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Osteoporosis International

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01-08-2017 | Original Article

The role of adipokines as prognostic factors of one-year mortality in hip fracture patients

Authors: T. Gulin, I. Kruljac, L. S. Kirigin Biloš, M. Gulin, M. Grgurević, M. Borojević

Published in: Osteoporosis International | Issue 8/2017

Abstract

Summary

This study investigated the impact of anthropometric parameters, adiponectin, leptin, homeostatic model assessment for insulin resistance (HOMA-IR), beta-isomerised C-terminal telopeptide of collagen type I (β-CTX), and routine biochemical tests on one-year mortality in hip fracture patients. We found that male patients with high adiponectin, leptin, and β-CTX levels had a 5-fold increase in all-cause one-year mortality.

Introduction

Several predictors of one-year hip fracture mortality have been identified including advanced age, male sex, low bone mineral density, and preexisting comorbidities. However, the impact of metabolic parameters on hip fracture mortality remains unknown. The aim of this study was to examine the effect of serum leptin and adiponectin levels, as well as other metabolic parameters on all-cause one-year hip fracture mortality.

Methods

This prospective study included 236 patients of all ages with non-traumatic hip fractures. Anthropometric parameters, adiponectin, leptin, HOMA-IR, β-CTX, and routine biochemical tests were recorded at admission and correlated with one-year mortality by using multivariate Cox proportional hazard models.

Results

The median patient age was 82 (75–87) years, and one-year mortality rate was 28.4%. In univariate analysis, adiponectin, age, β-CTX, and renal function were associated with mortality. However, in a multivariate model, male gender, high β-CTX, adiponectin, and leptin were independently associated with increased mortality. Thus, we constructed a nomogram that included all the latter variables in addition to age. The nomogram predicted mortality with a sensitivity of 74.8% (66.0–82.3) and specificity of 74.4% (57.9–87.0), and had an area under the curve of 0.784. Patients that scored <9.2 had a mortality of 10.1%, while those with >9.2 had a mortality of 49.2% (relative risk 5.4, 95% CI 2.8–10.2, P < 0.001).

Conclusion

Male patients with high adiponectin, leptin, and β-CTX levels have a 5-fold increase in all-cause one-year mortality after hip fracture.

Gulin T, Kruljac I, Kirigin L, Merc M, Pavić M, Trcin MT, Bokulić A, Megla ŽB, Kaštelan D (2016) Advanced age, high β-CTX levels, and impaired renal function are independent risk factors for all-cause one-year mortality in hip fracture patients. Calcif Tissue Int 98(1):67–75. doi:10.1007/s00223-015-0070-x CrossRefPubMed

Isomaa B, Almgren P, Tuomi T, Forsén B, Lahti K, Nissén M, Taskinen MR, Groop L (2001) Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24(4):683–689CrossRefPubMed

Wannamethee SG, Tchernova J, Whincup P, Lowe GD, Kelly A, Rumley A, Wallace AM, Sattar N (2007) Plasma leptin: associations with metabolic, inflammatory and haemostatic risk factors for cardiovascular disease. Atherosclerosis 191:418–426CrossRefPubMed

Beltowski J (2006) Leptin and atherosclerosis. Atherosclerosis 189:47–60CrossRefPubMed

Allison MA, Ix JH, Morgan C, McClelland RL, Rifkin D, Shimbo D, Criqui MH (2013) Higher leptin is associated with hypertension: the multi-ethnic study of atherosclerosis. J Hum Hypertens 27(10):617–622. doi:10.1038/jhh.2013.24 CrossRefPubMedPubMedCentral

Franks PW, Brage S, Luan J, Ekelund U, Rahman M, Farooqi IS, Halsall I, O'Rahilly S, Wareham NJ (2005) Leptin predicts a worsening of the features of the metabolic syndrome independently of obesity. Obes Res 13(8):1476–1484CrossRefPubMed

Amrock SM, Weitzman M (2014) Effect of increased leptin and C-reactive protein levels on mortality: results from the National Health and Nutrition Examination Survey. Atherosclerosis 236(1):1–6. doi:10.1016/j.atherosclerosis.2014.06.009 CrossRefPubMedPubMedCentral

