High-sensitivity C-reactive protein (hs-CRP) is a hepatocyte-derived inflammatory cytokine shown to be increased in the setting of acute heart failure (HF), particularly with increased intracardiac filling pressures. In the chronic HF setting, the relation between hs-CRP and echocardiographic indexes of left ventricular (LV) diastolic performance has not been examined. We measured plasma hs-CRP levels using a particle-enhanced immunonephelometry assay (Dade Behring, Inc., Deerfield, Illinois) in 136 subjects with chronic HF (LV ejection fraction [EF]<or=35%, New York Heart Association functional classes II to IV). We performed echocardiography, including color M-mode and tissue Doppler methods. We prospectively examined subjects' death, cardiac transplantation, and HF hospitalization status over 33+/-17 months. In our study cohort (mean LVEF 26+/-6%, median plasma hs-CRP 3.19 mg/L), plasma hs-CRP levels progressively increased with worsening LV diastolic dysfunction. In particular, plasma hs-CRP levels correlated with mitral E/A wave ratio (Spearman r=0.25, p=0.004), mitral deceleration time (r=-0.28, p=0.002), pulmonary vein systolic wave/diastolic wave ratio (r=-0.32, p<0.001), mitral E wave/color M-mode velocity of propagation ratio (r=0.28, p=0.001), and mitral E wave/tissue Doppler septal E' wave ratio (r=0.28, p=0.001). Plasma hs-CRP levels independently predicted adverse clinical events even after adjustment for LVEF and mitral E wave/tissue Doppler septal E' wave ratio (hazard ratio 2.28, 95% confidence interval 1.18 to 4.39). In conclusion, in patients with chronic systolic HF, expression of circulating CRP was associated with increasing echocardiographic indexes of diastolic dysfunction. High plasma hs-CRP levels portend poor long-term outcomes, particularly in those with severe concomitant systolic and diastolic dysfunctions.