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Excess risk of venous thromboembolism in hip fracture patients and the prognostic impact of comorbidity

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Abstract

Summary

Hip fracture patients were at increased excess risk of venous thromboembolism (VTE) up to 1 year following hip fracture. During the first year, interaction between hip fracture and comorbidity was observed among patients with severe and very severe comorbidity.

Introduction

We compared the risk of VTE in hip fracture patients with that in the general population. We also examined whether and to what extent the association between hip fracture and VTE varied by comorbidity level.

Methods

Nationwide cohort study based on Danish health registries, 1995–2015. We identified hip fracture patients (n = 110,563) and sampled a comparison cohort without hip fracture from the general population (n = 552,774). Comorbidity was assessed using the Charlson comorbidity index. We calculated attributable fraction, as the proportion of the VTE rate, among persons exposed to both hip fracture and comorbidity, attributed to exposure interaction.

Results

The cumulative incidences of VTE were 0.73% within 30 days and 0.83% within 31–365 days among hip fracture patients, and 0.05 and 0.43% in the general population. Adjusted hazard ratios (HRs) of VTE among hip fracture patients were 17.29 [95% confidence interval (CI) 14.74–20.28] during the first 30 days and 2.13 (95% CI 1.95–2.32) during 31–365 days following hip fracture. The relative risks of VTE were 1.03 (95% CI 0.96–1.11) and 1.11 (95% CI 1.00–1.23) after 1–5 years and 6–10 years. During the first 30 days and 31–365 days, 14%/28% of VTE rates and 5%/4% of VTE rates were attributable to the interaction between hip fracture and severe/very severe comorbidity, respectively. Mortality risks within 30 days of VTE were 29.4% in hip fracture and 11.0% in general population cohorts.

Conclusions

Hip fracture patients were at increased excess risk of VTE up to 1 year following their fracture. During the first year, interaction between hip fracture and comorbidity was observed among patients with severe and very severe comorbidity.

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References

  1. Omsland TK, Emaus N, Tell GS, Magnus JH, Ahmed LA, Holvik K, Center J, Forsmo S, Gjesdal CG, Schei B, Vestergaard P, Eisman JA, Falch JA, Tverdal A, Sogaard AJ, Meyer HE (2014) Mortality following the first hip fracture in Norwegian women and men (1999-2008). A NOREPOS study. Bone 63:81–86. https://doi.org/10.1016/j.bone.2014.02.016

    Article  PubMed  Google Scholar 

  2. Haentjens P, Magaziner J, Colon-Emeric CS, Vanderschueren D, Milisen K, Velkeniers B, Boonen S (2010) Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med 152(6):380–390. https://doi.org/10.7326/0003-4819-152-6-201003160-00008

    Article  PubMed  PubMed Central  Google Scholar 

  3. Brauer CA, Coca-Perraillon M, Cutler DM, Rosen AB (2009) Incidence and mortality of hip fractures in the United States. JAMA 302(14):1573–1579. https://doi.org/10.1001/jama.2009.1462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bjorkelund KB, Hommel A, Thorngren KG, Lundberg D, Larsson S (2009) Factors at admission associated with 4 months outcome in elderly patients with hip fracture. AANA J 77(1):49–58

    PubMed  Google Scholar 

  5. Khan MA, Hossain FS, Ahmed I, Muthukumar N, Mohsen A (2013) Predictors of early mortality after hip fracture surgery. Int Orthop 37(11):2119–2124. https://doi.org/10.1007/s00264-013-2068-1

    Article  PubMed  PubMed Central  Google Scholar 

  6. Vestergaard P, Rejnmark L, Mosekilde L (2007) Increased mortality in patients with a hip fracture-effect of pre-morbid conditions and post-fracture complications. Osteoporos Int 18(12):1583–1593. https://doi.org/10.1007/s00198-007-0403-3

