Subclinical atherosclerosis in systemic lupus erythematosus (SLE): the relative contribution of classic risk factors and the lupus phenotype.

OBJECTIVES We aimed to examine the strength of association between traditional cardiovascular risk factors and carotid plaque development in systemic lupus erythematosus (SLE) patients and controls. We also aimed to determine which lupus-related factors are associated with carotid plaque and whether SLE sensitizes patients to the effects of traditional factors. METHODS We studied 200 women with SLE and 100 controls. Demographic and risk factor data were collected and SLE features, including autoantibody profiles and therapy were noted. All subjects had B- mode ultrasound of their carotid arteries examined for the presence and distribution of plaque. RESULTS SLE patients <55 years old had more plaque (21% vs 3% P < 0.01) and more SLE patients had plaque in the internal carotid artery (11% vs 4%; P < 0.05). Traditional risk factor models performed less well in SLE compared with controls [area under Receiver Operator Characteristic curves (AUC ROC) = 0.76 vs 0.90; P < 0.01]. A multivariable model using SLE factors only, performed significantly better (AUC ROC = 0.87; P < 0.01). The final model in SLE included age and cigarette pack-years smoking as well as azathioprine exposure ever, antiphospholipid antibodies (APLA) and previous arterial events (AUC ROC = 0.88). CONCLUSIONS SLE patients have a higher prevalence and different distribution of carotid plaque than controls. SLE factors perform significantly better than traditional risk factors in their association with atherosclerosis in SLE and these factors add to the influence of traditional risk factors rather than sensitizing lupus patients to traditional factors. The SLE phenotype helps identify patients at increased risk of atherosclerosis.

[1]  G. Hansson Inflammation, atherosclerosis, and coronary artery disease. , 2005, The New England journal of medicine.

[2]  J. Reveille,et al.  Systemic lupus erythematosus in a multiethnic US cohort (LUMINA). XXIII. Baseline predictors of vascular events. , 2004, Arthritis and rheumatism.

[3]  I. Bruce,et al.  Systemic Lupus Erythematosus: An Independent Risk Factor for Endothelial Dysfunction in Women , 2004, Circulation.

[4]  J. Schwartz,et al.  Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. , 2003, The New England journal of medicine.

[5]  Paolo Raggi,et al.  Premature coronary-artery atherosclerosis in systemic lupus erythematosus. , 2003, The New England journal of medicine.

[6]  I. Bruce,et al.  Risk factors for coronary heart disease in women with systemic lupus erythematosus: the Toronto Risk Factor Study. , 2003, Arthritis and rheumatism.

[7]  Y. Shoenfeld,et al.  Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus , 2003, Annals of the rheumatic diseases.

[8]  M. Monestier,et al.  Reduction of atherosclerosis in low-density lipoprotein receptor-deficient mice by passive administration of antiphospholipid antibody. , 2003, Arthritis and rheumatism.

[9]  D. Isenberg,et al.  Cross-reactivity between anti-cardiolipin, anti-high-density lipoprotein and anti-apolipoprotein A-I IgG antibodies in patients with systemic lupus erythematosus and primary antiphospholipid syndrome. , 2003, Rheumatology.

[10]  V. Brancaccio,et al.  Anticardiolipin antibody titre and plasma homocysteine level independently predict intima media thickness of carotid arteries in subjects with idiopathic antiphospholipid antibodies , 2002, Lupus.

[11]  D. Gladman,et al.  Systemic lupus erythematosus disease activity index 2000. , 2002, The Journal of rheumatology.

[12]  A. Hamsten,et al.  Risk Factors for Cardiovascular Disease in Systemic Lupus Erythematosus , 2001, Circulation.

[13]  J. Jeng,et al.  Correlations between peripheral differential leukocyte counts and carotid atherosclerosis in non-smokers. , 2001, Atherosclerosis.

[14]  M. Abrahamowicz,et al.  Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. , 2001, Arthritis and rheumatism.

[15]  I. Bruce,et al.  Single photon emission computed tomography dual isotope myocardial perfusion imaging in women with systemic lupus erythematosus. I. Prevalence and distribution of abnormalities. , 2000, The Journal of rheumatology.

[16]  R. Neary,et al.  Risk in cardiovascular disease , 2000, BMJ : British Medical Journal.

[17]  Durrington Pn Risk in cardiovascular disease. Joint British societies recommend their computer program for risk calculations. , 2000 .

[18]  W A Wilson,et al.  International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. , 1999, Arthritis and rheumatism.

[19]  D. Renlund,et al.  A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients. Mycophenolate Mofetil Investigators. , 1998, Transplantation.

[20]  M. Hochberg,et al.  Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. , 1997, Arthritis and rheumatism.

[21]  D. Gladman,et al.  The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus. , 1997, Arthritis and rheumatism.

[22]  R. D'Agostino,et al.  Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. , 1997, American journal of epidemiology.

[23]  Z. Makita,et al.  Involvement of β2‐glycoprotein I and anticardiolipin antibodies in oxidatively modified low‐density lipoprotein uptake by macrophages , 1997, Clinical and experimental immunology.

[24]  P. Metcalf,et al.  B‐Mode‐Detected Carotid Artery Plaque in a General Population , 1994, Stroke.

[25]  R. Lahita,et al.  Low levels of total cholesterol, high-density lipoprotein, and apolipoprotein A1 in association with anticardiolipin antibodies in patients with systemic lupus erythematosus. , 1993, Arthritis and rheumatism.

[26]  M. Petri,et al.  Risk factors for coronary artery disease in patients with systemic lupus erythematosus. , 1992, The American journal of medicine.

[27]  E. DeLong,et al.  Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. , 1988, Biometrics.

[28]  J. Hanley,et al.  The meaning and use of the area under a receiver operating characteristic (ROC) curve. , 1982, Radiology.

[29]  L. Kuller,et al.  Comparison of risk factors for vascular disease in the carotid artery and aorta in women with systemic lupus erythematosus. , 2004, Arthritis and rheumatism.

[30]  P. Sidhu,et al.  A simple and reproducible method for assessing intimal-medial thickness of the common carotid artery. , 1997, The British journal of radiology.

[31]  W Riley,et al.  Risk factors and segment-specific carotid arterial enlargement in the Atherosclerosis Risk in Communities (ARIC) cohort. , 1996, Stroke.

[32]  W. Mckinney,et al.  Risk factors for site specific extracranial carotid artery plaque distribution as measured by B-mode ultrasound. , 1989, Journal of clinical epidemiology.