Sex-based differences in the inflammatory profile of peripheral artery disease and the association with primary patency of lower extremity vein bypass grafts

Abstract

This study was conducted to determine if there are sex-based differences in the inflammatory phenotype of patients undergoing lower extremity bypass (LEB) and if they correlate with clinical outcomes. This was a retrospective analysis of a prospective cohort of 225 patients (161 men and 64 women) who underwent autogenous vein LEB between February 2004 and May 2008. Fasting baseline blood samples were obtained before LEB, and the inflammatory biomarkers high-sensitivity C-reactive protein (CRP) and fibrinogen were assessed. All patients underwent ultrasound graft surveillance. CRP levels were dichotomized at 5 mg/L and fibrinogen levels at 600 mg/dL. There were no significant differences in age, race, history of hypertension or diabetes mellitus, body mass index, or coronary artery disease between men and women. Men were more likely to be current smokers (P = .02), have a history of hypercholesterolemia (P = .02), and be taking statins (P = .02). Women were more likely to present with critical limb ischemia (P = .03) and had higher median baseline CRP levels (5.15 mg/L; interquartile range [IQR], 1.51-18.62 mg/L) than men (2.70; IQR, 1.24-6.98 mg/L; P = .02). Median follow-up was 893 days (IQR, 539-1315 days). A multivariable Cox proportional hazards model for primary vein graft patency showed a significant interaction between sex and CRP (P = .03) and fibrinogen (P = .02). After adjustment for key covariates, primary vein graft patency was significantly less in women with CRP >5 mg/L compared with women with CRP <5 mg/L (P = .02). No such difference was seen in men (P = .95). Primary graft patency was also decreased in women with fibrinogen >600 mg/dL vs women with fibrinogen <600 mg/dL (P = .002); again, this pattern was not evident in men (P = .19). Women undergoing LEB for advanced peripheral artery disease have a different inflammatory phenotype than men. Elevated baseline levels of CRP and fibrinogen are associated with inferior vein graft patency in women but not in men. These findings indicate an important interaction between sex and inflammation in the healing response of vein grafts for LEB. Women with elevated preoperative CRP and fibrinogen levels may benefit from more intensive postoperative graft surveillance protocols.