Acute and Chronic Oral Magnesium ... - Wiley Online Library

4 downloads 871 Views 233KB Size Report
of Advocate Health Care approved the study .... The data were analyzed using the SPSS software ..... Oak Lawn, IL, for their cooperation and participation in this ...
www.lejacq.com

ID:4692

ORIGINAL PAPER

Acute and Chronic Oral Magnesium Supplementation: Effects on Endothelial Function, Exercise Capacity, and Quality of Life in Patients With Symptomatic Heart Failure Endothelial dysfunction is an important pathophysiologic mechanism in the progression of heart failure. The objective of the present study was to determine the effects of acute and chronic oral magnesium supplementation on endothelial function in patients with symptomatic heart failure. Twenty-two symptomatic chronic heart failure patients were randomized to receive 800 mg oral magnesium oxide daily or placebo for 3 months. Data collected included large and small arterial elasticity/compliance, hemodynamic parameters, exercise capacity, and quality-of-life score at baseline, 1 week, and 3 months. Patients who received magnesium had improved small arterial compliance at 3 months from baseline compared with placebo. This study suggests that chronic supplementation with oral magnesium is well tolerated and could improve endothelial function in symptomatic heart failure patients. (CHF. 2006;12:9–13) ©2006 CHF, Inc.

H

eart failure (HF) is a leading cause of morbidity and mortality in the United States. An estimated five million Americans are affected by HF, with approximately 500,000 new cases diagnosed each year.1,2 Endothelial dysfunction is recognized as an important pathophysiologic mechanism in the progression of HF and other vascular diseases. Potential mechanisms for these findings are: 1) elevated circulating cytokines, including tumor necrosis factor α; 2) impaired stimulated release of NO; 3) increased tissue levels of angiotensin-converting enzyme (ACE), which breaks down kinins; 4) increased free radical generation, which neutralizes NO; and 5) chronically decreased blood flow, which may impair flow-dependent NO release. In addition, increased circulating endothelin levels of pulmonary origin are reported in severe HF.3 In arteries with disrupted endothelium, removal of Mg2+ leads to vasocon-

striction, a response that is reversed when Mg2+ is replaced.4 Mg2+ reduces systemic resistance and mean arterial pressure in animals and humans, improves cardiac index, increases coronary artery blood flow, and reduces coronary vascular resistance.5–7 Two possible mechanisms for these effects are the inhibitory action of Mg2+ on Ca2+-mediated vascular tone and the release of prostacyclin, which antagonizes the pathologic platelet adhesion process. Support for the potential benefits of this therapy is seen in studies with preeclamptic patients, in whom platelet aggregation and microvascular occlusion are attributed to endothelial dysfunction.8,9 It has been hypothesized that the reduction and reversal of endothelial dysfunction is an important therapeutic tool in the management and prevention of HF. Aside from replacement therapy for low serum levels detected

during blood chemistry monitoring, however, there is little information about routine Mg2+ supplementation and its potential effects on HF outcomes. This study was designed to measure by noninvasive methods the effects of acute and chronic oral Mg2+ supplementation therapy vs. placebo on endothelial function, exercise capacity, quality of life, and outcomes in symptomatic HF patients.

Methods

Study Population. The study group comprised 22 stable patients with HF from the outpatient adult HF clinic at Advocate Christ Medical Center between November 2002 and April 2004. The Institutional Review Board of Advocate Health Care approved the study protocol in February 2002. Inclusion criteria included men and women over 21 years of age with stage C/New York Heart Association

