Impaired Reverse Cholesterol Transport is Associated with Changes in Fatty Acid Profile in Children and Adolescents with Abdominal Obesity.

BACKGROUND: Abdominal obesity is an important cardiovascular disease risk factor. Plasma fatty acids display a complex network of both pro and antiatherogenic effects. High density lipoproteins (HDL) carry out the antiatherogenic pathway called reverse cholesterol transport (RCT), which involves cellular cholesterol efflux (CCE), and lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities. OBJECTIVES: Our aim was to characterize RCT and its relation to fatty acids present in plasma in pediatric abdominal obesity. METHODS: Seventeen children and adolescents with abdominal obesity and 17 healthy controls were studied. Anthropometric parameters were registered. Glucose, insulin, lipid levels, CCE employing THP-1 cells, LCAT and CETP activities, plus fatty acids in apo B-depleted plasma were measured. RESULTS: The obese group showed a more atherogenic lipid profile, plus lower CCE (Mean±Standard Deviation) (6 ± 2 vs. 7 ± 2%; P < 0.05) and LCAT activity (11 ± 3 vs. 15 ±5 umol/dL.h; P < 0.05). With respect to fatty acids, the obese group showed higher myristic (1.1 ± 0.3 vs. 0.7 ± 0.3; P < 0.01) and palmitic acids (21.5 ± 2.8 vs. 19.6 ± 1.9; P < 0.05) in addition to lower linoleic acid (26.4 ± 3.3 vs. 29.9 ± 2.6; P < 0.01). Arachidonic acid correlated with CCE (r = 0.37; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05), palmitioleic acid with CCE (r = -0.35; P < 0.05), linoleic acid with CCE (r = 0.37; P < 0.05), lauric acid with LCAT (r = 0.49; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05) ecoisatrienoic acid with CCE (r = 0.40; P < 0.05) and lignoseric acid with LCAT (r = -0.5; P < 0.01). CONCLUSIONS: Children and adolescents with abdominal obesity presented impaired RCT, which was associated with modifications in proinflammatory fatty acids, such as palmitoleic and myristic, thus contributing to increased cardiovascular disease risk.

Impaired HDL-associated enzymes and proteins in children and adolescents with weight disorders and their association with novel cardiometabolic indexes.

BACKGROUND AND AIMS: Overweight/obesity (OW/OB) is associated with modifications in lipoprotein (Lp)-associated enzymes and proteins, such as cholesteryl ester transfer protein (CETP), Lp-associated phospholipase A2 (LpPLA2) and paraoxonase (PON)1. No evidence is available regarding underweight (UW). The following indexes have been proposed to better assess atherogenic risk related to weight alterations: triglycerides-glucose index (TyG), visceral adiposity index (VAI) and height-corrected lipid accumulation product (HLAP). AIM: To analyze the presence of alterations in Lp-associated enzymes and proteins in children and adolescents with UW and OW/OB and their relation to novel cardiometabolic indexes. METHODS AND RESULTS: Thirty male children and adolescents with UW, 66 with normal weight (NW) and 30 with OW/OB were included. Anthropometric parameters, glucose, Lp profile and the activities of CETP, LpPLA2 and PON1 were evaluated. Body mass index (BMI)-z, TyG, VAI and HLAP were calculated. UW and NW showed lower CETP activity than OW/OB (Mean ± SD) (218 ± 38vs.224 ± 26vs.237 ± 26%/mL.h; p < 0.05). UW and OW/OB showed lower PON1 activity than NW (318 ± 170vs.409 ± 200vs.310 ± 184 nmol/mL.min; p < 0.05). TyG was higher in OW/OB than UW (p < 0.01), whilst both HLAP (p < 0.05) and VAI (p < 0.01) followed a linear trend across weight categories. After adjusting for age and BMI-z, TyG was an independent predictor of CETP (r2 = 0.25, ß = -0.22, p < 0.01) and LpPLA2 (r2 = 0.21,ß = -0.21,p < 0.05), while VAI (r2 = 0.21,ß = -0.32,p < 0.01) and HLAP (r2 = 0.20,ß = -0.31,p < 0.01) of CETP. CONCLUSIONS: Both UW and OW/OB showed impaired antioxidant PON1 activity. Moreover, TyG, VAI and HLAP were all capable of predicting alterations in crucial modulators of Lp metabolism and vascular inflammation in children and adolescents with varying degrees of alterations in body weight.

