International recommendations highlight the superior value of cardiac troponins (cTns) for early diagnosis of myocardial infarction along with analytical requirements of improved precision and detectability. In this multicenter study, we investigated the analytical performance of a new high sensitive cardiac troponin I (hs-cTnI) assay and its 99th percentile upper reference limit (URL).Laboratories from nine European countries evaluated the ARCHITECTTotal imprecision of 3.3%–8.9%, 2.0%–3.5% and 1.5%–5.2% was determined for the low, medium and high controls, respectively. The lowest cTnI concentration corresponding to a total CV of 10% was 5.6 ng/L. Common interferences, sample dilution and carryover did not affect the hs-cTnI results. Slight, but statistically significant, differences with sample type were found. Concordance between the investigated hs-cTnI assay and contemporary cTnI assay at 99th percentile cut-off was found to be 95%. TnI was detectable in 75% and 57% of the apparently healthy population using the lower (1.1 ng/L) and upper (1.9 ng/L) limit of the LoD range provided by the ARCHITECTThe new ARCHITECT

Despite great progress in prevention strategies, pharmacotherapy and interventional treatment of coronary artery disease (CAD), cardiovascular events still constitute the leading cause of mortality and morbidity in the modern world. Traditional risk factors, including hypertension, diabetes mellitus, smoking, obesity, dyslipidemia, and positive family history account for the occurrence of the majority of these events, but not all of them. Adequate risk assessment remains the most challenging in individuals classified into low or intermediate risk categories. Inflammation plays a key role in the initiation and promotion of atherosclerosis and may lead to acute coronary syndrome (ACS) by the induction of plaque instability. For this reason, numerous inflammatory markers have been extensively investigated as potential candidates for the enhancement of cardiovascular risk assessment. This review aims to critically assess the clinical utility of well-established (C-reactive protein [CRP] and fibrinogen), newer (lipoprotein-associated phospholipase A2 [Lp-PLA2] and myeloperoxidase [MPO]) and novel (growth differentiation factor-15 [GDF-15]) inflammatory markers which, reflect different pathophysiological pathways underlying CAD. Although according to the traditional approach all discussed inflammatory markers were shown to be associated with the risk of future cardiovascular events in individuals with and without CAD, their clear clinical utility remains not fully elucidated. Current recommendations of numerous scientific societies predominantly advocate routine assessment of CRP in healthy people with intermediate cardiovascular risk. However, these recommendations substantially vary in their strength among particular societies. These discrepancies have a multifactorial background, including: (i) the strong prognostic value of CRP supported by solid scientific evidence and proven to be comparable in magnitude with that of total and high-density lipoprotein cholesterol, or hypertension, (ii) favourable analytical characteristics of commercially available CRP assays, (iii) lack of CRP specificity and causal relationship between CRP concentration and cardiovascular risk, and (iv) CRP dependence on other classical risk factors. Of major importance, CRP measurement in healthy men ≥50 years of age or healthy women ≥60 years of age with low-density lipoprotein cholesterol <130 mg/dL may be helpful in the selection of patients for statin therapy. Additionally, evaluation of CRP and fibrinogen or Lp-PLA2 may be considered to facilitate risk stratification in ACS patients and in healthy individuals with intermediate cardiovascular risk, respectively. Nevertheless, the clinical utility of CRP requires further investigation in a broad spectrum of CAD patients, while other promising inflammatory markers, particularly GDF-15 and Lp-PLA2, should be tested in individuals both with and without established CAD. Further studies should also focus on novel performance metrics such as measures of discrimination, calibration and reclassification, in order to better address the clinical utility of investigated biomarkers and to avoid misleadingly optimistic results. It also has to be emphasized that, due to the multifactorial pathogenesis of CAD, detailed risk stratification remains a complex process also involving, beyond assessment of inflammatory biomarkers, the patient's clinical characteristics, results of imaging examinations, electrocardiographic findings and other laboratory parameters (e.g. lipid profile, indices of renal function, markers of left ventricular overload and fibrosis, and biomarkers of myocardial necrosis, preferably cardiac troponins).

