C-reactive protein

C-Reactive Protein 

Definition

C-reactive protein (CRP) is a protein produced by the liver and found in the blood.

Purpose

C-reactive protein is not normally found in the blood of healthy people. It appears after an injury, infection, or inflammation and disappears when the injury heals or the infection or inflammation goes away. Research suggests that patients with prolonged elevated levels of C-reactive protein are at an increased risk for heart disease, stroke, hypertension (high blood pressure), diabetes, and metabolic syndrome (insulin resistance, a precursor of type 2 diabetes). The amount of CRP produced by the body varies from person to person, and this difference is affected by an individual's genetic makeup (accounting for almost half of the variation in CRP levels between different people) and lifestyle. Higher CRP levels tend to be found in individuals who smoke, have high blood pressure, are overweight and do not exercise, whereas lean, athletic individuals tend to have lower CRP levels.

The research shows that too much inflammation can sometimes have adverse effects on the blood vessels which transport oxygen and nutrients throughout the body. Atherosclerosis, which involves the formation of fatty deposits or plaques in the inner walls of the arteries, is now considered in many ways an inflammatory disorder of the blood vessels, similar to the way arthritis can be considered an inflammatory disorder of the bones and joints. Inflammation affects the atherosclerotic phase of heart disease and can cause plaques to rupture, which produces a clot and interfere with blood flow, causing a heart attack or stroke.

There is an association between elevated levels of inflammatory markers (including CRP) and the future development of heart disease. This correlation applies even to apparently healthy men and women who have normal cholesterol levels. CRP level can be used by physicians as part of the assessment of a patient's risk for heart disease because it is a stable molecule and can be easily measured with a simple blood test. In patients already suffering from heart disease, doctors can use CRP levels to determine which patients are at high risk for recurring coronary events.

Precautions

As of 2005, there are no precautions regarding the C-reactive protein test. The person withdrawing blood for the test should be notified if the patient is allergic to latex or has a fear of needles.

Description

C-reactive protein was discovered in 1930, but few people outside the medical community had heard of it until stories about it began hitting the mainstream media in early 2005. In 2005, two studies published in the January 6, 2005, issue of The New England Journal of Medicine provide the best evidence to date that the C-reactive protein level in a person's blood is an important and highly accurate predictor of future heart disease. C-reactive protein (CRP) is a sign of inflammation in the walls of arteries. The studies show that reducing the inflammation by lowering CRP levels with a class of drugs known as statins significantly lowers the rate of heart attacks and coronary-artery disease in people with acute heart disease. In fact, the studies indicated CRP levels may be as important—if not more important—in predicting and preventing heart disease as cholesterol levels are.

Persons with moderate or high levels of CRP can often reduce the levels with lifestyle changes, including quitting smoking, engaging in regular exercise, taking in healthy nutrition, taking a multivitamin daily, replacing saturated fats such as butter with monounsaturated fats (particularly olive oil), increasing intake of Omega-3 fatty acids, losing weight if overweight, and increasing fiber intake. Drugs called statins (usually used to reduce high levels of low density lipoproteins (LDL), the so-called bad cholesterol, can also reduce CRP levels. These drugs include: lovastatin (Mevacor), simvastatin (Zocor), rosuvastatin (Crestor), and the two drugs used in the 2005 CRP studies, pravastatin (Pravacol) and atorvastatin (Lipitor). Other drugs that lower CRP levels include the anti-cholesterol drug ezetimibe (Zetia) and the diabetes medication rosiglitazone (Avandia).

Not all physicians are convinced the two studies published in 2005 are accurate, noting that both studies were funded by pharmaceutical companies (Pfizer and Bristol-Meyer Squibb) that make statin drugs used to reduce CRP levels. Also, the lead authors of the studies have "strong financial ties to the cardiac drug industry," according to an article in the February 2005 issue of HealthFacts. The article also states that study participants already had severe heart disease and in one study, 36% of the participants smoked. It added that the CRP test is still unproven in predicting future acute heart problems in people with mild heart disease or healthy people at risk for developing heart disease.