    Article  CAS  PubMed  Google Scholar 

  7. Lawrence VA, Hilsenbeck SG, Noveck H, Poses RM, Carson JL (2002) Medical complications and outcomes after hip fracture repair. Arch Intern Med 162(18):2053–2057

    Article  PubMed  Google Scholar 

  8. Roche JJ, Wenn RT, Sahota O, Moran CG (2005) Effect of comorbidities and postoperative complications on mortality after hip fracture in elderly people: prospective observational cohort study. BMJ 331(7529):1374. https://doi.org/10.1136/bmj.38643.663843.55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kristensen PK, Thillemann TM, Soballe K, Johnsen SP (2016) Are process performance measures associated with clinical outcomes among patients with hip fractures? A population-based cohort study. Int J Qual Health Care. https://doi.org/10.1093/intqhc/mzw093

  10. Mahomed NN, Davis AM, Hawker G, Badley E, Davey JR, Syed KA, Coyte PC, Gandhi R, Wright JG (2008) Inpatient compared with home-based rehabilitation following primary unilateral total hip or knee replacement: a randomized controlled trial. J Bone Joint Surg Am 90(8):1673–1680. https://doi.org/10.2106/JBJS.G.01108

    Article  PubMed  Google Scholar 

  11. Lindahl TL, Lundahl TH, Nilsson L, Andersson CA (1999) APC-resistance is a risk factor for postoperative thromboembolism in elective replacement of the hip or knee—a prospective study. Thromb Haemost 81(1):18–21

    CAS  PubMed  Google Scholar 

  12. Parolari A, Colli S, Mussoni L, Eligini S, Naliato M, Wang X, Gandini S, Tremoli E, Biglioli P, Alamanni F (2003) Coagulation and fibrinolytic markers in a two-month follow-up of coronary bypass surgery. J Thorac Cardiovasc Surg 125(2):336–343. https://doi.org/10.1067/mtc.2003.2

    Article  PubMed  Google Scholar 

  13. (RADS) DCftUoEHM (2014) Baggrundsnotat: Tromboseprofylakse til ortopædkirurgiske patienter. http://www.regioner.dk/media/2728/bgn-parenkymkirurgi-version-21-juni-2016.pdf. Accessed 18 June 2017

  14. Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, Ortel TL, Pauker SG, Colwell CW Jr (2012) Prevention of VTE in orthopedic surgery patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(2 Suppl):e278S–e325S. https://doi.org/10.1378/chest.11-2404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. NICE guidelines (2010) Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital by National Clinical Guideline Centre - Acute and Chronic Conditions. https://www.nice.org.uk/guidance/cg92. Accessed 18 June 2017

  16. Eriksson BI, Bauer KA, Lassen MR, Turpie AG (2001) Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med 345(18):1298–1304. https://doi.org/10.1056/NEJMoa011100

    Article  CAS  PubMed  Google Scholar 

  17. McNamara I, Sharma A, Prevost T, Parker M (2009) Symptomatic venous thromboembolism following a hip fracture. Acta Orthop 80(6):687–692. https://doi.org/10.3109/17453670903448273

    Article  PubMed  PubMed Central  Google Scholar 

  18. Rosencher N, Vielpeau C, Emmerich J, Fagnani F, Samama CM (2005) Venous thromboembolism and mortality after hip fracture surgery: the ESCORTE study. J Thromb Haemost 3(9):2006–2014. https://doi.org/10.1111/j.1538-7836.2005.01545.x

    Article  CAS  PubMed  Google Scholar 

  19. Pedersen AB, Christiansen CF, Gammelager H, Kahlert J, Sorensen HT (2016) Risk of acute renal failure and mortality after surgery for a fracture of the hip: a population-based cohort study. Bone Joint J 98-B(8):1112–1118. https://doi.org/10.1302/0301-620X.98B8.37497

    Article  CAS  PubMed  Google Scholar 

  20. Schmidt M, Pedersen L, Sorensen HT (2014) The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol 29(8):541–549. https://doi.org/10.1007/s10654-014-9930-3

    Article  PubMed  Google Scholar 

  21. Schmidt M, Schmidt SA, Sandegaard JL, Ehrenstein V, Pedersen L, Sorensen HT (2015) The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol 7:449–490. https://doi.org/10.2147/CLEP

    Article  PubMed  PubMed Central  Google Scholar 

  22. Nymark T, Lauritsen JM, Ovesen O, Rock ND, Jeune B (2006) Short time-frame from first to second hip fracture in the Funen County Hip Fracture Study. Osteoporos Int 17(9):1353–1357. https://doi.org/10.1007/s00198-006-0125-y

    Article  CAS  PubMed  Google Scholar 

  23. Severinsen MT, Kristensen SR, Overvad K, Dethlefsen C, Tjonneland A, Johnsen SP (2009) Venous thromboembolism discharge diagnoses in the Danish National Patient Registry should be used with caution. J Clin Epidemiol. https://doi.org/10.1016/j.jclinepi.2009.03

  24. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40(5):373–383

    Article  CAS  PubMed  Google Scholar 

  25. Gooley TA, Leisenring W, Crowley J, Storer BE (1999) Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 18(6):695–706. (SICI)1097-0258(19990330)18:6/(SICI)1097-0258(19990330)18:6<695::AID-SIM60>3.0.CO;2-O

  26. VanderWeele TJ, Tchetgen Tchetgen EJ (2014) Attributing effects to interactions. Epidemiology 25(5):711–722. https://doi.org/10.1097/EDE.0000000000000096

    Article  PubMed  PubMed Central  Google Scholar 

  27. Pedersen AB, Johnsen SP, Sorensen HT (2012) Increased one-year risk of symptomatic venous thromboembolism following total hip replacement: a nationwide cohort study. J Bone Joint Surg (Br) 94(12):1598–1603. https://doi.org/10.1302/0301-620X.94B12.29358

    Article  CAS  Google Scholar 

  28. Le MY, Collins G, Bhandari M, Bessissow A, Boddaert J, Khiami F, Chaudhry H, De Beer J, Riou B, Landais P, Winemaker M, Boudemaghe T, Devereaux PJ (2015) Outcomes after hip fracture surgery compared with elective total hip replacement. JAMA 314(11):1159–1166. https://doi.org/10.1001/jama.2015.10842

    Article  Google Scholar 

  29. Pedersen AB, Sorensen HT, Mehnert F, Johnsen SP, Overgaard S (2015) Effectiveness and safety of different duration of thromboprophylaxis in 16,865 hip replacement patients—a real-word, prospective observational study. Thromb Res 135(2):322–328. https://doi.org/10.1016/j.thromres.2014.11.029

    Article  CAS  PubMed  Google Scholar 

  30. Kehlet H, Wilmore DW (2008) Evidence-based surgical care and the evolution of fast-track surgery. Ann Surg 248(2):189–198. https://doi.org/10.1097/SLA.0b013e31817f2c1a

    Article  PubMed  Google Scholar 

  31. Kristensen PK, Thillemann TM, Soballe K, Johnsen SP (2015) Can improved quality of care explain the success of orthogeriatric units? A population-based cohort study. Age Ageing. https://doi.org/10.1093/ageing/afv155

  32. Edmonds MJ, Crichton TJ, Runciman WB, Pradhan M (2004) Evidence-based risk factors for postoperative deep vein thrombosis. ANZ J Surg 74(12):1082–1097

    Article  PubMed  Google Scholar 

  33. Carrier M, Le GG, Wells PS, Rodger MA (2010) Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med 152(9):578–589. https://doi.org/10.1059/0003-4819-152-9-201005040-00008

    Article  PubMed  Google Scholar 

  34. Heit JA, Mohr DN, Silverstein MD, Petterson TM, O'Fallon WM, Melton LJ III (2000) Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 160(6):761–768

