Sex-specific association between preoperative foot infection and vein graft stenosis after distal bypass for chronic limb-threatening ischemia

OBJECTIVE: Sex differences in lower-extremity bypass outcomes remain controversial, and the mechanism is unclear. We examined whether female sex is associated with vein graft stenosis (VGS), predominantly due to intimal hyperplasia, after distal bypass for chronic limb-threatening ischemia (CLTI), and whether preoperative foot infection contributes. METHODS: We studied 318 limbs with CLTI undergoing para- or inframalleolar autogenous vein bypass at a single center (2000-2014; 74 women, 23%). All analyses were restricted to single-vein grafts; after excluding grafts occluding within 30 days, 232 formed the analytic cohort (182 men, 50 women). Female vs male outcomes were compared by 1:1 optimal matching (Mahalanobis distance within a propensity-score caliper on six covariates) and by inverse-probability-of-treatment weighting, which was the primary inference; death was treated as a competing risk. Stenosis was diagnosed by duplex surveillance, with histologic examination of excised segments. Wound, ischemia, and foot infection grades and preoperative C-reactive protein and fibrinogen were analyzed by sex with sex-by-exposure interaction terms; wound cultures were reviewed. RESULTS: After matching (48 pairs), the 5-year cumulative incidence of VGS remained higher in women (44% vs 9%; log-rank P = .004), and primary patency was lower (52% vs 88%; P = .003); secondary patency (85% vs 98%; P = .06) and limb salvage (P = .60) did not differ significantly. Weighting confirmed the excess [adjusted hazard ratio (HR), 2.13; 95% confidence interval, 1.13-4.02; P = .019]. Five-year mortality was 55% in men vs 35% in women; with death as a competing risk, stenosis incidence remained higher in women (34% vs 16%). Preoperative high-grade foot infection was associated with stenosis in women (HR, 4.27; 95% confidence interval, 1.56-11.70; P = .005) but not men (HR, 0.87; P = .74), with a significant sex-by-infection interaction (P = .026); wound and ischemia grades showed no sex difference. C-reactive protein and fibrinogen showed the same direction without a significant interaction. All 25 excised stenotic segments showed intimal hyperplasia without active inflammation, and organism type was unrelated to stenosis. In women, foot infection, poor vein quality, and run-off resistance were independent correlates. CONCLUSIONS: Women undergoing single-vein distal bypass for CLTI have a higher incidence of VGS despite balanced baseline risk, with the excess concentrated in those with preoperative foot infection. The findings suggest a sex-specific vein-wall response to infection-related inflammation and support intensified, infection-aware graft surveillance in women.