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Higher circulating adiponectin levels are associated with increased risk of atrial fibrillation in older adults
  1. Fima Macheret1,
  2. Traci M Bartz2,
  3. Luc Djousse3,
  4. Joachim H Ix4,
  5. Kenneth J Mukamal5,
  6. Susan J Zieman6,
  7. David S Siscovick7,
  8. Russell P Tracy8,
  9. Susan R Heckbert9,
  10. Bruce M Psaty9,
  11. Jorge R Kizer10
  1. 1Department of Medicine, Penn Presbyterian Medical Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
  2. 2Department of Biostatistics, University of Washington, Seattle, Washington, USA
  3. 3Division of Aging, Department of Medicine, Brigham and Women's Hospital and Boston VA Healthcare System, Boston, Massachusetts, USA
  4. 4Department of Medicine, and the Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California San Diego, and Nephrology Section, Veteran Affairs San Diego Health Care System, San Diego, California, USA
  5. 5Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
  6. 6Division of Geriatrics and Clinical Gerontology, National Institute on Aging, Bethesda, Maryland, USA
  7. 7New York Academy of Medicine, New York, New York, USA
  8. 8Departments of Pathology and Biochemistry, University of Vermont, Burlington, Vermont, USA
  9. 9Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, and Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA
  10. 10Department of Medicine, and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA
  1. Correspondence to Dr Jorge Kizer, Cardiovascular Clinical Research Unit, 1300 Morris Park Ave, Bronx, NY 10461, USA; jorge.kizer{at}


Background Adiponectin has cardioprotective properties, suggesting that lower levels seen in obesity and diabetes could heighten risk of atrial fibrillation (AF). Among older adults, however, higher adiponectin has been linked to greater incidence of adverse outcomes associated with AF, although recent reports have shown this association to be U-shaped. We postulated that higher adiponectin would be linked to increased risk for AF in older adults in a U-shaped manner.

Methods We examined the associations of total and high-molecular-weight (HMW) adiponectin with incident AF among individuals free of prevalent cardiovascular disease (CVD) participating in a population-based cohort study of older adults (n=3190; age=74±5 years).

Results During median follow-up of 11.4 years, there were 886 incident AF events. Adjusted cubic splines showed a positive and linear association between adiponectin and incident AF. After adjusting for potential confounders, including amino-terminal pro-B-type natriuretic peptide 1–76, the HR (95% CI) for AF per SD increase in total adiponectin was 1.14 (1.05 to 1.24), while that for HMW adiponectin was 1.17 (1.08 to 1.27). Additional adjustment for putative mediators, including subclinical CVD, diabetes, lipids and inflammation, did not significantly affect these estimates.

Conclusions The present findings demonstrate that higher, not lower, levels of adiponectin are independently associated with increased risk of AF in older adults despite its documented cardiometabolic benefits. Additional work is necessary to determine if adiponectin is a marker of failed counter-regulatory pathways or whether this hormone is directly harmful in the setting of or as a result of advanced age.

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