Endothelial and metabolic characteristics of patients with angina and angiographically normal coronary arteries - Comparison with subjects with insulin resistance syndrome and normal controls

OBJECTIVES: This study was performed to characterize the endothelial and me tabolic alterations of patients With angina and angiographically normal cor onary arteries ("cardiac" syndrome X [CSX]) compared with subjects with ins ulin 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 othe r hand, subjects with insulin resistance syndrome have shown high endotheli n-1 levels. METHODS: Thirty-five subjects were studied: 13 patients with angina pectori s and angiographically normal coronary arteries (CSX group); 9 subjects wit h insulin resistance syndrome (MSX group) and 13 normal controls. All subje cts 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, gluc ose infusion rates (index of insulin sensitivity) and their incremental are as (Delta AUCs [area under curves]) were measured during this period. RESULTS: Basal endothelin-1 levels were higher in CSX and MSX groups than i n 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 t han 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 Delta AUCs of N Ox (p < 0.05) were lower in CSX group than in MSX and normal controls, and the Delta AUCs of endothelin-1 were lower in group CSX than in normal contr ols. Glucose infusion rate was significantly lower in CSX and MSX groups th an in normal controls (p < 0.01), suggesting that in both CSX and MSX group s insulin resistance is present. A positive correlation was found between t he Delta AUCs of nitric oxide and the AUCs of glucose infusion rate. CONCLUSIONS: Blunted nitric oxide and endothelin responsiveness to intraven ously infused insulin is a typical feature of patients with angina pectoris and angiographically normal coronary arteries and may contribute to the mi crovascular dysfunction observed in these subjects. (C) 1999 by the America n College of Cardiology.