Vascular inflammation and impaired reverse cholesterol transport and lipid metabolism in obese children and adolescents.

BACKGROUND AND AIMS: Childhood obesity is associated to complications such as insulin resistance and dyslipidemia. High density lipoproteins (HDL) constitute the only lipoprotein fraction with ateroprotective properties. The aim of the present study was to analyze inflammatory markers, carbohydrate metabolism, lipid profile and HDL functionality in obese children and adolescents compared to healthy controls. METHODS AND RESULTS: Twenty obese children and adolescents (Body mass index z score >3.0) (9-15 years old) and 20 age and sex similar controls were included in the study. Triglyceride (TG), total cholesterol (TC), HDL-C, LDL-C, apolipoproteins (apo) A-I and B, glucose and insulin levels were quantified. Lipid indexes and HOMA-IR were calculated. Cholesterol efflux (CEC), lipoprotein associated phospholipase A2 (Lp-PLA2), lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein, plus paraoxonase and arylesterase (ARE) activities were evaluated. Obese children and adolescents showed significantly higher TG [69 (45-95) vs 96 (76-121); p < 0.05], non-HDL-C [99 ± 34 vs 128 ± 26; p < 0.01], TC/HDL-C [2.8 ± 0.6 vs 4.7 ± 1.5; p < 0.01], TG/HDL-C [1.1 (1.0-1.8) vs 2,2 (1.4-3.2); p < 0.01], and HOMA-IR [1.5 (1.1-1.9) vs. 2.6 (2.0-4.5); p < 0.01] values, plus Lp-PLA2 activity [8.3 ± 1.9 vs 7.1 ± 1.7 umol/ml.h; p < 0,05] in addition to lower HDL-C [57 ± 10 vs 39 ± 9; p < 0.01], apo A-I [143 ± 25 vs 125 ± 19; p < 0.05], and CEC [6.4 (5.1-6.8) vs. 7.8 (5.7-9.5); p < 0.01] plus LCAT [12.6 ± 3.3 vs 18.7 ± 2.6; p < 0.05] and ARE [96 ± 19 vs. 110 ± 19; p < 0.05] activities. Lp-PLA2 activity correlated with LDL-C (r = 0.72,p < 0.01), non-HDL-C (r = 0.76,p < 0.01), and apo B (r = 0.60,p < 0.01). LCAT activity correlated with triglycerides (r = -0.78,p < 0.01), HDL-C (r = 0.64,p < 0.01), and apo A-I (r = 0.62, p < 0.05). ARE activity correlated with HDL-C (r = 0.32,p < 0.05) and apoA-I (r = 0.43,p < 0.01). CEC was negatively associated with BMI z-score (r = -0.36,p < 0.05), and triglycerides (r = -0.28,p < 0.05), and positively with LCAT activity (r = 0.65,p < 0.05). In multivariate analysis, BMI z-score was the only parameter significantly associated to CEC (r2 = 0.43, beta = -0.38, p < 0.05). CONCLUSION: The obese group showed alterations in carbohydrate and lipid metabolism, which were associated to the presence of vascular specific inflammation and impairment of HDL atheroprotective capacity. These children and adolescents would present qualitative alterations in their lipoproteins which would determine higher risk of suffering premature cardiovascular disease.

Is periostin useful as a biomarker for fibrous dysplasia? / ¿Es útil periostina como biomarcador de displasia fibrosa?

