Several studies have shown that patients with systemic lupus erythematosus (SLE) have more frequent and more precocious atherosclerosis than the general population (1–3), but the etiology and pathophysiology of premature atherosclerosis in SLE are poorly understood (4). The mechanisms of atherosclerosis in SLE patients are probably multifactorial. Several possible mechanisms for ischemia, such as vasculitis, vasospasm, microvascular disease, and thrombosis with or without atherosclerosis, are potential causes of coronary events. Other identified risk factors for cardiovascular disease that may contribute to the coronary disease in SLE patients include circulating immune complexes, activated T cells, antiphospholipid antibodies, and hyperhomocysteinemia (2, 3, 5, 6).
Screening tests for coronary artery disease (CAD) are useful in high-risk patients (7). Detection of atherosclerosis in an early preclinical stage could avoid future cardiovascular events, since preventive interventions could be initiated in these patients (3). Moreover, the use of vascular imaging techniques in cardiovascular research could advance our understanding of the prevalence and mechanisms of CAD in patients with SLE (5).
Myocardial perfusion abnormalities have been reported in 16–82% of SLE patients (8–12). Patients in the general population who have traditional risk factors for CAD and abnormal findings on myocardial scintigraphy usually undergo coronary angiography. However, there have been no published studies of the angiographic evaluation of coronary arteries in SLE patients who have abnormal findings on myocardial scintigraphy.
The aim of this study was to evaluate findings on coronary artery angiography in SLE patients in whom myocardial scintigraphy revealed abnormalities. The secondary objective was to evaluate the possible association between the presence of atherosclerotic plaques on coronary angiography and the following parameters: traditional risk factors for CAD, the number of American College of Rheumatology (ACR) criteria met, the SLE Disease Activity Index (SLEDAI) score, and the Systemic Lupus International Collaborating Clinics/ACR (SLICC/ACR) damage index (DI) score.
- Top of page
- PATIENTS AND METHODS
In the present study, we found that 33% of 90 SLE patients with disease duration of >5 years had abnormal findings on myocardial scintigraphy. This is the first study in which coronary angiography was performed in SLE patients in whom abnormalities were identified on myocardial scintigraphy. We found that in 38% of the patients with abnormal scintigraphic features, coronary lesions were identified by angiography. In 67% of the SLE patients with abnormal scintigraphic findings and at least 4 risk factors for CAD, coronary angiography revealed the presence of stenosis.
In the general population, the measurement of subclinical disease provides an approach to identifying individuals who may be at high risk of developing clinical cardiovascular events (27). In the literature, there is no consensus about the best diagnostic method for evaluating subclinical CAD in SLE patients. Coronary angiography is too invasive and would be unethical to use for the initial evaluation of SLE patients with CAD risk factors. Coronary artery scanning by electron beam computed tomography (EBCT) has been used to measure noninvasively the deposition of calcium in the coronary artery walls. EBCT may be able to detect premature atherosclerosis in SLE patients (5, 28). However, this method is not widely available, and it is a very expensive procedure. Measurement of carotid artery intima-media thickness by B-mode ultrasound is a noninvasive method of predicting the future incidence of coronary disease in the general population (29). Potentially modifiable risk factors, including traditional coronary risk factors, SLE-related factors, and inflammation markers, have been found to be associated with vascular disease detected by this method (30, 31). No study has demonstrated the usefulness of this method for selecting SLE patients to undergo more invasive coronary tests.
Previous studies have demonstrated the prognostic value of myocardial perfusion scintigraphy with pharmacologically induced stress (dipyridamole infusion) performed with SPECT images using 99mTc-sestamibi in patients with CAD risk factors (32–34). This noninvasive tool shows high sensitivity (95–100%) and variable specificity (75–100%) (35). Hypoperfusion observed on myocardial scintigraphy suggests the presence of ischemia in the case of reversible perfusion defects and fibrosis in the case of fixed defects (36, 37). However, correlation between myocardial hypoperfusion and CAD is not perfect. The sensitivity of cardiac scintigraphy increases with an increasing number of injured vessels (37), and its predictive value depends on the population being tested (38).
