Interestingly, patients with chronic illness such as diabetes, asthma, and coronary artery disease also have lower levels of circulating sRAGE at baseline, permitting unbound ligands to bind RAGE and perpetuate an inflammatory response through NFkB.25–27 Baseline sRAGE levels were lower in our patients with SVD possibly predisposing them to (or caused by) a state of inflammation as seen in these other disease processes. This evidence concerns the gene AGER and diabetes mellitus.