BACKGROUND: The goal of this study was to examine a possible association between systemic microinflammation, as reflected by C-reactive protein (CRP) serum levels, and coronary vasomotion in patients with coronary risk factors but with angiographically normal coronary arteries. METHODS AND RESULTS: Coronary vasomotor function was studied in response to cold pressor testing (CPT) in 71 patients with normal angiograms. In all patients, CPT-induced changes in epicardial luminal area (LA; mm2) were assessed with quantitative angiography. Within 20 days, myocardial blood flow (MBF) responses to CPT were measured (mL x g(-1) x min(-1)) noninvasively with 13N-ammonia and PET imaging. The CPT-induced mean changes in LA and in MBF in patients with elevated CRP (> or =0.5 mg/dL) were significantly impaired compared with patients presenting with CRP levels within normal range (<0.5 mg/dL) (DeltaLA, -1.09+/-0.86 versus 0.45+/-0.63 mm2; DeltaMBF, 0.06+/-0.18 versus 0.44+/-0.31 mL x g(-1) x min(-1); P<0.0001, respectively). Coronary LA changes and MBF responses to CPT were inversely correlated with CRP serum levels (r=-0.84 and r=-0.63; P<0.0001). Lastly, regression analysis revealed a significant correlation between the changes in LA and MBF during CPT for patients with elevated CRP levels and those for patients with normal CRP levels (r=0.56 and r=0.66; P<0.001). CONCLUSIONS: These findings suggest a direct association between systemic microinflammation and altered coronary vasomotor function of both the epicardial conductance and the arteriolar resistance vessels.