Taking into account the antioxidant properties of zinc, it is difficult to explain the beneficial effects of HMG-CoA reductase inhibitors in the context of a well-known decreased zinc status. Therefore, intracellular zinc homeostasis was studied in patients with low-grade carotid atherosclerosis under treatment with HMG-CoA reductase inhibitors using a custom microarray-based approach developed by pooling information across microarray studies. Experimental data unravel an active zinc signaling in PBMC from low-grade atherosclerotic patients under lipid reduction therapy, suggesting that monitoring intracellular zinc status could be a key factor for an optimal strategy and targeting a level of intervention.