Arterial stiffness by oscillometric device and telomere lenght in juvenile idiopathic artrhitis with no cardiovascular risk factors: a cross-sectional study

In JIA patients, PWV is increased and TL is reduced, findings positively related to inflammatory activity.

PWV was assessed by an oscillometric non invasive device through brachial artery occlusion (CardioSDyna – MAPA +). Patients followed the American Heart Association recommended instructions [3] for standard assessment of arterial stiffness. They were oriented to not use any vasoactive drugs 12 h before the evaluation and to avoid caffeine four hours before procedure.

For measures, patients rested in the supine position for ten minutes in a quiet room. Patients should not spoke during the measurement to prevent the influence of speaking on arterial tone. Evaluations were always in the morning to control for the diurnal variation of arterial stiffness. Measurements were always made by the same observer and two consecutive measurements were performed.

For TL, 10 ml of peripheral blood sample was collected in a matched way to the routine assessment, not representing additional procedure. qPCR was performed. Peripheral mononuclear cells were purified. Genomic DNA was extracted by phenol/chloroform/ isoamyl alcohol [11]. The relative telomere length was performed by calculating the ratio (T/S) of a quantitative PCR product from the same sample using specific primers for telomeres and a single copy gene as described by Cawthon [12].

Inflammatory activity was assessed by Juvenile Arthritis Disease Activity Score with 27 joints (JADAS-27) [13].

Twenty-four JIA patients, twenty-one controls for TL and 20 controls for PWV were included. Between cases and controls for PWV, there was no significant difference in age, gender, ethnics and BMI. Between cases and controls for TL there was significant difference in age (15.5 ± 6.3 years vs. 11.4 ± 1.3 years, P = 0,005), no differences in gender, ethnics and BMI (Table 1). The JADAS median was 8 [0–20], indicating moderate to high disease activity. This result was more influenced by parents/patient global assessment of well-being by visual analog scale (Spearman test r = 0.872, P = 0, 001) than erythrocyte sedimentation rate (Spearman test r = 0.277, P = 0, 201). Oligoarticular subtype was 65.2% and there was no prematurity in the group (Table 1).

No patient was receiving anti-inflammatory drugs. Disease modifying activity drugs were used in 95.7% of the group, about 30% were in corticosteroids use and the same proportion of patients was using biologic drugs, only Anti-TNF (Table 1).

PWV was normal in all patients, JIA and controls. The average PWV was 5.1 ± 0.20 m/s vs. 4.98 ± 0.06 m/s, P = 0,66). There was no correlation between pulse pressure and PWV (r = 0.172, P = 0. 434) and JADAS (r = 0,283, P = 0.191). There was a minimal variation between genders: 39.8 ± 8.68 mmhg among males and 38.8 ± 10.0 mmhg in females.

There was a significant difference in T/S ratio for telomere length between JIA patients and controls (0.85 ± 0.34 vs.1.67 ± 1.38, P = 0.025) (Fig. 1). When age adjusted by ANCOVA, the difference remains significant (p = 0, 032). There was no significant difference between JIA subtypes, gender and no association between T/S ratio and JADAS and disease duration. The coefficient of variation was 11%.

TL was shortened in JIA group of patients, oligoarticular and polyarticular subtypes, with long disease duration, high to moderate disease activity and no cardiovascular risk factors, compared to controls. There was no difference in PWV values among these groups and there was no correlation between TL and PWV in this group of JIA patients.

Our findings shown no evidence of correlation between TL and PWV, variables highly influenced by aging, in a JIA group of patients, composed by oligoarticular and polyarticular subtypes, long disease duration and disease activity considered as moderate to high.

As far as we know, this is the first study to test the correlations between those variables in rheumatic diseases and in paediatrics.

PWV and pulse pressure values were normal in JIA patients. In literature, we found five studies to evaluate PWV in JIA patients using different methods and with a high heterogeneity in subtypes selected [14‐18] making comparisons difficult. We observed that studies that did not exclude cardiovascular risk factors had positive findings for PWV [14, 16‐18]. Our findings are in agreement with the Vlahos et al. study, which excluded those factors, and found no difference in PWV values by tonometry. We believe these findings could be pointing to a greater role of atherosclerosis in JIA patients, but no arteriosclerosis. More studies are necessary to clarify this setting. We found no other studies to use oscillometry in JIA, a method highly applicable and with good correlations with other methods to assess PWV [5].

In relation to TL, Prelog et al. and Dvergstein et al. [17, 18] tested T cells and found significant differences in JIA compared to controls. Both authors believe there is evidence to indicate premature immunosenescence in JIA. Dvergstein et al. found a naive T cell compartment with shortened telomeres and reduced proliferative capacity in JIA. In the study of Prelog et al., telomeric erosion was increased in CD4+, CD45RA+ with no correlations between age, sex, disease duration, use of methotrexate and corticosteroids, which are in agreement to our findings. In rheumatoid arthritis, a similar study also found no correlations between disease duration, disease activity index and therapy [9]. The authors support the idea that telomere shortening could be associated to an intrinsic defect in telomere maintenance or low activity of telomerase than to disease activity or immunosuppressive therapy. What is the meaning of telomere shortening in JIA remains a question to be answered for more studies, different than the cross-sectional design, which are majority in this area.