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Published in: Endocrine 3/2019

Open Access 01-12-2019 | Hyponatremia | Original Article

Sex-specific risks of death in patients hospitalized for hyponatremia: a population-based study

Authors: Buster Mannheimer, Jakob Skov, Henrik Falhammar, Jan Calissendorff, Jonatan D. Lindh, David Nathanson

Published in: Endocrine | Issue 3/2019

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Abstract

Purpose

Several studies have reported an association between hyponatremia and lethality. However, it remains elusive whether hyponatremia independently contributes to lethality. The aim of the study was to investigate associations between hyponatremia and lethality and differences in lethality between men and women hospitalized due to hyponatremia.

Methods

Four registries were utilized in this population-based retrospective study: The National Patient Registry, the Cause of Death Register, the Swedish Prescribed Drug Register and the Total Population Register (NPR) from which the controls were sampled. All hospitalized patients with a first-ever principal ICD10 diagnosis of hyponatremia or syndrome of inappropriate ADH secretion in the NPR between 1 October 2005 and 31 December 2014 were defined as cases. Cox regression with adjustment for potential confounders was used.

Results

14,359 individuals with a principal diagnosis of hyponatremia, and 57,382 matched controls were identified. Median age was 76 years and the majority were women (72%). Median age for women and men was 79 and 68 years, respectively. Adjusted hazard ratios (and 95% CI) for lethality in those with hyponatremia compared with controls were for the entire population 5.5 (4.4–7.0) and in the subgroup free from previously known underlying disease 6.7 (3.3–13.3). Lethality in women with hyponatremia was lower compared with men: HR: 0.56 (0.49–0.64). In the healthier group the lethality remained lower for women: HR: 0.49 (0.34–0.71).

