Skip to main content

Advertisement

SpringerLink
Log in

History of cardiovascular disease and cardiovascular biomarkers are associated with 30-day mortality in patients with hip fracture

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Hip fractures are associated with increased mortality and it is important to identify risk factors. This study demonstrates that preexisting cardiovascular disease as well as cardiovascular biomarkers that are associated with increased 30-day mortality. These findings can be used to identify high-risk patients who might benefit from specialized care.

Introduction

This study investigates the association between cardiovascular disease (CVD), cardiovascular biomarkers, and 30-day mortality following a hip fracture.

Methods

The Danish National Patient Registry was used to investigate the association between CVD and mortality following hip fracture in a nationwide population-based cohort study. In a subset of the included patients (n = 355), blood samples were available from a local biobank. These samples were used for analyzing the association between specific biochemical markers and mortality. The primary outcome was 30-day mortality.

Results

A total of 113,211 patients were included in the population-based cohort study. Among these, heart failure was present in 9.4%, ischemic heart disease in 15.9%, and ischemic stroke in 12.0%. Within 30 days after the hip fracture, 11,488 patients died, resulting in an overall 30-day mortality of 10.1%. The 30-day mortality was significantly increased in individuals with preexisting CVD with multivariably adjusted odds ratios of 1.69 (95% confidence interval, 1.60–1.78) for heart failure, 1.23 (1.17–1.29) for ischemic heart disease, and 1.06 (1.00–1.12) for ischemic stroke. In the local database including 355 patients, 41 (11.5%) died within 30 days. The multivariably adjusted odds ratio for 30-day mortality increased with increasing NT-proBNP (2.36 [1.53–3.64] per quartile) and decreased with increasing HDL cholesterol (0.58 [0.41–0.82] per quartile). On this basis, we established a model for predicting the probability of death based on the biochemical markers.

Conclusion

Preexisting CVD was associated with increased 30-day mortality after a hip fracture. Furthermore, high levels of NT-proBNP and low levels of HDL cholesterol were associated with increased 30-day mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Incalzi RA, Capparella O, Gemma A, Camaioni D, Sanguinetti C, Carbonin PU (1994) Predicting in-hospital mortality after hip fracture in elderly patients. J Trauma 36(1):79–82

    Article  CAS  PubMed  Google Scholar 

  2. Hu F, Jiang C, Shen J, Tang P, Wang Y (2012) Preoperative predictors for mortality following hip fracture surgery: a systematic review and meta-analysis. Injury 43(6):676–685

    Article  PubMed  Google Scholar 

  3. Kannegaard PN, van der Mark S, Eiken P, Abrahamsen B (2010) Excess mortality in men compared with women following a hip fracture. National analysis of comedications, comorbidity and survival. Age Ageing 39(2):203–209

    Article  PubMed  Google Scholar 

  4. Norring-Agerskov D, Laulund AS, Lauritzen JB, Duus BR, van der Mark S, Mosfeldt M, Jørgensen HL (2013) Metaanalysis of risk factors for mortality in patients with hip fracture. Dan Med J 60(8):A4675

    PubMed  Google Scholar 

  5. Praetorius K, Madsen CM, Abrahamsen B, Jorgensen HL, Lauritzen JB, Laulund ASB (2016) Low levels of hemoglobin at admission are associated with increased 30-day mortality in patients with hip fracture. Geriatr Orthop Surg Rehabil 7(3):1–6

    Article  Google Scholar 

  6. Gruson KI, Aharonoff GB, Egol KA, Zuckerman JD, Koval KJ (2002) The relationship between admission hemoglobin level and outcome after hip fracture. J Orthop Trauma 16(1):39–44

    Article  PubMed  Google Scholar 

  7. Norring-Agerskov D, Madsen CM, Abrahamsen B, Riis T, Pedersen OB, Jørgensen NR, Bathum L, Lauritzen JB, Jørgensen HL (2017) Hyperkalemia is associated with increased 30-day mortality in hip fracture patients. Calcif Tissue Int 101(1):9–16

    Article  CAS  PubMed  Google Scholar 

  8. Madsen CM, Jantzen C, Lauritzen JB, Abrahamsen B, Jorgensen HL (2015) Hyponatremia and hypernatremia are associated with increased 30-day mortality in hip fracture patients. Osteoporos Int 27(1):297–404

