Dysfunctional proinflammatory high‐density lipoproteins confer increased risk of atherosclerosis in women with systemic lupus erythematosus

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.