    Article  CAS  PubMed  Google Scholar 

  35. Mohr DN, Silverstein MD, Heit JA, Petterson TM, O'Fallon WM, Melton LJ (2000) The venous stasis syndrome after deep venous thrombosis or pulmonary embolism: a population-based study. Mayo Clin Proc 75(12):1249–1256

    Article  CAS  PubMed  Google Scholar 

  36. Sorensen HT, Horvath-Puho E, Pedersen L, Baron JA, Prandoni P (2007) Venous thromboembolism and subsequent hospitalisation due to acute arterial cardiovascular events: a 20-year cohort study. Lancet 370(9601):1773–1779

    Article  PubMed  Google Scholar 

  37. Vochteloo AJ, Moerman S, Tuinebreijer WE, Maier AB, de Vries MR, Bloem RM, Nelissen RG, Pilot P (2013) More than half of hip fracture patients do not regain mobility in the first postoperative year. Geriatr Gerontol Int 13(2):334–341. https://doi.org/10.1111/j.1447-0594.2012.00904.x

    Article  PubMed  Google Scholar 

  38. Gatt ME, Paltiel O, Bursztyn M (2004) Is prolonged immobilization a risk factor for symptomatic venous thromboembolism in elderly bedridden patients? Results of a historical-cohort study. Thromb Haemost 91(3):538–543. https://doi.org/10.1160/TH03-07-0481

    CAS  PubMed  Google Scholar 

  39. Johannesdottir SA, Horvath-Puho E, Dekkers OM, Cannegieter SC, Jorgensen JO, Ehrenstein V, Vandenbroucke JP, Pedersen L, Sorensen HT (2013) Use of glucocorticoids and risk of venous thromboembolism: a nationwide population-based case-control study. JAMA Intern Med 173(9):743–752. https://doi.org/10.1001/jamainternmed.2013.122

    Article  CAS  PubMed  Google Scholar 

  40. Schmidt M, Christiansen CF, Horvath-Puho E, Glynn RJ, Rothman KJ, Sorensen HT (2011) Non-steroidal anti-inflammatory drug use and risk of venous thromboembolism. J Thromb Haemost 9(7):1326–1333. https://doi.org/10.1111/j.1538-7836.2011.04354.x

    Article  CAS  PubMed  Google Scholar 

  41. Wu CS, Chang CM, Chen CY, Wu EC, Wu KY, Liang HY, Chao YL, Chung WS, Tsai HJ (2013) Association between antidepressants and venous thromboembolism in Taiwan. J Clin Psychopharmacol 33(1):31–37. https://doi.org/10.1097/JCP.0b013e3182777425

    Article  CAS  PubMed  Google Scholar 

  42. Schmidt M, Cannegieter SC, Johannesdottir SA, Dekkers OM, Horvath-Puho E, Sorensen HT (2014) Statin use and venous thromboembolism recurrence: a combined nationwide cohort and nested case-control study. J Thromb Haemost 12(8):1207–1215. https://doi.org/10.1111/jth.12604

    Article  CAS  PubMed  Google Scholar 

  43. Baron JA, Lu-Yao G, Barrett J, McLerran D, Fisher ES (1994) Internal validation of Medicare claims data. Epidemiology 5(5):541–544

    CAS  PubMed  Google Scholar 

  44. Hudson M, Avina-Zubieta A, Lacaille D, Bernatsky S, Lix L, Jean S (2013) The validity of administrative data to identify hip fractures is high—a systematic review. J Clin Epidemiol 66(3):278–285. https://doi.org/10.1016/j.jclinepi.2012.10.004

    Article  PubMed  Google Scholar 

  45. Thygesen SK, Christiansen CF, Christensen S, Lash TL, Sorensen HT (2011) The predictive value of ICD-10 diagnostic coding used to assess Charlson comorbidity index conditions in the population-based Danish National Registry of Patients. BMC Med Res Methodol 11:83. https://doi.org/10.1186/1471-2288-11-83

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark

    A. B. Pedersen, V. Ehrenstein, S. K. Szépligeti & H. T. Sørensen

  2. Department of Health Research & Policy (Epidemiology), Stanford University, Stanford, CA, USA

    H. T. Sørensen

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  1. A. B. Pedersen
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  2. V. Ehrenstein
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  3. S. K. Szépligeti
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  4. H. T. Sørensen
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Corresponding author

Correspondence to A. B. Pedersen.

