We examined the association between C-reactive protein (CRP) and left ventricular mass index (LVMI), and investigated prospectively the incidence of cardiovascular disease (CVD) in asymptomatic subjects with essential hypertension. A total of 629 subjects (mean age 62 years, 51% female) free of prior CVD were included in this study. In cross-sectional analysis at baseline, patients were divided into three groups according to serum CRP levels: <1, 1 to 2, and >2 mg/L. In multivariate analysis, LVMI increased in a stepwise fashion with increasing CRP levels in both men (127.2+/-2.9, 138.7+/-4.1, 141.8+/-3.5 g/m(2), respectively; F=6.85, p=0.001) and women (119.5+/-3.6, 129.2+/-4.9, 130.2+/-4.8 g/m(2); F=4.23, p=0.031). During follow-up (mean 32 months), 52 subjects (19 female) developed CVD. Kaplan-Meier analysis with log-rank tests showed a significantly poorer event-free survival rate in the group with elevated CRP levels (> or =1 mg/L) (chi(2)=8.22, p<0.01) and that with left ventricular hypertrophy (LVH) (chi(2)=19.91, p<0.01). When participants were divided into four groups on the basis of CRP level (<1 or > or =1 mg/L) and the absence or presence of LVH, the group with LVH/CRP> or =1 mg/L showed markedly poorer event-free survival (chi(2)=28.02, p<0.01), and the adjusted hazard ratio by multivariate Cox regression analysis was 2.65 (95% confidence interval [CI]=1.55-5.46, p<0.01). In the subgroup with LVH (n=362), a significantly lower event-free survival rate of CVD was also observed in the group with CRP> or =1 mg/L (hazard ratio [HR] 1.37, 95% CI: 1.02-1.85, p=0.025). Our findings demonstrate that the CRP level is independently associated with LVMI, and suggest that measurement of CRP may provide clinically important prognostic information to supplement LVH.