Cardiovascular Risk and Endothelial Dysfunction in Primary Sjogren Syndrome Is Related to the Disease Activity.

Anna Łuczak,Adrian Doroszko,Ewa Szahidewicz-Krupska,Michał Kulus,Rafał Małecki,Marta Madej

doi:10.3390/nu13062072

Abstract

The aim of our study was to evaluate if endothelial-dysfunction (ED) occurs in patients with primary Sjogren syndrome (pSS) and whether it is associated with the disease characteristics and activity. A total of 46 patients with pSS and 30 controls, without known cardiovascular disease, were enrolled in this study. A flow-mediated-dilation (FMD) of the brachial artery, plasma concentrations of the nitric oxide (NO) metabolic pathway (ADMA, L-arginine, SDMA, cGMP), and markers of endothelial inflammatory function (PAI-1, sE-selectin) and angiogenesis (angiostatin, VEGF) were analyzed. The FMD was significantly lower in pSS patients (7.56 ± 3.08 vs. 10.91 ± 1.02%, p = 0.043) and positively correlated with the Ro/SS-A-antibodies (r = 0.34, p = 0.03), pulmonary involvement (r = 0.52, p = 0.001) and inversely with ADMA (r = −0.35, p = 0.04). Plasma ADMA, L-arginine and angiostatin levels were significantly higher in pSS patients (0.39 ± 0.08 vs. 0.36 ± 0.06 µmol/L, p = 0.05; 29.07 ± 6.7 vs. 25.4 ± 5.23 µmol/L, p = 0.01; 152.25 ± 60.99 vs. 120.07 ± 38.7 pg/mL, p = 0.0, respectively). ADMA was associated with ESSDAI (r = 0.33, p = 0.02), SCORE (r = 0.57, p = 0.00003) and focus score (r = 0.38, p = 0.04). In the multiple regression analysis, the ESSDAI was significantly and independently associated with plasma ADMA levels (β = 0.24, p = 0.04). Moreover, plasma cGMP concentrations were negatively correlated with the disease duration (r = −0.31, p = 0.03). Endothelial function is impaired in patients with pSS and associated with the measures of disease activity, which supports the key-role of inflammation in developing and maintaining accelerated atherosclerosis.

Highlights

Cardiovascular disease (CVD), due to accelerated atherogenesis, has been recognized as an important morbidity and mortality cause in rheumatic autoimmune diseases
Knowing that inflammation can accelerate atherogenesis, we investigated whether chronic systemic inflammation can alter endothelial function and searched for an association between endothelial functional phenotype and disease activity
Increased angiostatin levels and the inverse association between VEGF and FMD observed in this study indicate that impaired angiogenesis could be a result of impaired endothelial function, which was demonstrated in animal models [34]

Summary

Introduction

Cardiovascular disease (CVD), due to accelerated atherogenesis, has been recognized as an important morbidity and mortality cause in rheumatic autoimmune diseases. This excess CV burden is partly mediated by chronic systemic inflammation along with the increased prevalence of conventional risk factors. Inflammation can accelerate the atherogenesis via inflammatory cell infiltration into the vascular wall and endothelial dysfunction (ED). Some evidence suggests that the vascular endothelium may be a key interface between inflammation and atherogenesis and its altered function precedes the development of morphological changes. Many studies have shown that endothelial function improves with risk reduction therapies or during treatment with anti-rheumatic drugs [4,5]

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