European Heart Journal

European Heart Journal 2000 21(1):53-57; doi:10.1053/euhj.1999.1740
Copyright © 2000 by the European Society of Cardiology.

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Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure

E Roig^a,f1, F Perez-Villa^a, M Morales^a, W Jiménez^b, J Orús^a, M Heras^a and G Sanz^a

^a Cardiovascular Institute, Hospital Clinical, University of Barcelona, Barcelona, Spain
^b Hormonal Laboratory, Hospital Clinical, University of Barcelona, Barcelona, Spain

revised June 7, 1999; accepted June 9, 1999

Abstract

Aims The aim of the study was to assess the incidence and clinical implications of increased plasma angiotensin II despite chronic ACE inhibitor therapy in patients with heart failure.

Methods and Results The studied population consisted of 70 patients (mean age 59±9 years). Plasma renin activity and plasma concentration of aldosterone, norepinephrine, atrial natriuretic peptide, angiotensin II, tumour necrosis factor, interleukin-6 and interleukin-1B were assessed at 6 months of ACE inhibitor therapy. Mean left ventricular ejection fraction was 24±5% and the end-systolic and end-diastolic diameters were 59±9 and 71±8mm, respectively. Despite chronic enalapril or captopril therapy, 35 patients (50%) had increased plasma angiotensin II (median 33pg.ml^–1, range 17–84), while it was in the normal range in the remaining 35 patients (median 10pg.ml^–1, range 5–15). Plasma renin activity (P=0·005), interleukin-6 (P=0·004), New York Heart Association functional class III-IV (P=0·006), furosemide dose (P=0·01), lack of beta-blocker therapy (P=0·04) and norepinephrine (P=0·04) were univariately associated with increased angiotensin II. Multivariate regression analysis identified the plasma renin activity (0·0004), norepinephrine (0·02) and interleukin-6 (0·03) as independent predictors of plasma angiotensin II. During follow-up (35±29 months), nine (12·8%) patients died and 13 had new heart failure episodes. Increased plasma angiotensin II, despite ACE inhibitor therapy, was a significant predictor of death or heart failure according to the Kaplan–Meier survival method by log rank test (P=0·002).

Conclusion Fifty per cent of patients with heart failure, had increased plasma angiotension II despite chronic ACE inhibitor therapy. These patients had higher neurohormonal activation and poor prognosis.

Key Words: Angiotensin II, ACE inhibitors, prognosis, heart failure

^f1 Correspondence: Eulàlia Roig, MD, Cardiovascular Institute, Hospital Clinic, C/Villarroel 170, Barcelona 08036, Spain.

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