C-reactive protein (CRP) is released in the body in response to inflammation. Although great quantities of CRP are released into the blood in response to acute infections or trauma, lower levels are released under conditions of chronic inflammation, such as dental disease or atherosclerosis. In order to further characterize CRP as a diagnostic test for patients developing heart disease, a more highly-sensitive test was developed, termed hs-CRP.
Atherosclerosis as an Inflammatory Process
The atherosclerotic process (development of heart disease) is now considered to be closely associated with inflammation. Low density lipoproteins (LDL) are important molecules for the transport of fatty substances through the blood, and contain large quantities of cholesterol. When the body contains excess cholesterol, the LDL molecules can become reduced in size and oxidized by free radicals. The modified LDL can more easily enter the blood vessel wall. Within the endothelium, the LDL undergoes extensive modifications resulting in the formation of new antigens that stimulate an immune response. Monocytes (white blood cells) enter the epithelium and mature into macrophages. The macrophages take up the LDL and become foam cells. As some of the foam cells die, a fatty core develops in the lesion. This lesion is known as a plaque and is covered by a fibrous cap. The plaque begins to bulge into the interior of the blood vessel. Heart attacks are not caused by constrictions of the vessel, but by unstable plaques that burst. This event causes stimulation of coagulating factors, and the formation of a clot that blocks blood flow to the heart.
What is the Role of C-reactive Protein in Heart Disease?
CRP has been extensively studied in relation to heart disease. There is no question that elevated CRP is found in persons with heart disease. However, other chronic conditions also can cause elevated CRP, including dental disease, and obesity. John Danesh and co-workers found that CRP was a relatively moderate predictor of heart disease, but added relatively little to that provided by assessments of other risk factors. Although some scientists had thought CRP could be a cause of heart disease, recent studies have shown that this is not the case. Research teams headed by Paul Elliott and Jeppe Zacho studied genetic variants associated with the CRP gene. As a result of these variants, termed polymorphisms, some people naturally produced more CRP, while other people produced less. Although people with higher CRP levels had more heart disease, statistical analysis of the data showed that the polymorphisms in themselves were not associated with an increased risk of the disease.
Who Should Have Their CRP Level Measured?
Only persons with at least a moderate risk of developing heart disease should be tested for CRP. Of course, CRP results should only be evaluated in conjunction with the results of a traditional lipid profile assay. Patients with a hs-CRP level of less than 1.0 milligram per liter of blood have a low risk of developing heart disease, while levels of higher than 3.0 mg/L indicate a high risk of developing the disease.
How Important is C-reactive Protein?
CRP rises in response to developing heart disease, but is an indicator and not a cause of the disease. CRP testing is advisable only with persons with moderate or higher risk of developing heart disease, and the results evaluated together with traditional risk factors, such as cholesterol, lipoproteins, and triglycerides.
References
- Berliner J, Watson A. A Role for Oxidized Phospholipids in Atherosclerosis. N Engl J Med. 2005 July 7; 353(1):9-11.
- Danesh, J.et al. C-reactive Protein and Other Circulating Markers of Inflammation in the Prediction of Coronary Heart Disease. N Engl J Med. 2004; 350 (14):1387-1452.
- Elliott P. et al. Genetic Loci Associated With C-reactive Protein Levels and Risk of Coronary Heart Disease. J Am Med Assn. 2009 July 1; 302(1);37.
- Libby P. The Pathogenesis of Atherosclerosis. In: Harrison's Principles of Internal Medicine, 15th ed. New York, McGraw-Hill; 2001: 1377-1382.
- Zacho J. Genetically Elevated C-reactive Protein and Ischemic Vascular Disease. N Eng J Med. 2008 Oct 30;359(18):1897-1908.
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