    Google Scholar 

  9. Mosfeldt M, Pedersen OB, Riis T, Worm HO, S v M, Jorgensen HL et al (2012) Value of routine blood tests for prediction of mortality risk in hip fracture patients. Acta Orthop 83(1):31–35

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hietala P, Strandberg M, Strandberg N, Gullichsen E, Airaksinen KEJ (2013) Perioperative myocardial infarctions are common and often unrecognized in patients undergoing hip fracture surgery. J Trauma Acute Care Surg 74(4):1087–1091

    Article  PubMed  Google Scholar 

  11. Sennerby U, Melhus H, Gedeborg R, Byberg L, Garmo H, Ahlbom A, Pedersen NL, Michaëlsson K (2009) Cardiovascular diseases and risk of hip fracture. Jama 302(15):1666–1673

    Article  CAS  PubMed  Google Scholar 

  12. Van Diepen S, Majumdar SR, Bakal JA, McAlister FA, Ezekowitz JA (2008) Heart failure is a risk factor for orthopedic fracture: a population-based analysis of 16 294 patients. Circulation 118(19):1946–1952

    Article  PubMed  Google Scholar 

  13. Tankó LB, Bagger YZ, Christiansen C (2003) Low bone mineral density in the hip as a marker of advanced atherosclerosis in elderly women. Calcif Tissue Int 73(1):15–20

    Article  CAS  PubMed  Google Scholar 

  14. Von der Recke P, Hansen MA, Hassager C (1999) The association between low bone mass at the menopause and cardiovascular mortality. Am J Med 106(3):273–278

    Article  PubMed  Google Scholar 

  15. Van der Klift M, Pols HAP, Hak AE, Witteman JCM, Hofman A, De Laet CEDH (2002) Bone mineral density and the risk of peripheral arterial disease: the Rotterdam study. Calcif Tissue Int 70(6):443–449

    Article  CAS  PubMed  Google Scholar 

  16. Devereaux PJ, Xavier D, Pogue J, Guyatt G, Sigamani A, Garutti I, Leslie K, Rao-Melacini P, Chrolavicius S, Yang H, Macdonald C, Avezum A, Lanthier L, Hu W, Yusuf S, POISE (PeriOperative ISchemic Evaluation) Investigators (2011) Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: cohort study. Ann Intern Med 154(8):523–528

    Article  CAS  PubMed  Google Scholar 

  17. Chong CP, Lam QT, Ryan JE, Sinnappu RN, Lim WK (2009) Incidence of post-operative troponin I rises and 1-year mortality after emergency orthopaedic surgery in older patients. Age Ageing 38(2):168–174

    Article  PubMed  Google Scholar 

  18. Sellers D, Srinivas C, Djaiani G (2018) Cardiovascular complications after non-cardiac surgery. Anaesthesia 73:34–42

    Article  PubMed  Google Scholar 

  19. Yasue H, Yoshimura M, Sumida H, Kikuta K, Kugiyama K, Jougasaki M, Ogawa H, Okumura K, Mukoyama M, Nakao K (1994) Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation 90(1):195–203

    Article  CAS  PubMed  Google Scholar 

  20. Mukoyama M, Nakao K, Saito Y, Ogawa Y, Hosoda K, Suga S, Shirakami G, Jougasaki M, Imura H (1990) Increased human brain natriuretic peptide in congestive heart failure. N Engl J Med 323(11):757–758

    Article  CAS  PubMed  Google Scholar 

  21. Nordling P, Kiviniemi T, Strandberg M, Strandberg N, Airaksinen J (2016) Predicting the outcome of hip fracture patients by using N-terminal fragment of pro-B-type natriuretic peptide. BMJ Open 6(2):1–6

    Article  Google Scholar 

  22. Oscarsson A, Fredrikson M, Sörliden M, Anskär S, Eintrei C (2009) N-terminal fragment of pro-B-type natriuretic peptide is a predictor of cardiac events in high-risk patients undergoing acute hip fracture surgery. Br J Anaesth 103(2):206–212

    Article  CAS  PubMed  Google Scholar 

  23. Ushirozako H, Ohishi T, Fujita T, Suzuki D, Yamamoto K, Banno T, Takase H, Matsuyama Y (2017) Does N-terminal pro-brain type natriuretic peptide predict cardiac complications after hip fracture surgery? Clin Orthop Relat Res 475(6):1730–1736

