PROGNOSTIC VALUE OF PLASMA SOLUBLE INTERCELLULAR-ADHESION MOLECULAR AND ENDOTHELIN-1 CONCENTRATION IN PATIENTS WITH CHRONIC CONGESTIVE-HEART-FAILURE

We tested the hypothesis that plasma endothelin-1 (ET-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in patients with congestive heart failure (CHF) are related to subsequent survival, and assessed whether the measurements of these substances provide additional prognostic information to that obtained from clinical and biochemical variables previously known to be associated with high mortality. Plasma levels of sICAM-1 and ET-1 were measured in 102 patients with CHF (left ventricular ejection fraction [LVEF] <0.45), and patients were followed vp for >18 months. The plasma level of sICAM-1 increased with the severity of CHF (normal, 149 +/- 10 ng/ml, mild CHF [New York Heart Association functional class II], 207 +/- 9.4 ng/ml, severe CHF [functional class III or IV], 293 +/- 18 ng/ml). The plasma level of ET-1 also increased with the severity of CHF (normal, 1.5 +/- 0.2 pg/ml, mild CHF, 2.1 +/- 0.1 pg/ml, severe CHF, 4.0 +/- 0.4 pg/ml). Plasma levels of both sICAM-1 and ET-1 decreased after treatment in 14 patients, with improvements in symptoms (from functional class IV to II) during the follow-vp period. There was a significant positive correlation between the plasma level of ET-1 and plasma sICAM-1 (r = 0.44, p <0.001). A significant negative correlation was between LVEF and plasma ET-1 (r = -0.34, p <0.001), and plasma sICAM-1 (r = -0.36, p <0.001). Cox proportional hazards analysis was performed to determine the significance of LVEF, plasma levels of norepinephrine, ET-1, and sICAM-1 as independent predictors of CHF; high levels of plasma ET-1 and sICAM-1 were found to be independent significant predictors. These findings indicate that the plasma levels of sICAM-1 and ET-1 increased with the severity of CHF and can provide prognostic information independent of clinical and biochemical variables previously associated with a poor prognosis.