ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 544

Power Doppler Ultrasound Signal Associates with Abnormal HDL Function and Suppression of Paraoxonase 1 Activity in Patients with Rheumatoid Arthritis

Christina Charles-Schoeman1, Ani Shahbazian2, Buzand Oganesian3, Cesar Olmos4, Ami Ben-Artzi5 and Veena Ranganath6, 1University of California, Los Angeles, Los Angeles, CA, 2Medicine-Rheumatology, University of California, Los Angeles, Los Angeles, CA, 3Medicine-Rheumatology, University of California, Los Angeles, Los ANgeles, CA, 4Medicine, Division of Rheumatology, University of California, Los Angeles, Los Angeles, CA, 5Rheumatology, University of California, Los Angeles, Beverly Hills, CA, 6Department of Medicine, Division of Rheumatology, University of California, Los Angeles, Los Angeles, CA

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: ,

Session Information

Date: Sunday, November 13, 2016

Session Title: Rheumatoid Arthritis – Clinical Aspects - Poster I: Clinical Characteristics/Presentation/Prognosis

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:  Musculoskeletal ultrasound (MSUS) can detect synovitis by Power doppler (PDUS) and can predict erosive progression on xrays in rheumatoid arthritis (RA) patients. Our previous work has reported an association of active RA with impairment in HDL function and suppression of paraoxonase-1 (PON1) activity, a novel risk factor for cardiovascular disease (CVD), which has been associated with carotid plaque in RA patients. In the current work we evaluated an association of PDUS signal with HDL function and PON1 activity in patients with RA.

Methods:   Assessment of PDUS was performed on 24 RA patients naive to biologics in a pilot 12 month open-label study of subcutaneous abatacept. Seven joints were scanned by MSUS of the most affected side (wrist, MCP joint 2/3, PIP joint 2/3 and MTP joint 2/5) according to Backhaus et al. (A&R 2009;61:1194-201). PDUS was scored semiquantitatively according to published consensus definitions (J Rheum. 2005;32:2485-7). HDL’s anti-oxidant function was measured by a cell free assay as described previously (A&R 2009; 60(10): 2870-9). PON1 activity was measured by a previously published assay with minor modifications (A&R 2012; 64(6):1828-37). Total and HDL cholesterol (HDL-C) levels were determined by standard methods.

Results:   Patients with the highest baseline PDUS score (first tertile PDUS) had significantly worse HDL function as measured by a higher HDL inflammatory index (HII) compared to patients with lower baseline PDUS signals in the second and third PDUS tertiles (table). A higher PDUS score was significantly correlated with a higher HII (r= 0.50, p=0.01, n=24). In contrast, HDL-C and PON1 activity levels were lower in patients with high PDUS scores (table) and a significant inverse correlation was noted between PDUS score and PON1 activity (r=- 0.45, p=0.03, n= 24). Associations between other disease assessments (ESR, DAS28, or CDAI) and HDL function and PON1 activity were noted, but were of lesser magnitude than correlations with PDUS score (r values = -0.20- 0.30, all p values >0.15). Following treatment with abatacept for a minimum of 3 months, patients with the greatest decreases in PDUS showed modest associations for greater improvement in HDL function, PON1 activity, and HDL-C levels compared to patients with the lesser change in PDUS (table).

Conclusion:   In a pilot study of 24 RA patients naïve to biologics, higher baseline PDUS scores identified patients with worse anti-oxidant function of HDL and lower PON1 activity. Improvement in PDUS score with abatacept treatment showed trends for improvement in HDL function, PON1 activity, and HDL-C levels. This data supports previous work suggesting a direct association of joint inflammation with abnormal HDL function, and suggests that further evaluation of PDUS as a non-invasive CV risk assessment tool in RA may be warranted.

 

  Tertile 1 PDUS-Baseline (n=8) Tertile 2 PDUS- Baseline (n=7) Tertile 3 PDUS- Baseline (n=9)
PDUS Score 12.4 ± 1.8 7.0 ± 1.0* 3.8 ± 1.1*
Age (years) 56 ± 12 39 ± 13* 53 ± 10
Gender (% female) 75 100 100
Ethnicity (% hispanic) 13 29 22
Race (% caucasian) 63 100 44
Methotrexate (% use) 63 57 22
Hydroxychloroquine (% use) 0 14 11
Prednisone (% use) 13 29 22
ESR (mm/hr) 56 ± 30 34 ± 17 39 ± 14
DAS28 (ESR, 4
variable) 		6.7 ± 0.7  6.3 ± 0.8 5.9 ± 0.4*
CDAI 41 ± 6 39 ± 5 31 ± 4*
Total Cholesterol (mg/dL) 197 ± 63 208 ± 75 210 ± 51
HDL Cholesterol (mg/dL) 58 ± 16 69 ± 20 70 ± 28
HDL Inflammatory Index (HII) 4.47 ± 2.00 1.78 ± 0.56* 2.01 ±0.72*
PON1 Activity 82 ± 61 89 ± 54 170 ± 130
  Tertile 1 PDUS ∆ (n=7) Tertile 2 PDUS ∆ (n=9) Tertile 3 PDUS ∆ (n=8)
Absolute Change in PDUS Score -8.3± 2.4 -2.9 ± 1.1* 0.63 ± 1.9*
Absolute Change in HII -1.36 ± 2.94 -0.22 ± 1.44 -0.53 ± 0.85
Absolute Change in PON1 Activity 8 ± 36 -33 ± 103  -45 ± 93
Absolute Change in HDL-C 25 ± 19 3 ± 44  7 ± 25

PDUS= power doppler ultrasound, ESR=erythrocyte sedimentation rate, DAS28=disease activity scale with 28 joint count, CDAI=clinical disease activity index, HDL= high density lipoprotein, PON1=paraoxonase 1. *P<0.05 compared to Tertile 1. Slight tertile size variability due to grouping of patients with the same PDUS baseline score/PDUS ∆ score in the same tertile for unbiased comparisons.

Disclosure: C. Charles-Schoeman, None; A. Shahbazian, None; B. Oganesian, None; C. Olmos, None; A. Ben-Artzi, None; V. Ranganath, Bristol-Myers Squibb, 2,Bristol-Myers Squibb, 5,Genentech and Biogen IDEC Inc., 2,Pfizer Inc, 2.

To cite this abstract in AMA style:

Charles-Schoeman C, Shahbazian A, Oganesian B, Olmos C, Ben-Artzi A, Ranganath V. Power Doppler Ultrasound Signal Associates with Abnormal HDL Function and Suppression of Paraoxonase 1 Activity in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/power-doppler-ultrasound-signal-associates-with-abnormal-hdl-function-and-suppression-of-paraoxonase-1-activity-in-patients-with-rheumatoid-arthritis/. Accessed November 28, 2020.

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