Wolk R, Berger P, Lennon RJ, Brilakis ES, Johnson BD, Somers VK (2004) Plasma leptin and prognosis in patients with established coronary atherosclerosis. J Am Coll Cardiol 44:1819–1824CrossRefPubMed

Söderberg S, Colquhoun D, Keech A, Yallop J, Barnes EH, Pollicino C, Simes J, Tonkin AM, Nestel P LIPID Study Investigators (2009) Leptin, but not adiponectin, is a predictor of recurrent cardiovascular events in men: results from the LIPID study. Int J Obes 33(1):123–130. doi:10.1038/ijo.2008.224 CrossRef

10.

Fernández-Riejos P, Najib S, Santos-Alvarez J, Martín-Romero C, Pérez-Pérez A, González-Yanes C, Sánchez-Margalet V (2010) Role of leptin in the activation of immune cells. Mediat Inflamm 2010:568343. doi:10.1155/2010/568343 CrossRef

11.

Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, Arita Y, Okamoto Y, Shimomura I, Hiraoka H, Nakamura T, Funahashi T, Matsuzawa Y, Osaka CAD Study Group Coronary artery disease (2003) Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 23(1):85–89CrossRefPubMed

12.

Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB (2004) Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 291(14):1730–1737CrossRefPubMed

13.

Kim DH, Kim C, Ding EL, Townsend MK, Lipsitz LA (2013) Adiponectin levels and the risk of hypertension: a systematic review and meta-analysis. Hypertension 62(1):27–32CrossRefPubMedPubMedCentral

14.

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

15.

Panula J, Pihlajamäki H, Mattila VM, Jaatinen P, Vahlberg T, Aarnio P, Kivelä SL (2011) Mortality and cause of death in hip fracture patients aged 65 or older: a population-based study. BMC Musculoskelet Disord 12:105. doi:10.1186/1471-2474-12-105 CrossRefPubMedPubMedCentral

16.

O'Daly BJ, Walsh JC, Quinlan JF, Falk GA, Stapleton R, Quinlan WR, O'Rourke SK (2013) Serum albumin and total lymphocyte count as predictors of outcome in hip fractures. Clin Nutr 29(1):89–93. doi:10.1016/j.clnu.2009.07.007 CrossRef

17.

Wiecek A, Adamczak M, Chudek J (2007) Adiponectin—an adipokine with unique metabolic properties. Nephrol Dial Transplant 22(4):981–988CrossRefPubMed

18.

Fisher AA, Srikusalanukul W, Davis MW, Smith PN (2012) Clinical profiles and risk factors for outcomes in older patients with cervical and trochanteric hip fracture: similarities and differences. J Trauma Manag Outcomes 6(1):2. doi:10.1186/1752-2897-6-2 CrossRefPubMedPubMedCentral

19.

Wu ZJ, Cheng YJ, Gu WJ, Aung LH (2014) Adiponectin is associated with increased mortality in patients with already established cardiovascular disease: a systematic review and meta-analysis. Metabolism 63(9):1157–1166. doi:10.1016/j.metabol.2014.05.001 CrossRefPubMed

20.

Cavusoglu E, Ruwende C, Chopra V, Yanamadala S, Eng C, Clark LT, Pinsky DJ, Marmur JD (2006) Adiponectin is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction in patients presenting with chest pain. Eur Heart J 27(19):2300–2309CrossRefPubMed

21.

Kistorp C, Faber J, Galatius S, Gustafsson F, Frystyk J, Flyvbjerg A, Hildebrandt P (2005) Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation 112(12):1756–1762CrossRefPubMed

22.

Forsblom C, Thomas MC, Moran J, Saraheimo M, Thorn L, Wadén J, Gordin D, Frystyk J, Flyvbjerg A, Groop PH, FinnDiane Study Group (2011) Serum adiponectin concentration is a positive predictor of all-cause and cardiovascular mortality in type 1 diabetes. J Intern Med 270(4):346–355. doi:10.1111/j.1365-2796.2011. 02406.x CrossRefPubMed

23.