Conclusions

Patients hospitalized due to hyponatremia faced an increased subsequent lethality that was independent of concomitant disease. This increase was nearly twice as large among men compared with women.
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Literature
1.
go back to reference A. Upadhyay, B.L. Jaber, N.E. Madias, Incidence and prevalence of hyponatremia. Am. J. Med. 119(7 Suppl 1), S30–S35 (2006)CrossRef A. Upadhyay, B.L. Jaber, N.E. Madias, Incidence and prevalence of hyponatremia. Am. J. Med. 119(7 Suppl 1), S30–S35 (2006)CrossRef
2.
go back to reference H.J. Adrogue, N.E. Madias, Hyponatremia. N. Engl. J. Med. 342(21), 1581–1589 (2000)CrossRef H.J. Adrogue, N.E. Madias, Hyponatremia. N. Engl. J. Med. 342(21), 1581–1589 (2000)CrossRef
3.
go back to reference S.M. Doshi, P. Shah, X. Lei, A. Lahoti, A.K. Salahudeen, Hyponatremia in hospitalized cancer patients and its impact on clinical outcomes. Am. J. Kidney Dis. 59(2), 222–228 (2012)CrossRef S.M. Doshi, P. Shah, X. Lei, A. Lahoti, A.K. Salahudeen, Hyponatremia in hospitalized cancer patients and its impact on clinical outcomes. Am. J. Kidney Dis. 59(2), 222–228 (2012)CrossRef
4.
go back to reference S. Hamaguchi, S. Kinugawa, M. Tsuchihashi-Makaya, S. Matsushima, M. Sakakibara, N. Ishimori, D. Goto, H. Tsutsui, Hyponatremia is an independent predictor of adverse clinical outcomes in hospitalized patients due to worsening heart failure. J. Cardiol. 63(3), 182–188 (2014)CrossRef S. Hamaguchi, S. Kinugawa, M. Tsuchihashi-Makaya, S. Matsushima, M. Sakakibara, N. Ishimori, D. Goto, H. Tsutsui, Hyponatremia is an independent predictor of adverse clinical outcomes in hospitalized patients due to worsening heart failure. J. Cardiol. 63(3), 182–188 (2014)CrossRef
5.
go back to reference L. Klein, C.M. O’Connor, J.D. Leimberger, W. Gattis-Stough, I.L. Pina, G.M. Felker, K.F. Adams Jr., R.M. Califf, M. Gheorghiade, O.-C. Investigators, Lower serum sodium is associated with increased short-term mortality in hospitalized patients with worsening heart failure: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study. Circulation. 111(19), 2454–2460 (2005)CrossRef L. Klein, C.M. O’Connor, J.D. Leimberger, W. Gattis-Stough, I.L. Pina, G.M. Felker, K.F. Adams Jr., R.M. Califf, M. Gheorghiade, O.-C. Investigators, Lower serum sodium is associated with increased short-term mortality in hospitalized patients with worsening heart failure: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study. Circulation. 111(19), 2454–2460 (2005)CrossRef
6.
go back to reference C.P. Kovesdy, E.H. Lott, J.L. Lu, S.M. Malakauskas, J.Z. Ma, M.Z. Molnar, K. Kalantar-Zadeh, Hyponatremia, hypernatremia, and mortality in patients with chronic kidney disease with and without congestive heart failure. Circulation. 125(5), 677–684 (2012)CrossRef C.P. Kovesdy, E.H. Lott, J.L. Lu, S.M. Malakauskas, J.Z. Ma, M.Z. Molnar, K. Kalantar-Zadeh, Hyponatremia, hypernatremia, and mortality in patients with chronic kidney disease with and without congestive heart failure. Circulation. 125(5), 677–684 (2012)CrossRef
7.
go back to reference H. Kusaka, S. Sugiyama, E. Yamamoto, E. Akiyama, Y. Matsuzawa, Y. Hirata, K. Fujisue, H. Kurokawa, J. Matsubara, K. Sugamura, H. Maeda, H. Jinnouchi, K. Matsui, H. Ogawa, Low-normal serum sodium and heart failure-related events in patients with heart failure with preserved left ventricular ejection fraction. Circ. J. 80(2), 411–417 (2016)CrossRef H. Kusaka, S. Sugiyama, E. Yamamoto, E. Akiyama, Y. Matsuzawa, Y. Hirata, K. Fujisue, H. Kurokawa, J. Matsubara, K. Sugamura, H. Maeda, H. Jinnouchi, K. Matsui, H. Ogawa, Low-normal serum sodium and heart failure-related events in patients with heart failure with preserved left ventricular ejection fraction. Circ. J. 80(2), 411–417 (2016)CrossRef
8.
