C-reactive protein trends and associations with total mortality in United States adults between 1999-2010

Abstract

INTRODUCTION: C-reactive protein (CRP) is a well-known biomarker of systemic inflammation. Elevation of CRP levels is predictive of incident cardiovascular disease morbidity and mortality. We investigated the trends in prevalence of elevated CRP levels (>3.0 mg/L), as well as mean CRP levels, in a general population of United States adults and then determine the associations with mortality. METHODS: Data from the 27,214 subjects aged ≥20 years in the National Health and Nutrition Examination Survey (NHANES) 1999-2010 were analyzed. Among them, 12,259 subjects from NHANES 1999-2004 had mortality data followed up through December 31, 2006. RESULTS: After adjusting for age, sex, race/ethnicity, body mass index, and medications for lowering blood pressure, glucose and lipids, the prevalence of elevated CRP decreased significantly from 36.7% in 1999-2002 to 32.0% in 2007-2010, corresponding to a decrease in mean CRP levels from 1.92 to 1.66 mg/L (both P<0.001). The trend remained significant after additional adjustment for several traditional cardiovascular risk factors and use of medications, including statins, angiotensin-converting enzyme inhibitors, metformin, aspirin and clopidogrel. However, the decreasing trends were attenuated after additional adjustment for total bilirubin (P=0.076 and 0.024), which increased from 0.62 to 0.73 mg/dL over 12 years (P<0.001). Of note, higher CRP levels were modestly associated with a higher risk of total mortality (adjusted hazard ratio: 1.07 [95%CI, 1.03-1.12] per 10 mg/L increase, P=0.001), and this association tended to be stronger in subjects with higher total bilirubin levels (P for interaction <0.001). CONCLUSION: The decreasing trend of CRP levels is encouraging and may be related to the increase in total bilirubin levels. Such trends may be explained in part by the increasing use of some medications such as statins that can increase bilirubin levels and decrease CRP levels. Moreover, the prediction of total mortality by CRP levels seems to be stronger in subjects with higher total bilirubin levels.