Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis.
OBJECTIVE
Women with systemic lupus erythematosus (SLE) have a 7-50-fold increased risk of coronary artery disease (CAD). In the general population, oxidized low-density lipoprotein (ox-LDL) increases the risk for CAD. Normal high-density lipoproteins (HDLs) protect LDL from oxidation; proinflammatory HDLs do not. This study was undertaken to determine whether patients with SLE, who have chronic inflammation that causes oxidative damage, have more proinflammatory HDL and higher levels of ox-LDL, thus predisposing them to atherosclerosis.


METHODS
One hundred fifty-four women with SLE, 48 women with rheumatoid arthritis (RA), and 72 healthy controls were studied. The ability of the patients' HDL to prevent oxidation of normal LDL was measured. Values >1.0 (the value assigned for LDL oxidation in the absence of HDL) after the addition of HDL indicated proinflammatory HDL. Plasma ox-LDL levels were measured as the amount of oxidation produced by the patient's LDL after the removal of HDL.


RESULTS
SLE patients had more proinflammatory HDL (mean +/- SD score 1.02 +/- 0.57, versus 0.68 +/- 0.28 in controls [P < 0.0001] and 0.81 +/- 0.22 in RA patients [P = 0.001 versus SLE patients]). A higher proportion of SLE patients had proinflammatory HDL: 44.7% of SLE patients versus 4.1% of controls and 20.1% of RA patients had scores >1.0 (P < 0.006 between all groups). Levels of ox-LDL correlated with levels of proinflammatory HDL (r = 0.37, P < 0.001). SLE patients with CAD had significantly higher proinflammatory HDL scores than patients without CAD (P < 0.001).


CONCLUSIONS
HDLs are proinflammatory in a significant proportion of SLE patients and are associated with elevated levels of ox-LDL. Abnormal HDLs impair the ability to prevent LDL oxidation and may predispose to atherosclerosis.
McMahon
Maureen
M
University of California at Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095, USA. mmcmahon@mednet.ucla.edu
Grossman
Jennifer
J
FitzGerald
John
J
Dahlin-Lee
Erika
E
Wallace
Daniel J
DJ
Thong
Bernard Y
BY
Badsha
Humeira
H
Kalunian
Kenneth
K
Charles
Christina
C
Navab
Mohamad
M
Fogelman
Alan M
AM
Hahn
Bevra H
BH
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications; D050197:Atherosclerosis / Q000097:blood* / Q000150:complications; D015415:Biomarkers; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000150:complications; D008875:Middle Aged; D010084:Oxidation-Reduction
D015415:Biomarkers; D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein