Prognostic value of serum hyponatremia for outcomes in patients with heart failure with preserved ejection fraction: An observational cohort study

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Abstract
Hyponatremia is a risk factor associated with poor prognosis in patients with heart failure (HF) with reduced ejection fraction. However, whether hyponatremia has a similar role in patients with HF with preserved ejection fraction (HFpEF) has remained controversial. Therefore, the present study aimed to investigate the clinical characteristics and 24‑month prognostic profile of a cohort of patients with HFpEF in China. From a registered observational cohort study on 1,027 subjects with HF, 496 patients with HFpEF were included. The association between baseline hyponatremia on admission and 24‑month adverse outcomes (including all‑cause mortality, re‑hospitalization for HF and stroke) was analyzed using logistic regression with the Cox proportional hazards model. Of the 496 patients with HFpEF with a mean age of 72.8 years and proportion of males of 53.0%, 71 patients were diagnosed with hyponatremia. Furthermore, 29 patients (5.8%) were lost to follow‑up. The hyponatremia group had lower blood pressure and serum hemoglobin, higher N‑terminal pro B‑type natriuretic peptide (NT‑proBNP) and D‑dimer, more patients with a history of atrial fibrillation and a higher proportion of spironolactone and loop diuretic use. According to a multivariate regression analysis, New York Heart Association functional classes III‑IV and a serum NT‑proBNP level above the median were risk factors for hyponatremia, while higher systolic blood pressure and β‑blocker use were protective factors against hyponatremia. In the Kaplan‑Meier analysis, hyponatremia was associated with all‑causes of mortality, re‑hospitalization for HF and a poor prognosis for patients suffering from strokes (log‑rank P<0.05 for all 3 endpoints). On multivariate logistic regression analysis with the Cox proportional hazard model, hyponatremia was an independent predictor of three adverse outcomes [all‑cause mortality: Hazard ratio (HR)=1.54, 95% CI=1.07‑2.91, P=0.034; re‑hospitalization for heart failure: HR=1.28, 95% CI=1.16‑2.47, P=0.013; stroke: HR=1.78, 95% CI=1.04‑2.89, P=0.016]. Collectively, the present results suggested that hyponatremia on admission was significantly associated with all‑cause mortality, re‑hospitalization and stroke within 24 months in a cohort of hospitalized patients with HFpEF in China. Thus, hyponatremia should be carefully monitored and frequently adjusted in patients with HFpEF (NCT04062500).

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