C-reactive protein: what the test shows and why it matters for an athlete
C-reactive protein is one of the most popular markers of inflammation. It is ordered when infection is suspected, to assess cardiovascular risk, and athletes increasingly give it as part of "check-ups". The editorial team explains where this protein comes from, what exactly the test shows and how to interpret it in a person who trains regularly.
What C-reactive protein is
C-reactive protein (CRP) is an acute-phase protein of inflammation synthesized by the liver. It got its name in 1930, when researchers discovered that the serum of patients with pneumococcal pneumonia reacts with the C-polysaccharide of the pneumococcus cell wall. Since then CRP has become one of the most studied markers of inflammation in medicine.
The synthesis of CRP is triggered by cytokines, primarily interleukin-6. When an infection, injury or tissue damage occurs in the body, immune cells release IL-6, and within hours the liver increases production of CRP. The concentration can rise hundreds of times compared with the baseline (Pepys, Hirschfield, 2003).
The biological role of CRP is the "marking" of damaged cells and microorganisms. It binds to phosphocholine on their surface and activates the complement system, facilitating the removal of dead cells and bacteria by phagocytes. That is, it is not just an indicator but an active participant in innate immunity.
The key advantage of CRP as a marker is speed. The level begins to rise 4–6 hours after the start of inflammation, reaches a peak in about 36–48 hours, and the half-life is about 19 hours. Therefore, after the cause is eliminated the concentration decreases relatively quickly, unlike, for example, the ESR.
Standard CRP and hs-CRP
In laboratories there are two variants of the test. The standard CRP test is designed to detect pronounced inflammation — infections, exacerbations of autoimmune diseases, postoperative complications. It works well in the range from a few to hundreds of milligrams per liter.
The high-sensitivity test (hs-CRP) measures the same protein but precisely determines very low concentrations — from tenths of a milligram per liter. It is used to assess chronic low-grade inflammation associated with atherosclerosis and cardiovascular risk.
A joint statement by the CDC and the American Heart Association (Pearson et al., 2003) proposed risk categories by hs-CRP: less than 1 mg/L — low, 1–3 mg/L — intermediate, over 3 mg/L — high. A result over 10 mg/L is not used for assessing cardiac risk: it indicates acute inflammation, and the test is repeated after recovery.
In the 2019 clinical guidelines (ACC/AHA) hs-CRP ≥2 mg/L is classified as a risk-enhancing factor that may influence decisions on prevention in people at intermediate risk. In the JUPITER study (Ridker et al., 2008) it was precisely elevated hs-CRP that was the criterion for including participants with normal LDL cholesterol.
| Type of test | Range | What it is used for |
|---|---|---|
| Standard CRP | From a few to hundreds of mg/L | Infections, acute inflammation, treatment monitoring |
| hs-CRP | From tenths of a mg/L | Chronic low-grade inflammation, cardiovascular risk |
How training affects CRP
A single exhausting effort — a marathon, ultramarathon, multi-day cycling race — causes a short-term inflammatory reaction. Damage to muscle fibers and the release of IL-6 by working muscles stimulate the liver, and CRP rises with a peak approximately a day or two after the finish. After a marathon, values can temporarily go beyond the usual reference interval.
By contrast, regular training in the long term is associated with a lower baseline CRP level. A systematic review by Kasapis and Thompson (2005) showed that physically active people have lower CRP in cross-sectional studies, and training programs in many intervention studies lowered this indicator. The effect is partly explained by a reduction of visceral fat, which is a source of pro-inflammatory cytokines.
Thus, for an athlete CRP has "two sides": an acute rise after hard work is normal recovery physiology, and a chronically low level at rest is one of the signs of healthy metabolism.
A problem may be a situation where the resting level remains elevated for a long time without infection: this may indicate insufficient recovery, a hidden focus of inflammation or other conditions. The consensus on overtraining syndrome (Meeusen et al., 2013) at the same time cautions: no single marker, including CRP, allows overtraining to be diagnosed.
Why an athlete needs this test
First, CRP helps distinguish a bacterial infection from a mild indisposition. High values (tens and hundreds of mg/L) more often accompany bacterial processes, whereas in viral infections the rise is usually more moderate. A doctor makes the decision on returning to training after illness taking symptoms into account, and CRP can be one of the guidelines.
Second, hs-CRP is an element of cardiovascular risk assessment, especially in veteran athletes, athletes with excess body mass, an unfavorable lipid profile or a family history of early heart attack.
Third, CRP is useful as a "context" indicator for other tests. Inflammation changes the level of ferritin (raises it), iron and zinc (lowers them), so without knowing the CRP it is easy to make a mistake in assessing micronutrient status.
- Differentiation of infections and the decision on returning to exertion.
- Assessment of chronic inflammation and cardiovascular risk (hs-CRP).
- Correct interpretation of ferritin, iron, zinc.
- Monitoring of injuries and inflammatory joint diseases.
Finally, with injuries and chronic joint pain, CRP together with ESR helps a doctor to suspect an inflammatory (for example, autoimmune) disease, not just mechanical overload.
Preparation and interpretation
To assess the baseline level, blood is given at rest, without intense or unusual training for at least 48–72 hours, without signs of infection. Since CRP fluctuates relatively little over the day, strict fasting is not critical, but for a comprehensive panel it is better to come in the morning on an empty stomach.
For cardiovascular risk assessment, two measurements of hs-CRP about two weeks apart are recommended, using the average value (Pearson et al., 2003). A one-time result may be accidentally overestimated because of an unnoticed cold or injury.
The CRP level is affected by excess fat mass, smoking, sleep deprivation, hormonal contraceptives and estrogen replacement therapy (which raise it), as well as statins (which lower it). These factors are important to take into account when comparing results.
No single CRP result makes a diagnosis. This is a nonspecific marker: it shows that inflammation is present, but does not say where and why. Interpretation should always take place together with symptoms and other tests.
Editorial conclusions
C-reactive protein is a fast marker of inflammation that the liver synthesizes in response to IL-6. It rises within hours and decreases within days after the cause is eliminated.
The high-sensitivity variant of the test (hs-CRP) allows the assessment of chronic low-grade inflammation and cardiovascular risk, but only outside acute conditions.
In athletes CRP temporarily rises after exhausting competitions, whereas regular training in the long term is associated with a lower baseline level.
Read also our materials on the causes of elevated and reduced CRP in athletes, on the ESR and on ferritin as a marker of iron reserves.
References
- Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111(12):1805–1812.
- Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003;107(3):499–511.
- Kasapis C, Thompson PD. The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. J Am Coll Cardiol. 2005;45(10):1563–1569.
- Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–2207.
- Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. Circulation. 2019;140(11):e596–e646.
- Sproston NR, Ashworth JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol. 2018;9:754.
- Meeusen R, Duclos M, Foster C, et al. Prevention, diagnosis, and treatment of the overtraining syndrome: joint consensus statement of the European College of Sport Science and the American College of Sports Medicine. Med Sci Sports Exerc. 2013;45(1):186–205.
Andriy Melnyk
A strength-sports coach and author of programs for beginner and intermediate levels. Writes about training planning.