go back to reference S. Mohan, S. Gu, A. Parikh, J. Radhakrishnan, Prevalence of hyponatremia and association with mortality: results from NHANES. Am. J. Med. 126(12), 1127–1137 e1121 (2013)CrossRef S. Mohan, S. Gu, A. Parikh, J. Radhakrishnan, Prevalence of hyponatremia and association with mortality: results from NHANES. Am. J. Med. 126(12), 1127–1137 e1121 (2013)CrossRef
9.
go back to reference S. Farmand, J.D. Lindh, J. Calissendorff, J. Skov, H. Falhammar, D. Nathanson, B. Mannheimer, Differences in associations of antidepressants and hospitalization due to hyponatremia. Am. J. Med. 131(1), 56–63 (2018)CrossRef S. Farmand, J.D. Lindh, J. Calissendorff, J. Skov, H. Falhammar, D. Nathanson, B. Mannheimer, Differences in associations of antidepressants and hospitalization due to hyponatremia. Am. J. Med. 131(1), 56–63 (2018)CrossRef
10.
go back to reference E.J. Hoorn, R. Zietse, Hyponatremia and mortality: moving beyond associations. Am. J. Kidney Dis. 62(1), 139–149 (2013)CrossRef E.J. Hoorn, R. Zietse, Hyponatremia and mortality: moving beyond associations. Am. J. Kidney Dis. 62(1), 139–149 (2013)CrossRef
11.
go back to reference H. Falhammar, J.D. Lindh, J. Calissendorff, S. Farmand, J. Skov, D. Nathanson, B. Mannheimer, Differences in associations of antiepileptic drugs and hospitalization due to hyponatremia: a population-based case-control study. Seizure. 59, 28–33 (2018)CrossRef H. Falhammar, J.D. Lindh, J. Calissendorff, S. Farmand, J. Skov, D. Nathanson, B. Mannheimer, Differences in associations of antiepileptic drugs and hospitalization due to hyponatremia: a population-based case-control study. Seizure. 59, 28–33 (2018)CrossRef
12.
go back to reference H. Falhammar, J.D. Lindh, J. Calissendorff, J. Skov, D. Nathanson, B. Mannheimer, Associations of proton pump inhibitors and hospitalization due to hyponatremia: a population-based case-control study. Eur. J. Intern. Med. 59, 65–69 (2018)CrossRef H. Falhammar, J.D. Lindh, J. Calissendorff, J. Skov, D. Nathanson, B. Mannheimer, Associations of proton pump inhibitors and hospitalization due to hyponatremia: a population-based case-control study. Eur. J. Intern. Med. 59, 65–69 (2018)CrossRef
13.
go back to reference A. Chawla, R.H. Sterns, S.U. Nigwekar, J.D. Cappuccio, Mortality and serum sodium: do patients die from or with hyponatremia? Clin. J. Am. Soc. Nephrol. 6(5), 960–965 (2011)CrossRef A. Chawla, R.H. Sterns, S.U. Nigwekar, J.D. Cappuccio, Mortality and serum sodium: do patients die from or with hyponatremia? Clin. J. Am. Soc. Nephrol. 6(5), 960–965 (2011)CrossRef
14.
go back to reference M.D. Zilberberg, A. Exuzides, J. Spalding, A. Foreman, A.G. Jones, C. Colby, A.F. Shorr, Epidemiology, clinical and economic outcomes of admission hyponatremia among hospitalized patients. Curr. Med. Res. Opin. 24(6), 1601–1608 (2008)CrossRef M.D. Zilberberg, A. Exuzides, J. Spalding, A. Foreman, A.G. Jones, C. Colby, A.F. Shorr, Epidemiology, clinical and economic outcomes of admission hyponatremia among hospitalized patients. Curr. Med. Res. Opin. 24(6), 1601–1608 (2008)CrossRef
15.
go back to reference B. Whelan, K. Bennett, D. O’Riordan, B. Silke, Serum sodium as a risk factor for in-hospital mortality in acute unselected general medical patients. QJM. 102(3), 175–182 (2009)CrossRef B. Whelan, K. Bennett, D. O’Riordan, B. Silke, Serum sodium as a risk factor for in-hospital mortality in acute unselected general medical patients. QJM. 102(3), 175–182 (2009)CrossRef
16.
go back to reference R. Wald, B.L. Jaber, L.L. Price, A. Upadhyay, N.E. Madias, Impact of hospital-associated hyponatremia on selected outcomes. Arch. Intern. Med. 170(3), 294–302 (2010)CrossRef R. Wald, B.L. Jaber, L.L. Price, A. Upadhyay, N.E. Madias, Impact of hospital-associated hyponatremia on selected outcomes. Arch. Intern. Med. 170(3), 294–302 (2010)CrossRef
17.
go back to reference E.J. Hoorn, F. Rivadeneira, J.B. van Meurs, G. Ziere, B.H. Stricker, A. Hofman, H.A. Pols, R. Zietse, A.G. Uitterlinden, M.C. Zillikens, Mild hyponatremia as a risk factor for fractures: the Rotterdam Study. J. Bone Min. Res. 26(8), 1822–1828 (2011)CrossRef E.J. Hoorn, F. Rivadeneira, J.B. van Meurs, G. Ziere, B.H. Stricker, A. Hofman, H.A. Pols, R. Zietse, A.G. Uitterlinden, M.C. Zillikens, Mild hyponatremia as a risk factor for fractures: the Rotterdam Study. J. Bone Min. Res. 26(8), 1822–1828 (2011)CrossRef
