Main Article Content
Abstract
Background: Despite its significant contribution to morbidity and mortality, studies reported that hyponatremia is still inadequately recognised and treated.
Objective: To obtain a prediction model for predicting the risk of hyponatremia in patients hospitalized from heart failure.
Methods: Patients included in this research were patients hospitalized from heart failure at Fatmawati Hospital in Jakarta, Indonesia during the 2011 – 2014 period. Logistic regression analysis was performed for the derivation of prediction model by including variables obtained during admission as the predictors. Brier-score and Nagelkerke R2 (NR2) were measured to assess overall predictive ability and area under the curve (AUC) of the Receiver Operating Characteristics (ROC) and calibration plot along with Hosmer-Lemeshow test were measured to assess discrimination and calibration ability, respectively. Internal validation was performed using a bootstrapping approach.
Results: Out of 464 patients included in the research 102 (22%) were hyponatremic during hospitalization. Accordingly, 306 non-hyponatremic patients were selected as controls matched by age and gender. Variables significantly associated with hyponatremia were serum sodium level, fatigue, ascites, positive inotropes, heparin and antibiotics. Prediction model containing those six variables exhibits good predictive ability both overall (brier-score=0.107, NR2=0.531) and specifically of discrimination (AUC of ROC curve=0.90) and calibration ability (p-value of HL test=0.899). Optimism observed from internal validation did not reduce its predictive performance.
Conclusion: Risk prediction for predicting the risk of hyponatremia in patients hospitalized from heart failure can be derived by including predictors taken from information obtained during admission.
Keywords
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References
- Goldsmith SR. Hyponatremia and outcomes in patients with heart failure. Heart. 2012;98(24):1761-2.
- Sato N, Gheorghiade M, Kajimoto K, Munakata R, Minami Y, Mizuno M, et al. Hyponatremia and in-hospital mortality in patients admitted for heart failure (from the ATTEND Registry). American Journal of Cardiology. 2013; 111(7):1019-25.
- Choi DJ, Han S, Jeon ES, Cho MC, Kim JJ, Yoo BS, et al. Characteristics, outcomes and predictors of long-term mortality for patients hospitalized for acute heart failure: A report from The Korean Heart Failure Registry. Korean circulation journal. 2011;41(7):363-71.
- Madan VD, Novak E, Rich MW. Impact of change in serum sodium concentration on mortality in patients hospitalized with heart failure and hyponatremia. Circulation: Heart Failure. 2011;4(5):637-3.
- Konishi M, Haraguchi G, Ohigashi H, Sasaoka T, Yoshikawa S, Inagaki H, et al. Progression of hyponatremia is associated with increased cardiac mortality in patients hospitalized for acute decompensated heart failure. Journal of Cardiac Failure. 2012;18(8):620-5.
- Tzoulis P, Evans R, Falinska A, Barnard M, Tan T, Woolman E, et al. Multicentre study of investigation and management of inpatient hyponatraemia in the UK. Postgraduate Medical Journal. 2014;90(1070):694-8.
- Whyte M, Down C, Miell J, Crook M. Lack of laboratory assessment of severe hyponatraemia is associated with detrimental clinical outcomes in hospitalised patients. International Journal of Clinical Practice. 2009;63(10):1451-5.
- Marco J, Barba R, Matia P, Plaza S, Mendez M, Canora J, et al. Low prevalence of hyponatremia codification in departments of internal medicine and its prognostic implications. Current Medical Research and Opinion. 2013;29(12):1757-62.
- Shchekochikhin DY, Schrier RW, Lindenfeld J, Price LL, Jaber BL, Madias NE. Outcome differences in community- versus hospital-acquired hyponatremia in patients with a diagnosis of heart failure. Circulation: Heart Failure. 2013;6(3):379-86.
- Bettari L, Fiuzat M, Shaw LK, Wojdyla DM, Metra M, Felker GM, et al. Hyponatremia and long-term outcomes in chronic heart failure--an observational study from the Duke Databank for Cardiovascular Diseases. Journal of Cardiac Failure. 2012;18(1):74-81.
- Corona G, Giuliani C, Parenti G, Norello D, Verbalis JG, Forti G, et al. Moderate hyponatremia is associated with increased risk of mortality: evidence from a meta-analysis. PLoS ONE. 2013;8(12):e80451.
