Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Patients with systemic lupus erythematosus (SLE) show a striking increase in risk of atherosclerotic cardiovascular disease (CVD) not explained by Framingham risk, when compared to age and gender matched controls. Immune dysregulation and innate immune responses associated to aberrant neutrophils (low density granulocytes, LDGs) may play a key role in conferring enhanced CV risk, driving vascular damage, oxidizing HDL and altering its function. Whether proinflammatory neutrophils are associated to and predict vascular inflammation, endothelial dysfunction, and eventually, clinical vascular events remains to be determined.
Methods: In this cross-sectional study, SLE patients fulfilling ACR classification criteria were compared to age and gender-matched controls. Clinical and demographic characteristics, Framingham Risk score, metabolic parameters, and lupus medications were recorded at each visit. Individuals underwent assessment of a) vascular function of various arterial territories: peripheral arterial tonometry of the microvasculature (Endopat), arterial stiffness by cardio-ankle vascular index (CAVI) and by Sphygmocor; b) aortic inflammation by FDG-PET/CT; and c) anatomical assessment of plaque by coronary CT angiogram. Circulating LDGs were quantified by flow cytometry. Cholesterol efflux capacity was quantified in radioactively-labeled cell lines upon exposure to control or lupus HDL.
Results: Lupus (n=54) and healthy controls (n=32) did not differ in gender, race, ethnicity or Framingham risk score. Mean disease duration was 16 ± 12 years and SLEDAI was 3.5 + 2.9. Arterial stiffness assessed by CAVI was increased in SLE (CAVI: 7.3[6.5-8.0]) vs. controls (6.3[5.9-7.4]; p = 0.004), and by Endopat augmentation index (AI75: 14.4 ± 18.7) vs. controls (5.5 ± 20.7, p = 0.022). Additionally, SLE patients displayed enhanced aortic inflammation by FDG-PET/CT (TBR: 1.63 [1.5-1.8]) vs. controls (1.56 [1.5-1.7], p=0.010). Differences between control and SLE persisted in multivariate regression analysis adjusting for Framingham Risk. HDL efflux was negatively associated with noncalcified plaque burden in SLE (b=-0.30, p=0.002), while LDGs were positively associated with noncalcified plaque burden (b=0.37, p<0.001), both persisting in multivariate regression analysis adjusting for Framingham Risk + body mass index or insulin resistance. In addition, number of lupus LDGs positively associated with damage (SLICC score (b=0.31, p=0.031)), CRP (b=0.46, p=0.001), and arterial stiffness (b=0.44, p=0.012).
Conclusion: Individuals with SLE demonstrate increased arterial stiffness and prominent arterial inflammation suggestive of widespread damage across both micro- and macro-vascular territories. These results support the hypothesis that aberrant neutrophil subsets significantly contribute to vascular damage and unstable plaque development in SLE. Results also support previous observations that neutrophils, through enhanced neutrophil extracellular trap formation, may disrupt HDL function and further promote atherogenesis.
To cite this abstract in AMA style:Purmalek M, Sakhardande S, Temesgen-Oyelakin Y, Joshi A, Lerman J, Davis M, Fike A, Dey A, Salahuddin T, Natarajan B, Playford MP, Teague H, Manna ZG, Chen M, Hasni S, Mehta NN, Kaplan M. Neutrophil Subsets, Arterial Inflammation, and Vascular Stiffness in Patients with Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/neutrophil-subsets-arterial-inflammation-and-vascular-stiffness-in-patients-with-systemic-lupus-erythematosus/. Accessed February 26, 2021.
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