In concomitant coronary and peripheral arterial disease, inflammation of the affected limbs predicts coronary artery endothelial dysfunction

Background: In Coronary artery disease (CAD), concomitant peripheral arterial disease (PAD) entails more severe coronary atherosclerosis. We investigated whether the inflammatory status of affected limbs impairs coronary artery endothelial function (CAEF). Methods: We measured the neutrophil myeloperoxidase content (NMPOxC) and plasma levels of interleukin-6 and C-reactive protein in the aorta, femoral vein. and coronary Sinus Of 22 CAD + PAD and 18 CAD-aloric patients. CAEF was assessed by the cold pressure test. Human coronary artery endothelial cells (HCAECs) were incubated with serum from the femoral vein and aorta of CAD + PAD patients to determine whether blood leaving the affected limb activates HCAECs. Results: In CAD + PAD patients, NMPOxC was higher across the femoral circulation than across the Coronary circulation (p<0.01) it was also higher than across healthy femoral circulation of CAD patients (p<0.01). These findings apply also to interleukin-6, but not to C-reactive protein. The transfemoral gradient of NMPOxC and interleukin-6 significantly correlated with CAEF The NMPOxC/CAEF relationship was much greater after exercise (R = 0.79, p<0.001). which increased neutrophil activation across the affected circulation. The post-exercise association remained significant after adjustment for potential confounders (p<0.01). Serum from the affected limb of CAD + PAD patients induced. in vitro, a significant release of MCP-1 from HCAECs versus serum from the aorta of the same patients (630 [550-740] vs. 547 [490-620]: p<0.05). Conclusions: In CAD + PAD, trigers from the affected circulation may activate the endothelium at distant sites. Thus, PAD, besides being a marker of cardiovascular risk, could exert a mechanistic function in CAD progression. (C) 2008 Elsevier Ireland Ltd. All rights reserved.