    Article  PubMed  PubMed Central  Google Scholar 

  24. Mahajan VS, Jarolim P (2011) How to interpret elevated cardiac troponin levels. Circulation 124(21):2350–2354

    Article  PubMed  Google Scholar 

  25. Thygesen K, Mair J, Katus H, Plebani M, Venge P, Collinson P, Lindahl B, Giannitsis E, Hasin Y, Galvani M, Tubaro M, Alpert JS, Biasucci LM, Koenig W, Mueller C, Huber K, Hamm C, Jaffe AS, the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care (2010) Recommendations for the use of cardiac troponin measurement in acute cardiac care. Eur Heart J 31:2197–2204

    Article  CAS  PubMed  Google Scholar 

  26. Dawson-Bowling S, Chettiar K, Cottam H, Worth R, Forder J, Fitzgerald-O’Connor I, Walker D, Apthorp H (2008) Troponin T as a predictive marker of morbidity in patients with fractured neck of femur. Injury 39(7):775–780

    Article  PubMed  Google Scholar 

  27. Izhaki A, Slesarenko Y, Boaz M, Haimovich Y, Rozenman Y (2011) Cardiac troponin T: an important predictor of late death and myocardial infarction following hip fracture: an eight-year prospective observational cohort study. Eur J Orthop Surg Traumatol 21(4):243–249

    Article  Google Scholar 

  28. Hietala P, Strandberg M, Kiviniemi T, Strandberg N, Airaksinen KEJ (2014) Usefulness of troponin T to predict short-term and long-term mortality in patients after hip fracture. Am J Cardiol 114(2):193–197

    Article  CAS  PubMed  Google Scholar 

  29. Lynge E, Sandegaard JL, Rebolj M (2011) The Danish National Patient Register. Scand J Public Health 39:30–33

    Article  PubMed  Google Scholar 

  30. Pedersen CB (2011) The Danish civil registration system. Scand J Public Health 39:22–25

    Article  PubMed  Google Scholar 

  31. Helweg-Larsen K (2011) The Danish register of causes of death. Scand J Public Health 39:26–29

    Article  PubMed  Google Scholar 

  32. 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 

  33. Kildemoes HW, Sørensen HT, Hallas J (2011) The Danish National Prescription Registry. Scand J Public Health 39:38–41

    Article  PubMed  Google Scholar 

  34. Stenhagen M, Ekström H, Nordell E, Elmståhl S (2013) Falls in the general elderly population: a 3- and 6- year prospective study of risk factors using data from the longitudinal population study good ageing in Skane. BMC Geriatr 13:81

  35. Cullen MW, Gullerud RE, Larson DR, Melton LJ, Huddleston JM (2011) Impact of heart failure on hip fracture outcomes: a population-based study. J Hosp Med 6(9):507–512

    Article  PubMed  Google Scholar 

  36. Kim BS, Kim T-H, Oh J-H, Kwon CH, Kim SH, Kim H-J, Hwang HK, Chung SM (2018) Association between preoperative high sensitive troponin I levels and cardiovascular events after hip fracture surgery in the elderly. J Geriatr Cardiol 15(3):215–221

    PubMed  PubMed Central  Google Scholar 

  37. Gordon D, Rifking BM (1989) High-density lipoprotein-- the clinical implications of recent studies. N Engl J Med 321(19):1311–1313

    Article  CAS  PubMed  Google Scholar 

  38. Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM et al (2007) HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 357(13):1301–1310

    Article  CAS  PubMed  Google Scholar 

  39. Rye K-A, Bursill CA, Lambert G, Tabet F, Barter PJ (2008) The metabolism and anti-atherogenic properties of HDL. J Lipid Res 50(Supplement):S195–S200

    Article  CAS  PubMed  Google Scholar 

  40. Lewis GF, Rader DJ (2005) New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res 96:1221–1232

  41. Urbina EM, Khoury PR, McCoy CE, Dolan LM, Daniels SR, Kimball TR (2013) Triglyceride to HDL-C ratio and increased arterial stiffness in children, adolescents, and young adults. [erratum appears in pediatrics. 2013 Oct;132(4):780. Pediatrics 131(4):e1082–e1090

    Article  PubMed  PubMed Central  Google Scholar 

  42. Gaziano JM, Hennekens CH, O’Donnell CJ, Breslow JL, Buring JE (1997) Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation 96(8):2520–2525

    Article  CAS  PubMed  Google Scholar 

  43. Vega GL, Barlow CE, Grundy SM, Leonard D, DeFina LF (2016) Triglyceride–to–high-density-lipoprotein-cholesterol ratio is an index of heart disease mortality and of incidence of type 2 diabetes mellitus in men. J Investig Med 62(2):345–349

