This study evaluated whether IgG anticardiolipinantibody (aCL) titre and traditional risk factors for atherosclerosis bore any relationship to the intima media thickness (IMT) of carotid arteries of patients with idiopathic antiphospholipid antibodies (aPL). IMT was assessed by high-resolution sonography at the common carotid, carotid bifurcation and internal carotid in 42 (13 male, 29 female, mean age 31§ 10 years) aPL subjects, 29 with primary thrombotic antiphospholipid syndrome and 13 with persistence of aPL in the absence of any underlying disorder. In the same subjects the following were measured: plasma fibrinogen (FNG), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI), homocysteine (HC), total cholesterol (CHO), triglycerides (TG), high density and low density lipoprotein (HDL and LDL), platelet numbers and aCL of IgG and IgM isotype. IMT of the internal carotid was greater in males than females (0.48±0.03 vs 0.39±0.01 mm, P = 0.02). IMT of the carotid bifurcation was greater in thrombotic than nonthrombotic subjects (0.50§ 0.02 vs 0.42§ 0.02 mm, P = 0.04). By simple regression, IMT of the common carotids correlated with age (P < 0.0001) IgG aCL titre (P = 0.001), FNG (P = 0.006), LDL (0.01), CHO (0.02) and PAI (P = 0.02). IMT of the carotid bifurcation correlated with age (P = 0.002), IgG aCL titre (P = 0.0002), FNG (P = 0.0001), HC (P = 0.009), CHO (P = 0.02), vWF (P = 0.01) and number of thrombotic events (P = 0.03). IMT of the internal carotids correlated with age (P = 0.002), IgG aCL titre (P = 0.0001), FNG (P = 0.0008), PAI (P = 0.002) and HC (P = 0.01). By stepwise multiple regression analysis, IgG aCL titre independently predicted IMT at all carotid segments examined (P always < 0.005). In addition, plasma FNG and HC also resulted independent predictors of IMT at the carotid bifurcation (P = 0.001 and P < 0.0001, respectively) and internal carotid (P = 0.03 and P < 0.0001, respectively). These data strongly support an atherogenic role for IgG aCL in patients with aPL. Measurement of plasma HC and FNG may help define aPL subjects at higher vascular risk who may require lowering of HC and FNG by vitamin and/or pharmacologic intervention. Lupus (2002) 11, 208–214.

Objective: To investigate the atherosclerosis hypothesis in primary antiphospholipid syndrome (PAPS). Methods: The intima media thickness (IMT) of carotid arteries and other cardiovascular risk factors was measured in 20 patients with PAPS (mean (SD) age 35 (12) years) and in 20 controls matched for age and sex (34 (12) years). Results: The frequency of smoking, hypertension, and dyslipidaemia was similar in the two groups, but plasma homocysteine was higher in patients with PAPS (mean (SD) 11.9 (6.2) v 8.2 (3.4) μmol/l, p = 0.037). The IMT was slightly greater in patients with PAPS than in controls at the carotid bifurcation (mean (SD) 0.61 (0.24) v 0.48 (0.09) mm, p = 0.04) and internal carotid artery (0.52 (0.22) v 0.40 (0.08), p = 0.01). These differences were more evident in patients aged >40 years than in those aged <30 years at the carotid bifurcation (0.76 (0.25) v 0.55 (0.06), p = 0.0007) and internal carotid artery (0.63 (0.25) v 0.45 (0.09), p = 0.02); no differences were seen in the younger age group compared with controls. Conclusion: Atherosclerosis is a possibility in patients with PAPS in their fourth decade of life or older.

During the past decade, there has been an increased description of Churg Strauss syndrome (CSS) characterized by vascular occlusions possibly linked to the thrombogenic potential of the eosinophil that is poorly appreciated. The purpose of this overview is 3-fold: the first to evaluate the available prevalence of thrombosis in Churg Strauss series, the second to demonstrate that any vascular district may be affected, and the third to describe the pathogenesis of thrombosis in CSS. A Pubmed, EMBASE, and Google search of CSS series from 1951 to date revealed a prevalence of arterial occlusion ranging between 3.1% and 18.7% and a prevalence of venous occlusion between 5.8% and 30%, whereas a specific survey for venous thromboembolism in CSS yielded a prevalence of 8.1%. Eosinophils store and release tissue factor as well as other cationic proteins: the former initiates coagulation while the latter inhibits natural anticoagulant activity and activate platelets eventually culminating in excessive thrombin generation and clot formation. In addition, antineutrophil cytoplasmic antibodies may shift the endothelial lining to proadhesive and prothrombotic surface. It is hoped that the review will represent a basis to foster novel research on this topic.