Ethics declarations

The study was approved by the Danish Data Protection Agency. Permission to use the data was obtained from the Danish National Patient Registry and the Civil Registration System (Aarhus University, journal number 2016-051-000001).

Conflicts of interest

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Appendix

Appendix

Hip fracture was defined as the presence of one or more of the following diagnosis codes: ICD-10 codes S72.0, S72.1, or S72.2

Venous thromboembolism: Deep venous thrombosis was defined using ICD-10 codes I801-3 and pulmonary embolism using ICD-10 code I26

Any osteoporotic fracture was defined with one of the following ICD-10 codes: S12.0, S12.1, S12.2, S12.7, S12.9, S22.0, S22.1, T08, S32.x; S42.2, S42.3, S42.4, 42.7, S42.8, S52.x, and S62.x

Surgery codes from Danish National Patient Register: KNFB.0-99 primary hip arthroplasty (total or partial) and KNFJ.4-9 open reduction and internal fixation of the hip fracture Disease categories and the International Classification of Diseases codes, the eighth edition (ICD-8) and the tenth edition (ICD-10), used to calculate the Charlson comorbidity index: Myocardial infarction: 410, I21-I23

Congestive heart failure: 427.09; 427.10; 427.11; 427.19; 428.99; 782.49; I50; I11.0; I13.0; I13.2

Peripheral vascular disease: 440; 441; 442; 443; 444; 445, I70-I74; I77 Cerebrovascular disease: 430-438; I60-I69; G45; G46

Dementia: 290.09-290.19; 293.09; F00-F03; F05.1; G30 Chronic pulmonary disease: 490-493; 515-518; J40-J47; J60-J67; J68.4; J70.1; J70.3; J84.1; J92.0; J96.1; J98.2-J98.3

Connective tissue disease: 712; 716; 734; 446; 135.99; M05; M06; M08; M09; M30-M36; D86 Ulcer disease: 530.91; 530.98; 531-534; K22.1; K25-K28

Mild liver disease: 571; 573.01; 573.04; B18; K70.0-K70.3; K70.9; K71; K73; K74; K76.0 Diabetes: 249.00; 249.06; 249.07; 249.09; 250.00; 250.06; 250.07; 250.09; E10.0; E10.1; E10.9; E11.0; E11.1; E11.9

Hemiplegia: 344; G81; G82

Moderate to severe renal disease: 403; 404; 580-584; 590.09; 593.19; 753.10-753.19; 792; I12; I13; N00-N05; N07; N11; N14; N17-N19; Q61

Diabetes with end organ damage: 249.01-249.05; 249.08; 250.01-250.05; 250.08; E10.2-E10.8; E11.2-E11.8

Any tumor: 140-194; C00-C75

Leukemia: 204-207; C91-C95

Lymphoma: 200-203; 275.59; C81-C85; C88; C90; C96

Moderate to severe liver disease: 070.00; 070.02; 070:04; 070.06; 070.08; 573.00; 456.00-456.09; B15.0; B16.0; B16.2; B19.0; K70.4; K72; K76.6; I85

Metastatic solid tumor: 195-199; C76-C80

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Pedersen, A.B., Ehrenstein, V., Szépligeti, S.K. et al. Excess risk of venous thromboembolism in hip fracture patients and the prognostic impact of comorbidity. Osteoporos Int 28, 3421–3430 (2017). https://doi.org/10.1007/s00198-017-4213-y

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