High-sensitivity C-reactive protein (hs-CRP) has previously been shown to be an independent predictor for the development of cardiovascular disease. However, little is known about the association between hs-CRP and the severity of cardiovascular events that occur. This study compared characteristics of incident myocardial infarctions (MIs) in 40 initially healthy women with very high baseline hs-CRP levels (>7.5 mg/L) with infarctions in 40 women with very low hs-CRP levels (< or =1 mg/L). At baseline, very high hs-CRP was associated with a clinical diagnosis of hypertension, higher body mass index, lower high-density lipoprotein, and higher triglycerides. Our analysis found that the 2 study groups had similar proportions of ST-segment elevations on electrocardiograms, peak cardiac enzyme levels, postinfarct left ventricular function, and burden of coronary atherosclerosis seen on angiography. However, subjects with very high hs-CRP levels developed infarctions significantly sooner than those with very low hs-CRP levels (median time to event 4.45 vs 6.64 years, respectively, p <0.0001). In addition, higher baseline levels of hs-CRP were associated with significantly more fatal MIs (0% vs 4.6% vs 9.6% in subjects with hs-CRP levels <1, 1 to <3, and > or =3 mg/L, respectively, p for trend = 0.02). In conclusion, this study demonstrates that in initially healthy women high levels of hs-CRP predict earlier occurrence of MIs and a greater likelihood that infarctions will be fatal.