C-Reactive Protein and Cardiovascular Risk in the Metabolic Syndrome and Type 2 Diabetes: Controversy and Challenge

C-reactive protein (CRP) has become the subject of avid interest in recent years, but the history of CRP began > 7 decades ago and has been one of discovery and continuing dispute. In 1930, Tillet and Francis1 observed a substance in the serum of people with pneumococcal infections that formed a precipitate when mixed with the C-polysaccharide coat of Streptococcus pneumoniae. This “Creactive” activity was absent from the sera of healthy individuals. MacLeod and Avery2 subsequently found this substance to be a protein and coined the term “acute phase” to characterize the serum of patients with various acute infections. Lofstrom3 found a similar acute-phase response in acute and chronic inflammatory conditions, and CRP became recognized as a nonspecific acute-phase protein. Highly conserved in evolution, CRP has similar structural and functional homology in many species, even including the hemolymph of the horseshoe crab.4 The story of CRP has evolved rapidly in the past decade. The development of high-sensitivity CRP (hs-CRP), a stable and inexpensive assay, has increased the potential to obtain more reliable determinations of circulating levels of this inflammatory cytokine, and thereby to refine cardiovascular risk assessment, particularly for those whose risk is intermediate, such as individuals with average levels of LDL cholesterol.