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 α-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 α-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 α-defensin concentration (>162 μg/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 α-defensin and high hs-CRP concentration had more than 5 times higher risk for cardiovascular mortality than those with either high α-defensin or high hs-CRP alone, and low α-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 α-defensin and hs-CRP was 0.71 (95% CI 0.57-0.85). The addition of α-defensin or hs-CRP to conventional risk factors significantly improved the accuracy of risk prediction model for cardiovascular mortality. No associations were found among α-defensin, hs-CRP, and lethal outcome for patients with CLI.

Conclusions: Combined analysis of α-defensin and hs-CRP, adds prognostic information with regard to the long-term cardiovascular prognosis among patients with IC.