C-reactive protein

Its concentration in the blood is useful for assessing the extent of an inflammatory state, but it is a non-specific diagnostic indicator.

C-reactive protein (CRP) is produced by the liver and is an acute-phase protein that is released as a result of inflammation.

What is it

Discovered in 1930 in the plasma of patients suffering from bacterial pneumonia and initially considered a pathogenic compound precisely because of its association with Streptococcus pneumoniae infection, the C-reactive protein then proved to be a defense tool of the organism, which plays a fundamental role in the immune reaction against microorganisms in general and beyond.

In particular, the C-reactive protein, produced by the liver, is part of that group of molecules called “acute phase proteins“, which are synthesized in the body and enter the bloodstream in the first instance during inflammatory processes of various origins. This protein therefore has a healing function, since it works in synergy with the immune system to eliminate the causes of the infection, but it is also useful for the diagnosis of an infection itself, already formed or in the process of formation.

Its concentration in the blood, which increases rapidly in response to infections caused by bacteria, fungi, viruses, protozoa or helminths or in conjunction with other pathological processes, therefore represents the indicator of an inflammation in progress. However, this is a non-specific indicator, but it can still be useful to assess the extent of the inflammatory state and its evolution over time.

How does that work

C-reactive protein performs its defensive action by favoring the elimination of what can be harmful to the body, whether they are pathogenic germs, foreign bodies, damaged tissues or altered cellular components.

Its production, which takes place mainly in the liver, is activated by the effect of certain substances (cytokines) that are released by immune cells during the inflammatory reaction.

When in contact with foreign agents that triggered the immune response, C-reactive protein binds to the particular chemical compounds that characterize its structure (for example sugars present on the surface of various microorganisms, lipids of cell membranes or nuclear proteins associated with genetic material) and in this way makes them more vulnerable to the destructive action of other defensive proteins present in the circulation (in this case the factors of the so-called “complement system”) and phagocytic cells, specialized in incorporating, digesting and disposing of harmful substances.

Following the triggering of the immune defense mechanisms and the related inflammatory reaction, the level of C-reactive protein in the blood, normally very low, rises very quickly (a few hours), reaching its maximum peak in two days. The values that are found from this acute phase onwards depend on the severity of the pathological process that induced the production of the protein and its evolution.

Its diagnostic significance

As already mentioned, the increase in the concentration of C-reactive protein in the blood, which can be found through special medical reports, is almost always the signal of a pathological event in progress, but in itself does not give any precise diagnostic indication.

The underlying event could be found among the following possibilities:

• bacterial, viral, fungal or parasitosis infections (from protozoa or helminths), localized (outbreaks) or systemic (sepsis or septicemia)
• Trauma
• burns
• autoimmune diseases (e.g. rheumatoid arthritis, systemic lupus erythematosus)
• inflammatory bowel diseases (e.g. Chron’s disease, ulcerative colitis)
• inflammatory changes resulting from metabolic disorders (e.g. gout, diabetes)
• Neoplasms
• tissue damage of ischemic origin (myocardial infarction, stroke)
• inflammatory phenomena associated with surgical interventions.

Infections or non-infectious diseases that cause C-reactive protein elevation can be localized in any tissue, organ or apparatus, from the skin to the central nervous system.

In the same way, an increase in C-reactive protein, since it can be associated with many different pathological conditions, is never accompanied by typical symptoms: the most common disorders in the presence of an inflammatory state are certainly pain and fever, but depending on the underlying disease these can also exist or not and be of very variable entity. The same clinical profile of the individual patient can lead to very different protein C reference values, without necessarily being linked to a deterioration in health and well-being.

Although the dosage of C-reactive protein in the blood can only provide a generic indication of disease, the clinical utility is not limited: once the doctor, through the investigations suggested by the other elements of the symptomatic picture, has reached the diagnosis of the pathological process that causes the increase of the protein, he can resort to its monitoring to evaluate the progress of the underlying disease and, In parallel, the effectiveness of the prescribed treatment.

Therefore, although the interpretation of the plasma values of C-reactive protein is complex and cannot ignore the complementary information obtained with other tests, its increase is certainly an alarm bell, while its decrease during the disease is generally a sign of a progression towards improvement.

Beyond the numerous pathological conditions mentioned, there are some physiological factors or in any case not associated with a state of disease that can influence the levels of the protein in the blood: for example, the baseline values tend to be higher in the neonatal period in the first hours of life, in old age, in the last months of pregnancy and in obese subjects and can be altered by the intake of certain drugs (some anti-inflammatories, contraceptives, cholesterol-lowering statins, etc.).

On the contrary, the concentration of C-reactive protein may remain low despite the presence of an ongoing inflammatory state in patients with liver failure, since in these cases the liver is no longer able to synthesize it.

C-reactive protein vs. ESR

Although non-specific, C-reactive protein is a more sensitive parameter than the other inflammatory index traditionally measured in the blood, known as ESR or erythrocyte sedimentation rate, which represents the rate at which red blood cells separate from plasma and settle to the bottom of the tube.

