Abstract 1316: Preclinical Atherosclerosis in Primary Antiphospholipid Syndrome: The Impact of Oxidative Properties of High Density Lipopoprotein

Abstract

Background: Antiphospholipid syndrome (APS) is characterised by increased thrombogenicity and/or pregnancy morbidity in the presence of raised levels of antiphospholipid antibodies (aPL). Increased oxidative properties of high density lipoprotein (HDL)(decreased activity of paraoxonase (PON)) is associated with increased risk for atherosclerosis and has been described in APS. The impact of PON on atherosclerotic disease progression in APS is unclear. We therefore examined the effect of PON on intima media thickness (IMT), and pulse wave velocity (PWV) in patients with positive aPL. Methods: We studied 77 women with positive aPL (aPL) aged 46.6±1.2 yrs (mean±SE) and a control group of 77 women aged 47.5±1.2 yrs matched for traditional cardiovascular risk factors. High resolution ultrasound was used to determine carotid IMT. Arterial stiffness was assessed non-invasively by carotid-radial PWV. PON activity was assessed by measuring p-nitrophenol formation and activity expressed as nmoles p-nitrophenol/ml serum/minute. Results: APL patients had significantly increased IMT and PWV compared to controls (0.75±0.02mm vs 0.65±0.01mm, p<0.001 and 9.14±0.18 m/s vs 8.56±0.21m/s, p<0.05 respectively). PON activity was significantly reduced in aPL compared to controls (91.5[64.3, 05.1]mmol/ml/min, median[IQR] vs 103.1[80.4, 111.5] mmol/ml/min, p<0.006). Although PON activity was not associated with vascular measures in controls, an inverse association was noted in aPL patients (r=−0.26 [cIMT] and r=−0.23 [PWV], both p<0.05). In multivariate analysis, accounting for cardiovascular risk factors, PON activity (β=−0.42, p<0.001), age (β=0.33, p<0.001) and systolic blood pressure (β=0.24, p<0.05) were independent determinants of cIMT while PON activity (β=−0.32, p<0.01) and systolic blood pressure (β=0.28, p<0.05) remained the only independent predictors of PWV in aPL positive patients. Conclusions: APS is associated with increased arterial stiffness and carotid intimal thickening. Paraoxonase activity is inversely associated with IMT and PWV in ApL positve patients. These findings indicate that oxidative stress may play an important role in the development of atherosclerosis in patients with primary antiphospholipid syndrome.