Martino Deidda1, Antonio Noto1, Christian Cadeddu Dessalvi1, Daniele Andreini2, Felicita Andreotti3, Eleuterio Ferrannini4, Roberto Latini5, Aldo P Maggioni6, Marco Magnoni7, Attilio Maseri8, Giuseppe Mercuro9. 1. Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy. 2. Centro Cardiologico Monzino, IRCCS, Milan, Italy; Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Italy. 3. Cardiovascular Medicine, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. 4. CNR Institute of Clinical Physiology, Pisa, Italy. 5. Mario Negri Institute of Pharmacological Research, IRCCS, Milan, Italy. 6. ANMCO Research Center, Heart Care Foundation, Florence, Italy; Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy. 7. IRCCS Ospedale San Raffaele and Università Vita-Salute San Raffaele, Milan, Italy. 8. Heart Care Foundation, Florence, Italy. 9. Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy. Electronic address: giuseppemercuro@gmail.com.
Abstract
BACKGROUND: Traditional cardiovascular risk factors (RFs) and coronary artery disease (CAD) do not always run parallel. We investigated functional-metabolic correlations of CAD, RFs, or neither in the CAPIRE (Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation) 2 × 2 phenotypic observational study. METHODS: Two hundred and fortyone subjects were included based on RF burden, presence/absence of CAD (assessed by computed tomography angiography), age and sex. Participants displayed one of four phenotypes: CAD with ≥3 RFs, no-CAD with ≥3 RFs, CAD with ≤1 RF and no-CAD with ≤1 RF. Metabolites were identified by gas chromatography-mass spectrometry and pathways by metabolite set enrichment analysis. RESULTS: Characteristic patterns and specific pathways emerged for each phenotypic group: amino sugars for CAD/high-RF; urea cycle for no-CAD/high-RF; glutathione for CAD/low-RF; glycine and serine for no-CAD/low-RF. Presence of CAD correlated with ammonia recycling; absence of CAD with the transfer of acetyl groups into mitochondria; high-risk profile with alanine metabolism (all p < 0.05). The comparative case-control analyses showed a statistically significant difference for the two pathways of phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism in the CAD/Low-RF vs NoCAD/Low-RF comparison. CONCLUSIONS: The present 2 × 2 observational study identified specific metabolic pathways for each of the four phenotypes, providing novel functional insights, particularly on CAD with low RF profiles and on the absence of CAD despite high-risk factor profiles.
BACKGROUND: Traditional cardiovascular risk factors (RFs) and coronary artery disease (CAD) do not always run parallel. We investigated functional-metabolic correlations of CAD, RFs, or neither in the CAPIRE (Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation) 2 × 2 phenotypic observational study. METHODS: Two hundred and fortyone subjects were included based on RF burden, presence/absence of CAD (assessed by computed tomography angiography), age and sex. Participants displayed one of four phenotypes: CAD with ≥3 RFs, no-CAD with ≥3 RFs, CAD with ≤1 RF and no-CAD with ≤1 RF. Metabolites were identified by gas chromatography-mass spectrometry and pathways by metabolite set enrichment analysis. RESULTS: Characteristic patterns and specific pathways emerged for each phenotypic group: amino sugars for CAD/high-RF; urea cycle for no-CAD/high-RF; glutathione for CAD/low-RF; glycine and serine for no-CAD/low-RF. Presence of CAD correlated with ammonia recycling; absence of CAD with the transfer of acetyl groups into mitochondria; high-risk profile with alanine metabolism (all p < 0.05). The comparative case-control analyses showed a statistically significant difference for the two pathways of phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism in the CAD/Low-RF vs NoCAD/Low-RF comparison. CONCLUSIONS: The present 2 × 2 observational study identified specific metabolic pathways for each of the four phenotypes, providing novel functional insights, particularly on CAD with low RF profiles and on the absence of CAD despite high-risk factor profiles.
Authors: Huali Jiang; Li Li; Weijie Chen; Benfa Chen; Heng Li; Shanhua Wang; Min Wang; Yi Luo Journal: Front Physiol Date: 2021-11-29 Impact factor: 4.566