PC128. Serum Resistin Is Associated With Impaired Endothelial Function and Poor Outcomes in Patients With Peripheral Artery Disease

Abstract

Resistin is a hormone secreted by adipocytes that has been associated with metabolic syndrome and cardiovascular disease. However, less is known on the role of resistin in patients with peripheral artery disease (PAD). The present study seeks to understand the relationship of serum resistin with endothelial function and cardiovascular outcomes in patients with PAD. We hypothesize that increased serum resistin is associated with worse endothelial function and an increased rate of major adverse cardiac events (MACE). One-hundred six patients who presented to clinic with complaints of claudication and an ankle-brachial index of <0.9 or history of revascularization for symptomatic PAD were recruited between 2011 and 2016. Patients were excluded if they had acute illness, renal or hepatic disease, or were taking immunosuppressants. Resistin was assayed using commercially available ELISA kits. Endothelial function was measured via brachial artery flow-mediated vasodilation (FMD) at baseline. Incident MACE were identified by subsequent chart review and defined as a composite end point of myocardial infarction, coronary revascularization, stroke, or death from a cardiac cause. Cox proportional hazards models were used to calculate hazard ratios for MACE. At baseline, despite similar Rutherford scores, medical comorbidities, and medication use, FMD was significantly lower with increasing resistin quartile (I, 9.1 ± 3.3%; II, 7.1 ± 3.5%; III, 5.8 ± 4.0%; IV, 5.6 ± 3.5%; P = .002; Fig 1). A univariate linear regression demonstrated that increasing resistin quartiles predicted lower FMD (II, −1.99 [95% confidence interval (CI), −3.96 to -0.02; P = .05]; III, −3.34 [95% CI, −5.29 to −1.39; P = .001]; IV, −3.52 [95% CI, −5.48 to -1.55; P = .001]). In multivariate linear regression, resistin quartiles III and IV predicted lower FMD relative to the first quartile after adjusting for age, race, body mass index, diabetes mellitus, hypertension, estimated glomerular filtration rate, C-reactive protein, and beta-blocker and angiotensin converting enzyme inhibitor use (III, −2.26 [95% CI, −4.51 to −0.01; P = .05]; IV, -2.53 [95% CI, −4.87 to -0.20; P = .03]). During a median follow-up period of 36 months (interquartile range, 29-45), 21 patients experienced the primary end point. In a Cox proportional hazards model adjusted for smoking status, coronary artery disease, and age, resistin was independently associated with an increased rate of MACE (HR, 1.10; 95% CI, 1.00-1.20; P = .04; Fig 2). Resistin is associated with impaired endothelial function and an increased rate of MACE in patients with PAD. Further research is needed to determine the potential mechanism by which resistin may increase MACE, and prospective studies should determine whether decreasing resistin has therapeutic benefit in patients with PAD.Fig 2: Kaplan-Meier estimate of freedom from major adverse cardiac event (MACE) in the lowest and highest resistin quartiles.View Large Image Figure ViewerDownload Hi-res image Download (PPT)