Elevated C-Reactive Protein Levels and Impaired Endothelial Vasoreactivity in Patients With Coronary Artery Disease

BACKGROUND: Elevated C-reactive protein (CRP) serum levels, an exquisitely sensitive objective marker of inflammation, relate to long-term prognosis in patients with coronary artery disease and in apparently healthy men. Because abnormalities of endothelial regulation of vascular function may contribute to the occurrence of coronary events, we tested the hypothesis that elevated CRP levels are associated with an abnormal systemic endothelial vascular reactivity. METHODS AND RESULTS: Endothelium-dependent (10 to 50 microg/min acetylcholine) and endothelium-independent (2 to 8 microg/min sodium nitroprusside) forearm blood flow responses were measured with venous occlusion plethysmography in 60 male patients with angiographically documented coronary artery disease. Forearm blood flow responses to acetylcholine were inversely correlated with CRP serum levels (r=-0.46, P:=0.001). With multivariate analysis that included the classic risk factors for coronary artery disease, elevated CRP serum level remained a statistically significant independent predictor of a blunted endothelial vasodilator capacity. Most important, normalization of elevated CRP levels over time was associated with a normalization of endothelium-mediated forearm blood flow responses after 3 months. CONCLUSIONS: Thus, elevated CRP serum levels indicative of a systemic inflammatory response are associated with a blunted systemic endothelial vasodilator function. The identification of elevated CRP levels as a transient independent risk factor for endothelial dysfunction might provide an important clue to link a systemic marker of inflammation to atherosclerotic disease progression.