Relevance of TSH evaluation in elderly in-patients with non-thyroidal illness.

BACKGROUND: Non-thyroidal illness (NTI) is frequent in hospitalized patients. Its recovery is characterized by a raise in TSH levels. However, the clinical significance of high TSH levels at admission in hospitalized elderly patients with NTI remains uncertain. AIM: To explore the relevance of baseline TSH evaluation in hospitalized elderly patients with NTI. METHODS: We examined the participants with NTI (n = 123) from our previous study (Sforza, 2017). NTI was defined as: low T3 (< 80 ng/dL) and normal or low total T4 in the presence of TSH values between 0.1 and 6.0 mU/L. Thyroid function tests were performed on day 1 and day 8 of the hospital stay. Positive TSH changes (+ ΔTSH) were considered when the day-8 TSH value increased more than the reference change value for TSH (+ 78%). Multiple logistic regression was used to evaluate the independent association of baseline TSH, sex, clinical comorbidities (by ACE-27) and medications with + ΔTSH. RESULTS: Out of 123 patients (77 ± 8 years, 52% female), 34 showed a + ΔTSH. These patients had a lower TSH at admission (p < 0.001) and intra-hospital mortality (p = 0.003) than the others. In multiple logistic regression, TSH > 2.11 mU/L at baseline was associated with reduced odds to show + ΔTSH [odds ratio (95 CI) 0.29 (0.11-0.75); p = 0.011] in a model adjusted by age, sex and ACE-27. DISCUSSION: Inappropriately higher TSH levels at admission in hospitalized elderly patients were associated with a reduced ability to raise their TSH levels later on. The present results confront the idea that TSH levels at admission are irrelevant in this clinical context.

Hypothyroidism in hospitalized elderly patients: a sign of worse prognosis.

PURPOSE: Overt hypothyroidism has adverse clinical consequences and might worsen prognosis in critically ill elderly patients. However, the difficult interpretation of thyroid function tests (TFT) due to non-thyroidal illness (NTI) has led to discouragement of screening for thyroid dysfunction. Our aim was to determine the prevalence of TFT compatible with hypothyroidism and to study its influence on mortality among hospitalized elderly patients. METHODS: In this prospective study we consecutively included all patients ≥60 years admitted by the Internal Medicine Department to the hospital ward (n = 451) of the Cesar Milstein Hospital in Buenos Aires, Argentina. TFT were done on day 1 and 8. Thyroid function categories were defined as overt and subclinical hypothyroidism, overt and subclinical hyperthyroidism, euthyroidism and NTI. Stage of chronic kidney disease (CKD), Adult Comorbidity Evaluation (ACE)-27, and intra-hospital mortality were recorded. The association between mortality and TFT categories was studied by Cox regression. RESULTS: Out of 451 patients (77.0 ± 7.9 years, 54% females) 76% were categorized as NTI, 4% as overt hypothyroid, 10% as subclinical hypothyroid, 1% as subclinical hyperthyroid and 9% as euthyroid. Overt hypothyroid patients showed significantly higher mortality than the rest of the groups (25%, p < 0.05) while ACE-27 was similar among all of them (p = 0.658). In addition, patients within the overt hypothyroid category showed a higher mortality rate than NTI in a model adjusted by Stage 5-CKD, ACE-27, sex and age [HR 3.1 (1.14-8.41), p < 0.026]. CONCLUSION: Overt hypothyroidism during hospitalization was associated with elevated mortality. Further studies would reveal if TFT alterations compatible with hypothyroidism should be diagnosed/treated in hospitalized elderly patients.

Estado inflamatorio y características de HDL En mujeres con anemia por deficiencia de hierro / Inflammatory biomarkers and HDL Characteristics in women with iron deficiency anemia

