The study aim is to compare cTnI values measured with three high-sensitivity (hs) methods in apparently healthy volunteers and patients admitted to emergency department (ED) with acute coronary syndrome enrolled in a large multicentre study. Heparinized plasma samples were collected from 1511 apparently healthy subjects from 8 Italian clinical institutions (mean age: 51.5 years, SD: 14.1 years, range: 18-65 years, F/M ratio:0.95). All volunteers denied chronic or acute diseases and had normal values of routine laboratory tests. Moreover, 1322 heparinized plasma sample were also collected by 9 Italian clinical institutions from patients admitted to ED with clinical symptoms typical of acute coronary syndrome. The reference study laboratory assayed all plasma samples with three hs-methods: Architect hs-cTnI, Access hs-cTnI and ADVIA Centaur XPT methods. Principal Component Analysis (PCA) was also used to analyze the between-method differences among hs-cTnI assays. On average, a between-method difference of 31.2% CV was found among the results of hs-cTnI immunoassays. ADVIA Centaur XPT method measured higher cTnI values than Architect and Access methods. Moreover, 99th percentile URL values depended not only on age and sex of reference population, but also on the statistical approach used for calculation (robust non-parametric vs bootstrap). Due to differences in concentrations and reference values, clinicians should be advised that plasma samples of the same patient should be measured for cTnI assay in the same laboratory. Specific clinical studies are needed to establish the most appropriate statistical approach to calculate the 99th percentile URL values for hs-cTnI methods.

The high-sensitivity immunoassays for cardiac troponin I (hs-cTnI) and cardiac troponin T (hs-cTnT) are recommended by all the most recent international guidelines as gold standard laboratory methods for the detection of myocardial injury and diagnosis of acute myocardial infarction (AMI). In this review article, the Authors aimed at discussing the relevant biochemical, physiological, and clinical issues related to biological variability of cTnI and cTnT. Cardiac troponins, measured with hs-cTn methods, show a better clinical profile than the other cardio-specific biomarkers (such as the natriuretic peptides, BNP and NT-proBNP). In particular, the hs-cTn methods are characterized by a low intra-individual index of variation (30% can be considered statistically significant. These favourable biological characteristics and analytical performance of hs-cTn methods significantly improved the accuracy in the diagnostic process of acute coronary syndromes (ACS) in patients admitted to emergence department. In addition, several studies have demonstrated the clinical usefulness of cardiovascular risk evaluation with hs-cTn methods in some groups of patients with clinical conditions at high cardiovascular risk (such as systemic hypertension, severe obesity, diabetes mellitus, renal insufficiency, and chronic obstructive pulmonary disease). However, screening programs in the general population with hs-cTn methods for cardiovascular risk stratification require further investigation to define the optimal target populations, timing of measurement, and preventive interventions.

Background: The aims of this study were: (1) to calculate reliable thyroid stimulating hormone (TSH) reference intervals using laboratory databases; (2) to evaluate the relationship between TSH, sex and age values in different large Italian populations. Methods: The TSH values stored in the laboratory information system of clinical laboratories of four Italian city hospitals, including 146,801 TSH measurements (with the respective age and sex data of individuals) were taken in consideration. Assuming a log-normal distribution, to log-transformed TSH values were applied the Dixon’s iterative principle in order to exclude the outliers. At the end of this iterative process 142,821 log-transformed TSH results remained. The four clinical laboratories measured serum TSH concentrations using the same TSH immunoassay method (Access TSH 3rd IS, using UniCel DxI platform). Results: The TSH reference interval calculated in the present study (0.362–5.280 mIU/L) is similar to that suggested by the manufacturer for the Access TSH 3rd IS assay (0.45–5.33 mIU/L). TSH values in females were significantly higher than in males (females: mean=2.06 mIU/L; standard deviation [SD]=1.26 mIU/L; n=101,243; males: mean=1.92 mIU/L; SD=1.19 mIU/L; n=41,578; p<0.0001). Moreover, a negative linear relationship was observed between TSH throughout all interval age values (from 0 to 105 years). Conclusions: The results of the present multicenter study confirm that data mining techniques can be used to calculate clinically useful reference intervals for TSH. From a pathophysiological point of view, our results suggest that some Northern populations of Italy might still suffer some harmful effects on the thyroid gland due to mild to moderate iodine intake deficiency. Specific clinical trials are needed to confirm these results.

Apparently healthy children often complain of chest pain, especially after physical exercise. Cardiac biomarker levels are often measured, but the clinical relevance of these assays in children is still debated, even when a cardiac disease is present. Coronary artery disease is exceedingly rare in children, but elevated circulating levels of cardiac troponin I (cTnI) and T (cTnT) in an acute setting may help detect heart failure due to an unknown cardiac disorder, or worsening heart failure, particularly in combination with other biomarkers such as B-type natriuretic peptides. However, the interpretation of biomarkers is often challenging, especially when institutions transition from conventional cTn assays to high-sensitivity (hs-cTn) methods, as well demonstrated in the emergency setting for adult patients. From a clinical perspective, the lack of established reference values in the pediatric age is the main problem limiting the use of hs-cTn methods for the diagnosis and managements of cardiac diseases in infants, children and adolescents. This review aims to discuss the possibility to use hs-cTnI and hs-cTnT to detect cardiac disease and to explore age-related differences in biomarker levels in the pediatric age. We start from some analytical and pathophysiological considerations related to hs-cTn assays. Then, after a systematic literature search, we discuss the current evidence and possible limitations of hs-cTn assay as indicators of cardiac disease in the most frequently cardiac disease in pediatric setting.

Background: Higher body mass index (BMI) is associated with better outcome compared with normal weight in patients with HF and other chronic diseases. It remains uncertain whether the apparent protective role of obesity relates to the absence of comorbidities. Therefore, we investigated the effect of BMI on outcome in younger patients without co-morbidities as compared to older patients with co-morbidities in a large heart failure (HF) population. Methods: In an individual patient data analysis from pooled cohorts, 5,819 patients with chronic HF and data available on BMI, co-morbidities and outcome were analysed. Patients were divided into four groups based on BMI (i.e. ≤ 18.5 kg/m², 18.5–25.0 kg/m²; 25.0–30.0 kg/m²; 30.0 kg/m²). Primary endpoints included all-cause mortality and HF hospitalization-free survival. Results: Mean age was 65 ± 12 years, with a majority of males (78%), ischaemic HF and HF with reduced ejection fraction. Frequency of all-cause mortality or HF hospitalization was significantly worse in the lowest two BMI groups as compared to the other two groups; however, this effect was only seen in patients older than 75 years or having at least one relevant co-morbidity, and not in younger patients with HF only. After including medications and N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin concentrations into the model, the prognostic impact of BMI was largely absent even in the elderly group with co-morbidity. Conclusions: The present study suggests that obesity is a marker of less advanced disease, but does not have an independent protective effect in patients with chronic HF. Graphic Categories of BMI are only predictive of poor outcome in patients aged > 75 years or with at least one co-morbidity (bottom), but not in those aged < 75 years without co-morbidities (top). The prognostic effect largely disappears in multivariable analyses even for the former group. These findings question the protective effect of obesity in chronic heart failure (HF).