Log in to MyACC
Metformin Effects on Coronary Endothelial Dysfunction in Prediabetes
Study Questions:
What is the effect of metformin therapy on coronary endothelial function and major adverse cardiac events (MACE) in patients with prediabetes with stable angina and nonobstructive coronary stenosis (NOCS)?
Methods:
The investigators enrolled 258 propensity score-matched (PSM) patients with stable angina undergoing coronary angiography in the study. Data from 86 PSM subjects with normoglycemia (NG), 86 PSM subjects with prediabetes (pre-DM), and 86 PSM subjects with prediabetes treated with metformin (pre-DM metformin) were analyzed. During coronary angiography, NOCS was categorized by luminal stenosis <40% and fractional flow reserve >0.80. In addition, they assessed the endothelial function, measuring coronary artery diameter of the left anterior descending coronary (LAD) at baseline and after the infusion of acetylcholine, by means of an intracoronary Doppler guide wire. MACE, as cardiac death, myocardial infarction, and heart failure, was evaluated at 24 months of follow-up. Overall survival and event-free survival were assessed by Kaplan-Meier survival curves and compared by the log-rank test.
Results:
At baseline, NG patients had a lower percentage of LAD endothelial dysfunction compared with pre-DM patients (p < 0.05). The pre-DM patients had a higher percentage of endothelial LAD dysfunction, as compared with the pre-DM metformin patients (p < 0.05). At the 24th month of follow-up, MACE was higher in pre-DM versus NG (p < 0.05). In pre-DM metformin patients, MACE was lower compared with pre-DM patients (p < 0.05).
Conclusions:
The authors concluded that metformin therapy may reduce the high risk of cardiovascular events in pre-DM patients by reducing coronary endothelial dysfunction.
Perspective:
This study reports that pre-DM patients have a higher rate of coronary endothelial dysfunction compared with NG patients, as endothelial-dependent vasodilatation, induced by intracoronary infusion of acetylcholine, was significantly impaired in pre-DM compared with NG patients. The study further suggests that metformin therapy in prediabetes improves not only the glucose blood levels and glycated hemoglobin values, but also the expression of all inflammatory/oxidative molecules and, consequently, the rate of MACE at 24 months of follow-up. American Diabetes Association guidelines suggest that patients with prediabetes be treated with metformin to reduce the risk of developing diabetes, and these data may help to improve utilization of metformin given additional benefits in addition to lowering glucose levels. Additional studies on a greater number of patients with prediabetes and with a longer follow-up are needed to better define cardiovascular benefits of metformin in those with prediabetes.
Keywords: Acetylcholine, Angina, Stable, Constriction, Pathologic, Coronary Angiography, Coronary Stenosis, Diabetes Mellitus, Type 2, Glucose, Heart Failure, Metabolic Syndrome, Metformin, Myocardial Infarction, Oxidative Stress, Prediabetic State, Primary Prevention, Vasodilation
< Back to Listings
