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

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 m...

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Published in:PloS one Vol. 10; no. 12; p. e0145930
Main Authors: Schulte, Christian, Molz, Simon, Appelbaum, Sebastian, Karakas, Mahir, Ojeda, Francisco, Lau, Denise M., Hartmann, Tim, Lackner, Karl J., Westermann, Dirk, Schnabel, Renate B., Blankenberg, Stefan, Zeller, Tanja
Format: Journal Article
Language:English
Published: United States Public Library of Science 31.12.2015
Public Library of Science (PLoS)
Subjects:
Aged
Angina
Angina pectoris
Angioplasty
Bioindicators
Biomarkers
Blood platelets
Cardiology
Cardiovascular disease
Cardiovascular diseases
Cardiovascular system
Causes of
Confidence intervals
Coronary artery
Coronary artery disease
Coronary Artery Disease - blood
Coronary Artery Disease - genetics
Coronary Artery Disease - mortality
Coronary heart disease
Coronary vessels
Death
Diabetes
Diagnostic systems
Family medical history
Family physicians
Female
Follow-Up Studies
Genetic aspects
Health aspects
Health risks
Heart attacks
Heart diseases
Hospitals
Humans
Kaplan-Meier Estimate
Laboratories
Male
Males
Medical diagnosis
Medicine
MicroRNA
MicroRNAs
MicroRNAs - blood
MicroRNAs - genetics
Middle Aged
miRNA
Mortality
Myocardial infarction
Patient Outcome Assessment
Patient outcomes
Patients
Polymerase chain reaction
Prognosis
Proportional Hazards Models
Prospective Studies
Risk Factors
SAP protein
Smooth muscle
Stents
Studies
Germany
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary: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. 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. 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). 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). 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.
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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.
Conceived and designed the experiments: CS SM RS KL SB TZ. Performed the experiments: CS SM DML TH TZ. Analyzed the data: CS SM SA MK FO RS TZ. Contributed reagents/materials/analysis tools: KL SB TZ. Wrote the paper: CS SM MK DW TZ.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0145930