Power doppler ultrasound signal predicts abnormal HDL function in patients with rheumatoid arthritis

Abstract

Active rheumatoid arthritis (RA) is associated with increased cardiovascular risk and impaired function of high-density lipoprotein (HDL). Previous work suggests that HDL may become dysfunctional through oxidative modifications within the RA joint. The current work evaluates an association of synovial power doppler ultrasound signal (PDUS) with HDL function and structure. Two open-label clinical therapeutic studies using PDUS as a disease outcome measure were included in this analysis, including a 12-month trial of subcutaneous abatacept in 24 RA patients and a 6-month trial of IV tocilizumab in 46 RA patients. Laboratory assays included assessments of HDL function and structure, HDL and total cholesterol levels, and a cytokine/chemokine panel. Patients with the highest baseline PDUS scores in both clinical studies, had worse HDL function, including suppression of paraoxonase 1 (PON1) activity as well as lower HDL-C levels. Associations between other disease assessments (DAS28 and CDAI) and HDL function/structure were noted but were generally of lesser magnitude and consistency than PDUS across the HDL profile. Treatment with tocilizumab for 6 months was associated with increases in cholesterol levels and improvements in the HDL function profile, which correlated with greater decreases in PDUS scores. Similar trends were noted following treatment with abatacept for 3 months. Higher baseline PDUS scores identified patients with worse HDL function. This data supports previous work suggesting a direct association of joint inflammation with abnormal HDL function.

Trial registration: ClinicalTrials.gov NCT01717859 NCT01299961.

Keywords: High-density lipoprotein; Rheumatoid arthritis; Ultrasound.

Fig. 1

Measures of HDL function, PON1 activity and cholesterol grouped by PDUS tertiles. Panel A shows paraoxonase, arylesterase, and lactonase activities, HII, HDL-C, and TC in patients participating in the abatacept study grouped by PDUS-7 tertile. Panel B shows paraoxonase, arylesterase, and lactonase activities, HII, HDL-C, TC, HDL-ApoA-I, and HDL-Hp in patients participating in the tocilizumab study grouped by PDUS-34 tertile. *p < 0.05 **p < 0.01 ***p < 0.001; pairwise comparisons conducted when ANOVA is statistically significant

Fig. 2

Measures of PDUS grouped by HDL function, PON1 activity and cholesterol tertiles. Panel A shows PDUS-7 values in patients participating in the abatacept study grouped by paraoxonase, lactonase, and arylesterase, HII, HDL-C, and TC tertiles. Panel B shows PDUS-34 values in patients participating in the tocilizumab study grouped by paraoxonase, lactonase, and arylesterase, HII, HDL-C, and TC tertiles. *p < 0.05 **p < 0.01 ***p < 0.001; pairwise comparisons conducted when ANOVA is statistically significant

Fig. 3

Baseline and 6-month tocilizumab treatment values of HDL function, PON1 activity, and cholesterol. *p < 0.05 **p < 0.01 ***p < 0.001