Coronary arterial calcification in rheumatoid arthritis: comparison with the Multi-Ethnic Study of Atherosclerosis

Abstract

Introduction: Although cardiovascular morbidity and mortality are increased in rheumatoid arthritis, little is known about the burden of subclinical coronary atherosclerosis in these patients.

Methods: Using computed tomography, coronary artery calcification was measured in 195 men and women with rheumatoid arthritis aged 45 to 84 years without clinical cardiovascular disease and compared with 1,073 controls without rheumatoid arthritis enrolled in the Baltimore cohort of the Multi-Ethnic Study of Atherosclerosis.

Results: The prevalence of coronary calcification (Agatston score > 0) was significantly higher in men, but not women, with rheumatoid arthritis after adjusting for sociodemographic and cardiovascular risk factors (prevalence ratio = 1.19; P = 0.012). Among participants with prevalent calcification, those with rheumatoid arthritis had adjusted mean Agatston scores 53 units higher than controls (P = 0.002); a difference greater for men than women (P for interaction = 0.017). In all analyses, serum IL-6 attenuated the association between rheumatoid arthritis and coronary calcification, suggesting its role as a potential mediator of enhanced atherosclerosis. Notably, increasing severity of rheumatoid arthritis was associated with a higher prevalence and extent of coronary calcification among both men and women with rheumatoid arthritis, and for all age categories. The largest percentage difference in coronary arterial calcification between rheumatoid arthritis patients and their nonrheumatoid arthritis counterparts was observed in the youngest age category.

Conclusions: Increasing rheumatoid arthritis disease severity was associated with a higher prevalence and greater extent of coronary artery calcification, potentially mediated through an atherogenic effect of chronic systemic inflammation. Gender and age differences in association with coronary calcification suggest that preventive measures should be emphasized in men with rheumatoid arthritis, and considered even in younger rheumatoid arthritis patients with low levels of traditional cardiovascular risk factors.

Figure 1

Adjusted mean Agatston calcium scores for participants with any coronary artery calcification (Agatston score > 0). Adjusted mean Agatston calcium scores for participants with any coronary artery calcification according to rheumatoid arthritis (RA) status and (a) gender and (b) age category. Analyses include 667 subjects with complete data. Analyses were adjusted for age, gender (where appropriate), race, hypertension, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol, diabetes, ever smoking, and use of lipid-lowering medication. Means are enumerated and 95% confidence intervals (CIs) are indicated. P for gender interaction = 0.017; P < 0.05 for both age group interaction comparing the youngest or oldest age group with the middle age group.

Figure 2

Adjusted associations of rheumatoid arthritis severity with prevalence of coronary artery calcification (Agatston score > 0). Tertiles of rheumatoid arthritis (RA) severity according to gender are gender-specific. Prevalence of any coronary calcium is given as a percentage of the total. Adjusted comparisons include age, gender (where appropriate), race, highest education level attained, hypertension, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol, diabetes, ever smoking, and use of lipid-lowering medication. Analyses include 1,222 subjects with complete data (RA, n = 193; control, n = 1,029). *P < 0.05 compared with the non-RA group. **P < 0.05 compared with both the non-RA group and the lowest tertile of RA severity.

Figure 3

Adjusted mean Agatston scores for participants with coronary artery calcification according to rheumatoid arthritis severity. Adjusted mean Agatston calcium scores for participants with any coronary artery calcification (CAC) (Agatston score > 0) according to tertiles of rheumatoid arthritis (RA) severity, by (a) gender and (b) age category. Analyses include 667 subjects with complete data. Tertiles of propensity for RA disease activity and severity according to age category are gender-specific. Analyses were adjusted for age, race/ethnicity, hypertension, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol, diabetes, ever smoking, and use of lipid-lowering medication. Means are enumerated and 95% confidence intervals (CIs) are indicated. P values for the linear trend of increasing RA severity with CAC are < 0.05 for the total group and in all subgroup analyses.