Prognostic significance of hyponatremia among ambulatory patients with heart failure and preserved and reduced ejection fractions

Hyponatremia in heart failure (HF) is an established predictor of adverse outcomes in hospitalized patients with reduced ejection fraction (EF). However, there is a paucity of data in ambulatory patients with HF with preserved ejection fraction (HFpEF). We examined the prevalence, risk factors, and long-term outcomes of hyponatremia (serum sodium ≤ 135 mEq/L) in ambulatory HFpEF and HF with reduced EF (HFrEF) in a national cohort of 8,862 veterans treated in Veterans Affairs clinics. Multivariable logistic regression models were used to identify factors associated with hyponatremia, and multivariable Cox proportional hazard models were used for analysis of outcomes. The cohort consisted of 6,185 patients with HFrEF and 2,704 patients with HFpEF with a 2-year follow-up. Hyponatremia was present in 13.8% and 12.9% patients in HFrEF and HFpEF, respectively. Hyponatremia was independently associated with younger age, diabetes, lower systolic blood pressure, anemia, body mass index <30 kg/mbsupesup, and spironolactone use, whereas African-American race and statins were inversely associated. In multivariate analysis, hyponatremia remained a significant predictor of all-cause mortality in both HFrEF (hazards ratio [HR] 1.26, 95% confidence interval [CI] 1.11 to 1.44, p < 0.001) and HFpEF (HR 1.40, 95% CI 1.12 to 1.75, p = 0.004) and a significant predictor of all-cause hospitalization in patients with HFrEF (HR 1.18, 95% CI 1.07 to 1.31, p = 0.001) but not in HFpEF (HR 1.08, 95% CI 0.92 to 1.27, p = 0.33). In conclusion, hyponatremia is prevalent at a similar frequency of over 10% in ambulatory patients with HFpEF and HFrEF. Hyponatremia is an independent prognostic marker of mortality across the spectrum of patients with HFpEF and HFrEF. In contrast, it is an independent predictor for hospitalization in patients with HFrEF but not in patients with HFpEF.