Population Distribution of High-Sensitivity C-reactive Protein among US Men: Findings from National Health and Nutrition Examination Survey 1999–2000

C-reactive protein, an acute-phase reactant, is produced in the liver and belongs to the pentraxin family of proteins (1). This protein is very sensitive to inflammation, and its concentration can increase rapidly in response to a wide range of stimuli. Originally described in 1930 (2), C-reactive protein measurements served mostly in a diagnostic, albeit a nonspecific one, and in a monitoring role in such fields as infectious diseases and rheumatology. In the past decade, as the role of inflammation in cardiovascular disease became appreciated, interest turned to C-reactive protein as a possible risk marker for cardiovascular disease. Since then, studies have shown that the C-reactive protein concentration is positively associated with cardiovascular disease incidence and mortality (3) even when the concentration is <3.0 mg/L, which was previously thought to be “normal” (4). As these research findings have reached the medical community, the use of C-reactive protein measurements has increased, but guidelines addressing the role of C-reactive protein testing in the primary and secondary prevention of cardiovascular disease have not been developed. To facilitate the development of such guidelines, several issues must be addressed, including population distributions of C-reactive protein concentrations and thresholds for interventions. A key piece of missing information has been the population distribution of C-reactive protein in the US, especially the distribution of C-reactive protein concentrations <3.0 mg/L. This information is helpful in calculating the fraction of cardiovascular disease attributable to increased C-reactive protein concentrations. The National Health and Nutrition Examination Survey (NHANES) III provided information only on the upper ranges of the C-reactive protein distribution (5)(6) because the C-reactive protein test used in that survey had a lower detection limit of 3.0 mg/L. Another missing piece of information is whether Creactive protein concentration distributions differ among major population groups. Previous research on the association …