- Hoorn EJ, Lindemans J, Zietse R. Development of severe hyponatraemia in hospitalized patients: treatment-related risk factors and inadequate management. Nephrology Dialysis Transplantation. 2006;21(1):70-6.
- Essebag V, Genest J, Suissa S, Pilote L. The nested case-control in cardiology. American Heart Journal. 2003;146:581-90.
- Biesheuvel CJ, Vergouwe Y, Oudega R, Hoes A, Grobbee DE, Moons KG. Advantages of the nested case-control design in diagnostic research. BMC Medical Research Methodology. 2008;8(48):1-7.
- Hosmer DW, Stanley L, Sturdivant RX. Applied logistic regression. New Jersey USA: Wiley; 2013.
- R Development Core Team. R: A languange and environment for statistical computing. In. 3.1.3 edn: R Foundation for Statistical Computing, Vienna, Austria; 2015.
- Bursac Z, Gauss CH, Williams DK, Hosmer DW. Purposeful selection of variables in logistic regression. Source Code for Biology and Medicine. 2008;3(17):1-8.
- Wynants L, Bouwmeester W, Moons KG, Moerbeek M, Timmerman D, Van Huffel S, et al. A simulation study of sample size demonstrated the importance of the number of events per variable to develop prediction models in clustered data. Journal of Clinical Epidemiology. 2015;68(12):1406-14.
- Steyerberg EW. Clinical prediction models: A practical approach to development, validation, and updating. Springer; 2010.
- Beukhof CM, Hoorn EJ, Lindemans J, Zietse R. Novel risk factors for hospital-acquired hyponatremia: A matched case-control study. Clinical Endocrinology (Oxford). 2007;66:367-72.
- Yancy CW, Jessup M, Bozkurt B, Masoudi FA, Butler J, McBride PE, et al. 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Journal of the American College of Cardiology. 2013; 62(16):e147-239.
- Conley S, Feder S, Redeker NS. The relationship between pain, fatigue, depression and functional performance in stable heart failure. Heart & Lung. 2015;44(2):107-12.
- Perez-Moreno AC, Jhund PS, Macdonald MR, Petrie MC, Cleland JG, Bohm M, et al. Fatigue as a predictor of outcome in patients with heart failure: Analysis of CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure). JACC: Heart Failure. 2014;2(2):187-97.
- Fink AM, Gonzalez RC, Lisowski T, Pini M, Fantuzzi G, Levy WC, et al. Fatigue, inflammation, and projected mortality in heart failure. Journal of Cardiac Failure. 2012;18(9):711-6.
- Oster JR, Singer I, Fishman LM. Heparin-induced aldosterone suppression and hyperkalemia. The American Journal of Medicine. 1995;98(6):575-86.
- Bengalorkar GM, Sarala N, Venkatrathnamma PN, Kumar TN. Effect of heparin and low-molecular weight heparin on serum potassium and sodium levels. Journal of Pharmacology & Pharmacotherapeutics. 2011;2(4):266-9.
- Norman NE, Sneed AM, Brown C, Ellis CA, Minard G, Brown RO. Heparin-induced hyponatremia. Annals of Pharmacotherapy. 2004;38(3):404-7.
- Huntsberry AM, Linnebur SA, Vejar M. Hyponatremia after initiation and rechallenge with trimethoprim-sulfamethoxazole in an older adult. Clinical Interventions in Aging. 2015;10:1091-6.
- Mori H, Kuroda Y, Imamura S, Toyoda A, Yoshida I, Kawakami M, et al. Hyponatremia and/or hyperkalemia in patients treated with the standard dose of trimethoprim-sulfamethoxazole. Internal Medicine. 2003;42(8):665-9.
- Swart RM, Hoorn EJ, Betjes MG, Zietse R. Hyponatremia and inflammation: The emerging role of interleukin-6 in osmoregulation. Nephron Physiology. 2011;118(2):45-51.
- Matheny ME, Ohno-Machado L, Resnic FS. Discrimination and calibration of mortality risk prediction models in interventional cardiology. Journal of Biomedical Informatics. 2005;38(5):367-75.
- Steyerberg EW, Eijkemans MJC, Harrell FE, Habbema JDF. Prognostic modeling with logistic regression analysis: In search of a sensible strategy in small data sets. Medical Decision Making. 2001;21(1):45-56.
- Steyerberg EW, Vergouwe Y. Towards better clinical prediction models: Seven steps for development and an ABCD for validation. European Heart Journal. 2014;35(29):1925-31.
