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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

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