RESEARCH - Dysfunctional proinflammatory HDLs confer increased risk of atherosclerosis in SLE

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Arthritis Rheum. 2009 Jul 30;60(8):2428-2437.

Dysfunctional proinflammatory high-density lipoproteins confer

increased risk of atherosclerosis in women with systemic lupus

erythematosus.

McMahon M, Grossman J, Skaggs B, Fitzgerald J, Sahakian L, Ragavendra

N, -Schoeman C, K, Wong WK, Volkmann E, Chen W, Gorn A,

Karpouzas G, Weisman M, Wallace DJ, Hahn BH.

Geffen School of Medicine, and UCLA Medical Center, University

of California, Los Angeles.

OBJECTIVE: Women with systemic lupus erythematosus (SLE) have an

increased risk of atherosclerosis. Identification of at-risk patients

and the etiology underlying atherosclerosis in SLE remain elusive. The

antioxidant capacity of normal high-density lipoproteins (HDLs) is

lost during inflammation, and these dysfunctional HDLs might

predispose individuals to atherosclerosis. The aim of this study was

to determine whether dysfunctional proinflammatory HDL (piHDL) is

associated with subclinical atherosclerosis in SLE.

METHODS: Carotid artery ultrasound was performed in 276 women with SLE

to identify carotid plaques and measure intima-media thickness (IMT).

The antioxidant function of HDL was measured as the change in

oxidation of low-density lipoprotein after the addition of HDL

cholesterol. Two antiinflammatory HDL components, paraoxonase 1 and

apolipoprotein A-I, were also measured.

RESULTS: Among the SLE patients, 48.2% were determined to have piHDL

on carotid ultrasound, while 86.7% of patients with plaque had piHDL

compared with 40.7% of those without plaque (P < 0.001). Patients with

piHDL also had a higher IMT (P < 0.001). After multivariate analysis,

the only factors found to be significantly associated with plaque were

the presence of piHDL (odds ratio [OR] 16.1, P < 0.001), older age (OR

1.2, P < 0.001), hypertension (OR 3.0, P = 0.04), dyslipidemia (OR

3.4, P = 0.04), and mixed racial background (OR 8.3, P = 0.04).

Factors associated with IMT measurements in the highest quartile were

the presence of piHDL (OR 2.5, P = 0.02), older age (OR 1.1, P <

0.001), a higher body mass index (OR 1.07, P = 0.04), a cumulative

lifetime prednisone dose >/=20 gm (OR 2.9, P = 0.04), and African

American race (OR 8.3, P = 0.001).

CONCLUSION: Dysfunctional piHDL greatly increases the risk of

developing subclinical atherosclerosis in SLE. The presence of piHDL

was associated with an increased prevalence of carotid plaque and with

a higher IMT. Therefore, determination of piHDL may help identify

patients at risk for atherosclerosis.

PMID: 19644959

http://www.ncbi.nlm.nih.gov/pubmed/19644959

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