Session Type: Abstract Submissions (ACR)
Previous literature supports an increase in cardiovascular (CV) morbidity and mortality in adults with inflammatory joint disease, however it is not known whether children with JIA also carry this risk. While the precise mechanism for accelerated atherosclerosis is unknown, impaired high density lipoprotein (HDL) functionality may contribute to increased CV risk in these patients. It has not been established if younger patients with JIA also have accelerated subclinical disease or alterations in HDL function.
HDL functionality, as measured by cholesterol efflux capacity and receptor expression, NMR spectroscopy, antioxidant activity, and promotion of endothelial function, were compared in JIA patients and controls. Carotid intima-media thickness (cIMT) was measured as a validated, non-invasive surrogate of subclinical atherosclerosis were also compared. Apolipoprotein B depleted serum capacity to promote cholesterol efflux via ABCA-I (J774 macrophages), ABCG-I (baby hamster kidney cells) and SR-BI (Fu5AH hepatoma cells) were measured. Change in mRNA expression of ABCA-I, ABCG-I, and SR-BI on murine bone marrow-derived macrophages upon exposure to serum was assessed. HDL particle distributions were characterized using NMR spectroscopy. Antioxidant activity by arylesterase and ability of serum to promote endothelial cell migration were compared.
29 patients with JIA and 14 healthy controls between the ages of 10-32 were studied. Patients were younger than controls (17.3±6 vs. 21.7±6 years, p= 0.05) and had lower HDL-C (47.0 (40, 56) vs. 56.0 (53, 63) mg/dL, p = 0.04). There was no difference in mean cIMT (0.5 ± 0.05 vs 0.5 ± 0.06, p = 0.27), however, alterations in HDL functionality were noted. JIA patient serum demonstrated greater cholesterol efflux via ABCA-I (17.3 (12.8, 19.7) vs. 10.0 (5.8, 16.0), p=0.05), but less efflux via ABCG-I (3.2 (2.0, 3.9) vs. 4.8 (3.5, 5.8), p=0.01) and SR-BI (6.9 (6.0, 8.4) vs. 9.2 (8.6, 10.2), p=0.002). Exposure of macrophages to patient serum resulted in less expression of ABCA-I (2±0.9 vs. 7±5.7 fold increase, p=0.01), but greater expression of ABCG-I (1.37 (0.88, 1.52) vs. 0.76 (0.71, 1.07) fold increase, p=0.04) and SR-BI (1.3± 0.47 vs. 0.65±0.25 fold increase, p=0.001). JIA patients had less large HDL (5.1 (3.7, 7.3) vs. 8.0 (6.7, 9.7) mg/dL, p=0.04) and less HDL particles (29.5 (27.9, 32.3) vs. 32.9 (31.6, 36.3) particles, p=0.05). Arylesterase activity was lower in JIA patients (128.9±27.6 vs. 152.0±45.2 umoles/min/mL, p = 0.04). Endothelial cell migration was lower upon exposure to patient serum (491.2±68.9 vs. 634.2±227.4 cells/field, p = 0.01).
Although JIA patients did not demonstrate increase in subclincal disease by cIMT compared to controls, they demonstrate changes in HDL functionality despite being on active treatment. These changes may lead to increased CV risk as these patients age further. While larger studies are critical to further characterize HDL functionality and subclinical disease in subsets of JIA patients, these patients warrant close monitoring of CV risk beginning at a younger age than the general population and aggressive, early implementation of CV risk management strategies.
S. J. Spalding,
S. J. Nicholls,
AstraZeneca Pharmaceuticals LP,
Roche Lilly USA, LLC,
Novartis Pharmaceutical Corporation,
Takeda Pharmaceuticals North America, Inc,
M. E. Husni,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/juvenile-idiopathic-arthritis-patients-demonstrate-alterations-in-hdl-functionality-without-accelerated-subclinical-atherosclerosis/