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.
European Journal of Internal Medicine, 2016, Vol 36, p. 36-43