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 i ntercellular 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 progno stic information to that obtained from clinical and biochemical variab les previously known to be associated with high mortality. Plasma leve ls of sICAM-1 and ET-1 were measured in 102 patients with CHF (left ve ntricular ejection fraction [LVEF] <0.45), and patients were followed vp for >18 months. The plasma level of sICAM-1 increased with the seve rity of CHF (normal, 149 +/- 10 ng/ml, mild CHF [New York Heart Associ ation 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 inc reased 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 bo th sICAM-1 and ET-1 decreased after treatment in 14 patients, with imp rovements in symptoms (from functional class IV to II) during the foll ow-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 signi ficant negative correlation was between LVEF and plasma ET-1 (r = -0.3 4, p <0.001), and plasma sICAM-1 (r = -0.36, p <0.001). Cox proportion al hazards analysis was performed to determine the significance of LVE F, plasma levels of norepinephrine, ET-1, and sICAM-1 as independent p redictors of CHF; high levels of plasma ET-1 and sICAM-1 were found to be independent significant predictors. These findings indicate that t he plasma levels of sICAM-1 and ET-1 increased with the severity of CH F and can provide prognostic information independent of clinical and b iochemical variables previously associated with a poor prognosis.