18.
go back to reference S.S. Waikar, D.B. Mount, G.C. Curhan, Mortality after hospitalization with mild, moderate, and severe hyponatremia. Am. J. Med. 122(9), 857–865 (2009)CrossRef S.S. Waikar, D.B. Mount, G.C. Curhan, Mortality after hospitalization with mild, moderate, and severe hyponatremia. Am. J. Med. 122(9), 857–865 (2009)CrossRef
19.
go back to reference L. Holland-Bill, C.F. Christiansen, U. Heide-Jorgensen, S.P. Ulrichsen, T. Ring, J.O. Jorgensen, H.T. Sorensen, Hyponatremia and mortality risk: a Danish cohort study of 279 508 acutely hospitalized patients. Eur. J. Endocrinol. 173(1), 71–81 (2015)CrossRef L. Holland-Bill, C.F. Christiansen, U. Heide-Jorgensen, S.P. Ulrichsen, T. Ring, J.O. Jorgensen, H.T. Sorensen, Hyponatremia and mortality risk: a Danish cohort study of 279 508 acutely hospitalized patients. Eur. J. Endocrinol. 173(1), 71–81 (2015)CrossRef
20.
go back to reference D. Baran, T.A. Hutchinson, The outcome of hyponatremia in a general hospital population. Clin. Nephrol. 22(2), 72–76 (1984)PubMed D. Baran, T.A. Hutchinson, The outcome of hyponatremia in a general hospital population. Clin. Nephrol. 22(2), 72–76 (1984)PubMed
21.
go back to reference R.J. Anderson, H.M. Chung, R. Kluge, R.W. Schrier, Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann. Intern. Med. 102(2), 164–168 (1985)CrossRef R.J. Anderson, H.M. Chung, R. Kluge, R.W. Schrier, Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann. Intern. Med. 102(2), 164–168 (1985)CrossRef
22.
go back to reference A.I. Arieff, Hyponatremia, convulsions, respiratory arrest, and permanent brain damage after elective surgery in healthy women. N. Engl. J. Med. 314(24), 1529–1535 (1986)CrossRef A.I. Arieff, Hyponatremia, convulsions, respiratory arrest, and permanent brain damage after elective surgery in healthy women. N. Engl. J. Med. 314(24), 1529–1535 (1986)CrossRef
23.
go back to reference J.A. Clayton, I.R. Le Jeune, I.P. Hall, Severe hyponatraemia in medical in-patients: aetiology, assessment and outcome. QJM. 99(8), 505–511 (2006)CrossRef J.A. Clayton, I.R. Le Jeune, I.P. Hall, Severe hyponatraemia in medical in-patients: aetiology, assessment and outcome. QJM. 99(8), 505–511 (2006)CrossRef
24.
go back to reference S.J. Ellis, Severe hyponatraemia: complications and treatment. QJM. 88(12), 905–909 (1995)PubMed S.J. Ellis, Severe hyponatraemia: complications and treatment. QJM. 88(12), 905–909 (1995)PubMed
25.
go back to reference G. Gill, B. Huda, A. Boyd, K. Skagen, D. Wile, I. Watson, C. van Heyningen, Characteristics and mortality of severe hyponatraemia-a hospital-based study. Clin. Endocrinol. 65(2), 246–249 (2006)CrossRef G. Gill, B. Huda, A. Boyd, K. Skagen, D. Wile, I. Watson, C. van Heyningen, Characteristics and mortality of severe hyponatraemia-a hospital-based study. Clin. Endocrinol. 65(2), 246–249 (2006)CrossRef
26.
go back to reference E.J. Hoorn, J. Lindemans, R. Zietse, Development of severe hyponatraemia in hospitalizedpatients: treatment-related risk factors and inadequate management. Nephrol. Dial. Transpl. 21(1), 70–76 (2006)CrossRef E.J. Hoorn, J. Lindemans, R. Zietse, Development of severe hyponatraemia in hospitalizedpatients: treatment-related risk factors and inadequate management. Nephrol. Dial. Transpl. 21(1), 70–76 (2006)CrossRef
27.
go back to reference C.M. Nzerue, H. Baffoe-Bonnie, W. You, B. Falana, S. Dai, Predictors of outcome in hospitalized patients with severe hyponatremia. J. Natl. Med. Assoc. 95(5), 335–343 (2003)PubMedPubMedCentral C.M. Nzerue, H. Baffoe-Bonnie, W. You, B. Falana, S. Dai, Predictors of outcome in hospitalized patients with severe hyponatremia. J. Natl. Med. Assoc. 95(5), 335–343 (2003)PubMedPubMedCentral
