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Elevated High-Density Lipoprotein Cholesterol Is Associated with Hyponatremia in Hypertensive Patients

Density plots comparing high-density lipoprotein cholesterol (HDL-C) at baseline in Systolic Blood Pressure Intervention Trial (SPRINT) participants who developed hyponatremia (red) during the study and patients who did not develop hyponatremia (blue). Baseline HDL-C was significantly more elevated in participants who later developed hyponatremia, for both males and females (P <.0001 in both sexes; Wilcoxon test).

Density plots comparing high-density lipoprotein cholesterol (HDL-C) at baseline in Systolic Blood Pressure Intervention Trial (SPRINT) participants who developed hyponatremia (red) during the study and patients who did not develop hyponatremia (blue). Baseline HDL-C was significantly more elevated in participants who later developed hyponatremia, for both males and females (P

 

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.

Methods

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).

Results

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).

Conclusions

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.

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-Ariel Israel, MD, PhD, Ehud Grossman, MD

This article originally appeared in the November 2017 issue of The American Journal of Medicine.

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