Serum resistin is associated with impaired endothelial function and a higher rate of adverse cardiac events in patients with peripheral artery disease.
OBJECTIVE
Resistin is a hormone that has been associated with metabolic syndrome and cardiovascular disease. The role of resistin in patients with peripheral artery disease (PAD) has not been fully explored. This study seeks to understand the relationship between serum resistin, vascular function, and cardiovascular outcomes in patients with PAD.


METHODS
There were 106 patients with PAD who were recruited between 2011 and 2016. Patients attended a baseline visit during which a comprehensive vascular physiology assessment including medical and surgical history, radial artery tonometry, and flow mediated-vasodilation (FMD) was completed. A blood sample was drawn, and serum resistin was assayed using enzyme-linked immunosorbent assay kits. Using the time of study enrollment as the time of origin, incident major adverse cardiac events (MACEs) were identified by subsequent chart review and defined as a composite end point of myocardial infarction, coronary revascularization, transient ischemic attack, stroke, or death from a cardiac cause.


RESULTS
Patients had a mean age of 68 ± 8 years, were largely white (75%), and had comorbidities commonly associated with PAD including hypertension (92%), hyperlipidemia (87%), coronary artery disease (37%), and diabetes mellitus (38%). After stratification by resistin quartile, higher resistin quartiles were significantly associated with an older age, a greater number of pack-years smoked, and a lower estimated glomerular filtration rate. Despite similar comorbidities and medication use, endothelial function, as measured by 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). In multivariable linear regression, higher resistin quartiles (III and IV) were associated with lower FMD relative to quartile I after adjusting for several patient characteristics, medications, and comorbidities (III, -2.26 [95% confidence interval (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 months), 21 patients experienced the primary end point. In a Cox proportional hazards model adjusted for smoking status, coronary artery disease, and age, each 1 ng/mL increase in resistin was associated with a 10% increased risk of MACEs (hazard ratio, 1.10; 95% CI, 1.00-1.20; P = .04).


CONCLUSIONS
In patients with PAD, higher levels of resistin were associated with impaired endothelial function and an increased rate of MACEs. These results suggest that resistin may be a marker or effector of impaired vascular physiology and adverse cardiac outcomes in patients with PAD. Further research is needed to determine the potential mechanisms by which resistin may impair endothelial function and increase MACEs in this population.
['Ramirez|Joel L|JL|', 'Khetani|Sukaynah A|SA|', 'Zahner|Greg J|GJ|', 'Spaulding|Kimberly A|KA|', 'Schaller|Melinda S|MS|', 'Gasper|Warren J|WJ|', 'Hills|Nancy K|NK|', 'Schafer|Anne L|AL|', 'Grenon|S Marlene|SM|']
D000368:Aged D015415:Biomarkers D004730:Endothelium, Vascular D005260:Female D006331:Heart Diseases D006801:Humans D008297:Male D008875:Middle Aged D058729:Peripheral Arterial Disease D011379:Prognosis D052243:Resistin D012189:Retrospective Studies D018570:Risk Assessment D012307:Risk Factors D015854:Up-Regulation D059289:Vascular Stiffness D014664:Vasodilation
Resistin Endothelial function Peripheral artery disease Adipokines Flow-mediated vasodilation