The C-reactive protein test costs $45 to $85, is performed in physicians' offices, labs, and hospitals. Medicare usually covers the cost as do most other insurance plans.

Preparation

No advance preparation for the CRP test is needed on the part of the patient. The test is conducted on a small sample of blood that usually takes about a minute to withdraw from a patient's vein. The CRP test is performed in a laboratory and the results are usually available in three to five days. A healthcare professional, usually a nurse or laboratory technician, will wrap and tighten a latex strap around the patient's upper arm. The site where blood will be drawn (usually the bend in the arm above the elbow) will be swabbed with alcohol. A small needle attached to a collection vial will be inserted into a vein and a small amount of blood will be withdrawn. When the vial is full, the needle and strap will be removed and a cotton ball will be taped over the injection site.

Aftercare

The tape and cotton can be removed when bleeding at the needle puncture site stops, usually within 15 to 20 minutes. The amount of bleeding should be very light.

Risks

There is an extremely slight risk of infection at the needle puncture site.

Normal results

Normal test results are CRP levels of less than one milligram (mg) per liter of blood. The ideal result is a CRP level of zero.

Abnormal results

C-reactive protein levels of 1-3 mg per liter of blood indicates a moderate risk of heart disease. CRP levels above 3 mg per liter of blood indicates a high risk for heart disease.

Key terms

Atherosclerosis — A common artery disease in which raised areas of degeneration and cholesterol deposits (plaques) form on the inner surfaces of the arteries, often obstructing blood flow.

Hypertension — High blood pressure.

Low density lipoproteins (LDL) — A blood-plasma lipoprotein that is high in cholesterol and low in protein content and that carries cholesterol to cells and tissue; also called bad cholesterol.

Omega-3 fatty acids — One of a group of beneficial fats found in oily fish, seeds, and whole grains.

Statins — A class of drugs commonly used to lower LDL cholesterol levels.

Resources

Books

Deron, Scott J. C-Reactive Protein: Everything You Need to Know About It and Why It's More Important than Cholesterol to Your Health. New York City: McGraw-Hill, 2003.

Fleming, Dr. Richard M., and Tom Monte. Stop Inflammation Now!: A Step-by-Step Plan to Prevent, Treat, and Reverse Inflammation-The Leading Cause of Heart Disease and Related Conditions. New York City: G.P. Putnam's Sons, 2004.

Periodicals

Abrams, Jonathan. "C-Reactive Protein Levels and Outcomes after Statin Therapy." Clinical Cardiology Alert (March 2005): 17-19.

"C-Reactive Protein Testing Not for Everyone." HealthFacts (February 2005): 1.

"Get the C-Reactive Protein Test." Medical Update (February 2005): 3.

Spiker, Ted. "Bonfire of the Arteries." Men's Health (December 2004): 114.

Zoler, Mitchel L. "Reducing CRP Is Key in Acute Coronary Syndrome: Study Results Validate that Lowering CRP Is Important, Even for Patients on a High-Dose Statin." Family Practice News (December 15, 2004): 15.

Organizations

American Heart Association. 7272 Greenville Ave., Dallas, TX 75231. (800) 242-8721. http://www.americanheart.org.

National Heart, Lung, and Blood Institute. Building 31, Room 5A52, 31 Center Dr. MSC 2486, Bethesda, MD 20892. (301) 592-8573. http://www.nhlbi.nih.gov.

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protein /pro·tein/ (pro´tēn) any of a group of complex organic compounds containing carbon, hydrogen, oxygen, nitrogen, and sulfur. Proteins, the principal constituents of the protoplasm of all cells, are of high molecular weight and consist of α-amino acids joined by peptide linkages. Twenty different amino acids are commonly found in proteins, each protein having a unique, genetically defined amino acid sequence that determines its specific shape and function. Their roles include enzymatic catalysis, transport and storage, coordinated motion, nerve impulse generation and transmission, control of growth and differentiation, immunity, and mechanical suppport.

