Impaired insulin sensitivity as an independent risk factor for mortality in patients with stable chronic heart failure.
OBJECTIVE
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 (S(I)) indicates abnormal energy metabolism and is related to decreased exercise capacity and muscle fatigue. The relationship between insulin resistance (i.e., low S(I)) 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 [Vo(2)] 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 S(I) below the median value (median: 1.82 min(-1) x microU x ml(-1).10(4); n = 52) had worse survival (at two years 61% [range 47% to 74%]) than patients with S(I) above 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 S(I) had a lower LVEF (24 +/- 2% vs. 33 +/- 3%) and peak Vo(2) (16.8 +/- 1.0 ml/kg/min vs. 19.7 +/- 1.0 ml/kg/min; both p < 0.05). On univariate Cox analysis, higher S(I) predicted better survival (RR 0.56, 95% CI 0.35 to 0.89; p = 0.015). On stepwise multivariate analysis, S(I) predicted mortality independently of other variables.


CONCLUSIONS
In patients with CHF, lower S(I) relates to higher mortality, independent of body composition and established prognosticators. Impaired S(I) may have implications in the pathophysiology of CHF disease progression. Therapeutically targeting impaired insulin sensitivity may potentially be beneficial in patients with CHF.
Doehner
Wolfram
W
Department of Clinical Cardiology, National Heart and Lung Institute, Imperial College, London, United Kingdom. wolfram.doehner@charite.de
Rauchhaus
Mathias
M
Ponikowski
Piotr
P
Godsland
Ian F
IF
von Haehling
Stephan
S
Okonko
Darlington O
DO
Leyva
Francisco
F
Proudler
Anthony J
AJ
Coats
Andrew J S
AJ
Anker
Stefan D
SD
D002908:Chronic Disease; D005500:Follow-Up Studies; D006333:Heart Failure / Q000378:metabolism* / Q000401:mortality*; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors