Background/Purpose: Clinical and biochemical data suggest that autoimmune diseases are associated with endothelial dysfunction and increased atherosclerosis. We have previously shown that asymmetric dimethylarginine (ADMA) levels and coronary flow reserve (CFR) are impaired in patients with early rheumatoid arthritis, but it is not known whether the same is true of patients with  primary Sjögren’s syndrome (SS). We therefore investigated sub-clinical cardiovascular involvement in primary SS patients by means of ADMA and coronary flow reserve (CFR) assessments.

Methods: The study involved 15 patients who fulfilled the ACR criteria for primary SS without any documentable cardiovascular disease and 20 age- and gender-matched control subjects. Dipyridamole transthoracic stress echocardiography was used to evaluate wall motion and CFR in the distal segment of the left anterior descending coronary artery before and after dipyridamole infusion (0.86 mg/kg over six minutes). A CFR value of <2.5 was considered a sign of impaired coronary functionPlasma ADMA levels were determined using high-performance liquid chromatography. Linearity was assessed in the range of ADMA 0.1-20 μM. The mean correlation coefficient was >0.99. The ADMA limit of quantitation (LOQ) was 0.01 μM.The continuous variables were expressed as mean values and standard deviations, and the non-continuous variables as median values and interquartile ranges (IQR). The data were analysed using SAS statistical software 9.2. All tests were two-tailed, and probability (p) values of less than 0.05 were considered statistically significant.

Results: All of the patients were affected by primary SS, the majority of patients were being treated with hydroxychloroquine (HCQ) at dose of 400 mg/day, two were taking methotrexate (MTX) and four azathioprine (AZA) at a mean dose of 150 mg/day (range 50-200 mg). Only 3 patients used corticosteroids – one at a dosage of 2.5 mg and two at 5 mg/daily. All of the patients were ANA and/or RF and anti-SSB and/or anti-SSA positive.  The patients’ mean age and ejection fraction were respectively 62 ± 8 years and 65% ± 6% (not significant). Although within the normal range, their CFR was lower than that of the controls ( median 3.0, IQR  2.5 – 3.5 vs median 3.4, IQR 3.2 – 3.82, P=0.02 ), whereas their ADMA levels were significantly higher (median 0.80 mM, IQR 0.78-0.82mM vs median 0.55mM, IQR 0.49-0.59mM respectively; P <0.0001) and their E/A ratios significantly lower ( median 0.8, IQR 0.7 - 1.1 vs median 1.3, IQR 1.3, 1.2 – 1.4; P <0.0001).

Conclusion: Higher ADMA levels suggest the presence of endothelial dysfunction and sub-clinical atherosclerosis in primary SS patients, even in the case of normal CFR. Our preliminary data indicate that ADMA may be a useful marker for identifying early endothelial dysfunction in primary SS patients.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/coronary-flow-reserve-and-asymmetric-dimethylarginine-levels-new-measurements-for-identifying-subclinical-atherosclerosis-in-patients-with-primary-sjogrens-syndrome/