Association between plasma endothelin-1 levels and Cheyne-Stokes respiration in patients with congestive heart failure

Study objectives: Elevated plasma endothelin-1 (ET-1) levels have been reported in association with hypoxia and congestive heart failure (CHF). Furthermore, Cheyne-Stokes respiration-central sleep apnea (CSR-CSA) has been found to correlate with the degree of pulmonary hypertension and the severity of CHF; however, the association between ET-1 levels and CSR-CSA has not been investigated previously. Setting: Veterans Affairs Medical Center. Interventions: We studied 46 consecutive patients with CHF (left ventricular function ≤ 40%) who underwent right-heart catheterization and overnight polysomnography. Thirty-nine patients completed the study. Sixteen patients (41%) had CSR-CSA, 5 patients (13%) had obstructive apnea, and 18 patients (46%) had no sleep-disordered breathing. Circulating plasma ET-1 levels were assayed in patients with CSR-CSA and in patients with no sleep-disordered breathing using commercially available enzyme-linked immunosorbent assay kits. Results: ET-1 levels were significantly elevated in patients with CSR-CSA (mean ± SD, 5.4 ± 1.3 pg/mL) compared to those without central apnea (3.9 ± 1.1 pg/mL; p < 0.01), and correlated with mean pulmonary artery pressure (r = 0.66, p < 0.01), pulmonary capillary wedge pressure (r = 0.56, p < 0.03), and central apnea frequency (r = 0.66, p < 0.01). In multivariate analysis, the severity of CSR-CSA was the only variable independently associated with plasma ET-1. Conclusions: We conclude that elevated plasma ET-1 levels are linked to the severity of CSR-CSA. Whether ET-1 represents an important pathogenic factor in CSR-CSA or marker of its occurrence requires further evaluation.