HLA-DRB1 Shared Epitope is Independently Associated with Severity of Coronary Calcification in Rheumatoid Arthritis -OP 0105
Authors: Giles, Post, Blumenthal, Petri, Szklo, Gelber, Detrano, Bathon
Disclaimer: Drs Giles and Bathon are authors of this abstract
The increased cardiovascular events and mortality observed in RA are not fully explained by traditional risk factors. Among RA disease-associated factors, the HLA-DR4 risk alleles known as the “shared epitope” (SE) are a potential independent risk factor for cardiovascular disease in RA. In this abstract, coronary arterial calcification (CAC), a measure of coronary atherosclerosis assessed using cardiac computed tomography (CT), is compared in RA patients according to SE status.
Methods Men and women with RA aged 45 to 84 years enrolled in the cohort study Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in RA (ESCAPE RA) were studied. Patients with prior cardiovascular events and procedures were excluded. SE alleles were assayed and categorized as to presence and number (0, 1, or 2). CAC was quantified and classified as to presence (none vs. any) and severity (above or below the age, gender, and race stratified 75th and 90th percentile cutoffs from comparable non-RA subjects enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). The presence and severity of CAC was compared among subjects according to SE status, adjusting for potential confounders of CAC (demographics, traditional cardiovascular risk factors, and RA disease associated characteristics).
Results 194 RA subjects were studied. Women made up 60% of the cohort. Any SE alleles were found in 70% of subjects. Any CAC was detected in approximately half of subjects (53%). Neither SE alleles, nor RF or anti-CCP antibody status differed according to the presence of CAC. However, SE alleles were associated with the severity of CAC:
Prevalence of Severe CAC according to SE Status
|
No SE |
1 SE Allele |
2 SE Alleles |
p |
CAC > 75th Percentile |
16.7% |
34.1% |
34.0% |
0.015 |
CAC > 90th Percentile |
5.1% |
18.2% |
23.4% |
0.009 |
* p-values represent the comparison of any SE alleles to no alleles
The relationships between SE and severity of CAC did not differ between subjects with 1 or 2 SE alleles. After adjusting for demographics, traditional cardiovascular risk factors, and RA characterisitics, the odds of CAC > 75th percentile was 3-fold greater in subjects with any SE alleles compared to those with no alleles (OR 2.98 (95% CI 1.26 – 7.07)) and the odds of CAC>90th percentile was almost 5-fold greater in subjects with any SE alleles compared to those with no alleles (OR 4.84 (95%CI 1.38 – 17.98)). Substituting RF or anti-CCP antibody status did not recreate the same relationships.
Conclusions HLA-DRB1 shared epitope alleles were significantly associated with the severity, but not presence, of CAC in RA, even after adjusting for pertinent confounders of CAC.
Editorial Comment These data derive from our Center and represent the first report of the association of SE with coronary pathology in RA. These findings are potentially important, as SE may be pathogenically involved in atherogenesis in RA patients, and perhaps in the general population. This possibility is supported by the finding that neither RF nor CCP antibodies recreated or substituted for the SE effect on CAC, suggesting that the SE effect may be separate from the RA disease process. Longitudinal follow-up is underway to explore whether RA patients with SE also have more rapid progression of CAC over time than those without SE.