Fibrous dysplasia (FD) is an infrequent non-hereditary bone disease caused by a somatic mutation of the GNAS gene. Periostin is a novel marker that increases during tissue healing and fibrous or inflammatory diseases. We conducted an exploratory case-control study to evaluate sensitivity of periostin as a biomarker of FD. The study comprised 15 patients with FD, and healthy age- and sex-matched subjects (controls). Serum periostin levels were assessed and comparisons were established between FD patients and controls, and between patients with the monostotic and the polyostotic form of FD. No statistically significant differences in serum periostin levels were observed between the cohort of FD patients studied here and the control group (FD: 51.1±10ng/ml vs. control: 44.2±15ng/ml; p=0.15), or between the clinical forms of FD (polyostotic: 51.8±9.1ng/ml vs. monostotic: 49.6±13 ng/ml; p=0.66). A sub-analysis performed to compare serum levels of periostin in FD patients with and without a history of fractures showed no statistically significant differences [fracture patients (n=4): 41.2±17ng/ml vs. non-fracture patients (n=11): 49.9±11 ng/ml; p=0.47].Lastly, sensitivity of periostin as a biomarker of FD was analyzed, and was found to have low sensitivity to estimate disease activity [ROC curve; cut-off points: 39.625(0.867-0.467)]. To conclude, in the cohort of FD patients studied here, periostin serum levels did not differ significantly from those of the control group or between the two forms of the disease, and showed low sensitivity as a biomarker of the disease. (AU)

La displasia fibrosa (DF) es una enfermedad infrecuente del hueso, no hereditaria producida por una mutación somática del gen GNAS. Periostina (Postn) es un novedoso marcador, cuyos niveles séricos se encuentran elevados en los procesos de reparación tisular, enfermedades fibrosas o inflamatorias. Llevamos a cabo un estudio exploratorio caso-control para evaluar la sensibilidad de Postn como biomarcador de DF. Se incluyeron en el estudio 15 pacientes con DF apareados por edad y género con sujetos sanos (controles) en los cuales se evaluó los niveles séricos de Postn en pacientes con DF y controles y según forma de presentación clínica. No observamos diferencias estadísticamente significativas en los niveles séricos de Postn y el grupo control (DF: 51.1±10ng/ml vs. control: 44.2±15ng/ml; p=0.15) como así tampoco por forma clínica de DF (poliostótica: 51.8±9.1ng/ml vs. monos-tótica: 49.6±13 ng/ml; p=0.66). Posteriormente realizamos un sub-análisis para evaluar los niveles séricos de Postn en los pacientes con DF y antecedentes de fracturas no observan-do diferencias estadísticamente significativas [fracturados (n=4): 41.2±17ng/ml vs. no frac-turados (n=11): 49.9±11 ng/ml; p=0.47]. Por último analizamos la sensibilidad Postn como biomarcador de DF, mostrando este poseer escasa sensibilidad para estimar actividad de la enfermedad [curva ROC; puntos de corte: 39.625 (0.867-0.467)]. En conclusión, los ni-veles séricos de Postn en nuestra cohorte de pacientes con DF no mostraron diferencias estadísticamente significativas comparadas con el grupo control o por forma clínica de presentación, mostrando una baja sensibilidad como biomarcador de enfermedad. (AU)

Increased Cholesteryl Ester Transfer Protein and Lipoprotein-Associated Phospholipase A2 Activities in Children and Adolescents Presenting High Triglyceride/High-Density Lipoprotein Cholesterol (TG/HDL-C) Ratio.

OBJECTIVE: To explore the association between Triglyceride/High-density lipoprotein cholesterol (TG/HDL-C) index and these enzymes and proteins in a pediatric population. METHODS: Children and adolescents (7-14 y old) were recruited (n = 150) and anthropometric data were registered. Glucose, TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C plus cholesteryl ester transfer protein (CETP), lipoprotein-associated phospholipase A2 (Lp-PLA2) and paraoxonase 1 (PON1) activities were determined. RESULTS: Twenty-five individuals presented TG/HDL-C ratio ≥ 3.0. These individuals exhibited higher TG [164 (126-186) vs. 65 (48-72) mg/dL; p < 0.01] CETP [250 (232-263) vs. 223 (193-237)% mL/min; p < 0.01] and Lp-PLA2 (4.5 ± 1.9 vs. 3.5 ± 1.3; p < 0.05) plus lower HDL-C [41 (37-49) vs. 52 (48-62) mg/dL; p < 0.01] compared to an age-matched group with TG/HDL-C < 3.0. TG/HDL-C ratio was associated to CETP (p < 0.01) and Lp-PLA2 (p < 0.05). Multiple lineal regression analyses showed TG/HDL-C index as an independent predictor of CETP (r2 = 0.29; beta = 0.49; p < 0.01) and Lp-PLA2 (r2 = 0.21; beta = 0.32; p < 0.05) activities. CONCLUSION: Children and adolescents with TG/HDL-C ≥ 3.0 presented a more atherogenic lipid profile and higher CETP and Lp-PLA2 activities, which would indicate alterations in lipoprotein metabolism and quality.

