Introduction: Cardiac Myosin Binding Protein-C (cMyBP-C) is a heart muscle thick filament protein that regulates contractility and lusitropy. Significant serum cMyBP-C levels occur independent of myocardial infarction (MI).
Hypothesis: Serum cMyBP-C levels reflect patients’ overall cardiovascular disease status and can be used to predict future events.
Methods: We prospectively enrolled patients who are undergoing exercise stress echocardiography, then collected blood samples at pre-test and immediately after stress. We followed patients for primary outcome (PO: sudden death, MI, revascularization, and hospitalization for any cardiac cause) and critical events (CE: death, MI, life-threatening arrhythmia, pulmonary embolism, stroke, and syncope) for 12-18 months.
Results: We enrolled 75 men (age 59±14) and 83 women (age 56±11). Exercise stress increased serum cMyBP-C on all subjects. cMyBP-C increases correlated with basal levels (r=0.77, p<0.001). cMyBP-C increases did not correlate to duration, intensity = (heartrate)X(pressure), ejection fraction, or tissue Doppler e’ of maximum myocardial relaxation velocity during early diastole. 7 CEs occurred during follow-up. Area under receiver operating curve of cMyBP-C in predicting CEs showed 0.91 (p<0.001). Cox multivariate regression of Log10(cMyBP-C) with age, sex, smoking, hypertension, dyslipidemia, diabetes, and known coronary artery disease showed that cMyBP-C was the only significant factor with hazard ratio of 13.8 (p<0.001) for CEs. 27 POs occurred during follow-up. An optimized basal cMyBP-C threshold PreC=127 ng/ml was derived from receiver operating curve analysis for POs. Cox multivariate regression of >Prec with age, sex, smoking, hypertension, dyslipidemia, diabetes, and known coronary artery disease showed that cMyBP-C was the only significant factor with hazard ratio of 8.1 (p=0.041) for POs.
Conclusion: Lack of correlation with exercise effort and basal cardiac dysfunction, but very high hazard of events combine to suggest that cMyBP-C levels reflect severity of overall cardiovascular stress; therefore, high cMyBP-C levels can indicate existence of significant cardiovascular disease that has high probability of an event occurring within 18 months.