An increased risk of cardiovascular disease, particularly of myocardial infarction and cardiovascular death, has been identified in patients with RA. Several investigations have identified an increase in carotid artery atherosclerosis in RA patients. However, to date, no published studies have investigated coronary atherosclerosis directly. Here, Chung et al (Arthritis Rheum 2005; 52(10): 3045) investigate coronary arterial calcification (CAC) assessed by electron beam computed tomography (EBCT) in RA and non-RA patients as a measure of coronary atherosclerosis.
Methods:
Patients from the Nashville, Tennessee area with early (disease duration less than 5 years) and established (disease duration greater than 10 years) RA were recruited to undergo EBCT for determination of CAC, quantified as the Agatston score. Non-RA control subjects underwent similar testing and were group matched to the RA subjects based on age, gender, and race. Subjects with cardiac risk factors, known cardiovascular disease, and previous cardiac revascularization procedures were included.
Results:
141 RA subjects (70 with early and 71 with established RA) and 86 non-RA control subjects were enrolled. Mean age was between 51 and 58 years, with approximately two-thirds of patients being female and approximately 90% Caucasian. Despite group matching, RA subjects with established RA were significantly older than control subjects (58 vs. 51 years, respectively; p<0.001). Baseline cardiovascular risk factors (e.g. family history of cardiovascular disease, lipoprotein fractions, statin use) were balanced between established RA and control subjects, with the exception of the prevalence of hypertension (67% vs. 38%, respectively, p<0.001) and mean serum homocysteine concentration (10.8 vs. 8.2 micromol/L, respectively; p<0.001). The prevalence of current smoking was significantly higher among both RA groups compared to the control group (22.9% and 29.6% vs. 9.3%, respectively; p=0.005); however, cumulative smoking in pack years was similar between the two groups. Mean disease duration was 2 years (from first symptom of disease) for early RA subjects and 20 years for established RA subjects.
Prevalence of CAC in RA and Control Subjects
| Non-Ra Control (n=86) |
Early RA (n=70) |
p | Established RA (n=71) |
p | |
| Median Agatston score | 0 | 0 | — | 40.2 | 0.001 |
| Prevalence with any CAC | 38.4% | 42.9% | 0.57 | 60.6% | 0.006 |
| Prevalence with Agatston score 1-109 | 24.4% | 25.7% | — | 19.7% | — |
| Prevalence with Agatston score >109 | 13.9% | 17.1% | — | 40.8% | — |
Likelihood of Severe Coronary Atherosclerosis (Agatston score > 109) in RA vs. Control Subjects
| Likelihood of Agatston score >109 (unadjusted) |
Likelihood of Agatston score >109 (adjusted for age and gender) |
Likelihood of Agatston score >109 (adjusted for cardiovascular risk factors) |
|
| Early RA vs. control | OR 1.21 (95%CI 0.65-2.26) | OR 1.31 (95%CI 0.65-2.64) | OR 1.44 (95%CI 0.67-3.10) |
| Established RA vs. control | OR 3.03 (95%CI 1.65-5.57) | OR 2.73 (95%CI 1.36-5.47) | OR 1.31 (95%CI 1.55-7.53) |
After adjusting for age and gender, only increasing pack-years of smoking and increasing ESR were significantly associated with the likelihood of having an Agatston score > 109 in RA patients (OR 1.02 per increment of 1 pack year of smoking or increment 1 mm/hr of ESR).
Conclusions:
CAC is more prevalent and more severe in RA patients with established disease compared to non-RA controls or RA patients with early disease. This increase is not explained by the prevalence of conventional risk factors. In RA patients, severe coronary atherosclerosis is significantly associated with increasing smoking and ESR.
Editorial Comment:
This is the first published investigation to demonstrate increased coronary pathology in RA and supports previous ultrasound studies of the carotid arteries to confirm an increased burden of atherosclerotic vascular disease in RA. The finding here that excess coronary calcification is a relatively late phenomenon in RA is significant, but may not necessarily indicate that coronary vascular changes are not occurring early in the RA disease process. The process of plaque calcification is complex, and may also be differentially affected in RA patients compared to controls. EBCT is only able to detect calcified, but not un-calcified plaque, which may actually be less stable than calcified plaque and more prone to rupture. Thus, if techniques to measure total atherosclerotic plaque were utilized, early RA patients might demonstrate differences from control subjects.
