It has been hypothesised that Frank's sign is indicative of cardiovascular disease[2][3] and/or diabetes.[4] Some studies have described Frank's sign as a marker of cardiovascular disease but not linked to the severity of the condition.[5] In contrast, other studies have rebutted any association between Frank's sign and coronary artery disease in diabetics.[6] There have also been reported cases of Frank's sign being a predictor of cerebral infarctions.[7] A link between Frank's sign and premature aging and the loss of dermal and vascular fibers has also been hypothesized.[8] Some studies have focused on association between bilateral earlobe crease and coronary artery disease.[9] It is probably prudent to consider Frank's Sign alongside other clinical markers of physiological ageing, rather than utilising it as a stand-alone sign in the identification of coronary artery disease.[10]