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The prognostic value of high-sensitivity C-reactive protein and prealbumin for short-term mortality in acutely hospitalized multimorbid elderly patients: A prospective cohort study

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The journal of nutrition, health & aging

Abstract

Objectives

To establish the predictive value on mortality after 2 months from hospital admission of two laboratory markers of nutritional and inflammatory status, high-sensitivity C-reactive protein (hs-CRP) and prealbumin, in a cohort of frail multimorbid elderly without terminal illness.

Design

Prospective cohort study.

Setting

Internal medicine ward of a large teaching hospital in Italy.

Participants

544 Caucasian patients with acute disease consecutively admitted from January to June 2013. 102 were excluded for being younger than 65 years old, having life expectancy <30 days or not having frailty syndrome. Further 42 patients were excluded for missing data or withdrawn at follow-up. Final analysis was performed on 400 subjects (179 M, 221 F, mean age 79±10).

Measurements

Serum prealbumin and hs-CRP were measured at admission. Death within 2 months from hospital admission was assessed through a telephonic interview with the caregiver for each patient discharged alive. Inhospital mortality was also recorded. Survival was calculated from date of admission to our unit.

Results

Mean prealbumin at admission was 17.3±7.7 mg/dl, while hs-CRP median was 24.2 mg/L (IQR 8.7 to 51.8). 108 patients (27%) died within two months from admission. In an age- and sexadjusted analysis, log(hs-CRP) levels at admission, but not prealbumin, were independently associated with an increased risk for mortality (HR 1.40, 95% CI 1.18 to 1.66, p<0.001). After multiple adjustments for covariates, including comorbidity burden measured through Charlson score, log(hs-CRP) remained significantly associated with mortality (HR 1.38, 95% CI 1.08 to 1.76, p=0.01). A Receiver Operating Characteristic (ROC) curve was performed to test the predictive value of hs-CRP at admission on two-month mortality (AUC 0.68, 95% CI 0.63 to 0.72, p<0.001). Cut-off value was set at 38.4 mg/L. After dichotomization of hs-CRP values according to this cut-off, hs-CRP=38.4 mg/L at admission proved to be a significant risk factor for mortality (HR 2.10, 95% CI 1.23 to 3.58, p=0.006).

Conclusion

Serum hs-CRP, but not prealbumin, values at admission are predictors of short-term mortality at hospital admission in elderly multimorbid patients. Inflammation seems to affect prognosis more than malnutrition in this setting and may therefore guide clinicians’ attitude towards therapeutic choices.

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Table 1
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Abbreviations

Hs-CRP:

High-Sensitivity C-Reactive Protein

IQR:

InterQuartile Range

HR:

Hazard Ratio

IGF-1:

Insulin Growth Factor-1

CRP:

C-Reactive Protein

AKI:

Acute Kidney Injury

CKD:

Chronic Kidney Disease

ROC:

Receiver Operating Characteristics

AUC:

Area Under the Curve

References

  1. Corish CA, Kennedy NP. Protein-energy undernutrition in hospital inpatients. Br J Nutr 2000;83(6): 575–591.

    Article  CAS  PubMed  Google Scholar 

  2. Visvanathan R. Undernutrition in older people: a serious and growing global problem. J Postgrad Med 2003;49: 352–360.

    CAS  PubMed  Google Scholar 

  3. Norman K, Pichard C, Lochs H, Pirlich M. Prognostic impact of disease-related malnutrition. Clin Nutr 2008;27(1): 5–15.

    Article  PubMed  Google Scholar 

  4. Ingenbleek Y, Bernstein L. The stressful condition as a nutritionally dependent adaptive dichotomy. Nutrition 1999;15(4): 305–320.

    Article  CAS  PubMed  Google Scholar 

  5. Chapman IM. The anorexia of aging. Clin Geriatr Med 2007;23(4): 735–756.

    Article  PubMed  Google Scholar 

  6. Cannizzo ES, Clement CC, Sahu R, Follo C, Santambrogio L. Oxidative stress, inflammaging and immunosenescence. J Proteomics 2011;74(11): 2313–2323.