Abnormal myocardial scintigraphic findings with normal coronary angiographic findings may occur in cases in which angiography cannot identify coronary disease because of inadequate projections, the presence of the diaphragm overlying the vessels, congenital anomalies of coronary arteries, and intra- and interobserver differences (37). False-positive results on myocardial scintigraphy could occur in patients with mitral valve prolapse, myocardial bridge, Chagas' disease, aortic stenosis, left bundle branch block, Wolff-Parkinson-White syndrome, breast and diaphragm attenuation, motion artifacts, and reconstruction artifacts (37, 39). In the present study, we tried to reduce factors that could potentially impair the scintigraphic results, as described in Patients and Methods. Moreover, none of our patients had Wolff-Parkinson-White syndrome, Chagas' disease, or significant valve disease that could cause abnormal scintigraphic results. The frequency of abnormal findings on myocardial scintigraphy in our study is consistent with those from other studies of SLE patients (8–12).
In recent years, several studies in the general population have focused on the role of the endothelium in regulating epicardial coronary artery vasomotor tone and in modulating coronary microvascular function (40, 41). Coronary microvascular endothelial dysfunction is a possible explanation for chest pain symptoms in patients with normal findings on coronary angiography or with minimal coronary atherosclerosis (42, 43). Moreover, severe endothelial dysfunction in the absence of obstructive CAD has been associated with an increased frequency of cardiac events (44). CAD risk factors that include the presence of arterial hypertension and hypercholesterolemia, the total number of CAD risk factors, and age >50 years have been associated with impairment of endothelial vasoactive function in coronary arteries (45–47). Lima et al (48) used a high-resolution ultrasound technique to measure brachial artery diameter at rest and after flow-induced dilation, and demonstrated that endothelial function is impaired in SLE patients even in the absence of traditional risk factors for CAD. SLE-related risk factors, such as inflammatory and immunologic factors, may be important triggers in the induction of the early stages of vascular disease.
The absence of detectable lesions on angiography in many of our SLE patients with abnormal myocardial scintigraphic findings does not exclude the possibility that atherosclerosis is present in an early/subclinical stage. Hasdai et al (41) showed that coronary endothelial dysfunction may be temporally associated with myocardial perfusion defects, which supports the role of coronary epicardial and microcirculation endothelium in regulating myocardial perfusion. Vessels that are apparently normal on angiography could be affected by an endothelial dysfunction that may be considered an early atherosclerotic process. Endothelial dysfunction may account for normal angiographic results in our patients with abnormal scintigraphic results (41–44). Indeed, in a recent study using a high-resolution ultrasound technique (49), we observed a significant association between myocardial perfusion defects and endothelial dysfunction in the brachial artery.
Although some studies have shown that assessment of the angiographic severity of coronary stenosis may be inadequate to accurately predict the time or location of a subsequent coronary occlusion associated with acute myocardial infarction (50–52), the value of coronary angiography remains unquestioned, and this procedure is considered the gold standard technique for defining the anatomy of coronary vessels and determining whether conservative or invasive treatment is the best approach.
In our study, the presence of CAD risk factors was associated with abnormal scintigraphic results. Performing coronary angiography in 21 SLE patients with abnormal myocardial scintigraphic results, we found that angiographic abnormalities were associated with the presence of at least 4 risk factors for CAD. We also found a significant association between the presence of angiographic abnormalities and arterial hypertension and postmenopause status, confirming the importance of traditional risk factors for CAD in the development of atherosclerosis in SLE patients and showing the necessity of developing strategies to better control these factors in SLE patients.
This is the first study in which angiography was performed to evaluate abnormal myocardial scintigraphic findings in SLE patients. Despite the relative limitation of the small number of patients in whom coronary angiography was performed, our study showed that 38% of patients with abnormal findings on myocardial scintigraphy had coronary lesions detected on angiography. Patients with abnormal myocardial scintigraphic findings and at least 4 risk factors for CAD had a higher risk of abnormal findings on coronary angiography. These data suggest that myocardial scintigraphy can be used to screen SLE patients and that all patients with abnormal scintigraphic findings and at least 4 risk factors for CAD should undergo coronary angiography.
- Top of page
- PATIENTS AND METHODS
We are grateful for the financial support by the FAPESP. We thank Wagner A. Leite, MD, and Japy A. Oliveira Filho, MD, PhD (Cardiology Division, Universidade Federal de São Paulo, Escola Paulista de Medicina), for performing the dipyridamole-induced stress tests. We also thank the members of the Invasive Cardiology Division for performing the coronary angiographies and Gilberto Alonso, MD, PhD, and Marta M. Sevillano, MD, for performing the analyses of the myocardial scintigraphy images.