Is there an association betwee Carotid Atherosclerosis and Inflammatory Markers in RA patienets?
Summary written by Jon Giles, M.D.
Major recent scientific interest has focused on the association of elevated serum levels of markers of inflammation (erythrocyte sedimentation rate and C-reactive protein) with cardiovascular disease. It is known that patients with rheumatoid arthritis are more at risk for cardiovascular disease and have a higher mortality from cardiovascular causes. Del Rincon and colleagues seek to show that the prevalence of atherosclerosis, as measured by carotid artery intima-media thickness or presence of carotid plaque, is higher in patients with rheumatoid arthritis as compared to healthy controls and correlates with levels of inflammatory markers in serum (Arthritis Rheum 48(7):1833, 2003).
Methods: Non-smoking subjects with rheumatoid arthritis over 40 years of age were recruited from the ORALE trial cohort (Outcome of Rheumatoid Arthritis Longitudinal Evaluation). Subjects were from a broad spectrum of outpatient clinical settings in and around Bexar County, Texas. Non-RA, non-smoking volunteers were recruited via local advertisement and each control subject was matched by sex and age with two RA subjects. Cardiovascular risk factors were identified based on self-report and medical record/medication review.
Subjects underwent a standardized carotid duplex scanning protocol as well as serum ESR and CRP measurements. The same technician performed all carotid duplex scans. Carotid duplex scans were read by a single, blinded reader for determination of carotid artery itima-media thickness (IMT) and carotid plaque.
Results: While no differences in baseline characteristics with respect to age, sex, and measured blood pressure were observed between the 204 RA patients compared to the 102 non-RA controls, significant differences with respect to the prevalence of hypercholesterolemia, diabetes, and in body-mass index were observed. RA subjects from the study cohort tended to have a higher body-mass index, were more likely to have diabetes, and less likely to have hypercholesterolemia. Baseline ESR and CRP was significantly higher in RA subjects than controls. 77% of RA subjects demonstrated rheumatoid factor positivity.
In both RA subjects and non-RA controls, a significant linear relationship was observed between carotid artery IMT (and presence of carotid plaque) with increasing ESR and CRP levels. This relationship remained significant after adjustment for age, sex, cardiovascular risk factors, and after further adjustment for normalization of proportionality in quartiles of ESR and CRP levels. The difference in the mean carotid artery IMT between RA subjects and controls was 0,055mm. However, this difference was not statistically significant, even after adjustment for age, sex, and cardiovascular risk factors.
Conclusion: A significant association exists between carotid artery intima-media thickness/presence of carotid plaque and systemic markers of inflammation and this association is independent of age, sex, and conventional cardiovascular risk factors. No significant difference in carotid artery IMT or prevalence of carotid plaque was seen between RA subjects compared to non-RA controls.
Editorial Comments: A number of published studies, including one by these same investigators, have shown that the prevalence of conventional cardiovascular risk factors in the RA population is not increased relative to age and sex matched controls. These results have prompted, but could not directly prove, the hypothesis that another risk factor that is, chronic inflammation is largely responsible for the observed increase in cardiovascular related morbidity and mortality in RA compared to controls. The current study moves this field further ahead in showing that a measure of subclinical cardiovascular disease (carotid IMT and plaque) is highly correlated with serum inflammatory markers in RA patients (as well as controls). The investigators were unable to demonstrate a statistically significantly higher mean IMT or higher prevalence of carotid plaque in RA patients compared to controls but this may have been due to the relatively small numbers of subjects studied (Type II statistical error). The dose response relationship between increasing ESR and CRP with increasing IMT or presence of plaque lends strong support to a causal relationship between inflammation and atherosclerosis. Diseases like RA that are characterized by intense chronic inflammation for decades are likely to provide the milieu for accelerated atherosclerosis.