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

Nutr Metab Cardiovasc Dis. 2014 Jul;24(7):751-9. doi: 10.1016/j.numecd.2014.01.006. Epub 2014 Feb 1.


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.

Keywords: Atherosclerosis; CCR5; Cardiovascular risk factors; Carotid intima-media thickness; HLA-DR; Hydroxychloroquine; Memory effector T cells; Systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / blood
  • Adult
  • Biomarkers / blood
  • Blood Pressure / drug effects
  • Body Mass Index
  • CD4-Positive T-Lymphocytes / metabolism
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / drug therapy
  • Carotid Artery, Common / drug effects
  • Carotid Artery, Common / physiopathology*
  • Carotid Intima-Media Thickness*
  • Case-Control Studies
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Female
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Immunologic Factors / metabolism*
  • Logistic Models
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / drug therapy
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Risk Factors


  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • Biomarkers
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Immunologic Factors
  • Hydroxychloroquine