Author + information
- Received December 1, 2004
- Revision received February 9, 2005
- Accepted February 14, 2005
- Published online September 20, 2005.
- Wolfram Doehner, MD, PhD⁎,†,⁎ (, )
- Mathias Rauchhaus, MD, PhD†,
- Piotr Ponikowski, MD, PhD‡,
- Ian F. Godsland, PhD§,
- Stephan von Haehling, MD⁎,†,‡,§,
- Darlington O. Okonko, BSc⁎,
- Francisco Leyva, MD⁎,§,
- Anthony J. Proudler, PhD§,
- Andrew J.S. Coats, DM∥ and
- Stefan D. Anker, MD, PhD⁎,†
- ↵⁎Reprint requests and correspondence:
Dr. Wolfram Doehner, Division of Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
Objectives The aim of this study was to determine the significance of insulin resistance as an independent risk factor for impaired prognosis in patients with chronic heart failure (CHF).
Background In CHF, impaired insulin sensitivity (SI) indicates abnormal energy metabolism and is related to decreased exercise capacity and muscle fatigue. The relationship between insulin resistance (i.e., low SI) and survival in patients with CHF has not been established.
Methods We prospectively studied 105 male patients with CHF due to ischemic (63%) or non-ischemic (37%) etiology. All patients were in clinically stable condition (age 62 ± 1 year, New York Heart Association [NYHA] functional class 2.6 ± 0.1, left ventricular ejection fraction [LVEF] 28 ± 2%, peak oxygen uptake [Vo2] 18.2 ± 0.7 ml/kg/min). Insulin sensitivity was assessed from glucose and insulin dynamic profiles during an intravenous glucose tolerance test using the minimal model technique.
Results During a mean follow-up period of 44 ± 4 months, 53 patients (50%) died. Patients with SIbelow the median value (median: 1.82 min−1 · μU · ml−1 · 104; n = 52) had worse survival (at two years 61% [range 47% to 74%]) than patients with SIabove the median value (n = 53; at two years 83% [range 73% to 93%]; risk ratio [RR] 0.38, 95% confidence interval [CI] 0.21 to 0.67; p = 0.001). Both patient groups were similar in terms of age, NYHA functional class, and body composition parameters (dual-energy X-ray absorptiometric scan; p > 0.2), but patients with a lower SIhad a lower LVEF (24 ± 2% vs. 33 ± 3%) and peak Vo2(16.8 ± 1.0 ml/kg/min vs. 19.7 ± 1.0 ml/kg/min; both p < 0.05). On univariate Cox analysis, higher SIpredicted better survival (RR 0.56, 95% CI 0.35 to 0.89; p = 0.015). On stepwise multivariate analysis, SIpredicted mortality independently of other variables.
Conclusions In patients with CHF, lower SIrelates to higher mortality, independent of body composition and established prognosticators. Impaired SImay have implications in the pathophysiology of CHF disease progression. Therapeutically targeting impaired insulin sensitivity may potentially be beneficial in patients with CHF.
This work was supported by a grant from the Clinical Research Council of the Royal Brompton Hospital in London. Dr. Doehner was supported by the “Verein der Freunde und Förderer der Berliner Charité,” Germany, and the National Heart and Lung Institute in London. Dr. Godsland is supported by the Heart Disease and Diabetes Research Trust. Dr. Anker is supported by a Vandervell Fellowship and a donation from Dr. Hubert Bailey. The Division of Applied Cachexia Research is supported by a grant from the Charité Medical School.
- Received December 1, 2004.
- Revision received February 9, 2005.
- Accepted February 14, 2005.
- American College of Cardiology Foundation