INTRODUCCIÓN La anemia por deficiencia de hierro (ADH) afecta a un 20% de la población argentina. Asimismo, la enfermedad cardiovascular aterosclerótica es una de las principales causas de muerte. Pese a que diversos estudios asociaron la ADH con la aterosclerosis, los mecanismos involucrados aún no se han identificado. OBJETIVOS Caracterizar el perfil metabólico, el estado inflamatorio y la composición química y funcionalidad de las lipoproteínas de alta densidad (HDL) en pacientes con ADH. MÉTODOS Se realizó un estudio caso-control, que involucró a 18 pacientes de sexo femenino con ADH y 18 mujeres sanas. Se determinó el perfil metabólico, la actividad de proteínas y enzimas asociadas a lipoproteínas (proteína transportadora de colesterol esterificado [CETP] y paraoxonasa [PON]), marcadores de inflamación (proteína C reactiva ultrasensible [PCRus], y fosfolipasa A2 asociada a lipoproteínas [Lp-PLA2]) y la composición y funcionalidad de las HDL (eflujo de colesterol celular y actividad antioxidante). RESULTADOS Las pacientes presentaron mayores niveles de triglicéridos (+46%; p<0,001) y menores de colesterol-HDL (-25%; p<0,05) que las controles. La actividad de la enzima antioxidante PON se encontró disminuida (-18%; p<0,05), mientras que la actividad de CETP fue mayor (+37%; p<0,001) en las pacientes. Esta alteración estuvo asociada al mayor contenido de triglicéridos (+30%; p<0,05) que presentaron las HDL de las pacientes (r=0,55; p<0,01). Aunque no se observaron diferencias en la capacidad para promover el eflujo de colesterol, la actividad antioxidante de las HDL de las pacientes se encontró disminuida (-36%; p<0,05). Por último, las pacientes presentaron mayor actividad de LpPLA2, un marcador de inflamación vascular, que las controles (+21%; p<0,05). DISCUSIÓN A través de modificaciones en el perfil lipídico y en la composición y funcionalidad de las HDL, la ADH representaría un estado de mayor susceptibilidad a la inflamación vascular y, por ende, al desarrollo de aterosclerosis.

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

CONTEXT: 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. OBJECTIVE: To analyse the associations of GH and homoeostasis model assessment (HOMA) with biomarkers of cardiovascular disease and to compare the above-mentioned variables between patients with active acromegaly and controls. DESIGN AND SETTING: This open cross-sectional study was conducted at a University Hospital. PATIENTS: Twenty-two outpatients were compared with sex- and age-matched control subjects. MAIN OUTCOMES: Included clinical features, hormonal status, markers of insulin resistance, lipoprotein profile and biomarkers of cardiovascular disease. RESULTS: Patients presented higher triglyceride (median [IQR]) (1·2[1·1-1·6] vs 0·9[0·6-1·1] mm, P < 0·05), low-density lipoprotein-cholesterol (LDL-C) (mean ± SD) (3·5 ± 0·9 vs 3·0 ± 0·7mm, P < 0·05), apoB (0·98 ± 0·23 vs 0·77 ± 0·22 g/l, P < 0·05), free fatty acid (0·69 ± 0·2 vs 0·54 ± 0·2 mM, P < 0·05), oxidized-LDL (120 ± 22 vs 85 ± 19 U/l, P < 0·05) and endothelin-1 (0·90 ± 0·23 vs 0·72 ± 0·17 ng/l, P < 0·05) levels, increased cholesteryl ester transfer protein (CETP) activity (179 ± 27 vs 138 ± 30%/ml/h, P < 0·01) and lower C reactive protein (CRP) (0·25[0·1-0·9] vs 0·85[0·4-1·4] mg/l; P < 0·05) levels than control subjects. Vascular cell adhesion molecule (VCAM-1) concentration was not different. By multiple linear regression analyses, HOMA explained the variability of triglycerides (25%), high-density lipoprotein-cholesterol (HDL-C) (30%) and CETP activity (28%), while GH independently predicted LDL-C (18%), oxidized-LDL (40%) and endothelin-1 levels (19%). CONCLUSIONS: In patients with active acromegaly, GH excess contributes to the development of insulin resistance, and the interaction between both disturbances would be responsible for the appearance of atherogenic pro-oxidative and pro-inflammatory factors. Insulin resistance would be preferably associated with an atherogenic lipoprotein profile and to high CETP activity, while high GH levels would independently predict the increase in LDL-C, ox-LDL and endothelin-1.

HOMA-IR and non-HDL-C as predictors of high cholesteryl ester transfer protein activity in patients at risk for type 2 diabetes.

BACKGROUND AND AIMS: Metabolic syndrome (MS) and type 2 diabetes are highly associated with an abnormal lipoprotein profile, which may be generated and accentuated by high cholesteryl ester transfer protein (CETP) activity. Given the difficulty in measuring CETP activity, the aim was to identify simple biochemical predictors of high CETP activity. DESIGN AND METHODS: Eighty five subjects at risk for type 2 diabetes were classified according to the presence of MS. Lipoprotein profile, HOMA-IR and endogenous CETP activity were evaluated. RESULTS: As expected, MS patients presented higher concentration of glucose, insulin, triglycerides and non-HDL-C and lower HDL-C levels. Moreover, MS patients exhibited increased HOMA-IR and CETP activity. Employing a ROC curve for MS, high CETP activity was defined as >250%ml⁻¹ h⁻¹. The predictive variables of high CETP were non-HDL-C≥160mg/dl (OR=11.1;95%IC=3.3-38.2;p<0.001) and HOMA-IR>2.1 (OR=4.4;95%IC=1.3-14.8;p<0.05). CONCLUSIONS: High non-HDL-C and insulin resistance were predictors for increased CETP activity which measurement is not accessible for clinical laboratories.

