Objective: To elucidate the underlying mechanisms between C-reactive protein (CRP) and cardiovascular disease, we examined the association of circulating CRP in healthy reference range (< or =1.0 mg/dl) measured by high-sensitive CRP assay with the metabolic syndrome (MS).

Design: Cross-sectional study of circulating CRP in adult men.

Subjects: A total of 3692 Japanese men aged 34-69 y.

Measurements: Serum CRP, total cholesterol, triglycerides, LDL-cholesterol, fasting glucose, fasting insulin, uric acid, systolic blood pressure, diastolic blood pressure, and body mass index (BMI).

Results: There was a statistically significant positive correlation between CRP and BMI (r=0.25), total cholesterol (r=0.096), triglycerides (r=0.22), LDL-cholesterol (r=0.12), fasting glucose (r=0.088), fasting insulin (r=0.17), uric acid (r=0.13), systolic blood pressure (r=0.12), and diastolic blood pressure (r=0.11), and a significant negative correlation of CRP with HDL-cholesterol (r=0.24). After adjusting for age, smoking, and all other components of MS, obesity, hypertriglyceridemia, hyper-LDL-cholesterolemia, diabetes, hyperinsulinemia, and hyperuricemia were significantly associated with both mildly (> or =0.06 mg/dl) and moderately (> or =0.11 mg/dl) elevated CRP. Compared with men who had no such components of the MS, those who had one, two, three, four, and five or more components were, respectively, 1.48, 1.84, 1.92, 3.42, and 4.17 times more likely to have mildly elevated CRP levels (trend P<0.001). As for moderately elevated CRP, the same association was observed.

Conclusions: These results indicate that a variety of components of the MS are associated with elevated CRP levels in a systemic low-grade inflammatory state.