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Diabetes Reduces the Quantity and Quality of Lower Extremity Collateral Arteriogenesis

Brajesh K. Lal, Ricardo G. Duran, Peter J. Pappas, George Manis, Frank T. Padberg, Jr., Walter N. Duran.
UMDNJ-New Jersey Medical School, Newark, N.J.
 
OBJECTIVES: Tissue preservation distal to arterial occlusive disease (PAD) occurs by growth and remodeling of pre-existing small channels into large collateral conduit arteries (collateral arteriogenesis). Diabetes (DM) adversely affects the outcome of PAD. We hypothesized that this may occur through reduced collateralization.

METHODS: Of 176 standardized angiograms performed for symptomatic PAD (claudication, rest pain, gangrene), 101 had isolated SFA occlusive disease with or without tibial disease (DM 47; non-DM 54). Angiograms of 10 asymptomatic limbs without PAD served as controls. We classified severity of symptoms and lesions using TASC categories; and runoff quality, using the SVS scoring system. We developed a digital image-analysis algorithm to quantify the collaterals in each angiogram (PAD Collateral Score, PAD-CS). We measured distal occlusive pressures before and after endovascular recanalization of 7 DM and 5 non-DM patients with SFA occlusions, to assess their ability to recruit established collaterals.

RESULTS: DM and non-DM patients were well matched for demographics, symptom severity, lesion severity, and runoff score. The PAD-CS was 7.4±2.1 in controls, 11.1±3.8 in DM and 19.3±3.9 in non-DM [Figure 1]. PAD-CS had low inter-observer variability (mean difference=-0.2±0.9) and correlated with manual collateral counts (r2=0.79). On univariate analysis PAD-CS correlated with DM (r=-0.46), runoff score (r=-0.13) and TASC symptom score (r=-0.29). On multivariate analysis PAD-CS was independently associated with DM (t=-6.23, p<0.001) and TASC symptom score (t=-4.45, p<0.001). Poor PAD-CS was associated with DM (r=-0.53, p<0.001) even after correcting for symptom severity. The recruitable collateral pressure was higher in non-DM vs. DM patients (p<0.03).

CONCLUSIONS: Collateral arteriogenesis of the legs can be quantified accurately by a novel digital image-analysis protocol. PAD-CS identifies clinically relevant collaterals since the scores correlate with the severity of ischemic symptoms. Diabetics develop fewer collaterals and their ability to recruit collaterals after an acute occlusion is impaired compared to non-diabetics. We provide novel evidence that diabetes plays an important role in the outcome of PAD by impairing the ability to compensate for limb ischemia.

AUTHOR DISCLOSURES: B.K. Lal, American College of Surgeons; American Heart Association; UMDNJ-Foundation; R.G. Duran, None; P.J. Pappas, None; G. Manis, None; F.T. Padberg, None; W.N. Duran, National Institutes of Health.

Figure 1.