Session Information
Date: Monday, October 22, 2018
Title: Muscle Biology, Myositis and Myopathies Poster II: Basic and Translational Science
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Damage to the vascular endothelium is strongly implicated in the pathogenesis of dermatomyositis (DM) and to a lesser degree other idiopathic inflammatory myopathies (IIM). Normal high density lipoproteins (HDL) protect the vascular endothelium from damage due to oxidized phospholipids, which accumulate under conditions of oxidative stress. The current work evaluated the function of HDL in a longitudinal cohort of 182 IIM patients.
Methods: The anti-oxidant capacity of HDL was measured by a cell free assay as described previously (A&R2009; 60(10): 2870-9) and reported as the HDL inflammatory index (HII). Lipoprotein cholesterol levels were measured by standard methods and traditional cardiovascular risk factors, medication use, and myositis disease characteristics were assessed for all patients. Univariate analysis evaluated the clinical characteristics of IIM patients by three groups of HDL function defined by HII; tertile 1 contained patients with the highest HII, consistent with severe HDL dysfunction, and tertile 3 contained patients with the lowest HII, consistent with the most protective HDL. Multivariate logistic regression analyses were performed to evaluate correlates of dysfunctional HDL in the IIM cohort.
Results: Patients with the most dysfunctional HDL, (tertile 1 HII) had the highest myositis disease activity levels, as measured by both physician global visual analogue scales (VAS) as well as serum CPK levels, compared to lower HII tertiles (Table 1). DM diagnosis was most prevalent in tertile 1 of HDL function (Table 1). There were no significant differences in demographics or traditional cardiovascular risk factors between tertiles. Disease activity measures and DM diagnosis remained significantly associated with dysfunctional HDL in independent multivariate models, after controlling for variables significantly different between tertiles in univariate analysis, as well as variables previously associated with abnormal HDL function including age and statin use (Table 2).
Conclusion: Abnormal anti-oxidant function of HDL was significantly associated with myositis disease activity and DM diagnosis in a large cohort of 182 IIM patients. Abnormal HDL function may warrant further investigation as a mechanism of microvascular damage and increased cardiovascular risk in DM patients.
Table 1Clinical data of IIM patients by tertiles of HDL anti-inflammatory function
|
|
Tertile 1 (n=61) |
Tertile 2 (n=61) |
Tertile 3 (n=60) |
|
HDL Inflammatory Index (HII) |
1.21 ± 0.62*† |
0.53 ± 0.09* |
0.23 ± 0.05† |
|
Age (years) |
50 ± 14 |
51 ± 15 |
51 ± 15 |
|
Female, (%) |
72 |
69 |
73 |
|
Race, (% Caucasian) |
72 |
83 |
73 |
|
Ethnicity, (% Hispanic) |
22 |
18 |
17 |
|
ESR |
34 ± 29 |
28 ± 24 |
27 ± 25 |
|
HSCRP |
7.7 ± 12.0 |
4.7 ± 8.3 |
6.5 ± 9.7 |
|
Lipid panel |
|||
|
Total Cholesterol |
209 ± 50 |
210 ± 52 |
205 ± 50 |
|
LDL Cholesterol |
121 ± 44 |
128 ± 46 |
113 ± 3 |
|
HDL Cholesterol |
59 ± 24 |
57 ± 20 |
58 ± 19 |
|
Triglycerides |
182 ± 137 |
156 ±93 |
169 ± 124 |
|
Traditional CVD risk factors |
|||
|
Body Mass Index |
27.7 ± 6.3 |
27.8 ± 6.5 |
27.6 ± 5.8 |
|
Hypertension, % |
26 |
30 |
28 |
|
Diabetes, % |
11 |
11 |
17 |
|
Current Smoker, % |
3 |
2 |
0 |
|
Past Smoker, % |
15 |
30 |
17 |
|
H/o CVD (% yes) |
2 |
2 |
3 |
|
Statin use, % |
11 |
8 |
14 |
|
IIM characteristics |
|||
|
Disease Duration (yrs) |
4.5 ± 7.8* |
3.6 ± 7.4 |
4.3 ± 5.0† |
|
DM Disease Diagnosis, (% DM) |
75 |
75 |
50# |
|
CPK Level, (U/L) |
867 ± 1989† |
405 ± 1123 |
562 ± 1199 |
|
Physician Global Disease Activity (VAS) |
43 ± 21* |
40 ± 18 |
34 ± 17 |
|
Physician Global Disease Activity (Likert) |
1.89 ± 0.95 |
1.69 ± 0.73 |
1.56 ± 0.65 |
|
Physician Global Disease Damage (VAS) |
37 ± 23 |
31 ± 25 |
34 ± 21 |
|
Physician Global Disease Damage (Likert) |
1.63 ± 0.96 |
1.40 ± 1.11 |
1.51 ± 0.85 |
|
% ILD |
47 |
28 |
47 |
|
Rituximab (% use) |
10 |
5 |
5 |
|
Cyclophosphamide (% use) |
7 |
7 |
3 |
|
Hydroxychloroquine (% use) |
18 |
18 |
28 |
|
IVIG (% use) |
21 |
23 |
19 |
|
Mycophenalate mofetil (%use) |
28 |
18 |
25 |
|
Prednisone (% use) |
70 |
64 |
76 |
|
Prednisone dose (daily) |
19 ± 24 |
15 ± 19 |
15 ± 18 |
|
Methotrexate (% use) |
18# |
36 |
19 |
|
Leflunomide (% use) |
2 |
0 |
5 |
|
Azathioprine (% use) |
12 |
5 |
19 |
|
*p value < 0.05 compared to tertile 3 †p value <0.05 compared to tertile 2 # p<0.05 for Chisquare test of categorical variables |
|||
Table 2Multivariable logistic regression models of dysfunctional HDL (tertile 1 HII)
|
Explanatory Variable |
Model 1 |
Model 2 |
|
Age, years |
1.009 (0.98-1.04) 1.75 (0.29-11.15) |
1.004 (0.98-1.03) 1.32 (0.21-8.34) |
|
Disease duration, years |
1.03 (0.96-1.10) 2.44 (0.26-25.7) |
1.02(0.95-1.09 1.80(0.19-20.84) |
|
DM diagnosis (vs PM) |
3.73 (1.51-9.78)* |
4.9 (1.7-15.8) * |
|
MTX use |
0.84 (0.30-2.34) |
0.84 (0.29-2.39) |
|
Statin use |
0.43 (0.11-1.64) |
0.94 (0.24-3.78) |
|
Physician Global Disease Activity |
1.03 (1.01-1.05)* 10.7 (1.7-76.8) |
– |
|
CPK level |
– |
1.0002 (1.0000-1.0006)* 26.7 (1.08-1653.4)* |
|
*p<0.05 Model 1: Physician global disease activity in VAS Model 2: CPK level |
||
To cite this abstract in AMA style:
Bae S, Wang J, Shahbazian A, Oganesian B, Golub I, Reddy ST, Charles-Schoeman C. Abnormal Function of High Density Lipoproteins in Idiopathic Inflammatory Myopathies [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/abnormal-function-of-high-density-lipoproteins-in-idiopathic-inflammatory-myopathies/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/abnormal-function-of-high-density-lipoproteins-in-idiopathic-inflammatory-myopathies/