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-alone 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, triggers 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.