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AA protein  see under amyloid.

acute phase protein  any of the non-antibody proteins found in increased amounts in serum during the acute phase response, including C-reactive protein and fibrinogen.

AL protein  see under amyloid.

amyloid A protein  AA amyloid.

amyloid light chain protein  AL amyloid.

amyloid precursor protein  (APP) a large transmembrane glycoprotein expressed on the cell surface and of uncertain function; endocytosis and cleavage can produce abnormal 40 to 43 amino acid peptides which aggregate to form A, associated with Alzheimer's disease.

Bence Jones protein  a low-molecular-weight, heat-sensitive urinary protein found in multiple myeloma, which coagulates when heated to 45°–55°C and redissolves partially or wholly on boiling.

binding protein 

1. any protein able to specifically and reversibly bind other substances, such as ions, sugars, nucleic acids, or amino acids; they are believed to function in transport.

2. transport p.

protein C  a vitamin K–dependent plasma protein that, when activated by thrombin, inhibits the clotting cascade by enzymatic cleavage of factors V and VIII and also enhances fibrinolysis. Deficiency results in recurrent venous thrombosis.

C4 binding protein  a complement system regulatory protein that inhibits activation of the classical pathway.

complete protein  one containing the essential amino acids in the proportion required in the human diet.

compound protein , conjugated protein any of those in which the protein is combined with nonprotein molecules or prosthetic groups other than as a salt; e.g., nucleoproteins, glycoproteins, lipoproteins, and metalloproteins.

C-reactive protein  a globulin that forms a precipitate with the C-polysaccharide of the pneumonococcus; the most predominant of the acute phase proteins.

cystic fibrosis transmembrane regulator protein  a transmembrane protein produced by the cystic fibrosis gene, primarily functioning as a chloride channel. Numerous mutated forms of the gene have been associated with clinical cystic fibrosis.

fibrillar protein  any of the generally insoluble proteins that comprise the principal structural proteins of the body, e.g., collagens, elastins, keratin, actin, and myosin.

G protein  any of a family of proteins of the intracellular portion of the plasma membrane that bind activated receptor complexes and, through conformational changes and cyclic binding and hydrolysis of GTP, effect alterations in channel gating and so couple cell surface receptors to intracellular responses.

glial fibrillary acidic protein  (GFAP) the protein forming the glial filaments of the astrocytes and used as an immunohistochemical marker of these cells.

globular protein  any of the water-soluble proteins yielding only α-amino acids on hydrolysis, including most of the proteins of the body, e.g., albumins and globulins.

guanyl-nucleotide-binding protein  G p.

heat shock protein  any of a group of proteins first identified as synthesized in response to hyperthermia, hypoxia, or other stresses and believed to enable cells to recover from these stresses. Many have been found to be molecular chaperones and are synthesized abundantly regardless of stress.

HIV proteins  proteins specific to the human immunodeficiency virus; presence of certain specific HIV proteins together with certain HIV glycoproteins constitutes a serological diagnosis of HIV infection.

incomplete protein  one having a ratio of essential amino acids different from that of the average body protein.

membrane cofactor protein  (MCP) an inhibitor of complement activation found in most blood cells, endothelial and epithelial cells, and fibroblasts.

myeloma protein  any of the abnormal immunoglobulins or fragments, such as Bence-Jones proteins, secreted by myeloma cells.

partial protein  incomplete p.

plasma proteins  all the proteins present in the blood plasma, including the immunoglobulins.

prion protein  (PrP) a protein of uncertain function, in humans coded for by a gene on the short arm of chromosome 20. The protease-resistant core is the functional, and perhaps only, component of prions; several abnormal forms have been identified and are responsible for prion disease.

protein S  a vitamin K–dependent plasma protein that inhibits blood clotting by serving as a cofactor for activated protein C.

S protein  see vitronectin.

