Predictors of Development of Diabetes in Patients With Chronic Heart Failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) Program
- David Preiss, MRCP1,
- Sofia Zetterstrand, PHD2,
- John J.V. McMurray, MD1,
- Jan Östergren, MD3,
- Eric L. Michelson, MD4,
- Christopher B. Granger, MD5,
- Salim Yusuf, MB BS, DPHIL6,
- Karl Swedberg, MD, PHD7,
- Marc A. Pfeffer, MD, PHD8,
- Hertzel C. Gerstein, MD9,
- Naveed Sattar, PHD1 and
- for the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity Investigators
- 1BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, U.K.;
- 2AstraZeneca R&D, Mölndal, Sweden;
- 3Department of Medicine, Karolinska University Hospital, Solna, Stockholm, Sweden;
- 4AstraZeneca LP, Wilmington, Delaware;
- 5Duke University Medical Center, Durham, North Carolina;
- 6HGM-McMaster Clinic, Hamilton, Ontario, Canada;
- 7Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;
- 8Brigham & Women's Hospital, Boston, Massachusetts;
- 9Department of Medicine and the Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.
- Corresponding author: Naveed Sattar, nsattar{at}clinmed.gla.ac.uk.
Abstract
OBJECTIVE The purpose of this study was to identify predictors of incident diabetes during follow-up of nondiabetic patients with chronic heart failure (CHF) in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program.
RESEARCH DESIGN AND METHODS A total of 1,620 nondiabetic patients had full baseline datasets. We compared baseline demographic, medication, and laboratory data for patients who did or did not develop diabetes and conducted logistic regression and receiver operator characteristic curve analyses.
RESULTS Over a median period of 2.8 years, 126 of the 1,620 patients (7.8%) developed diabetes. In multiple logistic regression analysis, the following baseline characteristics were independently associated with incident diabetes in decreasing order of significance by stepwise selection: higher A1C (odds ratio [OR] 1.78 per 1 SD increase; P < 0.0001), higher BMI (OR 1.64 per 1 SD increase; P < 0.0001), lipid-lowering therapy (OR 2.05; P = 0.0005), lower serum creatinine concentration (OR 0.68 per 1 SD increase; P = 0.0018), diuretic therapy (OR 4.81; P = 0.003), digoxin therapy (OR 1.65; P = 0.022), higher serum alanine aminotransferase concentration (OR 1.15 per 1 SD increase; P = 0.027), and lower age (OR 0.81 per 1 SD increase; P = 0.048). Using receiver operating characteristic curve analysis, A1C and BMI yielded areas under the curve of 0.723 and 0.712, respectively, increasing to 0.788 when combined. Addition of other variables independently associated with diabetes risk minimally improved prediction of diabetes.
CONCLUSIONS In nondiabetic patients with CHF in CHARM, A1C and BMI were the strongest predictors of the development of diabetes. Other minor predictors in part reflected CHF severity or drug-associated diabetes risk. Identifying patients with CHF at risk of diabetes through simple criteria appears possible and could enable targeted preventative measures.
Footnotes
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Clinical trial reg. nos. NCT00634400 (CHARM Alternative), NCT00634309 (CHARM Added), and NCT00634712 (CHARM Preserved), clinicaltrials.gov.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received September 18, 2008.
- Accepted January 21, 2009.
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Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
- © 2009 by the American Diabetes Association.