28.
go back to reference R.H. Sterns, Severe symptomatic hyponatremia: treatment and outcome. A study of 64 cases. Ann. Intern. Med. 107(5), 656–664 (1987).CrossRef R.H. Sterns, Severe symptomatic hyponatremia: treatment and outcome. A study of 64 cases. Ann. Intern. Med. 107(5), 656–664 (1987).CrossRef
29.
go back to reference C. Terzian, E.B. Frye, Z.H. Piotrowski, Admission hyponatremia in the elderly: factors influencing prognosis. J. Gen. Intern. Med. 9(2), 89–91 (1994)CrossRef C. Terzian, E.B. Frye, Z.H. Piotrowski, Admission hyponatremia in the elderly: factors influencing prognosis. J. Gen. Intern. Med. 9(2), 89–91 (1994)CrossRef
30.
go back to reference W.M. Tierney, D.K. Martin, M.C. Greenlee, R.L. Zerbe, C.J. McDonald, The prognosis of hyponatremia at hospital admission. J. Gen. Intern. Med. 1(6), 380–385 (1986)CrossRef W.M. Tierney, D.K. Martin, M.C. Greenlee, R.L. Zerbe, C.J. McDonald, The prognosis of hyponatremia at hospital admission. J. Gen. Intern. Med. 1(6), 380–385 (1986)CrossRef
31.
go back to reference J. Barsony, Y. Sugimura, J.G. Verbalis, Osteoclast response to low extracellular sodium and the mechanism of hyponatremia-induced bone loss. J. Biol. Chem. 286(12), 10864–10875 (2011)CrossRef J. Barsony, Y. Sugimura, J.G. Verbalis, Osteoclast response to low extracellular sodium and the mechanism of hyponatremia-induced bone loss. J. Biol. Chem. 286(12), 10864–10875 (2011)CrossRef
32.
go back to reference A. Eckart, P. Hausfater, D. Amin, A. Amin, S. Haubitz, M. Bernard, A. Baumgartner, T. Struja, A. Kutz, M. Christ-Crain, A. Huber, B. Mueller, P. Schuetz, Hyponatremia and activation of vasopressin secretion are both independently associated with 30-day mortality: results of a multicenter, observational study. J. Intern. Med. 284(3), 270–281 (2018)CrossRef A. Eckart, P. Hausfater, D. Amin, A. Amin, S. Haubitz, M. Bernard, A. Baumgartner, T. Struja, A. Kutz, M. Christ-Crain, A. Huber, B. Mueller, P. Schuetz, Hyponatremia and activation of vasopressin secretion are both independently associated with 30-day mortality: results of a multicenter, observational study. J. Intern. Med. 284(3), 270–281 (2018)CrossRef
33.
go back to reference J. Barsony, M.B. Manigrasso, Q. Xu, H. Tam, J.G. Verbalis, Chronic hyponatremia exacerbates multiple manifestations of senescence in male rats. Age. 35(2), 271–288 (2013)CrossRef J. Barsony, M.B. Manigrasso, Q. Xu, H. Tam, J.G. Verbalis, Chronic hyponatremia exacerbates multiple manifestations of senescence in male rats. Age. 35(2), 271–288 (2013)CrossRef
34.
go back to reference J.C. Ayus, S.G. Achinger, A. Arieff, Brain cell volume regulation in hyponatremia: role of sex, age, vasopressin, and hypoxia. Am. J. Physiol. Ren. Physiol. 295(3), F619–F624 (2008)CrossRef J.C. Ayus, S.G. Achinger, A. Arieff, Brain cell volume regulation in hyponatremia: role of sex, age, vasopressin, and hypoxia. Am. J. Physiol. Ren. Physiol. 295(3), F619–F624 (2008)CrossRef
35.
go back to reference J.K. Hix, S. Silver, R.H. Sterns, Diuretic-associated hyponatremia. Semin. Nephrol. 31(6), 553–566 (2011)CrossRef J.K. Hix, S. Silver, R.H. Sterns, Diuretic-associated hyponatremia. Semin. Nephrol. 31(6), 553–566 (2011)CrossRef
36.
go back to reference D. Kirby, D. Ames, Hyponatraemia and selective serotonin re-uptake inhibitors in elderly patients. Int. J. Geriatr. Psychiatry. 16(5), 484–493 (2001)CrossRef D. Kirby, D. Ames, Hyponatraemia and selective serotonin re-uptake inhibitors in elderly patients. Int. J. Geriatr. Psychiatry. 16(5), 484–493 (2001)CrossRef
Metadata
Title
Sex-specific risks of death in patients hospitalized for hyponatremia: a population-based study
Authors
Buster Mannheimer
Jakob Skov
Henrik Falhammar
Jan Calissendorff
Jonatan D. Lindh
David Nathanson
Publication date
01-12-2019
Publisher
Springer US
Published in
Endocrine / Issue 3/2019
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-019-02073-x

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