Abstract 2536: Noninvasive Ultrasonic Evaluated Endothelial Dysfunction Highly Predicts Future Diabetic Evolution and Fatal or Nonfatal Adverse Cardiovascular Events
Background: Although diabetes mellitus (DM) and endothelial dysfunction (ED) are thought to highly affect atherogenic processes, we know little about the clinical impact of ED on evolutional mechanisms of DM. This study assessed hypothesis that ED accelerates diabetic evolution.
Methods: ED was nonivasively graded by reactive changes in lumen diameter of right brachial artery following transient forearm occlusion for 5 minutes (FMD; flow-mediated endothelium-dependent vasodilation) in consecutive 518 patients with stable coronary artery disease using high-resolutional ultrasonography. The enrolled patients were categorized into 3 groups according to the values of FMD, and their glucose tolerance and clinical cardiovascular events were prospectively followed-up for 36 months or more. Diabetic evolution was defined as newly diagnosed DM by 75g-OGTT or new administration of an antidiabetic agent.
Results: For a mean follow-up period of 60 months with 100% follow-up, the patients with severe ED (FMD<4%; Group-L, n=174), more frequently manifested diabetic evolution [P<0.001, by Kaplan-Meier analysis], all cardiovascular events [P<0.001], and fatal cardiovascular events [P<0.001], compared to those with mild ED (4%<FMD<8%, Group-M, n=171) or those with preserved endothelial function (FMD 8% or more, Group-H, n=173). HbA1c significantly elevated in Group-L (P=0.009) but not in Group-M or Group-H. Cox proportional hazard model analysis including multiple clinical variables showed that severe ED was a significant predictor for future diabetic evolution (hazard ratio=2.69, P=0.011), for cardiovascular events (hazard ratio=3.75, P<0.001), and for fatal cardiovascular events (hazard ratio=10.34, P=0.022).
Conclusion: This is the first clinical ultrasonic vascular investigation demonstrating that endothelial dysfunction accelerates diabetic evolution and causes excess of fatal and non-fatal cardiovascular events.