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BACKGROUND AND AIM: Patients with systemic lupus erythematosus (SLE) have a higher prevalence of subclinical atherosclerosis and higher risk of cardiovascular (CV) events compared to the general population. The relative contribution of CV-, immune- and disease-related risk factors to accelerated atherogenesis in SLE is unclear. METHODS AND RESULTS: Fifty SLE patients with long-lasting disease (mean age 44 ± 10 years, 86% female) and 50 sex- and age-matched control subjects were studied. Common carotid artery intima-media thickness (CCA-IMT) was used as a surrogate marker of atherosclerosis. We evaluated traditional and immune- and disease-related factors, assessed multiple T-cell subsets by 10-parameter-eight-colour polychromatic flow cytometry and addressed the effect of pharmacological therapies on CCA-IMT. In SLE patients, among several cardiometabolic risk factors, only high-density lipoprotein levels (HDL) and their adenosine triphosphate-binding cassette transporter 1 (ABCA-1)-dependent cholesterol efflux capacity were markedly reduced (p < 0.01), whereas the CCA-IMT was significantly increased (p = 0.03) compared to controls. CCA-IMT correlated with systolic blood pressure, low-density lipoprotein (LDL) cholesterol and body mass index (BMI), but not with disease activity and duration. The activated CD4(+)HLA-DR(+) and CCR5(+) T-cell subsets were expanded in SLE patients. Patients under hydroxychloroquine (HCQ) therapy showed lower CCA-IMT (0.62 ± 0.08 vs. 0.68 ± 0.10 mm; p = 0.03) and better risk-factor profile and presented reduced circulating pro-atherogenic effector memory T-cell subsets and a parallel increased percentage of naïve T-cell subsets. CONCLUSION: HDL represents the main metabolic parameter altered in SLE patients. The increased CCA-IMT in SLE patients may represent the net result of a process in which 'classic' CV risk factors give a continuous contribution, together with immunological factors (CD4(+)HLA-DR(+) T cells) which, on the contrary, could contribute through flares of activity of various degrees over time. Patients under HCQ therapy present a modified metabolic profile, a reduced T-cell activation associated with decreased subclinical atherosclerosis.

Original publication

DOI

10.1016/j.numecd.2014.01.006

Type

Journal article

Journal

Nutr Metab Cardiovasc Dis

Publication Date

07/2014

Volume

24

Pages

751 - 759

Keywords

Atherosclerosis, CCR5, Cardiovascular risk factors, Carotid intima-media thickness, HLA-DR, Hydroxychloroquine, Memory effector T cells, Systemic lupus erythematosus, ATP Binding Cassette Transporter 1, Adult, Biomarkers, Blood Pressure, Body Mass Index, CD4-Positive T-Lymphocytes, Cardiovascular Diseases, Carotid Artery, Common, Carotid Intima-Media Thickness, Case-Control Studies, Cholesterol, HDL, Cholesterol, LDL, Female, Humans, Hydroxychloroquine, Immunologic Factors, Logistic Models, Lupus Erythematosus, Systemic, Male, Middle Aged, Multivariate Analysis, Risk Factors