G. J. Zahner1, J. Ramirez1, V. Ly1, K. A. Spaulding1,4, S. A. Khetani1,4, N. K. Hills2, C. Grunfeld3,5, A. L. Schafer2,3,6, W. J. Gasper1,4, M. Grenon1,4 1University Of California – San Francisco,Department Of Surgery,San Francisco, CA, USA 2University Of California – San Francisco,Department Of Epidemiology And Biostatistics,San Francisco, CA, USA 3University Of California – San Francisco,Department Of Medicine,San Francisco, CA, USA 4San Francisco VA Medical Center,Vascular Surgery Section,San Francisco, CA, USA 5San Francisco VA Medical Center,Metabolism Section,San Francisco, CA, USA 6San Francisco VA Medical Center,Endocrine Research Unit,San Francisco, CA, USA
Introduction:
Leptin, adiponectin, and resistin are in a class of hormones called adipokines that are produced by adipocytes and have been implicated in the causal pathway of atherosclerosis. Prior research has demonstrated an association between higher leptin levels and coronary heart disease (CHD); however, research on the association with peripheral artery disease (PAD) is less conclusive. Previous studies have demonstrated that leptin levels increase and adiponectin levels decrease with increasing fat mass, however, the degree of change is variable. The present study examined whether adipokine levels are associated with PAD, independent of fat mass.
Methods:
A cross-sectional sample of 179 vascular surgery outpatients (97% male, 73% Caucasian) were recruited from the San Francisco Veterans Affairs Medical Center (SFVAMC). PAD was defined as either an abnormal ABI (<0.9) plus symptoms of claudication or had previously undergone revascularization for symptomatic PAD (n=141). Controls had a normal ABI and no history of atherosclerotic disease (n=38). Adipokines were assayed using commercially available ELISA kits and values were log-transformed. Fat mass was measured using electrical impedance.
Results:
Compared to controls, patients with PAD were more likely to have diabetes, hypertension, and hyperlipidemia (p<.05). They also had smoked a greater number of pack years and had a lower estimated glomerular filtration rate (eGFR) (p<.05). In an analysis adjusting for body mass index (BMI) and traditional atherosclerotic risk factors, serum leptin was associated with PAD (OR 2.54, 95%CI 1.07-6.01, p=.03). No statistically significant associations were found between high molecular weight (HMW) adiponectin and PAD after adjusting for BMI, although the association approached statistical significance in multivariable analysis (OR 0.60, 95%CI .33-1.08, p=.09). Finally, resistin was not statistically associated with PAD in this study. Sensitivity analyses using either fat mass or fat mass/height2 rather than BMI yielded similar results.
Conclusion:
These results indicate that for a given BMI or fat mass, serum leptin levels are positively and independently associated with PAD. HMW adiponectin might be inversely associated with PAD, but larger studies are needed to conclusively make the determination. These results suggest that further research is warranted on the potential role of adipokines in the pathophysiology of PAD as well as to determine whether leptin levels may have clinical utility in predicting PAD outcomes.