Searching for a needle in a haystack may seem futile, but it's worth it if the needle is a hard-to-detect protein that may identify a person at high risk of a heart attack circulating within a haystack of human serum (liquid component of blood).
C-reactive protein (CRP), a molecule produced by the liver in response to inflammation, normally accounts for less than 1/60,000 of a person's total serum protein, or about 1 milligram per liter (mg/L) of serum. Recent evidence suggests that a CRP level between 1 and 3 mg/L indicates a moderate risk of cardiovascular disease while a level greater than 3 mg/L predicts a high risk. A clinical diagnostic procedure known as the high-sensitivity CRP (hsCRP) test has been used to detect higher-than-normal levels of the protein and warn a patient about elevated risk for cardiovascular disease. However, there is no certified reference material-in this case, a sample of human serum with accurately determined amounts of the CRP for various risk levels-against which the accuracy of methods for measuring CRP can be evaluated. The problem: normal, low-risk of cardiovascular disease CRP levels are so low that even mass spectrometry (a very sensitive technique for separating and identifying molecules based on mass) cannot easily quantify them.