Admission Inflammation Markers Influence Long-term Mortality in Elderly Patients Undergoing Hip Fracture Surgery: A Retrospective Cohort Study

Abstract

Objectives:: Hip fractures in elderly patients are associated with a high mortality rate. Most deaths associated with hip fracture result from complications after surgery. Recent studies suggest that some inflammation biomarkers may be useful to estimate excess mortality. This study aimed to investigate the prognostic value of admission inflammation biomarkers in elderly patients with hip fracture.

Methods:: We reports on a retrospective study of elderly hip fracture patients admitted to a hospital in China between January 2015 and December 2019. A total of 1085 patients were included in the study, and their demographic and pre-operative characteristics were analyzed. The inflammation biomarkers included monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), and C-reactive protein (CRP) to albumin ratio (CAR). The predictive performance of NLR, MLR and CAR was assessed by receiver operating characteristics (ROC) curve analysis and the association between admission inflammation markers and mortality was evaluated by Cox proportional regression.

Results:: The 30-day, 1-year, 2-year, and 4-year mortality were 1.6%, 11.5%, 21.4% and 48.9%, respectively. The optimal cut-off values of admission NLR, MLR and CAR for 1-year mortality were 7.28, 0.76, and 1.36. After adjusting the covariates, preoperative NLR ≥ 7.28 (HR = 1.419, 95% CI: 1.080–1.864, p = 0.012) were found to be only independent risk factors with 4-year all-cause mortality, the preoperative CAR ≥ 1.36 was independently associated with 1-year (HR = 1.700, 95% CI: 1.173–2.465, p = 0.005), 2 year (HR = 1.464, 95% CI: 1.107–1.936, p = 0.008), and 4-year (HR = 1.341, 95% CI: 1.057–1.700, p = 0.016) all-cause mortality, While age, CCI score, and low hemoglobin at admission were also risk factors for postoperative all-cause mortality.

Conclusion:: Admission CAR and NLR may be useful indicators for predicting the long-term mortality of elderly patients undergoing hip fracture surgery, and that more research is needed to validate these findings.

Keywords

C-reactive protein to albumin ratio / Hip fracture / Inflammation / Long-term mortality / Neutrophil to lymphocyte ratio

References

[1] Cooper C, Campion G, Melton LJ. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 1992;2:285–289.

[2] Abrahamsen B, van Staa T, Ariely R, Olson M, Cooper C. Excess mortality following hip fracture: a systematic epidemiological review. Osteoporos Int. 2009;20:1633–1650.

[3] Sedlar M, Kudrnova Z, Trca S, et al. Inflammatory response in patients undergoing hip surgery due to osteoarthrosis or different types of hip fractures. Osteoarthr Cartil. 2008;16:26–33.

[4] Imtiaz F, Shafique K, Mirza SS, Ayoob Z, Vart P, Rao S. Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med. 2012;5:2.

[5] Barbour KE, Lui LY, Ensrud KE, Hillier TA, LeBlanc ES, Ing SW, et al. Inflammatory markers and risk of hip fracture in older white women: the study of osteoporotic fractures. J Bone Miner Res. 2014;29:2057–2064.

[6] Kim BG, Lee YK, Park HP, Sohn HM, Oh AY, Jeon YT, et al. C-reactive protein is an independent predictor for 1-year mortality in elderly patients undergoing hip fracture surgery: a retrospective analysis. Medicine (Baltimore). 2016;95:e5152.

[7] Belangero W, Barla JD, Rienzi Bergalli DH, Olarte Salazar CM, Fernandez DS, Mite Vivar MA, et al. Nutrition and inflammation influence 1-year mortality of surgically treated elderly intertrochanteric fractures: a prospective international multicenter case series. Geriatr Orthop Surg Rehabil. 2019;10.

[8] Bingol O, Ozdemir G, Kulakoglu B, Keskin OH, Korkmaz I, Kilic E. Admission neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio to predict 30-day and 1-year mortality in geriatric hip fractures. Injury. 2020;51:2663–2667.

[9] Kim HJ, Lee S, Kim SH, Lee S, Sim JH, Ro YJ. Association of C-reactive protein to albumin ratio with postoperative delirium and mortality in elderly patients undergoing hip fracture surgery: a retrospective cohort study in a single large center. Exp Gerontol. 2023;172:112068.

[10] Chen YH, Chou CH, Su HH, Tsai YT, Chiang MH, Kuo YJ, et al. Correlation between neutrophil-to-lymphocyte ratio and postoperative mortality in elderly patients with hip fracture: a meta-analysis. J Orthop Surg Res. 2021;16:681.

[11] Atlas A, Duran E, Pehlivan B, Pehlivan VF, Erol MK, Altay N. The effect of increased neutrophil lymphocyte ratio on mortality in patients operated on due to hip fracture. Cureus. 2020;12:e6543.

