Prevalence of Hyponatremia and Association with Mortality: Results from NHANES



      Hyponatremia is the most common electrolyte abnormality in hospitalized patients and is associated with adverse outcomes, but its prevalence and significance in the general US population is unknown. Our aims were to determine the prevalence of hyponatremia and its association with mortality in the population.


      We performed a population-based, cross-sectional study of 14,697 adults aged ≥18 years who participated in the nationally representative National Health and Nutrition Examination Survey for 1999-2004. By using measurements of serum sodium corrected for dilutional effect of hyperglycemia, we determined the association of hyponatremia with patient characteristics, comorbidities, and prescription medications, and performed unadjusted and adjusted Cox proportional hazards regression to find the association of hyponatremia with all-cause mortality.


      We provide the first estimate of the prevalence of hyponatremia in the US population, which in our weighted analysis was 1.72%. Prevalence of hyponatremia was significantly higher in women (2.09%, P = .004) and increased with age. Hyponatremia was more common in subjects with hypertension, diabetes, coronary artery disease, stroke, chronic obstructive pulmonary disease, cancer, and psychiatric disorders, and less common in those with no comorbidities (1.04%, P < .001). There was a significant risk of death associated with hyponatremia in unadjusted (hazard ratio [HR], 3.61; P < .001) and adjusted Cox models controlling for demographics, smoking, comorbidities, and insurance status (HR, 2.43; P < .001). There was a U-shaped relationship between serum sodium and HR for mortality.


      Our findings suggest that hyponatremia is a predictor of mortality in the general population independently of age, gender, and comorbid conditions.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Upadhyay A.
        • Jaber B.L.
        • Madias N.E.
        Incidence and prevalence of hyponatremia.
        Am J Med. 2006; 119: S30-S35
        • Mannesse C.K.
        • Vondeling A.M.
        • van Marum R.J.
        • et al.
        Prevalence of hyponatremia on geriatric wards compared to other settings over four decades: a systematic review.
        Ageing Res Rev. 2012; 12: 165-173
        • Balling L.
        • Schou M.
        • Videbaek L.
        • et al.
        Prevalence and prognostic significance of hyponatraemia in outpatients with chronic heart failure.
        Eur J Heart Fail. 2011; 13: 968-973
        • Funk G.C.
        • Lindner G.
        • Druml W.
        • et al.
        Incidence and prognosis of dysnatremias present on ICU admission.
        Intensive Care Med. 2010; 36: 304-311
        • Kovesdy C.P.
        • Lott E.H.
        • Lu J.L.
        • et al.
        Hyponatremia, hypernatremia, and mortality in patients with chronic kidney disease with and without congestive heart failure.
        Circulation. 2012; 125: 677-684
        • Liamis G.
        • Milionis H.
        • Elisaf M.
        A review of drug-induced hyponatremia.
        Am J Kidney Dis. 2008; 52: 144-153
        • Rusinaru D.
        • Tribouilloy C.
        • Berry C.
        • et al.
        Relationship of serum sodium concentration to mortality in a wide spectrum of heart failure patients with preserved and with reduced ejection fraction: an individual patient data meta-analysis{†}: Meta-Analysis Global Group In Chronic heart failure (MAGGIC).
        Eur J Heart Fail. 2012; 14: 1139-1146
      1. Babayev R, Terner S, Chandra S, Radhakrishnan J, Mohan S. Trimethoprim associated hyponatremia. Am J Kid Dis. Epub July 29, 2013.