Objective.: To assess the role of nitrite (NO₂⁻), nitrate (NO₃⁻), and nitrative stress in thrombotic primary antiphospholipid syndrome (PAPS).Methods.: We investigated 46 patients with PAPS: 21 asymptomatic but persistent carriers of antiphospholipid antibodies (PCaPL), 38 patients with inherited thrombophilia (IT), 33 patients with systemic lupus erythematosus (SLE), and 29 healthy controls (CTR). IgG anticardiolipin (aCL), IgG anti-beta₂-glycoprotein I (anti-ß₂-GPI), IgG anti-high density lipoprotein (aHDL), IgG anti-apolipoprotein A-I (aApoA-I), crude nitrotyrosine (NT) (an indicator of nitrative stress), and high sensitivity C-reactive protein (CRP) were measured by immunoassays. Plasma nitrite (NO₂⁻), nitrate (NO₃⁻), and total antioxidant capacity (TAC) were measured by colorimetric spectroscopic assays.Results.: Average plasma NO₂⁻was lower in PAPS, PCaPL, and IT (p < 0.0001); average NO₃⁻was highest in SLE (p < 0.0001), whereas average NT was higher in PAPS and SLE (p = 0.01). In thrombotic PAPS, IgG aCL titer and number of vascular occlusions negatively predicted NO₂⁻(p = 0.03 and p = 0.001, respectively), whereas arterial occlusions and smoking positively predicted NO₃⁻(p = 0.05 and p = 0.005), and CRP positively predicted NT (p = 0.004). In the PCaPL group IgG aCL negatively predicted NO₃⁻(p = 0.03). In the SLE group IgG aCL negatively predicted NO₂⁻(p = 0.03) and NO₃⁻(p = 0.02).Conclusion.: PAPS is characterized by decreased NO₂⁻in relation to type and number of vascular occlusions and to aPL titers. Nitrative stress and low grade inflammation are linked phenomena in PAPS and may have implications for thrombosis and atherosclerosis.

To evaluate subclinical atherosclerosis in Behcet disease (BD), we performed a systematic review and meta-analysis of studies where atherosclerosis was determined by flow-mediated dilatation (FMD) and endothelial-mediated dilatation (EMD) and by measurement of intima media thickness (IMT) of carotid arteries. Systematic search of EMBASE and PubMed databases from January 2000 to January 2014 according to PRISMA guidelines. Nine studies met the inclusion criteria on FMD/EMD, 11 on IMT and 4 on both. BD had lower FMD than controls (SMD = -0.89, 95% CI: -0.660 to -1.11, p < 0.001), which was confirmed by subgroup analyses on active and inactive patients (SMD = -1.17, 95% CI: -1.45 to -0.89 and SMD = -0.72, 95% CI: -0.97 to -0.46, p = 0.0001 for both). EMD was lower in BD but with a large estimate (SMD = 0.38, 95% CI: -0.79 to -0.03, p = 0.06, I(2) = 82.2%). IMT was greater in BD and the large estimate (SMD = 0.95, 95% CI: 0.63-1.28, p < 0.0001, I(2) = 87.6%) persisted after subgroup analysis on active and inactive patients (I(2) = 88.4% and 86.7%, respectively). Pooling IMT studies by a Newcastle Ottawa Scale of 5 and 6/7 yielded lower estimates (SMD = 0.54, 95% CI: 0.32-0.75, p < 0.0001, I(2) = 58.7% and SMD = 1.72, 95% CI: 1.35-2.09 p < 0.05, I(2) = 48.6%). FMD is impaired in BD even in inactive state and IMT is greater despite a degree of statistical heterogeneity that reflects the clinical heterogeneity of BD. Future prospective studies should account for risk stratification of atherosclerosis in BD.