Background/Purpose: Patients with childhood-onset(cSLE) are at significantly increased risk of death from cardiovascular disease when they reach early adulthood. The Atherosclerosis Prevention Pediatric Lupus Erythematous (APPLE) trial was a randomized placebo-controlled trial evaluating the effect of atorvastatin on subclinical atherosclerosis over 3 years, as measured by carotid intima-media thickness (CIMT). Results showed a trend toward reduced CIMT progression in the atorvastatin treated group and that children with SLE have CIMT progression rates greater than children with familial hypercholesterolemia. Additional subgroup analyses showed that post pubertal children with elevated C-reactive protein benefited from statin therapy. Although traditional risk factors play an important role in atherosclerosis progression, they do not fully account for the increased risk seen in SLE and additional biomarkers are needed to identify high risk individuals. Since completion of the APPLE trial, pro-inflammatory high density lipoprotein function (piHDL) function has been identified as a biomarker predictive of both the presence and progression of subclinical atherosclerosis in adult women with SLE. Although higher levels of HDL cholesterol are generally considered to be protective against atherosclerosis, HDL may become inflammatory (piHDL) in the setting of chronic inflammation and promote LDL oxidation and atherosclerosis. This is the first study to evaluate piHDL functionas a predictor of accelerated CIMT progression incSLE.

Methods: Stored baseline plasma from the APPLE trial placebo group (n=94) was tested for piHDL function using a cell-free assay based on piHDL function. Plasma samples were stored at-80°C and had not been previously thawed. Baseline and last follow-up mean mean common CIMT measurements recorded in the APPLE trial were used to calculate the rate of CIMT progression. Accelerated CIMT progression was defined as> 0.002 mm/year. Univariate logistic regression was performed to determine the association between baseline piHDL function and accelerated CIMT progression.

Results: The cohort was 87% female with a mean age of 15.7 years (standard deviation +/- 2.4). The median piHDL function was 1.04 FU, interquartile range 0.49-2.08, similar to values seen in adult women with SLE. Univariate logistic regression showed that every one point increase in piHDL function was associated with a modest yet statistically significant 1.69-fold increased odds of accelerated mean-mean common CIMT progression (95% CI1.08-2.65, p= 0.22).

Conclusion: piHDL may be a useful biomarker to aid in identifying cSLE patients at increased risk for atherosclerosis progression. Further study is underway to evaluate the predictive role of piHDL function as part of a biomarker panel in cSLE.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/pro-inflammatory-high-density-lipoprotein-function-is-associated-with-accelerated-carotid-intimal-medial-thickness-progression-in-childhood-onset-sle/