Recently, the Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive lowering of systolic blood pressure is beneficial, but is associated with more adverse events. Hyponatremia was notably more frequent in the intensive treatment group. Investigating its risk factors is crucial for preventing this complication. Our objective in this study was to identify risk factors for hyponatremia in the adult population.

We investigated the baseline demographic, clinical, and laboratory data from the 9361 participants of SPRINT to identify the best predictors of hyponatremia (serum sodium ≤130 mEq/L), and adverse events, which could be attributed to hyponatremia, using machine learning and multivariable Cox proportional hazards models. We confirmed our results in the independent National Health and Nutrition Examination Survey (NHANES) cohort between the years 2005 and 2010 (16,501 participants).

Elevated baseline high-density lipoprotein cholesterol (HDL-C) was a strong predictor of future hyponatremia. Multivariable Cox regression showed hyponatremia events to be significantly increased for SPRINT participants with baseline HDL-C levels in the highest quintile (hazard ratio [HR] 2.8; 95% confidence interval [CI], 2.2-3.7; P <.001), and were also associated with treatment-related serious adverse events (HR 1.6; 95% CI, 1.3-2.1; P <.001). We confirmed the association between HDL-C and hyponatremia in the NHANES cohort (HR 2.5; 95% CI, 1.7-3.7; P <.001).

Elevated HDL-C (≥62 mg/dL) is a risk factor for hyponatremia. Thus, hypertensive patients with elevated HDL-C should be closely monitored for hyponatremia when treated for hypertension.