CLINICAL STUDIES
Endothelial and metabolic characteristics of patients with angina and angiographically normal coronary arteries
Comparison with subjects with insulin resistance syndrome and normal controls
PierMarco Piatti, MD*,
Gabriele Fragasso, MD ,
Lucilla D. Monti, MD ,
Andrea Caumo ,
Chuong Van Phan ,
Giampietro Valsecchi, PhD ,
Sabrina Costa ,
Elena Fochesato, MD*,
Guido Pozza, MD ,
Antonio E. Pontiroli, MD* and
Sergio Chierchia, MD, FESC, FACC
* Unita di Malattie Metaboliche, Cattedra di Medicina Interna, Divisione di Medicina, Milano, Italy
Cattedra di Clinica Medica Generale e Terapia Medica, Università Vita-Salute, Milano, Italy
Divisione di Statistica e Epidemiologia, Milano, Italy
Divisione di Cardiologia, IRCCS H. San Raffaele, Milano, Italy
Manuscript received July 7, 1998;
revised manuscript received May 27, 1999,
accepted June 29, 1999.
Reprint requests and correspondence: Dr. PierMarco Piatti, IRCCS H. San Raffaele, Via Olgettina 60, 20132 Milano, Italy
OBJECTIVES
This study was performed to characterize the endothelial and metabolic alterations of patients with angina and angiographically normal coronary arteries ("cardiac" syndrome X [CSX]) compared with subjects with insulin resistance syndrome ("metabolic" syndrome X [MSX]) and normal controls.
BACKGROUND
Previous studies have found high endothelin-1 levels, impaired endothelium-dependent vasodilation and insulin resistance in patients with angina pectoris and angiographically normal coronary arteries. On the other hand, subjects with insulin resistance syndrome have shown high endothelin-1 levels.
METHODS
Thirty-five subjects were studied: 13 patients with angina pectoris and angiographically normal coronary arteries (CSX group); 9 subjects with insulin resistance syndrome (MSX group) and 13 normal controls. All subjects received an acute intravenous bolus of insulin (0.1 U/kg) combined with a euglycemic clamp and forearm indirect calorimetry. Endothelin-1 levels, nitrite/nitrate (NOx) levels, end products of nitric oxide metabolism, glucose infusion rates (index of insulin sensitivity) and their incremental areas ( AUCs [area under curves]) were measured during this period.
RESULTS
Basal endothelin-1 levels were higher in CSX and MSX groups than in normal controls (8.19 ± 0.46 and 6.97 ± 0.88 vs. 3.67 ± 0.99 pg/ml; p < 0.01), while basal NOx levels were significantly higher in MSX group than in CSX and normal controls (36.5 ± 4.0 vs. 24.2 ± 3.3 and 26.8 ± 3.2 mol/liter, p < 0.05). After insulin administration, the AUCs of NOx (p < 0.05) were lower in CSX group than in MSX and normal controls, and the AUCs of endothelin-1 were lower in group CSX than in normal controls. Glucose infusion rate was significantly lower in CSX and MSx groups than in normal controls (p < 0.01), suggesting that in both CSX and MSX groups insulin resistance is present. A positive correlation was found between the AUCs of nitric oxide and the AUCs of glucose infusion rate.
CONCLUSIONS
Blunted nitric oxide and endothelin responsiveness to intravenously infused insulin is a typical feature of patients with angina pectoris and angiographically normal coronary arteries and may contribute to the microvascular dysfunction observed in these subjects.
|
Abbreviations and Acronyms
| | AUC | = area under the curve | | BMI | = body mass index | | CSX | = "cardiac" syndrome X | | ECG | = electrocardiograph | | ET-1 | = endothelin-1 | | FSIGT | = frequently sampled intravenous glucose tolerance test | | FGOx | = forearm glucose oxidation | | FGSt | = forearm glucose storage | | FGU | = forearm glucose uptake | | GIR | = glucose infusion rate | | HDL | = high-density lipoprotein | | MSX | = "metabolic" syndrome X | | NOx | = nitrite/nitrate | | RIA | = radioimmunoassay |
|
This article has been cited by other articles:

