Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Dec 31;10(12):e0145930.
doi: 10.1371/journal.pone.0145930. eCollection 2015.

miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients With Symptomatic Coronary Artery Disease

Free PMC article

miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients With Symptomatic Coronary Artery Disease

Christian Schulte et al. PLoS One. .
Free PMC article


Background: Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD). Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD. They were identified in a prospective study in relation to future myocardial infarction.

Objectives: The aim of our study was to further evaluate the prognostic value of these miRNAs in a large prospective cohort of patients with documented CAD.

Methods: Levels of miR-126, miR-197 and miR-223 were evaluated in serum samples of 873 CAD patients with respect to the endpoint cardiovascular death. miRNA quantification was performed using real time polymerase chain reaction (RT-qPCR).

Results: The median follow-up period was 4 years (IQR 2.78-5.04). The median age of all patients was 64 years (IQR 57-69) with 80.2% males. 38.9% of the patients presented with acute coronary syndrome (ACS), 61.1% were diagnosed with stable angina pectoris (SAP). Elevated levels of miRNA-197 and miRNA-223 reliably predicted future cardiovascular death in the overall group (miRNA-197: hazard ratio (HR) 1.77 per one standard deviation (SD) increase (95% confidence interval (CI) 1.20; 2.60), p = 0.004, C-index 0.78; miRNA-223: HR 2.23 per one SD increase (1.20; 4.14), p = 0.011, C-index 0.80). In ACS patients the prognostic power of both miRNAs was even higher (miRNA-197: HR 2.24 per one SD increase (1.25; 4.01), p = 0.006, C-index 0.89); miRA-223: HR 4.94 per one SD increase (1.42; 17.20), p = 0.012, C-index 0.89).

Conclusion: Serum-derived circulating miRNA-197 and miRNA-223 were identified as predictors for cardiovascular death in a large patient cohort with CAD. These results reinforce the assumption that circulating miRNAs are promising biomarkers with prognostic value with respect to future cardiovascular events.

Conflict of interest statement

Competing Interests: Stefan Blankenberg has received research funding from Boehringer Ingelheim, Bayer, Abbott Diagnostics, SIEMENS, Thermo Fisher and Roche Diagnostics and received honoraria for lectures or consulting from Boehringer Ingelheim, Bayer, Roche, Astra Zeneca, SIEMENS, Thermo Fisher and Abbott Diagnostics. All other authors have declared that no competing interests exist. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.


Fig 1
Fig 1. Kaplan Meier Plots for each analyzed miRNA.
miRNA levels are dichotomized using their second tertile. miRNA levels are presented in minus ΔCT values so that larger values correspond to high miRNA concentrations. The p-values given describe the log-rank test.

Similar articles

See all similar articles

Cited by 33 articles

See all "Cited by" articles


    1. Creemers EE, Tijsen AJ, Pinto YM. Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? Circulation research. 2012;110(3):483–95. Epub 2012/02/04. 10.1161/CIRCRESAHA.111.247452 . - DOI - PubMed
    1. Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, et al. Circulating microRNAs in patients with coronary artery disease. Circulation research. 2010;107(5):677–84. Epub 2010/07/03. 10.1161/CIRCRESAHA.109.215566 . - DOI - PubMed
    1. Small EM, Frost RJ, Olson EN. MicroRNAs add a new dimension to cardiovascular disease. Circulation. 2010;121(8):1022–32. Epub 2010/03/03. 10.1161/CIRCULATIONAHA.109.889048 - DOI - PMC - PubMed
    1. Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, et al. Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circulation Cardiovascular genetics. 2010;3(6):499–506. Epub 2010/10/06. 10.1161/CIRCGENETICS.110.957415 . - DOI - PubMed
    1. Gomes da Silva AM, Silbiger VN. miRNAs as biomarkers of atrial fibrillation. Biomarkers: biochemical indicators of exposure, response, and susceptibility to chemicals. 2014:1–6. Epub 2014/08/30. 10.3109/1354750x.2014.954001 . - DOI - PubMed

Publication types

Grant support

The AtheroGene study was supported by a grant of the ‘Stiftung Rheinland-Pfalz für Innovation’, Ministry for Science and Education (AZ 15202–386261/545), Mainz, Germany.