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Synergy of specific microRNAs (miRNAs) with cardiovascular risk factors to estimate atherosclerosis presence in ischemic stroke patients has not been investigated. The present study aimed to identify atherosclerosis-related circulating miRNAs and to evaluate interaction with other cardiovascular markers to improve the estimation of atherosclerosis presence. We performed a miRNA profiling study using serum of 15 patients with acute ischemic stroke who were classified by the presence of no (n = 8) or severe (n = 7) stenosis on intracranial and extracranial vessels, which identified miR-212, -372, -454, and -744 as miRNAs related with atherosclerosis presence. Of the 4 miRNAs, only miR-212 showed a significant increase in expression in atherosclerosis patients in a validation study (atherosclerotic patients, n = 32, non-atherosclerotic patients, n = 33). Hemoglobin A1c, a high-density lipoprotein cholesterol, and lipoprotein(a), both established risk markers, were independently related with atherosclerosis presence in the validation population. miR-212 enhanced the accuracy of atherosclerosis presence by the three existing markers (three markers, 78.5%; three markers+miR-212, 84.6%,  P &lt;0.05) and significantly added to the area under the receiver operating characteristic curve (three markers, 0.8258; three markers+miR-212, 0.8646,  P &lt;0.05). The inclusion of miR-212 increased the reclassification index calculated using net reclassification improvement (0.4527,  P &lt;0.05) and integrated discrimination improvement (0.0737,  P &lt;0.05). We identified circulating miR-212 as a novel marker of atherosclerosis. miR-212 enhanced the estimation of atherosclerosis presence in combination with hemoglobin A1c, high-density lipoprotein cholesterol, and lipoprotein(a). Thus, miR-212 is expected to improve the estimation of atherosclerosis using peripheral blood of patients.

Synergy of circulating miR-212 with markers for cardiovascular risks to enhance estimation of atherosclerosis presence