Background: The aim of the present study was to investigate whether change of coronary flow velocity of the distal left anterior descending artery (LAD) assessed during cold pressor test (CPT) with transthoracic Doppler echocardiography (TTE) was associated with endothelial or atherosclerotic biomarkers, including plasma free insulin-like growth factor-I (IGF-I), soluble CD40 ligand (sCD40L), adiponectin and leptin in subjects with chest pain and a normal coronary angiogram. Methods: In 190 subjects (mean age 54짹11 years, male:female=113:77) with chest pain and a normal coronary angiogram, peak diastolic velocity (PDV) of the distal LAD during CPT with TTE was assessed. Acetylcholine provocation test was performed in 58 subjects (mean age 51짹10 years) who were clinically suspected of vasospasm. CPT%PDV was defined as percent change in PDV during CPT. Associations between CPT%PDV and clinical parameters were analyzed. Results: According to multiple regression analysis, CPT%PDV was associated with plasma free IGF-I in the entire study population (棺=0.295, P<0.001 in all subjects; 棺=0.341, P=0.001 in males; 棺=0.243, P=0.037 in females; 棺=0.303, P=0.002 in non-smokers; and 棺=0.256, P=0.047 in smokers) and sCD40L in males (棺=-0.269, P=0.008) and smokers (棺=-0.261, P=0.046) (Table). Subjects with vasospasm to intracoronary acetylcholine had lower plasma free IGF-I (6.9짹3.3 vs 8.9짹3.4, P=0.026) and CPT%PDV (8.8짹24.9 vs 52.7짹26.0, P<0.001) than the others. Plasma adiponectin and leptin were not associated with CPT%PDV. Conclusion: Change of coronary flow velocity assessed using CPT with TTE may be related to endothelial markers, especially plasma free IGF-I.