The online version of this article (doi:10.1186/1475-2840-11-97) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
MS participated in the design of the study, collection of data, statistical analysis and drafting the paper. TM participated in the design of the study, collection of data and contributed to discussion. RO participated in analyzing the data and contributed to discussion. LP participated in analyzing the data and contributed to discussion. LS reviewed/edited the manuscript and contributed to discussion. HR reviewed/edited the manuscript and contributed to discussion. FD participated in the design of the study, reviewed/edited the manuscript and contributed to discussion. EP participated in the design of the study, statistical analysis reviewed/edited the manuscript and contributed to discussion. All authors read and approved the final manuscript.
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.
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.
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.
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.
AlZadjali MA, Godfrey V, Khan F, Choy A, Doney AS, Wong AK, Petrie JR, Struthers AD, Lang CC: Insulin resistance is highly prevalent and is associated with reduced exercise tolerance in nondiabetic patients with heart failure. J Am Coll Cardiol. 2009, 53: 747-753. 10.1016/j.jacc.2008.08.081. CrossRefPubMed
Ahmari SAL, Bunch TJ, Modesto K, Stussy V, Dichak A, Seward JB, Pellikka PA, Chandrasekaran K: Impact of Individual and Cumulative Coronary Risk Factors on Coronary Flow Reserve Assessed by Dobutamine Stress Echocardiography. Am J Cardiol. 2008, 101: 1694-1699. 10.1016/j.amjcard.2008.02.055. CrossRefPubMed
Rigo F, Gherardi S, Galderisi M, Sicari R, Picano E: The independent prognostic value of contractile and coronary flow reserve determined by dipyridamole stress echocardiography in patients with idiopathic dilated cardiomyopathy. Am J Cardiol. 2007, 99: 1154-1158. 10.1016/j.amjcard.2006.11.049. CrossRefPubMed
Santos JM, Kowatsch I, Tsutsui JM, Negrao CE, Canavesi N, Carvalho FC, Mady C, Ramires JA, Mathias W: Effects of exercise training on myocardial blood flow reserve in patients with heart failure and left ventricular systolic dysfunction. Am J Cardiol. 2010, 105: 243-248. 10.1016/j.amjcard.2009.09.009. CrossRefPubMed
Caiati C, Montaldo C, Zedda N, Montisci R, Ruscazio M, Lai G, Cadeddu M, Meloni L, Iliceto S: Validation of a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) for the evaluation of coronary flow reserve: comparison with intracoronary Doppler flow wire. J Am Coll Cardiol. 1999, 34: 1193-1200. 10.1016/S0735-1097(99)00342-3. CrossRefPubMed
Eroglu S, Sade LE, Bozbas H, Haberal A, Ozbicer S, Demir O, Muderrisoglu H: Association of serum adiponectin levels and coronary flow reserve in women with normal coronary angiography. J Cardiovasc Risk. 2009, 16: 290-296.
Gardin JM, Leifer ES, Fleg JL, Whellan D, Kokkinos P, Leblanc MH, Wolfel E, Kitzman DW: Relationship of Doppler-Echocardiographic left ventricular diastolic function to exercise performance in systolic heart failure: the HF-ACTION study. Am Heart J. 2009, 158: S45-S52. 10.1016/j.ahj.2009.07.015. PubMedCentralCrossRefPubMed
Suskin N, McKelvie RS, Burns RJ, Latini R, Pericak D, Probstfield J, Rouleau JL, Sigouin C, Solymoss CB, Tsuyuki R, et al: Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure. Eur Heart J. 2000, 21: 1368-1375. 10.1053/euhj.1999.2043. CrossRefPubMed
Campuzano R, Moya JL, Garcia-Lledo A, Tomas JP, Ruiz S, Megias A, Balaguer J, Asin E: Endothelial dysfunction, intima-media thickness and coronary reserve in relation to risk factors and Framingham score in patients without clinical atherosclerosis. J Hypertens. 2006, 24: 1581-1588. 10.1097/01.hjh.0000239294.17636.27. CrossRefPubMed
Dini FL, Ghiadoni L, Conti U, Stea F, Buralli S, Taddei S, De Tommasi SM: Coronary flow reserve in idiopathic dilated cardiomyopathy: relation with left ventricular wall stress, natriuretic peptides, and endothelial dysfunction. J Am Soc Echocardiogr. 2009, 22: 354-360. 10.1016/j.echo.2009.01.013. CrossRefPubMed
Saito T, Maehara K, Tamagawa K, Oikawa Y, Niitsuma T, Saitoh S, Maruyama Y: Alterations of endothelium-dependent and -independent regulation of coronary blood flow during heart failure. Am J Physiol Heart Circ Physiol. 2002, 282: H80-H86. PubMed
Magnusson M, Jovinge S, Shahgaldi K, Israelsson B, Groop L, Melander O: Brain natriuretic peptide is related to diastolic dysfunction whereas urinary albumin excretion rate is related to left ventricular mass in asymptomatic type 2 diabetes patients. Cardiovasc Diabetol. 2010, 9: 2-10.1186/1475-2840-9-2. PubMedCentralCrossRefPubMed
Dinh W, Lankisch M, Nickl W, Scheyer D, Scheffold T, Kramer F, Krahn T, Klein RM, Barroso MC, Futh R: Insulin resistance and glycemic abnormalities are associated with deterioration of left ventricular diastolic function: a cross-sectional study. Cardiovasc Diabetol. 2010, 9: 63-10.1186/1475-2840-9-63. PubMedCentralCrossRefPubMed
Willemsen S, Hartog JWL, Hummel YM, van Ruijven MHI, van der Horst ICC, van Veldhuisen DJ, Voors AA: Tissue advanced glycation end products are associated with diastolic function and aerobic exercise capacity in diabetic heart failure patients. Eur J Heart Fail. 2011, 13: 76-82. 10.1093/eurjhf/hfq168. CrossRefPubMed
- Insulin resistance and exercise tolerance in heart failure patients: linkage to coronary flow reserve and peripheral vascular function
Rasmus Huan Olsen
Lene Rørholm Pedersen
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
e.Med Kampagnen-Visual, Mail Icon II