Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure

Background. Endothelin is a family of potent vasoconstrictor peptides of vascular endothelial origin. Although it has been proposed that the vasoconstrictor effects of endothelin are produced at the local vascular level, increased plasma concentration of endothelin has been identified in cardiovascular disorders. Methods and Results. We tested whether immunoreactive endothelin-1 could be detected by radioimmunoassay in plasma of congestive heart failure patients and whether levels correlated with hemodynamic characteristics. Twenty congestive heart failure patients (New York Heart Association class II-IV) were sampled in the morning after an overnight fast, before medication. Cardiac index was decreased to 2.14±0.45 I/m/m², and pulmonary wedge pressure was increased to 22±7 mm Hg. The ranges of pulmonary pressures were: systolic, 22-100 mm Hg, mean, 13-61 mm Hg, and diastolic, 8-42 mm Hg. The endothelin-1 level was 9.07±4.13 pg/ml (range, 4-19 pg/ml), which was increased compared with 12 normals (3.7±0.6 pg/ml; range, 2.8-4.7 pg/ml); the difference was statistically significant (p<0.0001). Endothelin-1 significantly correlated with pulmonary pressures (systolic, r=0.78; mean, r=0.80; diastolic, r=0.77; al p<0.003) and pulmonary vascular resistance (r=0.65,p<0.01). Endothelin-1 strongly correlated with the resistance ratio (pulmonary vascular resistance/systemic vascular resistance) (r=0.88, p<0.0001). Stepwise multiple regression analysis confirmed the significance of these observations. Conclusions. Elevated immunoreactive endothelin-1 specifically correlated with the extent of pulmonary hypertension in congestive heart failure patients. Whether endothelin-1 is a regional mediator of pulmonary hypertension or a marker for its occurrence requires additional evaluation.