Objective: Hip fracture causes significant morbidity and mortality, necessitating the identification of biomarkers for risk stratification. This study aimed to evaluate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and incidence of postoperative complications and the 2-year all-cause mortality among hip fracture patients.
Methods: This retrospective cohort study involved 2595 patients aged from 45 years who received surgery for hip fracture between 2000 and 2022. Preoperative NT-proBNP levels were used to divide patients into three groups: low (< 123.27 pg/mL), moderate (123.27–349.93 pg/mL), and high (> 349.93 pg/mL) NT-proBNP group. Multivariate logistic regression and Cox proportional hazards models were used to evaluate the odds ratio (OR) for postoperative complications and the hazard ratio (HR) for mortality, after adjusting for potential confounders.
Results: Post-operative complications were reported in 171 (6.59%) patients with mortality of 226 (8.71%) during the 2-year follow-up. Compared to patients with low NT-proBNP group, the adjusted odds ratio for postoperative complications was 1.21 (95% CI 0.69–2.15) for those in the moderate NT-proBNP group and 2.33 (95% CI 1.35–4.03) for those in the high NT-proBNP group. Similarly, the adjusted hazard ratio for 2-year all-cause mortality was 1.51 (95% CI 0.91–2.50) for those in the moderate NT-proBNP group and 2.66 (95% CI 1.63–4.32) for those in the high NT-proBNP group. Higher pre-operative NT-proBNP levels were associated with an increased risk for postoperative complications and 2-year all-cause mortality (both p for trend < 0.001) among hip fracture patients. The results were consistent across various subgroup and sensitivity analyses.
Conclusion: Preoperative NT-proBNP is strongly associated with both postoperative complications and 2-year all-cause mortality among patients received hip fracture surgery. Higher levels of NT-proBNP before surgery may serve as a useful biomarker for risk stratification and guiding treatment decisions for this patient subpopulation.
| [1] |
J. A. Cauley, D. Chalhoub, A. M. Kassem, and G. E. H. Fuleihan, “Geographic and Ethnic Disparities in Osteoporotic Fractures,” Nature Reviews Endocrinology 10, no. 6 (2014): 338–351.
|
| [2] |
M. M. Cao, J. Y. Chi, Y. W. Zhang, et al., “The Efficacy and Safety of Intravenous Iron in Geriatric Hip Fracture Surgeries: A Systematic Review and Meta-Analysis,” World Journal of Surgery 46, no. 11 (2022): 2595–2606.
|
| [3] |
C. Zhang, J. Feng, S. Wang, et al., “Incidence of and Trends in Hip Fracture Among Adults in Urban China: A Nationwide Retrospective Cohort Study,” PLoS Medicine 17, no. 8 (2020): e1003180.
|
| [4] |
K. F. Axelsson, A. G. Nilsson, H. Wedel, D. Lundh, and M. Lorentzon, “Association Between Alendronate Use and Hip Fracture Risk in Older Patients Using Oral Prednisolone,” Journal of the American Medical Association 318, no. 2 (2017): 146–155.
|
| [5] |
D. Bliuc, N. D. Nguyen, V. E. Milch, T. V. Nguyen, J. A. Eisman, and J. R. Center, “Mortality Risk Associated With Low-Trauma Osteoporotic Fracture and Subsequent Fracture in Men and Women,” Journal of the American Medical Association 301, no. 5 (2009): 513–521.
|
| [6] |
Y. W. Zhang, P. P. Lu, Y. J. Li, et al., “Prevalence, Characteristics, and Associated Risk Factors of the Elderly With Hip Fractures: A Cross-Sectional Analysis of NHANES 2005-2010,” Clinical Interventions in Aging 16 (2021): 177–185.
|
| [7] |
T. J. Wang, M. G. Larson, D. Levy, et al., “Plasma Natriuretic Peptide Levels and the Risk of Cardiovascular Events and Death,” New England Journal of Medicine 350, no. 7 (2004): 655–663.
