Laura Boero

Relation of left ventricular ejection fraction and functional capacity with metabolism and inflammation in chronic heart failure with reduced ejection fraction (from the MIMICA Study).

Catabolism and inflammation play a role in the physiopathology of heart failure with reduced ejection fraction and are more pronounced in the advanced stages of the disease. Our aim was to demonstrate that in patients with stable heart failure with reduced ejection fraction adequately treated, a direct relation exists between functional impairment, as evaluated by left ventricular ejection fraction (LVEF) and the 6-minute walking distance (6MWD), and catabolic and inflammatory markers. In 151 outpatients with heart failure and a LVEF of < or =40% (median age 64 years, LVEF 29%, and 6MWD 290 m) we measured the laboratory and body composition parameters that indicate directly or indirectly inflammatory activation, anabolic-catabolic balance, and nutritional status. We performed an analysis stratified by quartiles of LVEF and 6MWD and linear regression analysis to explore our hypothesis. In the linear regression analysis, after adjusting for age, gender, and etiology, LVEF was not related to the metabolic, inflammatory, or nutritional parameters. The 6MWD was directly related to albumin (p = 0.002) and log transformation of dehydroepiandrosterone (p = 0.013) and inversely to adiponectin (p = 0.001) and the log-transformation of high-sensitivity C-reactive protein (p = 0.037). In conclusion, in a population with stable heart failure with reduced ejection fraction, the 6MWD was related to the degree of inflammatory activity and catabolism, but LVEF was not. Even a slightly diminished functional capacity implies underlying inflammation and catabolic activation.

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.

High risk of cardiovascular disease in iron overload patients

Eur J Clin Invest 2011; 41 (5): 479–486

Alterations in biomarkers of cardiovascular disease (CVD) in active acromegaly

Objectives  In acromegalic patients, cardiovascular and metabolic comorbidities contribute to enhance mortality. Available data on the lipoprotein profile of these patients are controversial. Our aim was to characterize the lipoprotein profile and emergent biomarkers of cardiovascular disease in active acromegalic patients in comparison with sex‐ and age‐matched healthy controls.

GH levels and insulin sensitivity are differently associated with biomarkers of cardiovascular disease in active acromegaly

Acromegaly is characterized by GH excess and insulin resistance. It is not known which of these disorders is responsible for the increased atherogenic risk in these patients.

Increased oxidized low density lipoprotein associated with high ceruloplasmin activity in patients with active acromegaly

Objective  Active acromegaly is associated with increased mortality from cardiovascular causes. Several studies have shown increased atherogenic risk factors and biomarkers of inflammation and atherosclerosis in association with growth hormone excess. The aim of this study was to evaluate oxidized low density lipoprotein (oxLDL) levels and some modulators of LDL oxidative modification in patients with acromegaly.

Proatherogenic disturbances in lipoprotein profile, associated enzymes and transfer proteins in women with iron deficiency anaemia

OBJECTIVE To characterize the lipid-related atherogenic risk factors in iron deficiency anaemia (IDA) patients. DESIGN AND METHODS Twenty IDA women were compared to healthy age-matched controls. Lipoprotein profile, cholesteryl ester transfer protein (CETP), paraoxonase (PON) 1 and lipoprotein-associated phospholipase A(2) (LpPLA(2)) activities and plasma levels of oxidized-LDL were evaluated. RESULTS Triglycerides were higher (median [range]) (1.0 [0.5-1.9] vs. 0.7 [0.5-1.5] mmol/L, p<0.05) and HDL-C lower (mean + or - SD) (1.3 + or - 0.3 vs. 1.6 + or - 0.4 mmol/L, p<0.01) in the patients group. CETP (197 + or - 29% vs. 151 + or - 29% mL(-1) h(-1), p<0.001), PON 1 (122 + or - 17 vs. 140 + or - 33 micromol mL(-1) min(-1), p<0.05) and LpPLA(2) (9.6 + or - 2.0 vs. 8.1 + or - 1.7 micromol mL(-1) h(-1), p<0.05) activities were different in IDA women. No difference was observed in oxidized-LDL. Haemoglobin correlated negatively with triglycerides (r=-0.35, p<0.05), CETP (r=-0.62, p<0.001) and LpPLA(2) (r=-0.34, p<0.05), while ferritin was positively associated with HDL-C (r=0.39, p<0.05) and inversely with CETP (r=-0.49, p<0.005). CONCLUSION The alterations in lipoprotein profile, CETP, PON 1 and LpPLA(2) activities described in the present study indicate that non-treated IDA might represent a proatherogenic state.

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.

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.

Prolactinomas: evolution after menopause

OBJETIVE The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause. SUBJECTS AND METHODS Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results: Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL 5t5and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining. CONCLUSIONS Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.