    Article  Google Scholar 

  44. Fisher AA, Southcott EN, Goh SL, Srikusalanukul W, Hickman PE, Davis MW, Potter JM, Budge MM, Smith PN (2008) Elevated serum cardiac troponin I in older patients with hip fracture: incidence and prognostic significance. Arch Orthop Trauma Surg 128(10):1073–1079

    Article  CAS  PubMed  Google Scholar 

  45. Peacock WF, De Marco T, Fonarow GC, Diercks D, Wynne J, Apple FS et al (2008) Cardiac troponin and outcome in acute heart failure. N Engl J Med 358(20):2117–2126

    Article  CAS  PubMed  Google Scholar 

  46. Karres J, Heesakkers NA, Ultee JM, Vrouenraets BC (2015) Predicting 30-day mortality following hip fracture surgery: evaluation of six risk prediction models. Injury 46(2):371–377

    Article  PubMed  Google Scholar 

  47. Copeland GP, Jones D, Walters M (1991) POSSUM: a scoring system for surgical audit. Br J Surg 78(3):355–360

    Article  CAS  PubMed  Google Scholar 

  48. Jiang HX, Majumdar SR, Dick DA, Moreau M, Raso J, Otto DD et al (2005) Development and initial validation of a risk score for predicting in-hospital and 1-year mortality in patients with hip fractures. J Bone Miner Res 20(3):494–500

    Article  CAS  PubMed  Google Scholar 

  49. Jansen S, Bhangu J, de Rooij S, Daams J, Kenny RA, van der Velde N (2016) The Association of Cardiovascular Disorders and Falls: a systematic review. J Am Med Dir Assoc 17(3):193–199

    Article  PubMed  Google Scholar 

  50. Schmidt M, Pedersen L, Sørensen HT (2014) The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol 29(8):541–549

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Biochemistry, Hvidovre Hospital, Kettegård Alle 30, 2650, Hvidovre, Denmark

    D. Norring-Agerskov, L. Bathum & H. L. Jørgensen

  2. Open Patient Data Explorative Network, University of Southern Denmark and Odense University Hospital, J.B. Winsløws Vej 9A, 5000, Odense C, Denmark

    D. Norring-Agerskov & N. R. Jørgensen

  3. Department of Clinical Biochemistry, Herlev og Gentofte Hospital, Herlev Ringvej 75, 2730, Herlev, Denmark

    C. M. Madsen

  4. Department of Clinical Immunology, Næstved Sygehus, Ringstedgade 61, 4700, Næstved, Denmark

    O. B. Pedersen

  5. Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark

    J. B. Lauritzen & H. L. Jørgensen

  6. Department of Orthopedic Surgery, Bispebjerg Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark

    J. B. Lauritzen

  7. Department of Clinical Biochemistry, Rigshospitalet, Valdemar Hansens Vej 13, 2600, Glostrup, Denmark

    N. R. Jørgensen

Authors
  1. D. Norring-Agerskov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. M. Madsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Bathum
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O. B. Pedersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. B. Lauritzen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. N. R. Jørgensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. L. Jørgensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors have contributed significantly to the manuscript. Study design: All authors. Processing and preparation of raw data for subsequent analyses: HLJ. Preparation of biobank material: DNA. Data analysis: DNA, CMM, and HLJ. Interpretation of data: All authors. Drafting of the manuscript: DNA. Critical review of the manuscript for intellectual content and approval of the final version: All authors. Guarantor: DNA.

Corresponding author

Correspondence to D. Norring-Agerskov.

Ethics declarations

This study was approved by the Danish Data Protection Agency (2012-58-0004)/local number BBH-2014-050, by Statistics Denmark (project number 704670) and by the ethics committee of the Capital Region of Denmark (H-B-2007-103 / 61361).

Conflicts of interest

None.

Human and animal rights and informed consent

Most of the data is derived from registers and the data was anonymized prior to our use. In this case, informed consent from the individual patients is not required according to Danish law. Informed consent was obtained for all the patients included in the biobank. Animals were not used in this study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Norring-Agerskov, D., Madsen, C.M., Bathum, L. et al. History of cardiovascular disease and cardiovascular biomarkers are associated with 30-day mortality in patients with hip fracture. Osteoporos Int 30, 1767–1778 (2019). https://doi.org/10.1007/s00198-019-05056-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-019-05056-w

Keywords

Search

Navigation