Despite these advances, much was still unknown when we began our studies seven years ago. What was the prevalence of atherosclerosis in SLE patients in relation to a control group? What elements of SLE affected risk? What were the contributions of conventional risk factors, disease severity, and treatment? Did therapy of SLE increase or decrease the risk of ASCVD? How and in whom should we intervene?
To devise a study that would address these questions, we assembled a group of rheumatologists and cardiologists, including Mary J. Roman, MD, professor of medicine at Weill Medical College of Cornell University, who agreed to become the lead cardiologist in the project. Because event rates—myocardial infarction and angina—are relatively low in this young population, and because it was impractical to recruit and study thousands of lupus patients, we needed a surrogate marker to define the prevalence of preclinical atherosclerosis.
Atherosclerosis was associated with longer disease duration, higher damage scores, and less aggressive immunosuppressive therapy. This finding argues that chronic inflammation is atherogenic in SLE.
A few months after our exploratory meetings in 1997 the team from Hospital for Special Surgery was invited to a conference sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Heart, Lung, and Blood Institute to discuss cardiovascular disease in SLE patients. This interdisciplinary group also concluded that the classical approach—one that involved hard clinical endpoints for atherosclerosis and enormous populations to define prevalence and risk factors—although preferable, was not feasible, and that markers for preclinical disease were required. We selected ultrasound evidence of carotid atherosclerosis.
Safe and Accessible Imaging
Ultrasound examination of the extra-cranial carotid arteries to detect the presence of discrete atherosclerotic plaque (established atherosclerosis) and to quantify intimal-medial thickness (a measure of “early” or diffuse atherosclerosis) is a safe, accurate, and sensitive method for detecting atherosclerosis in large populations. Carotid vascular disease is strongly correlated with the presence of atherosclerotic disease in other vascular systems, particularly the coronary bed, and has been shown to be an independent predictor of adverse clinical outcomes, most commonly myocardial infarction.9,10 Moreover, carotid ultrasonography, a non-invasive imaging modality, was both safer and less expensive that many of the other techniques we considered.
In 2000, we began the first case-control study to assess the prevalence, magnitude, and determinants of atherosclerosis in SLE in a population-based sample. We recruited, at time of outpatient visits, more than 200 sequential non-hospitalized patients with SLE. Patients were enthusiastic to participate because they were able to have an examination by a skilled cardiologist, Dr. Roman, and non-invasive imaging, as well as blood tests to assess their ASCVD risk profile.
