Unbiased plasma proteomics discovery of biomarkers for improved detection of subclinical atherosclerosis
Por:
Nunez, E, Fuster, V, Gomez-Serrano, M, Valdivielso, JM, Fernandez-Alvira, JM, Martinez-Lopez, D, Rodriguez, JM, Bonzon-Kulichenko, E, Calvo, E, Alfayate, A, Bermudez-Lopez, M, Escola-Gil, JC, Fernandez-Friera, L, Cerro-Pardo, I, Mendiguren, JM, Sanchez-Cabo, F, Sanz, J, Ordovas, JM, Blanco-Colio, LM, Garcia-Ruiz, JM, Ibanez, B, Lara-Pezzi, E, Fernandez-Ortiz, A, Martin-Ventura, JL, Vazquez, J
Publicada:
1 feb 2022
Ahead of Print:
1 feb 2022
Resumen:
Background Imaging of subclinical atherosclerosis improves cardiovascular risk prediction on top of traditional risk factors. However, cardiovascular imaging is not universally available. This work aims to identify circulating proteins that could predict subclinical atherosclerosis.
Methods Hypothesis-free proteomics was used to analyze plasma from 444 subjects from PESA cohort study (222 with extensive atherosclerosis on imaging, and 222 matched controls) at two timepoints (three years apart) for discovery, and from 350 subjects from AWHS cohort study (175 subjects with extensive atherosclerosis on imaging and 175 matched controls) for external validation. A selected three-protein panel was further validated by immunoturbidimetry in the AWHS population and in 2999 subjects from ILERVAS cohort study.
Findings PIGR, IGHA2, APOA, HPT and HEP2 were associated with subclinical atherosclerosis independently from traditional risk factors at both timepoints in the discovery and validation cohorts. Multivariate analysis rendered a potential three-protein biomarker panel, including IGHA2, APOA and HPT. Immunoturbidimetry confirmed the independent associations of these three proteins with subclinical atherosclerosis in AWHS and ILERVAS. A machine-learning model with these three proteins was able to predict subclinical atherosclerosis in ILERVAS (AUC [95%CI]:0.73 [0.70-0.74], p < 1 x 10(-99)), and also in the subpopulation of individuals with low cardiovascular risk according to FHS 10-year score (0.71 [0.69-0.73], p < 1 x 10(-69)).
Interpretation Plasma levels of IGHA2, APOA and HPT are associated with subclinical atherosclerosis independently of traditional risk factors and offers potential to predict this disease. The panel could improve primary prevention strategies in areas where imaging is not available. Copyright (C) 2022 The Authors. Published by Elsevier B.V.
Filiaciones:
Nunez, E:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Fuster, V:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
Icahn Sch Med Mt Sinai, New York, NY 10029 USA
Gomez-Serrano, M:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Valdivielso, JM:
Inst Recerca Biomed, Lleida, Spain
Fernandez-Alvira, JM:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
Martinez-Lopez, D:
IIS Fdn Jimenez Diaz, Madrid, Spain
Rodriguez, JM:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
Bonzon-Kulichenko, E:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Calvo, E:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Alfayate, A:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
Bermudez-Lopez, M:
Inst Recerca Biomed, Lleida, Spain
Escola-Gil, JC:
Inst Invest Biomed St Pau, Barcelona, Spain
CIBER Diabet & Enfermedades Metab CIBERDEM, Madrid, Spain
Fernandez-Friera, L:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
Cerro-Pardo, I:
IIS Fdn Jimenez Diaz, Madrid, Spain
Mendiguren, JM:
Banco Santander, Madrid, Spain
Sanchez-Cabo, F:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
Sanz, J:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
Icahn Sch Med Mt Sinai, New York, NY 10029 USA
Ordovas, JM:
Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA
Blanco-Colio, LM:
IIS Fdn Jimenez Diaz, Madrid, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Garcia-Ruiz, JM:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
Ibanez, B:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
IIS Fdn Jimenez Diaz, Madrid, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Lara-Pezzi, E:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Fernandez-Ortiz, A:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Hosp Clin San Carlos, IDISSC, Madrid, Spain
Martin-Ventura, JL:
IIS Fdn Jimenez Diaz, Madrid, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Vazquez, J:
Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Green Published, gold
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