Use of biomarkers to establish potential role and function of circulating microRNAs in acute heart failure

Eline L Vegter; Daniela Schmitter; Yanick Hagemeijer; Ekaterina S Ovchinnikova; Pim van der Harst; John R Teerlink; Christopher M O'Connor; Marco Metra; Beth A Davison; Daniel Bloomfield; Gad Cotter; John G Cleland; Michael M Givertz; Piotr Ponikowski; Dirk J van Veldhuisen; Peter van der Meer; Eugene Berezikov; Adriaan A Voors; Mohsin A F Khan

doi:10.1016/j.ijcard.2016.09.010

Use of biomarkers to establish potential role and function of circulating microRNAs in acute heart failure

Eline L Vegter, Daniela Schmitter, Yanick Hagemeijer, Ekaterina S Ovchinnikova, Pim van der Harst, John R Teerlink, Christopher M O'Connor, Marco Metra, Beth A Davison, Daniel Bloomfield, Gad Cotter, John G Cleland, Michael M Givertz, Piotr Ponikowski, Dirk J van Veldhuisen, Peter van der Meer, Eugene Berezikov, Adriaan A Voors, Mohsin A F Khan

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Circulating microRNAs (miRNAs) emerge as potential heart failure biomarkers. We aimed to identify associations between acute heart failure (AHF)-specific circulating miRNAs and well-known heart failure biomarkers.

METHODS: Associations between 16 biomarkers predictive for 180day mortality and the levels of 12 AHF-specific miRNAs were determined in 100 hospitalized AHF patients, at baseline and 48hours. Patients were divided in 4 pre-defined groups, based on clinical parameters during hospitalization. Correlation analyses between miRNAs and biomarkers were performed and complemented by miRNA target prediction and pathway analysis.

RESULTS: No significant correlations were found at hospital admission. However, after 48hours, 7 miRNAs were significantly negatively correlated to biomarkers indicative for a worse clinical outcome in the patient group with the most unfavorable in-hospital course (n=21); miR-16-5p was correlated to C-reactive protein (R=-0.66, p-value=0.0027), miR-106a-5p to creatinine (R=-0.68, p-value=0.002), miR-223-3p to growth differentiation factor 15 (R=-0.69, p-value=0.0015), miR-652-3p to soluble ST-2 (R=-0.77, p-value<0.001), miR-199a-3p to procalcitonin (R=-0.72, p-value<0.001) and galectin-3 (R=-0.73, p-value<0.001) and miR-18a-5p to procalcitonin (R=-0.68, p-value=0.002). MiRNA target prediction and pathway analysis identified several pathways related to cardiac diseases, which could be linked to some of the miRNA-biomarker correlations.

CONCLUSIONS: The majority of correlations between circulating AHF-specific miRNAs were related to biomarkers predictive for a worse clinical outcome in a subgroup of worsening heart failure patients at 48hours of hospitalization. The selective findings suggest a time-dependent effect of circulating miRNAs and highlight the susceptibility to individual patient characteristics influencing potential relations between miRNAs and biomarkers.

Original language	English
Pages (from-to)	231-239
Number of pages	9
Journal	International Journal of Cardiology
Volume	224
DOIs	https://doi.org/10.1016/j.ijcard.2016.09.010
Publication status	Published - 1 Dec 2016
Externally published	Yes

Keywords

Acute Disease
Aged
Aged, 80 and over
Biomarkers/blood
Databases, Factual/trends
Diuretics/therapeutic use
Female
Heart Failure/blood
Hospitalization/trends
Humans
Male
MicroRNAs/blood
Middle Aged
Xanthines/therapeutic use

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10.1016/j.ijcard.2016.09.010

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Vegter, E. L., Schmitter, D., Hagemeijer, Y., Ovchinnikova, E. S., van der Harst, P., Teerlink, J. R., O'Connor, C. M., Metra, M., Davison, B. A., Bloomfield, D., Cotter, G., Cleland, J. G., Givertz, M. M., Ponikowski, P., van Veldhuisen, D. J., van der Meer, P., Berezikov, E., Voors, A. A., & Khan, M. A. F. (2016). Use of biomarkers to establish potential role and function of circulating microRNAs in acute heart failure. International Journal of Cardiology, 224, 231-239. https://doi.org/10.1016/j.ijcard.2016.09.010

