Determination of physiological cardiac myosin-binging protein levels (cMyc) in healthy populations

Abstract Background Cardiac myosin–binding protein C (cMyC) is a cardiac-restricted protein that has more abundant, rapid release and clearance kinetics than cardiac troponin. The current ESC guideline suggests the cMyC may provide value as an alternative to cardiac troponin. The 99th percentile value is universally endorsed as the reference cut off to aid in the diagnosis of acute myocardial infarction (AMI), however, none of the report of healthy population of cMyC. Purpose The aim of this study was to evaluate the distribution of cMyC values in healthy subjects. Methods We used two cohorts in this retrospective study. 1) Healthy subjects; a total of 500 subjects (250 men and 250 women) who had annual health examinations in 2012 in the area of Kamigoto, a suburb of Nagasaki city in Southern Japan were enrolled. All participants showed none of abnormal findings including cell blood counts, chemical analysis, liver function tests, general urine tests, occult blood tests of stool, barium swallow, mammography for women, abdominal ultrasound sonography, and electrocardiogram. All blood samples were obtained in a fasting state in the morning. 2) Chest pain subjects; we collected samples from 250 subjects including 50 with non-ST elevation myocardial infarction visited admitted to a university hospital for measurement of high-sensitivity troponin T and coronary artery assessment by coronary angiography. We measured cMyC level in both cohorts by HISCL™-800 system (Sysmex corporation, Japan). The assay has a limit of detection of 0.5 ng/L and a lower limit of quantification of 1.3 ng/L. Result In healthy subjects, median age (IQR) was 44 (20, 82) in men and 50 (23, 91) in women. The 99th percentile of cMyC was 27.3 ng/L, which was around one-third lower than that in previous report (87 ng/L). In chest pain subjects, the concentrations of cMyC at presentation were significantly higher in those with versus without AMI (median, 66 ng/L versus 10 ng/L, P<0.001). Discriminatory power for AMI, as quantified by the area under the receiver-operating characteristic curve (AUC), was comparable for cMyC (AUC, 0.85 (95% CI 0.79–0.91) and hs-cTnT (AUC, 0.81 (95% CI 0.76–0.88)). Conclusion We defined the normal range of cMyC in healthy Japanese subjects. The level of cMyC at presentation provides discriminatory power comparable to hs-cTnT in the diagnosis of AMI. To determine the physiological value of a biomarker may be necessary to evaluate enough information about their health status. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Scientific Research