Change of Coronary Flow Velocity During the Cold Pressor Test Is Related to Endothelial Markers in Subjects With Chest Pain and a Normal Coronary Angiogram

BACKGROUND: Several studies demonstrated that endothelial or atherosclerotic biomarkers, including plasma free insulin-like growth factor-I(IGF-I), soluble CD40 ligand (sCD40L), adiponectin, and leptin have an influence on coronary endothelial function. HYPOTHESIS: The aim of the present study was to investigate whether change of coronary flow velocity of the distal left anterior descending artery (LAD) during the cold pressor test (CPT) with transthoracic Doppler echocardiography (TTE) was associated with these biomarkers in subjects with chest pain and a normal coronary angiogram. METHODS: In 190 subjects (mean age, 54±11 years; male:female, 113:77) with chest pain and a normal coronary angiogram, peak diastolic velocity (PDV) of the distal LAD during the CPT with TTE was assessed. Acetylcholine provocation test was performed in 58 subjects (mean age, 51±10 years) who were clinically suspected of vasospasm. CPT%PDV was defined as the percent change in PDV during the 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 (β=0.295, P<0.001 in all subjects; β=0.341, P=0.001 in males; β=0.243, P=0.037 in females; β=0.303, P=0.002 in nonsmokers; and β=0.256, P=0.047 in smokers), and sCD40L in males (β=-0.269, P=0.008)and smokers (β=-0.261, P=0.046). Subjects with vasospasm to intracoronary acetylcholine had lower plasma free IGF-I(6.9±3.3 vs 8.9±3.4, P=0.026) and CPT%PDV (8.8±24.9 vs 52.7±26.0, P<0.001) than the others. Plasma adiponectin and leptin were not associated with CPT%PDV. CONCLUSIONS: Change of coronary flow velocity assessed using the CPT with TTE may be related to endothelial markers, especially plasma free IGF-I.