Effect of high- versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure

OBJECTIVES We examined the effect of long term treatment with two doses of the angiotensin converting enzyme (ACE) inhibitor enalapril on various immu nological variables in patients with chronic congestive heart failure (CHF) . BACKGROUND Immunological mediators are increasingly recognized to play a pa thogenic role in the pathophysiology of CHF. Whether ACE inhibitor therapy modifies immunological variables has not previously been investigated. METHODS Seventy-five patients (mean age 52 +/- 11 pears) with CHF were rand omized between low(5 mg daily) and high-dose (40 mg daily) enalapril in a d ouble-blind trial. Circulating levels of immunological parameters (i.e., pr oinflammatory cytokines, chemokines and adhesion molecules) were measured a t baseline, at 10 weeks and at the end of the study (34 weeks). RESULTS All immunological parameters, except soluble interleukin (IL)-6 rec eptor, were increased in CHF compared with 21 healthy controls. During the study immunoreactive IL-6 levels decreased (p < 0.05) and soluble IL-6 rece ptor increased (p < 0.05) during high-dose but not during low-dose enalapri l therapy. Furthermore, IL-6 bioactivity decreased only during the high-dos e (p < 0.001), resulting in a significant difference in change during treat ment between the two dosage groups (p < 0.001). This decrease in IL-6 bioac tivity was significantly associated with decreased interventricular septum thickness as assessed by echocardiography (r = 0.56, p = 0.013). No other v ariables changed during treatment. CONCLUSIONS In patients with severe CHF, high-dose enalapril therapy is ass ociated with a significant decrease in IL-6 activity. However, despite trea tment with a high-dose ACE inhibitor, a persistent immune activation exists in these patients which may be of importance for the progression of CHF. ( C) 1999 by the American College of Cardiology.