Lipoprotein Profile and Serum Glycoprotein Acetylation As Markers of Cardiovascular Risk in Systemic Lupus Erythematosus

Simantini Sakhardande¹, Monica Purmalek¹, Yenealem Temesgen-Oyelakin², Maureen Sampson³, Aditya Joshi⁴, Alice Fike⁵, Michael Davis⁶, Taufiq Salahuddin⁷, Balaji Natarajan⁷, Joseph Lerman⁷, Zerai G. Manna⁸, Amit Dey⁹, Marcus Chen⁷, Sarfaraz Hasni⁸, Nehal N. Mehta⁷, Alan Remaley⁷ and Mariana Kaplan¹⁰, ¹Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, ²National Institute of Arthritis and Musculoskeletal and Skin Diseases,, National Institutes of Health, Bethesda, MD, ³Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD, ⁴National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, ⁵National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, ⁶NIH, Bethesda, MD, ⁷NHLBI, National Institutes of Health, Bethesda, MD, ⁸National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, ⁹National Institutes of Health, Bethesda, MD, ¹⁰NIAMS/NIH, Bethesda, MD

Meeting: ACR/ARHP Annual Meeting 2016

Date of first publication: September 28, 2016

Keywords: Atherosclerosis, Cardiovascular disease, glycoproteins and lipids, SLE

Session Information

Date: Tuesday, November 15, 2016

Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment IV: Biomarkers

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: The risk of atherosclerotic cardiovascular disease (CVD) is significantly increased in systemic SLE compared to age and gender matched controls. The implementation of nuclear magnetic resonance (NMR) analysis has allowed for the analysis of novel biomarkers of CVD, including assessment of lipoprotein particle counts/size as well as serum glycoprotein acetylation (GlycA) levels. GlycA is a proinflammatory biomarker that predicts 5 year all cause mortality and incident CVD in the general population. GlycA levels reflect the abundance of mobile N-acetyl sugar groups found in glycoproteins in circulating blood. We assessed the association of lipoprotein profiles and serum GlycA levels with vascular function, arterial inflammation, coronary plaque and lupus disease activity.

Methods: Clinical and demographic characteristics, SLE disease activity (by SLEDAI), damage accrual (by SLICC), Framingham risk score (FRS), and metabolic parameters were recorded at each visit. SLE (n=54) and matched healthy controls(n=32) underwent vascular function assessments by measuring peripheral arterial tonometry of the microvasculature (EndoPAT), arterial stiffness using a cardio-ankle vascular index (CAVI) and SphygmoCor, aortic inflammation by 18-fluorodeoxyglucose positron emission tomography/computerized tomography (FDG-PET/CT), and quantification of plaque by coronary CT angiogram (CTA). Lipoprotein profiles and GlycA levels were obtained by NMR analysis.

Results: Lupus and control individuals did not differ in gender, tobacco use, standard lipid profile or FRS but had higher prevalence of insulin resistance and BMI. Mean SLEDAI score was 3.5 ± 2.9. HDL, medium HDL and IDL particle counts were lower in SLE compared to controls (p<0.001), whereas medium VLDL particle counts and GlycA levels were significantly increased in SLE (p =0.034 and <0.001 respectively) when compared to controls. Among SLE patients, HDL particles negatively correlated with SLEDAI (r= -0.33, p=0.015) and non-calcified plaque by CTA (r= -0.29, p=0.003), VLDL particles positively correlated with non-calcified plaque (r=0.24, p=0.015) and arterial inflammation (r=0.36, p=0.014). Within SLE patients, GlycA levels significantly correlated with SLICC (r=0.29, p=0.047), insulin resistance (r=0.36, p=0.007), aortic inflammation, assessed by FDG-PET/CT (r= 0.35, p=0.019) and arterial stiffness using sphygmocor (r=0.57, p<0.001). In an unadjusted linear regression model, higher GlycA levels associated with increased arterial stiffness in SLE but not in controls (r=0.62, p<0.001) and this association remained significant after adjusting for FRS, BMI and insulin resistance. GlycA levels added incremental value in predicting non calcified plaque in lupus patients beyond FRS and Hs-CRP when added to nested models (r=5.41, p=0.020).

Conclusion: SLE individuals demonstrate significant increases in serum GlycA levels and a proatherogenic lipoprotein profile, even when lupus disease activity is low, in association with CVD risk markers. Future longitudinal analysis will assess the clinical implications of these findings and role of these tests as biomarkers of CVD in SLE.

Disclosure: S. Sakhardande, None; M. Purmalek, None; Y. Temesgen-Oyelakin, None; M. Sampson, None; A. Joshi, None; A. Fike, None; M. Davis, None; T. Salahuddin, None; B. Natarajan, None; J. Lerman, None; Z. G. Manna, None; A. Dey, None; M. Chen, None; S. Hasni, None; N. N. Mehta, None; A. Remaley, None; M. Kaplan, None.

To cite this abstract in AMA style:

Sakhardande S, Purmalek M, Temesgen-Oyelakin Y, Sampson M, Joshi A, Fike A, Davis M, Salahuddin T, Natarajan B, Lerman J, Manna ZG, Dey A, Chen M, Hasni S, Mehta NN, Remaley A, Kaplan M. Lipoprotein Profile and Serum Glycoprotein Acetylation As Markers of Cardiovascular Risk in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/lipoprotein-profile-and-serum-glycoprotein-acetylation-as-markers-of-cardiovascular-risk-in-systemic-lupus-erythematosus/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/lipoprotein-profile-and-serum-glycoprotein-acetylation-as-markers-of-cardiovascular-risk-in-systemic-lupus-erythematosus/