Functional impairment of the arterial wall in primary Sjögren's syndrome: Combined action of immunologic and inflammatory factors

Abstract

Objective. Primary Sjö gren's syndrome (SS) shares clinical and serologic features with rheumatoid arthritis and systemic lupus erythematosus, 2 diseases characterized by acceleration of atherosclerosis. Signs of precocious atherosclerosis have also been shown in SS, although the pathogenic basis of early arterial damage is unclear. The arterial wall was functionally evaluated in SS subjects with analysis of the role played by disease-related factors. Methods. Endothelium-dependent flow-mediated vasodilation (FMV) and endothelium-independent nitrate-mediated vasodilation (NMV) were evaluated in 45 women with SS and 59 age-matched female controls. In addition, serum soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1 (VCAM-1), and nitrotyrosine were detected. Results. Although patient FMV values did not differ from those of control subjects (mean ؎ SD 7.4 ؎ 3.6 versus 7.7 ؎ 1.9; not significant), NMV was lower in SS patients than in controls (mean ؎ SD 8.1 ؎ 3.5 versus 10.3 ؎ 2.1; P < 0.001). Patient NMV was inversely correlated with soluble VCAM-1 levels (r ‫؍‬ ؊0.38, P ‫؍‬ 0.001) and directly correlated with leukocyte count (r ‫؍‬ 0.26, P ‫؍‬ 0.03). An NMV decrease was confirmed in SS patient subsets with evidence of leukopenia, rheumatoid factor, anti-SSB antibodies, and joint involvement. However, patients with joint involvement or parotid enlargement, 2 of the sites mainly affected by chronic inflammation in SS, had an FMV lower than controls and patients without these clinical features. Conclusion. Our results suggest that a functional impairment of the arterial wall may sustain early phases of atherosclerotic damage in SS. A combined effect of disease-related chronic inflammatory and immunologic factors appears to support dysfunction of endothelium and vascular smooth muscle cells, respectively.

Prevalence of and Factors Associated With Increased Arterial Stiffness in Patients With Primary Sjögren's Syndrome

“…This finding apparently contrasts with Gerli et al, who observed a significant reduction in nitrate-mediated vasodilatation in women with primary SS with anti-SSB (10). Nonetheless, these authors did not find an association between anti-SSB and the presence of endothelial dysfunction evaluated by means of flow-mediated vasodilatation (10) or with CIMT (9), although in this latter study an association with anti-SSA was found. These conflicting results may be due in part to differences in patient characteristics and in the methods used for evaluating subclinical atherosclerosis, suggesting that they measure different phenotypes of atherosclerosis.…”

“…The size of the cohort was relatively small, and some statistical significance between subgroups was probably not reached because of a lack of statistical power. However, our study (44 patients and 78 controls) along with the study by Gerli et al (45 patients and 59 controls) (10) are the largest studies (cross-sectional) published to date. Conversely, all of our patients had anti-Ro/SSA, which contrasts with larger cohorts in which the prevalence of this antibody ranged from 50% (35) to 90% (6).…”

Subclinical Atherosclerosis in Systemic Autoimmune Disorders

“…Low HDL cholesterol levels was a constant finding among SS patients in several studies (Vaudo, Bocci et al 2005;Lodde, Sankar et al 2006;Gerli, Vaudo et al 2010). Of interest, HDL along with total cholesterol were found to be associated with immunoglobulin G levels.…”

“…Of interest, in the younger age group (<40y), hypertension was also associated with higher non obesity-related insulin levels, while in the older group (>40y), with age and obesity (Sabio, Vargas-Hitos et al 2011). Arterial hypertension did not seem to influence subclinical atherosclerotic disease in patients with pSS (Vaudo, Bocci et al 2005;Rachapalli, Kiely et al 2009;Gerli, Vaudo et al 2010). …”

“…On the other hand, nitrate mediated vasodilation (NMV) values -detecting smooth muscle relaxation independently of endothelial contribution-were lower in primary SS patients and particularly in those characterized by leukopenia, rheumatoid factor (RF), anti-SSB antibodies, and articular involvement. Of interest, NMV values, were directly correlated to the number of the circulating white blood cells and inversely correlated to vascular cell adhesion molecule 1 (VCAM-1) levels (Gerli, Vaudo et al 2010). …”