In contrast, not many, but consistent results show that decreased plasma levels of irisin are independently associated with endothelial dysfunction (137), flow-mediated arterial dilation (141) and presence and severity of coronary artery disease (CAD) (148), implying irisin may ameliorate vascular endothelial dysfunction and treating atherosclerosis, and this is also an explanation for the effective role of physical exercise in the prevention and management of cardiometabolic risk and in the treatment of metabolic syndrome and its complications. This evidence concerns the gene FNDC5 and endothelial dysfunction.