Association between Heat Shock Protein-60 and Development of Atrial Fibrillation: Results from the Multi-Ethnic Study of Atherosclerosis (MESA).
BACKGROUND
During atrial fibrillation (AF), a high rate of myocyte activation causes cellular stress and initiates the process of atrial remodeling, which further promotes persistence of AF. Although heat shock proteins (HSPs) have been shown to prevent atrial remodeling and suppress the occurrence of AF in cellular and animal experimental models, increased levels of HSP-60 have been observed in patients with postoperative AF, likely reflecting a response to cellular stress. To better understand the role of HSP-60 in relation to AF, we examined the association of HSP-60 levels in relation to the future development of AF in the Multi-Ethnic Study of Atherosclerosis (MESA).


METHODS
MESA is a cohort study that recruited 6,814 participants aged 45-84 years and free of known cardiovascular disease at baseline (2000-2002) from six field centers. We investigated 983 participants, selected at random from the total cohort, who had HSP-60 measured and were free of AF at baseline. We tested the association of HSP-60 levels with the incidence of AF using multivariate Cox models after adjustment for demographics, clinical characteristics, and biomarkers.


RESULTS
During an average of 10.6 years of follow-up, 77 participants developed AF. We did not observe a significant association between the log-transformed HSP-60 levels and development of AF on either unadjusted or multivariate analysis (adjusted hazard ratio: 1.02 per unit difference on natural log scale, 95% confidence interval: 0.77-1.34 ln (ng/mL).


CONCLUSIONS
Contrary to the findings from the preclinical studies, which demonstrated an important role of HSP-60 in the pathogenesis of AF, we did not observe a significant association between HSP-60 and occurrence of AF.
Division of Cardiology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island.
Abhishek
A
Maan
Department of Biostatistics, University of Washington, Seattle, Washington.
Neal W
NW
Jorgensen
Cardiac Arrhythmia Service and Heart Center, Massachusetts General Hospital, Boston, Massachusetts.
Moussa
M
Mansour
Division of Cardiology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island.
Samuel
S
Dudley
Laboratory for Clinical Biochemistry Research, University of Vermont College of Medicine, Burlington, Vermont.
Nancy S
NS
Jenny
Division of Cardiovascular Medicine, University of Maryland, Baltimore, Maryland.
Christopher
C
Defilippi
Departments of Epidemiology and Medicine, The Johns Hopkins University, Baltimore, Maryland.
Moyses
M
Szklo
Division of Epidemiology and Public Health, University of Minnesota, Minneapolis, Minnesota.
Alvaro
A
Alonso
Department of Internal Medicine, Cardiology/Cardiac Electrophysiology and Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Marwan M
MM
Refaat
Cardiac Arrhythmia Service and Heart Center, Massachusetts General Hospital, Boston, Massachusetts.
Jeremy
J
Ruskin
Department of Epidemiology, Cardiovascular Health Research Unit, University of Washington, Seattle, Washington.
Susan R
SR
Heckbert
Cardiac Arrhythmia Service and Heart Center, Massachusetts General Hospital, Boston, Massachusetts.
E Kevin
EK
Heist
D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood* / Q000208:ethnology*; D001281:Atrial Fibrillation / Q000097:blood / Q000208:ethnology*; D015415:Biomarkers / Q000097:blood; D018834:Chaperonin 60 / Q000097:blood*; D015897:Comorbidity; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000097:blood*; D011379:Prognosis; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D014481:United States / Q000208:ethnology
D015415:Biomarkers; D018834:Chaperonin 60; C060293:HSPD1 protein, human; D024101:Mitochondrial Proteins
atrial fibrillation; atrial stress response; heat shock protein