Specifically, elevated CRP levels (>e;5 mg/L) at baseline independently predict cardiovascular disease (CVD) mortality, the study found. The major effect occurs in patients who are rheumatoid factor (RF)–positive or who meet the American College of Rheumatology classification criteria for RA at baseline.
"The finding that a CRP concentration above the normal range is a significant predictor of death from CVD in groups of patients with inflammatory joint disease provides further evidence for the role of inflammation in promoting atherosclerotic disease," conclude the researchers, led by Nicola J. Goodson, PhD, MRCP, a rheumatologist at the University of Manchester in the UK. The study suggests that normalizing CRP and treating traditional risk factors for heart disease may improve outcomes for RA patients.
Major effect seen only in RF-positive patients
In the 10-year study of 506 patients with inflammatory polyarthritis (IP), 104 deaths occurred – 40 of which were due to CVD. Elevated CRP levels predicted death from CVD for both men and women in univariate analyses, results showed. After adjusting for age and sex, the CVD mortality association was strongest in the subgroup of patients who were RF-positive at baseline.
Elevated CRP levels remained a significant independent predictor of death from CVD, even after adjusting for age, sex, smoking status, Health Assessment Questionnaire (HAQ) score, RF positivity, and swollen joint counts, investigators found.
"This analysis is the first to show that the baseline level of CRP is a predictor of all-cause mortality, and specifically CVD mortality, in both sexes in the 10-year period following the onset of IP," the researchers wrote. "These data add to the studies showing that modest elevations in the CRP concentration in apparently healthy adults are associated with subsequent cardiovascular events."
Evidence mounting, but questions remain
"The evidence that inflammation is a key factor in causing premature atherosclerotic disease continues to mount," according to Martin Bergman, MD, assistant clinical professor at MCP Hahnemann University in Philadelphia and a rheumatologist at Taylor Hospital in Ridley Park, Pennsylvania. Dr. Bergman, who reviewed the study for CIAOMed, added, "What is also mounting is evidence that patients with RA are at an increased risk for mortality from CVD."
Dr. Bergman also noted that the question posed by this study is whether CRP is an "innocent bystander," a marker of disease, or a predictor of developing CVD.
"Based on [this] study, it would appear to be the latter," he concludes. "What is
interesting is that this predictor appears to be useful only in patients who have RA, and not in RF-negative patients," he states, adding that the explanation for this finding is not clear.
Goodson et al "do not go on to explain what is unique about patients with RA or RF
seropositivity, as opposed to patients who are seronegative for RF," Dr. Bergman points out. "One explanation they propose is that the patients who were seronegative for RF had a ‘lower inflammatory burden,' but that would argue against CRP being a causative agent, inasmuch as an elevated CRP would suggest an elevated inflammatory burden," he notes.
However, Dr. Bergman says, "this study shows an important relationship between an elevated CRP, the diagnosis of RA, and the likelihood of death from CVD."
Although these study findings suggest that elevated CRP may predict death from CVD in patients with inflammatory joint disease, Dr. Bergman questions whether the investigators "have established this association beyond a doubt. Still, given this provocative information, the impetus for treating patients more aggressively in the hope of normalizing CRP, as well as the overt evidence of disease activity, becomes even stronger," he emphasizes.
Reference
Goodson NJ, Symmons DP, Scott DG, et al. Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: A ten-year follow-up study of a primary care–based inception cohort. Arthritis Rheum. 2005;52:2293-2299.