title: Endothelial and metabolic characteristics of patients with angina and angiographically normal coronary arteries: comparison with subjects with insulin resistance syndrome and normal controls.
abstract: OBJECTIVE
  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 (deltaAUCs [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 deltaAUCs of NOx (p < 0.05) were lower in CSX group than in MSX and normal controls, and the deltaAUCs 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 deltaAUCs 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.
authors.affiliation: Unita' di Malattie Metaboliche, Cattedra di Medicina Interna, Divisione di Medicina, Milano, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Piatti
authors.forename: G
authors.initials: G
authors.lastname: Fragasso
authors.forename: L D
authors.initials: LD
authors.lastname: Monti
authors.forename: A
authors.initials: A
authors.lastname: Caumo
authors.forename: C
authors.initials: C
authors.lastname: Van Phan
authors.forename: G
authors.initials: G
authors.lastname: Valsecchi
authors.forename: S
authors.initials: S
authors.lastname: Costa
authors.forename: E
authors.initials: E
authors.lastname: Fochesato
authors.forename: G
authors.initials: G
authors.lastname: Pozza
authors.forename: A E
authors.initials: AE
authors.lastname: Pontiroli
authors.forename: S
authors.initials: S
authors.lastname: Chierchia
mesh_terms: D002153:Calorimetry, Indirect; D016022:Case-Control Studies; D019332:Endothelin-1 / Q000097:blood* / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D017566:Microvascular Angina / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood
chemical_list: D019332:Endothelin-1; D009569:Nitric Oxide; D005947:Glucose