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| Home > Articles > Published articles > Unbiased plasma proteomics discovery of biomarkers for improved detection of subclinical atherosclerosis |
(Institut de Recerca Biomèdica de Lleida) (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares) (Institut de Recerca Biomèdica de Lleida) (Institut d'Investigació Biomèdica Sant Pau) (IIS-Fundación Jiménez-Díaz) (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares) (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
| Date: | 2022 |
| Abstract: | 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 × 10), 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 × 10). 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. |
| Grants: | Ministerio de Ciencia, Innovación y Universidades BIO2015-67580-P Ministerio de Ciencia, Innovación y Universidades PGC2018-097019-B-I00 Ministerio de Ciencia, Innovación y Universidades PID2019-106814RB-I00 Ministerio de Ciencia, Innovación y Universidades SAF2016-80843-R Instituto de Salud Carlos III IPT17/0019 Instituto de Salud Carlos III PI15/02019 Instituto de Salud Carlos III PI18/00610 Instituto de Salud Carlos III RD16/0009 |
| Note: | Altres ajuts: CIBERCV; CIBERDEM; Fundació La Marató de TV3 (122/C/2015); Fundació "la Caixa" (project HR17-00247); Centro Nacional de Investigaciones Cardiovasculares (CNIC); Banco Santander; Diputació de Lleida; Fondos FEDER; Pro CNIC Foundation. |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Subclinical atherosclerosis ; Proteomics ; Biomarkers ; IGHA2 ; APOA ; HPT |
| Published in: | EBioMedicine, Vol. 76 (february 2022) , p. 103874, ISSN 2352-3964 |