Singer JR, Palmas W, Teresi J, Weinstock R, Shea S, Luchsinger JA (2012) Adiponectin and all-cause mortality in elderly people with type 2 diabetes. Diabetes Care 35(9):1858–1863. doi:10.2337/dc11-2215 CrossRefPubMedPubMedCentral

24.

Uetani E, Tabara Y, Kawamoto R, Onuma H, Kohara K, Osawa H, Miki T (2014) CDH13genotype-dependent association of high-molecular weight adiponectin with all-cause mortality: the J-SHIPP study. Diabetes Care 37(2):396–401. doi:10.2337/dc13-1658 CrossRefPubMed

25.

Poehls J, Wassel CL, Harris TB, Havel PJ, Swarbrick MM, Cummings SR, Newman AB, Satterfield S, Kanaya AM, Health ABC Study (2009) Association of adiponectin with mortality in older adults: the health, aging, and body composition study. Diabetologia 52(4):591–595. doi:10.1007/s00125-009-1261-7 CrossRefPubMedPubMedCentral

26.

Hascoet S, Elbaz M, Bongard V, Bouisset F, Verdier C, Vindis C, Genoux A, Taraszkiewicz D, Perret B, Galinier M, Carrié D, Ferrières J, Ruidavets JB (2013) Adiponectin and long-term mortality in coronary artery disease participants and controls. Arterioscler Thromb Vasc Biol 33(1):e19–e29. doi:10.1161/ATVBAHA.112.300079 CrossRefPubMed

27.

Van Berendoncks AM, Garnier A, Beckers P, Hoymans VY, Possemiers N, Fortin D, Martinet W, Van Hoof V, Vrints CJ, Ventura-Clapier R, Conraads VM (2010) Functional adiponectin resistance at the level of the skeletal muscle in mild to moderate chronic heart failure. Circ Heart Fail 3(2):185–194. doi:10.1161/CIRCHEARTFAILURE.109.885525 CrossRefPubMed

28.

Khan RS, Kato TS, Chokshi A, Chew M, Yu S, Wu C, Singh P, Cheema FH, Takayama H, Harris C, Reyes-Soffer G, Knöll R, Milting H, Naka Y, Mancini D, Schulze PC (2012) Adipose tissue inflammation and adiponectin resistance in patients with advanced heart failure: correction after ventricular assist device implantation. Circ Heart Fail 5(3):340–348. doi:10.1161/CIRCHEARTFAILURE.111.964031 CrossRefPubMedPubMedCentral

29.

Hui X, Lam KS, Vanhoutte PM, Xu A (2012) Adiponectin and cardiovascular health: an update. Br J Pharmacol 165(3):574–590. doi:10.1111/j.1476-5381.2011.01395.x Review CrossRefPubMedPubMedCentral

30.

Denzel MS, Scimia MC, Zumstein PM, Walsh K, Ruiz-Lozano P, Ranscht B (2010) T-cadherin is critical for adiponectin-mediated cardioprotection in mice. J Clin Invest 120(12):4342–4352. doi:10.1172/JCI43464 CrossRefPubMedPubMedCentral

31.

Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J, Möhlig M, Pfeiffer AF, Luft FC, Sharma AM (2003) Association between adiponectin and mediators of inflammation in obese women. Diabetes 52(4):942–947CrossRefPubMed

32.

Koch A, Sanson E, Voigt S, Helm A, Trautwein C, Tacke F (2011) Serum adiponectin upon admission to the intensive care unit may predict mortality in critically ill patients. J Crit Care 26(2):166–174. doi:10.1016/j.jcrc.2010.07.015 CrossRefPubMed

33.

Walkey AJ, Rice TW, Konter J, Ouchi N, Shibata R, Walsh K, deBoisblanc BP, Summer R (2010) Plasma adiponectin and mortality in critically ill subjects with acute respiratory failure. Crit Care Med 38(12):2329–2334. doi:10.1097/CCM.0b013e3181fa0561 CrossRefPubMedPubMedCentral

34.