|
| [8] |
L. B. Daniels, G. A. Laughlin, P. Clopton, A. S. Maisel, and E. Barrett-Connor, “Minimally Elevated Cardiac Troponin T and Elevated N-Terminal Pro-B-Type Natriuretic Peptide Predict Mortality in Older Adults: Results From the Rancho Bernardo Study,” Journal of the American College of Cardiology 52, no. 6 (2008): 450–459.
|
| [9] |
J. B. Echouffo-Tcheugui, S. Zhang, N. Daya, et al., “NT-proBNP and All-Cause and Cardiovascular Mortality in US Adults: A Prospective Cohort Study,” Journal of the American Heart Association 12, no. 11 (2023): e029110.
|
| [10] |
A. D. Høiseth, T. Omland, T. A. Hagve, P. H. Brekke, and V. Søyseth, “NT-proBNP Independently Predicts Long Term Mortality After Acute Exacerbation of COPD - a Prospective Cohort Study,” Respiratory Research 13, no. 1 (2012): 97.
|
| [11] |
F. Wang, Y. Wu, L. Tang, et al., “Brain Natriuretic Peptide for Prediction of Mortality in Patients With Sepsis: A Systematic Review and Meta-Analysis,” Critical Care 16, no. 3 (2012): R74.
|
| [12] |
A. Oscarsson, M. Fredrikson, M. Sörliden, S. Anskär, and C. Eintrei, “N-Terminal Fragment of Pro-B-Type Natriuretic Peptide Is a Predictor of Cardiac Events in High-Risk Patients Undergoing Acute Hip Fracture Surgery,” British Journal of Anaesthesia 103, no. 2 (2009): 206–212.
|
| [13] |
H. Ushirozako, T. Ohishi, T. Fujita, et al., “Does N-Terminal Pro-Brain Type Natriuretic Peptide Predict Cardiac Complications After Hip Fracture Surgery?,” Clinical Orthopaedics and Related Research 475, no. 6 (2017): 1730–1736.
|
| [14] |
P. Nordling, T. Kiviniemi, M. Strandberg, N. Strandberg, and J. Airaksinen, “Predicting the Outcome of Hip Fracture Patients by Using N-Terminal Fragment of Pro-B-Type Natriuretic Peptide,” BMJ Open 6, no. 2 (2016): e009416.
|
| [15] |
B. F. Zhang, D. Y. Li, D. X. Lu, and M. X. Wang, “The Serum NT-proBNP Is Associated With All-Cause Mortality in Geriatric Hip Fracture: A Cohort of 1354 Patients,” Archives of Osteoporosis 18, no. 1 (2023): 99.
|
| [16] |
Y. Wang, Y. Jiang, Y. Luo, et al., “Prognostic Nutritional Index With Postoperative Complications and 2-Year Mortality in Hip Fracture Patients: An Observational Cohort Study,” International Journal of Surgery 109, no. 11 (2023): 3395–3406.
|
| [17] |
Y. Jiang, X. Lin, Y. Wang, et al., “Preoperative Anemia and Risk of in-Hospital Postoperative Complications in Patients With Hip Fracture,” Clinical Interventions in Aging 18 (2023): 639–653.
|
| [18] |
H. Lv, L. Zhang, A. Long, et al., “Red Cell Distribution Width as an Independent Predictor of Long-Term Mortality in Hip Fracture Patients: A Prospective Cohort Study,” Journal of Bone and Mineral Research 31, no. 1 (2016): 223–233.
|
| [19] |
S. Tan, Y. Jiang, K. Qin, et al., “Systemic Immune-Inflammation Index and 2-Year All-Cause Mortality in Elderly Patients With Hip Fracture,” Archives of Gerontology and Geriatrics 129 (2025): 105695.
|
| [20] |
S. A. Adesina, S. U. Eyasan, I. O. Amole, et al., “Closed Reduction and Locked Intramedullary Nailing of Diaphyseal Long Bone Fractures Without Intra-Operative Imaging and Fracture Table,” International Orthopaedics 46, no. 1 (2022): 51–59.
