Author + information
- Received January 29, 2008
- Revision received April 25, 2008
- Accepted April 28, 2008
- Published online July 15, 2008.
- Atif Qasim, MD⁎,
- Nehal N. Mehta, MD⁎,
- Mahlet G. Tadesse, ScD†,
- Megan L. Wolfe, BS⁎,
- Thomas Rhodes, MSPH‡,
- Cynthia Girman, DrPH‡ and
- Muredach P. Reilly, MB⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Muredach P. Reilly, Cardiovascular Institute, University of Pennsylvania Medical Center, 909 BRB 2/3, 421 Curie Boulevard, Philadelphia, Pennsylvania.
Objectives We evaluated the hypothesis that plasma levels of adiponectin and leptin are independently but oppositely associated with coronary artery calcification (CAC), a measure of subclinical atherosclerosis. In addition, we assessed which biomarkers of adiposity and insulin resistance are the strongest predictors of CAC beyond traditional risk factors, metabolic syndrome, and plasma C-reactive protein (CRP).
Background Adipokines are fat-secreted biomolecules with pleiotropic actions that converge in diabetes and cardiovascular disease.
Methods We examined the association of plasma adipocytokines with CAC in 860 asymptomatic, nondiabetic participants in the SIRCA (Study of Inherited Risk of Coronary Atherosclerosis).
Results Plasma adiponectin and leptin levels had opposite and distinct associations with adiposity, insulin resistance, and inflammation. Plasma leptin was positively (top vs. bottom quartile) associated with higher CAC after adjustment for age, gender, traditional risk factors, and Framingham risk scores (tobit regression ratio 2.42 (95% confidence interval [CI]: 1.48 to 3.95; p = 0.002) and further adjustment for metabolic syndrome and CRP (tobit regression ratio: 2.31; 95% CI: 1.36 to 3.94; p = 0.002). In contrast, adiponectin levels were not associated with CAC. Comparative analyses suggested that levels of leptin, interleukin-6, and soluble tumor necrosis factor receptor-2, as well as the homeostasis model assessment of insulin resistance (HOMA-IR) index, predicted CAC scores, but only leptin and HOMA-IR provided value beyond risk factors, metabolic syndrome, and CRP.
Conclusions In SIRCA, although both leptin and adiponectin levels were associated with metabolic and inflammatory markers, only leptin was a significant independent predictor of CAC. Of several metabolic markers, leptin and the HOMA-IR index had the most robust, independent associations with CAC.
This work was supported by a Clinical and Translational Science Award (RFA-RM-06-002) from the National Center for Research Resources and by a Diabetes Endocrinology Research Award (P30 DK-019525) from the National Institutes of Health to the University of Pennsylvania, by RO1 HL-073278, RO1 DK-021224, P50 HL-083799 (SCCOR) and W.W. Smith Charitable Trust (grant H0204) awards to Dr. Reilly.
- Received January 29, 2008.
- Revision received April 25, 2008.
- Accepted April 28, 2008.
- American College of Cardiology Foundation