Implementation of cardiac troponin (cTn) assays has revolutionized the diagnosis, risk stratification, triage and management of patients with suspected myocardial infarction (MI). The Universal Definition of MI brought about a shift in the diagnostics of MI, from an approach primarily based on electrocardiography (ECG) to one primarily based on biomarkers. Currently, detection of a rise and/or fall in concentration or activity of myocardial necrosis biomarkers, preferentially cTns, with at least one value above the 99th percentile upper reference limit (URL), is the essential component for the diagnosis of MI. High-sensitivity cardiac troponin (hs-cTn) assays with their superior analytical performance were designed to further facilitate clinical decision making. The ability of hs-cTn assays to detect measurable cTn concentrations in at least 50% of healthy individuals, along with their improved precision (expressed as coefficient of variation ≤10% at the 99th percentile URL) associated with increased recognition of changing values, leads to enhanced risk stratification of patients with suspected MI, and also enables them to be used as prognostic tools potentially useful in other patient subsets. In this comprehensive review, we aim to integrate updated laboratory and clinical knowledge regarding hs-cTn assays in order to promote their optimal use in daily practice. We primarily focus on the role of hs-cTn assays in patients with suspected MI, discussing recommended diagnostic algorithms and result interpretation. Emphasis is also placed on the release of cTns following myocardial injury, the characteristics of antibodies used in available cTn immunoassays, and analytical performance of hs-cTn assays. In this paper, we also review potential challenges related to the selection of a healthy reference population in determining 99th percentile values, biological variation of hs-cTns, inequality between hs-cTn assays, and outline the current status of cTnI standardization. Finally, we discuss in detail the diagnostic and prognostic value of hs-cTn assays, including non-coronary causes of cTn elevation, the potential benefits and risks of point-of-care testing, and the unjustified skepticism of some clinicians regarding implementation of hs-cTn assays. In everyday clinical practice, hs-cTn assays are an important diagnostic advance, predominantly for patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), with suspected non-ST-segment elevation myocardial infarction (NSTEMI). In the NSTE-ACS setting, recently introduced short diagnostic algorithms using hs-cTn assays integrated with careful clinical and ECG assessment were found to substantially reduce the time to final diagnosis, shorten visits to the emergency department and allow earlier safe discharge of low risk subjects. Hs-cTn assays have significantly higher sensitivity and negative predictive value for NSTEMI in comparison to contemporary cTn tests, particularly in early NSTE-ACS presenters. However, due to frequently occurring mild hs-cTn elevations, they are also associated with lower specificity and reduced positive predictive value when compared to previous generations of assays. Our review underscores the need for the education of clinicians and medical laboratory professionals regarding appropriate use and interpretation of hs-cTn assays. Adequate training and clinical experience in using these tests are essential to translate the improved analytical performance of hs-cTn assays into enhanced risk stratification and hopefully better patient outcomes.

Introduction: Chronic kidney disease (CKD) is an independent factor for cardiovascular system complications, such as arterial hypertension, left ventricular hypertrophy (LVH), heart failure or accelerated atherosclerosis progression. The aim of the paper was to analyze left ventricular and arterial remodeling in patients with CKD stages 1–3 to identify the subclinical marker of cardiovascular system damage which changes first in the course of CKD. Methods: The examined group consisted of 90 patients with CKD stage 1–3 and 30 subjects constituting the control group. Left ventricular mass index (LVMI), left ventricular relative wall thickness (RWT) and ejection fraction (EF) were determined by echocardiographic examination. Pulse wave velocity (PWV) between the carotid and femoral arteries as well as common carotid artery intima–media thickness (IMT) was measured. 24-h ambulatory blood pressure monitoring was performed in all subjects. Results: No differences were found between blood pressure values in the examined groups of patients with CKD1, CKD2 and CKD3. Concentric remodeling was found in 20.0%, concentric hypertrophy in 22.2% and eccentric hypertrophy in 18.9% of patients. LVMI values in patients with CKD2 and 3 were higher than in the control group. IMT values in patients with CKD3 were higher than in patients with CKD2. PWV in patients with stage 3 CKD was significantly higher than in the control group (p < 0.05). Conclusions: In the course of CKD, the left ventricle undergoes remodeling earlier than large arterial vessels. Echocardiographic assessment of LVH in early stages of CKD may identify patients at increased cardiovascular risk.

Background: Midregional proadrenomedullin (MR-proADM) is emerging as a prognostic biomarker for detecting the failure of multiple organs. Establishment of scientifically robust reference intervals facilitates interpretation of laboratory test results. The objectives of this study were (i) to establish reliable reference intervals for plasma MR-proADM using a commercially available automated fluoroimmunoassay in apparently healthy individuals, and (ii) to identify biological determinants of MR-proADM concentrations. Methods: A total of 506 questionnaire-identified apparently healthy adults were enrolled in a single-center, cross-sectional study. A final reference group (n=172) was selected after exclusion of obese individuals, those with increased values of laboratory biomarkers indicating asymptomatic myocardial injury or dysfunction, ongoing inflammation, diabetes, dyslipidemia and renal dysfunction and outliers. Results: The 2.5th and 97.5th percentile intervals for MR-proADM values in the reference group (90% confidence interval) were 0.21 (0.19–0.23) and 0.57 (0.55–0.59) nmol/L, respectively. Although older age, higher values of HbA_1c, C-reactive protein, B-type natriuretic peptide and body mass index, together with a history of smoking and a decreased estimated glomerular filtration rate were significantly associated with increasing concentrations of MR-proADM in both univariate and multivariate analyses, magnitudes of these relationships were modest and did not substantially influence MR-proADM reference intervals. Sex-dependent difference in MR-proADM reference intervals was not detected [0.19 (0.16–0.22)–0.56 (0.54–0.60) nmol/L in females vs. 0.22 (0.20–0.25)–0.58 (0.57–0.63) nmol/L in males]. Conclusions: Our study successfully established robust reference intervals for MR-proADM concentrations in plasma. Considering the negligible influence of potential biological determinants on plasma MR-proADM, we recommend the adoption of single reference intervals for adult population as a whole.