Mild Hyponatremia Carries a Poor Prognosis in Community Subjects

ObjectiveHyponatremia has been shown to predict adverse outcome in congestive heart failure and pneumonia among other common clinical entities, but its significance in the general population is elusive.MethodsThe population-based Copenhagen Holter Study included 671 men and women aged 55 to 75 years with no history of cardiovascular disease, stroke, or cancer. Baseline evaluation included 48-hour ambulatory electrocardiogram monitoring, blood tests, and a questionnaire. Hyponatremia was defined as s-Na ≤ 134 mEq/L or s-Na ≤ 137 mEq/L according to previously accepted definitions. An adverse outcome was defined as deaths or myocardial infarction. Median follow-up was 6.3 years.ResultsFourteen subjects (2.1%, group A) had s-Na ≤ 134 mEq/L, and 62 subjects (9.2%, group B) had s-Na ≤ 137 mEq/L. No subject had s-Na < 129 mEq/L. An adverse outcome occurred in 43% of group A, 27% of group B, and 14% of subjects with s-Na >137mEq/L (controls) (P <.002). Adjusted hazard ratio for adverse outcome was 3.56 (95% confidence interval [CI], 1.53-8.28, P <.005) in group A compared with controls and 2.21 (95% CI, 1.29-3.80, P <.005) in group B after controlling for age, gender, smoking, diabetes, low-density lipoprotein cholesterol, and blood pressure. The hazard ratios were robust for additional adjusting for variables showing univariate association to hyponatremia (ie, beta-blocker and diuretic use, heart rate variability, creatinine, C-reactive protein, and NT-pro brain natriuretic peptide). By excluding diuretic users (18% of subjects), the adjusted hazard ratio for adverse outcome was 8.00 (95% CI, 3.04-21.0, P <.0001) in group A and 3.17 (95% CI, 1.76-5.72, P = .0001) in group B compared with controls.ConclusionHyponatremia is an independent predictor of deaths and myocardial infarction in middle-aged and elderly community subjects.