|
| [21] |
R. Gupta, C. N. Day, W. O. Tobin, and C. S. Crowson, “Understanding the Effect of Categorization of a Continuous Predictor With Application to Neuro-Oncology,” Neuro-Oncology Practice 9, no. 2 (2022): 87–90.
|
| [22] |
C. Custodero, Q. Wu, G. L. Ghita, et al., “Prognostic Value of NT-proBNP Levels in the Acute Phase of Sepsis on Lower Long-Term Physical Function and Muscle Strength in Sepsis Survivors,” Critical Care 23 (2019): 230.
|
| [23] |
M. E. Charlson, D. Carrozzino, J. Guidi, and C. Patierno, “Charlson Comorbidity Index: A Critical Review of Clinimetric Properties,” Psychotherapy and Psychosomatics 91, no. 1 (2022): 8–35.
|
| [24] |
M. M. Cao, Y. W. Zhang, R. W. Sheng, et al., “General Anesthesia Versus Regional Anesthesia in the Elderly Patients Undergoing Hip Fracture Surgeries: A Systematic Review and Meta-Analysis of Randomized Clinical Trials,” World Journal of Surgery 47, no. 6 (2023): 1444–1456.
|
| [25] |
E. Duceppe, A. Patel, M. T. V. Chan, et al., “Preoperative N-Terminal Pro-B-Type Natriuretic Peptide and Cardiovascular Events After Noncardiac Surgery: A Cohort Study,” Annals of Internal Medicine 172, no. 2 (2020): 96–104.
|
| [26] |
E. R. Levin, D. G. Gardner, and W. K. Samson, “Natriuretic peptides,” New England Journal of Medicine 339, no. 5 (1998): 321–328.
|
| [27] |
N. Hama, H. Itoh, G. Shirakami, et al., “Rapid Ventricular Induction of Brain Natriuretic Peptide Gene Expression in Experimental Acute Myocardial Infarction,” Circulation 92, no. 6 (1995): 1558–1564.
|
| [28] |
C. Fisher, C. Berry, L. Blue, J. J. Morton, and J. McMurray, “N-Terminal Pro B Type Natriuretic Peptide, but Not the New Putative Cardiac Hormone Relaxin, Predicts Prognosis in Patients With Chronic Heart Failure,” Heart 89, no. 8 (2003): 879–881.
|
| [29] |
M. Komajda, P. E. Carson, S. Hetzel, et al., “Factors Associated With Outcome in Heart Failure With Preserved Ejection Fraction: Findings From the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-PRESERVE),” Circulation. Heart Failure 4, no. 1 (2011): 27–35.
|
| [30] |
C. Kragelund, B. Grønning, L. Køber, P. Hildebrandt, and R. Steffensen, “N-Terminal Pro-B-Type Natriuretic Peptide and Long-Term Mortality in Stable Coronary Heart Disease,” New England Journal of Medicine 352, no. 7 (2005): 666–675.
|
| [31] |
K. K. Patton, P. T. Ellinor, S. R. Heckbert, et al., “N-Terminal Pro-B-Type Natriuretic Peptide Is a Major Predictor of the Development of Atrial Fibrillation: The Cardiovascular Health Study,” Circulation 120, no. 18 (2009): 1768–1774.
|
| [32] |
E. Braunwald, “Biomarkers in Heart Failure,” New England Journal of Medicine 358, no. 20 (2008): 2148–2159.
|
| [33] |
T. Hirata, Y. Arai, S. Yuasa, et al., “Associations of Cardiovascular Biomarkers and Plasma Albumin With Exceptional Survival to the Highest Ages,” Nature Communications 11, no. 1 (2020): 3820.
|
| [34] |
M. Èubrilo-Turek, V. Pilas, D. Striniæ, and K. Èala, “Serum Measurement of N-Terminal Pro-Brain Peptide Among Septic Patients,” Critical Care 12, no. Suppl 2 (2008): P443.
|
| [35] |
E. M. L. Bowman, E. L. Cunningham, V. J. Page, and D. F. McAuley, “Phenotypes and Subphenotypes of Delirium: A Review of Current Categorisations and Suggestions for Progression,” Critical Care 25, no. 1 (2021): 334.