Effect of Roux-en-Y Gastric Bypass on Lipoprotein Metabolism and Markers of HDL Functionality in Morbid Obese Patients.

PURPOSE: Morbid obesity represents the most severe form of obesity and surgical intervention would be its only successful treatment. Bariatric surgery could generate modifications in carbohydrate metabolism and in lipid profile plus lipoprotein-associated proteins and enzymes, such as lipoprotein-associated phoslipase A2 (Lp-PLA2), cholesteryl ester transfer protein (CETP), and paraoxonase (PON) 1. The aim of the present study was to analyze changes in inflammation markers, carbohydrate metabolism, and lipid parameters in patients who underwent bariatric surgery. METHODS: Thirty-seven patients with morbid obesity were recruited. Evaluations were performed before (T0) and 1 (T1) and 6 (T2) months after surgery. Glucose, insulin, high-sensitivity C-reactive protein (hsCRP), triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, apolipoproteins (apo) A-I, and B plus Interleukin 1ß and 6 levels in addition to CETP, Lp-PLA2, and PON 1 activities were determined. RESULTS: Body mass index decreased at T1 and T2 (p < 0.01). An improvement in all markers of insulin resistance (p < 0.05) was observed at T1. hsCRP levels diminished at T2 (p < 0.05). Triglyceride levels decreased at T1 and T2 (p < 0.05). HDL-C and apo A-I showed a decrease at T1 which was completely reversed at T2 (p < 0.05). Lp-PLA2 activity increased at T1, which was reversed at T2 (p < 0.05), and CETP activity was diminished at T2 (p < 0.05). PON and ARE activities decreased at T1 and partially recovered at T2 (p < 0.05). CONCLUSIONS: These results would be indicative of a favorable effect of bariatric surgery on markers of carbohydrate metabolism and cardiovascular disease lipid risk factors.

Leukocyte telomere length is associated with iron overload in male adults with hereditary hemochromatosis.

BACKGROUND: Hereditary hemochromatosis (HH) is a primary iron overload (IO) condition. Absolute telomere length (ATL) is a marker of cellular aging and DNA damage associated with chronic diseases and mortality. AIM: To evaluate the relationship between ATL and IO in patients with HH. METHODS: Cross-sectional study including 25 patients with HH: 8 with IO and 17 without IO (ferritin < 300 ng/ml) and 25 healthy controls. Inclusion criteria were: age > 18 years, male sex and HH diagnosis. Patients with diabetes or other endocrine and autoimmune diseases were excluded. ATL was measured by real-time PCR. RESULTS: HH patients with IO were older (P<0.001) and showed higher ferritin concentration (P<0.001). Patients with HH, disregarding the iron status, showed higher glucose and body mass index (BMI) than controls (both P<0.01). ATL was shorter in patients with IO than controls [with IO: 8 (6-14), without IO: 13 (9-20), and controls: 19 (15-25) kilobase pairs, P<0.01]; with a linear trend within groups (P for trend <0.01). Differences in ATL remained statistically significant after adjusting by age, BMI and glucose (P<0.05). DISCUSSION: Patients with IO featured shorter ATL while patients without IO showed only mild alterations vs. controls. Screening for IO is encouraged to prevent iron-associated cellular damage and early telomere attrition.

Activity of Lipoprotein-Associated Enzymes in Indigenous Children Living at Different Altitudes.

