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

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

In: PLOS ONE, Vol. 10, No. 12, 2015, p. e0145930.

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@article{ccb7040049af48ada671a6b6355a9461,
title = "miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients with Symptomatic Coronary Artery Disease",
abstract = "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.",
keywords = "Aged, Biomarkers, Coronary Artery Disease/blood, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Male, MicroRNAs/blood, Middle Aged, Patient Outcome Assessment, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors",
author = "Christian Schulte and Simon Molz and Sebastian Appelbaum and Mahir Karakas and Francisco Ojeda and Lau, {Denise M} and Tim Hartmann and Lackner, {Karl J} and Dirk Westermann and Schnabel, {Renate B} and Stefan Blankenberg and Tanja Zeller",
year = "2015",
doi = "10.1371/journal.pone.0145930",
language = "English",
volume = "10",
pages = "e0145930",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

RIS

TY - JOUR

T1 - miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients with Symptomatic Coronary Artery Disease

AU - Schulte, Christian

AU - Molz, Simon

AU - Appelbaum, Sebastian

AU - Karakas, Mahir

AU - Ojeda, Francisco

AU - Lau, Denise M

AU - Hartmann, Tim

AU - Lackner, Karl J

AU - Westermann, Dirk

AU - Schnabel, Renate B

AU - Blankenberg, Stefan

AU - Zeller, Tanja

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Aged

KW - Biomarkers

KW - Coronary Artery Disease/blood

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Kaplan-Meier Estimate

KW - Male

KW - MicroRNAs/blood

KW - Middle Aged

KW - Patient Outcome Assessment

KW - Prognosis

KW - Proportional Hazards Models

KW - Prospective Studies

KW - Risk Factors

U2 - 10.1371/journal.pone.0145930

DO - 10.1371/journal.pone.0145930

M3 - SCORING: Journal article

C2 - 26720041

VL - 10

SP - e0145930

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 12

ER -