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Background  Mean amplitude of glycemic excursion ( MAGE ) is commonly used to gauge the degree of glucose level fluctuations.  MAGE  plays a significant role in vascular endothelial dysfunction and cardiovascular events in patients with diabetes mellitus ( DM ), but its significance is not clear in non‐ DM  patients. Thus, we examined the impact of  MAGE  and vascular endothelial dysfunction on clinical outcomes in non‐ DM  patients with coronary artery disease.    Methods and Results  We followed non‐ DM  patients (n=65) for 12 months who underwent percutaneous coronary intervention and assessed the relationship among  MAGE , reactive hyperemia index ( RHI ) measured by reactive hyperemia peripheral arterial tonometry as endothelial function, and cardiovascular events. Cardiovascular events analyzed were cardiovascular death, myocardial infarction, unstable angina, and revascularizations. Compared with patients with  MAGE  <65 mg/dL (normal glycemic excursions), the group with  MAGE ≥ 65 mg/dL (high glycemic excursions) had significantly higher high‐sensitivity C‐reactive protein (0.10±0.11 mg/dL versus 0.18±0.13 mg/dL,  P =0.006) and lower  RHI  (0.64±0.21 versus 0.51±0.22,  P =0.035). The multivariable analysis identified high  MAGE  and low  RHI  (≤0.56) as risk factors associated with cardiovascular events (hazard ratio, 5.6; 95%  RI,  1.72–18.4 [ P =0.004] versus hazard ratio, 4.5; 95%  RI,  1.37–14.9 [ P =0.013]). When the prognosis was classified by combination with  MAGE  and  RHI , the incidence of cardiovascular events was 46.7% (high  MAGE +low  RHI ), 26.7% (high  MAGE +high  RHI ), 20.0% (low  MAGE +low  RHI ), and 6.6% (low  MAGE +high  RHI ) in descending order ( P =0.014). Receiver operating characteristic curve analysis revealed that  MAGE ,  RHI , and  MAGE + RHI  were each associated with cardiovascular events (area under the curve 0.780, 0.727, and 0.796, respectively).    Conclusions   MAGE  was associated with cardiovascular events in non‐ DM  patients with coronary artery disease. Furthermore, the combination with  MAGE  and  RHI  was useful for further subdivision of the risk of cardiovascular events.

journal of the american heart association

Effects of the Mean Amplitude of Glycemic Excursions and Vascular Endothelial Dysfunction on Cardiovascular Events in Nondiabetic Patients With Coronary Artery Disease