title: Hyponatremia, all-cause mortality, and risk of cancer diagnoses in the primary care setting: A large population study.
abstract: BACKGROUND
  Hyponatremia has been associated with increased all-cause mortality in hospitalized individuals. In this study we examine the risk of all-cause mortality in primary care subjects with hyponatremia, while also exploring the association with subsequent diagnosis of cancer.
  
  
  METHODS
  Retrospective cohort study on subjects who underwent blood tests, consulting their general practitioner 2000-2012 in Copenhagen, Denmark. Reference range for sodium was 135-145mmol/L, and mild, moderate, and severe hyponatremia were defined as 130-135, 125-129, and <125mmol/L, respectively. Primary outcome was all-cause mortality, and secondary outcomes overall and specific types of cancer diagnoses.
  
  
  RESULTS
  Among 625,114 included subjects (mean age 49.9 [SD±18.4] years; 43.5% males), 90,926 (14.5%) deaths occurred. All-cause mortality was increased in mild, moderate, and severe hyponatremia (age-adjusted mortality rates [IRs, incidence rates] 26, 30, and 36 per 1000 person-years (py), respectively and incidence rate ratios [IRRs] 1.81 [95% CI: 1.76-1.85], 2.11 [2.00-2.21], and 2.52 [2.26-2.82], respectively) compared with individuals with normonatremia (IR 14 per 1000 py). For the secondary endpoint an increased level-dependent risk was found with lower sodium levels in relation to cancer overall, head and neck cancers, and pulmonary cancer, with severe hyponatremia associated with the highest IRRs (1.77 [1.39-2.24], 5.24 [2.17-12.63]), and 4.99 [3.49-7.15], respectively).
  
  
  CONCLUSIONS
  All levels of hyponatremia are associated with all-cause mortality in primary care patients and hyponatremia is linked to an increased risk of being diagnosed with any cancer, particularly pulmonary and head and neck cancers.
authors.affiliation: Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark; Department of Endocrinology, Amager and Hvidovre University Hospital, Copenhagen, Denmark. Electronic address: cselmer@gmail.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Selmer
authors.affiliation: Copenhagen General Practitioners Laboratory, Copenhagen, Denmark.
authors.forename: Jesper Clausager
authors.initials: JC
authors.lastname: Madsen
authors.affiliation: Institute of Health, Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.affiliation: Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.
authors.forename: Gunnar Hilmar
authors.initials: GH
authors.lastname: Gislason
authors.affiliation: Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Department of Endocrinology, Herlev University Hospital, Herlev, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Faber
mesh_terms: D000328:Adult; D000368:Aged; D002423:Cause of Death; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006258:Head and Neck Neoplasms / Q000453:epidemiology*; D006801:Humans; D007010:Hyponatremia / Q000097:blood / Q000453:epidemiology*; D007177:Inappropriate ADH Syndrome / Q000453:epidemiology*; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009369:Neoplasms / Q000453:epidemiology; D011320:Primary Health Care; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D012964:Sodium / Q000097:blood
chemical_list: D012964:Sodium
keywords: Cancer; Hyponatremia; Mortality; Neoplasm; SIADH; Sodium