Elevated C-reactive protein levels are associated with postoperative events in patients undergoing lower extremity vein bypass surgery

Abstract

Objectives: Inflammatory markers such as high-sensitivity C-reactive protein (hsCRP) are associated with an increased risk of cardiovascular events and with the severity of peripheral arterial disease. The effects of inflammation on the development of vein graft disease remain speculative. We hypothesized that high levels of inflammatory markers would identify patients at increased risk for adverse events (graft failure, major cardiovascular events) after lower extremity bypass surgery.

Methods: Patients (n = 91) scheduled to undergo lower extremity bypass using autogenous vein were enrolled into a prospective study at two institutions. Exclusion criteria included the presence of major infection. A baseline plasma sample was obtained on the morning of lower extremity bypass. Biomarkers for inflammation included hsCRP, fibrinogen, and serum amyloid A (SAA). Values between patients with and without critical limb ischemia were compared. Proportions of events among dichotomized populations (upper limit of normal of each laboratory assay) were compared by log-rank test.

Results: Of the patients undergoing lower extremity bypass, 69% were men, 53% were diabetic, 81% were smokers, and their mean ankle-brachial index was 0.51 +/- 0.19. The indication for lower extremity bypass was critical limb ischemia in 55%. There were no perioperative deaths and two early graft occlusions. During a mean follow-up of 342 days (range, 36-694 days) there were four deaths, 27 graft-related events, and 10 other cardiovascular events. No relationships were found between events and demographics, comorbidities, baseline ankle-brachial index, or statin use. High-sensitivity CRP (P = .005), fibrinogen (P < .001), and SAA (P = .0001) levels were associated with critical limb ischemia at presentation. Among patients with an elevated hsCRP (>5 mg/L) immediately before surgery, major postoperative vascular events occurred in 60% (21/35), compared with a 32% (18/56) rate in those with a baseline CRP <5 mg/L (P = .004, log-rank test). On multivariable analysis, only elevated hsCRP correlated with adverse graft-related or cardiovascular events (P = .018).

Conclusions: The inflammatory biomarkers of hsCRP, fibrinogen, and SAA correlate with peripheral arterial disease severity at presentation in patients undergoing lower extremity bypass. Patients with elevated hsCRP are at increased risk for postoperative vascular events, most of which are related to the vein graft. These findings suggest a potential relationship between inflammation and outcomes after lower extremity vein bypass surgery.

Conflict of interest statement

Competition of interest: Dr Ridker is listed as a co-inventor on patents held by the Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease.

Figures

Fig 1

Scatter plots indicate preoperative levels of inflammatory markers from 91 patients presenting for lower extremity bypass with critical and noncritical limb ischemia (CLI).A, High-sensitivity C-reactive protein (hsCRP) (mg/L). B, Fibrinogen (mg/dL). C, Serum amyloid A (SAA) (mg/dL). Data are presented as the median and interquartile range.

Fig 2

A, Scatter plot indicates the preoperative level of high-sensitivity C-reactive protein (hsCRP) in 91 patients, and compares those who experienced a postoperative composite end point (myocardial infarction, cerebrovascular accident, death, contralateral limb or graft-related event) with those who did not. Data are presented as the median and interquartile range. B, Freedom from reaching composite end point in subjects with elevated preoperative hsCRP (>5 mg/L) compared with those with levels within the reference range (≤5 mg/L) by Kaplan-Meier method (P = .018; log-rank test). C, Freedom from graft-related events (stenosis, revision, occlusion, or amputation of index leg) in subjects with elevated preoperative hsCRP (>5 mg/L) compared with those with levels within the reference range (≤5 mg/L) by Kaplan-Meier method (P = .094; log-rank test).