Piemonti L, Calori G, Mercalli A, Lattuada G, Monti P, Garancini MP, Costantino F, Ruotolo G, Luzi L, Perseghin G (2003) Fasting plasma leptin, tumor necrosis factor-alpha receptor 2, and monocyte chemoattracting protein 1 concentration in a population of glucose-tolerant and glucose-intolerant women: impact on cardiovascular mortality. Diabetes Care 26(10):2883–2889CrossRefPubMed

35.

Ku IA, Farzaneh-Far R, Vittinghoff E, Zhang MH, Na B, Whooley MA (2011) Association of low leptin with cardiovascular events and mortality in patients with stable coronary artery disease: the Heart and Soul Study. Atherosclerosis 217(2):503–508. doi:10.1016/j.atherosclerosis.2010.10.047 CrossRefPubMed

36.

Bornstein SR, Licinio J, Tauchnitz R, Engelmann L, Negrão AB, Gold P, Chrousos GP (1998) Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in cortisol andleptin secretion. J Clin Endocrinol Metab 83(1):280–283CrossRefPubMed

37.

Arnalich F, López J, Codoceo R, Jim nez M, Madero R, Montiel C (1999) Relationship of plasma leptin to plasma cytokines and human survival in sepsis and septic shock. J Infect Dis 180(3):908–911CrossRefPubMed

38.

Bian X, Liu N, Bai Y, Zheng L, He P, Su X, Du F, Yang X, Li D (2014) Association of leptin with mortality in patients on maintenance hemodialysis: a prospective study. Iran J Kidney Dis 8(4):314–320PubMed

39.

Tonelli AR, Aytekin M, Feldstein AE, Dweik (2012) Leptin levels predict survival in pulmonary arterial hypertension. RA Pulm Circ 2(2):214–219. doi:10.4103/2045-8932.97607 CrossRef

40.

Lehtonen A, Huupponen R, Tuomilehto J, Lavonius S, Arve S, Isoaho H, Huhtaniemi I, Tilvis R (2008) Serum testosterone but not leptin predicts mortality in elderly men. Age Ageing 37(4):461–464. doi:10.1093/ageing/afn048 CrossRefPubMed

41.

Brennan AM, Li TY, Kelesidis I, Gavrila A, Hu FB, Mantzoros CS (2007) Circulating leptin levels are not associated with cardiovascular morbidity and mortality in women with diabetes: a prospective cohort study. Diabetologia 50(6):1178–1185CrossRefPubMed

42.

Lieb W, Sullivan LM, Harris TB, Roubenoff R, Benjamin EJ, Levy D, Fox CS, Wang TJ, Wilson PW, Kannel WB, Vasan RS (2009) Plasma leptin levels and incidence of heart failure, cardiovascular disease, and total mortality in elderly individuals. Diabetes Care 32(4):612–616. doi:10.2337/dc08-1596 CrossRefPubMed

43.

Leto R, Desruelles D, Gillet JB, Sabbe MB (2015) Admission hyperglycaemia is associated with higher mortality in patients with hip fracture. Eur J Emerg Med 22(2):99–102. doi:10.1097/MEJ.0000000000000119 CrossRefPubMed

44.

Kerby JD, Griffin RL, MacLennan P, Rue LW 3rd (2012) Stress-induced hyperglycemia, not diabetic hyperglycemia, is associated with higher mortality in trauma. Ann Surg 256(3):446–452. doi:10.1097/SLA.0b013e3182654549 CrossRefPubMed

45.

Gulcelik NE, Bayraktar M, Caglar O, Alpaslan M, Karakaya J (2011) Mortality after hip fracture in diabetic patients. Exp Clin Endocrinol Diabetes 119(7):414–448. doi:10.1055/s-0030-1270466 CrossRefPubMed

Title: The role of adipokines as prognostic factors of one-year mortality in hip fracture patients
Authors: T. Gulin
I. Kruljac
L. S. Kirigin Biloš
M. Gulin
M. Grgurević
M. Borojević
Publication date: 01-08-2017
Publisher: Springer London
Published in: Osteoporosis International / Issue 8/2017
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-017-4068-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The role of adipokines as prognostic factors of one-year mortality in hip fracture patients

Abstract

Summary

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

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