Cardiometabolic and immune factors associated with increased common carotid artery intima-media thickness and cardiovascular disease in patients with systemic lupus erythematosus.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy; The Heart Transplantation Division, Ospedale Niguarda Ca' Granda, Milan, Italy. Electronic address: ammirati.enrico@hsr.it.
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Ammirati
The Department of Medicine, San Raffaele Scientific Institute, Milan, Italy. Electronic address: bozzolo.enrica@hsr.it.
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Bozzolo
San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: rachele.contri@gmail.com.
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Contri
Center for The Study of Atherosclerosis, Italian Society for The Study of Atherosclerosis Lombardia Chapter, Bassini Hospital Cinisello Balsamo, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy. Electronic address: andrea.baragetti@unimi.it.
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Baragetti
San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy; The Flow Cytometry Resource, Advanced Cytometry Technical Applications Laboratory, Milan, Italy; Nestlé Institute of Health Science, Flow Cytometry, EPFL Innovation Park, 1015 Lausanne, Switzerland. Electronic address: palini.alessio@hsr.it.
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Palini
San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: cianflone.domenico@hsr.it.
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Cianflone
San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: banfi.michela@hsr.it.
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Banfi
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy. Electronic address: Patrizia.Uboldi@unimi.it.
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Uboldi
The Hull York Medical School, York, UK. Electronic address: grace.bottoni@gmail.com.
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Bottoni
San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: Scotti.isabella@hsr.it.
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Scotti
Center for The Study of Atherosclerosis, Italian Society for The Study of Atherosclerosis Lombardia Chapter, Bassini Hospital Cinisello Balsamo, Milan, Italy. Electronic address: Angela.Pirillo@guest.unimi.it.
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Pirillo
Center for The Study of Atherosclerosis, Italian Society for The Study of Atherosclerosis Lombardia Chapter, Bassini Hospital Cinisello Balsamo, Milan, Italy; The Multimedica IRCCS, Milan, Italy. Electronic address: Grigore.centroatero@gmail.com.
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Grigore
Center for The Study of Atherosclerosis, Italian Society for The Study of Atherosclerosis Lombardia Chapter, Bassini Hospital Cinisello Balsamo, Milan, Italy. Electronic address: Garlaschelli.centroatero@gmail.com.
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Garlaschelli
The University of Oxford, UK. Electronic address: claudia.monaco@kennedy.ox.ac.uk.
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Monaco
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; The Multimedica IRCCS, Milan, Italy. Electronic address: Alberico.Catapano@unimi.it.
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Catapano
The Department of Medicine, San Raffaele Scientific Institute, Milan, Italy. Electronic address: sabbadini.mariagrazia@hsr.it.
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Sabbadini
The Department of Medicine, San Raffaele Scientific Institute, Milan, Italy. Electronic address: manfredi.angelo@hsr.it.
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Manfredi
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, UK. Electronic address: Danilo.Norata@unimi.it.
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Norata
D064286:ATP Binding Cassette Transporter 1 / Q000097:blood; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000188:drug therapy; D017536:Carotid Artery, Common / Q000187:drug effects / Q000503:physiopathology*; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D007155:Immunologic Factors / Q000378:metabolism*; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007155:Immunologic Factors; D006886:Hydroxychloroquine
Atherosclerosis; CCR5; Cardiovascular risk factors; Carotid intima-media thickness; HLA-DR; Hydroxychloroquine; Memory effector T cells; Systemic lupus erythematosus