Insulin resistance and exercise tolerance in heart failure patients: linkage to coronary flow reserve and peripheral vascular function.
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 (VO(2)peak), 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/m(2)) isoglycemic clamp.


RESULTS
Fat free mass adjusted insulin sensitivity was significantly correlated to VO(2)peak (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 VO(2)peak 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.
Dept Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark. snoer@dadlnet.dk
Martin
M
Snoer
Tea
T
Monk-Hansen
Rasmus Huan
RH
Olsen
Lene Rørholm
LR
Pedersen
Lene
L
Simonsen
Hanne
H
Rasmusen
Flemming
F
Dela
Eva
E
Prescott
D015502:Absorptiometry, Photon; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D016009:Chi-Square Distribution; D003718:Denmark; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005080:Exercise Test; D005081:Exercise Therapy; D017079:Exercise Tolerance; D005260:Female; D053805:Fractional Flow Reserve, Myocardial; D015309:Glucose Clamp Technique; D006333:Heart Failure / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D063177:Pulse Wave Analysis; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume; D014463:Ultrasonography; D059289:Vascular Stiffness; D016277:Ventricular Function, Left
D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin