Hyponatremia, all-cause mortality, and risk of cancer diagnoses in the primary care setting: a large population study

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.