Song Cui1, Kefeng Li2, Lawrence Ang3, Jinghua Liu1, Liqian Cui4, Xiantao Song1, Shuzheng Lv1, Ehtisham Mahmud5. 1. Department of Cardiology, Beijing Anzhen Hospital, Affiliated With Capital Medical University, Beijing, China. 2. School of Medicine; Sulpizio Cardiovascular Center, University of California-San Diego, San Diego, California. Electronic address: kli@ucsd.edu. 3. Division of Cardiovascular Medicine, Sulpizio Cardiovascular Center, University of California-San Diego, San Diego, California. 4. School of Medicine; Sulpizio Cardiovascular Center, University of California-San Diego, San Diego, California. 5. Division of Cardiovascular Medicine, Sulpizio Cardiovascular Center, University of California-San Diego, San Diego, California. Electronic address: emahmud@mail.ucsd.edu.
Abstract
OBJECTIVES: The aim of this study was to evaluate the diagnostic utility of plasma metabolomic biomarkers for in-stent restenosis (ISR). BACKGROUND: ISR remains an issue for patients after percutaneous coronary intervention. Identification of biomarkers to predict ISR could be invaluable for patient care. METHODS: Next-generation metabolomic profiling was performed in the discovery phase from the plasma of 400 patients undergoing percutaneous coronary intervention. In the validation phase, targeted analysis was conducted using stable isotope dilution-multiple reaction monitoring mass spectrometry in another independent group of 500 participants. RESULTS: A set of 6 plasma metabolites was discovered and validated for the diagnosis of ISR as early as 1 month after percutaneous coronary intervention. This biomarker panel classified patients with ISR and control subjects with sensitivity of 91% and specificity of 90% in the discovery phase. The diagnostic accuracy in the independent validation phase was 90% (95% confidence interval: 87% to 100%). The defined 6 metabolites all belong to sphingolipid and phospholipid metabolism, including phosphatidylcholine diacyl C36:0, phosphatidylcholine diacyl C34:2, phosphatidylinositol diacyl C36:4, phosphatidic acid C34:1, ceramide, and sphingomyelin diacyl 18:1/20:1. These biomarkers play essential roles in cell signaling that regulates the proliferation and migration of vascular smooth muscle cells. CONCLUSIONS: Next-generation metabolomics demonstrates powerful diagnostic value in estimating ISR-related metabolic disturbance. The defined plasma biomarkers provide better early diagnostic value compared with conventional imaging techniques.
OBJECTIVES: The aim of this study was to evaluate the diagnostic utility of plasma metabolomic biomarkers for in-stent restenosis (ISR). BACKGROUND: ISR remains an issue for patients after percutaneous coronary intervention. Identification of biomarkers to predict ISR could be invaluable for patient care. METHODS: Next-generation metabolomic profiling was performed in the discovery phase from the plasma of 400 patients undergoing percutaneous coronary intervention. In the validation phase, targeted analysis was conducted using stable isotope dilution-multiple reaction monitoring mass spectrometry in another independent group of 500 participants. RESULTS: A set of 6 plasma metabolites was discovered and validated for the diagnosis of ISR as early as 1 month after percutaneous coronary intervention. This biomarker panel classified patients with ISR and control subjects with sensitivity of 91% and specificity of 90% in the discovery phase. The diagnostic accuracy in the independent validation phase was 90% (95% confidence interval: 87% to 100%). The defined 6 metabolites all belong to sphingolipid and phospholipid metabolism, including phosphatidylcholine diacyl C36:0, phosphatidylcholine diacyl C34:2, phosphatidylinositol diacyl C36:4, phosphatidic acid C34:1, ceramide, and sphingomyelin diacyl 18:1/20:1. These biomarkers play essential roles in cell signaling that regulates the proliferation and migration of vascular smooth muscle cells. CONCLUSIONS: Next-generation metabolomics demonstrates powerful diagnostic value in estimating ISR-related metabolic disturbance. The defined plasma biomarkers provide better early diagnostic value compared with conventional imaging techniques.
Authors: Sanoj Chacko; Mamas A Mamas; Magdi El-Omar; David Simon; Sohaib Haseeb; Farzin Fath-Ordoubadi; Bernard Clarke; Ludwig Neyses; Warwick B Dunn Journal: Metabolomics Date: 2021-08-23 Impact factor: 4.290