Published Online
on August 5, 2002

A more recent version of this article appeared on August 27, 2002

This Article Full Text (PDF) All Versions of this Article: 106/9/1055    most recent 01.CIR.0000030935.89559.04v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jorde, U. P. Articles by Le Jemtel, T. H. Search for Related Content PubMed Articles by Jorde, U. P. Articles by Le Jemtel, T. H. Related Collections Congestive Cardiovascular Pharmacology

Submitted on June 3, 2002
Revised on July 8, 2002
Accepted on July 10, 2002

Elevated Plasma Aldosterone Levels Despite Complete Inhibition of the Vascular Angiotensin-Converting Enzyme in Chronic Heart Failure

Ulrich P. Jorde MD, Timothy Vittorio MD, Stuart D. Katz MD, Paolo C. Colombo MD, Farhana Latif MD, and Thierry H. Le Jemtel MD^*

From the Division of Circulatory Physiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY (U.P.J., T.V., P.C.C.); the Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Conn (S.D.K.); and the Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, New York, NY (F.L., T.H.L.J.).

^* To whom correspondence should be addressed. E-mail: lejemtel{at}aecom.yu.edu.

Background—Plasma aldosterone levels are elevated in patients with chronic heart failure (CHF) taking angiotensin-converting enzyme (ACE) inhibitors. Elevated aldosterone levels may reflect incomplete inhibition of the vascular converting enzyme during long-term ACE inhibition. We simultaneously measured plasma aldosterone levels and the degree of inhibition of the vascular converting enzyme in patients with CHF.

Methods and Results—Thirty-four subjects with CHF receiving the maximum recommended doses of ACE inhibitors for a duration of 3 to 105 months were studied. The pressor response to exogenous angiotensin I (AI) was measured and normalized for the pressor response to angiotensin II (AII) to assess inhibition of the vascular converting enzyme (AII/AI ratio). Aldosterone levels were determined by solid-phase radioimmunoassay. Eleven of the 34 subjects had plasma aldosterone levels above the upper limit of normal, ie, >15.0 ng/dL. Seven of these 11 subjects (64%) had an AII/AI ratio 0.05, indicating complete inhibition of the vascular converting enzyme. In the entire cohort, the AII/AI ratio did not correlate with the duration of ACE inhibitor therapy.

Conclusions—Plasma aldosterone levels are elevated in patients with CHF during long-term ACE inhibitor therapy despite complete inhibition of the vascular converting enzyme. Complete inhibition of the vascular converting enzyme does not obviate the need for aldosterone receptor blockade in patients with CHF.

Key words: heart failure • angiotensin • aldosterone

This article has been cited by other articles:

				S. Klotz, D. Burkhoff, I. M. Garrelds, F. Boomsma, and A.H.J. Danser The impact of left ventricular assist device-induced left ventricular unloading on the myocardial renin-angiotensin-aldosterone system: therapeutic consequences? Eur. Heart J., April 1, 2009; 30(7): 805 - 812. [Abstract] [Full Text] [PDF]

				L. Frankenstein, C. Zugck, D. Schellberg, M. Nelles, H. Froehlich, H. Katus, and A. Remppis Prevalence and prognostic significance of adrenergic escape during chronic {beta}-blocker therapy in chronic heart failure Eur J Heart Fail, February 1, 2009; 11(2): 178 - 184. [Abstract] [Full Text] [PDF]

				M. Tsukashita, A. Marui, T. Nishina, E. Yoshikawa, H. Kanemitsu, J. Wang, T. Ikeda, and M. Komeda Spironolactone alleviates late cardiac remodeling after left ventricular restoration surgery J. Thorac. Cardiovasc. Surg., July 1, 2008; 136(1): 58 - 64. [Abstract] [Full Text] [PDF]

				H. Otani, F. Otsuka, K. Inagaki, J. Suzuki, T. Miyoshi, Y. Kano, J. Goto, T. Ogura, and H. Makino Aldosterone Breakthrough Caused by Chronic Blockage of Angiotensin II Type 1 Receptors in Human Adrenocortical Cells: Possible Involvement of Bone Morphogenetic Protein-6 Actions Endocrinology, June 1, 2008; 149(6): 2816 - 2825. [Abstract] [Full Text] [PDF]

				T. J Vittorio, K. Ahuja, M. Kasper, H. Turalic, C.-H. Tseng, U. P Jorde, and C. Gor Comparison of high- versus low-tissue affinity ACE-inhibitor treatment on circulating aldosterone levels in patients with chronic heart failure Journal of Renin-Angiotensin-Aldosterone System, December 1, 2007; 8(4): 200 - 204. [Abstract] [PDF]

				K. Funabiki, K. Onishi, K. Dohi, T. Koji, K. Imanaka-Yoshida, M. Ito, H. Wada, N. Isaka, T. Nobori, and T. Nakano Combined angiotensin receptor blocker and ACE inhibitor on myocardial fibrosis and left ventricular stiffness in dogs with heart failure Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2487 - H2492. [Abstract] [Full Text] [PDF]

				H. S. Lim, R. J. MacFadyen, and G. Y. H. Lip Diabetes Mellitus, the Renin-Angiotensin-Aldosterone System, and the Heart Arch Intern Med, September 13, 2004; 164(16): 1737 - 1748. [Abstract] [Full Text] [PDF]

				R. Paoletti, A. M. Gotto Jr, and D. P. Hajjar Inflammation in Atherosclerosis and Implications for Therapy Circulation, June 15, 2004; 109(23_suppl_1): III-20 - III-26. [Abstract] [Full Text]

				M. Karmazyn, Q. Liu, X. T. Gan, B. J. Brix, and L. Fliegel Aldosterone Increases NHE-1 Expression and Induces NHE-1-Dependent Hypertrophy in Neonatal Rat Ventricular Myocytes Hypertension, December 1, 2003; 42(6): 1171 - 1176. [Abstract] [Full Text] [PDF]

				D. Fraccarollo, P. Galuppo, S. Hildemann, M. Christ, G. Ertl, and J. Bauersachs Additive improvement of left ventricular remodeling and neurohormonal activation by aldosterone receptor blockade with eplerenone and ACE inhibition in rats with myocardial infarction J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1666 - 1673. [Abstract] [Full Text] [PDF]

				K. T Weber, Yao Sun, L. A Wodi, A. Munir, E. Jahangir, R. A Ahokas, I. C Gerling, A. E Postlethwaite, and K. J Warrington Toward a broader understanding of aldosterone in congestive heart failure Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 155 - 163. [Abstract] [PDF]

				O. Ben-Yehuda Hypertension, angiotensin II, aldosterone, and race J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1156 - 1158. [Full Text] [PDF]

				R. W. Braith, R. M. Mills, C. S. Wilcox, G. L. Davis, J. A. Hill, and C. E. Wood High-dose angiotensin-converting enzyme inhibition restores body fluid homeostasis in heart-transplant recipients J. Am. Coll. Cardiol., February 5, 2003; 41(3): 426 - 432. [Abstract] [Full Text] [PDF]