TY - JOUR
T1 - Circulating microRNAs predict future fatal myocardial infarction in healthy individuals - The HUNT study
AU - Bye, Anja
AU - Røsjø, Helge
AU - Nauman, Javaid
AU - Silva, Gustavo J.J.
AU - Follestad, Turid
AU - Omland, Torbjørn
AU - Wisløff, Ulrik
N1 - Publisher Copyright:
© 2016.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Coronary heart disease is the most common cause of death, and the number of individuals at risk is increasing. To better manage this pandemic, improved tool for risk prediction, including more accurate biomarkers are needed. The objective of this study was to assess the utility of circulating microRNAs (miRs) to predict future fatal acute myocardial infarction (AMI) in healthy participants.We performed a prospective nested case-control study with 10-year observation period and fatal AMI as endpoint. In total, 179 miRs were quantified by real-time polymerase chain reaction in serum of 112 healthy participants (40-70 years) that either (1) suffered from fatal AMI within 10 years [n = 56], or (2) remained healthy [n = 56, risk factor-matched controls]. Candidate miRs were validated in a separate cohort of healthy individuals (n = 100).Twelve miRs were differently expressed in cases and controls in the derivation cohort (p < 0.05). Among these, 10 miRs differed significantly between cases and controls in the validation cohort (p < 0.05). We identified gender dimorphisms, as miR-424-5p and miR-26a-5p were associated exclusively with risk in men and women, respectively. The best model for predicting future AMI consisted of miR-106a-5p, miR-424-5p, let-7g-5p, miR-144-3p and miR-660-5p, providing 77.6% correct classification for both genders, and 74.1% and 81.8% for men and women, respectively. Adding these 5 miRs to the Framingham Risk Score, increased the AUC from 0.72 to 0.91 (p < 0.001).In conclusion, we identified several miRs associated with future AMI, revealed gender-specific associations, and proposed a panel of 5 miRs to enhance AMI risk prediction in healthy individuals.
AB - Coronary heart disease is the most common cause of death, and the number of individuals at risk is increasing. To better manage this pandemic, improved tool for risk prediction, including more accurate biomarkers are needed. The objective of this study was to assess the utility of circulating microRNAs (miRs) to predict future fatal acute myocardial infarction (AMI) in healthy participants.We performed a prospective nested case-control study with 10-year observation period and fatal AMI as endpoint. In total, 179 miRs were quantified by real-time polymerase chain reaction in serum of 112 healthy participants (40-70 years) that either (1) suffered from fatal AMI within 10 years [n = 56], or (2) remained healthy [n = 56, risk factor-matched controls]. Candidate miRs were validated in a separate cohort of healthy individuals (n = 100).Twelve miRs were differently expressed in cases and controls in the derivation cohort (p < 0.05). Among these, 10 miRs differed significantly between cases and controls in the validation cohort (p < 0.05). We identified gender dimorphisms, as miR-424-5p and miR-26a-5p were associated exclusively with risk in men and women, respectively. The best model for predicting future AMI consisted of miR-106a-5p, miR-424-5p, let-7g-5p, miR-144-3p and miR-660-5p, providing 77.6% correct classification for both genders, and 74.1% and 81.8% for men and women, respectively. Adding these 5 miRs to the Framingham Risk Score, increased the AUC from 0.72 to 0.91 (p < 0.001).In conclusion, we identified several miRs associated with future AMI, revealed gender-specific associations, and proposed a panel of 5 miRs to enhance AMI risk prediction in healthy individuals.
KW - Atherosclerosis
KW - Biomarkers
KW - Risk prediction
UR - http://www.scopus.com/inward/record.url?scp=84971425347&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84971425347&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2016.05.009
DO - 10.1016/j.yjmcc.2016.05.009
M3 - Article
C2 - 27192016
AN - SCOPUS:84971425347
SN - 0022-2828
VL - 97
SP - 162
EP - 168
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
ER -