Endothelial dysfunction in peripheral arterial disease is related to increase in plasma markers of inflammation and severity of peripheral circulatory impairment but not to classic risk factors and atherosclerotic burden

Objective: We undertook this study to evaluate in patients with peripheral arterial disease (PAD) the relationship of endothelial dysfunction, which is directly related to progression and clinical complications of atherosclerosis, with variables including classic risk factors, inflammation, severity of peripheral circulatory impairment, and atherosclerotic burden. Methods. This cross-sectional study included outpatients seen in an academic angiologic unit. Eighty-eight consecutive patients with PAD (ankle/brachial index [ABI] < 0.90) were studied. The control group consisted of 30 age-matched and sex-matched healthy subjects. Main outcome measures were endothelial function in the form of brachial artery flow-mediated dilation (FMD), plasma levels of C-reactive protein (CRP) and fibrinogen, severity of PAD according to ABI, and atherosclerotic burden, ie, atherosclerosis in one leg or in two or more other sites. Results: Compared with patients with FMD greater than 6.2% (ie, 5th percentile of FMD in control subjects), patients with FMD less than 6.2% had a similar prevalence of classic risk factors but higher median levels of CRP (1.6 vs 6.0 mg/L; P < .01) and fibrinogen (200 vs 374 mg/dL; P < .01). The two inflammatory markers were negatively correlated with FMD (P < .01). ABI was higher in patients with FMD greater than 6.2% than in those with worse endothelial function (0.72 +/- 0.15 vs 0.62 +/- 16; P < .01); there was no difference with respect to atherosclerotic burden. Multivariate analysis showed that the association of CRP, fibrinogen, and ABI with FMD less than 6.2% was unrelated to classic risk factors. In a second model, which included CRP, fibrinogen, and ABI, all three variables were independently related to FMD less than 6.2%. Conclusion: Inflammation and severity of circulatory impairment are implicated in the pathophysiology of dysfunctional endothelium in PAD.