CRP, C-reactive protein, is a sensitive marker of general inflammation. CRP has been suggested to correlate with higher heart disease risk. Eminent expert in immunology and CRP, Professor Mark Pepys, reviews evidence for correct use of CRP. What is correct interpretation of CRP levels in heart disease and other medical conditions? What is the significance of measuring CRP to assess heart disease risks? Dr. Anton Titov, MD. CRP (C-reactive Protein) is the classical acute phase protein. It is the first protein in the plasma. It was discovered back in 1929. Professor Dr. Mark Pepys, MD. A few years after that CRP was shown to behave as an acute phase protein. This is what it meanss. You may have any tissue damage, infection, almost any sort of pathology. This damages the body. Then more CRP C-reactive Protein is produced. As a result, the CRP concentration in the plasma increases. Subsequently many other proteins have been found to behave similarly. But CRP is almost uniquely dynamic. CRP C-reactive Protein increases from very low concentration. It can go up by ten thousand fold in concentration in response to an acute injury or an acute infection. There is only one other protein that behaves with similar dynamism. Dr. Anton Titov, MD. That protein is called "serum amyloid A" protein. It is a completely unrelated protein. But it is of interest to us, because it can make amyloid. Professor Dr. Mark Pepys, MD. This we've been talking about before. But let’s leave that aside. CRP is uniquely useful in clinical medicine as a marker of this acute phase response. There are several things that have to be understood about CRP. Professor Dr. Mark Pepys, MD. The first is this. C-reactive Protein is completely non-specific. The CRP can never be diagnostic of any particular disease. You can only interpret the CRP concentration in the context of knowing everything about the patient. You have to know the patient's history. You have to know all their demography. You have to know what diseases they've got, what treatments they use. Only then can you you interpret the CRP value. C-reactive Protein is useful. Dr. Anton Titov, MD. But if you have all that information, the CRP is immensely useful. It tells you whether patients have got some genuine tissue-damaging pathology or not. CRP is a screening test for organic disease. C-reactive Protein tells you whether a patient has got a particular disease. C-reactive Protein tells you whether the disease is getting better or worse. CRP informs you whether your treatment is working or not working. Professor Dr. Mark Pepys, MD. There are a few serious diseases, where the CRP doesn't increase. It is very surprising. It is unlike nearly everything else, where the CRP does increase. But in those people, if they get an infection, bacterial or viral infection, then the C-reactive Protein increases. C-reactive Protein is a good test for an intercurrent infection. This is true even in that rare group of diseases, where the CRP doesn't go up with the disease on its own. We come back to these three indications for measuring CRP. Patient comes to the doctor. "I have got terrible pain in my chest and I feel breathless". Dr. Anton Titov, MD. You measure the CRP. It is normal. You have excluded heart attack, pulmonary embolism, pneumothorax, broken ribs. A lot of these things you can diagnose just by examining the patient. C-reactive Protein narrows diagnostic options down. Most of those things you can diagnose clinically. Professor Dr. Mark Pepys, MD. A physician knows if a patient has a broken rib or not. On one hand, you can exclude certain diseases. A physical can have a different treatment method to investigating that patient. On the other hand if CRP is raised, it doesn't tell you what the diagnosis is. But C-reactive Protein tells you that "there is something serious going on with this patient”. Then we have to investigate. The investigations, depending on the clinical context, might be just "well, we will observe you for a week and come back next week and we will measure the CRP again". Or it might mean admitting a patient into hospital. Professor Dr. Mark Pepys, MD. Then a physician could do a blood culture, and this, that and the other". Sometimes the concentration of CRP is more than a 100 milligrams per liter in a patient. Professor Dr. Mark Pepys, MD. You know nothing else about the patient. Then statistically the chances are about 80% that patient has got a serious bacterial infection. It already guides you in the correct direction. Dr. Anton Titov, MD. C-reactive Protein is a very useful screening test. Secondly, sometimes you know what the diagnosis is. The patient's got Crohn's disease, they've got rheumatoid arthritis, they've had a heart attack, they are in the hospital. We measure the patient's body temperature a couple of times a day. There is a chart at the bottom of every bed with the body temperature. The body temperature's got a very tiny dynamic range. Professor Dr. Mark Pepys, MD. Body temperature varies depending on how many blankets the patient's got. Body temperature fluctuates whether a patient had a hot cup of tea or a cold drink. The time of the day affects body temperature. It depends upon what their meal was, and so on. Body temperature is very variable in a very tiny dynamic range! CRP is very useful clinically. Dr. Anton Titov, MD. All doctors understand it. C-reactive Protein is much more useful. It would be useful to have a CRP chart at the end of the bed. We need point-of-care CRP testing on a prick of blood. Professor Dr. Mark Pepys, MD. This is just like you do with diabetes testing for blood sugar. You should have a CRP test. Everybody who is sick enough to be in hospital deserves to have a CRP test done every day. C-reactive Protein must be done at least every time they have blood taken. It is incredibly useful in that context. CRP values have a huge range. Yes! C-reactive Protein has a huge range. It is very precisely measured. C-reactive Protein is a wonderfully useful test. Then there is this other group of diseases. Systemic lupus erythematosus, ulcerative colitis, and acute leukemia. Those are the three major diseases. Multiple myeloma is another disease. Dr. Anton Titov, MD. These are quite important diseases. Professor Dr. Mark Pepys, MD. A patient can be dying of those diseases and the CRP remains normal. Nobody quite understands why. Fortunately, those disease are very easy to diagnose without the CRP. You don't need the CRP. You just need to examine the patient and do some other diagnostic tests. You can know that they've got that particular disease. But those diseases all predispose patients to infection. There is a risk of bacterial, viral, other intercurrent infections. Infections can be life-threatening, and CRP in those situation does go up. You may have a patient with lupus [SLE]. CRP is more than 60 milligrams per liter. Until shown otherwise, this patient has got an infection, certainly got an infection. You have to look for and treat their infection, If you don't treat an infection, they could die of that infection. C-reactive Protein is very useful. Professor Dr. Mark Pepys, MD. Extremely useful. In leukemia, in myeloma, we have established this decades ago. You know, the CRP test is very widely used. I made the World Health Organization International Reference Standard for CRP in the 1980s. So every CRP that is measured everywhere in the world, that is the reference standard. C-reactive Protein is eventually calibrated on this standard. I made that reference standard. That made things very useful because it standardized the tests. All the manufacturers calibrate C-reactive Protein against that. There are secondary standards. Professor Dr. Mark Pepys, MD. I have also provided the CRP standards for the International Federation of Clinical Chemistry. The EU has a standard. C-reactive Protein is a good test, it is a very robust clinical chemistry test. Dr. Anton Titov, MD. C-reactive Protein deserves to be as widely used as it is. It is extremely widely used. That is the good news.