Christoffer Polcwiartek1, Steen Møller Hansen2, Kristian Kragholm3, Maria Lukács Krogager2, Mette Aldahl4, Lars Køber5, Christian Torp-Pedersen6, Svend Eggert Jensen7, Peter Søgaard7. 1. Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; Unit of Epidemiology and Biostatistics, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address: c.polcwiartek@gmail.com. 2. Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; Unit of Epidemiology and Biostatistics, Aalborg University Hospital, Aalborg, Denmark. 3. Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; Unit of Epidemiology and Biostatistics, Aalborg University Hospital, Aalborg, Denmark; Department of Cardiology, North Denmark Regional Hospital, Hjørring, Denmark. 4. Unit of Epidemiology and Biostatistics, Aalborg University Hospital, Aalborg, Denmark. 5. Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 6. Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; Unit of Epidemiology and Biostatistics, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. 7. Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Abstract
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.
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.