Early remodeling of lower extremity vein grafts: inflammation influences biomechanical adaptation

Abstract

Background: The remodeling of vein bypass grafts after arterialization is incompletely understood. We have previously shown that significant outward lumen remodeling occurs during the first month of implantation, but the magnitude of this response is highly variable. We sought to examine the hypothesis that systemic inflammation influences this early remodeling response.

Methods: A prospective observational study was done of 75 patients undergoing lower extremity bypass using autogenous vein. Graft remodeling was assessed using a combination of ultrasound imaging and two-dimensional high-resolution magnetic resonance imaging.

Results: The vein graft lumen diameter change from 0 to 1 month (22.7% median increase) was positively correlated with initial shear stress (P = .016), but this shear-dependent response was disrupted in subjects with an elevated baseline high-sensitivity C-reactive protein (hsCRP) level of >5 mg/L. Despite similar vein diameter and shear stress at implantation, grafts in the elevated hsCRP group demonstrated less positive remodeling from 0 to 1 month (13.5% vs 40.9%, P = .0072). By regression analysis, the natural logarithm of hsCRP was inversely correlated with 0- to 1-month lumen diameter change (P = .018). Statin therapy (beta = 23.1, P = .037), hsCRP (beta = -29.7, P = .006), and initial shear stress (beta = .85, P = .003) were independently correlated with early vein graft remodeling. In contrast, wall thickness at 1 month was not different between hsCRP risk groups. Grafts in the high hsCRP group tended to be stiffer at 1 month, as reflected by a higher calculated elastic modulus (E = 50.4 vs 25.1 Mdynes/cm2, P = .07).

Conclusions: Early positive remodeling of vein grafts is a shear-dependent response that is modulated by systemic inflammation. These data suggest that baseline inflammation influences vein graft healing, and therefore, inflammation may be a relevant therapeutic target to improve early vein graft adaptation.

Figure 1

A, Mean index segment lumen percent change dichotomizing the population by hsCRP levels (Elevated hsCRP > 5 mg/L), demonstrating less outward lumen remodeling in those subjects with elevated hsCRP levels, P=.0072. B, Linear regression of natural-logarithmic transformed hsCRP levels and percent lumen change from the time of surgery to 1-month, R=.371, P=.018.

Figure 1

A, Mean index segment lumen percent change dichotomizing the population by hsCRP levels (Elevated hsCRP > 5 mg/L), demonstrating less outward lumen remodeling in those subjects with elevated hsCRP levels, P=.0072. B, Linear regression of natural-logarithmic transformed hsCRP levels and percent lumen change from the time of surgery to 1-month, R=.371, P=.018.

Figure 2

A, Linear regression of the entire population comparing initial shear stress and mean index segment lumen dilation from 0–1 months, R=.387, P=.016. B, Subset of patients with hsCRP ≤ 5 mg/L, R=.5, P=.014, and C, Subset of patients with elevated hsCRP > 5 mg/L demonstrating loss of correlation between initial shear and lumen dilation, R=.103, P=.725.

Figure 2

A, Linear regression of the entire population comparing initial shear stress and mean index segment lumen dilation from 0–1 months, R=.387, P=.016. B, Subset of patients with hsCRP ≤ 5 mg/L, R=.5, P=.014, and C, Subset of patients with elevated hsCRP > 5 mg/L demonstrating loss of correlation between initial shear and lumen dilation, R=.103, P=.725.

Figure 2

A, Linear regression of the entire population comparing initial shear stress and mean index segment lumen dilation from 0–1 months, R=.387, P=.016. B, Subset of patients with hsCRP ≤ 5 mg/L, R=.5, P=.014, and C, Subset of patients with elevated hsCRP > 5 mg/L demonstrating loss of correlation between initial shear and lumen dilation, R=.103, P=.725.

Figure 3

A, Representative example of a high-resolution 2-D magnetic resonance T2 weighted image using black blood module of a human saphenous vein graft. B, The area inscribed by the two lines represents the T2 weighted wall area. The lumen area is .327 cm² while the total vessel area is .566 cm².