The two tests may have different indications, but they can also play complementary roles both among themselves and with respect to other diagnostic investigations. It is, in fact, possible to find simultaneously in the same patient clinical indications that are not necessarily conflicting, namely both a high concentration of C-reactive protein and an increase in the ESR parameter.

However, C-reactive protein more accurately reflects the acute phase of inflammation because its plasma levels increase more promptly (in a few hours, as already seen) than ESR values (which rise 4-7 days after the onset of the disease) and decrease more rapidly in response to therapy and based on healing or improvement of the underlying disease.

In surgery, for example, the level of C-reactive protein is very useful to follow the progress of the post-operative course: under normal conditions its value undergoes an increase within 2-6 hours of surgery and normalizes within the third-fifth day, so its increase that lasts longer must lead to suspect an infectious complication.

The interpretation of the examination in other situations in which an acute or chronic inflammatory process is taking place is based from time to time on the values found, which in principle are proportional to the severity of the pathological state, and on their variation over time.

A simple blood sample is enough

The dosage of C-reactive protein is a simple laboratory analysis, which is carried out with a blood sample. It is therefore a minimally invasive and completely painless control examination, which can be carried out with common tools even in the context of a simple medical examination. To be analyzed is in particular the serum, ie the liquid part of the blood obtained after eliminating the cellular component (red blood cells, white blood cells and platelets) and coagulation factors.

The exam does not require particular preparation apart from the usual fast of 8-10 hours and, at the request of some laboratories, the maintenance of the upright position for at least 30 minutes.

The normal values, i.e. those that are detected in the absence of inflammatory processes, range from 0 to 6 mg / L (or 0.00-0.60 mg / 100 ml), taking into account that in women the parameter may be slightly higher than in men, without prejudice to individual variability factors that could influence the amount being measured.

In pathological conditions, C-reactive protein values can increase considerably, depending on the extent and extent of inflammation. The order of magnitude of the values found can give an idea of the intensity of the underlying disease and suggest the insights to be carried out to diagnose it.

In general, values between 6 and 10 mg / L can be an indication of a non-acute inflammatory state, as can occur in the non-active stages of a chronic disease, while values between 10 and 100 mg / L may mean that acute inflammation is underway but of mild or moderate degree and values above 100 mg / L that the process is instead intense and extensive.

As we can see, therefore, having high C-reactive protein is a signal, albeit non-specific and not always clear, of a possible inflammation. In the case of infections, however, the extent of the elevation of C-reactive protein is also influenced by the specific cause: infections of viral origin are generally associated with lower values than those accompanying bacterial infections. In addition, even among the bacterial ones there may be different results depending on the type of germ in question, as well as the site of the infectious outbreak.

In any case, even in the presence of evident low concentrations of C-reactive protein, the evaluation of the result of blood tests must always be carried out by your doctor, or in any case by other specialists and professionals able to detect, starting from the same laboratory tests on the patient’s blood sample, all any risk factors that can be deduced from them, as well as monitoring the progress of any chronic inflammatory diseases or similar.

C-reactive protein and cardiovascular risk

A separate discussion deserves the relationship between serum C-reactive protein levels and cardiovascular risk, which is the subject of investigation by the most recent research and can be useful in the rapid identification of therapies and forms of prevention of cardiovascular diseases, starting from nutrition and lifestyle.

The finding of higher than normal baseline values in subjects who present the classic signs of the so-called metabolic syndrome (high blood sugar, insulin resistance, high levels of cholesterol and triglycerides, obesity, hypertension), suggests the possibility that the dosage of C-reactive protein may prove useful, from the point of view of preventive medicine, as an indicator of the risk of myocardial infarction or stroke.

To explain the increase of C-reactive protein in this clinical condition would be the alterations of the atherosclerotic vascular walls, at the level of which inflammatory processes are triggered.

Since in these cases the increase in C-reactive protein is lower than that found in conjunction with infections and inflammatory diseases, in recent years a “high sensitivity” test (HS-CRP, High Sensivity C-reactive protein) has been developed capable of dosing it accurately in a range between 0.5 and 15 mg / L. According to some studies, baseline levels above 2.4 mg / L would result in a cardiovascular risk twice as high as compared to that associated with values below 1 mg/L.

Being, however, a non-specific index of inflammation, the reliability of C-reactive protein as a screening of heart and circulatory health is still discussed and, in any case, it is recommended to use it only in combination with other blood tests that are altered in the metabolic syndrome (total cholesterol and HDL, apolipoproteins B and A1, homocysteine, triglycerides, blood glucose, etc.) and which can, as a whole, provide indications for the prevention of acute cardiovascular events (through specific treatments and interventions on nutrition and lifestyle) and constitute an overall good method to detect and monitor cardiac risk.

Similar considerations can be made regarding the use of the test as a tumor marker: since the neoplastic pathology is often associated with the activation of inflammatory processes, in subjects suffering from some types of cancer there is generally an increase in the basal levels of the protein, of a magnitude similar to those typical of cardiovascular disease. The examination can therefore also be useful in the field of oncology, for the purpose of early diagnosis of cancer, but only if accompanied by specific investigations suggested by the overall clinical picture.