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.
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.
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%.
Inflammation and severity of circulatory impairment are implicated in the pathophysiology
of dysfunctional endothelium in PAD.