BACKGROUND: High altitude is associated with hypobaric hypoxia, and metabolic modifications. In particular, alterations to lipoprotein-associated enzymes have been reported under hypoxia. OBJECTIVE: To determine the association between paraoxonase 1 (PON-1) and Cholesteryl-ester transfer protein (CETP) activities and altitude in two groups of Argentinean Indigenous schoolchildren living at different altitudes. METHODS: A cross-sectional study compared 151 schoolchildren from San Antonio de los Cobres (SAC), 3,750 m, with 175 schoolchildren from Chicoana (CH), 1,400 m. Anthropometric data, lipids, apolipoprotein (apo) A-I, apo B, plus PON-1 and CETP activities were determined. RESULTS: The prevalence of overweight/obesity was significantly lower in SAC than in CH. Z- BMI (0.3 vs 0.7), Apo A-I/Apo B (1.67 vs. 1.85) and PON-1 (170 vs. 243 nmol/mL.min) were significantly lower in SAC than in CH, respectively. Total cholesterol (156 vs 144 mg/dL), triglycerides (TG) (119 vs. 94 mg/dL), apo A-I (133 vs. 128 mg/dL), apo B (84 vs. 73 mg/dL), hematocrit (48 vs. 41%), transferrin (295 vs. 260 mg/dL) and CETP (181 vs. 150%/mL.h) were significantly higher in SAC than in CH. There was a significant univariate association between altitude and transferrin (r0.38), hematocrit (r0.75), TG (r0.24), apo B (r0.29), PON-1 (r-0.40), and CETP (r0.37). Multiple linear regression analyses showed that altitude was significantly associated with children's TG (ß = 0.28, R2 = 0.14), HDL-C (ß = â€’0.27; R2 = 0.23), apo B (ß = 0.32; R2 = 0.14), CETP (ß = 0.38; R2 = 0.15) and PON-1 (ß = â€’0.36; R2 = 0.16), adjusted for age, gender and BMI. CONCLUSION: SAC children presented a more atherogenic lipid profile, plus lower PON1 and higher CETP activities, than CH children.

- 174 G>C IL-6 polymorphism and primary iron overload in male patients.

Primary iron overload (IO) is commonly associated with mutations in the hereditary hemochromatosis gene (HFE). Nonetheless, other genetic variants may influence the development of IO beyond HFE mutations. There is a single nucleotide polymorphism (SNP) at - 174 G>C of the interleukin (IL)-6 gene which might be associated with primary IO. Our aim was to study the association between the SNP - 174 G>C gene promoter of IL-6 and primary IO in middle-aged male patients. We studied 37 men with primary IO diagnosed by liver histology. Controls were age-matched male volunteers (n = 37). HFE mutations and the SNP - 174 G>C gene promoter of IL-6 were evaluated by PCR-RFLP. Logistic regression was used to evaluate the association between primary IO and SNP - 174 G>C gene promoter of IL-6. Patients and control subjects were in Hardy-Weinberg equilibrium for the SNP - 174 G>C gene promoter of IL-6 (p = 0.17). Significantly different genotype frequencies were observed between patients (43% CC, 43% CG, and 14% GG) and control subjects (10% CC, 41% CG, and 49% GG) (OR = 4.09, 95% CI = 2.06-8.13; p < 0.0001). The multiple logistic regression analysis showed that IO was significantly associated with CC homozygosis in the SNP - 174 G>C gene promoter of IL-6 (OR = 6.3, 95% CI = 1.9-21.4; p < 0.005) in a model adjusted by age and body mass index. In conclusion, CC homozygosis in the SNP - 174 G>C gene promoter of IL-6 can be proposed as one of the gene variants influencing iron accumulation in male adults with HFE mutations. Studies in larger cohorts are warranted.

Association between Apo B Levels in Mothers and in their Pre-school Age Offspring.

OBJECTIVE: The study aims to determine the association between apo B levels in mothers and their pre-school offspring. METHODS: Anthropometric measurement (e.g. BMI), lipids, lipoproteins, and apolipoproteins (e.g. apo B) levels in mothers and their children were obtained in November 2015 in Buenos Aires. RESULTS: Eighty-four children (42M) aged 5.3±1.6 years and their mothers aged 33.8±7.2 years were examined. The prevalence of overweight was 39.2 % (33) in mothers and 22.6 % (19) in children, and the prevalence of obesity was 38.1% (32) in mothers and 10.7% (9) in children. Multiple linear regression analysis showed that maternal apo B levels were associated with apo B levels in their offspring, adjusted for confounding variables (Beta=0.29; p=0.03; R2=0.25). Furthermore, offspring born to mothers with high apo B levels were six times likelier to have high apo B levels (OR), 5.7; (95% CI 1.3-25.5). CONCLUSION: This study suggests that maternal apo B levels were significantly associated with apo B concentration in their pre-school age children.

Markers of inflammation and cardiovascular disease in recently diagnosed celiac disease patients.

AIM: To evaluate novel risk factors and biomarkers of cardiovascular disease in celiac disease (CD) patients compared with healthy controls. METHODS: Twenty adult patients with recent diagnosis of CD and 20 sex, age and body mass index-matched healthy controls were recruited during a period of 12 mo. Indicators of carbohydrate metabolism, hematological parameters and high sensitive C reactive protein were determined. Moreover, lipoprotein metabolism was also explored through evaluation of the lipid profile and the activity of cholesteryl ester transfer protein and lipoprotein associated phospholipase A2, which is also considered a specific marker of vascular inflammation. The protocol was approved by the Ethic Committee from School of Pharmacy and Biochemistry, University of Buenos Aires and from Buenos Aires Italian Hospital, Buenos Aires, Argentina. RESULTS: Regarding the indicators of insulin resistance, CD patients showed higher plasma insulin levels [7.2 (5.0-11.3) mU/L vs 4.6 (2.6-6.7) mU/L, P < 0.05], increased Homeostasis Model Assessment-Insulin Resistance [1.45 (1.04-2.24) vs 1.00 (0.51-1.45), P < 0.05] and lower Quantitative Sensitive Check index [0.33 (0.28-0.40) vs 0.42 (0.34-0.65), P < 0.05] indexes. Folic acid concentration [5.4 (4.4-7.9) ng/mL vs 12.2 (8.0-14.2) ng/mL, P < 0.01] resulted to be lower and High-sensitivity C reactive protein levels higher (4.21 ± 6.47 mg/L vs 0.98 ± 1.13 mg/L, P < 0.01) in the patient group. With respect to the lipoprotein profile, CD patients showed lower high density lipoprotein-cholesterol (HDL-C) (45 ± 15 mg/dL vs 57 ± 17 mg/dL, P < 0.05) and apo A-I (130 ± 31 mg/dL vs 155 ± 29 mg/dL, P < 0.05) levels, as well as higher total cholesterol/HDL-C [4.19 (3.11-5.00) vs 3.52 (2.84-4.08), P < 0.05] and apo B/apo A-I (0.75 ± 0.25 vs 0.55 ± 0.16, P < 0.05) ratios in comparison with control subjects. No statistically significant differences were detected in lipoprotein-associated lipid transfer protein and enzymes. CONCLUSION: The presence and interaction of the detected alterations in patients with CD, would constitute a risk factor for the development of atherosclerotic cardiovascular disease.

Oxidative stress, HDL functionality and effects of intravenous iron administration in women with iron deficiency anemia.

BACKGROUND AND AIMS: Iron deficiency anemia (IDA) affects around 20-30% of adults worldwide. An association between IDA and cardiovascular disease (CVD) has been reported. Oxidative stress, inflammation and low concentration of high-density lipoproteins (HDL) were implicated on endothelial dysfunction and CVD in IDA. We studied the effects of iron deficiency and of an intravenous iron administration on oxidative stress and HDL characteristics in IDA women. METHODS: Two studies in IDA women are presented: a case-control study, including 18 patients and 18 age-matched healthy women, and a follow-up study 72hr after the administration of intravenous iron (n = 16). Lipids, malondialdehyde, cholesteryl ester transfer protein (CETP), paraoxonase-1 (PON-1) and HDL chemical composition and functionality (cholesterol efflux and antioxidative activity) were measured. Cell cholesterol efflux from iron-deficient macrophages to a reference HDL was also evaluated. RESULTS: IDA patients showed higher triglycerides and CETP activity and lower HDL-C than controls (all p < 0.001). HDL particles from IDA patients showed higher triglyceride content (+30%,p < 0.05) and lower antioxidative capacity (-23%,p < 0.05). Although HDL-mediated cholesterol efflux was similar between the patients and controls, iron deficiency provoked a significant reduction in macrophage cholesterol efflux (-25%,p < 0.05). Arylesterase activity of PON-1 was significantly lower in IDA patients than controls (-16%,p < 0.05). The intravenous administration of iron was associated with a decrease in malondialdehyde levels and an increase in arylesterase activity of PON-1 (-22% and +18%, respectively, p < 0.05). CONCLUSION: IDA is associated with oxidative stress and functionally deficient HDL particles. It remains to be determined if such alterations suffice to impair endothelial function in IDA.