- Steyerberg EW, Harrell FE, Borsboom GJ. Internal validation of predictive models: Efficiency of some procedures for logistic regression analysis. Journal of Clinical Epidemiology. 2001;54:774-81.
- Smith GC, Seaman SR, Wood AM, Royston P, White IR. Correcting for optimistic prediction in small data sets. American Journal of Epidemiology l. 2014;180(3):318-24.
- Austin PC, Steyerberg EW. Events per variable (EPV) and the relative performance of different strategies for estimating the out-of-sample validity of logistic regression models. Statistical Methods in Medical Research. 2014; 26(2):796-808.
- Vickers AJ, Jang K, Sargent D, Lilja H, Kattan MW. Systematic review of statistical methods used in molecular marker studies in cancer. Cancer. 2008;112(8):1862-8.
References
Goldsmith SR. Hyponatremia and outcomes in patients with heart failure. Heart. 2012;98(24):1761-2.
Sato N, Gheorghiade M, Kajimoto K, Munakata R, Minami Y, Mizuno M, et al. Hyponatremia and in-hospital mortality in patients admitted for heart failure (from the ATTEND Registry). American Journal of Cardiology. 2013; 111(7):1019-25.
Choi DJ, Han S, Jeon ES, Cho MC, Kim JJ, Yoo BS, et al. Characteristics, outcomes and predictors of long-term mortality for patients hospitalized for acute heart failure: A report from The Korean Heart Failure Registry. Korean circulation journal. 2011;41(7):363-71.
Madan VD, Novak E, Rich MW. Impact of change in serum sodium concentration on mortality in patients hospitalized with heart failure and hyponatremia. Circulation: Heart Failure. 2011;4(5):637-3.
Konishi M, Haraguchi G, Ohigashi H, Sasaoka T, Yoshikawa S, Inagaki H, et al. Progression of hyponatremia is associated with increased cardiac mortality in patients hospitalized for acute decompensated heart failure. Journal of Cardiac Failure. 2012;18(8):620-5.
Tzoulis P, Evans R, Falinska A, Barnard M, Tan T, Woolman E, et al. Multicentre study of investigation and management of inpatient hyponatraemia in the UK. Postgraduate Medical Journal. 2014;90(1070):694-8.
Whyte M, Down C, Miell J, Crook M. Lack of laboratory assessment of severe hyponatraemia is associated with detrimental clinical outcomes in hospitalised patients. International Journal of Clinical Practice. 2009;63(10):1451-5.
Marco J, Barba R, Matia P, Plaza S, Mendez M, Canora J, et al. Low prevalence of hyponatremia codification in departments of internal medicine and its prognostic implications. Current Medical Research and Opinion. 2013;29(12):1757-62.
Shchekochikhin DY, Schrier RW, Lindenfeld J, Price LL, Jaber BL, Madias NE. Outcome differences in community- versus hospital-acquired hyponatremia in patients with a diagnosis of heart failure. Circulation: Heart Failure. 2013;6(3):379-86.
Bettari L, Fiuzat M, Shaw LK, Wojdyla DM, Metra M, Felker GM, et al. Hyponatremia and long-term outcomes in chronic heart failure--an observational study from the Duke Databank for Cardiovascular Diseases. Journal of Cardiac Failure. 2012;18(1):74-81.
Corona G, Giuliani C, Parenti G, Norello D, Verbalis JG, Forti G, et al. Moderate hyponatremia is associated with increased risk of mortality: evidence from a meta-analysis. PLoS ONE. 2013;8(12):e80451.
Hoorn EJ, Lindemans J, Zietse R. Development of severe hyponatraemia in hospitalized patients: treatment-related risk factors and inadequate management. Nephrology Dialysis Transplantation. 2006;21(1):70-6.
Essebag V, Genest J, Suissa S, Pilote L. The nested case-control in cardiology. American Heart Journal. 2003;146:581-90.
Biesheuvel CJ, Vergouwe Y, Oudega R, Hoes A, Grobbee DE, Moons KG. Advantages of the nested case-control design in diagnostic research. BMC Medical Research Methodology. 2008;8(48):1-7.
Hosmer DW, Stanley L, Sturdivant RX. Applied logistic regression. New Jersey USA: Wiley; 2013.
R Development Core Team. R: A languange and environment for statistical computing. In. 3.1.3 edn: R Foundation for Statistical Computing, Vienna, Austria; 2015.