    Article  CAS  PubMed  Google Scholar 

  7. Jenny NS (2012) Inflammation in aging: cause, effect or both? Discov Med 13(73):451–460.

    PubMed  Google Scholar 

  8. Salvioli S, Capri M, Valensin S, Tieri P, Monti D, Ottaviani E, Franceschi C. Inflamm-aging, cytokines and aging: state of the art, new hypotheses on the role of mitochondria and new perspectives from systems biology. Curr Pharm Des 2006;12(24): 3161–3171.

    Article  CAS  PubMed  Google Scholar 

  9. Maggio M, De Vita F, Lauretani F, Buttò V, Bondi G, Cattabiani C, Nouvenne A, Meschi T, Dall’Aglio E, Ceda GP. IGF-1, the cross road of the nutritional, inflammatory and hormonal pathways to frailty. Nutrients 2013;5: 4184–4205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jensen GL, Bistrian B, Roubenoff R, Heimburger DC. Malnutrition syndromes: a conundrum vs continuum. J Parenter Enteral Nutr 2009;33: 710–716.

    Article  Google Scholar 

  11. Jensen GL. Malnutrition and inflammation–“Burning down the house”: inflammation as an adaptive physiologic response versus self-destruction? J Parenter Enteral Nutr 2015;39(1): 56–62;doi: 10.1177/0148607114529597.

    Article  Google Scholar 

  12. Carriere I, Dupuy AM, Lacroux A, Cristol JP, Delcourt C, Pathologies Oculaires Liées à l’Age Study Group. Biomarkers of inflammation and malnutrition associated with early death in healthy elderly people. J Am Geriatr Soc 2008;56: 840–846.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Giovannini S, Onder G, Liperoti R, Russo A, Carter C, Capoluongo E, Pahor M, Bernabei R, Landi F. Interleukin-6, C-reactive protein, and tumor necrosis factoralpha as predictors of mortality in frail, community-living elderly individuals. J Am Geriatr Soc 2011;59: 1679–1685.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ferrando-Martinez S, Romero-Sanchez MC, Solana R, Delgado J, de la Rosa R, Munoz-Fernandez MA, Ruiz-Mateos E, Leal M. Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans. Age 2013;35: 251–259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Holland DC, Meers C, Lawlor ME, Lam M. Serial prealbumin levels as predictors of outcomes in a retrospective cohort of peritoneal and hemodialysis patients. J Ren Nutr 2001;11(3): 129–138.

    Article  CAS  PubMed  Google Scholar 

  16. Terrier N, Jaussent I, Dupuy AM, Morena M, Delcourt C, Chalabi L, Rouanet C, Canaud B, Cristol JP. Creatinine index and transthyretin as additive predictors of mortality in haemodialysis patients. Nephrol Dial Transplant 2008;23: 345–353.

    Article  CAS  PubMed  Google Scholar 

  17. Yoo SH, Kim JS, Kwon SU, Yun SC, Koh JY, Kang DW. Undernutrition as a predictor of poor clinical outcomes in acute ischemic stroke patients. Arch Neurol 2008;65(1): 39–43.

    Article  PubMed  Google Scholar 

  18. Gao C, Zhang B, Zhang W, Pu S, Yin J, Gao Q. Serum prealbumin (transthyretin) predict good outcome in young patients with cerebral infarction. Clin Exp Med 2011;11: 49–54.

    Article  CAS  PubMed  Google Scholar 

  19. Devakonda A, George L, Raoof S, Esan A, Saleh A, Bernstein LH. Transthyretin as a marker to predict outcome in critically ill patients. Clin Biochem 2008;41: 1126–1130.

    Article  CAS  PubMed  Google Scholar 

  20. Cano NJM, Pichard C, Roth H, Court-Fortuné I, Cynober L, Gérard-Boncompain M, Cuvelier A, Laaban JP, Melchior JC, Raphael JC, Pison CM, Clinical Research Group of the Société Francophone de Nutrition Entérale et Parentérale. C-reactive protein and body mass index predict outcome in end-stage respiratory failure. Chest 2004;126: 540–546.

