Effects of Metformin Therapy on Coronary Endothelial Dysfunction in Patients With Prediabetes With Stable Angina and Nonobstructive Coronary Artery Stenosis: The CODYCE Multicenter Prospective Study

Abstract

To evaluate 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). RESEARCH DESIGN AND METHODS Metformin therapy may be needed to reduce coronary heart disease risk in patients with prediabetes. A total of 258 propensity score-matched (PSM) patients with stable angina undergoing coronary angiography were enrolled 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, we assessed the endothelial function, measuring coronary artery diameter of 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. 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 Metformin therapy may reduce the high risk of cardiovascular events in pre-DM patients by reducing coronary endothelial dysfunction.

Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillation

“…Recent studies have begun to shed light on the immunometabolism regulator role of metformin in cardiovascular disease [6]. C. Sardu and his colleagues proved that the use of metformin can regulate the adipose tissue metabolism and improve the cardiac performance in pre-diabetic patients [22][23][24][25], and these effects are predominantly anti-inflammatory. Moreover, inflammation has long be regarded as a vital contributor to AF [26].…”

Relation of cardiac adipose tissue to coronary calcification and myocardial microvascular function in type 1 and type 2 diabetes

“…A recent study analyzed the adipose tissue surrounding coronary arteries during coronary artery bypass grafting interventions; Two important findings were demonstrated (1) there was increased inflammation of the adipose tissue surrounding the coronary arteries during acute myocardial infarction; and (2) treatment with metformin had an ameliorative effect on the inflammation in the peri-coronary fat and reduced the risk of major cardiovascular events at 12-month follow-up in persons with prediabetes and acute myocardial infarction [24]. Along these lines, a recent study performed in a clinical setting during coronary angiography in non-obstructive coronary stenosis, demonstrated favourable effects of metformin on coronary endothelial dysfunction as well as cardiovascular event-rate in persons with prediabetes [25].…”

Influence of Hormonal Disorders on Endothelial Dysfunction in Patients With Arterial Hypertension and Comorbide Endocrinopathies

“…THERAPY ED was assessed by changing the VEGF-A levels and a significant increase in all groups of patients was found in comparison with the controls (respectively, control, groups 1, 2 and 3 (pg/ml): 270.11±18.34 pg/ml; 379.24±19.17 pg/ml; 327.10±26.25 pg/ml; 480.19±29.12 pg/ml; (p <0.05)). In group 2, VEGF-A was lower than in group 1, which is probably due to the protective effect of Metformin which was an inclusion criteria for T2DM patients, on the functional state of endothelium [16,17]. The maximum level of VEGF-A was observed in patients of group 3.…”