        • Waikar S.S.
        • Mount D.B.
        • Curhan G.C.
        Mortality after hospitalization with mild, moderate, and severe hyponatremia.
        Am J Med. 2009; 122: 857-865
        • Ghali J.K.
        Mechanisms, risks, and new treatment options for hyponatremia.
        Cardiology. 2008; 111: 147-157
        • Chawla A.
        • Sterns R.H.
        • Nigwekar S.U.
        • Cappuccio J.D.
        Mortality and serum sodium: do patients die from or with hyponatremia?.
        Clin J Am Soc Nephrol. 2011; 6: 960-965
        • Asadollahi K.
        • Beeching N.
        • Gill G.
        Hyponatraemia as a risk factor for hospital mortality.
        QJM. 2006; 99: 877-880
        • Frenkel W.N.
        • van den Born B.J.
        • van Munster B.C.
        • et al.
        The association between serum sodium levels at time of admission and mortality and morbidity in acutely admitted elderly patients: a prospective cohort study.
        J Am Geriatr Soc. 2010; 58: 2227-2228
        • Arampatzis S.
        • Frauchiger B.
        • Fiedler G.M.
        • et al.
        Characteristics, symptoms, and outcome of severe dysnatremias present on hospital admission.
        Am J Med. 2012; 125: 1125.e1-1125.e7
        • Renneboog B.
        • Musch W.
        • Vandemergel X.
        • et al.
        Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits.
        Am J Med. 2006; 119: 71.e1-71.e8
        • Decaux G.
        Is asymptomatic hyponatremia really asymptomatic?.
        Am J Med. 2006; 119: S79-S82
        • Gankam Kengne F.
        • Andres C.
        • Sattar L.
        • et al.
        Mild hyponatremia and risk of fracture in the ambulatory elderly.
        QJM. 2008; 101: 583-588
        • Hoorn E.J.
        • Rivadeneira F.
        • van Meurs J.B.
        • et al.
        Mild hyponatremia as a risk factor for fractures: the Rotterdam Study.
        J Bone Miner Res. 2011; 26: 1822-1828
        • Angeli P.
        • Wong F.
        • Watson H.
        • Gines P.
        Hyponatremia in cirrhosis: results of a patient population survey.
        Hepatology. 2006; 44: 1535-1542
        • Shea A.M.
        • Curtis L.H.
        • Szczech L.A.
        • Schulman K.A.
        Sensitivity of International Classification of Diseases codes for hyponatremia among commercially insured outpatients in the United States.
        BMC Nephrol. 2008; 9: 5
        • Boscoe A.
        • Paramore C.
        • Verbalis J.G.
        Cost of illness of hyponatremia in the United States.
        Cost Eff Resour Alloc. 2006; 4: 10
        • Vaishya R.
        • Kaur J.
        • Seema
        • et al.
        Mortality predictors in severe hyponatraemia in emergency inpatients.
        J Indian Med Assoc. 2012; 110: 94-97
        • Doshi S.M.
        • Shah P.
        • Lei X.
        • et al.
        Hyponatremia in hospitalized cancer patients and its impact on clinical outcomes.
        Am J Kidney Dis. 2012; 59: 222-228
        • Gill G.
        • Huda B.
        • Boyd A.
        • et al.
        Characteristics and mortality of severe hyponatraemia–a hospital-based study.
        Clin Endocrinol (Oxf). 2006; 65: 246-249
      2. Centers for Disease Control and Prevention, Hyattsville, MD. National Center for Health Statistics. Questionnaires, Datasets, and Related Documentation. Available at: Accessed September 23, 2012.

      3. National Center for Health Statistics. Office of Analysis and Epidemiology. National Health and Nutrition Examination Survey (NHANES) 1999-2004 Linked Mortality Files, Mortality Follow-up Through 2006: Matching Methodology. Available at: Accessed September 23, 2012.

      4. Centers for Disease Control and Prevention. National Center for Health Statistics. 1999-2000 Lab Methods. 2010 [updated May 14, 2010]. Available at: Accessed September 23, 2012.

      5. Centers for Disease Control and Prevention. National Center for Health Statistics. 2001-2002 Lab Methods. May 14, 2010. Available at: Accessed September 23, 2012.

      6. Centers for Disease Control and Prevention. National Center for Health Statistics. 2003-2004 Lab Methods. 2011 [updated March 30, 2011]. Available at: Accessed September 23, 2012.

