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Vascular Abnormalities, Paraoxonase Activity, and Dysfunctional HDL in Primary Antiphospholipid Syndrome
Marietta Charakida, MD, PhD;
Christian Besler, MD;
Joana R. Batuca;
Shirish Sangle, MD;
Susanna Marques, MD;
Miguel Sousa, MD;
Guosu Wang;
Dimitris Tousoulis, MD, PhD;
Jose Delgado Alves, MD, PhD;
Stavros P. Loukogeorgakis, MD, PhD;
Charles Mackworth-Young, MD;
David D’Cruz, MD, FRCP;
Thomas Luscher, MD, FESC;
Ulf Landmesser, MD, FESC;
John E. Deanfield, BCh, MB, FRCP
JAMA. 2009;302(11):1210-1217.
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.
Author Affiliations: Department of Vascular Physiology, The Institute of Child Health, University College London, London, England (Drs Charakida, Loukogeorgakis, and Deanfield and Ms Wang); Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland (Drs Besler, Luscher, and Landmesser); Department of Pharmacology, New University of Lisbon, Lisbon, Portugal (Dr Delgado Alves and Ms Batuca); Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London, England (Drs Sangle, Marques, Sousa, and D’Cruz); Department of Cardiology, Hippokration Hospital, Athens University Medical School, Athens, Greece (Dr Tousoulis); and Department of Rheumatology, Charing Cross Hospital, London, England (Dr Mackworth-Young).
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