Among breast cancer patients receiving cardiotoxic therapies, cathepsin C was significantly associated with a reduced risk of incident cardiac dysfunction (HR 0.61; 95% CI 0.41-0.90).
Cohort (n=547)
Proteomic and metabolomic profiling identified novel biomarkers, such as cathepsin C, associated with cardiac remodeling and dysfunction in breast cancer patients receiving cardiotoxic therapies.
Hazard Ratio: 0.61 (95% CI 0.41–0.9)
BACKGROUND AND AIMS: The objective of this study was to define the relationships between the circulating proteome and metabolome with cardiac structure and function in patients with breast cancer receiving cardiotoxic therapies. METHODS: Proteomics and metabolomics profiling was performed in a longitudinal, prospective cohort study of breast cancer patients receiving anthracyclines and/or trastuzumab, using the Olink Explore 3072 platform and rapid liquid chromatography-mass spectrometry, respectively. Multivariable linear mixed-effect models evaluated the contemporaneous (same visit) and lagged (subsequent visit) associations between repeated measures of individual proteins or metabolites with quantitative echocardiographic measures of cardiac structure left ventricular (LV) mass and left atrial volume index and function LV ejection fraction (LVEF), longitudinal and circumferential strain, E/e', and ventricular-arterial coupling. Cox regression and pathway enrichment analyses were conducted for biomarkers demonstrating significant associations with cardiac function. RESULTS: Across 547 breast cancer participants (median age 50 years), 203 unique proteins and 16 unique metabolites were significantly associated with measures of cardiac structure and function in contemporaneous and lagged analyses. Notably, cathepsin C was associated with LVEF false discovery rate (FDR), P = .017, longitudinal strain (FDR, P = .046), left atrial volume index (FDR, P = .035), and incident cardiac dysfunction, defined by an LVEF decline ≥10% to <50% (hazard ratio .61, 95% confidence interval .41, .90). The 147 proteins associated with cardiac function were enriched in biological processes reflective of protein deubiquitination, protein modification by small protein removal, macromolecule catabolic processes, and global metabolic pathways. Individual metabolites significantly associated with cardiac function (LVEF, longitudinal strain) included n-acetylglutamine, aspartic acid, acetylasparagine, alanyl-alanine, and prolyl-glycine (FDR, P-value < .001), and belonged to amino acids and derivatives and peptides. CONCLUSIONS: These findings provide translational insights into cancer therapy-related cardiac dysfunction and remodelling and identify potential new biomarkers of cardiotoxicity. There is an important need for validation of these findings and a deeper understanding of the biology of these biomarkers.
“In this issue of the European Heart Journal, the study by Ky and colleagues represents an important step forward in addressing these critical knowledge gaps. In a longitudinal cohort of 547 patients with breast cancer receiving anthracyclines and/or trastuzumab, the investigators integrated plasma proteomic and metabolomic profiling with echocardiographic phenotyping across three prospectively collected time points (baseline, 2–3 months, and 12 months after therapy initiation). This longitudinal framework is especially relevant in cardio-oncology, particularly in the setting of anthracycline-based chemotherapy, where the transition from subclinical myocardial injury to overt cardiac dysfunction may evolve over months or even years.”
A study in the European Heart Journal found higher levels of microplastics in the blood of patients who had a heart attack, linking environmental pollution to acute coronary events.
Ky et al. (Tue,) conducted a cohort in Breast cancer receiving cardiotoxic therapies (n=547). Circulating proteins and metabolites (e.g., cathepsin C) was evaluated on Incident cardiac dysfunction (LVEF decline ≥10% to <50%) (HR 0.61, 95% CI 0.41-0.90). Among breast cancer patients receiving cardiotoxic therapies, cathepsin C was significantly associated with a reduced risk of incident cardiac dysfunction (HR 0.61; 95% CI 0.41-0.90).
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