|
 |

|
 |
 
R. Muniyappa, M. Montagnani, K. K. Koh, and M. J. Quon
Cardiovascular Actions of Insulin
Endocr. Rev.,
August 1, 2007;
28(5):
463 - 491.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Lteif, P. Vaishnava, A. D. Baron, and K. J. Mather
Endothelin Limits Insulin Action in Obese/Insulin-Resistant Humans
Diabetes,
March 1, 2007;
56(3):
728 - 734.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Jadhav, W. Ferrell, I. A. Greer, J. R. Petrie, S. M. Cobbe, and N. Sattar
Effects of Metformin on Microvascular Function and Exercise Tolerance in Women With Angina and Normal Coronary Arteries: A Randomized, Double-Blind, Placebo-Controlled Study
J. Am. Coll. Cardiol.,
September 5, 2006;
48(5):
956 - 963.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S Jadhav, J Petrie, W Ferrell, S Cobbe, and N Sattar
Insulin resistance as a contributor to myocardial ischaemia independent of obstructive coronary atheroma: a role for insulin sensitisation?
Heart,
December 1, 2004;
90(12):
1379 - 1383.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. D. Monti, C. Landoni, E. Setola, E. Galluccio, P. Lucotti, E. P. Sandoli, A. Origgi, G. Lucignani, P. Piatti, and F. Fazio
Myocardial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in Type 2 diabetic patients
Am J Physiol Heart Circ Physiol,
September 1, 2004;
287(3):
H1225 - H1231.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Piatti, C. Di Mario, L. D. Monti, G. Fragasso, F. Sgura, A. Caumo, E. Setola, P. Lucotti, E. Galluccio, C. Ronchi, et al.
Association of Insulin Resistance, Hyperleptinemia, and Impaired Nitric Oxide Release With In-Stent Restenosis in Patients Undergoing Coronary Stenting
Circulation,
October 28, 2003;
108(17):
2074 - 2081.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. J. Wilkes, A. Hevener, and J. Olefsky
Chronic Endothelin-1 Treatment Leads to Insulin Resistance In Vivo
Diabetes,
August 1, 2003;
52(8):
1904 - 1909.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M Kidawa, M Krzeminska-Pakula, J Z Peruga, and J D Kasprzak
Arterial dysfunction in syndrome X: results of arterial reactivity and pulse wave propagation tests
Heart,
April 1, 2003;
89(4):
422 - 426.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Piatti, G. Fragasso, L. D. Monti, E. Setola, P. Lucotti, I. Fermo, R. Paroni, E. Galluccio, G. Pozza, S. Chierchia, et al.
Acute Intravenous l-Arginine Infusion Decreases Endothelin-1 Levels and Improves Endothelial Function in Patients With Angina Pectoris and Normal Coronary Arteriograms: Correlation With Asymmetric Dimethylarginine Levels
Circulation,
January 28, 2003;
107(3):
429 - 436.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Fernandez-Real, G. Penarroja, C. Richart, A. Castro, J. Vendrell, M. Broch, A. Lopez-Bermejo, and W. Ricart
G Protein {beta}3 Gene Variant, Vascular Function, and Insulin Sensitivity in Type 2 Diabetes
Hypertension,
January 1, 2003;
41(1):
124 - 129.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Gulli, R. Cemin, P. Pancera, G. Menegatti, C. Vassanelli, and A. Cevese
Evidence of parasympathetic impairment in some patients with cardiac syndrome X
Cardiovasc Res,
November 1, 2001;
52(2):
208 - 216.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Rodriguez-Porcel, A. Lerman, P. J. M. Best, J. D. Krier, C. Napoli, and L. O. Lerman
Hypercholesterolemia impairs myocardial perfusion and permeability: role of oxidative stress and endogenous scavenging activity
J. Am. Coll. Cardiol.,
February 1, 2001;
37(2):
608 - 615.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Desideri, A. Gaspardone, M. Gentile, A. Santucci, P. A. Gioffre, and C. Ferri
Endothelial Activation in Patients With Cardiac Syndrome X
Circulation,
November 7, 2000;
102(19):
2359 - 2364.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. M. PIATTI, L. D. MONTI, I. ZAVARONI, G. VALSECCHI, C. VAN PHAN, S. COSTA, M. CONTI, E. P. SANDOLI, B. SOLERTE, G. POZZA, et al.
Alterations in Nitric Oxide/Cyclic-GMP Pathway in Nondiabetic Siblings of Patients with Type 2 Diabetes
J. Clin. Endocrinol. Metab.,
July 1, 2000;
85(7):
2416 - 2420.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
J.-M. Fernandez-Real, B. Lainez, J. Vendrell, M. Rigla, A. Castro, G. Penarroja, M. Broch, A. Perez, C. Richart, P. Engel, et al.
Shedding of TNF-alpha receptors, blood pressure, and insulin sensitivity in type 2 diabetes mellitus
Am J Physiol Endocrinol Metab,
April 1, 2002;
282(4):
E952 - E959.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|