MicroRNAs are associated with cardiac biomarkers, cardiac structure and function and incident outcomes in heart failure

Author:

Spahillari Aferdita1ORCID,Jackson Laurel2,Varrias Dimitrios3,Michelhaugh Sam A.4,Januzzi James L.5,Shahideh Bobby2,Daghfal David2,Valkov Nedyalka5,Murtagh Gillian2,Das Saumya5ORCID

Affiliation:

1. Department of Medicine, Division of Cardiology Duke University Durham NC USA

2. Abbott Core Diagnostics Abbott Laboratories Abbott Park IL USA

3. Albert Einstein College of Medicine/Jacobi Medical Center Bronx NY USA

4. Georgetown University School of Medicine Washington DC USA

5. Department of Medicine, Division of Cardiology Massachusetts General Hospital, Harvard Medical School 55 Fruit St Boston MA 02114 USA

Abstract

AbstractAimsThe association between microRNAs (miRNAs) and established cardiac biomarkers is largely unknown. We aimed to measure the association between plasma miRNAs and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), cardiac troponin I, soluble urokinase‐type plasminogen activator receptor (suPAR), and galectin‐3 with cardiac structure and function and clinical outcomes.Methods and resultsWe quantified 32 plasma miRNAs using the FirePlex miRNA assay and measured biomarkers in 139 individuals with symptomatic heart failure (HF). We used principal component (PC) analysis and linear regression to evaluate the association between miRNAs and biomarkers with ventricular size and function by echocardiography and Cox modelling for the incidence of a first composite event of HF hospitalization, heart transplant, left ventricular assist device implant, or death. The mean (standard deviation) age at baseline was 64.3 (12.4) years, 33 (24%) were female, and 122 (88%) were White. A total of 45 events occurred over a median follow‐up of 368 (interquartile range 234, 494) days. Baseline NT‐proBNP (β = −2.0; P = 0.001) and miRNA PC2 (β = 2.6; P = 0.002) were associated with baseline left ventricular ejection fraction. NT‐proBNP (β = 20.6; P = 0.0004), suPAR (β = −39.6; P = 0.005), and PC4 (β = 21.1; P = 0.02) were associated with baseline left ventricular end‐diastolic volumes. NT‐proBNP [hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.28–2.18, P = 0.0002], galectin‐3 (HR 2.02, 95% CI 1.05–3.91, P = 0.036), PC3 (HR 1.75, 95% CI 1.23–2.49, P = 0.002), and PC4 (HR 1.67, 95% CI 1.1–2.52, P = 0.016) were independently associated with incident events.ConclusionsBiomarkers and miRNA PCs are associated with cardiac structure and function and incident cardiovascular outcomes. Combining information from miRNAs provides prognostic information beyond biomarkers in HF.

Funder

National Institutes of Health

Division of Intramural Research

National Center for Advancing Translational Sciences

Abbott Laboratories

Publisher

Wiley

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