Prognostic role of serum sodium levels across different serum potassium levels in heart failure patients: A Danish register-based cohort study

BACKGROUND: In heart failure (HF), evidence on the prognosis of simultaneously abnormal sodium and potassium levels remains unknown. Therefore, we investigated associations between sodium levels and 90-day all-cause mortality across potassium levels in HF patients.

METHODS: Using Danish registers, we identified HF patients with sodium and potassium levels within 90 days following a redeemed loop diuretic prescription from 2000 to 2012. We grouped sodium (<139, 139-143, >143 mmol/L) and potassium levels (<3.5 [hypokalemia], 3.5-4.0, 4.1-4.6, 4.7-5.0, >5.0 mmol/L [hyperkalemia]). First, by adjusting for potassium groups using multivariable Cox regression, we compared mortality of sodium <139 mmol/L and >143 mmol/L with 139-143 mmol/L as reference. Second, by combining sodium and potassium groups, we compared mortality of the resulting 15 combinations using sodium 139-143 mmol/L and potassium 4.1-4.6 mmol/L as reference.

RESULTS: We included 16,343 HF patients (median age: 77.0 years; males: 53.7%). When adjusting for potassium groups, sodium <139 mmol/L and >143 mmol/L were associated with excess mortality (hazard ratio [HR]: 1.91, 95% confidence interval [CI]: 1.74-2.09; HR: 1.45, 95% CI: 1.25-1.68; respectively). When stratifying across potassium groups (interaction term: P = 0.291), we observed excess mortality with hyperkalemia for sodium <139 mmol/L (HR: 3.30, 95% CI: 2.76-3.96) and >143 mmol/L (HR: 3.46, 95% CI: 2.31-5.18), whereas mortality risk was lower for sodium 139-143 mmol/L (HR: 1.67, 95% CI: 1.30-2.14). Correspondingly, hypokalemia was associated with excess mortality (<139 mmol/L: HR: 3.53, 95% CI: 2.76-4.52; 139-143 mmol/L: HR: 2.47, 95% CI: 1.88-3.24; >143 mmol/L: HR: 2.67, 95% CI: 1.73-4.12). Lowest mortality risk appeared with sodium 139-143 mmol/L combined with remaining potassium groups.

CONCLUSION: Abnormal sodium is an important risk factor for mortality in HF patients receiving diuretics, and the importance is independent of potassium levels.