Lipoprotein-associated phospholipase A2: a new marker to determine cardiovascular risk in hypercholesterolemic dyslipidaemic children.

Background Inflammation and hypercholesterolaemia contribute to atherosclerotic changes which can start in childhood. Children with hyperlipidaemias are at high risk for early coronary atherosclerosis. This study evaluates the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2), carotid intima-media thickness (CIMT) and flow-mediated dilatation in hypercholesterolaemic dyslipidaemic children. Methods We performed a case-control study consisting of 43 cases, aged 2 to 17 years, and 24 age-matched controls. Fasting blood samples were obtained from both groups for the measurement of a lipid profile (total cholesterol, LDL-C, HDL-C and triglycerides) and Lp-PLA2 in mass units. The latter was determined with a turbidimetric immunoassay method (PlacTest, DiaDexus Inc.) applied to an automated analyser. CIMT and flow-mediated dilatation measurements were undertaken by a paediatric cardiologist, using high-resolution B-mode ultrasonography. Results Total cholesterol, LDL-C and Lp-PLA2 concentrations were significantly higher in the cases than in the controls ( p < 0.001 for all three parameters). While CIMT values were also significantly higher in the patients compared to the controls ( P = 0.001), flow-mediated dilatation values were significantly lower ( P = 0.001). We found positive correlations between Lp-PLA2 and total cholesterol ( r = 0.41, P = 0.001), Lp-PLA2 and LDL-C ( r = 0.36, P = 0.004), Lp-PLA2 and CIMT ( r = 0.44, P = 0.019) and LDL-C and CIMT ( r = 0.41, P = 0.032); there were negative correlations between Lp-PLA2 and flow-mediated dilatation ( r = -0.15, P = 0.045), total cholesterol and flow-mediated dilatation ( r = -0.45, P = 0.017), LDL-C and flow-mediated dilatation ( r = -0.51, P = 0.006) and CIMT and flow-mediated dilatation ( r = -0.45, P = 0.016). Conclusion Lp-PLA2 concentrations are significantly elevated in hypercholesterolaemic dyslipidaemic children. Given the association of Lp-PLA2 with markers of atherosclerosis (total cholesterol, LDL-C, CIMT and flow-mediated dilatation), the finding of increased concentrations of Lp-PLA2 could be used to identify early atherosclerotic changes in hypercholesterolaemic dyslipidaemic children and may inform their clinical management.

A panel of oxidative stress assays does not provide supplementary diagnostic information in Behcet's disease patients.

BACKGROUND: Recent findings suggest a role of oxidative stress in the pathogenesis of Behcet's disease (BD), but the utility of oxidative stress-associated assays in offering diagnostic information or in the monitoring of disease activity is largely unassessed. OBJECTIVE AND METHODS: We aimed to measure oxidative and inflammatory markers, along with the markers of reactive nitrogen species, S-nitrosothiols and 3-nitrotyrosine, in BD patients (n = 100) and healthy volunteers (n = 50). These markers were evaluated in regard to their role in the pathogenesis of BD as well as their relation to clinical presentation, disease activity and duration. RESULTS: Median values for erythrocyte sedimentation rate (ESR), C-reactive protein, leukocyte count, and IL-18 levels, as well as myeloperoxidase (MPO) activity, were statistically higher in the patient group compared to controls. Some inflammation markers (ESR, neutrophil and leukocyte counts) were statistically higher (p < 0.05) in the active period. In contrast, oxidative stress-associated measures (erythrocyte lipid peroxidation, antioxidant enzymes and measures of serum antioxidant capacity), revealed no statistically significant differences between the median values in BD patients versus healthy control subjects (p > 0.05 in all statistical comparisons), nor was there any difference in median levels of these oxidative stress markers in active disease versus disease remission. S-nitrosothiols and 3-nitrotyrosine were undetectable in BD plasma. CONCLUSIONS: The application of oxidative stress-associated measures to BD blood samples offered no supplemental diagnostic or disease activity information to that provided by standard laboratory measures of inflammation. S-nitrosothiols and 3-nitrotyrosine appeared not to be markers for active BD; thus the search for biochemical markers that will indicate the active period should be continued with larger studies.

Effects of estrogen-only therapy on LDL oxidation in women with hysterectomy: does paraoxonase genotype play a role?

OBJECTIVES: This study investigated the effects of estrogen-only therapy on lipid profile (through susceptibility of low density lipoproteins to oxidation) and on oxidant-antioxidant parameters in surgical menopausal women. PON genotypes are also evaluated considering that they may be associated with the personal differences observed in antioxidant effects induced by estrogen. METHODS: Thirty women who had undergone hysterectomy+bilateral ovariectomy in the last 3 years, with causes other than malignancy were included and given estrogen-only (Premarin-Wyeth Inc. 0.625 mg/day/6 months, equine conjugated estrogen). Blood samples were collected at baseline, first and sixth month of treatment. Serum (total antioxidant activity-TAO and PON activity), erythrocyte (TBARS and catalase activity), LDL and Cu2+ induced ox-LDL (TBARS and diene levels) samples were evaluated and PON1 192 polymorphisms were determined by PCR amplification & restriction enzyme digestion. RESULTS: At the sixth month, a higher TAO activity (p=0.016) and a lower eTBARS (p=0.028) were detected compared to the basal values. LDL and Cu induced ox-LDL TBARS levels at the sixth month of treatment were significantly (p=0.012 and 0.026, respectively) lower compared to the pretreatment values. Baseline eTBARS (p=0.007), LDL TBARS (p=0.044) and eCAT (p=0.033) activities were significantly higher in homozygote Q allele carriers compared to subjects with R allele. LDL TBARS and Cu2+ induced ox-LDLTBARS of QQ subjects (p=0.018 and 0.050) as well as LDL TBARS of QR subjects (p=0.044) showed a significant decrease with estrogen-only treatment. CONCLUSIONS: Our study drives the attention to PON polymorphism in postmenopausal women who have risk for atherosclerosis. Although our data is limited, this study is the first that focuses on the role of PON genotypes in antiatherosclerotic effects of estrogen-only and provides important points for further studies.