Open Access Original investigation

Insulin resistance and exercise tolerance in heart failure patients: linkage to coronary flow reserve and peripheral vascular function

Martin Snoer1*, Tea Monk-Hansen1, Rasmus H Olsen1, Lene R Pedersen1, Lene Simonsen2, Hanne Rasmusen1, Flemming Dela3 and Eva Prescott1

Author Affiliations

1 Dept Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark

2 Department of Clinical Physiology and Nuclear Medicine, Bispebjerg University Hospital, Copenhagen, Denmark

3 Xlab Center for Healthy Aging, Department of Biomedical Science, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

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Cardiovascular Diabetology 2012, 11:97 doi:10.1186/1475-2840-11-97

Published: 13 August 2012

Abstract

Background

Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage.

Methods

39 patients with LVEF < 35% (median LV ejection fraction (LVEF) 31 (interquartile range (IQ) 26–34), 23/39 of ischemic origin) underwent echocardiography with measurement of CFR. Peak coronary flow velocity (CFV) was measured in the LAD and coronary flow reserve was calculated as the ratio between CFV at rest and during a 2 minutes adenosine infusion. All patients performed a maximal symptom limited exercise test with measurement of peak oxygen uptake (VO2peak), digital measurement of endothelial function and arterial stiffness (augmentation index), dual X-ray absorptiometry scan (DEXA) for body composition and insulin sensitivity by a 2 hr hyperinsulinemic (40 mU/min/m2) isoglycemic clamp.

Results

Fat free mass adjusted insulin sensitivity was significantly correlated to VO2peak (r = 0.43, p = 0.007). Median CFR was 1.77 (IQ 1.26-2.42) and was correlated to insulin sensitivity (r 0.43, p = 0.008). CFR (r = 0.48, p = 0.002), and arterial stiffness (r = −0.35, p = 0.04) were correlated to VO2peak whereas endothelial function and LVEF were not (all p > 0.15). In multivariable linear regression adjusting for age, CFR remained independently associated with VO2peak (standardized coefficient (SC) 1.98, p = 0.05) whereas insulin sensitivity (SC 1.75, p = 0.09) and arterial stiffness (SC −1.17, p = 0.29) were no longer associated with VO2peak.

Conclusions

The study confirms that insulin resistance is associated with exercise intolerance in heart failure patients and suggests that this is partly through reduced CFR. This is the first study to our knowledge that shows an association between CFR and exercise capacity in heart failure patients and links the relationship between insulin resistance and exercise capacity to CFR.

Keywords:
Coronary flow reserve; Heart failure; Exercise capacity; Insulin sensitivity; Arterial stiffness