Leonardo Gómez Rosso

Altered lipidome and antioxidative activity of small, dense HDL in normolipidemic rheumatoid arthritis: Relevance of inflammation

OBJECTIVE High-density lipoprotein (HDL) particles exert potent antiatherogenic activities, including antioxidative actions, which are relevant to attenuation of atherosclerosis progression. Such activities are enriched in small, dense HDL and can be compromised under conditions of chronic inflammation like rheumatoid arthritis (RA). However, structure-function relationships of HDL largely remain indeterminate. METHODS The relationships between HDL structure and function were evaluated in normolipidemic patients with active RA (DAS28 > 3.2; n = 12) and in normolipidemic age-matched controls (n = 10). Small, dense HDL3b and 3c particles were isolated from plasma or serum by density gradient ultracentrifugation and their physicochemical characteristics, lipidome (by LC/MS/MS) and antioxidative function (as protection of normolipidemic LDL from free radical-induced oxidation) were evaluated. RESULTS As expected, active RA patients featured significantly elevated plasma levels of high-sensitivity C-reactive protein (hsCRP; p < 0.001) and serum amyloid A (SAA; p < 0.01) relative to controls. Antioxidative activity and weight % chemical composition of small, dense HDL did not differ between RA patients and controls (p > 0.05), whereas HDL phosphosphingolipidome was significantly altered in RA. Subgroup analyses revealed that RA patients featuring high levels of inflammation (hsCRP>10 mg/l) possessed small, dense HDL with reduced antioxidative activities (p < 0.01). Furthermore, antioxidative activity of HDL was inversely correlated with plasma hsCRP (p < 0.01). CONCLUSIONS These data revealed that (i) despite normolipidemic state, the lipidome of small, dense HDL was altered in RA and (ii) high levels of inflammation can be responsible for the functional deficiency of small, dense HDL in RA.

Low plasma triiodothyronine levels in heart failure are associated with a reduced anabolic state and membrane damage

BACKGROUND Low plasma triiodothyronine (T(3)) levels are considered a prognostic predictor of death in heart failure (HF) patients. AIM To study an association between plasma T(3) levels and several cardiac, neurohormonal, and metabolic markers of HF. METHODS A total of 133 ambulatory HF patients (114 males; mean age 63.2 years) with left ventricular ejection fraction <40% were enrolled. TSH, total tetraiodothyronine (T(4)) and T(3), N-terminal pro-brain natriuretic peptide (NT-proBNP), and other cardiac and metabolic parameters were measured. The lowest tertile of T(3) (group 1) was compared against the two upper ones (group 2). RESULTS In simple logistic regression, the lowest T(3) tertile was associated with more advanced HF disease status: older (age: odds ratio (OR)=1.05; confidence interval (CI) 95% 1.01-1.09, P=0.004), lower functional capacity (walking test: OR=0.996; CI 95% 0.993-0.999, P=0.008), higher NT-proBNP (OR=1.64; CI 95% 1.19-2.27, P=0.003) and adiponectin levels (OR=1.07; CI 95% 1.02-1.11, P=0.004), lower DHEAS log-transformed (OR=0.50; CI 95% 0.31-0.80, P=0.004), and the presence of lower phase angle values as measured by body bioelectrical impedance analysis (OR=3.18; CI 95% 1.50-6.71, P=0.04) and worse renal function (OR=0.96; CI 95% 0.94-0.98, P=0.003). T(3) levels in the lowest tertile were independently associated with low phase angle values (OR=2.95, CI 95% 1.16-7.50, P=0.02) and the log transformation of DHEAS (OR=0.56; CI 95% 0.32-0.97, P=0.04). CONCLUSION We have demonstrated an association between plasma T(3) levels in the lower range and other deranged hormonal and metabolic parameters in HF patients.

Association of Lipoprotein-associated Phospholipase A2 Activity with Components of the Metabolic Syndrome in Apparently Healthy Boys

BACKGROUND Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been proposed as a biomarker of risk of cardiovascular disease (CVD). OBJECTIVE To determine the association between Lp-PLA(2) activity and BMI, insulin-resistance, components of the metabolic syndrome (MS), and lifestyle behaviors in healthy adolescent boys. METHODS Data were collected cross-sectionally from 164 adolescents from an amateur rugby club. BMI, blood pressure (BP), Tanner stages, glucose, insulin, lipids, and Lp-PLA(2) activity were measured. Questionnaires for lifestyle behaviors were completed. RESULTS Approximately 26% of the adolescents were obese and 23% overweight. There was a univariate association between Lp-PLA(2) and BMI (r=0.16;p=0.042), triglycerides (r=0.26;p=0.001), LDL-C (r=0.46;p<0.001), apo B (r=0.55;p<0.001), whereas waist circumference , BP, glucose, HOMA-IR, and HDL-C were not correlated. None of the lifestyle behaviors were significantly correlated with Lp-PLA(2). In order to analyze Lp-PLA(2) association with known CVD risk conditions, adolescents were categorized according to overweight/obesity and to the presence of metabolic syndrome. Conversely, as it was for LDL-C and apo B concentration, Lp-PLA(2) activity was not higher in adolescents with obesity. Multiple regression analysis showed that apo B was significantly associated with Lp-PLA(2) adjusted for age, BMI, triglycerides and LDL-C (R2=0.32). CONCLUSION Lp-PLA(2) activity was only associated with apo B adjusted for several confounding variables, suggesting that its clinical utility to identify individuals at risk for CVD does not surpass LDL-C and apo B in healthy adolescents. As plaque morphology may change with age, associations of Lp-PLA(2) with CVD may likewise vary with age.