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Objectives To evaluate the distribution by age and sex of serum high-sensitivity C-reactive protein (hsCRP) in an urban Chinese population and to provide a profile prediction for the risk of bacterial infection, inflammatory diseases, or tissue damages in the body. Methods Serum hsCRP was determined using the Roche Tina-quant immuno-turbidimetric assay on a Hitachi 7600–010 automatic biochemical analyzer (Roche Diagnostics) in 1,572 males and 1,800 females, including 78 pregnant women, who were derived from the National Health and Nutrition Survey in 2010–2012. Results The average hsCRP concentration in urban China was 0.68 mg/L for males and 0.65 mg/L for females. Significant differences in hsCRP were found among different age groups (P < 0.05). Monitoring results showed no significant differences among the 6–11, 45–59, and ≥ 60-year-old groups in the comparison of hsCRP between males and females in large cities. However, hsCRP concentration was significantly higher in men aged 12–17 and 18–44 years than in women. Conclusion The distribution of the hsCRP status of residents in large cities in China was influenced by age and gender, and the hsCRP levels of both sexes increased gradually with age. In addition, hsCRP concentration was higher in healthy pregnant women than in non-pregnant women. Basing on our results, we recommend that this parameter be included in future national and intational screening for early detection of various illnesses.