
  • 5 White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107: I4-8.
    PubMedGoogle Scholar
  • 6 Cohen AT, Agnelli G, Andersson FA. et al. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost 2007; 98: 756-764.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Rosendaal FR. Risk factors for venous thrombotic disease. Thromb Haemost 1999; 82: 610-619.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Dowling NF, Austin H, Diley A. et al. The epidemiology of venous thromboembolism in Caucasians and African-Americans: the GATE Study. J Thromb Haemost 2003; 1: 80-87.
    CrossrefPubMedGoogle Scholar
  • 9 Noboa S, Le Gal, Lacut K. et al. Family history as a risk factor for venous thromboembolism. Thromb Res 2008; 122: 624-629.
    CrossrefPubMedGoogle Scholar
  • 10 Bezemer ID, van der Meer FJ, Eikenboom JC. et al. The value of family history as a risk indicator for venous thrombosis. Arch Intern Med 2009; 169: 610-615.
    CrossrefPubMedGoogle Scholar
  • 11 Zöller B, Li X, Sundquist J. et al. Parental history and venous thromboembolism: a nationwide study of age and sex-specific familial risks in Sweden. J Thromb Haemost 2011; 9: 64-70.
    CrossrefPubMedGoogle Scholar
  • 12 van Sluis GL, Söhne M, El Kheir DY. et al. Family history and inherited thrombophilia. J Thromb Haemost 2006; 4: 2182-2187.
    CrossrefPubMedGoogle Scholar
  • 13 Risch N. The genetic epidemiology of cancer: interpreting family and twin studies and their implications for molecular genetic approaches. Cancer Epidemiol Biomarkers Prev 2001; 10: 733-741.
    PubMedGoogle Scholar
  • 14 Girolami A, Fabris F, Girolami B. Clinical aspects of venous thrombophilia. Pa- thophysiol Haemost Thromb 2002; 32: 258-262.
    PubMedGoogle Scholar
  • 15 Martinelli I, De Stefano V. Rare thrombosis of cerebral, splanchnic and upper-extremity veins. A narrative review. Thromb Haemost 2010; 103: 1136-1144.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism. Circulation 1996; 93: 2212-2245.
    CrossrefPubMedGoogle Scholar
  • 17 Stein PD, Matta F, Musani MH. et al. Silent pulmonary embolism in patients with deep venous thrombosis: a systematic review. Am J Med 2010; 123: 426-431.
    CrossrefPubMedGoogle Scholar
  • 18 Desmarais S, De Moerloose P, Reber G. et al. Resistance to activated protein C in an unselected population of patients with pulmonary embolism. Lancet 1996; 347: 1374-1375.
    CrossrefPubMedGoogle Scholar
  • 19 Bounameaux H. Factor V Leiden paradox: risk of deep-vein thrombosis but not of pulmonary embolism. Lancet 2000; 356: 182-183.
    CrossrefPubMedGoogle Scholar
  • 20 Couturaud F, Leroyer C, Julian JA. et al. Factors that predict risk of thrombosis in relatives of patients with unprovoked venous thromboembolism. Chest 2009; 136: 1537-1545.
    CrossrefPubMedGoogle Scholar
  • 21 Zöller B, Li X, Sundquist J. et al. Familial risks for unusual forms of venous thrombosis: a nationwide epidemiological study in Sweden. J Intern Med 2010; 269 DOI: 10.1111/j.1365-2796.2010.02326.x..
    CrossrefPubMedGoogle Scholar
  • 22 Hemminki K, Shu X, Li X. et al. Familial risks for hospitalization with endocrine diseases. J Clin Endocrinol Metab 2008; 93: 4755-4758.
    CrossrefPubMedGoogle Scholar
  • 23 Sundquist K, Li X, Hemminki K. Familial risk of ischemic and hemorrhagic stroke. A large-scale study of the Swedish population. Stroke 2006; 37: 1668-1673.
    CrossrefPubMedGoogle Scholar
  • 24 Hemminki K, Li X, Sundquist J. et al. Familial risks for type 2 diabetes in Sweden. Diabetes Care 2010; 33: 293-297.
    CrossrefPubMedGoogle Scholar
  • 25 Sundquist K, Xinjun Li. Differences in maternal and paternal transmission of coronary heart disease. Am J Prev Med 2006; 30: 480-486.
    CrossrefPubMedGoogle Scholar
  • 26 Statistics Sweden.. The Swedish Multigeneration Register (1960-1990): Registret över totalbefolkningen/RTB. In Swedish.. Stockholm: Statistics Sweden; 2005
    Google Scholar
  • 27 The National Board of Health and Welfare.. The Swedish Hospital Discharge Register and the Cause of Death Register (1961-2001). In Swedish.. Stockholm: The National Board of Health and Welfare; 2004
    Google Scholar
  • 28 Socialstyrelsen.. Patientregistret 1987-1996 Kvalitet och innehäll. In Swedish.. Stockholm: Epidemiologiskt Centrum, Socialstyrelsen; 1998
    Google Scholar
  • 29 Baron JA, Gridley G, Weiderpass E. et al. Venous thromboembolism and cancer. Lancet 1998; 351: 1077-1080.
