PMID- 38325523 OWN - NLM STAT- MEDLINE DCOM- 20240424 LR - 20240424 IS - 1097-6744 (Electronic) IS - 0002-8703 (Linking) VI - 271 DP - 2024 May TI - Plasma proteomics for prediction of subclinical coronary artery calcifications in primary prevention. PG - 55-67 LID - S0002-8703(24)00020-6 [pii] LID - 10.1016/j.ahj.2024.01.011 [doi] AB - BACKGROUND AND AIMS: Recent developments in high-throughput proteomic technologies enable the discovery of novel biomarkers of coronary atherosclerosis. The aims of this study were to test if plasma protein subsets could detect coronary artery calcifications (CAC) in asymptomatic individuals and if they add predictive value beyond traditional risk factors. METHODS: Using proximity extension assays, 1,342 plasma proteins were measured in 1,827 individuals from the Impaired Glucose Tolerance and Microbiota (IGTM) study and 883 individuals from the Swedish Cardiopulmonary BioImage Study (SCAPIS) aged 50-64 years without history of ischaemic heart disease and with CAC assessed by computed tomography. After data-driven feature selection, extreme gradient boosting machine learning models were trained on the IGTM cohort to predict the presence of CAC using combinations of proteins and traditional risk factors. The trained models were validated in SCAPIS. RESULTS: The best plasma protein subset (44 proteins) predicted CAC with an area under the curve (AUC) of 0.691 in the validation cohort. However, this was not better than prediction by traditional risk factors alone (AUC = 0.710, P = .17). Adding proteins to traditional risk factors did not improve the predictions (AUC = 0.705, P = .6). Most of these 44 proteins were highly correlated with traditional risk factors. CONCLUSIONS: A plasma protein subset that could predict the presence of subclinical CAC was identified but it did not outperform nor improve a model based on traditional risk factors. Thus, support for this targeted proteomics platform to predict subclinical CAC beyond traditional risk factors was not found. CI - Copyright (c) 2024 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Royer, Patrick AU - Royer P AD - Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Region Vastra Gotaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg, Sweden; Department of Critical Care, University Hospital of Martinique, Fort-de-France, France. FAU - Bjornson, Elias AU - Bjornson E AD - Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. FAU - Adiels, Martin AU - Adiels M AD - Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden. FAU - Alvez, Maria Bueno AU - Alvez MB AD - Science for Life Laboratory, Department of Protein Science, KTH Royal Institute of Technology, Stockholm, Sweden. FAU - Fagerberg, Linn AU - Fagerberg L AD - Science for Life Laboratory, Department of Protein Science, KTH Royal Institute of Technology, Stockholm, Sweden. FAU - Backhed, Fredrik AU - Backhed F AD - Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Region Vastra Gotaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg, Sweden. FAU - Uhlen, Mathias AU - Uhlen M AD - Science for Life Laboratory, Department of Protein Science, KTH Royal Institute of Technology, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. FAU - Gummesson, Anders AU - Gummesson A AD - Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Region Vastra Gotaland, Sahlgrenska University Hospital, Department of Clinical Genetics and Genomics, Gothenburg, Sweden. FAU - Bergstrom, Goran AU - Bergstrom G AD - Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Region Vastra Gotaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg, Sweden. Electronic address: goran.bergstrom@hjl.gu.se. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240205 PL - United States TA - Am Heart J JT - American heart journal JID - 0370465 RN - 0 (Biomarkers) RN - 0 (Blood Proteins) SB - IM MH - Humans MH - Middle Aged MH - *Coronary Artery Disease/blood/diagnostic imaging/diagnosis/epidemiology MH - Female MH - *Proteomics/methods MH - Male MH - *Vascular Calcification/blood/diagnostic imaging MH - *Biomarkers/blood MH - *Blood Proteins/analysis MH - *Primary Prevention/methods MH - Machine Learning MH - Risk Factors MH - Predictive Value of Tests MH - Tomography, X-Ray Computed/methods MH - Sweden/epidemiology COIS- Conflict of interest None. EDAT- 2024/02/08 00:42 MHDA- 2024/04/25 00:55 CRDT- 2024/02/07 19:14 PHST- 2024/01/30 00:00 [received] PHST- 2024/01/30 00:00 [accepted] PHST- 2024/04/25 00:55 [medline] PHST- 2024/02/08 00:42 [pubmed] PHST- 2024/02/07 19:14 [entrez] AID - S0002-8703(24)00020-6 [pii] AID - 10.1016/j.ahj.2024.01.011 [doi] PST - ppublish SO - Am Heart J. 2024 May;271:55-67. doi: 10.1016/j.ahj.2024.01.011. Epub 2024 Feb 5.