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Plasma miRNAs improve the prediction of coronary atherosclerosis in patients with rheumatoid arthritis

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Abstract

Objective

MicroRNAs (miRNAs) regulate gene expression and are disease biomarkers. Rheumatoid arthritis (RA) patients have accelerated atherosclerosis leading to excess cardiovascular morbidity and mortality, but traditional risk factors for cardiovascular risk stratification are inadequate. In the general population, miRNAs improve cardiovascular risk estimation beyond traditional risk factors. Our objective was to develop a miRNA panel that predicts coronary atherosclerosis in RA patients.

Methods

Plasma small RNA next-generation sequencing (NGS) was performed on 161 RA patients whose Agatston scores for coronary artery calcium were previously measured. Random forest analysis of plasma NGS miRNA expression was used to determine which miRNAs best differentiated between those patients with and without coronary artery calcium. Top predictive miRNAs were assayed by quantitative PCR (qPCR). Elastic net regression was used to develop the most parsimonious models with qPCR-measured miRNA concentrations and clinical variables (age, sex, ACC/AHA 10-year risk score, DAS28 score, and diabetes) separately to predict the presence of coronary artery calcium and high coronary artery calcium. C-statistics were used to assess performance model performance.

Results

The top miRNAs which differentiated those with and without coronary atherosclerosis based on random forest analysis included let-7c-5p, miR-30e-5p, miR-30c-5p, miR-4446-3p, miR-126-5p, miR-3168, miR-425-5p, miR-126-3p, miR-30a-5p, and miR-125a-5p. For coronary artery calcium prediction, addition of all miRNAs except miR-126-3p to clinical factors improved the c-statistic modestly from 0.86 to 0.87. For high coronary artery calcium prediction, addition of all miRNAs except miR-30c-5p to clinical factors improved the c-statistic from 0.75 to 0.80.

Conclusion

A plasma miRNA panel improved the prediction of high coronary artery calcium beyond traditional risk factors and RA disease activity. Further evaluation of the miRNA panel for prediction of coronary events in RA is necessary.

Key Point

• A plasma microRNA panel including let-7c-5p, miR-30a-5p, miR-30e-5p, miR-125a-5p, miR-126-3p, miR-126-5p, miR-425-5p, miR-3168, and miR-4446-3p improved the prediction of high coronary artery calcium beyond clinical factors in patients with rheumatoid arthritis.

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Funding

Veterans Health Administration CDA IK2CX001269, Arthritis Foundation Delivering on Discovery grant, Alpha Omicron Pi, NIH Grants: P01HL116263, and CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences. The contents of this study are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.

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Authors and Affiliations

  1. Tennessee Valley Healthcare System, U.S. Department of Veterans Affairs, Nashville, TN, USA

    Michelle J. Ormseth

  2. Vanderbilt University Medical Center, 1161 21st Avenue South, T-3113 MCN, Nashville, TN, 37232-2681, USA

    Michelle J. Ormseth, Joseph F. Solus, Quanhu Sheng, Sheau-Chiann Chen, Fei Ye, Qiong Wu, Annette M. Oeser, Ryan Allen, Kasey C. Vickers & C. Michael Stein

  3. University of Alberta, Edmonton, Canada

    Paolo Raggi

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  1. Michelle J. Ormseth
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Correspondence to Michelle J. Ormseth.

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Ormseth, M.J., Solus, J.F., Sheng, Q. et al. Plasma miRNAs improve the prediction of coronary atherosclerosis in patients with rheumatoid arthritis. Clin Rheumatol 40, 2211–2219 (2021). https://doi.org/10.1007/s10067-020-05573-8

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  • DOI: https://doi.org/10.1007/s10067-020-05573-8

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