@article{71f609f2f2bb4a61a0a52c926745a4b8,

title = "Use of biomarkers to establish potential role and function of circulating microRNAs in acute heart failure",

abstract = "BACKGROUND: Circulating microRNAs (miRNAs) emerge as potential heart failure biomarkers. We aimed to identify associations between acute heart failure (AHF)-specific circulating miRNAs and well-known heart failure biomarkers.METHODS: Associations between 16 biomarkers predictive for 180day mortality and the levels of 12 AHF-specific miRNAs were determined in 100 hospitalized AHF patients, at baseline and 48hours. Patients were divided in 4 pre-defined groups, based on clinical parameters during hospitalization. Correlation analyses between miRNAs and biomarkers were performed and complemented by miRNA target prediction and pathway analysis.RESULTS: No significant correlations were found at hospital admission. However, after 48hours, 7 miRNAs were significantly negatively correlated to biomarkers indicative for a worse clinical outcome in the patient group with the most unfavorable in-hospital course (n=21); miR-16-5p was correlated to C-reactive protein (R=-0.66, p-value=0.0027), miR-106a-5p to creatinine (R=-0.68, p-value=0.002), miR-223-3p to growth differentiation factor 15 (R=-0.69, p-value=0.0015), miR-652-3p to soluble ST-2 (R=-0.77, p-value<0.001), miR-199a-3p to procalcitonin (R=-0.72, p-value<0.001) and galectin-3 (R=-0.73, p-value<0.001) and miR-18a-5p to procalcitonin (R=-0.68, p-value=0.002). MiRNA target prediction and pathway analysis identified several pathways related to cardiac diseases, which could be linked to some of the miRNA-biomarker correlations.CONCLUSIONS: The majority of correlations between circulating AHF-specific miRNAs were related to biomarkers predictive for a worse clinical outcome in a subgroup of worsening heart failure patients at 48hours of hospitalization. The selective findings suggest a time-dependent effect of circulating miRNAs and highlight the susceptibility to individual patient characteristics influencing potential relations between miRNAs and biomarkers.",

keywords = "Acute Disease, Aged, Aged, 80 and over, Biomarkers/blood, Databases, Factual/trends, Diuretics/therapeutic use, Female, Heart Failure/blood, Hospitalization/trends, Humans, Male, MicroRNAs/blood, Middle Aged, Xanthines/therapeutic use",

author = "Vegter, {Eline L} and Daniela Schmitter and Yanick Hagemeijer and Ovchinnikova, {Ekaterina S} and {van der Harst}, Pim and Teerlink, {John R} and O'Connor, {Christopher M} and Marco Metra and Davison, {Beth A} and Daniel Bloomfield and Gad Cotter and Cleland, {John G} and Givertz, {Michael M} and Piotr Ponikowski and {van Veldhuisen}, {Dirk J} and {van der Meer}, Peter and Eugene Berezikov and Voors, {Adriaan A} and Khan, {Mohsin A F}",

year = "2016",

month = dec,

day = "1",

doi = "10.1016/j.ijcard.2016.09.010",

language = "English",

volume = "224",

pages = "231--239",

journal = "International Journal of Cardiology",

issn = "0167-5273",

publisher = "Elsevier Ireland Ltd",

}

Vegter, EL, Schmitter, D, Hagemeijer, Y, Ovchinnikova, ES, van der Harst, P, Teerlink, JR, O'Connor, CM, Metra, M, Davison, BA, Bloomfield, D, Cotter, G, Cleland, JG, Givertz, MM, Ponikowski, P, van Veldhuisen, DJ, van der Meer, P, Berezikov, E, Voors, AA & Khan, MAF 2016, 'Use of biomarkers to establish potential role and function of circulating microRNAs in acute heart failure', International Journal of Cardiology, vol. 224, pp. 231-239. https://doi.org/10.1016/j.ijcard.2016.09.010

TY - JOUR

T1 - Use of biomarkers to establish potential role and function of circulating microRNAs in acute heart failure

