Comprehensive Proteomics Profiling Identifies Circulating Biomarkers to Distinguish Hypertrophic Cardiomyopathy From Other Cardiomyopathies With Left Ventricular Hypertrophy.

backgroundDistinguishing hypertrophic cardiomyopathy (HCM) from other cardiomyopathies with left ventricular hypertrophy (LVH), such as hypertensive LVH, transthyretin amyloid cardiomyopathy, and aortic stenosis, is sometimes challenging. Using plasma proteomics profiling, we aimed to identify circulating biomarkers and dysregulated signaling pathways specific to HCM.

methodsIn this multicenter case-control study, plasma proteomics profiling was performed in cases with HCM and controls with hypertensive LVH, transthyretin amyloid cardiomyopathy, and aortic stenosis. Two-thirds of patients enrolled earlier in each disease group were defined as the training set and the remaining one-third as the test set. Protein concentrations in HCM were compared with those in hypertensive LVH (comparison 1), transthyretin amyloid cardiomyopathy (comparison 2), and aortic stenosis (comparison 3). Candidate proteins that meet the following 2 criteria were selected: (1) higher abundance in HCM throughout all 3 comparisons or lower abundance in HCM throughout all 3 comparisons with univariable

resultsOverall, 4979 proteins in 1415 patients (HCM, n=879; hypertensive LVH, n=331; transthyretin amyloid cardiomyopathy, n=169; aortic stenosis, n=36) were analyzed. Of those, 5 proteins were selected as candidate proteins. The logistic regression model with these 5 proteins had an area under the receiver operating characteristic curve of 0.86 (95% CI, 0.82-0.89) in the test set. The MAPK (mitogen-activated protein kinase) and HIF-1 (hypoxia-inducible factor 1) pathways were dysregulated in HCM throughout the 3 comparisons.

conclusionsThis study identified circulating biomarkers that distinguish HCM from other cardiomyopathies with LVH independently from confounders and revealed signaling pathways associated with HCM.