Relations between circulating microRNAs and atrial fibrillation: data from the Framingham Offspring Study.
BACKGROUND
MicroRNA (miRNA) expression in atrial tissue has been implicated in pathologic susceptibility to atrial fibrillation (AF). Nevertheless, data on how circulating levels relate to AF are limited.


OBJECTIVE
The purpose of this study was to test the hypothesis that circulating miRNAs are associated with AF.


METHODS
Among 2445 Framingham Heart Study Offspring participants, we measured the expression of 385 circulating whole blood miRNAs by high-throughput quantitative reverse transcriptase polymerase chain reaction. We related miRNA levels with prevalent and new-onset AF.


RESULTS
Mean age of the cohort was 66.3 ± 8.9 years, and 56% were women; 153 participants had clinically apparent AF at baseline, and 107 developed AF during median follow-up of 5.4 years. miRNA-328 (miR-328) expression was lower among participants with prevalent AF (8.76 cycle threshold) compared to individuals with no AF (7.75 cycle threshold, P <.001). The association between miR-328 and prevalent AF persisted after adjustment for age, sex, and technical covariates (odds ratio 1.21, P = 1.8 × 10(-4)) but was attenuated in analyses adjusting for clinical AF risk factors (odds ratio 1.14, P = .017). In contrast to the associations between miR-328 and prevalent AF, none of the circulating miRNAs were associated with incident AF.


CONCLUSIONS
Circulating levels of miR-328, a miRNA known to promote atrial electrical remodeling by reducing L-type Ca(2+) channel density, were associated with prevalent AF. Adjustment for risk factors that promote atrial remodeling, including hypertension, attenuated the association between miR-328 and AF, potentially implicating miR-328 as a potential mediator of atrial remodeling and AF vulnerability.
National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts; Epidemiology Division, Department of Quantitative Health Sciences, University of Massachusetts Medical School Worcester, Massachusetts. Electronic address: mcmanusd@ummhc.org.
David D
DD
McManus
National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Computational Biomedicine Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
Honghuang
H
Lin
National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
Kahraman
K
Tanriverdi
Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
Michael
M
Quercio
National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts.
Xiaoyan
X
Yin
National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Department of Mathematics and Statistics, Boston University, Boston, Massachusetts; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
Martin G
MG
Larson
Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts.
Patrick T
PT
Ellinor
National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Population Research Branch and Division of Intramural Research, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, Massachusetts.
Daniel
D
Levy
National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
Jane E
JE
Freedman
Section of Cardiovascular Medicine, Department of Medicine, Boston University, Boston, Massachusetts; Preventive Medicine Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts; Epidemiology Department, Boston University School of Public Health, Boston, Massachusetts.
Emelia J
EJ
Benjamin
D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D035683:MicroRNAs / Q000097:blood*
D035683:MicroRNAs
Atrial fibrillation; Circulation; Epidemiology; Risk factors; microRNA