Associations between disease activity, markers of HDL functionality and arterial stiffness in patients with rheumatoid arthritis.

BACKGROUND AND AIMS: Rheumatoid arthritis (RA) is a chronic, inflammatory disease associated with increased risk of cardiovascular disease (CVD). Measures of HDL metabolism/function were shown to be altered in RA patients with high disease activity. We aimed at evaluating the effect of HDL characteristics on arterial stiffness in RA patients classified according to the inflammatory disease activity. METHODS: RA patients were classified according to disease activity (DAS-28) into active RA (n = 27; DAS-28 > 3.2) and inactive RA patients (n = 17; DAS-28 < 3.2). A control group of healthy individuals was also studied (n = 33). Clinical and biochemical characteristics, cholesteryl ester transfer protein (CETP) and paraoxonase 1 (phenylacetate and paraoxonase) activities and carotid-femoral pulse wave velocity (cf-PWV) were determined. RESULTS: Anthropometric characteristics were similar in all groups. In accordance with the inflammatory status, active RA patients presented elevated hsCRP levels (p < 0.001). There were no differences in the lipid profile between groups. Similarly, features of insulin resistance were absent in RA patients (p = non-significant). Active RA patients presented higher CETP activity than the other two groups (p = 0.026). Phenylacetate and paraoxonase activities were altered in active RA patients in comparison with the other groups (p = 0.034 and p = 0.041, respectively). Cf-PWV was significantly higher in active RA patients in comparison with controls, following adjustment by age (p = 0.030). Age (ßst = 0.468, p = 0.013) and apo A-I levels (ßst = -0.405, p = 0.029) were independent predictors of cf-PWV in a model including hsCRP, HOMA-IR, and phenylacetate activity (r(2) = 0.42). CONCLUSIONS: High DAS-28 identifies patients with alterations in HDL characteristics. Plasma levels of apo A-I can be used as a marker of arterial stiffness in RA.

CONDITIONING FACTORS FOR HIGH CARDIOVASCULAR RISK IN PATIENTS WITH CUSHING SYNDROME.

OBJECTIVE: To characterize the alterations in carbohydrate and lipoprotein metabolism, to evaluate markers of lipoprotein functionality, and to identify the presence of novel atherogenic risk factors in patients with Cushing syndrome (CS) in comparison with sex- and age-matched controls. METHODS: In an open, cross-sectional study, 32 nontreated patients with active CS were consecutively recruited from the Endocrinology Service at "José de San Martín" Clinical Hospital, University of Buenos Aires, Argentina, between April 11, 2010 and December 11, 2012. The patients were compared with sex- and age-matched controls. RESULTS: Versus controls, patients with CS presented with excess weight, central obesity, and hypercortisolism. They also exhibited an insulin-resistant state, with high resistin levels (median [interquartile range], 16 [10 to 22] ng/mL versus 6 [5 to 9] ng/mL; P<.0001), a more atherogenic lipoprotein profile, high oxidized low-density lipoprotein levels (oxLDL; mean ± SD, 100 ± 31 U/L versus 75 ± 32 U/L; P<.05) and high sensitive C-reactive protein levels (median [interquartile range], 1.2 [0.6 to 3.1] mg/L versus 0.6 [0.3 to 1.1] mg/L; P<.05), and increased leukocyte count (mean ± SD, 9.5 ± 2.6 × 10(3) cells/µL versus 6.5 ± 1.4 × 10(3) cells/µL; P<.0001). Multivariate analyses showed that the increase in waist circumference was associated with both the diagnosis of CS and the degree of insulin resistance. Resistin concentration was related to a greater extent to the diagnosis of CS than to homeostasis model assessment-insulin resistance. Triglyceride and oxLDL levels were only significantly associated with the diagnosis of CS. CONCLUSION: Hypercortisolism is related to the increase observed in triglycerides and oxLDL levels, and, in combination with insulin resistance, acts to increase waist circumference and amplify the inflammatory process, key factors for the development of cardiovascular disease.