        • Deubner N.
        • Berliner D.
        • Frey A.
        • et al.
        Dysnatraemia in heart failure.
        Eur J Heart Fail. 2012; 14: 1147-1154
        • Nguyen M.K.
        • Ornekian V.
        • Butch A.W.
        • Kurtz I.
        A new method for determining plasma water content: application in pseudohyponatremia.
        Am J Physiol Renal Physiol. 2007; 292: F1652-F1656
        • Katz M.A.
        Hyperglycemia-induced hyponatremia–calculation of expected serum sodium depression.
        N Engl J Med. 1973; 289: 843-844
        • Hillier T.A.
        • Abbott R.D.
        • Barrett E.J.
        Hyponatremia: evaluating the correction factor for hyperglycemia.
        Am J Med. 1999; 106: 399-403
        • Dimeski G.
        • Morgan T.J.
        • Presneill J.J.
        • Venkatesh B.
        Disagreement between ion selective electrode direct and indirect sodium measurements: estimation of the problem in a tertiary referral hospital.
        J Crit Care. 2012; 27 (326 e9-16)
        • Huang W.Y.
        • Weng W.C.
        • Peng T.I.
        • et al.
        Association of hyponatremia in acute stroke stage with three-year mortality in patients with first-ever ischemic stroke.
        Cerebrovasc Dis. 2012; 34: 55-62
        • Farber M.O.
        • Weinberger M.H.
        • Robertson G.L.
        • et al.
        Hormonal abnormalities affecting sodium and water balance in acute respiratory failure due to chronic obstructive lung disease.
        Chest. 1984; 85: 49-54
        • Vitting K.E.
        • Gardenswartz M.H.
        • Zabetakis P.M.
        • et al.
        Frequency of hyponatremia and nonosmolar vasopressin release in the acquired immunodeficiency syndrome.
        JAMA. 1990; 263: 973-978
        • Ramasamy I.
        Severe hyponatraemia during therapy with ramipril.
        BMJ Case Rep. 2009; : 2009
        • Hume A.L.
        • Jack B.W.
        • Levinson P.
        Severe hyponatremia: an association with lisinopril?.
        DICP. 1990; 24: 1169-1172
        • Smith J.M.
        Clinical implications of treating depressed older adults with SSRIs: possible risk of hyponatremia.
        J Gerontol Nurs. 2010; 36 (quiz 8-9): 22-27
        • StataCorp
        Survey Introduction to Survey Commands. Survey Data Reference Manual: Release 12.
        Stata Press, College Station, TX2011
        • Hawkins R.C.
        Age and gender as risk factors for hyponatremia and hypernatremia.
        Clin Chim Acta. 2003; 337: 169-172
        • Petersson I.
        • Nilsson G.
        • Hansson B.G.
        • Hedner T.
        Water intoxication associated with non-steroidal anti-inflammatory drug therapy.
        Acta Med Scand. 1987; 221: 221-223
        • Webberley M.J.
        • Murray J.A.
        Life-threatening acute hyponatraemia induced by low dose cyclophosphamide and indomethacin.
        Postgrad Med J. 1989; 65: 950-952
        • Page A.J.
        • Reid S.A.
        • Speedy D.B.
        • et al.
        Exercise-associated hyponatremia, renal function, and nonsteroidal antiinflammatory drug use in an ultraendurance mountain run.
        Clin J Sport Med. 2007; 17: 43-48
        • Rault R.M.
        Case report: hyponatremia associated with nonsteroidal antiinflammatory drugs.
        Am J Med Sci. 1993; 305: 318-320
        • Kang S.H.
        • Kim H.W.
        • Lee S.Y.
        • et al.
        Is the sodium level per se related to mortality in hospitalized patients with severe hyponatremia?.
        Clin Nephrol. 2012; 77: 182-187
        • Sajadieh A.
        • Binici Z.
        • Mouridsen M.R.
        • et al.
        Mild hyponatremia carries a poor prognosis in community subjects.
        Am J Med. 2009; 122: 679-686