|
| [36] |
B. S. Kim, T. H. Kim, J. H. Oh, et al., “Association Between Preoperative High Sensitive Troponin I Levels and Cardiovascular Events After Hip Fracture Surgery in the Elderly,” Journal of Geriatric Cardiology 15, no. 3 (2018): 215–221.
|
| [37] |
M. A. Araguas, A. Herrera, I. Garrido, J. Mateo, A. P. Mayoral, and M. Muñoz, “Risk Factors for Major Adverse Cardiovascular Events After Osteoporotic Hip Fracture Repair Surgery,” Injury 51, no. 1 (2020): S30–S36.
|
| [38] |
J. Bekeris, L. A. Wilson, D. Bekere, et al., “Trends in Comorbidities and Complications Among Patients Undergoing Hip Fracture Repair,” Anesthesia and Analgesia 132, no. 2 (2021): 475–484.
|
| [39] |
C. Li and W. Niu, “NT-proBNP in Early Pregnancy and Future Hypertension-More Explorations Needed,” JAMA Cardiology 7, no. 9 (2022): 989.
|
| [40] |
A. G. Almeida, “NT-proBNP and Myocardial Fibrosis: The Invisible Link Between Health and Disease,” Journal of the American College of Cardiology 70, no. 25 (2017): 3110–3112.
|
| [41] |
D. Norring-Agerskov, C. M. Madsen, L. Bathum, et al., “History of Cardiovascular Disease and Cardiovascular Biomarkers Are Associated With 30-Day Mortality in Patients With Hip Fracture,” Osteoporosis International 30, no. 9 (2019): 1767–1778.
|
| [42] |
L. Yang, H. Yang, Q. Chen, H. Shen, and Z. Wang, “Analysis of Risk Factors for 90-Day Mortality After Surgery in Elderly Patients With Intertrochanteric Fractures and a History of Cardiovascular Disease,” Annals of Palliative Medicine 11, no. 1 (2022): 155–162.
|
| [43] |
P. L. Myhre, B. L. Claggett, A. M. Shah, et al., “Changes in Cardiac Biomarkers in Association With Alterations in Cardiac Structure and Function, and Health Status in Heart Failure With Reduced Ejection Fraction: The EVALUATE-HF Trial,” European Journal of Heart Failure 24, no. 7 (2022): 1200–1208.
|
| [44] |
Y. Luo, Y. Jiang, H. Xu, et al., “Risk of Post-Operative Cardiovascular Event in Elderly Patients With Pre-Existing Cardiovascular Disease Who Are Undergoing Hip Fracture Surgery,” International Orthopaedics 45, no. 12 (2021): 3045–3053.
|
| [45] |
Y. Sun, M. Ma, D. Cao, et al., “Inhibition of Fap Promotes Cardiac Repair by Stabilizing BNP,” Circulation Research 132, no. 5 (2023): 586–600.
|
| [46] |
L. Xu, W. Lyu, P. Wei, et al., “Lower Preoperative Serum Uric Acid Level May Be a Risk Factor for Postoperative Delirium in Older Patients Undergoing Hip Fracture Surgery: A Matched Retrospective Case-Control Study,” BMC Anesthesiology 22, no. 1 (2022): 282.
|
| [47] |
S. H. Chen, B. F. Zhang, and Y. M. Zhang, “The Association Between Prealbumin Concentration at Admission and Mortality in Elderly Patients With Hip Fractures: A Cohort Study,” Archives of Osteoporosis 19, no. 1 (2024): 27.
|
| [48] |
Y. Zhang, D. Yu, X. Xu, Y. Guo, Z. Zhao, and S. Ji, “Prealbumin Adjusted Prognostic Nutritional Index May Predict the Postoperative Survival and Free Walking Abilities of Patients With Hip Fractures: A Multi-Center Follow-Up Study,” Clinical Interventions in Aging 20 (2025): 1571–1582.
|
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2026 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.