    CrossrefPubMedGoogle Scholar
  • 30 Ludvigsson JF, Welander A, Lassila R. et al. Risk of thromboembolism in 14,000 individuals with coeliac disease. Br J Haematol 2007; 139: 121-127.
    CrossrefPubMedGoogle Scholar
  • 31 Kristinsson SY, Pfeiffer RM, Björkholm M. et al. Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma a population-based study. Blood 115: 4991-4998.
    PubMedGoogle Scholar
  • 32 Rosen M, Hakulinen T. Use of disease registers. Handbook of epidemiology.. Berlin: Springer-Verlag; 2005: 231-251.
    Google Scholar
  • 33 Li X, Sundquist J, Sundquist K. Socioeconomic and occupational risk factors for rheumatoid arthritis: a nationwide study based on hospitalizations in Sweden. J Rheumatol 2008; 35: 986-991.
    PubMedGoogle Scholar
  • 34 Souto JC, Almasy L, Borrell M. et al. Genetic susceptibility to thrombosis and its relationship to physiological risk factors: the GAIT study. Am J Hum Genet 2000; 67: 1452-1459.
    CrossrefPubMedGoogle Scholar
  • 35 Engesser L, Broekmans AW, Briet E. et al. Hereditary protein S deficiency: Clinical manifestations. Ann Intern Med 1987; 106: 677-682.
    CrossrefPubMedGoogle Scholar
  • 36 Breslow NE, Day NE. Statistical methods in cancer research. Volume II - The design and analysis of cohort studies. IARC Sci Publ 1987; 82: 1-406.
    PubMedGoogle Scholar
  • 37 Rothman K, Greenland S. Modern Epidemiology. 2nd ed. Philadelphia: Lippincott-Raven; 1998
  • 38 Esteve J, Benhamou E, Raymond L. Statistical Methods in Cancer Research.. Lyon: IARC; 1994
  • 39 National Cancer Institute. US National Institutes of Health. Surveillance Epidemiology and End Results: Standard Populations (Millions) for Age-Adjustment. Available at: http://seer.cancer.gov/stdpopulations/ . Accessed February 2, 2010.
    PubMedGoogle Scholar
  • 40 Hemminki K, Vaittinen P, Dong C. et al. Sibling risks in cancer: clues to recessive or X-linked genes?. Br J Cancer 2001; 84: 388-391.
    CrossrefPubMedGoogle Scholar
  • 41 Newcombe RG. Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med 1998; 17: 857-872.
    Google Scholar
  • 42 Segers K, Dahlbäck B, Nicolaes GA. Coagulation factor V and thrombophilia: background and mechanisms. Thromb Haemost 2007; 98: 530-542.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Isma N, Svensson PJ, Gottsäter A. et al. Upper extremity deep venous thrombosis in the population-based Malmö thrombophilia study (MATS). Epidemiology, risk factors, recurrence risk, and mortality. Thrombosis Res 2010; 125: e335-338.
    CrossrefPubMedGoogle Scholar
  • 44 Rosengren A, Freden M, Hansson P-O. et al. Psychosocial factors and venous thromboembolism: a long-term follow-up study of Swedish men. J Thromb Haemost 2008; 6: 558-564.
    CrossrefPubMedGoogle Scholar
  • 45 Petrauskiene V, Falk M, Waernbaum I. et al. The risk of venous thromboembolism is markedly elevated in patients with diabetes. Diabetologia 2005; 48: 1017-1021.
    CrossrefPubMedGoogle Scholar
  • 46 Hammar N, Alfredsson L, Rosen M. et al. A national record linkage to study acute myocardial infarction incidence and case fatality in Sweden. Int J Epidemiol 2001; 30: S30-34.
    CrossrefPubMedGoogle Scholar
  • 47 Lindblad U, Rästam L, Ranstam J. et al. Validity of register data on acute myocardial infarction and acute stroke: the Skarborg Hypertension Project. Scand J Soc Med 1993; 21: 3-9.
    PubMedGoogle Scholar
  • 48 The National Board of Health and Welfare. Validity of the diagnoses from the Swedish In-Care Register 1987 and 1995. In Swedish.. Stockholm: Epidemiologiskt Centrum, Socialstyrelsen; 2000
    Google Scholar
  • 49 Johansson LA, Westerling R. Comparing Swedish hospital discharge records with death certificates: implications for mortality statistics. Int J Epidemiol 2000; 29: 495-502.
    CrossrefPubMedGoogle Scholar
  • 50 Statens beredning för medicinsk utvärdering (SBU).. Blodpropp - förebyggande, diagnostik och behandling av venös trombembolism SBU-rapport 158. In Swedish.. Stockholm: The Swedish Council on Technology Assessment in Health Care; 2002: I-III.
    Google Scholar