Circulating microRNAs strongly predict cardiovascular death in patients with coronary artery disease—results from the large AtheroGene study

M Karakas, C Schulte, S Appelbaum… - European heart …, 2017 - academic.oup.com
M Karakas, C Schulte, S Appelbaum, F Ojeda, KJ Lackner, T Münzel, RB Schnabel
European heart journal, 2017academic.oup.com
Introduction Stratification for subsequent coronary events among patients with coronary
artery disease (CAD) is of considerable interest because of the potential to guide secondary
preventive therapies. Recently, we identified eight microRNAs (miRNAs), which facilitated
acute coronary syndrome (ACS) diagnosis. In this study, we aimed to evaluate their potential
role as prognostic biomarkers for cardiovascular disease. Methods The serum
concentrations of eight candidate miRNAs-miR-19a, miR-19b, miR-132, miR-140-3p, miR …
Introduction
Stratification for subsequent coronary events among patients with coronary artery disease (CAD) is of considerable interest because of the potential to guide secondary preventive therapies. Recently, we identified eight microRNAs (miRNAs), which facilitated acute coronary syndrome (ACS) diagnosis. In this study, we aimed to evaluate their potential role as prognostic biomarkers for cardiovascular disease.
Methods
The serum concentrations of eight candidate miRNAs -miR-19a, miR-19b, miR-132, miR-140-3p, miR-142-5p, miR-150, miR-186, and miR-210 were measured in a cohort of 1112 patients with documented CAD—including 430 patients with ACS and 682 patients with stable angina pectoris. Cardiovascular death was the main outcome measure.
Results
During a median follow-up of 4.0 years, most miRNAs reliably predicted cardiovascular death in ACS patients. Cox regression analyses indicated that in particular miR-132 (HR 2.85 per 1 SD increase, P = 0.022), miR-140-3p (HR 2.88 per 1 SD increase, P = 0.022), and miR-210 (HR 3.10 per 1 SD increase, P = 0.039) were able to precisely predict cardiovascular death. Circulating miR-132, miR-140-3p, and miR-210 clearly improved various model performance measures, including C-statistics (AUC [area under the receiver-operating characteristic curve] for miR-132: 0.737; AUC for miR-140-3p: 0.756; AUC for miR-210: 0.754).
Conclusions
This is the largest study so far evaluating the prognostic value of circulating miRNAs in cardiovascular disease. Our study shows that single miRNAs derived from peripheral blood predict mortality in secondary prevention settings, and thereby represent valuable biomarkers for risk estimation in CAD.
Oxford University Press