Johanna C. Fuentes, MD;1 Adrian A. Salmon, MD;1 Marc A. Silver, MD1,2 From the Department of Medicine1 and the Heart Failure Institute,2 Advocate Christ Medical Center, Oak Lawn, IL Address for correspondence: Marc A. Silver, MD, Clinical Professor and Chairman, Department of Medicine, Director, Heart Failure Institute, Advocate Christ Medical Center, 4440 West 95th Street, Suite 319 South, Oak Lawn, IL 60453 E-mail: [email protected] Manuscript received August 8, 2005; accepted August 9, 2005 oral Mg2+ supplements in symptomatic HF

january . february 2006

9

Congestive Heart Failure® (ISSN 1527-5299) is published bimonthly (Feb., April, June, Aug., Oct., Dec.) by CHF, Inc., Three Parklands Drive, Darien, CT 06820-3652. Copyright ©2005 by CHF, Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in Congestive Heart Failure® do not necessarily reflect those of the Editor and Publisher. For copies in excess of 25 or for commercial purposes, please contact Sarah Howell at [email protected] or 203.656.1711 x106.

(NYHA) functional classes II–III systolic or diastolic HF for at least 6 months. The patients were taking recommended medications for HF, including diuretics, ACE inhibitors, angiotensin receptor blockers (ARBs), β-adrenergic receptor blockers, and digitalis.10 Exclusion criteria were serum creatinine >3 mg/dL, cirrhosis, severe peripheral vascular disease, doxorubicin cardiomyopathy, pregnancy, third degree atrioventricular block, chronic diarrhea, inflammatory bowel disease, patients already taking supplemental Mg2+, or history of elevated serum Mg2+ level. The patients were instructed to continue taking their baseline HF medications, avoid changes in their dietary habits, and discontinue vasodilators 24 hours before measurements. Study Design and Measurements. After obtaining informed consent, patients were randomized to oral Mg2+ (400 mg MgO b.i.d., for a total of 482.6 mg of elemental Mg2+) or identical placebo (maltodextrin, crosscarmellose sodium, and microcrystalline cellulose) tablets for 3 months in addition to their HF medical therapy, in a double-blind, randomized fashion. Data obtained at the beginning of the study included baseline demographic characteristics, clinical history, physical exam, NYHA functional class, body mass index, the Minnesota Living with Heart Failure questionnaire (LHFQ) score,11–13 dietary evaluation to establish daily intake of Mg2+, ejection fraction by transthoracic echocardiogram, and serum Mg2+ level. Large arterial compliance, designated C1 or large artery elasticity (LAE), and small arterial compliance, designated C2 or small artery elasticity (SAE) artery elasticity index, or arterial compliance at rest was obtained using the pressure pulse contour analysis technique with the CardioVascular Profiling Instrument model CR-2000 (Hypertension Diagnostics, Inc., Eagan, MN). Quantification of SAE provides an index of endothelial function. A reduction would indicate vascular structural 10

oral Mg2+ supplements in symptomatic HF

abnormalities. Previous work has correlated these measures with standard measurements of endothelial function.14–20 Hemodynamic parameters were also obtained using the CR-2000 profiling instrument, including mean arterial blood pressure, heart rate, systemic vascular resistance, stroke volume, estimated cardiac output, and estimated cardiac index. After obtaining the arterial compliance and hemodynamic parameters, exercise capacity was determined by having the patients perform a 6-minute walk.21,22 The distance covered was measured in meters. Quality of life was assessed using the LHFQ score. The daily Mg2+ intake was calculated with a qualitative and quantitative dietary evaluation using the US Department of Agriculture Interactive Healthy Eating Index, accessed at http://209.48.219.53 on November 2, 2004. All of the baseline evaluations were repeated in each subject at 1 week and 3 months following study drug initiation. The primary end point of the study was the impact of acute and chronic Mg2+ supplementation on endothelial function as measured by LAE and SAE. The secondary end points were changes in hemodynamic parameters, exercise capacity (6-minute walk), and improvement in LHFQ score as a measure of quality of life during the 3-month follow-up period. Statistical Analyses. The data were analyzed using the SPSS software package (SPSS Inc., Chicago, IL). Mann-Whitney U test analysis was applied to the between-group differences and a Wilcoxon signed rank test was applied to the intergroup changes. A value of p