Positive association between circulating free insulin-like growth factor-1 levels and coronary flow reserve in arterial systemic hypertension

Background: The reduction of coronary flow reserve (CFR) found in arterial hypertension may be due to changes in afterload, left ventricular (LV) structure, and metabolic factors. Also, insulin-like growth factor-1 (IGF-1) may be associated with the magnitude of CFR in relation to its modulating action on cardiac and endothelial function. Methods: A total of 44 newly diagnosed, untreated hypertensive patients, who were free of diabetes mellitus and coronary artery disease, underwent M-mode analysis, second-harmonic Doppler echocardiographic assessment of CFR (dipyridamole infusion 0.56 mg/kg intravenously in four patients), determination of circulating free IGF-1, and insulin resistance. Based on CFR levels, hypertensive subjects were divided into two groups: 18 with normal CFR (≥2) and 26 with impaired CFR (<2). Results: Patients with normal CFR had lower diastolic blood pressure, heart rate, and LV mass index but higher free circulating IGF-1 than patients with reduced CFR (P < .001). Insulin resistance was not significantly different between the two groups. In a first multilinear regression analysis that included demographic and echocardiographic variables, insulin resistance was independently associated with CFR (standardized β coefficient = -0.31, P < .05) in the overall population. However, in a subsequent model which included also IGF-1, the relationship between insulin resistance and CFR disappeared, whereas IGF-1 was the main independent determinant of CFR (β = 0.51, P < .0002). Conclusions: Free IGF-1 circulating levels are independently associated with CFR in hypertensive individuals free of overt coronary artery disease. A possible beneficial effect exerted by IGF-1 on coronary blood flow may be supposed in arterial hypertension.