C-reactive protein is produced by the liver in response to inflammatory signalling, primarily interleukin-6. It is the most commonly used clinical marker of systemic inflammation and acute phase response. The high-sensitivity CRP assay, hsCRP, can detect the low levels of chronic inflammation that characterise metabolic dysfunction and early cardiovascular disease, below the threshold detectable by the standard CRP assay used for acute illness. This distinction matters clinically: hsCRP is the appropriate test for longevity and cardiovascular risk assessment.
The JUPITER Trial
The JUPITER trial enrolled nearly 18,000 adults with low LDL cholesterol but elevated hsCRP, demonstrating that this population had substantially elevated cardiovascular event rates despite apparently normal cholesterol. The trial showed that statin therapy in this high-CRP population significantly reduced cardiovascular events, but more importantly established that elevated hsCRP is an independent cardiovascular risk factor that identifies risk not captured by lipid panels alone. CRP is now included in several major cardiovascular risk calculators.
What an Optimal hsCRP Looks Like
The standard reference range for hsCRP considers below 10 mg/L normal for the detection of acute illness. For cardiovascular risk assessment, the clinically useful categories are: below 1 mg/L low risk; 1 to 3 mg/L moderate risk; above 3 mg/L high risk. The optimal level for longevity purposes appears to be below 0.7 mg/L. Most adults consuming a standard Western diet in their forties and fifties have hsCRP levels between 1 and 3 mg/L, which is widely considered normal but represents meaningful inflammatory burden.
Sources
- Ridker, P.M., et al. (2008). Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. New England Journal of Medicine, 359(21), 2195-2207.
- Ridker, P.M. (2003). Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation, 107(3), 363-369.
- Danesh, J., et al. (2004). C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. New England Journal of Medicine, 350(14), 1387-1397.