Fima Macheret1, Traci M Bartz2, Luc Djousse3, Joachim H Ix4, Kenneth J Mukamal5, Susan J Zieman6, David S Siscovick7, Russell P Tracy8, Susan R Heckbert9, Bruce M Psaty9, Jorge R Kizer10. 1. Department of Medicine, Penn Presbyterian Medical Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 2. Department of Biostatistics, University of Washington, Seattle, Washington, USA. 3. Division of Aging, Department of Medicine, Brigham and Women's Hospital and Boston VA Healthcare System, Boston, Massachusetts, USA. 4. Department 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. Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. 6. Division of Geriatrics and Clinical Gerontology, National Institute on Aging, Bethesda, Maryland, USA. 7. New York Academy of Medicine, New York, New York, USA. 8. Departments of Pathology and Biochemistry, University of Vermont, Burlington, Vermont, USA. 9. Cardiovascular 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. Department of Medicine, and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
Abstract
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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