SAA protein  serum amyloid A p.

serum proteins  proteins in the blood serum, including immunoglobulins, albumin, complement, coagulation factors, and enzymes.

serum amyloid A protein  SAA p.; a high-molecular-weight protein synthesized in the liver; it is an acute phase protein and circulates in association with HDL lipoprotein. It is the precursor to AA amyloid and accumulates in inflammation.

sphingolipid activator protein  (SAP) any of a group of non-enzymatic lysosomal proteins that stimulate the actions of specific lysosomal hydrolases by binding and solubilizing their sphingolipid substrates.

transport protein  a protein that binds to a substance and provides a transport system for it, either in the plasma or across a plasma membrane.

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C-reactive protein

n.

An antibody found in the blood in certain acute and chronic conditions including infections and cancers. It is a nonspecific indicator of inflammation and, therefore, not diagnostic of any one disease.

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C-reactive protein (CRP)

[-rē·ak′tiv]

a protein not normally detected in the serum but present in many acute inflammatory conditions and with necrosis. CRP appears in the serum before the erythrocyte sedimentation rate begins to rise, often within 24 to 48 hours of the onset of inflammation. After a myocardial infarction it is present in 24 hours, begins to fall 3 days later, and is absent after 2 weeks. Acute rheumatic fever is monitored with serial estimations of CRP because the serum level of the protein is the most sensitive indicator of rheumatic activity. Bacterial infections and widespread neoplastic disease are also associated with C-reactive protein in the serum. CRP disappears when an inflammatory process is suppressed by salicylates, steroids, or both. Also called serum C-reactive protein.

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C-reactive protein,

n protein usually not present in normal serum but detected with necrosis and a large number of inflammatory conditions, such as bacterial infection, rheumatic fever, and some neoplastic diseases.

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protein (prō´tēn),

n a group of complex organic nitrogenous compounds; the principal constituent of cell protoplasm. Polymers of amino acids that are joined by peptide or amide bonds.

protein, anabolic,

n See steroid, C-19 cortico.

protein, Bence Jones,

n.pr a special protein found in the blood and urine of patients with multiple myeloma and occasionally other diseases involving bone marrow, such as sarcoma and leukemia.

protein, bone morphogenetic (BMP)

n one of several genetically produced proteins that promotes the formation of bone and cartilage.

protein, C-reactive,

n a mucoprotein whose presence in serum is always abnormal. It may be present in a variety of inflammatory or necrotic disease processes. It is almost always present in the serum in acute rheumatic fever.

protein chemical score (CS),

n the result of a comparison between the amount of essential amino acid in a dietary protein and the amount in a reference protein.

protein, complementary,

n a protein that is incomplete on its own but may become complete when combined with other proteins to provide all the amino acids necessary for normal metabolism.

protein, complete,

n a protein that contains ample amounts of all the amino acids necessary for normal metabolism; animal proteins.

protein, deficiency,

n See deficiency, protein.

protein efficiency ratio (PER),

n a calculation designed to assess an individual protein's ability to sustain growth.

protein incomplete,

n a protein that is missing one or more of the amino acids necessary for normal metabolism; vegetable protein.

protein kinase,

n a protein that catalyzes the transfer of a phosphate group from adenosine triphosphate to produce a phosphoprotein.

protein, plasma,

n blood serum contains 6.5 to 8 grams percent of a complex mixture of proteins, including albumin, globulin, and fibrinogen.

protein, reference,

n a protein, usually egg, against which other proteins may be measured to evaluate their capability for supporting synthesis.

protein, spare,

n one of several roles a carbohydrate food may play in a well-balanced diet. Many foods that are technically classified as carbohydrates, including some whole grains and beans, contain relatively significant amounts of protein that may, therefore, be referred to as spare.

protein specificity,

n the arrangement of protein molecules in numerous spatial configurations to suit the special needs of the physical and chemical activities of the cell. The wide degree of variability of protein structures permits a high degree of specificity of tissue within one body. This characteristic of protein specificity is of great significance in blood transfusions, tissue grafts, and many allergic manifestations.

protein, thromboplastic,

n See factor III.

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C-reactive protein

a serum protein produced in response to inflammation, infection or tissue damage; abbreviated CRP. It is immunosuppressive, promotes phagocytosis, inhibits platelets and activates complement.