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Accelerated atherosclerosis is a recognised leading cause of morbidity and mortality in systemic lupus erythematosus (SLE),1 and therefore the identification of patients with SLE at risk for cardiovascular (CV) events is important. However, the mechanisms of premature atherosclerosis associated with SLE are still unknown, with lupus itself a possible candidate and the role of traditional and non-traditional risk factors still uncertain.2–4 It has been recently suggested that mechanisms inherent to SLE might predispose the vascular wall to acceleration of the atherosclerotic process through traditional risk factors.5
METHODS AND RESULTS
We performed high resolution carotid ultrasonography in 48 consecutive patients (43 women, 5 men, aged 19–77 years) fulfilling the American Rheumatism Association criteria for SLE,6 without clinical evidence of overt atherosclerosis or diabetes. Plaque at carotid bifurcation was found in 6/48 (13%) and abnormal intimal medial thickness (IMT, considered “abnormal” if > 0.7 mm) in 8/48 (17%) patients.
Older age and high blood pressure were confirmed to be strongly associated with carotid lesions. Patients with plaque or abnormal IMT were significantly older (mean (SD) 69 (7) v 39 (12) years or 62 (14) v 39 (14) years, p<0.0001 and p = 0.0014, respectively) and higher blood pressure (>140/90 mm Hg or treatment with antihypertensive drugs) was also more common in plaque positive (67%) than in plaque negative (7%) patients (p = 0.0001).
Moreover, among traditional risk factors, we found that men with SLE tended to have plaque more often (20%) than women with SLE (12%), in accord with recent observations both on patients with SLE and the general population.4,7
We did not find any relationship between carotid abnormalities, cumulative prednisone intake, or inflammation markers (erythrocyte sedimentation rate, fibrinogen, and C reactive protein). As recently pointed out,2 inflammation markers, which fluctuate as a consequence of disease activity and treatment, cannot serve as suitable risk markers in SLE, even if increasing evidence indicates that atherosclerosis is an inflammatory disease.
An intriguing finding of our study was the negative association between carotid abnormalities and antinuclear antibodies (ANA). Plaque was more common in ANA negative patients (40%) than in ANA positive patients (9%) (p = 0.0495). Our observation may be consistent with the recent study of Roman et al,3 who found that anti-Sm and anti-RNP autoantibodies were less common in patients with plaque, and none of the six Sm positive patients of our series had plaque. Interestingly, it has been recently suggested that Sm antibodies exert a protective effect against coronary artery calcification in SLE.8
Although the role of autoantibodies in atherosclerosis,9 and particularly in accelerated atherosclerosis of SLE, is still a matter of debate,3,10 the proposed existence of two clinical patterns of SLE, one at higher risk of CV events, characterised by limited autoantibody production, and the other at lower risk but with a wider autoantibody spectrum,3 opens a new promising research agenda.
Because in atherosclerosis there is evidence for an involvement of humoral immunity, an inappropriate autoimmune response inherent to the process of SLE might have a role in chronic plaque development. On the other hand, aggressive immunosuppressant drugs for more severe diseases might lower or even suppress autoantibody production. Moreover, a genetic predisposition linked to autoantibody repertoires and to clinical subsets of disease cannot be ruled out.
More studies are needed to assess whether ANA testing might represent an additional tool for identifying patients with SLE at risk for CV events.
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