Author + information
- †Department of Radiology, University of Washington, Seattle, Washington
- ‡Department of Bioengineering, University of Washington, Seattle, Washington
- ↵∗Reprint requests and correspondence:
Dr. Chun Yuan, Department of Radiology and Bioengineering, University of Washington, 850 Republican Street, #124, Seattle, Washington 98109.
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disorder that is characterized by the production of various autoantibodies and the presence of chronic systemic inflammation. A clinical manifestation of SLE that was once neglected but is now gaining increasing attention is the high prevalence of cardiovascular disease in these patients. Epidemiological studies have estimated that the risk of myocardial infarction and stroke is increased by 5- to 10-fold in SLE patients compared with the general population (1,2), making it one of the most potent risk factors for cardiovascular events. Indeed, a bimodal pattern of mortality has been described in SLE patients, with coronary death being the leading cause of long-term mortality several years after diagnosis (3). Furthermore, it is expected that the importance of cardiovascular risk assessment and management will keep growing in the years to come, as improvements in treatment strategies lead to overall longer survival rates in SLE patients.
Although coronary vasculitis can be responsible for a clinical event, atherosclerosis is a much more common pathological finding in the coronary arteries in SLE patients, which appear to have accelerated progression compared with the decades-long natural history of atherosclerosis in the general population (4). A number of case-control studies have used vascular imaging to compare subclinical atherosclerosis between SLE patients and age- and sex-matched control subjects. These studies have predominantly involved cardiac computed tomography to assess coronary artery calcification and carotid ultrasound to assess intima-media thickness and carotid plaques (5–8). Overall, these studies suggest that atherosclerosis is more prevalent and severe in SLE patients compared with control subjects, which cannot be explained by traditional risk factors. Accordingly, the disease itself has been hypothesized as a strong contributing factor for accelerated atherosclerosis and/or increased plaque vulnerability.
As previous imaging studies have primarily used traditional approaches focusing on atherosclerotic burden, it remains unknown whether differences in atherosclerotic plaque morphology, tissue composition, or vulnerable features exist in SLE patients compared with the general population, as well as what may be characteristic of atherosclerosis in SLE patients. This knowledge would help to elucidate pathogenesis of cardiovascular events in SLE patients. In a postmortem study of rheumatoid arthritis, another autoimmune disorder associated with increased cardiovascular risk, Aubry et al. (9) found that patients with rheumatoid arthritis actually had a lesser extent of atherosclerosis but a higher incidence of vulnerable plaques and vessel wall inflammation compared with control subjects. In a recent study using multidetector computed tomography to study noncalcified coronary plaque, Kiani et al. (10) reported that noncalcified plaques were associated with SLE activity measures.
Of note, recent advances in vascular imaging have allowed a much more detailed characterization of vessel wall pathologies than traditional imaging approaches used in previous studies. In particular, cardiac magnetic resonance (CMR) has demonstrated its capability to measure plaque tissue composition and, with the use of contrast agents, assess plaque inflammatory activities (11–13). These advanced vascular imaging approaches afford new opportunities to clarify atherosclerotic changes that are characteristic of SLE as well as lupus-specific risk factors.
The study by Varma et al. (14) in this issue of iJACC represents one of the first endeavors using advanced vascular imaging for improved understanding of SLE-associated vessel wall changes in the coronary artery. Inversion-prepared, contrast-enhanced CMR was used to examine coronary wall enhancement in 27 SLE patients without cardiac symptoms, who were then compared with healthy control subjects as well as patients with established coronary atherosclerosis. Distinct coronary wall enhancement was noted in SLE patients and patients with coronary atherosclerosis, but not in healthy control subjects. Furthermore, the enhancement is generalized in most SLE patients in contrast to the “patchy” pattern in patients with established coronary atherosclerosis.
The SLE group in this study is not as well defined due to missing relevant clinical information such as disease duration and medication use, which limited the interpretation of imaging findings. The extent of the difference between SLE patients and control subjects may represent an overestimation of the true differences between SLE patients and the general population because control subjects needed to demonstrate normal coronary arteries on angiography per study protocol. Despite these caveats, the findings from contrast-enhanced CMR clearly provide novel information beyond that of previous studies by showing generalized coronary wall enhancement in SLE patients.
Although the imaging findings add new evidence to the coronary involvement in SLE patients, their proper interpretations can be challenging. Arterial wall enhancement by a gadolinium-based contrast agent is nonspecific and can indicate a number of underlying pathologies such as fibrosis, edema, neovascularization, and inflammation, which are associated with either atherosclerosis or vasculitis. The diffuse and nonregional pattern of enhancement favors vasculitis as the underlying disease. Yet coronary vasculitis is considered a rare condition compared with coronary atherosclerosis and is incompatible with the high prevalence of abnormality. Another viable explanation is that early-stage atherosclerosis that is characterized by endothelial dysfunction and/or intimal hyperplasia, without confluent necrotic core or calcification. The moderate correlations between coronary wall enhancement measurements and traditional cardiovascular risk factors and pulse wave velocity support atherosclerosis as the underlying disease. However, most correlations, with the exception of pulse-wave velocity, were analyzed using the mixed-study sample, in which the inclusion of the group with established coronary atherosclerosis, hence a different pattern of coronary wall enhancement, limited the value of the correlations.
In the absence of histological validation, perhaps a longitudinal study following the subjects over time will help to clarify some of the questions regarding the nature of coronary wall enhancement seen in the SLE group. Will generalized or patchy wall enhancement develop in control subjects? Will the generalized coronary wall enhancement in SLE patients persist, perish, or partition? Will medications matter? The interscan reproducibility of contrast-enhanced CMR was not addressed in this study, but will be key to understanding imaging findings and establishing the technique as a novel approach for risk assessment in SLE patients and others.
Another remaining question is to what extent the finding of generalized coronary wall enhancement indicates increased cardiovascular risk and defines a subgroup of SLE patients who warrants further clinical workup or treatment. Although the imaging finding could indicate pathological changes in the coronary artery, the very high prevalence of enhancement in the SLE group suggests that this phenomenon alone may not be sufficient for this purpose. Further understanding of the natural history of coronary wall enhancement and its associations with other imaging findings are needed.
With more questions raised than answered, the pioneering work by Varma et al. (14) calls for further collaborative efforts between cardiologists, rheumatologists, and radiologists to address these unique challenges in the contemporary management of SLE patients.
↵∗ Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Dr. Sun has reported that he has no relationships relevant to the contents of this paper to disclose. Dr. Yuan has received research grants from Philips Healthcare.
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