NEW YORK – Imaging seems to be the sine qua non of determining cardiovascular disease risk in patients with rheumatoid arthritis.
Dr. Jeffrey D. Greenberg noted that, over the last 10-15 years, epidemiologic studies have shown patients with rheumatoid arthritis (RA) have a twofold increase in the risk of myocardial infarction and stroke and an increase in cardiovascular-related deaths. "An important issue we face is how can we risk stratify our patients to predict who will develop cardiovascular disease? Imaging is a promising area that may help us develop biomarkers of risk or better understand pathophysiological mechanisms of RA."
The need for precise tools with which to predict risk has become more urgent with the recently published findings that carotid ultrasound measurement of carotid intima-media thickness has been found to predict coronary events in patients with RA, independent of traditional cardiovascular risk factors and manifestations of RA.
The study, conducted by Dr. Matthew R. Evans and his associates at Brooke Army Medical Center, Fort Sam Houston, Tex., found that there appears to be a dose-dependent relationship between plaque and risk, with a 2.5-fold increase with unilateral plaque and 4.3-fold increase with bilateral carotid plaque, suggesting that atherosclerosis plays a significant role in acute coronary events in patients with RA (Arthritis Rheum. 2011 [doi:10.1002/art.30265]).
In discussing Dr. Evans’s research at his presentation at a rheumatology meeting sponsored by New York University, Dr. Greenberg said that this is the first study to demonstrate the predictive value of measuring carotid intima-media thickness and plaque for cardiovascular events in RA patients.
In the Evans study, carotid ultrasounds were performed on 636 RA patients as part of the prospective ORALE (Outcome of Rheumatoid Arthritis Longitudinal Evaluation) study. These patients were followed for 3,402 person-years and, during that time, 84 patients experienced 121 new or recurrent acute coronary syndrome (ACS) events, such as myocardial infarction, unstable angina, cardiac arrest, or death from ischemic heart disease. The rate of ACS events was 3.5/100 patient-years for this group. If only those without a prior history of ACS were analyzed, this group had 66 ACS events, with an incidence of 2.1 ACS/100 person-years.
Multivariate analysis of baseline factors associated with incident or recurrent acute coronary syndromes revealed that two markers of atherosclerosis were independent predictors of a subsequent coronary event. Having a past cardiovascular event raised the risk almost threefold (hazard ratio, 2.87 [1.75, 4.73]; P = .001) and carotid intima-media thickness also raised the risk significantly (HR, 1.61 [1.24, 2.08]; P = .001). After substituting carotid plaque for intima-media thickness, the investigators found a 2.5-fold increase in risk for unilateral plaque and almost a sixfold increase in risk for bilateral plaque.
The findings confirmed that traditional demographic and cardiovascular risk factors also predict coronary events as would be expected. These include male gender (HR, 1.94 [1.11, 3.39]; P =.05), diabetes (HR, 2.24 [1.44, 3.50]; P = .001), and hypertension (HR=1.56 [1.00, 2.44]; P =.05). Measures of RA severity, such as swollen joint counts (HR, 1.03 [1.01, 1.06]; P = .01) and cumulative prednisone dose of 20 g (HR, 2.12, [1.32, 3.42]; P = .01), also had predictive value.
Dr. Greenberg, who is director of the Arthritis Translational Registry and Biorepository at NYU Hospital for Joint Diseases, is involved in ongoing studies using advanced MRI and PET techniques to visualize and quantify some of key histologic features of plaque that are most likely to rupture, which he calls "vulnerable plaque." These histologic features include macrophage content, plaque neovascularization, a lipid-rich necrotic core, and a thin fibrous cap.
Dr. Greenberg receives consulting fees from Genentech Inc.