High catecholamine levels following activation of the sympathetic nervous system have been associated with the development of endothelial CMD either via direct cardiomyocyte toxicity or by inducing coronary artery spasms (evidence of decreased plasma levels of microRNA 125a-5p and increased levels of its target endothelin-1) resulting in inadequate myocardial blood supply [29–31]. This evidence concerns the gene EDN1 and coronary vasospasm.