Biological variation of cardiac myosin-binding protein C in healthy individuals

Abstract

Objectives Cardiac myosin-binding protein C (cMyC) is a novel biomarker of myocardial injury, with a promising role in the triage and risk stratification of patients presenting with acute cardiac disease. In this study, we assess the weekly biological variation of cMyC, to examine its potential in monitoring chronic myocardial injury, and to suggest analytical quality specification for routine use of the test in clinical practice. Methods Thirty healthy volunteers were included. Non-fasting samples were obtained once a week for ten consecutive weeks. Samples were tested in duplicate on the Erenna® platform by EMD Millipore Corporation. Outlying measurements and subjects were identified and excluded systematically, and homogeneity of analytical and within-subject variances was achieved before calculating the biological variability (CVI and CVG), reference change values (RCV) and index of individuality (II). Results Mean age was 38 (range, 21–64) years, and 16 participants were women (53%). The biological variation, RCV and II with 95% confidence interval (CI) were: CVA (%) 19.5 (17.8–21.6), CVI (%) 17.8 (14.8–21.0), CVG (%) 66.9 (50.4–109.9), RCV (%) 106.7 (96.6–120.1)/−51.6 (−54.6 to −49.1) and II 0.42 (0.29–0.56). There was a trend for women to have lower CVG. The calculated RCVs were comparable between genders. Conclusions cMyC exhibits acceptable RCV and low II suggesting that it could be suitable for disease monitoring, risk stratification and prognostication if measured serially. Analytical quality specifications based on biological variation are similar to those for cardiac troponin and should be achievable at clinically relevant concentrations.

Sex Hormones and Adrenal Steroids: Biological Variation Estimated Using Direct and Indirect Methods

“…The participants (16 women and 14 men) were median 36 years old (10th to 90th percentile, 24 to 59 years). All were healthy by the inclusion criteria; these results are previously described by Alaour et al (12). The characteristics of the patients and sampling interval of the data withdrawn from the laboratory databases is shown in online Supplemental Table 2.…”

“…Ten healthy volunteers were recruited from each of 3 different centers: Bergen (Haukeland University Hospital), Oslo (University of Oslo and Akershus University Hospital), and London (King's College London and Guys and St Thomas' Hospital), totaling 30 volunteers (7,11). The study has been described in detail earlier by Alaour et al (12). Screening of potential participants used the following inclusion criteria: healthy individuals between 18 and 75 years.…”

“…Exclusion criteria were pregnancy, any evident disease, use of prescription drugs (except oral contraceptive pills), any chronic illness (including previous history of endocrine illness) or cancer, and any of the following abnormalities on screening blood tests: estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m 2 , Nterminal prohormone of brain natriuretic peptide (NT-proBNP) greater than the local reference limit, cardiac troponin T (hs-cTnT) > 99th percentile value (>14 ng/L). A unified standard operating protocol was used across all centers to minimize preanalytical variability (12). In brief, for each volunteer, non-fasting venous blood was drawn after a resting period of 15 min between 8:00 AM and 10:00 AM on the same weekday ±1 day.…”

Biological variation, reference change values and index of individuality of GDF-15

“…We carried out a multicenter study at Haukeland University Hospital, Akershus University Hospital in Norway, King’s College London and Guy’s and St Thomas’ Hospital, United Kingdom. The study design was planned according to the EFLM checklist for biological variation studies (BIVAC) [ 8 ], and is described earlier [ 9 ]. Thirty healthy volunteers were recruited, 16 were women and two were daily smokers.…”

“…In total 17/30 (57%) individuals had ≥4 duplicate measurements above the LOD, and were eligible for further analysis. Analytical outliers were removed according to Burnett test, and outliers in mean values according to Reeds criteria [ 9 ]. The serial values for each individual were checked for linear trend using liner regression; subjects with significant trend (p-value of 0.01) were removed.…”