[12] Niessen R, Bihin B, Gourdin M, Yombi JC, Cornu O, Forget P. Prediction of postoperative mortality in elderly patient with hip fractures: a single-Centre, retrospective cohort study. BMC Anesthesiol. 2018;18:183.

[13] Wang ZC, Jiang W, Chen X, Yang L, Wang H, Liu YH. Systemic immune-inflammation index independently predicts poor survival of older adults with hip fracture: a prospective cohort study. BMC Geriatr. 2021;21:155.

[14] Giannoulis D, Calori GM, Giannoudis PV. Thirty-day mortality after hip fractures: has anything changed? Eur J Orthop Surg Traumatol. 2016;26:365–370.

[15] Choi HJ, Kim E, Shin YJ, Choi BY, Kim YH, Lim TH. The timing of surgery and mortality in elderly hip fractures: a retrospective, multicenteric cohort study. Indian J Orthop. 2014;48:599–604.

[16] Cui Z, Feng H, Meng X, Zhuang S, Liu Z, Ye K, et al. Age-specific 1-year mortality rates after hip fracture based on the populations in mainland China between the years 2000 and 2018: a systematic analysis. Arch Osteoporos. 2019;14:55.

[17] Lv H, Zhang L, Long A, Mao Z, Shen J, Yin P, et al. Red cell distribution width as an independent predictor of long-term mortality in hip fracture patients: a prospective cohort study. J Bone Miner Res. 2016;31:223–233.

[18] Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375:132–140.

[19] Afari ME, Bhat T. Neutrophil to lymphocyte ratio (NLR) and cardiovascular diseases: an update. Expert Rev Cardiovasc Ther. 2016;14:573–577.

[20] Temiz A, Ersozlu S. Admission neutrophil-to-lymphocyte ratio and postoperative mortality in elderly patients with hip fracture. Ulus Travma Acil Cerrahi Derg. 2019;25:71–74.

[21] Tekin SB, Bozgeyik B, Mert A. Relationship between admission neutrophil/lymphocyte, thrombocyte/lymphocyte, and monocyte/lymphocyte ratios and 1-year mortality in geriatric hip fractures: triple comparison. Ulus Travma Acil Cerrahi Derg. 2022;28:1634–1640.

[22] Norring-Agerskov D, Bathum L, Pedersen OB, Abrahamsen B, Lauritzen JB, Jørgensen NR, et al. Biochemical markers of inflammation are associated with increased mortality in hip fracture patients: the Bispebjerg Hip Fracture Biobank. Aging Clin Exp Res. 2019;31:1727–1734.

[23] Bohl DD, Shen MR, Hannon CP, Fillingham YA, Darrith B, Della Valle CJ. Serum albumin predicts survival and postoperative course following surgery for geriatric hip fracture. J Bone Joint Surg Am. 2017;99:2110–2118.

[24] Capkin S, Guler S, Ozmanevra R. C-reactive protein to albumin ratio may predict mortality for elderly population who undergo hemiarthroplasty due to hip fracture. J Invest Surg. 2021;34:1272–1277.

[25] Guzon-Illescas O, Perez Fernandez E, Crespi Villarias N, et al. Mortality after osteoporotic hip fracture: incidence, trends, and associated factors. J Orthop Surg Res. 2019;14:203.

[26] Pillai A, Eranki V, Shenoy R, Hadidi M. Age related incidence and early outcomes of hip fractures: a prospective cohort study of 1177 patients. J Orthop Surg Res. 2011;6:5.

[27] Cher EWL, Allen JC, Howe TS, Koh JSB. Comorbidity as the dominant predictor of mortality after hip fracture surgeries. Osteoporos Int. 2019;30:2477–2483.

[28] Barcelo M, Torres OH, Mascaro J, Casademont J. Hip fracture and mortality: study of specific causes of death and risk factors. Arch Osteoporos. 2021;16:15.

[29] Ackermann L, Schwenk ES, Lev Y, Weitz H. Update on medical management of acute hip fracture. Cleve Clin J Med. 2021;88:237–247.

[30] Sterling RS. Gender and race/ethnicity differences in hip fracture incidence, morbidity, mortality, and function. Clin Orthop Relat Res. 2011;469:1913–1918.

[31] Pech-Ciau BA, Lima-Martinez EA, Espinosa-Cruz GA, Pacho-Aguilar CR, Huchim-Lara O, Alejos-Gomez RA. Hip fracture in the elderly: epidemiology and costs of care. Acta Ortop Mex. 2021;35:341–347.

[32] Xu BY, Yan S, Low LL, Vasanwala FF, Low SG. Predictors of poor functional outcomes and mortality in patients with hip fracture: a systematic review. BMC Musculoskelet Disord. 2019;20:568.

[33] Cauley JA, Cawthon PM, Peters KE, Cummings SR, Ensrud KE, Bauer DC, et al. Risk factors for hip fracture in older men: the osteoporotic fractures in men study (MrOS). J Bone Miner Res. 2016;31:1810–1819.

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2023 2023 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.