    Article  PubMed  Google Scholar 

  21. Pedayachee L, Rodseth RN, Biccard BM. A meta-analysis of the utility of C-reactive protein in predicting early, intermediate-term and long term mortality and major adverse cardiac events in vascular surgical patients. Anaesthesia 2009;64: 416–424.

    Article  Google Scholar 

  22. Whiteley W, Jackson C, Lewis S, Lowe G, Rumley A, Sandercock P, Wardlaw J, Dennis M, Sudlow C. Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6. PLoS Med 2009;6(9):e1000145.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Elkind MSV, Luna JM, Mc Clure LA, Zhang Y, Coffey CS, Roldan A, Del Brutto OH, Pretell EJ, Pettigrew LC, Meyer BC, Tapia J, White C, Benavente OR, LIMITS Investigators. C-reactive protein as a prognostic marker after lacunar stroke–Levels of Inflammatory Markers in the Treatment of Stroke Study. Stroke 2014;45: 707–716.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Xie Q, Zhou Y, Xu Z, Yang Y, Kuang D, You H, Ma S, Hao C, Gu Y, Lin S, Ding F. The ratio of CRP to prealbumin levels predict mortality in patients with hospitalacquired acute kidney injury. BMC Nephrol 2011;12: 30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kalantar-Zadeh K, McAllister CJ, Lehn RS, Lee GH, Nissenson AR, Kopple JD. Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients. Am J Kidney Dis 2003;42: 761–773.

    Article  PubMed  Google Scholar 

  26. Rattanasompattikul M, Molnar MZ, Zaritsky JJ, Hatamizadeh P, Jing J, Norris KC, Kovesdy CP, Kalantar-Zadeh K. Association of malnutrition-inflammation complex and responsiveness to erythropoiesis-stimulating agents in long-term hemodialysis patients. Nephrol Dial Transplant 2013;28(7): 1936–1945.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rodriguez-Mañas L, Féart C, Mann G, Vina J, Chatterji S, Chodzko-Zajko W, Gonzalez-Colaço Harmand M, Bergman H, Carcaillon L, Nicholson C, Scuteri A, Sinclair A, Pelaez M, Van der Cammen T, Beland F, Bickenbach J, Delamarche P, Ferrucci L, Fried LP, Gutierrez-Robledo LM, Rockwood K, Rodriguez Artalejo F, Serviddio G, Vega E, FOD-CC Group. Searching for an operational definition of frailty: a Delphi method based consensus statement. The Frailty Operative Definition-Consensus Conference Project. J Gerontol A Biol Sci Med Sci 2013;68(1): 62–67.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Rockwood K, Song X, Mac Knight C, Bergman H, Hogan DB, Mc Dowell I, Mitnitski A. A global clinical measure of fitness and frailty in elderly people. CMAJ 2005;173(5): 489–495.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  30. Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol 1994;47(11): 1245–1251.

    Article  CAS  PubMed  Google Scholar 

  31. Caccialanza R, Palladini G, Klersy C, Cereda E, Bonardi C, Quarleri L, Vadacca G, Albertini R, Merlini G. Serum prealbumin: an independent marker of short-term energy intake in the presence of multiple-organ disease involvement. Nutrition 2013;29(3): 580–582.

    Article  CAS  PubMed  Google Scholar 

  32. Rothkrantz-Kos S; Bekers O, Gubbels A, Drent M, Schmitz MP, van Dieijen-Visser MP. Evaluation of two new high-sensitivity methods for C-reactive protein. Ann Clin Biochem 2003;40(Pt 4):398–405.

    Article  CAS  PubMed  Google Scholar 

  33. Laviano A, Koverech A, Mari A. Cachexia: clinical features when inflammation drives malnutrition. Proc Nutr Soc, in press. 2015; Doi:10.1017/S0029665115000117.

    Google Scholar 

  34. Davis CJ, Sowa D, Keim KS, Kinnare K, Peterson S. The use of prealbumin and C-reactive protein for monitoring nutrition support in adult patients receiving enteral nutrition in an urban medical center. J Parenter Enteral Nutr 2012;36(2): 197–204.

