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SAN FRANCISCO -- C-reactive proteins, which are released into the bloodstream as a result of inflammation, may not be an accurate early predictive marker for chronic diseases such as osteoarthritis, according to a new study by Duke University Medical Center researchers. The finding calls into question the clinical usefulness of the proteins as an indicator of disease.
Instead, the researchers found, levels of C-reactive proteins circulating in the blood are more an indicator of a patient's weight that can be influenced by gender and ethnicity. While not the elusive predictor for osteoarthritis that many rheumatologists have been seeking, C-reactive protein levels could serve as a useful indicator of an osteoarthritis patient's response to therapy, according to the Duke researchers.
C-reactive proteins are produced by the liver in response to inflammation or infections, and their levels in the blood can rise dramatically in many chronic disease states. While previous studies by other researchers have suggested that elevated levels of C-reactive protein may be a predictive marker for disease, they did not take into account the role of weight or ethnicity, the Duke researchers said.
The results of the Duke study were presented March 7, 2004, at the 50th annual scientific meeting of the Orthopedic Research Society.
"Contrary to previous reports, the level of C-reactive protein in the blood is not a useful indicator of osteoarthritis because of its strong association with body mass index (BMI), the commonly used measure of obesity," said Duke's Virginia Kraus, M.D., lead investigator for the study. "Additionally, C-reactive protein levels are higher in African-Americans and women in general, so gender and ethnicity must also be taken in account when interpreting C-reactive protein levels in diagnosing common chronic diseases."
To date, the gold standard for diagnosing osteoarthritis has been the X-ray. However, since this radiographic approach can only image bone and not cartilage, it has not been a useful tool for diagnosing early-stage disease. Clinicians had hoped that C-reactive protein levels, as measured in the blood, could provide this early predictor of osteoarthritis, said Kraus.
For her analysis, Kraus wanted to discover if there was a correlation between the levels of C-reactive proteins with the degree of osteoarthritis as measured by X-rays. She analyzed clinical data and blood samples collected by Joanne Jordan, M.D., of the University of North Carolina at Chapel Hill. Jordan directs the Johnston County, N.C., Osteoarthritis Project, an ethnically diverse sample of patients with osteoarthritis.
After ruling out patients with other disorders such as rheumatoid arthritis, Kraus had a sample of 670 patients. The sample was 49 percent African-American, 41.5 percent male, with an average age of 62.
Unlike previous studies, Kraus included BMI as one of the patient characteristics to be studied. The BMI is intended to take into account the relationship of weight and height, and it is calculated by dividing weight in kilograms by height in meters squared. The average BMI for the study was 30, with a range of 18.5 to 25 being considered normal.
"The levels of C-reactive protein were higher in African-Americans and women, and were strongly associated with BMI," Kraus said. "C-reactive protein levels were also strongly positively associated with all definitions of osteoarthritis based on radiographic status, with the levels increasing as the severity of the disease increased.
"However, after the statistical analysis, all these associations between C-reactive protein levels and degree of osteoarthritis were explained entirely by BMI differences," she concluded. "For that reason, we do not think that C-reactive protein levels can be a useful predictor of osteoarthritis."
It is known that the immune system molecule known as interleukin-6 (IL-6) is the primary activator of the C-reactive protein gene in the liver. Interestingly, according to Kraus, fat tissue, especially the "bad" fat that collects around the waist, is the major source of IL-6.
"This is what probably accounts for the strong relationship between C-reactive protein and BMI," she said. "We know that exercise has the ability to decrease levels of C-reactive proteins. For this reason, measuring C-reactive protein levels in our osteoarthritis patients who are prescribed exercise may give us useful information about how patients are responding to therapy."
Osteoarthritis is a growing national health issue, with more than 40 million Americans suffering from the disorder, known as the "wear-and-tear" form of arthritis. The other major form, rheumatoid arthritis, occurs when the body's immune system attacks the linings of joints.
It is estimated that more than 70 percent of Americans over the age of 65 show some signs of osteoarthritis, which is characterized by the slow degeneration of the buffering layer of cartilage within joints. It occurs most commonly in knees, hips, hands, neck and the lower back.
The research was funded by a National Institutes of Aging Claude D. Pepper grant, the Centers for Disease Control/Association of Schools of Public Health, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Other members of the team included Duke's Thomas Stabler, as well as G. Luta, J.B. Renner and A.D. Dragomir, University of North Carolina at Chapel Hill.