Backgrounds The measurement of coronary flow reserve (CFR) using cold pressor test (CPT) and transthoracic Doppler echocardiography (TTE) has been used as a method to estimate coronary endothelial function. Also, plasma free insulin-like growth factor-1 (IGF-1), soluble CD40 ligand (sCD40L), adiponectin and leptin have known to be associated with atherosclerosis and cardiovascular disease risk factors. The aim of this study was to investigate whether these biomarkers are associated with coronary vasoreactivity to manifest coronary endothelial function in the subjects with normal coronary angiogram and chest pain. Methods In one hundred ninety subjects (mean age 54짹11 years, M:F = 113:77) with normal coronary angiogram, the peak diastolic flow velocity (PDV) of distal left anterior descending artery (dLAD) was assessed by TTE at rest and during CPT. Plasma free IGF-1, sCD40L, adiponectin and leptin levels as well as major cardiovascular risk factors were measured. CPT%PDV was defined as the percentage changes in PDV during CPT. Results Plasma free IGF-1 level was correlated with CPT%PDV (r = 0.253, p = 0.007 and r = 0.227, p = 0.047, in men and women, respectively). In a multiple linear regression analysis, CTP%PDV was independently associated with free IGF-1 level in both sexes (棺 = 0.323, p = 0.002 and 棺 = 0.265, p = 0.020, in men and women, respectively), sCD40L and fasting glucose level in men (棺 = -0.260, p = 0.010 and 棺 = -0.188, p = 0.047). Conclusion Free IGF-1 and sCD40L levels were independently associated with coronary vasoreactivity assessed during CPT in subjects with normal coronary angiogram and chest pain.