Markers of inflammation in relation to long-term cardiovascular mortality in patients with lower-extremity peripheral arterial disease

Background: Elevated levels of inflammatory mediators reflect vascular inflammation, and play a significant role in the genesis of atherosclerosis, plaque instability and rupture. Methods and material: Plasma alpha-defensin and serum high sensitivity C reactive protein (hs-CRP) levels were examined in 463 patients with lower-extremity peripheral arterial disease (PAD). The relationships between inflammatory markers and lethal outcome were examined by Cox regression, and receiver operating characteristic (ROC) analysis. Results: Overall, 126 patients died, hereof 59 of cardiovascular causes. The patients with chronic critical limb ischemia (CLI) at baseline had significantly higher alpha-defensin and hs-CRP levels compared with patients with intermittent claudication (IC). For patients with IC, the relative risk for cardiovascular mortality was three times higher in patients within the upper tertile of alpha-defensin concentration (>162 mu g/l), when compared with those in the two lower tertiles (HR 3.04 95% CI 1.26-7.32). The multivariable model revealed that IC-patients with high alpha-defensin and high hs-CRP concentration had more than 5 times higher risk for cardiovascular mortality than those with either high a-defensin or high hs-CRP alone, and low alpha-defensin or low hs-CRP concentrations (HR 5.16, 95% CI 1.78-14.8). Area under the ROC curve for combined use of high values of alpha-defensin and hs-CRP was 0.71 (95% CI 0.57-0.85). The addition of alpha-defensin or hs-CRP to conventional risk factors significantly improved the accuracy of risk prediction model for cardiovascular mortality. No associations were found among alpha-defensin, hs-CRP, and lethal outcome for patients with CLI. Conclusions: Combined analysis of alpha-defensin and hs-CRP, adds prognostic information with regard to the long-term cardiovascular prognosis among patients with IC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.