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.