    Article  CAS  Google Scholar 

  35. Seres DS. Surrogate nutrition markers, malnutrition, and adequacy of nutrition support. Nutr Clin Pract 2005;20: 308–313.

    Article  PubMed  Google Scholar 

  36. Lacki JK, Samborski W, Mackiewicz S, Mackiewicz U. Do changes in clinical improvement in rheumatoid arthritis patients treated with immunosuppressive drugs reflect the changes in acute phase proteins? Ups J Med Sci 1995;100: 233–242.

    Article  CAS  PubMed  Google Scholar 

  37. Pinilla JC, Hayes P, Laverty W, Arnold C, Laxdal V. The C-reactive protein to prealbumin ratio correlates with the severity of multiple organ disfunction. Surgery 1998;124: 799–806.

    Article  CAS  PubMed  Google Scholar 

  38. Zhang Y, Protogerou AD, Iaria P, Safar ME, Xu Y, Blacher J. Prognosis in the hospitalized very elderly: the PROTEGER study. Int J Cardiol 2013;168: 2714–2719.

    Article  PubMed  Google Scholar 

  39. Jensen GL, Mirtallo J, Compher C, Dhaliwal R, Forbes A, Grijalba RF, Hardy G, Kondrup J, Labadarios D, Nyulasi I, Castillo Pineda JC, Waitzberg D, International Consensus Guideline Committee. Adult starvation and disease-related malnutrition: a proposal for etiology-based diagnosis in the clinical practice setting from the International Consensus Guideline Committee. J Parenter Enteral Nutr 2010;34: 156–159.

    Article  Google Scholar 

  40. Donini LM, Savina C, Ricciardi LM, Coletti C, Paolini M, Scavone L, De Felice MR, Laviano A, Rossi Fanelli F, Cannella C. Predicting the outcome of artificial nutrition by clinical and functional indices. Nutrition 2009;25: 11–19.

    Article  PubMed  Google Scholar 

  41. Sullivan DH, Bopp MM, Robertson PK. Protein-energy undernutrition and lifethreatening complications among the hospitalized elderly. J Gen Intern Med 2002;17: 923–932.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Guo Y, Palmer JL, Kaur G, Hainley S, Young B, Bruera E. Nutritional status of cancer patients and its relationship to function in an inpatient rehabilitation setting. Support Care Cancer 2005;13: 169–175.

    Article  PubMed  Google Scholar 

  43. Semel J, Gray JM, Ahn HJ, Nasr H, Chen JJ. Predictors of outcome following hip fracture rehabilitation. PM&R 2010;2: 799–805.

    Article  Google Scholar 

  44. Chen J, Peng H, Xiao L, Zhang K, Yuan Z, Chen J, Wang Z, Wang J, Huang H. Inflammation but not dietary macronutrients insufficiency associated with the malnutrition-inflammation score in hemodialysis population. PLoS One 2013;8(12): e83233.

    Article  Google Scholar 

  45. Stratton RJ, Hébuterne X, Elia M. A systematic review and meta-analysis of the impact of oral nutritional supplements on hospital readmissions. Ageing Res Rev 2013;12: 884–897.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy

    Antonio Nouvenne, A. Ticinesi, M. Maggio, L. Borghi & T. Meschi

  2. Internal Medicine and Critical Subacute Care Unit, Geriatric-Rehabilitation Department, Parma University Hospital, Parma, Italy

    Antonio Nouvenne, A. Ticinesi, B. Prati, L. Borghi & T. Meschi

  3. Geriatrics Unit, Geriatric-Rehabilitation Department, Parma University Hospital, Parma, Italy

    F. Lauretani

  4. Laboratory of Clinical Chemistry and Hematology, Department of Pathology and Laboratory Medicine, Parma University Hospital, Parma, Italy

    G. Lippi

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  1. Antonio Nouvenne
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Nouvenne, A., Ticinesi, A., Lauretani, F. et al. The prognostic value of high-sensitivity C-reactive protein and prealbumin for short-term mortality in acutely hospitalized multimorbid elderly patients: A prospective cohort study. J Nutr Health Aging 20, 462–468 (2016). https://doi.org/10.1007/s12603-015-0626-5

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