Vascular Abnormalities, Paraoxonase Activity, and... : JAMA: The Journal of the American Medical Association (original) (raw)

Preliminary Communication

Vascular Abnormalities, Paraoxonase Activity, and Dysfunctional HDL in Primary Antiphospholipid Syndrome

Marietta Charakida
Christian Besler
Joana R. Batuca
Shirish Sangle
Susanna Marques
Miguel Sousa
Guosu Wang
Dimitris Tousoulis
Jose Delgado Alves
Stavros P. Loukogeorgakis
Charles Mackworth-Young
David D'Cruz
Thomas Luscher
Ulf Landmesser
John E. Deanfield

JAMA: The Journal of the American Medical Association

302

(

)

1210

1217

September 16, 2009

| DOI: 10.1001/jama.2009.1346

Context

Accelerated atherosclerosis has been described in antiphospholipid syndrome, but the vascular abnormalities and the underlying mechanisms remain unclear.

Objectives

To compare vascular structure and function in patients with positive antiphospholipid antibodies (aPL) with controls and to assess their relationship with paraoxonase activity.

Design, Setting, and Participants

A cross-sectional study of 77 women with positive antiphospholipid antibodies from a lupus outpatient clinic in London, England (90% of the eligible population) and 77 controls matched on frequency basis for age and cardiovascular risk factors between June 2006 and April 2009. Carotid intima media thickness (CIMT), flow-mediated dilatation, pulse wave velocity, and paraoxonase activity were measured in all patients. Anti-inflammatory and antioxidant properties of high-density lipoprotein (HDL) were examined.

Main Outcome Measures

CIMT, pulse wave velocity, flow-mediated dilatation, and paraoxonase.

Results

Women with aPL had greater CIMT and pulse wave velocity compared with controls (mean [SD], 0.75 [0.16] vs 0.64 [0.09] mm; 95% confidence interval [CI], -0.14 to -0.06; P < .001; and 9.2 [1.6] vs 8.5 [1.8] m/s; 95% CI, -1.14 to -0.06; P = .04) and lower flow-mediated dilatation (6.2% [4.1%] vs 9.6% [4.2%]; 95% CI, 2.02%-4.69%; P < .001). Paraoxonase activity was lower in women with aPL vs controls (median [interquartile range], 91.2 [64.3-105.1] vs 103.0 [80.5-111.5] μmol p-nitrophenol/L/serum/min; 95% CI, 0.004-0.007; P = .005) and was inversely associated with CIMT and pulse wave velocity in women with aPL (standardized beta coefficient = -0.4 and -0.3, respectively; P < .05 for both), but not in the control group. High-density lipoprotein from women with aPL inhibited endothelial nitric oxide production in human aortic endothelial cells, in contrast with controls. The beneficial effects of HDL from women with aPL on vascular cell adhesion molecule 1 expression, superoxide production, and monocyte adhesion following activation of human aortic endothelial cells were largely blunted.

Conclusions

Compared with controls, women with aPL had greater functional and structural arterial abnormalities, which were associated with lower activity of paraoxonase. In patients with aPL, HDL reduced nitric oxide bioavailability and had impaired anti-inflammatory and antioxidant properties.