Circulating blood markers and functional impairment in peripheral arterial disease

OBJECTIVES: To determine whether higher levels of inflammatory blood markers, D-dimer, and homocysteine were associated with greater impairment in lower extremity functioning in persons with peripheral arterial disease (PAD). DESIGN: Cross-sectional. SETTING: Three Chicago-area medical centers. PARTICIPANTS: Four hundred twenty-three persons with PAD (ankle-brachial index (ABI) <0.90). MEASUREMENTS: Lower extremity performance was assessed using the 6-minute walk and with usual- and fast-paced 4-m walking speed. Blood markers were D-dimer, C-reactive protein (CRP), interleukin-6 (IL-6), soluble vascular cellular adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), and homocysteine. Calf muscle area was measured using computed tomography. RESULTS: Adjusting for confounders, higher levels of D-dimer (P<.001), IL-6 (P<.001), sVCAM-1 (P=.006), CRP (P=.01), homocysteine (P=.004), and sICAM-1 (P=.046) were associated with poorer 6-minute walk performance. Higher levels of D-dimer (P<.001), IL-6 (P=.003), sVCAM-1 (P=.001), and homocysteine (P=.005) were associated with slower usual-paced 4-m walking speed. Higher levels of D-dimer, sVCAM-1, sICAM-1, IL-6, and homocysteine were associated with slower fast-paced walking speed. Results were attenuated after additional adjustment for calf muscle area. CONCLUSION: Higher levels of inflammation and D-dimer were associated with poorer lower extremity performance in participants with PAD, independent of confounders including ABI.