AU - Vegter, Eline L

AU - Schmitter, Daniela

AU - Hagemeijer, Yanick

AU - Ovchinnikova, Ekaterina S

AU - van der Harst, Pim

AU - Teerlink, John R

AU - O'Connor, Christopher M

AU - Metra, Marco

AU - Davison, Beth A

AU - Bloomfield, Daniel

AU - Cotter, Gad

AU - Cleland, John G

AU - Givertz, Michael M

AU - Ponikowski, Piotr

AU - van Veldhuisen, Dirk J

AU - van der Meer, Peter

AU - Berezikov, Eugene

AU - Voors, Adriaan A

AU - Khan, Mohsin A F

PY - 2016/12/1

Y1 - 2016/12/1

N2 - BACKGROUND: Circulating microRNAs (miRNAs) emerge as potential heart failure biomarkers. We aimed to identify associations between acute heart failure (AHF)-specific circulating miRNAs and well-known heart failure biomarkers.METHODS: Associations between 16 biomarkers predictive for 180day mortality and the levels of 12 AHF-specific miRNAs were determined in 100 hospitalized AHF patients, at baseline and 48hours. Patients were divided in 4 pre-defined groups, based on clinical parameters during hospitalization. Correlation analyses between miRNAs and biomarkers were performed and complemented by miRNA target prediction and pathway analysis.RESULTS: No significant correlations were found at hospital admission. However, after 48hours, 7 miRNAs were significantly negatively correlated to biomarkers indicative for a worse clinical outcome in the patient group with the most unfavorable in-hospital course (n=21); miR-16-5p was correlated to C-reactive protein (R=-0.66, p-value=0.0027), miR-106a-5p to creatinine (R=-0.68, p-value=0.002), miR-223-3p to growth differentiation factor 15 (R=-0.69, p-value=0.0015), miR-652-3p to soluble ST-2 (R=-0.77, p-value<0.001), miR-199a-3p to procalcitonin (R=-0.72, p-value<0.001) and galectin-3 (R=-0.73, p-value<0.001) and miR-18a-5p to procalcitonin (R=-0.68, p-value=0.002). MiRNA target prediction and pathway analysis identified several pathways related to cardiac diseases, which could be linked to some of the miRNA-biomarker correlations.CONCLUSIONS: The majority of correlations between circulating AHF-specific miRNAs were related to biomarkers predictive for a worse clinical outcome in a subgroup of worsening heart failure patients at 48hours of hospitalization. The selective findings suggest a time-dependent effect of circulating miRNAs and highlight the susceptibility to individual patient characteristics influencing potential relations between miRNAs and biomarkers.

AB - BACKGROUND: Circulating microRNAs (miRNAs) emerge as potential heart failure biomarkers. We aimed to identify associations between acute heart failure (AHF)-specific circulating miRNAs and well-known heart failure biomarkers.METHODS: Associations between 16 biomarkers predictive for 180day mortality and the levels of 12 AHF-specific miRNAs were determined in 100 hospitalized AHF patients, at baseline and 48hours. Patients were divided in 4 pre-defined groups, based on clinical parameters during hospitalization. Correlation analyses between miRNAs and biomarkers were performed and complemented by miRNA target prediction and pathway analysis.RESULTS: No significant correlations were found at hospital admission. However, after 48hours, 7 miRNAs were significantly negatively correlated to biomarkers indicative for a worse clinical outcome in the patient group with the most unfavorable in-hospital course (n=21); miR-16-5p was correlated to C-reactive protein (R=-0.66, p-value=0.0027), miR-106a-5p to creatinine (R=-0.68, p-value=0.002), miR-223-3p to growth differentiation factor 15 (R=-0.69, p-value=0.0015), miR-652-3p to soluble ST-2 (R=-0.77, p-value<0.001), miR-199a-3p to procalcitonin (R=-0.72, p-value<0.001) and galectin-3 (R=-0.73, p-value<0.001) and miR-18a-5p to procalcitonin (R=-0.68, p-value=0.002). MiRNA target prediction and pathway analysis identified several pathways related to cardiac diseases, which could be linked to some of the miRNA-biomarker correlations.CONCLUSIONS: The majority of correlations between circulating AHF-specific miRNAs were related to biomarkers predictive for a worse clinical outcome in a subgroup of worsening heart failure patients at 48hours of hospitalization. The selective findings suggest a time-dependent effect of circulating miRNAs and highlight the susceptibility to individual patient characteristics influencing potential relations between miRNAs and biomarkers.

KW - Acute Disease

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers/blood

KW - Databases, Factual/trends

KW - Diuretics/therapeutic use

KW - Female

KW - Heart Failure/blood

KW - Hospitalization/trends

KW - Humans

KW - Male

KW - MicroRNAs/blood

KW - Middle Aged

KW - Xanthines/therapeutic use

U2 - 10.1016/j.ijcard.2016.09.010

DO - 10.1016/j.ijcard.2016.09.010

M3 - Article

C2 - 27661412

SN - 0167-5273

VL - 224

SP - 231

EP - 239

JO - International Journal of Cardiology

JF - International Journal of Cardiology

ER -

Use of biomarkers to establish potential role and function of circulating microRNAs in acute heart failure

Abstract

Keywords

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