Novel Cardiovascular Risk Factors in Premature Coronary Atherosclerosis Associated with Systemic Lupus Erythematosus

YOUNG HEE RHO, CECILIA P. CHUNG, ANNETTE OESER, JOSEPH SOLUS, PAOLO RAGGI, TEBEB GEBRETSADIK, AYUMI SHINTANI, and C. MICHAEL STEIN

ABSTRACT.

Objective. Several mediators of inflammation are associated with atherosclerotic cardiovascular disease in the general population, but their relationship to accelerated atherosclerosis associated with an inflammatory disease such as systemic lupus erythematosus (SLE) is not known.

Methods. We compared concentrations of cytokines (TNF-α , IL-1α , and VEGF), inflammatory enzymes (MPO and MMP-9), acute-phase reactants (ESR, CRP, and SAA) and adhesion molecules (VCAM, ICAM, and E-selectin) in 109 patients with SLE and 78 controls. The relationship between inflammatory markers and coronary atherosclerosis detected as calcified plaque by electron beam CT was determined in patients with SLE.

Results. Concentrations of all markers of inflammation other than VCAM, MMP-9, and IL-1α were significantly higher in SLE. In multivariable analyses adjusting for Framingham risk score, cumulative corticosteroid dose, and diabetes, E-selectin (OR 1.90, 95% CI 1.08–3.33), VCAM (OR 1.99, 1.18–3.37), ICAM (OR 2.30, 1.13–4.7), and TNF-α (OR 2.36, 1.10–5.06) were significantly associated with the severity of coronary calcium.

Conclusion. Concentrations of adhesion molecules and TNF-α are associated with coronary atherosclerosis in SLE independent of the Framingham risk score. (First Release July 15 2008; J Rheumatol 2008;35:1789-94)

Key Indexing Terms:

SYSTEMIC LUPUS ERYTHEMATOSUS
ATHEROSCLEROSIS
CELL ADHESION MOLECULE
TUMOR NECROSIS FACTOR-α
CYTOKINES

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From the Divisions of Clinical Pharmacology and Rheumatology and Departments of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee; Division of Cardiology, Emory University, Atlanta, Georgia; and Department of Biostatistics, School of Medicine, Vanderbilt University, Nashville, Tennessee, USA.

Supported by NIH grants HL65082 and GM5M01-RR00095.

Y.H. Rho, MD; C.P. Chung, MD, MPH; A. Oeser, BS, Divisions of Clinical Pharmacology and Rheumatology; J. Solus, PhD, Departments of Molecular Physiology and Biophysics, Vanderbilt University; P. Raggi, MD, Division of Cardiology, Emory University; T. Gebretsadik, MPH; A. Shintani, PhD, MPH, Department of Biostatistics, School of Medicine; C.M. Stein, MD, Divisions of Clinical Pharmacology and Rheumatology, Vanderbilt University.

Address reprint requests to Dr. C.M. Stein, 560 RRB, Department of Clinical Pharmacology, School of Medicine, Vanderbilt University, 23rd Ave. S. at Pierce Ave., Nashville, TN 37232-6602. E-mail: michael.stein@vanderbilt.edu

Accepted for publication April 11, 2008.

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