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. DESIGN: Open transversal study. PATIENTS: Fifteen patients with active acromegaly and 15 controls were studied. MEASUREMENTS: We evaluated the levels of oxLDL, thiobarbituric acid reactive substances (TBARS), ceruloplasmin, bilirubin, uric acid and total reactive antioxidant potential, and the activities of ceruloplasmin, myeloperoxidase, superoxide distmutase, paraoxonase 1, and platelet activating factor acethylhydrolase. Statistical analysis was performed including body mass index as a covariate or as a fixed variable. RESULTS: Patients with acromegaly showed significantly higher levels of oxLDL (120 +/- 19 vs. 86 +/- 20 U/l, P < 0.001) and endothelin (P < 0.05), increased ceruloplasmin activity (P < 0.01) and a trend towards higher values in TBARS concentration (P = 0.07) in comparison to healthy controls. OxLDL was positively associated with GH, IGF-I and its binding protein 3 (r = 0.63, P < 0.001; r = 0.53, P < 0.01; and r = 0.56, P < 0.01; respectively). OxLDL showed direct associations with endothelin-1 (r = 0.53, P < 0.01) and ceruloplasmin activity (r = 0.43, P < 0.05). The other parameters evaluated were similar in both groups. CONCLUSIONS: The increase in plasma oxLDL levels, a direct marker of the plaque formation, could constitute a link between atherosclerosis and active acromegaly. LDL oxidation would not be the consequence of diminished antioxidant defences, but of an enhancement in prooxidant factors like ceruloplasmin.

Low adiponectin levels in primary hypertriglyceridemic male patients.

BACKGROUND AND AIMS: Adiponectin is an adipokine highly and specifically expressed by adipose cells with antiatherogenic and antiinflammatory activities. The aim of the present study was to evaluate plasma adiponectin concentration in patients with primary hypertriglyceridemia and its relationship with metabolic parameters. METHODS AND RESULTS: Male patients with primary hypertriglyceridemia and without the metabolic syndrome (n=22) were compared with normotriglyceridemic individuals (n=25). Plasma adiponectin concentration was measured by standardised enzyme-linked immunosorbent assay. Body mass index, waist circumference, glucose, insulin and non-esterified fatty acid levels, lipoprotein profile, and CETP activity were evaluated. Adiponectin levels were significantly decreased in hypertriglyceridemic patients in comparison with normotriglyceridemic subjects (4292+/-1717 vs. 6939+/-3249 ng/ml, p<0.005, respectively). Adiponectin was negatively associated with glucose (r=-0.44, p<0.01), insulin (r=-0.37, p<0.01), HOMA (r=-0.40, p<0.01), triglycerides (r=-0.36, p<0.01), VLDL-C (r=-0.34, p<0.05), and CETP (r=-0.47, p<0.001). Positive and significant correlations were observed with QUICKI (r=0.49, p<0.001) and HDL-C (r=0.33, p<0.05). In the multiple linear regression analysis, considering waist circumference, QUICKI, Log-triglycerides, HDL-C, and CETP as independent variables, Log-adiponectin showed a positive correlation with QUICKI, with an r(2)=0.229 and p<0.001. Therefore, the independent variable QUICKI explained the 23% of the variance in Log-adiponectin concentration. CONCLUSIONS: We found low adiponectin levels in a population of primary hypertriglyceridemic men without the metabolic syndrome and an independent relationship between adiponectin concentration and insulin resistance. A reduction in insulin sensitivity and its impact on adiponectin concentration could be linked to high non-esterified fatty acid levels, increased triglyceride synthesis in the liver and impaired catabolism of triglyceride-rich lipoproteins.

Beneficio de la rosuvastatina en el tratamiento de la hipertensión arterial y el remodelamiento ventricular / Beneficial effects of rosuvastatin in patients with arterial hypertension and ventricular remodeling

This paper describes the beneficial effects of rosuvastatin in patients with arterial hypertension in ventricular remodeling. As a conclusion, our data supports new evidence to encourage the use of statins for the treatment of cronic arterial hypertension and venticular remodeling