Bursac Z, Gauss CH, Williams DK, Hosmer DW. Purposeful selection of variables in logistic regression. Source Code for Biology and Medicine. 2008;3(17):1-8.
Wynants L, Bouwmeester W, Moons KG, Moerbeek M, Timmerman D, Van Huffel S, et al. A simulation study of sample size demonstrated the importance of the number of events per variable to develop prediction models in clustered data. Journal of Clinical Epidemiology. 2015;68(12):1406-14.
Steyerberg EW. Clinical prediction models: A practical approach to development, validation, and updating. Springer; 2010.
Beukhof CM, Hoorn EJ, Lindemans J, Zietse R. Novel risk factors for hospital-acquired hyponatremia: A matched case-control study. Clinical Endocrinology (Oxford). 2007;66:367-72.
Yancy CW, Jessup M, Bozkurt B, Masoudi FA, Butler J, McBride PE, et al. 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Journal of the American College of Cardiology. 2013; 62(16):e147-239.
Conley S, Feder S, Redeker NS. The relationship between pain, fatigue, depression and functional performance in stable heart failure. Heart & Lung. 2015;44(2):107-12.
Perez-Moreno AC, Jhund PS, Macdonald MR, Petrie MC, Cleland JG, Bohm M, et al. Fatigue as a predictor of outcome in patients with heart failure: Analysis of CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure). JACC: Heart Failure. 2014;2(2):187-97.
Fink AM, Gonzalez RC, Lisowski T, Pini M, Fantuzzi G, Levy WC, et al. Fatigue, inflammation, and projected mortality in heart failure. Journal of Cardiac Failure. 2012;18(9):711-6.
Oster JR, Singer I, Fishman LM. Heparin-induced aldosterone suppression and hyperkalemia. The American Journal of Medicine. 1995;98(6):575-86.
Bengalorkar GM, Sarala N, Venkatrathnamma PN, Kumar TN. Effect of heparin and low-molecular weight heparin on serum potassium and sodium levels. Journal of Pharmacology & Pharmacotherapeutics. 2011;2(4):266-9.
Norman NE, Sneed AM, Brown C, Ellis CA, Minard G, Brown RO. Heparin-induced hyponatremia. Annals of Pharmacotherapy. 2004;38(3):404-7.
Huntsberry AM, Linnebur SA, Vejar M. Hyponatremia after initiation and rechallenge with trimethoprim-sulfamethoxazole in an older adult. Clinical Interventions in Aging. 2015;10:1091-6.
Mori H, Kuroda Y, Imamura S, Toyoda A, Yoshida I, Kawakami M, et al. Hyponatremia and/or hyperkalemia in patients treated with the standard dose of trimethoprim-sulfamethoxazole. Internal Medicine. 2003;42(8):665-9.
Swart RM, Hoorn EJ, Betjes MG, Zietse R. Hyponatremia and inflammation: The emerging role of interleukin-6 in osmoregulation. Nephron Physiology. 2011;118(2):45-51.
Matheny ME, Ohno-Machado L, Resnic FS. Discrimination and calibration of mortality risk prediction models in interventional cardiology. Journal of Biomedical Informatics. 2005;38(5):367-75.
Steyerberg EW, Eijkemans MJC, Harrell FE, Habbema JDF. Prognostic modeling with logistic regression analysis: In search of a sensible strategy in small data sets. Medical Decision Making. 2001;21(1):45-56.
Steyerberg EW, Vergouwe Y. Towards better clinical prediction models: Seven steps for development and an ABCD for validation. European Heart Journal. 2014;35(29):1925-31.
Steyerberg EW, Harrell FE, Borsboom GJ. Internal validation of predictive models: Efficiency of some procedures for logistic regression analysis. Journal of Clinical Epidemiology. 2001;54:774-81.
Smith GC, Seaman SR, Wood AM, Royston P, White IR. Correcting for optimistic prediction in small data sets. American Journal of Epidemiology l. 2014;180(3):318-24.
Austin PC, Steyerberg EW. Events per variable (EPV) and the relative performance of different strategies for estimating the out-of-sample validity of logistic regression models. Statistical Methods in Medical Research. 2014; 26(2):796-808.
Vickers AJ, Jang K, Sargent D, Lilja H, Kattan MW. Systematic review of statistical methods used in molecular marker studies in cancer. Cancer. 2008;112(8):1862-8.